Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa.

A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4 antibodies to Bm14, and associations between antibody reactivity and the different variables were statistically analyzed. IgG4 reactivity to Bm14 was highly positively associated with CFA, and to a lesser extent with age. However, an expected association with household exposure to infective filarial larvae was not found. Bm14 antibody reactivity thus appeared mainly to reflect actual infection of individuals with adult filarial worms rather than ongoing exposure to transmission. The analyses moreover suggested that many of the CFA negative but Bm14 positive individuals had early or low level infections where antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including break of transmission and post-elimination surveillance, in LF control.

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

BACKGROUND: In 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. METHODS: Between 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. RESULTS: The 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. CONCLUSION: A 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.

Users' and health service providers' perception on quality of laboratory malaria diagnosis in Tanzania.

BACKGROUND: Correct diagnosis of malaria is crucial for proper treatment of patients and surveillance of the disease. However, laboratory diagnosis of malaria in Tanzania is constrained by inadequate infrastructure, consumables and insufficient skilled personnel. Furthermore, the perceptions and attitude of health service providers (laboratory personnel and clinicians) and users (patients/care-takers) on the quality of laboratory services also present a significant challenge in the utilization of the available services. This study was conducted to assess perceptions of users and health-care providers on the quality and utilization of laboratory malaria diagnostic services in six districts from three regions in Tanzania. METHODS: Questionnaires were used to collect information from laboratory personnel, clinicians and patients or care-takers. RESULTS: A total of 63 laboratory personnel, 61 clinicians and 753 patients/care-takers were interviewed. Forty-six (73%) laboratory personnel claimed to be overworked, poorly motivated and that their laboratories were under-equipped. About 19% (N = 12) of the laboratory personnel were lacking professional qualification. Thirty-seven clinicians (60.7%) always requested for blood smear examination to confirm malaria. Only twenty five (41.0%) clinicians considered malaria microscopy results from their respective laboratories to be reliable. Forty-five (73.8%) clinicians reported to have been satisfied with malaria diagnostic services provided by their respective laboratories. Majority (90.2%, N = 679) of the patients or care-takers were satisfied with the laboratory services. CONCLUSION: The findings show that laboratory personnel were not satisfied with the prevailing working conditions, which were reported to undermine laboratory performance. It was evident that there was no standard criteria for ordering malaria laboratory tests and test results were under-utilized. Majority of the clinicians and patients or care-takers were comfortable with the overall performance of laboratories, but laboratory results were having less impact on patient management.

Monitoring lymphatic filariasis control in Tanzania: effect of repeated mass drug administration on circulating filarial antigen prevalence in young schoolchildren.

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. We monitored the effect of four repeated MDAs with this combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP), on the circulating filarial antigen (CFA) status of young schoolchildren. A new batch of Standard 1 pupils from 10 rural primary schools in Tanga Municipality were examined for CFA each year in September/October (691-848 children per survey; mean age of 7.5-8.1 years), from immediately before the first MDA until eight months after the fourth MDA. The overall pre-MDA prevalence of CFA was 25.2%. Only minor and non-significant change in prevalence was seen after the first two MDAs. However, this was followed by substantial and statistically significant decreases in subsequent surveys, and eight months after the fourth MDA the prevalence was only 6.4%. Continuous entomological surveillance in a village accommodating one of the schools showed progressive decrease in transmission right from the first MDA. The usefulness of screening young schoolchildren for CFA as a tool for monitoring the impact of MDA on LF transmission is discussed.

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.

Spatio-temporal variation in malaria transmission intensity in five agro-ecosystems in Mvomero district, Tanzania.

