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.

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination.

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.

Toward a framework and indicators for monitoring Roll Back Malaria.

Roll Back Malaria (RBM) is a new global partnership that aims to halve the malaria burden by the year 2010. A framework and indicators for monitoring the outcomes and impact of RBM have been defined through an extensive consultative process. The framework identifies critical areas for monitoring RBM action relating to 1) the impact on malaria burden, 2) improvements in malaria prevention and treatment, 3) related health sector development, and 4) support for RBM action (including partnerships). A set of RBM indicators has been defined that corresponds to these critical areas but that reflects the major variations in malaria epidemiology and the principal interventions in different parts of the world. Countries would select indicators that are appropriate for their situation. Four global indicators are proposed for use by all countries in which RBM action is under way. Data collection procedures are discussed, and it is indicated how monitoring RBM action can build on existing data-collection mechanisms.

The use of grid sampling methodology for rapid assessment of the distribution of bancroftian filariasis.

The recent World Health Assembly Resolution to eliminate lymphatic filariasis as a public health problem once more brings to the fore the need for reliable data for the effective planning of disease control programmes. Most countries do not have data on the distribution of lymphatic filariasis and are therefore not in the position to initiate control programmes based on sound baseline data. We tested in Ghana in 1998-99 a method for the Rapid Assessment of the Geographical Distribution of Bancroftian Filariasis (RAGFIL) that uses a spatial sampling grid with 50 km between sampled villages, rapid assessment surveys for filariasis prevalence in the sampled villages and spatial analysis to estimate the geographical distribution of filariasis throughout the study area. The prevalence contours obtained with the 50 x 50-km sampling grid were operationally similar to those obtained with a 25 x 25-km grid. The predicted prevalence was not statistically different from the sample survey prevalence in 57 independent villages and the 50 x 50-km grid appears adequate for rapid mapping of filariasis. For the purpose of filariasis mapping, the antigen test would seem a better diagnostic test than clinical examination for hydrocoele. We recommend that a regional approach to mapping be used because of the importance of cross-border foci as demonstrated by our findings from the north of Ghana. Application of the method will provide the minimal information required for effective planning of treatment programmes, and will facilitate estimation of the number of people to be treated. It will also help improve estimates of the number of people at risk and affected, and of the burden of disease due to lymphatic filariasis in Africa.

The effects of ivermectin on onchocercal skin disease and severe itching: results of a multicentre trial.

OBJECTIVE: To determine the effects of ivermectin in annual, 3-monthly and 6-monthly doses on onchocercal skin p6isease (OSD) and severe itching. METHOD: A multicentre, double-blind placebo controlled trial was conducted among 4072 residents of rural communities in Ghana, Nigeria and Uganda. Baseline clinical examination categorized reactive skin lesions as acute papular onchodermatitis, chronic papular onchodermatitis and lichenified onchodermatitis. Presence and severity of itching was determined by open-ended and probing questions. Clinical examination and interview took place at baseline and each of 5 subsequent 3-monthly follow-up visits. RESULTS: While prevalence and severity of reactive lesions decreased for all 4 arms, those receiving ivermectin maintained a greater decrease in prevalence and severity over time. The difference between ivermectin and placebo groups was significant for prevalence at 9 months and for severity at 3 months. Differences between placebo and ivermectin groups were much more pronounced for itching. From 6 months onward, the prevalence of severe itching was reduced by 40-50% among those receiving ivermectin compared to the trend in the placebo group. CONCLUSION: This is an important effect on disease burden as severe itching is for the affected people the most troubling complication of onchocerciasis. The difference among regimens was not significant, and the recommended regimen of annual treatment for the control of ocular onchocerciasis appears also the most appropriate for onchocerciasis control in areas where the skin manifestations predominate. The final determination of the effect on skin lesions requires a longer period of study.

Density-dependent processes in the transmission of human onchocerciasis: relationship between the numbers of microfilariae ingested and successful larval development in the simuliid vector.

A previous paper reported that the intake of Onchocerca volvulus microfilariae (mff) by different species of Simulium is essentially proportional to the parasite load in the skin of infected carriers. This paper examines the fate of the ingested mff in susceptible vectors to assess the relationship between parasite intake and infective larval output in blackfly species with and without well-developed cibarial armatures. Analysis is based on data from 3 onchocerciasis endemic areas: Guatemala (S. ochraceum s.l.), West Africa (S. damnosum s.l./S. sirbanum) and the Amazonian focus between South Venezuela and Northern Brazil (S. guianense and S. oyapockense s.l.). The data, which include published and unedited information collected in the field, record experimental studies of parasite uptake by wild flies maintained in captivity until the completion of the extrinsic incubation period. The relationship between L3 output (measured as the mean number of successful larvae/fly or, as the proportion of flies with infective larvae) and average microfilarial intake, was strongly non-linear. This non-linearity was best represented by a sigmoid function in case of armed simuliids (S. ochraceum s.l., S. oyapockense s.l.), or by a hyperbolic expression in that of unarmed flies (S. damnosum s.l., S. guianense). These results are compatible, respectively, with the patterns of 'initial facilitation' and 'limitation' described in culicid vectors of lymphatic filariases. A maximum mean number of 1-3 L3/fly was observed in all 4 vectors. It is concluded that O. volvulus larval development to the infective stage is regulated by density-dependent mechanisms acting at the early phase of microfilarial migration out of the blackfly's bloodmeal. Damage by the bucco-pharyngeal armature may also be density dependent. A hypothesis, based on this density dependence is forwarded to explain initial facilitation, so far only recorded in vectors with well-developed cibarial teeth. Our results provide quantitative support for the conjecture that chemotherapy alone is likely to have a greater impact on reducing onchocerciasis transmission in endemic areas where the main vector has a toothed fore-gut than in foci where the vectors have unarmed cibaria.

The burden of tropical diseases.

More than half the world's population is at risk of the tropical diseases malaria, leprosy, schistosomiasis, lymphatic filariasis, onchocerciasis, Chagas disease, African trypanosomiasis and leishmaniasis, and half a billion people are infected with at least one of these diseases. We present statistic on the population at risk and the infected population, and on the major morbidity and mortality attributable to each of these diseases. During the next decade the prevalence of leprosy, Chagas disease, and onchocerciasis is expected to fall, but for the other tropical diseases the epidemiological situation may remain stagnant or even worsen.

Epidemiological modelling for onchocerciasis control.

Planning and evaluation of parasitic disease control is complicated by the many interacting factors that jointly determine the epidemiological trends under different control strategies. The Onchocerciasis Control Programme (OCP) of the World Health Organization in West Africa has recognized this problem and uses epidemiological modelling as on aid to addressing control questions. Dik Habbema, Edoh Soumbey Alley, Anton Plaisier, Gerrit van Oortmorssen and Hans Remme describe the organization of modelling in the OCP and summarize the most important achievements thus far. The experience with applied modelling in OCP is of considerable interest for other disease control programmes.