The elimination of Trypanosoma brucei gambiense? Challenges of reservoir hosts and transmission cycles: Expect the unexpected.

The World Health Organisation has set the goal for elimination of Human African Trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense (gHAT), as a public health problem for 2020 and for the total interruption of transmission to humans for 2030. Targeting human carriers and potential animal reservoir infections will be critical to achieving this ambitious goal. However, there is continuing debate regarding the significance of reservoir host animals, wild and domestic, in different epidemiological contexts, whilst the extent and duration of the asymptomatic human carrier state is similarly undefined. This paper reviews the status of the knowledge of latent infections in wild and domestic animal reservoir hosts towards the goal of better understanding their role in the transmission dynamic of the disease. Focus areas include the transmission cycles in non-human hosts, the infectivity of animal reservoirs to Glossina palpalis s.l., the longevity of infection and the stability of T. b. gambiense biological characteristics in antelopes and domestic animals. There is compelling evidence that T. b. gambiense can establish and persist in experimentally infected antelopes, pigs and dogs for a period of at least two years. In particular, metacyclic transmission of T. b. gambiense has been reported in antelope-G.p.palpalis-antelope and pig-G.p.gambiensis-pig cycles. Experimental studies demonstrate that the infectiveness of latent animal reservoir infections with T. b. gambiense is retained in animal-Glossina-animal cycles (antelopes and pigs) for periods of three years and human infectivity markers (human serum resistance, zymodeme, DNA) are stable in non-human hosts for the same period. These observations shed light on the epidemiological significance of animal reservoir hosts in specific ecosystems characterized by presently active, as well as known "old" HAT foci whilst challenging the concept of total elimination of all transmission by 2030. This target is also compromised by the existence of human asymptomatic carriers of T. b. gambiense often detected outside Africa after having lived outside tsetse infested areas for many years - sometimes decades. Non-tsetse modes of transmission may also play a significant but underestimated role in the maintenance of foci and also preclude the total elimination of transmission - these include mother to child transmission and sexual transmission. Both these modes of transmission have been the subject of case reports yet their frequency in African settings remains to be ascertained when the context of residual foci are discussed yet both challenge the concept of the possibility of the total elimination of transmission.

Mapping, monitoring, and surveillance of neglected tropical diseases: towards a policy framework.

As national programmes respond to the new opportunities presented for scaling up preventive chemotherapy programmes for the coadministration of drugs to target lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma, possible synergies between existing disease-specific policies and protocols need to be examined. In this report we compare present policies for mapping, monitoring, and surveillance for these diseases, drawing attention to both the challenges and opportunities for integration. Although full integration of all elements of mapping, monitoring, and surveillance strategies might not be feasible for the diseases targeted through the preventive chemotherapy approach, there are opportunities for integration, and we present examples of integrated strategies. Finally, if advantage is to be taken of scaled up interventions to address neglected tropical diseases, efforts to develop rapid, inexpensive, and easy-to-use methods, whether disease-specific or integrated, should be increased. We present a framework for development of an integrated monitoring and evaluation system that combines both integrated and disease-specific strategies.

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya.

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

Spatial modelling and the prediction of Loa loa risk: decision making under uncertainty.

Health decision-makers working in Africa often need to act for millions of people over large geographical areas on little and uncertain information. Spatial statistical modelling and Bayesian inference have now been used to quantify the uncertainty in the predictions of a regional, environmental risk map for Loa loa (a map that is currently being used as an essential decision tool by the African Programme for Onchocerciasis Control). The methodology allows the expression of the probability that, given the data, a particular location does or does not exceed a predefined high-risk threshold for which a change in strategy for the delivery of the antihelmintic ivermectin is required.

Immuno-parasitological assessment of bancroftian filariasis in a highly endemic area along the River Sabaki, in Malindi district, Kenya.

