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The Lancet Student

Communicable Diseases

Emerging Threats To Controlling Neglected Tropical Diseases

Friday, January 21st, 2011

Neglected tropical diseases blight the lives of billions of people and threaten the health of millions more. For years these have evolved hand-in-hand with poverty and cripple impoverished populations, greatly impeding global development outcomes. Lisa McClenaghan has written a riveting article on the subject!

Panel 1: Neglected Tropical Diseases

Ascariasis
Buruli ulcer
Chagas disease
Dengue
Dracunculiasis
Hookworm
Human African trypanosomiasis
Leishmaniasis
Leprosy
Lymphatic filariasis
Onchocerciasis
Shistosomiasis
Trachoma
Trichuriasis

Introduction The Neglected Tropical Diseases (NTDs) are an ill-defined group of infections which constitute the most common group of diseases afflicting the 2.7 billion people living on less than $2 per day [1]. Not only do they cause significant morbidity, but the socioeconomic burden of these conditions is high [2]. Yet, because the majority of sufferers are poor, voiceless and represent an insignificant market share, these diseases have received little attention until recently, and existing control efforts are inefficient and inadequate [1,3]. In addition, a number of factors such as climate change, ecological change, population growth and drug resistance threaten control efforts, and are expected to increase the prevalence, and distribution, of NTDs unless strategies can be modified to cope with an increasing burden.

Climate change Over the past 100 years, the earth’s average surface temperature has increased by 0.6°C [4], while experts predict that average temperature could further increase by 2100 by between 1.4 and 5.8°C [4]. In the context of NTDs, this is significant because the physiological activity of both vector and parasite are sensitive to climatic changes [5, 6]. For example, dengue and filariasis are transmitted by mosquitoes, which require standing water and a warm ambient temperature to breed, mature and enable virus replication [7]. Global warming will be accompanied by alterations in the hydrologic cycle [6, 8], which will impact upon rainfall and water availability. This will affect the distribution and prevalence of parasites which are transmitted by water-borne vectors, such as schistosomiasis [6]. Similarly, Onchocerca volvulus is transmitted by the black fly, which breeds near bodies of water. Peak biting density is observed during the wet season [6], indicating that we should expect to see an increase in the density of transmission of certain NTDs during extreme rainfall.

(more…)

“Doctor please don’t leave me…”: A 1st year medical student’s journey through life and death in South Africa

Friday, December 10th, 2010

By Anand Selvam
Boston University School of Medicine, US

Ms. Dube, same age as me, looked considerably older in her cachectic state. Her eyes were sunken and her clavicles cut deep ridges from her neck. Her spindly arms and legs hung grotesquely from her distended abdomen, like a spider’s legs from its body. She and her yet-to-be-born twins were confined to an isolation room with multidrug-resistant (MDR) tuberculosis and lymphoma. She understood that her twins were likely to be lost following the radiation treatment for her lymphoma. However, her first hurdle was initiating antiretroviral (ARV) therapy. Her CD4 count was only 9 (normal > 500 cells/mL). Nevertheless, Ms. Dube held a remarkable outlook on life. We both knew her prognosis was poor but this did not stop her from enjoying life. She always wore a bright smile and carried a little ‘boom box’ with which she played the latest radio tunes. Struggling with every breath, she continued to sing and dance from her bed, encouraging me to join her. She embodied the spirit of the South African people.

Lily Flower - A symbol of deathThe South African medical system truly employs the “see one, do one, teach one” method of learning.  By the end of my first week at Siyaphila clinic in Durban, South Africa, I was to perform my first lumbar puncture (LP) on the ineffable Ms. Dube.  What was more amazing than me completing the LP successfully was that Ms. Dube had not flinched in the slightest.  No local anaesthetic. Nothing.

Ms. Dube was a real fighter, and seemingly fearless, yet she looked unwell the following morning during rounds. Her unrelenting cheer was gone and her speech was forced.  Something was definitely wrong. After finishing rounds I hurried back to check on her. I should have been forewarned by the nurses scurrying about but I went straight to Ms. Dube’s bedside without stopping to investigate.  She was coughing and gasping for air.  I asked her some questions but she could not speak, only responding with incomprehensible grunts and moans.  The intern Noxi peeked in, simultaneously gave Ms. Dube a once over and then told me to check her vitals. She left before I could respond.  Ms. Dube’s eyes went wide with fear as she was no longer able to gasp for air.  I called for help but the nurses were nowhere to be found. Noxi was on the phone. There were no senior residents or attending physicians at Siyaphila. I was alone in the isolation room with Ms. Dube. She could not breathe. Her pulse was weak. The only sound she emitted was a deep-rooted gurgling. Mucus was pouring from her mouth and nostrils. I turned her onto her side and tried to clear the mucus away as best I could but to no avail. She was drowning in her own secretions.

All the while I was wondering, “Where is everyone?  Why is no one helping?  What am I supposed to do?” my mind was still racing as to how I was going to save Ms. Dube, “Should I start CPR? She still has a faint pulse so I can’t start compressions. And there’s no resuscitation cart…” As I was robotically trying to process all of this, Ms. Dube began clutching at the air and trying to get out of the bed.  I tried holding her back but she was too strong. She had a vice-like grip and her eyes were frantic. She fell into my arms and then on top of me to the ground, became incontinent, and let out one final guttural cry before becoming still.

All the while, the remaining patients in the isolation room had been cruelly forced to watch this death struggle. Fortunately, Mrs. Patel, the elderly cleaning lady heard the commotion and came to my aid. She helped me move Ms. Dube back onto the bed.  Before she left she patted me on the shoulder and gave me an understanding nod. Yet I still couldn’t move.  I couldn’t accept that Ms. Dube’s vibrant life was gone.

It happened so fast. And it seemed like it happened without warning. But somehow everyone else knew. I came to understand as my stay in South Africa progressed. Death was a way of life, so to speak, in this part of the world. It was easy to become numb to it.  It was too painful to deal with death time and time again, every single day. It was emotionally draining. This was why the nurses left. It wasn’t that they didn’t care. It was that they cared too much. It was a naturally human response to the unrelenting waves of death.

A physician in South Africa once told me, “Never despair, and if you do, you must work on in despair.”  These are just a few of the many words of courage and wisdom that will continue to follow me throughout my medical career. Going to South Africa after my first year of medical school provided me with a unique perspective on end-of-life care.  End of life is defined as a phase of life when a person is living with an illness that will worsen and eventually cause death [1].

I learned more about life and death in a single day than I had in all my previous experiences.  I learned about compassion, the patient’s right to dignity, and my own humanity, all of which are important tenets of palliative care. Palliative care focuses on providing relief of suffering, psychosocial support, and closures near the end of life [2]; though almost always a primary goal near the end of life, palliative care delivery is often inadequate.  Reasons to explain unsatisfactory care include patient and physician reluctance to acknowledge suffering and death, and limited discussion and training in care for dying patients [3].

This was a similar trend in South Africa. There was very little time to process the loss of Ms. Dube and we hardly mentioned her afterwards.  The following day brought further challenges in what many South Africans refer to as ‘trench life’ in the health care field’s battle against HIV/AIDS.

I also met Ms. Dlamini during my first week in South Africa at McCord Hospital. She looked relatively healthy compared to other patients I had seen thus far. Her face was full and her eyes bright. So I was shocked to discover that she had a CD4 count of only one. Dr. Court, one of the registrars (i.e. resident), explained the gravity of the situation to her. He gesticulated wildly and said, “amasosha panzi panzi panzi!” In Zulu this meant that she was ‘very low in soldiers.’ The rough English translation was “your CD4 count is very, very, very low!” Nevertheless, Ms. Dlamini barely flinched. Her lack of response was not a problem of misunderstanding. I came to realize that she, like most of the South African patients I would meet, was courageous beyond description. She calmly listened to the news that she qualified for ARVs and could be transferred to Siyaphila clinic, McCord Hospital’s step-down clinic for ARV initiation and palliative care.

There was a serenity about Siyaphila that the bedlam often found, which McCord could not afford. While some patients went to Siyaphila to die, others arrived with a sense of hope for health and recovery. Since Ms. Dlamini did not have any visitors, I spent several afternoons chatting with her. It was only after wheeling her into the courtyard under the bright rays of the South African sun that I learned who Ms. Dlamini really was. I learned that she used to be a dancer and dance instructor before she became too ill to teach or perform. I learned that she was a daughter, sister, and mother. I learned that she had been abused and raped by her promiscuous partner and that she subsequently contracted the HIV infection. I learned that she was too scared to seek treatment and had run away from her home and children, all the while fearing for her life.

Every patient’s story was unique and worth delving into. I learned more from my patients about HIV, social class unrest, and the remnants of Apartheid, than I did from any book or travel guide. They were at once both unlimited in their wisdom and also in their inspiration. Ms. Dlamini was such a patient. Even in the face of such hardships she continually thanked us for our care and never complained.

It was often difficult to flush out symptoms from patients because they rarely volunteered new problems they were having. This was why we were surprised to find Ms. Dlamini complaining of severe diarrhoea and uncontrolled epistaxis during morning rounds. Ms. Dlamini appeared volume depleted with decreased skin turgor, sunken eyes, and generalized wasting. Multiple attempts to gain intravenous access were unsuccessful.  The decision was made to transfer Ms. Dlamini back to McCord Hospital. She needed a central line placement and such resuscitative procedures were not generally undertaken at Siyaphila.

At this point everyone dispersed. I stayed with Ms. Dlamini to comfort her amongst all the commotion. A few minutes later, one of the nurses came by and said I should practice placing my first nasogastric tube on Ms. Dlamini. I ran to gather the supplies but found Ms. Dlamini hyperventilating and spontaneously bleeding upon my return. I quickly asked her for consent but she refused. This was one of the few times I was refused to perform a procedure during my stay in South Africa. Something was clearly wrong. At this point I placed an oxygen mask on her and prepared her for transport.

Ms. Dlamini kept removing the oxygen mask and was becoming increasingly frantic.  This was starting to remind me of Ms. Dube from the previous day. When the nurse stopped by again Ms. Dlamini asked for her sister to be called. The nurse said something to the effect of, “Don’t be silly, everything is going to be alright.” And then I was alone again with Ms. Dlamini. She could barely speak and I was at a loss for words. After the previous day, I was not about to tell a patient, “Oh don’t worry, you’re going to be okay.”

I just stood next to her and held her hand. This was all I could manage but I thought it was better than leaving her alone. After about ten minutes, another student reminded me that we needed to catch the shuttle back to McCord Hospital for a meeting. The ambulance transporting Ms. Dlamini arrived simultaneously. I bid adieu to Ms. Dlamini but she became even more frantic upon hearing this. I explained that I would rejoin her on the wards of McCord Hospital in about an hour. She was not buying it. I stayed with her for a few moments longer until I heard the van honking for me out front. I said, “I’m sorry, but I need to leave now. I will see you soon.” I turned to leave and when I was halfway to the door I heard the words that will live with me for the rest of my life; she implored, “Please doctor…don’t leave me.” I turned back and I saw her withered hand outstretched and her eyes pleading. And then she uttered those words again, “Please doctor, don’t leave me…” Those words hung in the air, unanswered, cutting me down in my tracks. All I could manage was a weak, “I’m sorry…” My legs felt like lead as I backed out of the ward, waving and trying to keep up a strong front.

As fate would have it, Ms. Dlamini would die as she was being transferred back to McCord Hospital. This, in addition to the fact that Ms. Dube had died in my arms the previous day, and two others had died overnight was just too much for me to handle. I actually felt like every patient I touched was dying. This was more than just being a ‘black cloud.’ This was like being the grim reaper.

I did not sleep properly for days after Ms. Dlamini’s death. I kept running the sequence of events of that day in my head over and over again. I had left Ms. Dlamini to die alone.  There was no one there to comfort her, no one to hold her hand. There was only the cold, metallic stretcher to bear her weight. I still wake up on occasion in a cold sweat, that haunting image seared in my mind and those words ever-reverberating.

My words are woefully inadequate in describing what I saw and felt during those three months in South Africa. However, I feel that there are several aspects of my experience that can be taken away and applied by health care professionals anywhere. It has been my experience that discussing end-of-life care is almost universally avoided, including within the health care field. It is much easier to ignore thinking about death rather than acknowledge its inevitable occurrence. So often we shy away from death, because we fear it and also because we would rather not feel our own mortality so acutely. To examine and discuss someone else’s death means that we have to contemplate our own lives in a deeper and often uncomfortable manner.

As such, our profession places a high value on the ability to insulate ones self from the emotional rigors of our work. We are taught to avoid becoming too emotionally invested in the care of our patients. However, true empathy and connection are necessary to provide good care for patients. Rather than be avoided, such traits should be “standard doctor’s tools” used to cure, to soothe, and to improve the lives of dying patients [4,5].

In South Africa I was unable to hide from the unrelenting waves of death. It is this so-called ‘trench life’ against HIV/AIDS that breaks down all barriers. While there is no substitute for enduring such suffering and loss, I believe we all stand to benefit from learning to deal with death. Unfortunately, our medical education is almost completely bereft of such a discussion. Whereas physicians tend to focus on physical aspects of patient care, patients and families tend to view the end of life with broader psychosocial and spiritual meaning, shaped by a lifetime of experiences [6]. Our biomedical focus is a natural outgrowth of our medical training, which emphasizes the physical self, often at the expense of the emotional or spiritual self. Recognizing this deficit in our training is important in providing better palliative care. In addition, we must recognize that there is no single definition of a “good death.” Quality care at the end of life is highly individual and should acknowledge the values and preferences of the patient [6].

While we all deal with stress, disaster, and death differently, we must remember the crux of our profession’s mission. We must remember our humanity and the humanity of our patients. I believe that to die alone is the worst way to die. However, a major fear many of us face is that of being inadequate when dealing with a patient who is dying. This often drives us away from our patients at a time of great need. What do we say? How do we act? Communication with the dying should focus far more on the art of listening than on the act of speaking. When a caregiver does speak, it should be to help patients tell their life story:  their accomplishments, their interests, their regrets, their hopes, the people in their life, and aspects of their spirituality [4, 5]. By spending time with a patient, by listening intently, and helping the patient reconcile their life and impending death, caregivers can facilitate therapeutic communication.

I have found that the most important thing we can do is to be there for our patients.  Acknowledge their presence. Hold their hand. Let them know that they matter. As a first year medical student, those were the only tactics I could employ. However, those simple actions proved to be very powerful in the weeks that followed while I was in South Africa.  

The beauty of death is that it does not discriminate; it is the great equalizer. Race, colour, and class are meaningless when it comes time for one to leave this world. Stripped of all corporeal ties, death occurs at the moment when one is at his most vulnerable. I hope the next time I face such a moment I will be there for my patient.

