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East African countries struggle with visceral leishmaniasis

2009; Elsevier BV; Volume: 374; Issue: 9687 Linguagem: Inglês

10.1016/s0140-6736(09)61401-x

1474-547X

Talha Burki,

Zoonotic diseases and public health

Visceral leishmaniasis is increasing in some east African states. But with few donors, a lack of awareness, and erratic national policies, disease control fairs poorly in the region, says Talha Burki. Aid agencies are growing concerned about the lack of leishmaniasis control in some east African nations. In March, 2009, the Sudanese Government expelled aid agencies from north Sudan. Médecins Sans Frontières (MSF) was on the verge of opening a leishmaniasis programme in the east; this programme had to be cancelled. Unless another agency steps in—which seems very improbable—many patients will have no access to diagnosis, drugs, and treatment centres. “Considering the 100% case mortality if there's no treatment” said Koert Ritmeijer from MSF “that means high mortality”. Gedaref state in east Sudan is the epicentre of visceral leishmaniasis in east Africa. WHO is despatching drugs to the area, but Jorge Alvar of WHO concedes that further interventions are unlikely, at least for the meantime. The country is administered federally, a structure that can be unwieldy. “The federal Ministry of Health has never shown a particular interest in kala-azar control”, notes Ritmeijer. Visceral leishmaniasis—in Sudan, and elsewhere—affects the most impoverished people in the most remote areas. “It would be different if kala-azar was an endemic disease in Khartoum”, Ritmeijer added. Visceral leishmaniasis affects around 500 000 people every year. Patients have anaemia, an enlarged spleen and liver, and a darkening of the skin; hence the illness's other name: kala-azar—Hindi for black fever. Transmitted by the sandfly, it kills more than 50 000 people worldwide; among parasitic diseases, only malaria is more deadly. Two-thirds of patients are in southeast Asia. The second largest foci is east Africa: perhaps as many as 40 000 cases every year, and incidence is on the rise. Data for visceral leishmaniasis are scarce: most endemic countries have not established effective surveillance systems. Sudan—a nation roughly the size of western Europe—is no exception. Alvar estimates that the country sees 30 000 cases of visceral leishmaniasis every year; 20 000 in north Sudan, an area that includes endemic eastern states. The disease exhibits wave behaviour; the last few years have seen an increase in incidence in eastern Sudan. “What we have seen in the past”, Ritmeijer told The Lancet “is that outbreaks of new epidemic cycles always start in eastern Sudan; and from there spread into south Sudan and Ethiopia”. This is the main kala-azar belt in east Africa. In Ethiopia, recent years have seen the disease spread to previously non-endemic districts such as Libo Kemkem, where—as commonly occurs with kala-azar—it was initially misdiagnosed as malaria. Around 3000 Ethiopians contract visceral leishmaniasis every year. There are some encouraging developments. “Political commitment to fighting visceral leishmaniasis is high”, said Alvar. “A national taskforce has been established, including mobile teams for active case detection and mapping the disease.” 30% of patients in Ethiopia are malnourished, a condition which facilitates the spread of kala-azar; there is evidence that children who have previously had malnutrition are also more susceptible to the disease. More worryingly, Sudan and Ethiopia are facing a surge in leishmania/HIV coinfection, with northwest Ethiopia reporting coinfection rates of 34%. According to WHO, “HIV infection increases the risk of developing visceral leishmaniasis by a factor 100–1000 in endemic areas”. Without antiretroviral drugs, most patients with HIV/AIDS die within 2 years of contracting visceral leishmaniasis. In fact, “all coinfected patients sooner or later relapse—and sooner or later die—despite leishmaniasis treatment”, Alvar told The Lancet. It's an “immunological gridlock”, explains Manica Balasegaram from Drugs for Neglected Diseases Initiative (DNDi): “coinfected patients are very vulnerable to other opportunistic infections, because they are already immunologically compromised”. HIV/AIDS services must integrate coinfection treatment schemes into their east African programmes, Balasegaram added. The extent of the problem is unknown: visceral leishmaniasis is not on the US Centers for Disease Control and Prevention list of opportunistic infections; hence HIV/AIDS notification systems do not usually have information about coinfection. Matters are further complicated by the nature of drugs to treat leishmaniasis. Pentavalent antimonials are the only drugs licensed for use in east Africa. These are toxic anyway, but for coinfected patients they are especially dangerous. Frustratingly, the remaining drugs to treat leishmaniasis are safer but less