Lymphatic filariasis is endemic in the coastal areas of Kenya, with four major foci identified in the early 1970s. The prevalence and intensity of Wuchereria bancrofti infection, together with antifilarial antibody responses, were assessed in a historically highly endemic focus along the River Sabaki, in Malindi district. The prevalences of microfilaraemia and antigenaemia (detected by Og4C3 ELISA) were >20% and >40%, respectively, and both increased steadily with age. The high prevalences of antifilarial IgG1 (86%) and IgG4 (91%) responses indicate that most people living in this setting are exposed to W. bancrofti infection. The children investigated had higher levels of antifilarial IgG1 than the adults. The results of this study, based on a battery of currently available parasitological and immunological methods, provide an epidemiological update on lymphatic filariasis on the northern Kenyan coast. They show that the River Sabaki area is still an important focus for bancroftian filariasis and highlight the importance of implementing an elimination programme, to interrupt the transmission of W. bancrofti in all areas of endemicity in Kenya. The detailed baseline data collected in the River Sabaki area make the communities studied ideal as sentinel sites for epidemiological monitoring and the evaluation of the impact of mass drug administrations to eliminate lymphatic filariasis.

Chronic clinical manifestations related to Wuchereria bancrofti infection in a highly endemic area in Kenya.

Clinical examinations were conducted in an effort to provide baseline data for a pilot filariasis elimination programme implemented in a Wuchereria bancrofti-endemic focus in Malindi district, Kenya. Of 186 males aged 15 years and above examined, 64 individuals (34.4%) had hydrocele, and the prevalence of the manifestation in those above 40 years old was 55.3%. The prevalence of leg lymphoedema in persons aged 15 years and above was 8.5%, with a higher rate in males (12.6%) than in females (5.7%). The overall prevalence of inguinal adenopathy was 8.6%, and males had a significantly higher (12.9%) prevalence of adenopathy than females (5.1%) (P<0.001). The data in the present study provided support for consideration of filarial infection as a possible cause of inguinal lymphadenopathy in bancroftian filariasis-endemic areas. The results of this study also indicate that lymphatic filariasis is a serious public health problem in the northern coastal areas and morbidity control programmes should be implemented to alleviate the suffering of those affected.

Public-private partnerships in blindness prevention: reaching beyond the eye.

The control of river blindness (onchocerciasis) has been one of the major public health achievements of recent decades. Initially, vector control was used to stop transmission of the parasite Onchocerca volvulus by blackflies (Simulium) but the introduction of ivermectin (Mectizan) as a means of morbidity control enabled new strategies of distribution to be developed based on community directed treatment. The donation of Mectizan by Merck & Co. Inc. for onchocerciasis control in 1987 'as long as needed' was a public health landmark to be followed by a donation from GlaxoSmithKline of albendazole in 1997 for lymphatic filariasis to which Merck also responded by agreeing to extend their donation to include the coadministration of Mectizan and albendazole. Both the drugs, however, have wider impacts than those specific to filarial parasites and are effective against a range of intestinal parasites, whilst ivermectin has an important effect on ectoparasites. The wider benefits of the annual public health intervention-collateral benefits--therefore include deworming, improved nutritional status, increased growth, improved school performance and attendance, and improved haemoglobin status as a result of the impact of albendazole on hookworm, a major cause of anaemia. More recently, studies suggest that worm-free children have a significantly reduced frequency of malaria specific episodes of fever and Ascaris-infected children have a two-fold higher frequency of cerebral or severe malaria than those without Ascaris. These findings suggest that programmes based on annual interventions to control river blindness and lymphatic filariasis can contribute disproportionately more to a range of public health problems than has been hitherto recognized, thereby assisting in attaining the millennium development goal targets.

Short communication: impact of long-term (14 years) bi-annual ivermectin treatment on Wuchereria bancrofti microfilaraemia.

Ivermectin has been and continues to be extensively used to control onchocerciasis in areas of hyper and mesoendemicity within the African Programme of Onchocerciasis Control. As programmes to eliminate lymphatic filariasis (LF) caused by Wuchereria bancrofti expand, areas of coendemicity with onchocerciasis will be incorporated into LF programmes. This study reports that in villages which were hyperendemic for onchocerciasis after some 14 years of treatment with ivermectin, no W. bancrofti could be detected in a population of 1210 individuals whilst in adjacent villages a prevalence of around 3% was found. Despite the long period of ivermectin treatment Mansonella perstans did not appear to respond to ivermectin in this setting.

