Ecological Drivers of Mansonella perstans Infection in Uganda and Patterns of Co-endemicity with Lymphatic Filariasis and Malaria.

BACKGROUND: Mansonella perstans is a widespread, but relatively unknown human filarial parasite transmitted by Culicoides biting midges. Although it is found in many parts of sub-Saharan Africa, only few studies have been carried out to deepen the understanding of its ecology, epidemiology, and health consequences. Hence, knowledge about ecological drivers of the vector and parasite distribution, integral to develop spatially explicit models for disease prevention, control, and elimination strategies, is limited. METHODOLOGY: We analyzed data from a comprehensive nationwide survey of M. perstans infection conducted in 76 schools across Uganda in 2000-2003, to identify environmental drivers. A suite of Bayesian geostatistical regression models was fitted, and the best fitting model based on the deviance information criterion was utilized to predict M. perstans infection risk for all of Uganda. Additionally, we investigated co-infection rates and co-distribution with Wuchereria bancrofti and Plasmodium spp. infections observed at the same survey by mapping geographically overlapping areas. PRINCIPAL FINDINGS: Several bioclimatic factors were significantly associated with M. perstans infection levels. A spatial Bayesian regression model showed the best fit, with diurnal temperature range, normalized difference vegetation index, and cattle densities identified as significant covariates. This model was employed to predict M. perstans infection risk at non-sampled locations. The level of co-infection with W. bancrofti was low (0.3%), due to limited geographic overlap. However, where the two infections did overlap geographically, a positive association was found. CONCLUSIONS/SIGNIFICANCE: This study presents the first geostatistical risk map for M. perstans in Uganda. We confirmed a widespread distribution of M. perstans, and identified important potential drivers of risk. The results provide new insight about the ecologic preferences of this otherwise poorly known filarial parasite and its Culicoides vector species in Uganda, which might be relevant for other settings in sub-Saharan Africa.

Biting patterns and seasonality of Anopheles gambiae sensu lato and Anopheles funestus mosquitoes in Kamuli District, Uganda.

BACKGROUND: We investigated the biting patterns and seasonal abundances of Anopheles gambiae s.l. and An. funestus mosquitoes in Kamuli District, Uganda. METHODS: Hourly indoor and outdoor catches of human biting mosquitoes were sampled from 19.00 to 07.00 hours for four consecutive nights each month using bed net traps in forty-eight houses randomly selected from Bugabula county where insecticide-treated bed nets (ITNs) had been used for at least five years and Budiope county where ITNs had not been used. The indoor and outdoor human-biting fractions, time of biting of the anophelines and climatic data were recorded from January to December 2010. Data were analysed using Multi-way analysis of variance, Kruskal-wallis rank sum test and Pearson correlation. The number of mosquitoes caught biting humans and resting indoors, the indoor and outdoor human biting densities and biting rates during different hours of the night, and mosquito abundances for a twelve-month sampling period in both zones are reported. RESULTS: Approximately four times more Anopheles mosquitoes were caught biting humans in Budiope County than in the Bugabula zone, with An. gambiae s. l. catches exceeding those of An. funestus. In both zones, peak night biting occurred between 23.00 and 05.00 hours. The majority of bites occurred between 03.00 and 06.00 hours for both Anopheles gambiae s. l. and funestus group. Outdoor biting densities of Anopheles gambiae s. l. exceeded the indoor biting densities throughout the night in both zones, while the indoor and outdoor human biting densities of An. funestus group were apparently equal. The outdoor and indoor human biting rates were similar in both zones. In Bugabula county, the abundance of An. gambiae s.l. was rainfall-dependent, while the An. funestus group could thrive with or without rain fall. In Budiope county, both An. gambiae s.l. and An. funestus mosquitoes thrived all year round regardless of the amount of rainfall. CONCLUSION: Considering the biting patterns, and seasonal abundances exhibited by Anopheles gambiae s.l. and An. funestus mosquitoes in Kamuli district, intensive use of ITNs combined with indoor residual spraying, environmental management and improved house designs in the context of integrated vector management may be the appropriate vector control strategy.

