Paul E. Simonsen

Mathematical modelling and the control of lymphatic filariasis

The current global initiative to eliminate lymphatic filariasis represents one of the largest mass drug administration programmes ever conceived for the control of a parasitic disease. Yet, it is still not known whether the WHO-recommended primary strategy of applying annual single-dose mass chemotherapy with a combination of two drugs for 4-6 years will effectively break parasite transmission from all endemic communities. Here we review recent work on the development and application of a deterministic mathematical model of filariasis transmission, to show how models of parasite transmission will help resolve the key currently debated questions regarding the ultimate effectiveness of the global strategy to control filariasis. These critical questions include the required duration of mass treatment in different endemic areas, the optimal drug coverage required to meet control targets within prescribed timeframes, the impact and importance of adding vector control to mass chemotherapy regimens, and the likelihood of the development of drug resistance by treated worm populations. The results demonstrate the vital role that integrating these models into control programming can have in providing effective decision-support frameworks for undertaking the optimal design and monitoring of regional and global filariasis-control programmes. Operationally, the models show that the effectiveness of the strategy to achieve filariasis control will be determined by successfully addressing two key factors: the need to maintain high community treatment coverages, and the need to include vector control measures especially in areas of high endemicity.

Is the current decline in malaria burden in sub-Saharan Africa due to a decrease in vector population?

BackgroundIn sub-Saharan Africa (SSA), malaria caused by Plasmodium falciparum has historically been a major contributor to morbidity and mortality. Recent reports indicate a pronounced decline in infection and disease rates which are commonly ascribed to large-scale bed net programmes and improved case management. However, the decline has also occurred in areas with limited or no intervention. The present study assessed temporal changes in Anopheline populations in two highly malaria-endemic communities of NE Tanzania during the period 1998-2009.MethodsBetween 1998 and 2001 (1st period) and between 2003 and 2009 (2nd period), mosquitoes were collected weekly in 50 households using CDC light traps. Data on rainfall were obtained from the nearby climate station and were used to analyze the association between monthly rainfall and malaria mosquito populations.ResultsThe average number of Anopheles gambiae and Anopheles funestus per trap decreased by 76.8% and 55.3%, respectively over the 1st period, and by 99.7% and 99.8% over the 2nd period. During the last year of sampling (2009), the use of 2368 traps produced a total of only 14 Anopheline mosquitoes. With the exception of the decline in An. gambiae during the 1st period, the results did not reveal any statistical association between mean trend in monthly rainfall and declining malaria vector populations.ConclusionA longitudinal decline in the density of malaria mosquito vectors was seen during both study periods despite the absence of organized vector control. Part of the decline could be associated with changes in the pattern of monthly rainfall, but other factors may also contribute to the dramatic downward trend. A similar decline in malaria vector densities could contribute to the decrease in levels of malaria infection reported from many parts of SSA.

Change in composition of the Anopheles gambiae complex and its possible implications for the transmission of malaria and lymphatic filariasis in north-eastern Tanzania

BackgroundA dramatic decline in the incidence of malaria due to Plasmodium falciparum infection in coastal East Africa has recently been reported to be paralleled (or even preceded) by an equally dramatic decline in malaria vector density, despite absence of organized vector control. As part of investigations into possible causes for the change in vector population density, the present study analysed the Anopheles gambiae s.l. sibling species composition in north-eastern Tanzania.MethodsThe study was in two parts. The first compared current species complex composition in freshly caught An. gambiae s.l. complex from three villages to the composition reported from previous studies carried out 2–4 decades ago in the same villages. The second took advantage of a sample of archived dried An. gambiae s.l. complex specimens collected regularly from a fourth study village since 2005. Both fresh and archived dried specimens were identified to sibling species of the An. gambiae s.l. complex by PCR. The same specimens were moreover examined for Plasmodium falciparum and Wuchereria bancrofti infection by PCR.ResultsAs in earlier studies, An. gambiae s.s., Anopheles merus and Anopheles arabiensis were identified as sibling species found in the area. However, both study parts indicated a marked change in sibling species composition over time. From being by far the most abundant in the past An. gambiae s.s. was now the most rare, whereas An. arabiensis had changed from being the most rare to the most common. P. falciparum infection was rarely detected in the examined specimens (and only in An. arabiensis) whereas W. bancrofti infection was prevalent and detected in all three sibling species.ConclusionThe study indicates that a major shift in An. gambiae s.l. sibling species composition has taken place in the study area in recent years. Combined with the earlier reported decline in overall malaria vector density, the study suggests that this decline has been most marked for An. gambiae s.s., and least for An. arabiensis, leading to current predominance of the latter. Due to differences in biology and vectorial capacity of the An. gambiae s.l. complex the change in sibling species composition will have important implications for the epidemiology and control of malaria and lymphatic filariasis in the study area.