In Africa, malaria is predominantly a rural disease where agriculture forms the backbone of the economy. Various agro-ecosystems and crop production systems have an impact on mosquito productivity, and hence malaria transmission intensity. This study was carried out to determine spatial and temporal variations in anopheline mosquito population and malaria transmission intensity in five villages, representing different agro-ecosystems in Mvomero district, Tanzania, so as to provide baseline information for malaria interventions. The agro-ecosystems consisted of irrigated sugarcane, flooding rice irrigation, non-flooding rice irrigation, wet savannah and dry savannah. In each setting, adult mosquitoes were sampled monthly using light traps recommended by the Centers for Disease Control and Prevention (CDC) from August 2004 to July 2005. A total of 35,702 female mosquitoes were collected. Anopheles gambiae sensu lato was the most abundant (58.9%) mosquito species. An. funestus accounted for 12.0% of the mosquitoes collected. There was a substantial village to village variation and seasonality in the density of Anopheles mosquito population, with peaks in May towards the end of the warm and rainy season. Significantly larger numbers of anophelines were collected from traditional flooding rice irrigation ecosystem (70.7%) than in non-flooding rice irrigation (8.6%), sugarcane (7.0%), wet savannah (7.3%) and dry savannah (6.4%). The overall sporozoite rates for An. gambiae and An. funestus were 3.4% and 2.3%, respectively. The combined overall sporozoite rate (An. gambiae+An. funestus) was 3.2%. The mean annual entomological inoculation rate (EIR) for An. gambiae s.l. was 728 infective bites per person per year and this was significantly higher in traditional flooding rice irrigation (1351) than in other agro-ecosystems. The highest EIRs for An. gambiae s.l. and An. funestus were observed during May 2005 (long rainy season) and December 2004 (short rainy season), respectively. The findings support the evidence that malaria transmission risk varies even between neighbouring villages and is influenced by agro-ecosystems. This study therefore, demonstrates the need to generate spatial and temporal data on transmission intensity on smaller scales taking into consideration agro-ecosystems that will identify area-specific transmission intensity to guide targeted control of malaria operations.

The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia.

The effect of eight half-yearly treatment rounds with diethylcarbamazine (DEC; 6mg/kg bodyweight) on Wuchereria bancrofti-specific circulating filarial antigen (CFA), a marker of adult worm infection, was followed in 79 individuals who were CFA-positive before start of treatment. Half of these were also microfilariae (mf)-positive. Microfilaraemia decreased rapidly after onset of treatment and became undetectable after four treatments. Circulating antigenaemia also decreased progressively, but at a much slower rate. After two, four and eight treatment rounds, the mean CFA intensity was reduced by 81, 94 and 98%, and the prevalence of CFA positivity was 85, 66 and 57%, compared with pre-treatment, respectively. CFA clearance rates were negatively related to pre-treatment CFA intensities, and were higher among pre-treatment mf-negative individuals than among pre-treatment mf-positive individuals. Even among patients who had pre-treatment CFA intensities above the upper measuring level (32000antigen units), and who continued to have intensities above this level after treatment, a decrease in post-treatment CFA intensities was obvious from a continuous decrease in ELISA optical density values. Repeated DEC therapy thus appears to have a slow but profound and persistent macrofilaricidal effect, which in the long run may be beneficial to populations undergoing DEC-based control interventions by reducing the probability of future morbidity development.

The effect of repeated half-yearly diethylcarbamazine mass treatment on Wuchereria bancrofti infection and transmission in two East African communities with different levels of endemicity.

The effect of repeated half-yearly mass treatment with diethylcarbamazine (DEC, 6 mg/kg body weight) on infection and transmission of Wuchereria bancrofti was assessed and compared in communities with high and low endemicity in eastern Africa, with pretreatment microfilaria (mf) and circulating filarial antigen (CFA) prevalences of 29.4% and 53.2% in the high endemicity community and 3.1% and 18.7% in the low endemicity community, respectively. Human infection was monitored by repeated cross-sectional surveys, and transmission by weekly light trap collection of vector mosquitoes in selected houses in each community. Treatments resulted in a progressive decrease in microfilaremia and circulating antigenemia in both communities, with relative reductions being considerably higher for mf than for CFA. Among pretreatment mf-positive individuals, more than 60% were diagnosed as mf negative and mean mf intensities were reduced by 99% in both communities after two treatment rounds. In contrast, only moderate reductions were seen in circulating antigenemia among pretreatment CFA-positive individuals, with mean intensities still being 24-39% of pretreatment values after two treatment rounds. Among the pretreatment mf/CFA-positive individuals, clearance to a CFA-negative status was negligible. Complete CFA clearance was only observed among pretreatment CFA-positive but mf negative individuals who also had much lower initial mean CFA levels than the mf-positive individuals. After treatment, the intensity of transmission decreased in the high-endemicity community, but this appeared mainly to be a consequence of a drought-induced reduction in vector density rather than to reduced mf load in the human population, since the proportion of mosquitoes carrying infective larvae was not reduced. No change in transmission or mosquito infectivity was observed after treatment in the low-endemicity community. Implications of these observations for the control of Bancroftian filariasis are discussed.