Note:  The information provided, while attempting to be factually based, should not be assumed to be correct.  The opinions offered in this essay are solely those of the author.  Patient identities have been made anonymous.  I confirm that I am the sole author of the attached essay and take responsibility for the integrity of its substance, as well as the decision to submit for publication.


References

  1. Qaseem A, Snow V, et al.  Evidence-Based Interventions to Improve the Palliative Care of Pain, Dyspnea, and Depression at the End of Life:  A Clinical Practice Guideline from the American College of Physicians.  Ann Intern Med 2008; 148(2): 141-46.
  2. Lo B, Quill T, Tulsky J.  Discussing Palliative Care with Patients.  Ann Intern Med 1999; 130(9): 744-49.
  3. Field MJ, Cassel CK, eds. Approaching Death: Improving Care at the End of Life.  Washington, DC: National Academy Pr; 1997.
  4. Cassem NH, Stewart RS.  Management and care of the dying patient.  Int J Psychiatry Med 1975; 6: 293-304.
  5. Huffman JC, Stern TA.  Compassionate Care of the Terminally Ill.  Primary Care Companion J Clin Psychiatry 2003; 5(3): 131-36.
  6. Steinhauser KI, et al.  Factors Considered Important at the End of Life by Patients, Family, Physicians, and Other Care Providers.  JAMA 2000; 284(19): 2476-82.

The global health burden of HIV transmission attributable to alcohol consumption

Thursday, September 16th, 2010

By Arvinder S Sood
3rd Year medical student, Imperial College London
ass07(a)ic.ac.uk

Despite repeated health warnings from doctors and health ministers, the global health burden of alcohol consumption has shown no signs of slowing. The economic and health implications posed by alcohol are often overlooked in favour of its social benefits, and it is precisely this fact that makes alcohol such a dangerous commodity. The prevalence of alcohol-related chronic diseases and injury are well documented. Between 1999 and 2005 there was a 41% increase in alcohol-related mortality and in the last 30 years, mortality has risen over 450% in the UK1.With this in mind, society cannot underestimate the social complexity of alcohol as a strong risk factor for disease transmission, such as HIV/AIDS, especially in the context of global health.

Recent studies have highlighted the correlation between alcohol consumption and HIV sero-positivity2. A multi-dimensional approach is needed to explain how alcohol acts as a risk factor. However, we must first understand the interdependent relationship between alcohol consumption and HIV transmission. Those who consume excessive amounts of alcohol are more likely than the general population to contract HIV. Equally, those who are HIV-positive are more likely to misuse alcohol during their lifetime3. HIV can be transmitted via several routes, but arguably the two most important ones are high-risk sexual behaviour and injecting drugs, both of which are augmented by alcohol use. Research has proven that a history of heavy alcohol use increases the tendency for a particular individual to engage in high-risk sexual activities, including multiple sex partners, unprotected intercourse, sex with high-risk partners (e.g. injection drug users, prostitutes) and the exchange of sex for money or drugs4, 5-7. The effects of alcohol are known to have profound effects on the mental state, such as impairment of judgement and consciousness. More specifically, alcohol is said to act directly on the brain to reduce inhibitions and reduce risk awareness8. Excessive alcohol use can therefore put the individual in a very vulnerable position – a position of irrational thinking and poor decision-making.

This begs the question as to why alcohol is so commonly abused. The reasoning is not so simple. In many societies, alcohol-use is deep-rooted in social and cultural beliefs – it is recognised as a symbol of masculinity and often viewed as a way of life. According to some critics, the media should be held responsible for promoting advertisements that glamorise alcohol. Furthermore, there are certain privileges attached to alcohol, for instance the pardoning of socially unacceptable behaviour if proven to be under the influence of alcohol. McKirnan and colleagues suggested this practice may be especially common among homosexual men21. Observations have been made that men who drink prior to or during homosexual contact are more likely to part-take in high-risk sexual behaviour than heterosexuals5, 9-11.

To further our discussion, reliable studies have shown that people who strongly believe that alcohol increases sexual arousal and performance are more likely to engage in risky sex after drinking12-15. This is one of several pieces of evidence suggesting that alcohol is a strong risk factor in increasing HIV transmission. What is not yet clear, however, is the definitive science underpinning this association. Preliminary investigations have provided an insight into how alcohol affects the course of HIV transmission. One theory put forward is that alcohol decreases the immune response to HIV infection, allowing the virus to overcome the host’s defence mechanisms. Emerging laboratory evidence suggests that alcohol may alter cellular structures to increase both the HIV infectivity and vulnerability of cells22. In addition, increased viral replication and progression of AIDS related illness are enhanced by alcohol consumption20.

The burden of alcohol is exacerbated by its impact on the medical aspects of AIDS. Evidence has revealed that alcohol increases the susceptibility and severity of opportunistic infections that are more prevalent in people with AIDS16. Infections common to both alcohol and AIDS include tuberculosis, pneumonia caused by the bacterium Streptococcus pneumoniae, and viral hepatitis C which is the principal cause of death amongst the HIV-positive population16-17. Advances in medicine have led to the development of highly active antiretroviral therapy (HAART), a collection of powerful antiviral medications, which is the first line of treatment to slow the progression of HIV and the associated AIDS-related infections. Results for HIV-positive people receiving HAART have been very encouraging with many patients now enjoying a longer and better quality of life. It has been suggested that alcohol hinders antiretroviral therapy and certain evidence has highlighted the troublesome effects of alcohol during this treatment regime. Firstly, alcoholism results in reduced self control due to associated medical and psychiatric complications, which leads to a delay in seeking treatment. Secondly, alcohol can cause gastrointestinal irritation, resulting in a failure to comply with the complex medication schedule18. Moreover, alcohol itself weakens the response of the body to HIV therapy by increasing viral replication and drug resistance, restricting nutrition, and impairing liver function with subsequent poor drug metabolism23.

With the global health burden of alcohol becoming an increasing problem, we must find solutions to tackle this crisis. According to the World Health Organisation (WHO), the harmful use of alcohol causes about 2.3 million premature deaths per year worldwide (3.7% of global mortality) and is responsible for 4.4% of the global disease burden24. Perhaps, the most encouraging aspect of alcohol use is that it is modifiable through community and individual-based interventions. Basic tools such as public campaigns to increase awareness of alcohol-related harms, dispelling certain myths and misconception about alcohol and cognitive counselling are available. Time is also of an essence with regards to effective HIV treatment and prevention. Early detection of HIV infection facilitates the prompt beginning of behavioural changes aimed at reducing transmission25. To compound this further, many people who test HIV-positive fail to seek medical care until the disease has reached an advanced stage26. Having facilities whereby patients seeking treatment for their alcohol and drug-use are also routinely screened for HIV may go some way to alleviate this problem. Furthermore, we must now realise that alcohol-abuse treatment be considered primary HIV prevention. Research has shown that reducing alcohol use among HIV patients not only decreases the medical and psychiatric complications associated with alcohol use, but also reduces other drug use and HIV transmission18. Avins and colleagues found a 58% reduction in injection drug use among heterosexual patients one year after treatment for alcohol abuse27.

Our efforts should be diverted towards focusing on screening and prevention for HIV risk actors on those with severe alcohol dependence. Of a particular concern, however, is prevention of alcoholism amongst the youth population. AIDS is a leading cause of death among people aged 15 to 24 in urban, inner-city North America7, and new injection users usually become infected with HIV or viral hepatitis with two years of starting19. Therefore, sensible policies would suggest that HIV prevention programmes for youths should target alcohol consumption, in addition to injecting drug use and sexual risk reduction.

The problems associated with alcohol are very much common within the public domain. With research ongoing society is now starting to learn about other alcohol-related diseases, such as HIV/AIDS, which were previously discarded. A review of health policies and restructuring of health-care delivery is just a starting point in this journey to tackle the global health burden created by alcohol abuse.

References

1. Calling time: The nation’s drinking as a major health issue, Academy of Medical Sciences, 2004/The human cost of alcohol misuse BMA 2009
2. Mbulaiteye SM, Ruberantwari A, Nakiyingi JS, Carpenter LM, Kamali A, Whitworth JA. Alcohol and HIV: a study among sexually active adults in rural southwest Uganda. Int J Epidemiol. 2000 Oct;29(5):911-5.
1. Petry, N.M. Alcohol use in HIV patients: What we don’t know may hurt us. International Journal of STD and AIDS 10(9):561-570, 1999.
2. Windle, M. The trading of sex for money or drugs, sexually transmitted diseases (STDs), and HIV-related risk behaviors among multisubstance using alcoholic inpatients. Drug and Alcohol Dependence 49(1):33-38, 1997.
3. Avins, A.L.; Woods, W.J.; Lindan, C.P.; et al. HIV infection and risk behaviors among heterosexuals in alcohol treatment programs. JAMA 271(7):515-518, 1994.
4. Boscarino, J.A.; Avins, A.L.; Woods, W.J.; et al. Alcohol-related risk factors associated with HIV infection among patients entering alcoholism treatment: Implications for prevention. Journal of Studies on Alcohol 56(6):642-653, 1995.
5. Malow, R.M.; Dévieux, J.G.; Jennings, T.; et al. Substance-abusing adolescents at varying levels of HIV risk: Psychosocial characteristics, drug use, and sexual behavior. Journal of Substance Abuse 13:103-117, 2001.
6. MacDonald, T.K.; MacDonald, G.; Zanna, M.P.; and Fong, G.T. Alcohol, sexual arousal, and intentions to use condoms in young men: Applying alcohol myopia theory to risky sexual behavior. Health Psychology 19(3):290-298, 2000.
7. Stall, R.; McKusick, L.; Wiley, J.; et al. Alcohol and drug use during sexual activity and compliance with safe sex guidelines for AIDS: The AIDS Behavioral Research Project. Health Education Quarterly 13(4):359-371, 1986.
8. Purcell, D.W.; Parsons, J.T.; Halkitis, P.N.; et al. Substance use and sexual transmission risk behavior of HIV-positive men who have sex with men. Journal of Substance Abuse 13(1-2):185-200, 2001.
9. Maslow, C.B.; Friedman, S.R.; Perlis, T.E.; et al. Changes in HIV seroprevalence and related behaviors among male injection drug users who do and do not have sex with men: New York City, 1990-1999. American Journal of Public Health 92(3):382-384, 2002.
10. Cooper, M.L. Alcohol use and risky sexual behavior among college students and youth: Evaluating the evidence. Journal of Studies on Alcohol (Suppl. 14):101-117, 2002.
11. Dermen, K.H.; Cooper, M.L.; and Agocha, V.B. Sex-related alcohol expectancies as moderators of the relationship between alcohol use and risky sex in adolescents. Journal of Studies on Alcohol 59(1):71-77, 1998.
12. George, W.H.; Stoner, S.A.; Norris, J.; et al. Alcohol expectancies and sexuality: A self-fulfilling prophecy analysis of dyadic perceptions and behavior. Journal of Studies on Alcohol 61(1):168-176, 2000.
13. Dermen, K.H., and Cooper, M.L. Inhibition conflict and alcohol expectancy as moderators of alcohol’s relationship to condom use. Experimental and Clinical Psychopharmacology 8(2):198-206, 2000.
14. Fauci, A.S., and Lane, H.C. Human immunodeficiency virus (HIV) disease: AIDS and related disorders. In: Braunwald, E.; Fauci, A.S.; Kasper, D.L.; et al. Harrison’s Principles of Internal Medicine, 15th Edition. New York: McGraw-Hill, 2001. pp. 1852-1913.
15. Cook, R.T. Alcohol abuse, alcoholism, and damage to the immune system: A review. Alcoholism: Clinical and Experimental Research 22(9):1927-1942, 1998.
16. Lucas, G.M.; Gebo, K.A.; Chaisson, R.E.; and Moore, R.D. Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic. AIDS 16(5):767-774, 2002.
17. Fuller, C.M.; Vlahov, D.; Ompad, D.C.; et al. High-risk behaviors associated with transition from illicit non-injection drug use among adolescent and young adult drug users: A case-control study. Drug and Alcohol Dependence 66(2):189-198, 2002.
18. Marianna K. Baum, Carlin Rafie, Shenghan Lai, Sabrina Sales, John Bryan Page, Adriana Campa. AIDS Research and Human Retroviruses. May 2010, 26(5): 511-518. doi:10.1089/aid.2009.0211.
19. McKirnan, D.J.; Vanable, P.A.; Ostrow, D.G.; and Hope, B. Expectancies of sexual “escape” and sexual risk among drug and alcohol-involved gay and bisexual men. Journal of Substance Abuse 13(1-2):137-154, 2001.
20. Bagby Gregory J, Barve Shirisj, (2006) Alcohol abuse may increase susceptibility to HIV infection, Alcoholism: Clinical & Experimental Research
21. Centers for Disease Control and Prevention (CDC). Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR-Morbidity and Mortality Weekly Report 47(RR-5):42-82, 1998.
22. Alcohol misuse needs a global response: The Lancet, Volume 373, Issue 9662, Page 433, 7 February 2009. Doi:10.1016/S0140-6736(09)60146-X
23. Samet, J.H.; Mulvey, K.P.; Zaremba, N.; and Plough, A. HIV testing in substance abusers. American Journal of Drug and Alcohol Abuse 25(2):269-280, 1999.
24. Samet, J.H.; Freedberg, K.A.; Stein, M.D.; et al. Trillion virion delay: Time from testing positive for HIV to presentation for primary care. Archives of Internal Medicine 158(7):734-740, 1998.
25. Avins, A.L.; Lindan, C.P.; Woods, W.J.; et al. Changes in HIV-related behaviors among heterosexual alcoholics following addiction treatment. Drug and Alcohol Dependence 44(1):47-55, 1997.

Harm reduction schemes in Malaysia and their impact on HIV transmission

Thursday, August 26th, 2010

By Elliott Davis

King’s College London
elliott.davis(a)kcl.ac.uk

In 2005, the World Health Organisation (WHO) estimated that three quarters of all HIV positive individuals in Malaysia contracted the virus through intravenous drug use. Described by the UN as a “concentrated epidemic”, the result was a country failing in its Millennium Development Goal of reversing the spread of HIV/AIDS. Since 2005, however, the Malaysian government has radically altered its approach to managing intravenous drug use in the country. Its previously tough stance has been softened, while needle exchange and methadone maintenance programmes have been piloted and are now starting to be rolled-out across the country. These schemes remain in their infancy, yet recent evidence suggests they are already starting to have a positive impact on HIV infection rates.

