The Economics of African Trypanosomiasis Across the continent of Africa, infectious diseases are rampant.

Diseases like HIV and Malaria have drawn significant media attention, and global awareness is starting to spawn large campaigns focused on modulating the impact of these diseases. Unfortunately, many neglected tropical diseases are still causing huge problems throughout the nations of Africa (Kennedy, 2008). Trypanosomiasis is a neglected tropical disease that is re-emerging in epidemic proportions all across Africa (Brun, 2010). This essay will focus on analyzing and evaluating the global economic environment contributing to the exacerbation of African Trypanosomiasis, as well as the economic impact of Trypanosomiasis on Africa itself. The Nations of Africa entered the 21st century facing the monumental challenge of combating poverty in a continent, which contains almost all of the worlds poorest nations (WHO, 2012). Trypanosomiasis, which affects both human and animal health, lies at the heart of Africas struggle against poverty (Brun, 2010). This neglected disease perpetuates the cycle of poverty by decreasing worker productivity and consuming a large portion of health resources. Addressing the issue of Trypanosomiasis has the potential to impact on all eight Millennium Development Goals and potentially loosen the suffocating grip of poverty (Ahmed, 2004). If the governments of Africa and developed countries remain indecisive and apathetic towards dealing with neglected tropical diseases, then Trypanosomiasis will continue to block the nations of Africa from achieving the millennium development goals. African Trypanosomiasis, also known as African sleeping sickness is caused by the parasite, Trypanosoma brucei. T. brucei is a flagellate protozoon that is endemic to

specific regions of sub-Saharan Africa (Baylis, 1998). Similar to how Malaria is transmitted through a mosquito insect vector, so too is Trypanosomiasis. The parasitic trypanosomes are transmitted between hosts by an insect intermediary known as the Tsetse fly (Baylis, 1998). This insect vector harbors the trypanosomes and transmits them intra-dermally upon biting. The Tsetse flies acquire the infective agents during blood meals from humans or other animals harbouring the pathogenic protozoa (Vickerman, 1998). T. brucei has established an infamous reputation due to its distinct ability to evade the immune defenses of its hosts. The T. brucei parasite is highly virulent and strongly pathogenic (Vickerman, 1988). There are currently no vaccines or chemoprophylaxis available for Trypanosomiasis, so the only ability doctors have to combat the disease is retroactively using extremely strong chemotherapy drugs that are highly toxic (Legros, 2002). African sleeping sickness threatens millions of people across 37 countries of sub-Saharan Africa, however it is incredibly difficult to assess the specific burden of Trypanosomiasis because many of the disease endemic countries lack the public health surveillance and diagnostic expertise needed to quantify the disease epidemiology (Simarro, 2008). The countries of Africa reported 56 thousand cases of Trypanosomiasis to the WHO in 2010, however it is estimated that this only represent 45 percent of the actual infected population (WHO, 2012). Many cases of Trypanosomiasis remain undiagnosed because early symptoms like fatigue, muscle wasting and weight loss are common to a wide array of conditions, and these symptoms are not attributed to Trypanosomiasis unless diagnostic testing is pursued (Simarro, 2008). The inherent poverty of many African nations, results in a substantial

dependence on developed countries to supply health resources; this reality is exemplified by the fact that no new drugs for the treatment of Trypanosomiasis have been developed since 1991, despite the current drugs being incredible toxic and frequently lethal (Ryder, 2010). Within the developed world, innovation and development are driven by the prospect of financial gain, but the market of impoverished Africans holds very little promise in terms of investment return. Pharmaceutical companies benefit from being able to sell large quantities of a drug at a price mark-up in the range of 500 to 800 percent, but sales at high retail prices are only possible if the prospective market can afford the product (Togerson, 2011). In the absence of prospective financial return, pharmaceutical companies have limited incentive to pursue research in the area of neglected tropical diseases. The impoverished areas of Africa must depend on the moral conscience of the developed world and institutions like the WHO to pursue new treatment options without financial incentive. If the developed world ignores their moral obligation to help their fellow man then the outlook for innovative new drug therapies is very bleak. Since 1972, the American pharmaceutical company Sanofi-Aventis has been the sole manufacturer of the anti-parasitic drugs used for the treatment of Trypanosomiasis, but on October 12th, 2011 Aventis announced they would be discontinuing production of the 3 trypanocidal drugs in their line (Ryder, 2010). Aventis chose to make this business decision based on the fact that the marginal cost of drug production vastly exceeds the sale price of each drug (Ryder, 2010). The population affected by Trypanosomiasis consists of highly impoverished rural dwelling Africans; this vulnerable population does not have the financial ability to purchase trypanocidal drugs at retail prices. Instead of selling the anti-parasitic drugs to