Lymphatic filariasis on the coast of Ghana.

Parasitological, clinical and entomological surveys for lymphatic filariasis were carried out in 6 villages and 3 towns on the coast of Ghana. Few or no filarial infections were observed in the towns or in the villages east of Accra. However, Wuchereria bancrofti microfilaraemia was common in the 4 western villages, with overall prevalences of 9.2%-25.4% and overall microfilariae (mf) geometric mean intensities of 321-1172 mf/mL of blood. In the same villages, hydrocele affected 8.5%-27.9% of adult males (aged > or = 20 years), and 5.6%-6.6% of adult individuals had elephantiasis (mainly of the legs). In general, the patterns of filarial infection and disease in the endemic villages resembled those observed in endemic villages in the coastal part of East Africa, with the exception that in the Ghanaian focus more females than males were affected by elephantiasis. Entomological surveys revealed that Anopheles gambiae s.l. and A. funestus were vectors of filariasis in the endemic villages. Only negligible prevalences of microfilaraemia were observed in town communities located close to highly endemic villages. Control of filariasis in this area is difficult with presently available measures, and new control tools, especially development of new drug regimens for mass treatment, are greatly needed.

Bancroftian filariasis: analysis of infection and disease in five endemic communities of north-eastern Tanzania

Clinical and parasitological surveys for bancroftia filariasis were carried out in five endemic communities in north-eastern Tanzania, covering a population of 3086 individuals. High microfilarial (mf) prevalences (17.7%-34.7%) and mf geometric mean intensities (251-1122 microfilariae/ml) were observed in the communities. The mf prevalence generally increased with age, but often levelled out in the older age groups. Larger variability was observed in individual mf intensities and no clear association between mf geometric mean intensity and age or sex was seen. Hydrocele was the most common clinical manifestation (with a prevalence of 30.2%-40.0% in male subjects aged > or = 20 years) followed by leg elephantiasis (with a prevalence of 2.0%-6.8% in all subjects aged > or = 20 years). In four of the five communities, there was no significant difference in mf prevalence in males aged > or = 20 years between those with and without hydrocele. In all the communities, the mf geomtric mean intensities in microfilaraemic males with and without hydrocele were not significantly different. The present study therefore did not indicate any association between hydrocele in males (the most common type of chronic clinical manifestation seen) and presence or absence of microfilaraemia. In contrast, only two (4.4%) of the 45 subjects with leg elephantiasis were microfilaraemic. In children aged 1-15 years, mf prevalence was significantly higher among those with microfilaraemic mothers (18.0%) than among those with amicrofilaraemic mothers (7.9%). The children of microfilaraemic mothers were therefore at 2.3-fold higher risk of becoming microfilaraemic than the children of amicrofilaraemic mothers. No relationship between the mf prevalence of the children and the mf status of their fathers was observed.

Lymphatic Filariasis Control in Tanzania: Effect of Repeated Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission

Background In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP). Methodology/Principal Findings Infection and transmission was monitored during a five-year period (one pre-intervention and four post-intervention years) in a highly endemic community (Kirare village) in north-eastern Tanzania. The vectors were Anopheles gambiae, An. funestus and Cx. quinquefasciatus. After start of intervention, human microfilaraemia initially decreased rapidly and statistically significant (prevalence by 21.2% and 40.4%, and mean intensity by 48.4% and 73.7%, compared to pre-treatment values after the first and second MDA, respectively), but thereafter the effect levelled off. The initial decrease in microfilaraemia led to significant decreases in vector infection and vector infectivity rates and thus to a considerable reduction in transmission (by 74.3% and 91.3% compared to pre-treatment level after first and second MDA, respectively). However, the decrease in infection and infectivity rates subsequently also levelled off, and low-level transmission was still noted after the third MDA. The MDAs had limited effect on circulating filarial antigens and antibody response to Bm14. Conclusion/Significance Critical issues that may potentially explain the observed waning effect of the MDAs in the later study period include the long intervals between MDAs and a lower than optimal treatment coverage. The findings highlight the importance of ongoing surveillance for monitoring the progress of LF control programmes, and it calls for more research into the long-term effect of repeated ivermectin/albendazole MDAs (including the significance of treatment intervals and compliance), in order to optimize efforts to control LF in sub-Saharan Africa.

