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This Week in The Lancet

  • Volume 377 1719 (2011)
  • May 21, 2011

Emerging Threats To Controlling Neglected Tropical Diseases

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

Buruli ulcer
Chagas disease
Human African trypanosomiasis
Lymphatic filariasis

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.

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 [5]. This is significant because evidence shows that in areas where rainfall has increased, there has been a disproportionate increase in extreme downpours [9]. Furthermore, warming above 34°C generally has a detrimental impact upon vectors and parasites [10]. 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 [9], 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 [12] 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 [6]. 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 [6]. Deforestation advanced exponentially during the twentieth century, with an estimated 2-3% of forests being destroyed each year worldwide [13]. 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 [14]. This threatens the control of NTDs because it creates conditions which are conducive to transmission of infectious disease [14], 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 [15] 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 [15]. Secondly, healthcare demand for high-mortality diseases such as tuberculosis is likely to increase in the wake of population growth, secondary to overcrowding [16]. 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 [11], as discussed previously.

Population growth is an important driving force behind migration and outbreaks of civil conflict [15], 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 [17].

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 [5] 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 [18]. Similarly, poor hygiene and overcrowding are conducive to the transmission of Chlamydia trachomatis (trachoma), a leading cause of blindness throughout the developing world [19].  Urbanization is closely and positively correlated to HIV prevalence [15], thereby facilitating the spread of NTDs by increasing the immunocompromised population [20]. Lastly, urban growth diverts public spending and resources away from rural areas [15] 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 [21]. Although NTDs are more biologically stable than malaria and HIV [22], this is especially important because control relies largely on vector control and pharmacotherapy to which resistance has begun to emerge [1].  Moreover, the reliance on a single drug for treatment of diseases such as onchocerciasis broadens the potential for resistance to develop [21]. There are few known efficacious second-line drugs which can be used if resistant strains do emerge [21], and relatively few replacements being developed [23], 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 [23]. 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 [1]. This poses dilemmas for public health policy makers. For example, regular de-worming is the recommended practice to prevent helminth infection [24], 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 [24] 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 [24].

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  [26], therefore it is vital that treatment is tested locally for resistance before being introduced across the region [24].

Conclusion A recent report from WHO [19] 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 [27] of current policies and partnerships alongside health systems strengthening [28] in endemic countries would be an excellent place to start.

Lisa McClenaghan

Want to know more about NTDs? Check out the WHO report here


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