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
Human African trypanosomiasis
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 . Not only do they cause significant morbidity, but the socioeconomic burden of these conditions is high . 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 , while experts predict that average temperature could further increase by 2100 by between 1.4 and 5.8°C . 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 . 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 . Similarly, Onchocerca volvulus is transmitted by the black fly, which breeds near bodies of water. Peak biting density is observed during the wet season , indicating that we should expect to see an increase in the density of transmission of certain NTDs during extreme rainfall.
Conversely, there is evidence to suggest that climate change may actually reduce transmission of NTDs in some regions. Heavy rainfall can reduce mosquito populations by flushing larvae from their habitat . This is significant because evidence shows that in areas where rainfall has increased, there has been a disproportionate increase in extreme downpours . Furthermore, warming above 34°C generally has a detrimental impact upon vectors and parasites . However, vectors such as mosquitoes are diverse in terms of preferred conditions, ensuring that some variety of parasitic disease is ubiquitous [6, 11]. Moreover, minimum temperatures have been increasing more rapidly than maximum temperatures , therefore it is likely that the rate at which temperatures in cooler regions become suitable for vectors will exceed the rate at which temperatures in presently suitable regions become unsuitably hot for vectors.
Ecological change Ecological modifications have been recognised as major threats to the emergence and re-emergence of infectious diseases [6, 11], because they facilitate the breeding of vectors and transmission of parasites. A recent study  conducted in Côte d’Ivoire noted that the areas within a few kilometres of hydro-agricultural dams and irrigated rice fields in contained the country’s highest prevalence of Buruli ulcer. Assuming that confounding factors have little part to play, the continuing development of hydrological systems to advance agriculture may bring about an increase in Buruli ulcer prevalence, if control measures are not put in place.
Deforestation is carried out for a variety of reasons; these include road-building, human re-settlement and farming. Road-building enables non-immune populations, including loggers, construction workers and tourists, to come into contact with indigenous parasites against which they have no immunity, thereby becoming a reservoir for NTDS and facilitating their transmission . Additionally, growth of the fox population following deforestation in Latin America has attracted more sandflies to the area, which has increased the transmission of leishmaniasis . Deforestation advanced exponentially during the twentieth century, with an estimated 2-3% of forests being destroyed each year worldwide . Given the association with exploding vector and parasite populations, this constitutes a significant threat to the control of NTDs.
Population growth The world population is projected to increase from the present figure of 6.8 billion to beyond 9 billion by 2050 . This threatens the control of NTDs because it creates conditions which are conducive to transmission of infectious disease , as well as increasing the number of people who are at risk of contracting NTDs. Fertility rates remain highest in poor rural areas of developing countries  which already carry the bulk of the disease burden attributable to NTDs, therefore the impact of population growth will be amplified here. This impact is mediated through a number of factors. For example, developing countries whose health systems are already stretched beyond capacity will be unable to scale up efforts to prevent and treat disease . Secondly, healthcare demand for high-mortality diseases such as tuberculosis is likely to increase in the wake of population growth, secondary to overcrowding . Efforts to control NTDs are therefore at risk of being pushed further down the agenda. Thirdly, environmental degradation secondary to population growth has been shown to increase transmission of NTDs , as discussed previously.
Population growth is an important driving force behind migration and outbreaks of civil conflict , which, themselves exacerbate the burden of NTDs. Migration may be forced as a result of conflict; an increasing number of Burmese refugees are moving to Thailand’s urban centres in search of work. One species of mosquito, Culex cinquefasciatus, is capable of transmitting Wuchereria bancrofti (lymphatic filariasis) and is rife in urban Thailand, raising the possibility of re-emergence of filariasis in areas where it has previously been eradicated .
Urbanization secondary to population growth may increase the transmission of NTDs because of cross-country spread of parasites and the favourable conditions for transmission which ensue in cities. A projected rise in urbanization from 45% in 1995 to 61% by 2030  threatens to increase the burden of NTDs, in particular because much of this will occur in developing countries where the populations of unsanitary townships will swell disproportionately. Dengue is of particular concern here because dense habitation and more pools of stagnant water (in car tyres and disused containers) provide additional opportunities for Aedes Aegypti mosquitoes to breed and bite . Similarly, poor hygiene and overcrowding are conducive to the transmission of Chlamydia trachomatis (trachoma), a leading cause of blindness throughout the developing world . Urbanization is closely and positively correlated to HIV prevalence , thereby facilitating the spread of NTDs by increasing the immunocompromised population . Lastly, urban growth diverts public spending and resources away from rural areas  therefore those suffering from NTDs who remain outside the cities are denied the healthcare they require to manage their condition.