HIV and AIDS continue to represent a significant public health risk across South and South-east Asia. Recent estimates by the WHO suggest that there are now around 3.8 million children and adults living with HIV in the region. This means only sub-Saharan Africa has a greater burden of infection, with an estimated 22.4 million individuals being HIV positive [1].

In several South and South-east Asian countries, HIV prevalence rates exceed 1 per cent of the 15 to 49-year-old population. Cambodia (1.6 per cent), Thailand (1.4 per cent) and Burma (Myanmar, 1.3 per cent) are among those most severely affected [2]. In Malaysia, which is often lauded for the quality of its healthcare service, the HIV prevalence rate is much lower at 0.5 per cent. But while this figure is below that of even the United States (0.6 per cent), the country faces its own serious challenge. This is because three quarters of the estimated 69,000 HIV positive individuals living inMalaysia contracted the virus through intravenous drug use [2-3].

The extent of the problem was brought into sharp focus by a United Nations (UN) report in 2005. Reflecting on the country’s progress towards achieving its Millennium Development Goals (MDGs), the UN stated that: “Malaysia has achieved commendable successes towards all the MDGs except in halting and reversing the spread of HIV/AIDS” [4-5]. Branding the problem a “concentrated epidemic”, the report went on to point out that, although the general population was perceived to be at low risk, infection rates among high-risk groups – specifically intravenous drug users (IDUs), sex workers and prison inmates – were bordering on 20 per cent. This figure is forty times higher than the 0.5 per cent prevalence rate reported for the Malaysian population as a whole [2-5].

With its MDG of reversing the rise in HIV prevalence by 2015 under threat, the Malaysian government acted swiftly in a bid to stem the tide of rising infections, sparking a rapid and dramatic turnaround in the country’s previous drug policy.

Prior to 2005, Malaysia had exercised a zero tolerance approach when it came to drug use, declaring it “public enemy number one” and hailing 2003 as a “year of total war against drugs” [6-7].

This tough stance extended beyond mere rhetoric, with one of the government’s main aims being the creation of a drug free society by 2015 [7]. Previous attempts to introduce needle exchange schemes had been dismissed out of hand [6] and drug rehabilitation programmes were overseen not by the Ministry of Health but by the Internal Affairs Ministry, which had a wider remit for national security [8]. Capitalpunishment remained the maximum penalty for anyone convicted of trafficking [9]. Meanwhile, any individual recording a positive urine test for either opiate or cannabis use was likely to face a mandatory two year sentence in a government-run drug rehabilitation centre, followed by a further two years’ probation [6, 10].

To many commentators, this hard line stance resulted in a disjointed approach to not only HIV management but also to health policy in general. First and foremost, there was good evidence that the programmes in place simply didn’t work – with up to 90 per cent of those attending rehabilitation centres going on to relapse [7]. In addition, government policy marked a dangerous precedent in a country where various studies have suggested that up to 43.9 per cent and 89.9 per cent of IDUs are respectively HIV and hepatitis C positive [10-11].

Encouragingly, the evidence to date already suggests that the change in approach is starting to yield results. The Malaysian government has worked with a number of Non-Government Organisations (NGOs) to introduce harm reduction schemes, namely methadone maintenance and needle-exchange projects.

From an initial pilot scheme of three centres in 2006, the needle exchange programme had extended to cover eight of the country’s 13 states by 2008. In the same year, some 1.8 million needles were distributed to more than 12,000 users. Meanwhile, over 7,000 individuals are now registered with central government-run methadone clinics, with a further 10,000 people receiving opiate replacement therapy through private practices [6].

The introduction of methadone maintenance schemes, in particular, seems to have had a major knock-on effect in terms of health benefits. A number of studies from around the world have already suggested that individuals involved in these schemes are more compliant with anti-retroviral treatment (ART) regimens, resulting in improved healthcare outcomes [12-13]. By 2007, up to 25 per cent of Malaysian ART patients were IDUs, marking a sharp rise from the figure of 7 per cent reported in 2003 [6].

Although harm reduction programmes remain a relatively new invention in Malaysia, the progress made so far has been heralded as a step in the right direction. Research from UNICEF suggests that the number of new HIV infections occurring in the country each day has fallen from 17 to ten between 2004 and 2009. There has also been a noticeable drop in the number of these infections associated with intravenous drug use, from the previous 75 per cent to 57 per cent [14] (see Figure 1).

tableFigure 1: HIV infection rates in Malaysia [2, 14]

Yet there remain problems. A recent article in The Lancet pointed out that IDUs continue to drive the epidemic in Malaysia. Around 1.3 per cent of the population are believed to be IDUs. And although HIV testing is now almost universal amongst these individuals (at close to 100 per cent), just 5.1 per cent said they used a condom during their last sexual encounter. Less than 30 per cent, meanwhile, reported using sterile equipment [15].

Compare these figures with the Ukraine, which is frequently cited as the country in the world with the most significant IDU-driven HIV epidemic, and the extent of the task still facing the Malaysian government becomes clear. Although only 27.6 per cent of Ukrainian IDUs had been tested for HIV in the past 12 months, over 80 per cent use sterile equipment and almost 60 per cent used a condom the last time they had sex [15-16].

The importance of these statistics cannot be over-stated. One recent survey of 526 IDUs not involved in drug treatment programmes across five cities in Peninsula Malaysia reported that 68.6 per cent of those questioned continued to share equipment and that 34 per cent were regularly involved in paid sex. Presciently, the study also identified the sharing of injecting equipment and having multiple sexual partners as the two most significant risk factors for HIV infection [11].

There have also been reports that, initially at least, local anti-drug legislation was slow to catch up with the new approach. Writing in 2007, one group of researchers reported that some pilot methadone maintenance and needle exchange projects had been raided by police with attendees beingarrested [7].

Though there is much work still to do in Malaysia, the results achieved so far do suggest that introducing simple measures like needle exchange programmes and methadone maintenance therapy can have a significant impact on HIV infection rates.

As a result of the initial success of these schemes there appears to be increasing goodwill towards them. Last year alone, the number of government-run health clinics operating needle exchange programmes increased from seven to 12, with RM43.1 million (£9.3 million) being invested in the scheme over a five-year programme. In the coming years, the president of the Malaysian AIDS Council has set a target of granting access to these schemes to a minimum of 60 per cent of IDUs [17].

Time will tell how successful these measures are long-term. However, it could well be that Malaysia emerges as a model of just how effective harm reduction measures can be in curbing the spread of HIV/AIDS in developing nations.

References

1. Joint United Nations Programme on HIV/AIDS and World Health Organisation (2009). AIDS epidemic update: December 2009. Geneva, UNAIDS.
2. United Nations Children’s Fund (2007). The state of the world’s children 2008. New York, UNICEF.
3. World Health Organisation (2007). Country cooperation strategy at a glance: Malaysia [online]. Available:http://www.who.int/countryfocus/cooperation_strategy/ccsbrief_mys_en.pdf [accessed 30 March 2010].
4. United Nations Country Team: Malaysia (2005). Achieving the millennium development goals: successes and challenges. Kuala Lumpur, United Nations Development Programme.
5. United Nations General Assembly (2005). Monitoring the declaration of commitment of HIV/AIDS. New York, United Nations.
6. Kamarulzaman A. (2009). Impact of HIV prevention programs on drug users in Malaysia. Journal of Acquired Immune Deficiency Syndrome 52(S1):17-19.
7. Reid G, Kamarulzaman A, Sran SK. (2007). Malaysia and harm reduction: The challenges and responses. The International Journey of Drug Policy18(2): 136-140.
8. Scorzelli JF. (1992). Has Malaysia’s antidrug effort been effective? Journal of Substance Abuse Treatment 9(2): 171-176.
9. Mazlan M, Schottenfield RS, Chawarski MC. (2006). New challenges and opportunities in managing substance abuse in Malaysia. Drug and Alcohol Review 25(5): 473-478.
10. Chawarski MC, Mazlan M, Schottenfeld RS. (2006). Heroin dependence and HIV infection in Malaysia. Drug and Alcohol Dependence 82(S1): 39-42.
11. Vicknasingam B, Narayanan S, Navaratnam V. (2009). The relative risk of HIV among IDUs not in treatment in Malaysia. AIDS Care 21(8): 984-991.
12. Palepu A, Tyndall MW, Joy R, Kerr T, Wood E, Press N, Hogg RS, Montaner JS. (2006). Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: the role of methadone maintenance therapy. Drug and Alcohol Dependence 84(2): 188-194.
13. Roux P, Carrieri MP, Villes V, Dellamonica P, Poizot-Martin I, Ravaux I, Spire B; MANIF2000 cohort study group. (2008). The impact of methadone or buprenorphine treatment and ongoing injection on highly active antiretroviral therapy (HAART) adherence: evidence from the MANIF2000 cohort study. Addiction 103(11): 1828-1836.
14. United Nations Children’s Fund (2009). HIV and AIDS in Malaysia: Fact sheet. Kuala Lumpur, UNICEF Malaysia Communications.
15. Arasteh K, Jarlais DCD. (2008). Injecting drug use, HIV, and what to do about it. The Lancet 372: 1709-1710.
16. United Nations Regional Task Force on Injecting Drug Use and HIV/AIDS for Asia and the Pacific. (2009). Malaysia country advocacy brief: injecting drug use and HIV. Geneva, UNAIDS.
17. Edwards A. (2009). Needle syringe exchange programme injects hope. The Star, May 2009.

The global burden of tuberculosis

Monday, August 9th, 2010

Tuberculosis (TB) is an extensively prevalent, preventable and treatable infectious disease causing great health and financial burden. TB ranks among the top ten causes of death worldwide and in 2007 alone caused 1.8 million deaths (1). The present era has provoked further concerns with the advent of multi-drug resistant strains of Mycobacterium tuberculosis. In recognition of its significance the World Health Organisation declared tuberculosis a Global emergency in 1994 (2). This article reviews the differences in the burden of tuberculosis between the developed and the developing world and highlights the present challenges of this global menace.

Epidemiological Burden

Approximately 2 billion people across the globe are estimated to be infected with the bacterium, of which 10% are likely to become symptomatic during their lifetime (3). The burden of TB is considerably greater in developing countries compared to the developed ones. For instance the prevalence rate per 100,000 population according to the World Health Organisation (WHO) report of 2009 is diagrammatically illustrated below. (4) 

fig1

The top twenty countries most affected by TB are developing countries and account for four-fifths of all cases. Furthermore, the number of cases in all regions increased during 1995-2005 other than those with established market economies (5).

Incidence

The incidence of TB has increased in the last two decades in the African continenhat from 170 cases to 350 per 100,000 population. In contrast, it has almost halved in the American continents (4). The trend in the South-East Asian, Western Pacific and Eastern Mediterranean have been fairly consistent, whereas Europe has shown a decline in the incidence of TB. 

fig2

Incidence per 100, 000

Mortality

The disparity between the prosperous world and its underprivileged counterparts is clearly evident in the mortality statistics for TB. Thus the annual mortality of TB is greatest in Africa (544,000 deaths/ 74 per 100,000 population) and South- East Asia (512,000 deaths/31 per 100,000 population).

These statistics are in striking contrast to Europe (66,000 deaths/ 7.4 per 100,000 population) and the American continents (49,000 deaths/ 5.5 per 100,000 population). (5) The present threat of TB is in terms of extra-pulmonary manifestations of disease, with increasing resistance seen to conventional anti-tuberculous drugs (Multi-drug-resistant TB) and co-infection with Human Immuno-deficiency (HIV) virus. 

fig3

Mortality per 100, 000

Extrapulmonary TB

The major risk factor predisposing to extra-pulmonary TB is immunosuppression, which is evident from the fact that the occurrence of extra-pulmonary TB has risen since the arrival of HIV/AIDS. More than half of patients with co-existing HIV and TB infection have extra-pulmonary involvement (6). Bones, lymph nodes and pleura are the most common sites of involvement. The Infectious disease society of America, American thoracic society and Centres for disease control and prevention recommend screening of HIV infection in tuberculosis patients (7).
The most prevalent site for extra-pulmonary TB is Lymph nodes (6). Cervical lymphadenitis is predominantly seen though other groups such as inguinal and axillary may also be involved. The Spine is the first site in which the involvement of the skeletal system is seen. In extra-pulmonary tuberculosis, arthritis and osteomyelitis may spread to other sites (8).

Meningitis is the chief presenting complaint in CNS involvement and intra-cranial Tuberculomas. The latter may manifest itself as space-occupying lesions. Extrapulmonary TB is indicated by a history of travel or habitation in an area of high risk, the presence of ascites with lymphocyte elevation and negative bacterial cultures and pericardial effusion when other causes have been excluded.

TB and HIV

Epidemiological studies suggest an increased incidence and prevalence of HIV in TB burdened regions of the world. South Africa, in which TB is the single most frequent cause of natural death, constitutes 0.7% of the world population and is home to 17% of the world’s total HIV population (9). Facts from 2008 show that of those infected with TB in Africa, 45% were co-infected with HIV, whereas the corresponding figures in Europe were just 3% (4). Conversely TB is the most prevalent infection in persons suffering from HIV (10). The co-existence of TB and HIV has caused serious threats in hampering the spread of two infections. Immunosuppression due to HIV leads to reactivation of latent TB whereas TB itself causes an increase in viral load of HIV causing increased morbidity and mortality (11).

The Way Forward

The facts elucidated above demonstrate the disparity of the TB burden in the developing nations compared to their prosperous counter-parts. There is a prompt need to act speedily and effectively to address and control the menace.

In 2008, it was estimated that the global annual expenditure pertaining to TB would be 3.8 to 5 billion dollars. In addition, 1.3 billion dollars were expected to be spent for drug-resistant TB. Out of these, just one-third, i.e. approximately 1.7 billion dollars were expected to be spent by the developing countries (12). Thus, the regions with the greatest proportion of the disease spent only modest sums compared to the affluent societies. This is due to the paucity of economic resources in such nations. For instance, the government of Pakistan’s health expenditure per person annually is just around 10 US dollars, whereas the international average is 434 US dollars (13). This necessitates the need for enhancing the funds for the health sector. In addition to this, prioritization of the health problems, education of the masses, efforts to reduce the spread of disease from infected individuals, provision of effective treatment to the affected persons, identification and reduction of multi-drug resistant strains of Mycobacterium tuberculosis and collaboration between the governmental and the private sectors in the above measures are some of the methods which can curtail the hazard to prevent the suffering of future generations.

Haris Riaz
Final year student
Dow Medical College, Karachi, Pakistan
harisriaz73(a)yahoo.com

References

1. Shen X, Deriemer K, Yuan Z, Shen M, Xia Z, Gui X, Wang L, Mei J, “Deaths among tuberculosis cases in Shanghai, China: who is at risk? BMC Infect Dis v.9;2009

2. TB —a global emergency. WHO report on the tuberculosis epidemic, 1994.Geneva: World Health Organization;1994. (Accessed on 5/9/2009)

3. Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: Global trends and interactions with the HIV epidemic. Arch Intern Med. 2003;163:1009–21.