the countries directly, Aventis has sold the drugs to the World Health Organization; the WHO is then responsible for distributing and administering these drugs to vulnerable populations (WHO, 2009). As a method for decreasing their costs the WHO has petitioned Aventis on moral grounds and pressured the drug company to decrease their prices, so that the drugs could be made more widely available. There are many people who would argue that Aventis has a moral obligation to continue their production of trypanocidal drugs, but legally speaking Aventis is responsible for maximizing profits for its shareholders, therefore any drug line losing money should be discontinued (Canteh, 2010). Aventis stated in its annual report that we are proud of our past partnership with the WHO and the strides we have made towards combating parasitic diseases, but unfortunately Aventis will be discontinuing production of the drugs: Melarsoprol, Nifedipine and Balaxter (WHO, 2011). Pharmaceutical executives make strategy decisions for their corporations usually without considering the ramifications that those decisions will have hundreds of miles away in sub-Saharan Africa. Discontinuing the production of trypanocidal drugs will have enormous economic implications across Africa, because the disease pool will swell and new epidemics will emerge. The control and elimination of Trypanosomiasis can be approached from two directions: health professionals can control the disease reservoir by treating the infected individuals, or the government can control the tsetse population, thus decreasing the rate of vector-borne transmission (Kristjanson, 1999). Any action that contributes to an increase in the number of infected people can spawn massive outbreaks of Trypanosomiasis. In 1999, civil war in the Democratic

Republic of Congo stopped the WHO from supplying trypanocidal drugs to the country for 8 months (WHO, 2000). This short period of neglected treatments caused 4 epidemics within the Congo, resulting in 10 thousand deaths, which was a 400 percent increase from the previous year (WHO, 2012). If a continent wide shortage of trypanocidal drugs does arise, there would be massive economic ramifications. The DALYs lost from each case of Trypanosomiasis is estimated at 9 years (Fevre, 2008). If the nations of Africa faced a 3 to 4 fold increase in Trypanosomiasis incidence, then Africa could be faced with a continent wide DALY total in excess of 4 million years (Fevre, 2008). Trypanosomiasis typically remains undiagnosed for 3 to 4 years, manifesting as chronic fatigue, sarcopenia and weight loss (Brun, 2010). Additionally, the parasitic overload within the body creates a perpetual immuno-compromised state that leads to patients frequently acquiring secondary infections. These clinical manifestations cause severe decreases in productivity. Any Loss of productivity can be devastating for most rural dwelling Africans because failing to farm, hunt or work can leave these individuals in complete financial ruin. In 2001, a joint committee of African nations agreed to start large-scale trypanosome screening programs across Africa. The pan-African screening program involved 12 mobile labs that would travel around to the tsetse infested areas of the Congo, Sudan and Angola (Robays, 2004). The screening labs were equipped with serological tests that would help to unmask latent cases of Trypanosomiasis and potentially decrease the size of the disease pool. Screening for Trypanosomiasis works on the premise of herd immunity, as the number of carriers is reduced, the rate of disease transmission will decrease (Simarro, 2008). The results of this initiative were almost immediate. The programs lead to the lowest prevalence of Trypanosomiasis in recent history (Simarro,

2008). Then in 2005, the pan-African screening program was discontinued because it carried enormous inherent cost and it was starting to experience diminishing returns (Robays, 2004). Other health issues arose across Africa that took precedence over the screening program; Trypanosomiasis was at a 30-year low and issues like drought, famine and HIV required increased resources. In the 7 years since the program was terminated, Trypanosomiasis has re-emerged with a vengeance (WHO, 2011). Neglecting the screening programs for Trypanosomiasis in spite of their inherent success, may seem idiotic to wealthy individuals from the developed world, but many African nations have such a limited supply of health resources that they must allocate their funds to the most pressing issues of the day. In an ideal world all available methods would be used to combat this horrible disease, but in reality this is unfeasible because of the stringent financial pressures facing African governments. Another potential pathway that can lead to the exacerbation of Trypanosomiasis incidence is failure to control the tsetse population. The tsetse fly vector is responsible for transmitting the Trypanosome parasite, so when the tsetse population is high there is a heightened risk of disease transmission (Brun, 2010). Tsetse control has long been an important option for reducing the impact of Trypanosomiasis, however the elimination programs have seldom been sustained due to extenuating circumstances. The high cost of the tsetse elimination campaigns and the dramatic environmental impact of DDT based insecticides have decreased the number of active elimination campaigns (Bett, 2008). The periodicity of these campaigns is not only dangerous because it allows the tsetse to regenerate in large numbers, but the intermittent campaigns are actually favoring the evolutionary development of insecticide resistant tsetse strains (Bett, 2008).