Impact of long-term ivermectin (Mectizan) on Wuchereria bancrofti and Mansonella perstans infections in Burkina Faso: strategic and policy implications.

Parasitological and clinical surveys were used to determine the long-term impact of ivermectin on the prevalence of Wuchereria bancrofti and Mansonella perstans filarial infections, when the drug was given under community-directed-treatment strategies for onchocerciasis control. The study was undertaken in 11 communities in south-western Burkina Faso. Six of the villages investigated had been treated with ivermectin at least once a year for five of 6 years, with a mean coverage of approximately 65% in each round. The other five, adjacent villages, which were matched with the ivermectin-treated communities by size, ethnicity and social and economic activities, had never been treated because they were not endemic for onchocerciasis. Each subject was checked by the microscopical examination of a smear of 'night' blood, by measurement of the level of circulating antigens from adult W. bancrofti, and by clinical examination for hydrocele (if male) and lymphoedema. The prevalences of lymphoedema and hydrocele in the treated villages were similar to those in the untreated. The prevalences and intensities of W. bancrofti and M. perstans microfilaraemia were, however, significantly lower in the ivermectin-treated communities. The implications of this study are discussed in relation to the old Onchocerciasis Control Programme (OCP) and to the ongoing African Programme for Onchocerciasis (APOC), where extensive and sustained ivermectin distribution is planned through community-based treatment programmes. As with onchocerciasis in Africa, the success of annual treatments to control lymphatic filariasis will depend not only on the number of regular rounds of treatment given but on adequate coverages being achieved in each round. Wherever ivermectin is being distributed alone, for onchocerciasis control, its impact on other filarial infections, notably W. bancrofti, should be evaluated routinely. Any opportunity to add donated albendazole to such distributions should be taken, both to limit the transmission of W. bancrofti and for the wider public-health benefits.

Identification of the vectors of lymphatic filariasis in the Lower Shire Valley, southern Malawi.

An investigation of lymphatic filariasis vectors in Malawi is reported. Anopheles funestus, A. arabiensis, and A. gambiae sensu stricto had high rates of filarial infection (2.2-3.1%) and carried infective larvae. Anopheles funestus was the predominant species collected (77.6%) and was the primary vector during the study period of April to May 2002.

The use of spatial analysis in mapping the distribution of bancroftian filariasis in four West African countries.

The geographical distribution of human infection with Wuchereria bancrofti was investigated in four West African countries (Benin, Burkina Faso, Ghana and Togo), using a commercial immunochromatographic test for filarial antigen. Efforts were made to cover each health-system implementation unit and to ensure no sampling point was >50 km from another, but otherwise the 401 study communities were selected at random. The aim was to enable spatial analysis of the data, to provide a prediction of the overall spatial relationships of the infection. The results, which were subjected to an independent random validation in Burkina Faso and Ghana, revealed that prevalence in the adult population of some communities exceeded 70% and that, over large areas of Burkina Faso, community prevalences were between 30% and 50%. Most of Togo, southern Benin and much of southern Ghana appeared completely free of the infection. Although there were foci on the Ghanaian coast with prevalences of 10%-30%, such high prevalences did not extend into coastal Togo or costal Benin. The prevalence map produced should be useful in prioritizing areas for filariasis control, identifying potential overlap with ivermectin-distribution activities undertaken by onchocerciasis-control programmes, and enabling inter-country and sub-regional planning to be initiated. The results indicate that bancroftian filariasis is more widely distributed in arid areas of Burkina Faso than hitherto recognized and that the prevalences of infection have remained fairly stable for at least 30 years. The campaign to eliminate lymphatic filariasis as a public-health problem in Africa will require significantly more resources (human, financial, and logistic) than previously anticipated.

Vector-borne infections in the tropics and health policy issues in the twenty-first century.