Bayesian geostatistical modelling of malaria and lymphatic filariasis infections in Uganda: predictors of risk and geographical patterns of co-endemicity.

BACKGROUND: In Uganda, malaria and lymphatic filariasis (causative agent Wuchereria bancrofti) are transmitted by the same vector species of Anopheles mosquitoes, and thus are likely to share common environmental risk factors and overlap in geographical space. In a comprehensive nationwide survey in 2000-2003 the geographical distribution of W. bancrofti was assessed by screening school-aged children for circulating filarial antigens (CFA). Concurrently, blood smears were examined for malaria parasites. In this study, the resultant malariological data are analysed for the first time and the CFA data re-analysed in order to identify risk factors, produce age-stratified prevalence maps for each infection, and to define the geographical patterns of Plasmodium sp. and W. bancrofti co-endemicity. METHODS: Logistic regression models were fitted separately for Plasmodium sp. and W. bancrofti within a Bayesian framework. Models contained covariates representing individual-level demographic effects, school-level environmental effects and location-based random effects. Several models were fitted assuming different random effects to allow for spatial structuring and to capture potential non-linearity in the malaria- and filariasis-environment relation. Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting models. Maps of predicted hyper-endemic malaria and filariasis were furthermore overlaid in order to define areas of co-endemicity. RESULTS: Plasmodium sp. parasitaemia was found to be highly endemic in most of Uganda, with an overall population adjusted parasitaemia risk of 47.2% in the highest risk age-sex group (boys 5-9 years). High W. bancrofti prevalence was predicted for a much more confined area in northern Uganda, with an overall population adjusted infection risk of 7.2% in the highest risk age-group (14-19 year olds). Observed overall prevalence of individual co-infection was 1.1%, and the two infections overlap geographically with an estimated number of 212,975 children aged 5 - 9 years living in hyper-co-endemic transmission areas. CONCLUSIONS: The empirical map of malaria parasitaemia risk for Uganda presented in this paper is the first based on coherent, national survey data, and can serve as a baseline to guide and evaluate the continuous implementation of control activities. Furthermore, geographical areas of overlap with hyper-endemic W. bancrofti transmission have been identified to help provide a better informed platform for integrated control.

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.

Analysis of the 24-h microfilarial periodicity of Mansonella perstans.

The Mansonella perstans microfilarial (mf) periodicity in peripheral blood was analysed in a group of 32 healthy individuals from an endemic community in Uganda. The majority of individuals had maximum mf intensity during the first and minimum during the last 12 h of the day. Mean mf ratios (i.e. time-specific counts in relation to mean count for the individual) indicated a weak but significant diurnal periodicity with peak intensity around 0800 h. Trigonometric analysis of the ratios, assuming a harmonic wave pattern of periodicity, gave a periodicity index of 11.1 and a peak time of 0645 h. The higher mf intensities in the early morning appeared to coincide with the preferred biting hour of the vectors. The observed weak pattern of mf periodicity indicates that the sampling time of blood specimens for diagnosis will have only minor effect on diagnostic sensitivity.

Mansonella perstans filariasis in Uganda: patterns of microfilaraemia and clinical manifestations in two endemic communities.

Surveys for Mansonella perstans infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100microl of finger-prick blood. Among 575 and 991 examined individuals aged >or=1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1-4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15-19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4mf/100microl) than in the Luwero community (29.9mf/100microl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and M. perstans microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280].

A randomised, double-blind field trial of ivermectin alone and in combination with albendazole for the treatment of Mansonella perstans infections in Uganda.