4. WHO report on Tuberculosis, 2009. Available at URL http://www.who.int/tb/publications/global_report/2009/update/a-1_full.pdf Accessed on 27-7-2010

5. WHO Report on Global Tuberculosis control, 2001.WHO/CDS/TB/2001.287 (Accessed on 28/8/2009) Rieder HL, Snider DE Jr, Cauthen GM. Extrapulmonary tuberculosis in the United States. Am Rev Respir Dis 1990;141:347-51.

6. Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America: treatment of tuberculosis.Am J Respir Crit Care Med 2003; 167:603-62.

7. Golden M. Extra-pulmonary Tuberculosis: An overview. American Family Physician 2005. Am Fam Physician. 2005 Nov 1;72(9):1761-8. Review

8. Karim SSA, Churchyard GJ, Karim QA, Lawn SD: HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response. Lancet. Author manuscript; available in PMC 2010 January 7.

9. Alexander PE. De P. The emergence of extensively drug-resistant tuberculosis (TB): TB/HIV coinfection, multidrug-resistant TB and the resulting public health threat from extensively drug-resistant TB, globally and in CanadaCan J Infect Dis Med Microbiol. 2007 September; 18(5): 289–291.

10. Goletti D, Weissman D, Jackson RW, et al. Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol. 1996;157:1271–8. Available at URL: (Accessed on 20/9/2009) http://www.globalhealth.org/images/pdf/gho/2008_id_expenditures.pdf

11. Zubair M H, Zubair M M, Riaz H. rota virus mortality: A dilemma for the developing world. J Pak Med Assoc. 2009 Aug;59(8):582.

Hepatitis C: A real cause for concern in Pakistan

Monday, August 2nd, 2010

Hepatitis is an insidious disease, to such an extent that a carrier’s mild symptoms might go unrecognised, let alone confident identification of the type of Hepatitis virus causing the disease. It is only through a high index of suspicion along with recognition of high-risk groups and frequent screening campaigns, that people infected with Hepatitis C can be identified. Furthermore, in Pakistan, diagnosed patients seem more concerned over the cost of polymerase chain reaction (PCR) tests for the confirmatory detection of Hepatitis C [1] as well as the added cost and timeframe of interferon therapy, than of the implications of the actual diagnosis.

In a study that we are currently conducting in the Mayo Hospital Outdoorpatients’ Department, Lahore, Pakistan, funded by the Students’ Patients’ Welfare Society of King Edward Medical University,* we have been looking at the reaction of patients upon being diagnosed with Hepatitis B or C by serological tests for HBsAg and Anti-HCV. Patients neither twitch nor switch their facial expressions upon being labelled as positive, quite surprisingly, even though we, as medical students, are extremely careful that we inform our patients in simple terms about the sensitivity and specificity issues of serological testing, and the significant requirement for a PCR test and therapy, if confirmed. Patients seem far more concerned about the cost of the PCR test rather than their carrier status and consider it an added burden even though our serological testing is offered free of cost. As medical students, we are often asked in a very casual tone as to why Hepatitis infection renders their blood inept for donation!

We find such observations to be truly peculiar and surprising considering that other diseases -especially AIDS – can elicit a far more serious and concerned reaction from patients. Although this may appear to be a controversial statement to undermine AIDS, the statistics suggest something else. The prevalence of AIDS in Pakistan has been found to vary between 0% and 0.0064% in 1998![2] The total number of actual studies documenting this prevalence are limited, however, so further conclusions can not be made.

Prevalence of Hepatitis C

Even though our study is still in its infancy and our sample sizes relatively small, the results strongly suggest a prevalence rate of Hepatitis C in excess of 10%. There is only small adjustment of these values when allowance is given for the sensitivity and specificity of Anti-HCV (99.8% and 99.9%, respectively) [3] and the fact that this test only detects the presence of antibodies to HCV.

In well documented studies, Hepatitis C seropositivity is varied. It is reported as 16% for Anti-HCV and 28% for HCV RNA by PCR in Faisalabad [4]. In another study, 26% is the reported rate in Lahore for individuals in the general public older than 20 years of age, and 34% for individuals in the general public of Gujranwala [5]. In comparison, the prevalence rate of Hepatitis C in Japan amongst blood donors was estimated at 0.49% [6] and in the USA it was estimated at 1.8% [7]. In India, 1.85% was the reported rate in healthy blood donors [8].

As is evident from these studies, only the general public has been used for classifying the true prevalence rate and not samples from hospital settings or elsewhere. As such epidemiological studies in Pakistan are generally lacking, we were not aware of the Hepatitis C prevalence rate. We began to understand the seriousness of Hepatitis C in Pakistan once we started detecting cases ourselves, being careful to exclude patients with liver disease.

Why is Hepatitis C so prevalent in Pakistan?

Instead of quickly jumping to the idea that lack of awareness is the cause for prevalence of Hepatitis C in Pakistan, some other factors need to be examined. Most important is the fact that no vaccine for Hepatitis C exists because of its viral complexity [9]. This naturally implies that a vaccination programme similar to Hepatitis B cannot exist [ 10].

The initial symptoms are mild and extremely non-specific, such as fatigue, nausea, mild tenderness, poor appetite, etc [1]. It is extremely difficult to identify the possibility of Hepatitis C in such cases as these symptoms are merely passed off by the Pakistani community. Coupled with the lack of regular screening campaigns and actual epidemiological studies, this problem goes unaddressed. Also chronic infection develops in 70–80% of cases and is typically silent [11]. In 20% of patients with chronic infection, cirrhosis develops within about 20 years [11]. Hepatocellular Carcinoma (HCC) develops in 1–4% of patients with cirrhosis each year after an average of 30 years [11]. Individuals infected with Hepatitis C realise their diagnosis after suffering from HCC and cirrhosis, rather than being diagnosed via opportunistic screening.

The question still remains: why is the prevalence rate so high? One possible explanation links the vaccination of smallpox and simultaneous Hepatitis C infections, which explains why its prevalence rate is so high in the population greater than 20 years of age compared with younger individuals [5]. However this factor has never been further examined. It’s obvious, however, that it is hinting towards an important risk factor: sharing of needles and needle stick injuries.

There have been only small studies examining the risk factors associated with Hepatitis C. Identification of risk factors is critical because it would alter the way new prevention strategies are devised and advertised. In our study of this issue, needle stick injuries are very frequent, especially among women who sew clothes at home and may share the same needle. Exposure via dental treatment has also been significant: among local clinics there is no way to confirm whether dentists employ good sanitation measures (autoclaving of equipment, etc.) . However, even with proper disinfection, contaminating material may still be present in the internal areas of the equipment [12]. Gynaecological history has been significant with regards to home births: so-called trained professionals that assist in the births have no knowledge of aseptic measures, often using the same set of instruments on multiple patients without sterilisation. Of special note here is the current maternal mortality ratio in Pakistan – the estimated maternal mortality ratios per 100 000 livebirths ranges from a low of 281 in Karachi to a high of 673 in Khuzdar [Balochistan] [13]. Haemorrhage (52.9%), puerperal sepsis (16.3%), and eclampsia (14.4%) are the leading causes for direct maternal deaths [13]. The frequency of deaths from both haemorrhage and puerperal sepsis may indicate the use unsterilised equipment. This repetitive use of unsterilised equipment also pertains to barber shops and establishments where body piercing is performed. In a study, patients with Hepatitis C analysed by Anti-HCV ELISA were more likely to have daily face shaves (adjusted OR=5.1, 95% CI: 1.5–17.0) and armpit shaves (adjusted OR=2.9, 95% CI: 1.3–6.5) by a barber [14]. Multiple therapeutic injections in Pakistan have also been pointed as culprits in at least two studies [14,15]. In one such study, cases were more likely to have received therapeutic injections in the past 10 years (1–10 vs. 0 therapeutic injections; adjusted OR=2.8, 95% CI: 1.1–7.1; > 10 vs. 0 therapeutic injections; adjusted OR=3.1, 95% CI: 1.2–7.9) [14]. This study identifies injected drug use, blood transfusion, pricked with a needle, re-use of syringes, and even being over the age of 35 years as separate independent risk factors for HCV infection from amongst blood samples of apparently healthy people of the province of Punjab, Pakistan [16].

Role of the government and various organisations in addressing HCV

The government of Pakistan is, at present, trying to address this situation by partnering with the World Health Organization (WHO) to empower and strengthen the national programme for prevention and control of Hepatitis for early detection, and encouraging research in cost effective treatment. They are also in the process of setting diagnosis and counselling centres throughout the country for the treatment of Hepatitis, as announced by the national programme manager on the national channel Pakistan Television [17]. The Sindh government has planned to vaccinate 1.4 million newborns and 245 000 adults against Hepatitis B and provide treatment to about 16 600 patients of Hepatitis C under the “Chief Minister’s initiative for Hepatitis-free Sindh” [18]. However, no follow up report has been published in any leading newspaper.

The Hepatitis C trust, London, has taken up the initiative to create awareness for people of Pakistan about Hepatitis C, as published in its 2006 end of year update report in which they described their awareness raising initiative [19]. Human Development Promotion Group (HDPG) in association with Glaxo Smith Kline (A multinational pharmaceutical company) undertook a one-month awareness campaign (June-July, 2002) against Hepatitis B & C in the district Charsadda. HDPG survey data from the area showed that people were unaware about the basic information about this disease. The campaign concentrated on creating awareness by involving student communities, politicians, and youths. Numerous activities including gatherings, walks, placards, banners, and visiting schools were inculcated in their campaign. HDPG claim to have been successful in creating awareness in a sizeable population of Charsadda [20].

Role of media

Beginning 10 years ago, the media initiated a huge campaign to increase awareness about AIDS, focusing largely on the fact that it is incurable. In Pakistan, it would be more relevant and appropriate, however, to raise awareness about Hepatitis C, as the prevalence rate is much greater than that of AIDS. The way AIDS progresses is also not much different from Hepatitis C, with non-specific symptoms at first followed by a latent phase and then full blown immunodeficiency [21]. Although it has significantly reduced some similar risk factors, especially the continuous use of the same blade on everyone by the barber, the attention of the general public has however diverted more in favour of AIDS.

Various channels do address other healthcare issues. There is usually a limited amount of coverage on healthcare issues on Dawn News and Geo News channels. Maternal and child healthcare constitute most of these messages. Pakistan Television also offers some coverage of maternal and child healthcare issues [22]. Regular news and reports do frequently mention the situation of healthcare in Pakistan and the associated factors as evidenced by the videos [23,24]. There are also infrequent debates and discussions regarding the healthcare system of Pakistan [25]. The Dawn Newspaper has a section “Letter to the Editor” that may infrequently publish health-related messages expressed in the form of “Letters” [26].

Of peculiar interest is the regular and frequent publications in leading Urdu newspapers, such as Jang and Nawai-Waqt, of homoeopathic treatment options, not only for diseases that can be potentially cured by allopathic medications such as Hepatitis C, but also for diseases that are virtually incurable such as AIDS and diabetes mellitus. The degree of confidence offered is usually 100%. These can take the shape of advertisements on television as well as painted on the sides of buses, wagons, and rickshaws. These have a major effect on the attitude of the public because a major attractive factor in this business is the promise of a 100% cure for diseases otherwise deemed incurable by current medical knowledge and research [27].

This warrants the existence of regulatory bodies to keep track of the flow of not only this information, but also of potentially misleading advertisements such as those by Safeguard Soap, which claim to guard against every known bacterial and viral disease (including Swine Flu) known to mankind (interestingly, superficial fungal and parasitic infections never get a mention) [28].

The pursuit of a vaccine

A vaccine is an obvious development that can significantly decrease the incidence of Hepatitis C infection. Given the viral complexity and extreme genetic heterogeneity of the Hepatitis virus, there is no vaccine available as yet [29]. However various novel techniques are being considered in pursuit of the development. In 2005, Chen and Li attempted to express immunogenicity in mice by using Hepatitis B Core antigen (HBcAg) as the immuno-carrier to express HCV T epitope. Their results were encouraging, having induced strong non-specific lymphocyte proliferation in the group of mice receiving the vaccine [30]. Genotype-specific vaccines are also being sought [31]. However, the vaccine that can end the drought once and for all may be the IC41 peptide vaccine developed by the company Intercell. Studies into this new vaccine have yielded very encouraging results. IC41 is a synthetic peptide vaccine containing seven relevant Hepatitis C virus (HCV) T-cell epitopes. It has been shown to be safe, well tolerated, and induces HCV specific TH1 immune response [32]. Studies into the immunogenic capability and safety of different injection routes of IC41 have also taken place, yielding very encouraging results [33]. The safety of IC41 is permitting evaluation of further clinical trials in HCV infected individuals.

Conclusion

Given such an alarming situation, it is imperative that the Pakistani government starts nationwide campaigns against Hepatitis C, the same way it did against AIDS about 10 years ago. Case control, cohort, and cross-sectional studies should all be conducted and all the risk factors must be identified in great detail. This should then be used as a criterion for making new policies concentrating on prevention of Hepatitis C. It cannot be stressed enough just how significant random screening campaigns are for identification of positive cases.

Public attitude must be altered and the best way to approach the public in today’s world is through media. Public-health messages, preventive measures, and treatment options available must all be advertised on air and through newspapers. Funds should also be allocated to offer PCR and therapy free of cost to people who have been detected as positive. Every media channel should be used to air as many public-health messages as possible in order to address the entire population of Pakistan.

Only through a nationwide government-supported campaign can the prevalence rate of Hepatitis C and its transmission in Pakistan be significantly reduced.

Ayaz Mahmood Khawaja
King Edward Medical University (Lahore, Pakistan), Final year medical student
dr.ayazmk(a)yahoo.com

Ubaid ur Rehman
Allama Iqbal Medical College (Lahore, Pakistan), Final year medical student
drubaid(a)live.com

Mehmood ul haque
Allama Iqbal Medical College (Lahore, Pakistan), Final year medical student sunny_pakistani(a)hotmail.com

References

1. Information acquired from http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/ accessed 5th March 2010.

2. A A Hyder, O. A. Khan (1998). “HIV/AIDS in Pakistan: the context and magnitude of an emerging threat.” Journal of Epidemiology and Community Medicine 52: 579-585.

3. Description in Accu-Chek pamphlet and product description at http://www.tootoo.com/d-p8336137-HCV_test/

4. AHMAD Nasir, ASGHAR Muhammed, SHAFIQUE Muhammad, QURESHI Javedanver. (2007). “An evidence of high prevalence of Hepatitis C virus in Faisalabad, Pakistan.” Saudi medical journal 28: 390-395.