Lymphatic filariasis related perceptions and practices on the coast of Ghana : implications for prevention and control

A qualitative study to investigate lymphatic filariasis related perceptions and practices that may be relevant for the design of appropriate health education and control programmes was conducted in four endemic villages in coastal Ghana. The villagers were aware of the common manifestations of filariasis, such as adenolymphangitis (ADL), lymphoedema, elephantiasis and hydrocele, which were specifically described with local terminology. ADL attacks were identified as the most dreaded health problem in the communities, and elephantiasis and hydrocele also ranked high in importance among reported diseases. Generally the respondents did not accept the mosquito theory of transmission, but they believed in other physical, and in spiritual and hereditary causes. Hydrocele was considered to have no link to the other disease manifestations. The manifestations were most often treated with herbal preparations which were used orally, smeared on affected parts or given as enema. In some cases the affected parts were scarified before herbal preparations were applied. The manifestations affected the work output of its victims and subjected them to hardships such as teasing, unsuitability for marriage, sexual dysfunction and divorce. Although the etiology was seen as different, the local perception of the developmental process of elephantiasis closely paralleled that of the biomedical understanding. It is suggested that this coincidence is used as an entry point for health education, to advance a broader biomedical knowledge on etiology, transmission and treatment options, and thereby to ensure co-operation of the target populations in the control of this complex disease.

Comparative evaluation of three new tools for diagnosis of bancroftian filariasis based on detection of specific circulating antigens

Three new and commercially available tools for diagnosis of Wuchereria bancrofti infections based on detection of specific circulating antigens were evaluated and compared in the same group of individuals from a highly endemic village in southern Ghana. The tests were: (1) the ICT card test for serum specimens; (2) the TropBio ELISA test for serum specimens; and (3) the TropBio ELISA test for filter-paper specimens. A high degree of positive/negative response similarity was observed for the 3 tests, and the sensitivity for detecting microfilaraemic cases was 100% for all tests. The antigen levels measured in the TropBio serum test and the TropBio filter-paper test were statistically significantly correlated. Among antigen-positive endemic individuals the antigen levels in these 2 tests furthermore showed a positive association with the microfilarial intensity, but a statistical significant correlation was seen only for the filter-paper version of the test. The results are promising for the use of the 3 tests as diagnostic tools in bancroftian filariasis.

Diversity of Plasmodium falciparum clones infecting children living in a holoendemic area in north-eastern Tanzania

The diversity of Plasmodium falciparum clones and their role in progression from asymptomatic to symptomatic condition in children have been investigated. Attempts to identify whether particular parasite genotypes were associated with the development of clinical symptoms have been made. A cohort of 34 initially asymptomatic parasitaemic children aged 1-5 years were followed daily for 31 days. Clinical examinations were made each day for signs and symptoms of clinical malaria, followed by parasitological investigation. Nineteen children developed symptoms suggestive of clinical malaria during this period. Daily blood parasite samples from 13 children who developed clinical malaria symptoms and 7 who remained asymptomatic were genotyped by PCR-amplification of the polymorphic regions of the merozoite surface proteins 1 and 2 (MSP1 and MSP2) and the glutamate rich protein (GLURP) genes. Infections were found to be highly complex in both groups of children. Every isolate examined from both groups had a mixture of parasite clones. Daily changes were observed in both parasite density and genotypic pattern. The mean number of genotypes per individual was estimated at 4.9 and 2.7 for asymptomatic and symptomatic groups of children, respectively. Analysis of allele frequency distributions showed that these differed significantly for the MSP1 locus only.

Mansonella perstans filariasis in Africa.

Mansonella perstans is a vector-borne human filarial nematode, transmitted by tiny blood-sucking flies (biting midges). It is widespread in many parts of Sub-Saharan Africa and also occurs in parts of Central and South America. Despite the commonness of this parasite very few studies have been carried out on its epidemiology and on the morbidity resulting from it, and only few thorough drug trials have been conducted to look for effective and suitable drugs and drug regimens for treatment and control. Here, we review currently available knowledge on M. perstans infections in Africa, including documented aspects of biology, vectors, transmission, diagnosis, epidemiology, morbidity and treatment. It is concluded that there is an urgent need for more research on this widespread but greatly neglected infection in order to properly assess its public health significance and as a background for identifying and recommending optimal means and strategies for treatment and control.