Over the past 2 decades scientific advances and evolving strategies have significantly contributed to improved tools for control of vector-borne infections. These are: diagnostics--rapid assessment methods, non-invasive or minimally so yet sensitive and specific; new chemotherapeutics; pyrethroid insecticides and biological insecticidal products; refined strategies, such as combination therapy, rotation of insecticides for resistance management, community-directed treatment, standardized monitoring and evaluation to define programme progress; better epidemiological knowledge through improved identification of parasites and vectors; GIS, remote sensing and climate models which provide tools for epidemic prediction, planning control programmes and permit effective policy analysis; greater involvement of NGDOs (non-governmental development organizations) and CSOs (civil society organizations) in control; advent of donation programmes which involve community-based or directed mass drug distribution. Future problems could be: (1) the over-emphasis on inflexible financing by the insistence of donors on SWAps (sector-wide investment), (2) the over-reliance on pyrethroid pesticides, (3) the over-expectation that basic research will provide new drugs and vaccines for resource-poor settings in the necessary time scales, and (4) the failure to recognize that biological processes have an inherent capacity for change which outstrips the capacity of health services to respond. Malaria is a paradigm of an 'emerging disease'. (5) The challenge of implementing a 'vertical' approach to disease control within national health programmes, in the face of significant donor opposition to such programmes is a challenge even when such approaches will secure a 'public good'.

Cuticular-hydrocarbon discrimination between Anopheles gambiae s.s. and An. arabiensis larval karyotypes.

Examination of chromatograms of karyotyped larvae of Anopheles gambiae s.s. and Anopheles arabiensis has revealed that there are differences in the profile of their epicuticular hydrocarbons. A discriminant analysis of the quantitative hydrocarbon data has shown that the An. gambiae Mopti 2Rbc/bc karyotype from Mali could be separated from the Forest 2La/a karyotype from Liberia in > 80% of cases. Similar analysis permitted > 80% separation of individuals of two karyotypes of Anopheles arabiensis: 2Rab/ + from Burkina Faso, and 2Rb/b from Madagascar.

Current status and future prospects of the Global Lymphatic Filariasis Programme.

Lymphatic filariasis is recognized as one of the world's most disabling diseases. Adult lymphatic filarial nematodes live for several years; they infest the lymphatic and blood systems, and are transmitted via mosquito vectors. Acute and chronic disease can develop, manifesting as acute inflammation, hydrocoele, lymphoedema and elephantiasis. The development of a global programme for the elimination of lymphatic filariasis (focusing on disease caused by Wuchereria bancrofti) followed a resolution by the World Health Assembly in 1997 that endemic countries should develop programmes to eliminate lymphatic filariasis as a public health problem. This developed from an earlier recommendation by the International Task Force for Disease Eradication in 1993 that lymphatic filariasis was one of six diseases that could, in theory, be eradicated. Herein we review the current status and future prospects of the Global Lymphatic Filariasis Programme, which was launched in 2000.

Satellite mapping of Loa loa prevalence in relation to ivermectin use in west and central Africa.

For many years, ivermectin has been widely distributed throughout west Africa for the safe and effective control of onchocerclasis. However, recent events in Loa-loa-endemic areas of Cameroon, where severe adverse reactions have occurred, now constrain the public-health use of this drug in the forest habitat of the L. loa vector. We have created a model of L. loa prevalence to identify areas where high endemicity may be associated with the occurrence of such reactions. The model results have been mapped and the areas of overlap between high L. loa prevalence and planned ivermectin distribution for onchocerciasis control identified.

Variation in cuticular hydrocarbons among strains of the Anopheles gambiae sensu stricto by analysis of cuticular hydrocarbons using gas liquid chromatography of larvae.

Cuticular hydrocarbons of larvae of individual strains of the Anopheles gambiae sensu stricto were investigated using gas liquid chromatography. Biomedical discriminant analysis involving multivariate statistics suggests that there was clear hydrocarbon difference between the Gambian(G3), the Nigerian (16CSS and, its malathion resistant substrain, REFMA) and the Tanzanian (KWA) strains. The high degree of segregation (95%) in hydrocarbons among the four strains investigated indicates that further analysis is needed to enable understanding of hydrocarbon variation in samples of An. gambiae especially from areas where these populations co-exist.