Erling M. Pedersen

Role of Vector Control in the Global Program to Eliminate Lymphatic Filariasis

Lymphatic filariasis (LF) is a major cause of acute and chronic morbidity in the tropical and subtropical parts of the world. The availability of safe, single-dose, drug treatment regimens capable of suppressing microfilaremia to very low levels, along with improvements in techniques for diagnosing infection, has resulted in the targeting of this major mosquito-borne disease for global elimination. The Global Program to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the principal objective of breaking the cycles of transmission of Wuchereria bancrofti and Brugia spp. through the application of annual mass drug administrations (MDAs) to entire at-risk populations. Although significant progress in initiating MDA programs in endemic countries has been made, emerging challenges to this approach have raised questions regarding the effectiveness of using MDA alone to eliminate LF without the inclusion of supplementary vector control. Here, we review advances in knowledge of vector ecology, vector-parasite relationships, and both empirical and theoretical evidence regarding vector management to assess the feasibility and strategic value of including vector control in the GPELF initiative to achieve the global elimination of LF.

Permethrin-impregnated bednet effects on resting and feeding behaviour of lymphatic filariasis vector mosquitoes in Kenya.

The impact of permethrin‐impregnated bednets on resting and feeding behaviour of mosquito vectors of Wuchereria bancrofti, causing human lymphatic filariasis was studied in six pairs of villages (treated and untreated) before and after intervention. The study villages were in Kwale District, near the coast of Kenya, where Bancroftian filariasis is highly endemic, transmitted by a combination of both anopheline and culicine mosquito vectors. Mosquitoes were collected weekly in each village, indoors (using pyrethrum spray catches) and outdoors (using pit traps) during 3–4 months following the long rainy season. Of the filariasis vector species of mosquitoes collected in 1994 before intervention, 33.6% were members of the Anopheles gambiae complex, 30% were An. funestus and 36.4% were Culex quinquefasciatus. PCR analysis of the An. gambiae complex species collected in 1995 demonstrated that 98.5% were An. gambiae sensu stricto, 1% An. arabiensis and 0.5% An. merus.

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 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.

The role of monitoring mosquito infection in the Global Programme to Eliminate Lymphatic Filariasis

In addition to monitoring infection in the human host, there is also a need to assess larval infection in the vector mosquito population to evaluate the success of interventions for eliminating lymphatic filariasis transmission from endemic communities. Here, we review the current status of the available tools for quantifying vector infection and existing knowledge and evidence regarding potential infection thresholds for determining transmission interruption, to assess the potential for using vector infection monitoring as a tool for evaluating the success of filariasis treatment programmes.

Lymphatic filariasis in Uganda: baseline investigations in Lira, Soroti and Katakwi districts.

Baseline epidemiological investigations on lymphatic filariasis were conducted for the first time in Uganda in 3 communities in the districts of Lira (Alebtong area), Soroti (Lwala area) and Katakwi (Obalanga area), located to the north of Lake Kyoga at an altitude of 1000-1100 m above sea level. Individuals from the communities were examined, in April-August 1998, for Wuchereria bancrofti specific circulating antigen (by ICT card test), microfilaraemia (by counting chamber and stained blood-smear techniques) and chronic clinical manifestations of lymphatic filariasis. Endophilic mosquitoes were sampled and dissected for filarial larvae. Prevalences of circulating filarial antigen positivity were 29%, 18% and 30% in the Alebtong, Lwala and Obalanga communities, respectively. Microfilaria (mf) prevalences were 18%, 9% and 21%, and geometric mean mf intensities among mf-positive individuals were 306, 171 and 402 mf/mL blood, in the same communities. Examination of stained blood smears revealed mf of both W. bancrofti and Mansonella perstans, but more than 80% of mf-positive individuals harboured the first of these parasites. Prevalences of hydrocoele in adult (> or = 20 years) males were 28%, 7% and 17%, and prevalences of limb elephantiasis in adults were 9%, 4% and 4%, in the Alebtong, Lwala and Obalanga communities, respectively. Anopheles gambiae s.l. (mainly An. gambiae s.s.) and An. funestus were common in all 3 communities, and showed W. bancrofti infectivity rates of 1.1-1.7% and 1.3-2.9%, respectively. It is concluded that lymphatic filariasis is highly endemic in these high-altitude areas of Uganda, with An. gambiae s.l. and An. funestus being the main vectors.

Non-filarial elephantiasis in the Mt. Elgon area (Kapchorwa District) of Uganda

Following reports of a high frequency of elephantiasis in Kwen County (Kapchorwa District) on the slopes of Mt. Elgon in Uganda, a baseline survey for lymphatic filariasis was carried out in three villages in the affected area. Individuals aged 1 year and above were examined for chronic manifestations of lymphatic filariasis, and for specific circulating filarial antigens and microfilariae of Wuchereria bancrofti. Elephantiasis was observed in all age groups from 10 years and above. The overall prevalence was 4.5%, and the prevalence among individuals aged >/=20 years was 8.2%. Males and females were equally affected. However, there were only few cases of hydrocele (overall prevalence in males of 1.0%) and blood examinations were negative for W. bancrofti circulating antigens and microfilariae. Sampling of potential filariasis mosquito vectors revealed low densities of Anopheles gambiae s.l. and An. funestus, and none of these were infected with filarial larvae. In view of the low hydrocele to elephantiasis ratio, the absence of filarial infection in humans and mosquitoes, the high altitude (1500-2200 m above sea level) and the volcanic soil type, it is concluded that elephantiasis seen in this area is not of filarial origin but most likely is due to podoconiosis (endemic non-filarial elephantiasis).

Rapid assessment of the geographical distribution of lymphatic filariasis in Uganda, by screening of schoolchildren for circulating filarial antigens.

Abstract To permit improvements in the targeting of control activities, the geographical distribution of lymphatic filariasis in Uganda was assessed by using a rapid immunochromatographic card test to check school-aged children for Wuchereria bancrofti-specific circulating filarial antigens (CFA). Survey sites were selected to represent the various ecological and topographical diversities in the country. Overall, 17,533 children from 76 sites were examined. CFA-positive cases were detected at 31 of the sites, with prevalences ranging from 0.4% to 30.7%. There appeared to be strikingly more lymphatic filariasis in the north of the country than in the south. The main focus was north of the Victoria Nile, where 27 (66%) of 41 sites had CFA-positive cases, often at high prevalences. Only four (11.4%) of the 35 sites south of the Victoria Nile had CFA-positive cases, and all four were along the western rift valley and had relatively low CFA prevalences. Geostatistical interpolation was used to create a map showing the geographical distribution of CFA prevalences in Uganda (by ordinary kriging), and to assess the population exposed to W. bancrofti transmission. Estimates based on population data from 2002 indicated that approximately 8.7 million people (35.3% of the national population) lived in areas where > 1% of the school-aged children were CFA-positive. CFA prevalences generally decreased with increasing altitude, and no CFA-positive cases were found at sites that were > 1300 m above sea level. Although it gives an under-estimate of the overall community prevalence (a fact that should be taken into account when interpreting the present results and comparing them with the results of other surveys), the screening of schoolchildren for CFA was found to be a simple and useful approach for mapping the geographical distribution of lymphatic filariasis.