Drug resistance This is a major obstacle to control programmes for infectious diseases . Although NTDs are more biologically stable than malaria and HIV , this is especially important because control relies largely on vector control and pharmacotherapy to which resistance has begun to emerge . Moreover, the reliance on a single drug for treatment of diseases such as onchocerciasis broadens the potential for resistance to develop . There are few known efficacious second-line drugs which can be used if resistant strains do emerge , and relatively few replacements being developed , limiting the scope for total eradication of the NTDs and allowing for their re-emergence in areas in which prevalence had been reduced.
It is now widely acknowledged that drug resistant strains of leishmaniasis and trypanosomiasis exist . Additionally, hookworm infection and schistosomiasis have been flagged as parasites which are developing resistance to current treatments, despite their sensitivity to more than one drug . This poses dilemmas for public health policy makers. For example, regular de-worming is the recommended practice to prevent helminth infection , however, widespread resistance has developed among soil-transmitted helminths in livestock following frequent de-worming [24, 25], raising the concern that a similar pattern may emerge among humans. The efficacy of mebendazole is reported to be declining; a recent double-blind randomized controlled trial  demonstrated that single dose mebendazole (Phardazone®) has a cure rate which is only 5% greater than placebo for the treatment of hookworm in rural Vietnam. This is significant because the ‘Partners for Parasite Control’ programme currently being rolled out across Vietnam uses Phardazone® as the mainstay of treatment .
In addition, drug efficacy can vary geographically. The effectiveness of albendazole for the treatment of trichuriasis has been shown to be lower in Asia than in Africa and the Americas , therefore it is vital that treatment is tested locally for resistance before being introduced across the region .
Conclusion A recent report from WHO  oozes optimism regarding the potential for better control of NTDs, and yet acknowledges that the aforementioned factors are a serious hindrance to progress. In addition, poverty, poor access to essential medicines and lack of political will have long been recognised as exacerbating factors, and unrealised confounding factors may have a greater influence than we suspect. Halting these threats requires unanimous and devoted international cooperation; integration [1, 2, 3] and expansion  of current policies and partnerships alongside health systems strengthening  in endemic countries would be an excellent place to start.
Want to know more about NTDs? Check out the WHO report here
- Hotez PJ, Molyneux DH, Fenwick A. Control of Neglected Tropical Diseases. N Eng J Med 2007; 357:1018-27.
- Leise B, Rosenberg M, Schratz A. Programmes, partnerships and governance for elimination and control of neglected tropical diseases. Lancet 2010; 375: 67-76.
- Gyapong JO, Gyapong M, Yellu N, Anakwah K, Amofah G, Bockarie M et al. Integration of control of neglected tropical diseases into health-care systems: challenges and opportunities. Lancet 2010; 375: 160-65.
- IPCC. Climate Change 2001: The Scientific Basis. Contribution of working group 1 to the third assessment report of the Intergovernmental Panel on Climate Change. Cambridge: Cambridge University Press; 2001. http://www.ipcc.ch/ipccreports/tar/wg1/index.htm (accessed 15/05/10).
- McMichael AJ, Woodruff RE, Hales S. Climate change and human health: present and future risks. Lancet 2006; 367: 859-69.
- Patz JA, Graczyk TK, Geller N, Vittor AY. Effects of environmental change on emerging parasitic diseases. Int J Parisitology 2000; 30: 1395-405.
- Hales S, de Wet N, Maindonald J, Woodward A. Potential effect of population and climate changes on global distribution of dengue fever: an empirical model. Lancet 2002; 360: 830-34.
- Zhou X, Yang G, Yang G, Wang X, Hong Q, Sun L et al. Potential impact of climate change on schistosomiasis transmission in China. Am J Trop Hyg 2008; 78(2): 188-94.
- Kovats RS, Campbell-Lendrum DH, McMichael AJ, Woodward A, Cox J St. H. Early effects of climate change: do they include vector-borne disease? Phil Trans R Soc Lond 2001; 356: 1057-68.