5. Aslam, M. M. D. A., Junaid (2001). “Seroprevalence of the Antibody to Hepatitis C in Select Groups in the Punjab Region of Pakistan.” Journal of Clinical Gastroenterology 33(5): 407-411.

6. Junko Tanaka, J. K., Keiko Katayama, Yutaka Komiya, Masaaki Mizui, Retsuji Yamanaka, Kou Suzuki, Yuzo Miyakawad, Hiroshi Yoshizawa (2004). “Sex- and Age-Specific Carriers of Hepatitis B and C Viruses in Japan Estimated by the Prevalence in the 3,485,648 First-Time Blood Donors during 1995-2000.” Intervirology 47(1): 32-40.

7. Miriam J. Alter, P. D., Deanna Kruszon-Moran, M.S., Omana V. Nainan, Ph.D., Geraldine M. McQuillan, Ph.D., Fengxiang Gao, M.D., Linda A. Moyer, B.S., Richard A. Kaslow, M.D., M.P.H., and Harold S. Margolis, M.D. (1999). “The Prevalence of Hepatitis C Virus Infection in the United States, 1988 through 1994.” The New England Journal of Medicine 341: 556-562.

8. Aswini K. Panigrahi, S. K. P., Rajesh K. Dixit, Kanury V. S. Rao, Subrat K. Acharya, Srinivasan Dasarathy, Ambika Nanu (1997). “Magnitude of Hepatitis C virus infection in India: Prevalence in healthy blood donors, acute and chronic liver diseases.” Journal of Medical Virology 51(3): 167-174.

9. Randal, J. (1999). “Hepatitis C Vaccine Hampered by Viral Complexity, Many Technical Restraints.” Journal of National Cancer Institute 91(11): 906-908.

10. Extended Programme of Immunization: www.healthnwfp.gov.pk/EPI.doc accessed 5th March 2010.

11. Hepatitis C: http://emedicine.medscape.com/article/177792-followup

12. Hu, T., G. Li, et al. (2007). “Risk of Hepatitis B virus transmission via dental handpieces and evaluation of an antisuction device for prevention of transmission.” Infect Control Hosp Epidemiol 28: 80-82.

13. Fikree, F., F. Midhet, et al. (1997). “Maternal mortality in different Pakistani sites: ratios, clinical causes and determinants.” Acta Obstetricia et Gynecologica Scandinavica 76(7): 637-645.

14. Bari, A., S. Akhtar, et al. (2001). “Risk factors for Hepatitis C virus infection in male adults in Rawalpindi–Islamabad, Pakistan.” Tropical Medicine & International Health 6(9): 732-738.

15. Pasha, O., S. Luby, et al. (1999). “Household members of Hepatitis C virus-infected people in Hafizabad, Pakistan: infection by injections from health care providers.” Epidemiology and infection 123(03): 515-518.

16. IDREES, M., L. Amreek, et al. (2008). “High prevalence of Hepatitis C virus infection in the largest province of Pakistan.” Journal of digestive diseases 9(2): 95-103.

17. Information acquired from http://www.dawn.com/wps/wcm/connect/dawn-content-library/dawn/the-newspaper/local/lahore/lahore-who-wants-pakistan-to-update-medical-syllabus-030, accessed 30th April 2010.

18. Information acquired from http://www.dawn.com/2008/11/04/local8.htm accessed 30th April 2010.

19. Information acquired from http://www.hepctrust.org.uk/ accessed 30th April 2010.

20. Information acquired from http://www.hdpg.org/compaign.html accessed 30th April 2010.

21. Information acquired from http://www.emedicinehealth.com/hivaids/page3_em.htm#HIV/AIDS Symptoms accessed 5th March 2010.

22. Information acquired from http://www.youtube.com/watch?v=SY4CxVR2I24 accessed 30th April 2010.

23. “Health Situation In pakistan An exclussive report By Saghir Naqash” http://www.youtube.com/watch?v=vXPT2LJjsS4 accessed 30th April 2010.

24. Street Barbers Pose Serious Health Risks In Pakistan 2010-Addiel Sabir http://www.youtube.com/watch?v=l7DT9vvgHIo accessed 30th April 2010.
25. Problems with Health Care in Pakistan – Live with Talat PART3 http://www.youtube.com/watch?v=6HHUysrTc14 accessed 30th April 2010.
26. Information acquired from http://www.dawn.com/wps/wcm/connect/dawn-content-library/dawn/the-newspaper/letters-to-the-editor/breast-cancer-in-pakistan-209) accessed April 30th 2010.
27. Information acquired from http://www.thenews.com.pk/daily_detail.asp?id=234642 accessed 30th April 2010

28. Safeguard Soap Commercial http://www.chaltatv.com/view_video.php?viewkey=524afda05122893c2fe8

29. Randal, J. (1999). “Hepatitis C Vaccine Hampered by Viral Complexity, Many Technical Restraints.” J. Natl. Cancer Inst. 91(11): 906-908.

30. Chen, J. and F. Li (2006). “Development of Hepatitis C virus vaccine using Hepatitis B core antigen as immuno-carrier.” WORLD JOURNAL OF GASTROENTEROLOGY 12(48): 7774.

31. Yusim, K., W. Fischer, et al. (2010). “Genotype 1 and Global Hepatitis C T-cell Vaccines Designed to Optimize Coverage of Genetic Diversity.” Journal of General Virology.

32. Klade, C. S., H. Wedemeyer, et al. (2008). “Therapeutic Vaccination of Chronic Hepatitis C Nonresponder Patients With the Peptide Vaccine IC41.” Gastroenterology 134(5): 1385-1395.e1381.

33. Firbas, C., T. Boehm, et al. (2010). “Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine.” Vaccine 28(12): 2397-2407.

* SPWS is a non-profit organization run solely by undergraduate medical students, funded by dedicated donors, at King Edward Medical University, Lahore, Pakistan. http://www.spwske.com/

Controlling Gambian Sleeping Sickness – Search and Destroy

Thursday, March 25th, 2010

CATT screeningScreening for sleeping sickness using the Card Agglutination Test for Trypanosomiasis (CATT)

Human African trypanosomiasis (HAT), also known as Sleeping Sickness, is a fatal parasitic disease transmitted by the bite of the tsetse fly. It is distributed in pockets throughout sub-Saharan Africa, placing an estimated 60 million people at risk of infection [1]. There are two forms of this deadly disease: in West Africa, infection with Trypanosoma brucei gambiense gives rise to a chronic disease, mainly affecting humans – Gambian sleeping sickness; in East Africa, infection with Trypanosoma brucei rhodesiense generates acute disease in humans, and also circulates in a relatively unaffected livestock reservoir.

Both forms are characterised by a two-stage disease pathogenesis. The first stage is characterised by an initial skin chancre at the site of the infective bite, swollen lymph glands, waves of fever, enlarged spleen and generalised skeletal muscle atrophy. Specifically with Gambian sleeping sickness the lymph glands of the posterior cervical triangle are enlarged – an important diagnostic feature known as Winterbottom’s sign. In the second stage, parasites enter and damage the central nervous system causing progressive neurological damage, which manifests in a number of ways, effecting mental, sensory and motor processes, as well as disturbances to the circadian rhythm (hence the name of the disease). The Rhodesian form progresses rapidly; more than 80% of deaths occur within six months of the onset of illness while, in contrast, the Gambian form may progress for years.

Active screening is necessary for any disease with an extended asymptomatic pre-clinical period and historically the strategy of active case-finding and treatment has been very successful in controlling Gambian sleeping sickness; huge declines in reported cases were seen between 1930 and 1960. However, in the immediate post-colonial era sleeping sickness control programmes lost their impetus and the gradual decline in incidence showed a dramatic reversal. Thankfully, since 1997, the number of reported cases has once again begun to fall [2]. Active case-finding remains the mainstay of successful disease control and the screening techniques have developed to some extent. Nevertheless, under-reporting is a significant problem [3] and sleeping sickness has become a truly ‘neglected tropical disease’. Over time HAT has simply not attracted sufficient resources for innovative diagnostic and therapeutic strategies to be developed. This trend is changing and there is now an increasing recognition of the neglected tropical diseases, and real efforts to push diagnosis and treatment up the research agenda [4].

Sleeping sickness tends to persist in well-established epidemiological foci and while these foci may expand and contract in epidemic waves, new foci are rarely seen. However, in late 2007, polymerase chain reaction (PCR) analysis of human blood samples from a previously ‘silent’ region around Lake Albert in western Uganda generated positive signals for T. b. gambiense. The PCR assay for T. b. gambiense [5] detects and amplifies the single copy T. b. gambiense-specific glycoprotein gene, which is widely accepted as an appropriate ‘indicator’ gene for this parasite. These PCR findings stimulated the Ugandan Ministry of Health and the University of Edinburgh (UK) with support from World Health Organisation (WHO) to support further investigations. I had the privilege of observing the first active search for T. b. gambiense infections in the area surrounding Lake Albert in September 2008 as a representative of the postgraduate Global Health student body from the College of Medicine and Veterinary Medicine at the University of Edinburgh. The Ugandan Ministry of Health brought with them extensive experience of screening activities from the established Gambian sleeping sickness focus in north-western Uganda.

Several thousand people were screened at central sites in two districts of Uganda, Hoima and Bulisa. Finger prick blood samples were taken for serological testing using the Card Agglutination Test for Trypanosomiasis (CATT). The CATT test detects anti-trypanosomal antibodies in patient blood and was designed for use in field surveys; the test is available in kit form from WHO, and is the mainstay of active screening for T. b. gambiense. However, treatment which is dangerous, complicated, and expensive is only justified when the parasites are seen directly [6]. All CATT whole blood positive individuals therefore provided a second blood sample for CATT on 1/4, 1/8 and 1/16 plasma dilutions and parasite detection by micro-haematocrit centrifugation. CATT whole-blood positive individuals were also examined for clinical signs by cervical lymph node palpitation. Micro-haematocrit centrifugation of blood in capillary tubes concentrates parasites in the white blood cell layer and parasites are then visible under a microscope [7]. In addition small droplets of patient blood were placed on Whatman FTA cards (chemically treated filter paper matrices specially designed to hold DNA for long term storage) for PCR analysis in the UK.

Parasites were not found in the blood of any of the screened individuals by micro-haematocrit centrifugation, nor did any of the individuals examined show enlarged lymph nodes. However these findings disguised a much more complicated situation. Several individuals were serologically positive by the CATT test (down to 1/16 plasma dilution) and several of the blood samples were positive for T. brucei s.l. parasite DNA by PCR [8]. Further investigation was necessary; was the micro-haematocrit centrifugation method simply not sensitive enough to detect low levels of parasites in these people or is the CATT test worryingly non-specific for detecting low levels of parasite?

In April 2009, I was again privileged to take part in the follow-up study. We sought out the CATT whole blood positive cases that had been seen six months earlier. This time the most sensitive parasitological detection method, the mini-anion exchange centrifugation technique (mAECT) [9] was also used, administered by an expert, Tanoé Miézan. mAECT uses anion chromatography to separate trypanosomes from the venous blood sample in which they are collected, before centrifugation to concentrate the parasites for viewing by microscopy. All parasitological detection was performed indoors, since trypanosome lysis is precipitated by exposure to direct sunlight. Again, no parasite positive cases were found yet again, we saw several CATT and PCR positive results, though these were not in direct agreement. The epidemiological picture became even more peculiar when these CATT and PCR results did not match those seen in the initial screening phase. In this instance cervical lymph node palpitations were not performed.

For me, these experiences highlight our lack of a definitive, field-friendly diagnostic screening tool for Gambian sleeping sickness. The sensitivity of CATT in north-west Uganda has been questioned for failing to detect parasite-positive cases [10]. In contrast to serological techniques, molecular tools offer a direct method of parasite detection but PCR requires equipment, expertise and resources well beyond the scope of an average mobile screening team. Furthermore, PCR has not been properly evaluated against the established serological and direct parasite detection methods. We would expect PCR to be more sensitive and it is difficult to predict what our results mean for the detection of very early or possibly even non-virulent or self-limiting forms of the disease. In my opinion, molecular methods such as PCR need to be validated in a less complicated epidemiological setting. Though classical PCR is perhaps never going to be a field friendly screening tool, other molecular methods such as LAMP (loop-mediated isothermal amplification) may fulfil that role [11]. At the very least, we need to be able to interpret the epidemiological significance of PCR-based research findings.

These results also raise the question of whether we truly understand T. b. gambiense infection? Although it is widely assumed to be pathogenic and ultimately fatal in all instances, the time course of infection is not well understood and a long asymptomatic chronic infection stage may exist before parasites become visible. We rarely know when an individual became infected and do not know how long it takes for individuals to show parasites in their blood. If there are instances of human trypanotolerance, and/or non pathogenic T. b. gambiense strains in circulation, then the current epidemiological paradigm would need to be reworked with major implications for long term planning of disease control programmes [12].

Finally I had a glimpse of the logistical difficulties faced by active screening teams; affected communities lived in remote villages, frequently only accessible by bicycle/footpaths. At the initial screening it is unlikely that all the individuals in an area were aware of our presence and were willing to travel to our screening post. At follow-up we collected people by four-wheel drive vehicle yet seeking out these people and persuading them to leave their daily tasks to come with us was not easy. Difficulties also arose as the team came together from different organisations with different experiences of T. b. gambiense in different sociological, cultural and environmental settings. It rapidly became apparent that we were working to different case definitions and that not all the necessary laboratory equipment had been sourced. I was continually impressed by the resourcefulness of the screening teams, exemplified when the seal broke on the centrifuge; it was quickly replaced by a bicycle inner tube!

Significant efforts are being made to improve the diagnosis of HAT; for example, the Foundation for Innovative New Diagnostics (FIND), is a public-private partnership established to find novel and improved solutions for the diagnosis of sleeping sickness and other diseases. FIND are pursuing improved fluorescent microscopy and LAMP for molecular diagnosis for sleeping sickness, as well as novel serological antibody and antigen detection tests, see www.finddiagnostics.org.

These experiences have highlighted the need for improving not only the tools we use, but also our fundamental understanding of sleeping sickness biology in order to properly interpret screening results. As diagnostic techniques become more sensitive we must ask ourselves what a positive signal means in terms of disease in the infected individual. In the absence of clinical signs, what response is appropriate in terms of follow-up treatment for that individual and for prevention of transmission to their neighbours. Only when a positive signal definitively equates to ‘infection’ should treatment with the currently available drugs ensue. For the PCR positive ‘cases’ detected in the present study, Ministry of Health, Uganda will continue to monitor their status.