effective. Drug supply is already problematic. There are five therapies available at present; all monotherapies, and all of which have serious shortcomings. One—liposomal amphotericin B—has a 97% success rate in India, but is very expensive, and requires cold storage from point-of-despatch. Another, the only oral treatment—miltefosine—is teratogenic and requires 28 days treatment, raising concerns about compliance. For east Africa, resistance remains a distinct possibility; in India, antimonial drugs are essentially useless, with resistance of up to 60% reported in some places. Moreover, antimonial drugs require 30-day hospital-based, parenteral treatment; an enormous imposition for most patients—and their families—in the developing world. “It's very important that we look at feasible treatment options that will reduce the length for which patients stay in hospital”, says Balasegaram. This will both encourage patients to seek medical help, and reduce the massive opportunity cost of treatment. There is no single new therapy in phase 2 or 3 trials, but DNDi is attempting to develop combination therapies that could cut the length of treatment to around 10 days, although there is still some way to go. Outside the laboratory, there are problems with national guidelines. Uganda—which sees a few hundred cases every year—has no provision for purchasing the K39 dipstick, a highly effective diagnostic that would cost the country no more US$500 per year. Sudan also declines to use the dipstick; as a result clinicians tend to rely on clinical diagnosis with consequent overdiagnosis and misallocation of already stretched resources. In Kenya, kala-azar policy specifies that all serologically-proven leishmaniasis be confirmed by spleen aspirate, a test that can only be done in district hospitals. Even Ethiopia has been reluctant to introduce new drugs. Finally, there is Somalia. Wracked by warfare, the nation commonly described as a “failed state” has no real infrastructure. “It's impossible to evaluate burden of disease”, affirmed François Chappuis of MSF. Visceral leishmaniasis flourishes where people are malnourished and displaced—conditions which strongly apply to Somalia. MSF runs an operation in Bakool region in south central Somalia, treating around 1600 patients per year. “There has been a tremendous increase in cases in the past 2 years”, Chappuis notes. “We have the feeling that at least we're working in the main area”, adds Ritmeijer, positing that other foci are likely to be smaller. Nonetheless, the country is scarcely prepared to combat outbreaks of infectious disease. The situation could easily deteriorate. Vector control is an equally murky subject. “There has never been a study of control measures in East Africa”, Chappuis remarked. “You cannot extrapolate from India: everything is different there.” Certainly bednets are not the answer: huts are often too small, it is tricky to persuade people to use them during the hottest parts of the year, and besides many Africans sleep outside. One possible solution is spraying livestock and treating blankets with insecticide. But without further research it is impossible for experts to make recommendations. “Attempts to hand projects in neglected diseases back to the ministries of health often end up as failures”, explains Chappuis. “It's not necessarily a question of money; the ministries of health just don't pay attention to these diseases, especially if they occur in remote areas.” Even in terms of such diseases, visceral leishmaniasis is particularly ill-attended. “There are so few donors”, says Alvar. The Spanish Government funds interventions in east Africa, and the World Bank is active in southeast Asia. But other agencies have not been as forthcoming. For the future, it is especially essential that researchers maintain efforts to develop affordable new drugs, says Soraya Rodriguez—Spanish Secretary of State for International Co-operation. In endemic countries, “a lot depends on what kala-azar will do”, says Ritmeijer. If numbers are high, governments are jolted into action; if incidence falls, then attention focuses elsewhere. Not ideal for a disease which follows an epidemic cycle. One change, seemingly frivolous, might be made straight away: the name. “No-one knows how to pronounce it correctly”, said Alvar (leesh-maniasis). It is not merely semantics. According to some experts, the word “leishmaniasis'—whether joined with “cutaneous”, “mucocutaneous”, or “visceral”—impedes efforts to raise awareness. By the end of 2010, Alvar aims to have established the global strategy for leishmaniasis. This strategy will encompass a technical report, accurate epidemiological information, regional strategies—vital for a transborder problem in which epidemiology and ecology vary from place-to-place—and updated information about drug administration. He hopes that as the strategy starts to come together, international funders will become involved in fighting this most neglected of diseases.