The current tsetse elimination campaigns involve aerial insecticide spraying, these campaigns are prohibitively expensive and they are not performed frequently enough to be effective (Zaim, 2002). The government of Angola spent 23 million dollars on tsetse control in 2009, and they saw the rates of Trypanosomiasis fall by almost 30 percent (WHO, 2010). Unfortunately, the following year the tsetse control campaigns were cut from the government budget. The highly impoverished nations of sub-Saharan Africa cannot afford huge annual expenditures for these proactive campaigns, thus more cost effective long-term interventions are needed. Another issue with the current insecticide based elimination protocol is the fact that DDT, the active ingredient in most insecticides is toxic to humans (Zaim, 2002). DDT is highly water-soluble and tends to congregate in the ground water, which is highly problematic in countries where there is already and inherent water shortage. Continually dousing areas with DDT based insecticides can contaminate the water table for a large geographic area (Zaim, 2002). A cost-benefit analysis was performed in Tanzania by the WHO to determine if continued DDT use would prevent significant loss of life and eliminate sufficient disease burden to justify its continued usage, despite its inherent environmental impact and toxic effects (Zaim, 2002). The WHO determined that in areas where Trypanosomiasis is highly prevalent the benefits of aerial insecticide bombardment outweigh the costs of DDT ground water accumulation, however in areas where disease prevalence is moderate DDT usage is not justified (WHO, 2008). The economic implications of Trypanosomiasis reach far beyond human infection; the infection of many animal species, specifically farm livestock have enormous economic ramifications. Trypanosomiasis is an important constraint, if not the

most important constraint, to livestock farming in tropical Africa (Allsopp, 2001). More then a third of the land area across Africa is infested with tsetse flies, which means over 56 million cattle are exposed to the risk of contracting Trypanosomiasis, as are millions of goats, sheep, donkeys camels and horses (Kristjanson, 1999). These various forms of livestock are the primary means of food and income for most rural dwelling Africans, which means any factor that decreases livestock yield, would profoundly affect African farmers. African livestock producers are administering an estimated 35 million curative and preventative Trypanosomiasis treatments annually, and at a price of 8 dollars per treatment, the disease is costing producers and governments more then 280 million dollars per year (Kristjanson, 1999). Unfortunately, many farmers do not have access to the trypanocidal drugs required to cure their livestock so their animals remain infected. Infected animals are essentially sterile as a result of the nutrient deficiency associated with parasite overload and milk production is dramatically reduced do to parasite induced protein deficiency (Habtemariam,1983). In addition, infected livestock experience a decrease is lean body mass as a result of the sarcopenia associated with protein deficiency, which means the livestock yield less meat for the farmers to sell. The inherent loss of milk and meat sales that is associated with diseased livestock has a cyclic effect because farmers have less access to liquid capital and thus farmers will cultivate less land and yield less crop (Bett, 2008). Farmers also cultivate less land due to an inherent fear of tsetse habitats; farmers will avoid cultivating land with thick brush, bogs or swamps because tsetse flourish in these areas and they dont want to risk infection. Fevre et al. (2003) estimated

annual losses in Gross Domestic Product for the 10 countries completely infested by tsetse to be in excess of 450 million dollars. Within a continent smothered by suffocating poverty, Trypanosomiasis has devastating consequences on livestock production and agricultural yields, which propagates the cycle of poverty further. In order for African farmers to expand their entrepreneurial potential it is critical that tsetse are controlled, so that livestock production and agricultural output can be maximized. Some of the economic implications associated with African Trypanosomiasis have been casually investigated over the course of this paper. The developed world bares a lot of responsibility when it comes to combating Trypanosomiasis. If the pharmaceutical companies of developed nations do not manufacture the drug therapies required to treat Trypanosomiasis then the inherent drug shortage could potentially spawn huge disease outbreaks across Africa. In addition, the periodicity of patient screening protocols and tsetse elimination campaigns are proving highly ineffective because governments are not committing to these control mechanisms long term. The economics of Trypanosomiasis are governed by a complex interplay between both foreign and domestic factors. It is imperative that the WHO and African governments collectively work to secure a long-term trypanocidal drug manufacturer and implement sustainable tsetse control campaigns. Failing to address the issue of Trypanosomiasis will only exacerbate the already severe poverty that exists within Africa.