Acknowledgements: Grateful thanks are extended to the Ugandan Ministry of Health, especially Dr Abbas Kakembo, Dr Charles Wamboga, Dr Dimi Okutoi, Julius Asingwire and Albino Louga. I am also extremely grateful to WHO consultant Dr Tanoé Miézan, my PhD supervisors at the University of Edinburgh Professor Sue Welburn and Dr Kim Picozzi and Professor Ian Maudlin for his comments on this manuscript. Finally, I would like to thank the local communities and government workers from Hoima and Bulisa, Uganda.

Sally Wastling is studying for a PhD in infectious diseases at Edinburgh University in the UK
sallywastling(at)gmail.com

References

1. Cattand P, Jannin J, Lucas P (2001) Sleeping sickness surveillance: an essential step towards elimination. Trop Med Int Health 6: 348-361.

2. Simarro PP, Jannin J, Cattand P (2008) Eliminating human African trypanosomiasis: where do we stand and what comes next? PLoS Med 5: e55.

3. Welburn SC, Maudlin I, Simarro PP (2009) Controlling sleeping sickness – a review. Parasitology 136: 1943-1949.

4. Molyneux DH Neglected tropical diseases–beyond the tipping point? Lancet 375: 3-4.

5. Picozzi K, Fevre EM, Odiit M, Carrington M, Eisler MC, et al. (2005) Sleeping sickness in Uganda: a thin line between two fatal diseases. British Medical Journal 331: 1238-1241.

6. WHO (1998) Control and Surveillance of African Trypanosomiasis.Report of a WHO Expert Commitee on Sleeping Sickness.

7. Woo PT (1970) The haematocrit centrifuge technique for the diagnosis of African trypanosomiasis. Acta Trop 27: 384-386.

8. Moser DR, Cook GA, Ochs DE, Bailey CP, McKane MR, et al. (1989) Detection of Trypanosoma-Congolense and Trypanosoma-Brucei Subspecies by DNA Amplification Using the Polymerase Chain-Reaction. Parasitology 99: 57-66.

9. Miezan TW, Meda AH, Doua F, Cattand P (1994) [Evaluation of the parasitologic technics used in the diagnosis of human Trypanosoma gambiense trypanosomiasis in the Ivory Coast]. Bull Soc Pathol Exot 87: 101-104.

10. Enyaru JCK, Matovu E, Akol M, Sebikali C, Kyambadde J, et al. (1998) Parasitological detection of Trypanosoma brucei gambiense in serologically negative sleeping-sickness suspects from north-western Uganda. Annals of Tropical Medicine and Parasitology 92: 845-850.

11. Mori Y, Notomi T (2009) Loop-mediated isothermal amplification (LAMP): a rapid, accurate, and cost-effective diagnostic method for infectious diseases. Journal of Infection and Chemotherapy 15: 62-69.

12. Checchi F, Filipe JA, Barrett MP, Chandramohan D (2008) The natural progression of Gambiense sleeping sickness: what is the evidence? PLoS Negl Trop Dis 2: e303.

Tuberculosis in Chiapas, Mexico: A Human Rights Perspective

Thursday, March 4th, 2010

Introduction

Sustainable healthcare provision, requires effectively functioning systems from clinical to governmental level. This is a challenging task and only by identify and improving weaknesses within the whole system is will things progress. No matter how good a clinician is, or how hard they work, if the support systems are failing, they will not be able to work effectively.

Human rights have become an invaluable tool for improving health systems, aswell as broader social factors effecting health, such as discrimination and violence. Article 12 of the International Covenant on Economic, Social and Cultural Rights, which has come to be known as ‘the right to health’, requires governmental recoginition of everyone’s right to ‘the highest attainable standard of physical and mental health’. The Universal Declaration of Human Rights also explicitly recognises health rights, particularly in Article 25, where wider social determinants of health including food, clothing and medical care are also specifically noted. The highest attainable standard of health requires health systems to function effectively, on all levels. Failing in this due to incompetance and neglect constitutes violations of these rights, as the ‘highest attainable standard of health’ is not being achieved.

This article discusses how a number of organizations in the Mexican state of Chiapas are applying human rights frameworks to the case of tuberculosis (TB). It will identify failings in the realisation of the highest attainable standard of health, and explore ways to ensure sustainable improvement in health care provision to indigenous populations in this area.

Mexico – Middle-Income, High Inequality

Mexico is classified by The World Bank as a middle-income country, with a Gross National Product of US$1,086 billion. In spite of its financial resources, Mexico has high levels of inequality, with 20% of the population living on less than US$2 per day (1). It also has the poorest Human Development Index rating of all the OECD countries (2). A recent report also criticized for having health indicators well below the average for the OECD, with specific mention of access inequalities and inadequate health insurance coverage for the poor (3).

Chiapas is the southern-most state of Mexico, bordering Guatemala to the south. 26% of the Chiapas population is composed of indigenous groups, the majority of which are of Mayan descent – the inhabitants of this region before the arrival of the Spanish in the early 1500s (4). Despite being rich in a variety of natural resources and a significant producer of Mexico’s hydroelectric power, Chiapas is one of the poorest Mexican states.

The indigenous people of Chiapas have suffered a long history of discrimination, marginalisation and prejudice, punctuated with violent episodes, from the bloody arrival of the Spanish in the early 1500s, to the 1997 ‘Acteal Massacre’ of 15 children, 21 women (four of whom where pregnant) and nine men, in a church by a group of paramilitaries. The situation culminated in the 1994 uprising of anti-governmental groups, predominantly composed of empassioned indigenous peoples. The best known of these groups is the Ejercito Zapatista de Liberacion Nacional (EZLN), more commonly referred to as the ´Zapatistas’. The EZLN intended to force the end of the mistreatment of indigenous people in Mexico, predominantly using a stratagy of non-complaince and civil resistance. The EZLN formed a parallel government which still controls a number of areas in Chiapas

Health as a Political Tool

The political climate in Chiapas has led to the fragmentation, politicisation, and general degradation of already limited governmental provisions, required for the realisation of human rights. Beyond simply not providing it, healthcare has been used as a political tool to fragment, and therefore weaken, some of the poorest communities in Mexico (5). This politicisation of both governmental, and anti-governmental health services, has resulted in people being denied treatment including childhood vaccinations, and receiving abuse from health workers, due to their political affiliation and or ethnicity (5). Attempting to sway pollitical opinion by denying unwell people their right to available treatment, is unacceptable and unjustifiable regardless of context.

Statistics show that healthcare resource allocation inversely correlates with marginalisation in Mexico, with health expenditure per-capita for insured people being up to twelve times higher than for those without health insurance (6). Looking at TB in mexico, these inequalities in health care provision are striking.

TB in Chiapas

Chiapas has one the highest TB incidence rates in Mexico, with a TB mortality rate twice the national average, the highest of any Mexican state (7). However, independent research has found significantly higher rates of TB in Chiapas, indicating that the situation in Chiapas may in fact be much worse than suggested by governmental research (5).

Particular factors relating to the development of TB, that are common in the rural indigenous communities of Chiapas, include high rates of malnutrition, cooking with solid fuels, dirt-floored housing, poor sanitation, cramped and over-crowded accommodation, poor access to medical services and poor working conditions (8,9). Such factors are also central to the development of many other other communicable and non-communicable diseases, hence steps to address such factors can have health implications beyond TB.

The Mexican Official Norm (10) details the specific approach that should be taken concerning the monitoring, identification, and treatment of TB in Mexico. Furthermore, in 2009 Chiapas included a pledge in their constitution to meet the United Nations Millennium Development Goals, including Goal 6, which specifically refers to TB. These developments create the appearance of political will, however, the failings identified by human rights organizations show that in practice, neither national nor international standards are not being met (8).

A number of specific TB cases in Chiapas are presently being used to highlight human rights abuses resulting from failures in healthcare provision, that under international law, Mexico is legally bound to address. Patients failed to recieve health related information in which was culturally, linguistically and contextually appropriate; there were unjustified breaches of patient confidentiality; and experianced politicisation, discrimination, stigmatisation, and cultural insensitivity within service provision. The Direct Observed Short Course (DOTS) as advised by the World Health Organisation (11) was poorly implemented, including inappropriate treatment regimes; lack of medications resulting in gaps during treatment; lack of contact tracing; the failure to provide medication to TB contacts and many people had simply been given incorrect diagnosises (8). All these factors have had significant negative impacts upon patients in Chiapas (8). Using the evidence and understanding from these patient cases will allow for the specific failings in the the system to be addressed and bring about broader health improvements to health care in Chiapas

It is important to identify the key factors that resulted in failures of service provision. For example, it is the state’s responsibility to inform national government of medication requirements relating to patients identified as having TB. This has been highlighted as one of the points at which the system has broken down in the specific cases being investigated. This was compounded through inadequate identification of TB cases (5).

Monitoring systems also show major flaws: for example, all of the 145 cases of TB identified in the Los Altos region of Chiapas during 2000 (8) have had their records lost, and subsequently have received no follow-up (personal correspondence between CCESC-DDS, ECOSUR and Chiapas Health Secretary Jurisdiccion Sanitaria No.II). Furthermore, discrepancies between government and independent research indicate that inadequate TB surveillance mechanisms, through lack of identification, are underestimating disease prevalence, and are not identifying patients in need of treatment (5). The situation has resulted from multiple avoidable factors, for which financial support was available but not used. For example, in 2008, 60% of the health budget for Chiapas was simply not used (12) at the same time as medications for TB were not available at a clinical level. Money that should have been used to purchase medication remained unused, and was subsequently returned to central government resulting in a reduction in the consecutive year’s health budget. Such large scale organisational failings clearly have a considerable impact the standard of health attainable for patients, and are subsiquently completely unacceptable.

Effective management of TB can only be achieved through comprehensive, well executed programmes, with a strong grounding in political will (13). The cases presently being highlighted show multiple failings at all levels of health care provision, indicating a lack of the necessary political will. Human rights form the basis of the legal obligations of states to their population, applicable to all persons without discrimination of any kind. In general, governments are aware that poor human rights records are damaging to their position in the international community. International pressure could therefore influence political will in Mexico where it is needed, but this has not been forthcoming.

Organisations in Chiapas have initially analysed the situation from a human rights perspective, and then used this work to address the situation. For example, CCESC-DDS lobbied at the Mexican Congress using the research that had been done, and successfully ensured an audit and review of the TB program in Chiapas. This process is to be followed up by an independent inter-organisational right to health observatory, who will also monitor other important health issues in Chiapas.

The case of TB is used here to highlight human rights violations. Through legal procedures they hope to initiate improvements in the regulation of human rights in Chiapas, which in turn will improve health care provision for all. Many of the issues raised with reference to TB, such as the lack of medicines, lack of staff, and issues of access are equally applicable to other health and civil society issues. These cases have informed various civil society groups about rights-based issues, many of which are now seeking further education in human rights and ways to use these legal frameworks with reference to their own work in Chiapas.

Conclusions

The example of TB in Chiapas highlights multiple failings in the realisation, and direct abuse, of universal human rights to which the indigenous people of Chiapas are entitled. Human rights are inalienable, and it is clear that appropriate steps for their realisation have not been taken in public health delivery. This lack, in particular the right to health, has resulted from complex interactions between social, political, and historical factors. Although these factors have led to the present situation, they do not justify it. Facilitation the achievment of these rights is the duty of the Mexican, and Chiapas state, government. The failures in the realisation of these rights constitute human rights violations, and therefore requires appropriate attention. It is primarily the responsibility of the Mexican government to identify why such abuses came about, and take the required action to improve the functioning of health provision in Chiapas. It falls to them to compensate people who have suffered as a result of previous rights abuses and to enable the realization of human rights for the people of Chiapas. It is also the responsibility of the international community, including the other members of the OECD, to hold Mexico to its human rights obligations. Ignoring the rights abuses in Mexico undermines one of the most important social developments of our times – universal human rights declarations. This article is an example of the practical application of human rights in relation to health, and we encourage other groups and organizations to look at issues from this angle. For more information please see ccesc-chiapas@blogspot.com, or email observatoriosalud@gmail.com with information about other organizations using a similar approach.

Keir Philip is a fourth year student at the University of Sheffield in the UK
mda05kep@sheffield.ac.uk

The author would like to acknowledge the help of Marcos Arana, his supervisor during his time in Mexico, in the writing of this paper

Acromyms

CCESC-DDS – Centro de Capacitación en Ecología y Salud para Campesinos-Defensoría del Derecho a la Salud (Center for Training in Ecology and Health for Rural workers- Right to Health Defence Group)

ECOSUR – El Colegio de la Frontera Sur (The College of the Southern Border, an academic research institution)

OECD – Organisation for Economic Co-Operation and Development

WHO – World Health Organisation

References

(1) World Bank accessed 15.01.2009 http://web.worldbank.org/WBSITE/EXTERNAL/COUNTRIES/LACEXT/MEXICOEXTN/0,,contentMDK:20185184~menuPK:338403~pagePK:1497618~piPK:217854~theSitePK:338397,00.html

(2) UNDP accessed 15.09.2009 http://hdrstats.undp.org/en/countries/country_fact_sheets/cty_fs_MEX.html

(3) OECD 2009. Economic Survey of Mexico 2009Accessed 15.09.2009 at http://www.oecd.org/documen/53/0,3343,en_33873108_33873610_43393781_1_1_1_1,00.html

(4) INEGI, II conteo de Población y Vivienda 2005

(5) PHR (2006). Excluded People, Eroded Communities: Realizing the Right to Health in Chiapas, Mexico accessed 15.09.2009 at http://physiciansforhumanrights.org/library/report-excludedpeople-2006.html

(6) Loranzo R, Zurita B, Franco F, et al (2001). Mexico: Marginality, Need, and Resource Allocation at the Country level. In: Evens T, Whitehead M, Diderichsen F, Bhuiya A, Wirth M (eds). Challenging Inequalities in Health: From Ethics to Action. New York: Oxford University Press. 290-291

(7) Secretaría de Salud 2009 accessed 15.09.2009 at http://www.salud.df.gob.mx/ssdf/index2.php?option=com_content&do_pdf=1&id=673

(8) Nájera-Ortiz JC, Sánchez-Pérez HJ, et al (2008). Demographic, health services and socio-economic factors associated with pulmonary tuberculosis mortality in Los Altos Region of Chiapas, Mexico. International Journal of Epidemiology. 37(4): 786-795

(9) Bruce N, Perez-Padilla R, Albalak R, (2000). Indoor air pollution in developing countries: a major environmental and public health Challenger. Bull World Health Organ. vol.78 no.9 Genebra 2000

(10) NOM-006-SSA2-1993. NORMA OFICIAL MEXICANA NOM-006-SSA2-1993, PARA LA PREVENCION Y CONTROL DE LA TUBERCULOSIS EN LA ATENCION PRIMARIA A LA SALUD. – 26/01/1995 accessed on 19.09.2009 at http://info4.juridicas.unam.mx/ijure/nrm/1/252/default.htm?s=iste

(11) WHO 2005. Global Tuberculosis Control: Surveillance, Planning, Financing. WHO Report 2005 (WHO/HTM/TB/2005.49). Geneva: World Health Organization, 2005.