- Githeko AK, Lindsay SW, Confalonieri UE, Patz JA. Climate change and vector-borne diseases: a regional analysis. Bulletin of the World Health Organisation 2000; 78(9): 1136-1143.
- McMichael AJ. Environmental and social influences on emerging infectious diseases: past, present and future. Phil Trans R Soc Lond 2004; 359: 1049-58.
- Brou T, Broutin H, Elguero E, Asse H, Geugan J-F. Landscape diversity related to Buruli ulcer disease in Côte d’Ivoire. PLoS Negl Trop Dis 2008; 2(7): e271.
- Patz JA, Daszak P, Tabor GM, Aguirre AA, Pearl M, Epstein J et al. Unhealthy Landscapes: Policy Recommendations on Land Use Change and Infectious Disease Emergence. Environ Health Perspect 2004; 112: 1092-98.
- United Nations. World Population Prospects: the 2008 Revision (Volume 1). New York: Department of Economic and Social Affairs, Population Division; 2008. http://esa.un.org/unpd/wpp2008/publications/vol_1/FINAL_Vol.1_FULL%20DOCUMENT_Cover_Languages_Chapters_DEM.%20TABLES_MARCH%2011_%202010_PRESS%20QUALITY.pdf (accessed 25/05/10).
- All Party Parliamentary Group on Population, Development and Reproductive Health. Return of the population growth factor: Its impact on the Millennium Development Goals. Report of Hearings by the All Party Parliamentary Group on Population, Development and Reproductive Health; January 2007. http://www.appg-popdevrh.org.uk/Publications/Population%20Hearings/APPG%20Report%20-%20Return%20of%20the%20Population%20Factor.pdf (accessed 24/05/10).
- Pimental D, Cooperstein S, Randell H, Filiberto D, Sorrentino S, Kaye B et al. Ecology of increasing diseases: Population growth and environmental degradation.’ Hum Ecol 2007; 35: 653-68.
- Beyrer B, Villar JC, Suwanvanichkij V, Singh S, Baral SD, Mills EJ. Neglected diseases, civil conflicts and the right to health. Lancet 2007; 370: 619-627.
- Wu P-C, Lay J-G, Guo H-R, Lin C-Y, Lung S-C, Su H-J. Higher temperature and urbanization affect the spatial patterns of dengue fever transmission in subtropical Taiwan. Sci Total Environ 2009; 407(7): 2224-33.
- WHO Department of Control of Neglected Tropical Diseases. Neglected tropical diseases: hidden successes, emerging opportunities. Geneva: WHO; 2009. http://whqlibdoc.who.int/publications/2009/9789241598705_eng.pdf (accessed 21/11/10).
- WHO. Leishmaniasis [webpage]. http://www.who.int/vaccine_research/diseases/vector/en/index3.html (accessed 19/05/10).
- Molyneux DH, Bradley M, Hoerauf A, Kyelem D, Taylor MJ. Mass drug treatment for filariasis and onchocerciasis. Trends Parisitol 2003; 19(11): 516-22.
- Molyneux DH. “Neglected” diseases but unrecognised successes – challenges and opportunities for infectious disease control. Lancet 2004; 364: 380-83.
- Lawrence D. What’s in a name? Drug resistance in helminth parasites. Lancet 2008; 8: 536.
- Flohr C, Tuyen LN, Lewis S, Minh TT, Campbell J, Britton J et al. Low efficacy of mebendazole against hookworm in Vietnam: two randomized controlled trials. Am J Trop Med Hyg 2007; 76(4): 732-36.
- Molyneux DH, Hotez PJ, Fenwick A.”Rapid impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med 2005; 2(11): e336.
- Bennett A, Guyatt H. Reducing intestinal nematode infection: efficacy of albendazole and mebendazole. Parisitol Today 2000; 16: 71-74.
- Conteh L, Engels T, Molyneux DH. Socioeconomic aspects of neglected tropical diseases. Lancet 2010; 375: 239-247.
- WHO & the Carter Center. Integrated control of the neglected tropical diseases: a neglected opportunity ripe for action. Paper jointly prepared by the World Health Organisation and the Carter Centre for presentation to the Global Health and the United Nations meeting. Atlanta, Georgia: the Carter Centre; 2008. http://www.who.int/neglected_diseases/NTD_integrated_control.pdf (accessed 19/05/10).