Works Cited

Ahmed, A., & Cleeve, E. (2004). Tracking the millennium development goals in sub-saharan africa. International Journal of Social Economics, 31(1/2), 12-29. Allsopp, R. (2001). Options for vector control against trypanosomiasis in africa. Trends in Parasitology, 17(1), 15-19. Anene, B. M., Onah, D. N., & Nawa, Y. (2001). Drug resistance in pathogenic african trypanosomes: What hopes for the future? Veterinary Parasitology, 96(2), 83-100. Baumgartner, J., Gilioli, G., Tikubet, G., & Gutierrez, A. P. (2008). Eco-social analysis of an east african agro-pastoral system: Management of tsetse and bovine trypanosomiasis. Ecological Economics, 65(1), 125-135. Baylis, M., & Stevenson, P. (1998). Trypanosomiasis and tsetse control with insecticidal pourons fact and fiction? Parasitology Today, 14(2), 77-82. Bett, B., Irungu, P., Nyamwaro, S. O., Murilla, G., Kitala, P., Gathuma, J., et al. (2008). Estimation of tsetse challenge and its relationship with trypanosomosis incidence in cattle kept under pastoral production systems in kenya. Veterinary Parasitology, 155(3-4), 287-298. Brun, R., Blum, J., Chappuis, F., & Burri, C. (2010). Human african trypanosomiasis. The Lancet, 375(9709), 148-159. Conteh, L., Engels, T., & Molyneux, D. H. (2010). Socioeconomic aspects of neglected tropical diseases. The Lancet, 375(9710), 239-247. Etchegorry, M. G., Helenport, J. P., Pecoul, B., Jannin, J., & Legros, D. (2001). Availability and affordability of treatment for human african trypanosomiasis. Tropical Medicine & International Health, 6(11), 957-959. Fvre, B. Wissmann, S. C. Welburn, P. Pascal L. The Burden of Human African Trypanosomiasis. PLoS Negl Trop Dis. 2008 December; 2(12): e333. Published online 2008 December 23. doi: 10.1371/journal.pntd.0000333 Habtemariam, T., Howitt, R. E., Ruppanner, R., & Riemann, H. P. (1983). The benefitcost analysis of alternative strategies for the control of bovine trypanosomiasis in ethiopia. Preventive Veterinary Medicine, 1(2), 157-168. Kennedy, P. G. E. (2008). The continuing problem of human african trypanosomiasis (sleeping sickness). Annals of Neurology, 64(2), 116-126. Kristjanson, P. M., Swallow, B. M., Rowlands, G. J., Kruska, R. L., & de Leeuw, P. N. (1999). Measuring the costs of african animal trypanosomosis, the potential benefits of control and returns to research. Agricultural Systems, 59(1), 79-98.

10

Leak, S. G. A., Mulatu, W., Authi, E., d'Ieteren, G. D. M., Peregrine, A. S., Rowlands, G. J., et al. (1993). Epidemiology of bovine trypanosomiasis in the ghibe valley, southwest ethiopia 1. tsetse challenge and its relationship to trypanosome prevalence in cattle. Acta Tropica, 53(2), 121-134. Legros, D., Ollivier, G., Gastellu-Etchegorry, M., Paquet, C., Burri, C., Jannin, J., et al. (2002). Treatment of human african trypanosomiasis-present situation and needs for research and development. The Lancet Infectious Diseases, 2(7), 437-440. Robays, J., Bilengue, M. M. C., Stuyft, P. V. d., & Boelaert, M. (2004). The effectiveness of active population screening and treatment for sleeping sickness control in the democratic republic of congo. Tropical Medicine & International Health, 9(5), 542-550. Ryder, N. S. (2010). Discontinued drugs in 2008: Anti-infectives. Expert Opinion on Investigational Drugs, 19(1), 1-21. Simarro, P. P., Jannin, J., & Cattand, P. (2008). Eliminating human african trypanosomiasis: Where do we stand and what comes next. PLoS Medicine, 5(2), e55. Sinyangwe, L., Delespaux, V., Brandt, J., Geerts, S., Mubanga, J., Machila, N., et al. (2004). Trypanocidal drug resistance in eastern province of zambia. Veterinary Parasitology, 119(23), 125-135. Torgerson, P. R., & Macpherson, C. N. L. (2011). The socioeconomic burden of parasitic zoonoses: Global trends. Veterinary Parasitology, 182(1), 79-95. Vickerman, K., Tetley, L., Hendry, K. A. K., & Turner, C. M. R. (1988). Biology of african trypanosomes in the tsetse fly. Biology of the Cell, 64(2), 109-119. World Health Organization. Annual Reports. Infectious Disease. (2000-2012). Retrieved from www.who.int/ Zaim, M., & Guillet, P. (2002). Alternative insecticides: An urgent need. Trends in Parasitology, 18(4), 161-163.

11

12

13