(12) El Financiero en Linea. Viernes 7 de agosto 2009 accessed 15.09.09 at http://www.elfinanciero.com.mx/ElFinanciero/Portal/cfpages/contentmgr.cfm?docId=207758&docTipo=1&orderby=docid&sortby=ASC

(13) Maartens G, Wilkinson R, (2007). Tuberculosis. The Lancet; 370: 2030-43 Published on line August 23, 2007 at http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61262-8/fulltext

The radication of polio – A successful story (almost) and where we went wrong

Thursday, January 28th, 2010

Introduction

Poliomyelitis is an acute viral infection caused by RNA virus of the family picornaviridae (1). It is primarily infection of the alimentary tract but may affect the CNS and in about 1% of cases may lead to paralysis and death (2). It usually affects children less than 5 years of age. Poliomyelitis was known to occur in pre-historic times and was seen in Egyptian mummies and paintings dating 3700 BC (3).

There are 3 serotypes of the wild polio virus – 1, 2, and 3 (3). Of all cases between January 2007 and June 2008, serotype 1 and 3 were detected in fecal samples of the AFP cases. No cases ascribed to serotype 2 has been detected anywhere in the world since 1999 (4,7).

Risk Assessment and Problem Statement

In the pre-vaccination era polio ravaged all countries of the world and no region was free of it. Since 1954, the vaccines were used extensively ushering in the vaccination era (5). This era in time saw implementation of some landmark eradication strategies. These measures on a global level helped in eliminating the disease from countries which successfully implemented their health policies. The polio endemic countries as of August 2008 were India, Afghanistan, Pakistan and Nigeria (6). Twenty five other countries reported cases of imported virus which were genetically traced back to those found in India or Nigeria (6).

During 2007, a total of 1,387 (1,315 were Wild Polio Viruses) confirmed cases were reported whereas in 2008 up to the month of November, a total of 1,449 WPV cases were recorded, worldwide (7). In India, while 874 cases were recoded in 2007, the number dropped to 532 in the year of 2008 upto the month of November. The majority of these cases hail from the states of UP and Bihar (7). It is obvious the situation has reached a stalemate with the number of new cases almost constant for some years and in some countries polio has even managed to stage a comeback, such as seen in the strife-torn Nigeria (9).

The Logic Behind Polio Eradication

Poliomyelitis was believed to be eradicable because man is the only host and a long term carrier state is not known to occur. The poliovirus is also relatively easy to detect because it causes a distinct, although not diagnostic, clinical entity—namely acute flaccid paralysis (AFP)— it is readily identifiable as a causative agent of the disease by simple laboratory tests, and, most importantly, it is easily controlled in endemic and epidemic situations by a widely available and affordable vaccine that leads to lifelong immunity (8). The vaccine is ideally suited for eradication programs as it interrupts the transmission of the WPV by multiplying the in the intestine. It mimics the natural history of infection of the WPV and can also be transmitted through a recently vaccinated child to close contacts around him who are not immunized. The half life of the excreted virus is 48 hours in the sewage and spread can occur in that period.

After the initial euphoria of success with the smallpox eradication, polio became the next logical vaccine-preventable disease to be targeted for eradication – both because of the morbidity caused by the disease and the theoretical eradication potential of the vaccine. Launched in October 1988 by the 41st World Health Assembly (WHA Resolution 41.28), the Global Polio Eradication Initiative aimed to eradicate poliomyelitis from the planet by the year 2000. It is the largest international public health initiative ever undertaken, costing several billion dollars and immunizing billions of children worldwide. It has also been mired in controversy almost since its outset (9).

The initial target date, 2000, unfortunately came and went without eradication in sight. So too did the next scheduled date of 2005 (a target set by Rotary International, the most important non-governmental supporter of the Global Polio Eradication Initiative). As yet no future target date has been set (9).

What is Being Done? – The WHO and Indian Perspective

The Global Polio Eradication Initiative has been spearheaded by the World Health Organization (WHO), Rotary International, and the US Centers for Disease Control and Prevention (CDC) and UNICEF and it aimed at polio eradication by 2000 (6).

There are four core strategies to stop transmission of the wild poliovirus in areas that are affected by the disease or considered at high risk of re-infection (6):

1. High infant immunization coverage with four doses of oral poliovirus vaccine (OPV) in the first year of life.

2. Supplementary doses of OPV to all children under five years of age during Pulse Polio Sessions.

3. Surveillance for wild poliovirus through reporting and laboratory testing of all acute flaccid paralysis (AFP) cases among children under fifteen years of age.

4. Targeted “mop-up” campaigns once wild poliovirus transmission is limited to a specific focal area.

The strategy, as with smallpox, aims to achieve maximum vaccine coverage to terminate the circulation of the virus in the population coupled with a reliable surveillance tool for the detection of remaining pockets of virus circulation and to monitor progress. Herd immunity is achieved with high routine vaccine coverage (at least 90% for all 3 doses) (10).

This primary strategy is supported by mass immunization programmes (immunising all infants less than 5 years of age independently of the routine immunisation programme on a single day or few days) – this is known as the Pulse Polio Programme in India (11). Most endemic regions and countries follow the MIPs with Mop Up programmes which locate all the cases missed during the MIP rounds. The viral spread is measured in terms of the Acute Flaccid Paralysis Rate in children less than 15 years of age. In the eventuality of a case detection, the index case is surrounded with an immunization ring to restrict the spread of the wild virus (12).

Surveillance forms a major component of the eradication campaign. A laboratory network co-ordinated by the WHO and consisting of over 125 laboratories throughout the world has been established, and is organized in three levels–national laboratories for virus isolation and preliminary characterization, regional reference laboratories for confirmation and more specialized testing and specialist laboratories (12).

Why are These Measures Unsuccessful?

While it is a general consensus that the apparent plateau in the eradication campaign is multifactorial in causation, it is a known fact that different factors are of relative importance in different countries. Arguably, one of the most important pull downs is campaign fatigue that has set into the GPEI’s implementation. This is almost universal in all the endemic nations, especially India and Nigeria (9).

In Pakistan, it as been attributed to outright refusal by parents and shortage of female health workers. The situation is made worse by the security situation in some regions such as the Swat valley where the vaccinators are not able to even reach. These conflict ridden areas are reporting an increasing number of new polio cases (13).

In a calamitous setback in mid-2003, Nigeria’s northern states halted the vaccination campaign for a year after politically fuelled rumors swept the region that the vaccine contained the AIDS virus or was part of a Western plot to sterilize Muslim girls. Within a couple of years, 18 once polio-free countries have had outbreaks traceable to Nigeria. Though most have since been tamed, Indonesia and Nigeria itself remain major worries (14,15).

The situation is similarly bleak in India, a country which is tantalizingly close to eradicating the disease. The enormous population load, dense living conditions, an inadequate public health sector and illiteracy have acted as the banes of the eradication drive. Health workers have repeatedly reported being turned away from homes by mothers who felt that the government was not doing enough for their children (14). On the other hand, Afghanistan continued to suffer from the disease’s march during the recent war on its soil, with civic amenities and health services falling to a dismal low. Ongoing conflicts have had a major impact on the polio eradication in the endemic countries, with immunization teams being hampered from reaching out. In a number of situations the vaccines have been spoilt, whole stocks in total because of the improper storage facilities.

The situation in the Uttar Pradesh state in India has worsened in recent time mainly because of the falling vaccination cover and in Bihar because of increasing parental resistance. This has been noticed despite exemplary efforts on part of the government and the local authorities to step up the campaign (16). Even more problematic here has been the difficulty in achieving successful immunisation, despite multiple rounds of vaccination, because of very high population density, crowding and high levels of diarrhoeal disease interfering with the immunogenicity of the oral polio vaccine (17).

In recent times, probably the most worrying of all problems in polio control has been the poor migration control between endemic and non endemic regions. The stark example was the reporting of a case of polio from Karnataka state in India, which had reported no case of the disease in nearly three years. The case was traced back to a contact in Uttar Pradesh state putting in the spotlight on as to how important it is to have proper migration controls in place.

Finally, in contrast to smallpox, what complicates polio eradication is the much greater difficulty in recognition of infection despite the occurence of AFP. The great majority (>99%) of infections are asymptomatic, greatly complicating surveillance and monitoring (9).

New Indian Initiatives

Even though efforts for eradication has been given up with respect to most diseases (19), especially tuberculosis and leprosy, the goal of the National Polio Surveillance Project, India, stays firmly on the lines of the international Polio Eradication Initiative – and that is to completely eradicate polio so that “no child will ever again know the crippling effects of polio.”(18).

The collaboration has set the following goals to make sure that the eradication drive succeeds (20):

1. Maintaining the Acute Flaccid Paralysis detection target at >1 case per 100,000 population.

2. Maintaining the completeness and time accountability of the AFP reports impeccably at 90% and 80% respectively.

3. Investigating the reported AFP cases within 48 hours in >80% cases.

4. Collection of stool samples from reported cases in < 14 days in more than 80% cases.

5. Follow-up exam of the reported cases at least 60 days after paralysis onset to verify the presence of residual paralysis or weakness (Target > 80%).

6. Confirming the arrival of specimens at the national laboratory < 3 days of being sent (Target > 80%)

7. Confirming the specimens arriving at the laboratory in “good condition” (Target > 80%)

These measures are in addition of the four main ones defined earlier.

Conclusion

A lot has changed since the world leaders in health decided to eradicate Poliomyelitis from the world. The achievable target was pushed back out of reach due to a number of practical problems. With the Polio Eradication Initiative working at full swing in the nations with the residual polio cases, the eradication of this debilating disease is not far away but a few challenges remain to be overcome before this can occur.

Viren Kaul is a TLS RA and final year student at Sir Ganga Ram Hospital in Delhi, India
Vindhya Palled is a medical student at the Karnataka Institute of Medical Sciences in Hubli, India
Jishu Kaul is a medical student at Dayanand Medical College in Ludhiana, India
jishuviren(at)gmail.com

References

1. Wikipedia – Poliovirus: http://en.wikipedia.org/wiki/Poliovirus

2. Encyclopedia Britannica: http://www.britannica.com/EBchecked/topic/467378/polio

3. eMedicine – Poliomyelitis, S Vidyadhara et al – http://emedicine.medscape.com/article/1259213-overview

4. Park and Park text book of preventive and social medicine – Bhanot publications.

5. Wikipedia – Polio Vaccine: http://en.wikipedia.org/wiki/Polio_vaccine

6. WHO: Programmes and Projects: Media Center: Poliomyelitis: http://www.who.int/mediacentre/factsheets/fs114/en/index.html

7. WHO annual bulletins 2007 and 2008.

8. The Lancet Infectious Diseases, doi:10.1016/S1473-3099(04)00999-5.

9. Eradication of disease – the case study of polio, South African Medical Journal, Nov 2007, Barry D. Schoub. (http://findarticles.com/p/articles/mi_6869/is_11_97/ai_n28533884/)

10. Data courtesy: GPEI. (http://www.polioeradication.org/content/fixed/national.shtml)

11. Pulse Polio Immunization Campaign, Government of India (http://www.health.mp.gov.in/ppip.HTM)

12. National Polio Surveillance Project, a Government of India and WHO collaboration. (http://www.npspindia.org/Surveillance%20Strategy.asp)

13. OneWorld South Asia – Insecurity hampering polio eradication in Pakistan – October 10th, 2008. (http://southasia.oneworld.net/todaysheadlines/insecurity-hampering-polio-eradication-in-pakistan)

14. The New York Times – Rumor, Fear and Fatigue Hinder Final Push to End Polio – March 20th, 2006. (http://www.nytimes.com/2006/03/20/international/asia/20polio.html?pagewanted=print)

15. Jegede AS. What led to the Nigerian boycott of the polio vaccination campaign? PLoS Medicine 2007; 4: 0001-0006.

16. Wild poliovirus weekly update. Global Polio Eradication Initiative. 30 May 2007. http:// www.polioeradication.org/casecount.asp (last accessed 4 June 2007).

17. John TJ, Shah NK, Thacker N. Indian Academy of Pediatrics and Polio Eradication in India. Indian Pediatr 2006; 43: 765-768.

18. National Polio Surveillance Project – A government of India – WHO collaboration – http://www.npspindia.org/index.asp

19. http://www.sciencemag.org/cgi/content/full/312/5775/852

20. NPSP, India – http://www.npspindia.org/WHO%20indicators.asp – Eradication targets.

“Where Words Come out From the Depths of Truth…”

Thursday, December 24th, 2009

The Nobel Laureate Rabindranath Tagore wrote in his collection of song offerings to the almighty, GeetanjaliAs we go into the depths of truth we realize the magnitude of injustice in this world“. A fine example of this injustice is the disease Tuberculosis, which though a fully treatable disease has attained the status of an epidemic in India and other developing countries.

Introduction

Tuberculosis is an airborne infectious disease caused by the bacteria Mycobacterium tuberculosis. Droplets and droplet nuclei containing bacteria spread into the air when a person with active TB disease of the lungs breathes, coughs, sneezes, speaks or sings. Every person with TB bacteria in the lungs (sputum-positive case) has the potential to infect others. Tuberculosis can also affect other body parts such as pelvic organs, intestines, meninges and lymph nodes.

Mycobacterium tuberculosis can survive within the human body for many years. Incubation period of the disease therefore varies from few weeks to several years. The disease occurs when the body’s resistance is sufficiently lowered. Malnutrition is one of the major causes leading to low body resistance. Unsanitary, overcrowded conditions, lack of education, poor quality of life, population explosion, global travel, all these also predispose to infection. Infection with HIV/AIDS is another reason for TB infection setting in.

Symptoms of TB include chronic cough, presence of blood in sputum, unexplained fever and unexpected weight-loss. If any of the above mentioned are seen then the patient should undertake the sputum test. The sputum smear is a cost effective and simple test. It can be easily done free of cost in all Government Designated Microscopy centres. A sputum positive patient is one who is coughing up the bacteria in his sputum. This is responsible for the rapid spread of the disease in the community. An average TB patient, if untreated can infect 12 others (1). Thus, to prevent the rise in the number of patients, all contacts of an identified patient should be screened and tested for the disease. TB is one of the major causes of loss of human life, infertility, loss of productivity and social stigma, especially against women and children.

The Problem

Overall, one-third of the world’s population is currently infected with the TB bacillus. 5-10% of people who are infected with TB bacilli become sick or infectious at some time during their lifetime and historically, tuberculosis has been one of the world’s biggest killers.

Globally, there were an estimated 9.27 million incident cases of TB in 1997 (2). Most of the estimated cases in 2007 were in Asia (55%) and Africa (31%) (2). Tuberculosis has been nearly eliminated from the developed world, and the prevalence rates have dropped drastically (3). At the same time, Asia and Africa share 86% of the case burden from the disease. It is estimated that within the next 10 years, 300 million people will become infected by TB. Nearly one third of over 11,000 business leaders from all over the world expect tuberculosis to affect their business in the next 5 years, and one out of ten expect the effect to be serious (4). Keeping all these facts in mind, we can no longer afford to have tubular vision, only when we have accepted the enormity of the problem that we can we work towards a reasonable solution

TB in India

One fourth of all TB patients are in India, making it the country with the highest TB burden in the world. More than 1,000 people die every day, almost 400,000 each year (5). TB is also the biggest killer of people in the productive age group i.e. 15-49 years. Recovery takes 3 to 4 months, but very often, the poor lose their jobs because of the social stigma against the disease, and the loss of wages has disastrous consequences to entire families. The loss to Indian economy is US$ 300 million in direct costs, and US$ 3 billion in indirect costs (1). The prevalence of infection in India (as judged by the standard tuberculin test) is about 30% (6). The prevalence of bacteriological confirmed disease was 4 per 1000, and the incidence of new cases was about 1.5 per 1000 (7).
There is horrifying discrimination against TB patients. Every year 100,000 women suffering from TB are expelled from their families to die of disease and starvation, and 300,000 children are thrown out of school (8) because of TB or forced to leave school because a wage earning parent has TB. One important reason for the failure of TB eradication is the social problems associated with the disease, which has existed since times immemorial. Centuries ago, TB was considered as a curse of the gods and any patient was treated like an outcast. But even in today’s era of science and technology the situation has not improved; we still seem to be living in the dark ages. Discrimination against women of all ages continues. In many families an infected girl child is not treated at all, instead is left to die. People are forced to leave their jobs if their employers get knowledge of their condition. All these myths and taboos need to be dispelled and TB shown to be a common bacterial infection like many others so the patient can be treated with magnanimity, compassion and love by friends, family and society.

HIV and TB

HIV and TB form a lethal combination, each speeding the other’s progress. HIV weakens the immune system. Someone who is HIV-positive and infected with TB bacilli is many times more likely to become sick with TB than someone infected with TB bacilli who is HIV-negative. TB is a leading cause of death amongst people who are HIV-positive. In Africa, HIV is the single most important factor contributing to the increase in incidence of TB since 1990.

The DOTS Programme

Control means reduction in the prevalence and incidence of disease in the community. The WHO definition of control is when the prevalence of infection is less than 1% in the age 0-14 years. In the absence of a reliable vaccine, the most powerful weapon to achieve this is active case finding and treatment (10).

Treatment of tuberculosis has been standardised by the WHO promoted programme called DOTS (Directly Observed Therapy Short-course), launched in 2006. DOTS has been proved to be the most successful and cost-effective method of TB treatment and has succeeded in markedly decreasing the prevalence of the disease from the world. DOTS is a 6 month therapy in which a patient needs to take the medication 60 times in a appointed DOTS centre in the presence of a volunteer or a semi-trained professional. The medicines are not given for home consumption. This is because people are either careless, or fear the disclosure of their condition and hence stop taking the medicines on a regular basis. Default can lead to MDR (Multi Drug Resistant) TB, the treatment of which is expensive and not easily accessible. DOTS-plus for MDR is not universally available, actually the first step in controlling MDR-TB is prevention by full implementation of DOTS, in order to combat an emerging epidemic. Effective DOTS program is the prerequisite for implementation of DOTS-plus (11). Each patient of MDR infects 12 others with MDR, this has led to the very real fear of an MDR epidemic.

DOTS has been shown to be effective in many situations across the world but the main reason for its success was effective planning and implementation. India launched its DOTS program in 1997 and to date more than 97% of the country has DOTS coverage.

Community Approach

We recently started getting involved with Operation ASHA which is one of the largest Non-Governmental Organizations working for TB control and treatment. It is currently serving a population of 2,000,000 slum dwellers in urban India, operating in 10 cities in 5 states: Delhi, Punjab, UP, Rajasthan and Haryana. Operation ASHA has perfected a low cost, patient-friendly, replicable model, which can be effectively utilized in other parts of the world (http://s01.opasha.org/).

“Tuberculosis is a scar on the face of Earth,” says Dr. Shelly Batra, MD, the Founder-President of Operation ASHA. She is a renowned gynaecological surgeon working with a major hospital in Delhi. For two decades she has operated on needy patients free of cost and worked pro-bono for patient education.

“Three years back we decided to focus on one public health problem where the need is immense,’ says Dr. Batra, “and we decided on TB as our focus. TB elimination is one of the millennium development goals of the United Nations (12), thus WHO and major international agencies are providing tremendous support by way of free diagnostics and medicines, which constitute eighty percent of our costs. Our cost leverage is 25 times. We spend only 15 dollars to treat a patient, because medicines, which constitute $310, and public facilities worth another $50 are provided free by the government. This makes sure that the donor’s money produces maximum results because of our highly cost effective and result oriented programme.”

Operation ASHA’s aim is to provide TB treatment at a time and place convenient to patients, at centers located deep in the urban slums. In the WHO’s DOTS program, patients need to visit a treatment center about 70 times over a seven month period. Therefore accessibility of DOTS centers is a key issue. The government of India’s Revised National TB Control Programme (RNTCP) provides adequate facilities by way of public hospitals, physicians, diagnostics like sputum testing centres, and there are more than adequate amounts of ATT medicines available in the warehouses of public hospitals. What are lacking are adequate DOTs centres, for which the government is inviting and encouraging public-private partnerships. Right now, there is a high rate of default or missing doses, partly because the DOTS centers (from which medication has to be taken) are few and far between, and open at inconvenient times. It has been found in one study that the distance and travel costs to a TB service center were the factors associated with delay in seeking diagnosis of tuberculosis (13). A large number of TB patients belong to the marginalized section of society, who cannot afford to let their family starve for the sake of medication.

Operation ASHA has solved the problem by establishing a critical network of centers, embedded deep in the urban slums, that increases the accessibility of the drugs and other facilities for the patients. TB treatment has been made available at the doorsteps of the slum dwellers. Moreover, these centers are open early in the morning or late at night, so patients can carry on with their day to day activities and get their treatment at a time that does not make them lose their daily wages. Operation ASHA has involved the community for delivering DOTS, and has enrolled providers and counsellors, all of whom belong to the community they serve.

DOTS centers are manned by providers, who, while carrying out their daily business, also provide TB treatment to patients. Providers provide the space for running a DOTS centres in their premises. Centres have been opened in temples, small shops, phone booths, religious centers and high traffic areas such as bus stops and entrances to slums. Anyone who wishes to serve the community, can become a DOTS provider. A DOTS provider is trained by the Operation ASHA staff. A simple 2 hours training is all that is needed. Providers are offered basic remuneration, and are the part time employees of the organization. To make sure the providers stay focused and sincere, the system has been designed in such a way that their regular business does not suffer. The providers are paid an incentive- based salary, which is approximately 25% of their monthly earnings. Their status in the society is enhanced considerably because they are treated like doctors who are curing people of a deadly disease. Moreover, there are economic benefits to those engaged in business because of increase of visits to their establishments.

All that is needed to open a DOTS center is the space of about 5 sq feet, in which to keep a rack containing the individually labelled boxes of medicines, and also a water jug, weighing machine, disposable glasses for water, patients cards given by the RNTCP and colour coded boxes containing OTC drugs to treat fever, acidity and vomiting. Most patients come to DOTS centres early morning, this includes workers, women, and school children. Factory workers doing evening shifts come in the evening after work. All a provider has to do, when a patient comes, is to identify the patients’ box of medicine, make the patient swallow it in his presence, and put a tick on the card. The OTC drugs are there not only to treat side effects of the disease, they are given to anyone in the community who needs them, thus everyone, not only TB patients, are encouraged to visit the center, which is recognised as a community health center, not a just TB treatment center. This is helps reduce the stigma against TB.

For every two centers, Operation ASHA has one full time counsellor who has many responsibilities. Suspected cases are sent by the counsellor to visit the nearest diagnostic facility, where sputum test is performed, and then to the public hospital, where the physician examine the patient, and decides on the medicine. It is the job of the counsellor to get the entire box of 6 months treatment allotted and kept in the DOTS center nearest to the patient’s house. Well before starting treatment, the counsellor has to educate the patient and entire families in order to minimize default. Patients are warned of the dangers of missing the dose and subsequently developing MDR-TB. The patients’ families are persuaded to treat the person with kindness and compassion.

The counsellor has to spend 4 hours in the DOTS center every morning, when there are the most patients, and help the provider in giving the medicine. At this time, patients’ questions are answered and doubts are cleared. The counsellors also carry out daily checks to see if any patients have missed a dose. In case of a patient skipping a dose, they trace the patient to his house and repeat the counselling in front of the patient’s entire family to bring him back into the system. The counsellors are chosen from the community they serve so that they are familiar with the patients and their families, and can trace patients to their houses in areas where there are small huts, and no house number or road number for identification. Because of this intensive counseling, Operation ASHA’s default rate is less than 2%, by far the best in the world.

Counsellors also visit five families in their geographical area on a daily basis. They go door to door and educate people about the symptoms of TB, thus they are carrying out active case finding. They also conduct fortnightly camps, which are attended by about 50 to 100 slum dwellers, where again patients are educated about TB and encouraged to come forward for testing. With all this, the detection rate has gone up by 78% in South Delhi region. The counsellors are chosen with great care – they need to have a high school diploma and are made to undergo 4-6 weeks of training at the NGO’s Delhi office, after which they have to pass a written test and a mock counselling session. Only then are they recruited and sent into the field. The counsellors get an incentive based salary where incentives are given both for zero default and for finding new cases in the community.

“TB is not just a disease, it is a socio-economic issue,” declares Dr. Shelly Batra. “TB treatment has great economic benefits. It can safely be said that TB treatment leads to improved productivity, economic upliftment and empowerment of women and children and societies as a whole.”

At top management level this organization has senior doctors, businessmen and bureaucrats who raise funds to support the work by collecting donations and organizing sales and auctions of Indian handicrafts in India and the US.

Having scripted one of the best treatment fights in the world, Operation ASHA enjoys patronage from some of the best academicians, institutes, and governments of the world. We were taken around on a tour of the facilities and the set-up is exemplary in its organization. It was a pleasure getting to see how a small step became a highly successful venture with path-breaking results, which have been lauded by the Government of India, and many other world bodies. This year, Operation ASHA has been elected on the board of Stop-TB partnership, a partnership housed by the WHO, to represent the NGOs of the developing world.

Thus we can conclude by saying that this burning issue needs to be tackled on a war footing and needs a “hammer and tongs” approach. We can make an impact only if we can treat a large number of patients simultaneously. DOTS expansion and providing flexi-DOTS are the need of the hour. This, in the present scenario, seems the best approach for eradication.

Rimi’s Story

Before finishing, we would like to recount a patient’s narrative:

One of Operation ASHA’s patients is a 12 year old girl, Rimi. She lives in the slums of Delhi, and had been unable to go to school for more than a month because of constant chest pain and low grade fever. Her father had suffered from tuberculosis of the lungs, and had been treated successfully about a year before in a government hospital. Since he had suffered the disease himself, he was naturally concerned about his daughter’s recent symptoms. He met with the volunteers of Operation ASHA who took Rimi into their care and started her on treatment.

Rimi takes her medicines from Operation ASHA’s local DOTS provider, who lives about ten yards from her house. She visits the treatment centre early in the morning, and hence she doesn’t need to miss even a single day of school.

Rimi now feels fit and fine. The fever has left her, so has the chest pain. She is living a normal life, going to school and playing with other children. Once a fortnight her parents reward her by taking her to the cinema or buying her an ice-cream. She is happy and optimistic about the future.

“When I finish school, I want to train to be a nurse,” she declares. “Then I want to work with Operation ASHA, so that I can help others, just as you have helped me.”

If Rimi can help, so can all of us. Operation ASHA spends an unbelievably low amount to treat a TB patient and give them back their life of dignity and self respect. It made us think that for little more than a price of a meal, a life was being saved at these centers. A little introspection is all that is needed, and each one of us can contribute to this cause. While carrying on our day to day jobs and earning a living, we could simultaneously devote some of our time to community work, and that will make all the difference. After all it’s not just the fight of those suffering from the disease but of all of us. If TB is to be eradicated, it will take more than just a few guidelines. It needs all of us to take care of our brethren, to go above the red tape and the constant excuses, and replace jargon with concrete actions. Once all of us decide to do our part, just as the members of Operation ASHA have done, it will not be long before TB control becomes a reality.

Radhika Batra is a first year medical student at Santosh Medical College and Viren Kaul is a Lancet Student Regional Advisor and an intern at the Sir Ganga Ram Hospital in Delhi in India.
radhikabatra15(at)yahoo.com
jishuviren(at)gmail.com

References

1. Govt of India (2006). TB India 2006, RNTCP Status report. DOTS for all- All for DOTS, Ministry of Health and Family Welfare, New Delhi

2. WHO Global TB Report 2009. WHO/HTM/TB/2009.411

3. Bennett D. E. et al, Am J Respir Crit Care Med. 2008 Feb

4. Tackling Tuberculosis; a Business Response, Feb 2008, World Economic Forum

5. Govt of India (2006). Annual report 2005-2006, Ministery of Health a Family Welfare, New Delhi

6. National Tuberculosis Institute, Bangalore(1974)Bull WHO, WHO 51:473-487

7. WHO (2000) Joint Tuberculosis Program Review, India, Feb 2000, Regional Office for South East Asia, New Delhi

8. TB India 2008, Ministry of Health and Family Welfare, Government of India, March 2008

9. WHO (2000) Research for Action, Understanding and Controlling Tuberculosis in India

10. WHO (1982) Tech.Rep. Ser.No.671

11. WHO (2004) – TB/HIV- A clinical manual, 2nd edition

12. WHO(2003) World Health Report 2003, Shaping the future

13. Saly S, Onozaki I, Ishikawa N., 2006, “Decentralized DOTS shortens delay to TB treatment significantly in Cambodia ”, Kekkaku, 2006 Jul;81(7):467-74