The effect of a single dose of ivermectin alone (150-200microg/kg body weight) or in combination with albendazole (total of 400mg) in Mansonella perstans infection was assessed in a randomised, double-blind field trial in two endemic communities in Mukono and Luwero districts of Uganda. No side effects were observed or reported during the first 7 days after treatment. The effect on microfilaraemia was analysed among individuals with >or=20 microfilariae (mf) per 100mul of blood at baseline, who took the treatment and who attended follow-up examinations at 6 months and 12 months after treatment (48 and 46 in Mukono and 48 and 40 in Luwero for the ivermectin and combination treatment, respectively). In both communities, the combination treatment appeared slightly more effective than ivermectin alone, but the difference was not statistically significant. Both drug regimens were more effective in Luwero than in Mukono, probably owing to different diets in the two areas. However, in general both treatment regimens in both communities had limited effect on microfilarial intensities, and only one individual (given combination treatment in Luwero) was mf-negative at 6 months and 12 months after treatment. [ClinicalTrials.gov identifier: NCT00215280].

Neglected tropical diseases in Uganda: the prospect and challenge of integrated control.

So-called 'neglected tropical diseases' (NTDs) are becoming less neglected, with increasing political and financial commitments to their control. These recent developments were preceded by substantial advocacy for integrated control of different NTDs, on the premise that integration is both feasible and cost-effective. Although the approach is intuitively attractive, there are few countrywide experiences to confirm or refute this assertion. Using the example of Uganda, this article reviews the geographical and epidemiological bases for integration and assesses the potential opportunities for, and operational challenges of, integrating existing control activities for several of these diseases under an umbrella vertical programme.

A role for Mansonia uniformis mosquitoes in the transmission of lymphatic filariasis in Uganda?

The possible role of Mansonia uniformis mosquitoes in the transmission of lymphatic filariasis was assessed in an endemic area of Uganda, by examining their diurnal biting cycle, host preference and ability to support the development of experimental and natural Wuchereria bancrofti infections. Anopheles gambiae s.l. served as controls. Human landing catches revealed that outdoor biting peaked early in the evening (19:00-20:00h), while indoor biting peaked around midnight (23:00-24:00h). By far the majority of indoor collected M. uniformis had derived their blood meals from humans. Both biting and feeding behaviour were therefore compatible with a potential for transmission. In experimentally fed M. uniformis (total of 1915), the microfilariae were seen to ex-sheath and to start migration, but the L1s accumulated in the thorax and only few developed further. In dissections from Day 11 onwards, 4.6% (43/932) of M. uniformis had L2 larvae and 0.7% (7/932) had L3 larvae of W. bancrofti. The corresponding figures for An. gambiae s.l. were 13.4% and 4.6%, respectively. Dissection of wild caught M. uniformis (total of 6823) did not reveal any natural infections with W. bancrofti infective larvae, whereas wild caught An. gambiae s.l. had an infective rate of 1.3%. Other filarial species, and mermithids, were common in M. uniformis. It is concluded that M. uniformis has a limited potential to support development of W. bancrofti to the infective stage, and it does not appear to play a role as a vector under natural conditions.

Epidemiology and geography of Schistosoma mansoni in Uganda: implications for planning control.

Intestinal schistosomiasis caused by infection with Schistosoma mansoni is a widespread public health problem in Uganda. Although long known to be endemic, its current distribution within the country requires updating of parasitological data to help guide planned control. We report such data collected between 1998 and 2002 from 201 schools and 68 communities across Uganda. In accordance with epidemiological expectation, prevalence and intensity increased with age, peaking at 10-20 years and thereafter declined moderately with age, whereas intensity declined more rapidly with age, and the prevalence of infection in a school was non-linearly related to the mean intensity of infection. We used geographical information systems to map the distribution of infection and to overlay parasitological data with interpolated environmental surfaces. The derived maps indicate both a widespread occurrence of infection and a marked variability in infection prevalence, with prevalence typically highest near the lakeshore and along large rivers. No transmission occurred at altitudes >1400 m or where total annual rainfall was <900 mm; limits which can help estimate the population at risk of schistosomiasis. The results are discussed in reference to the ecology of infection and provide an epidemiological framework for the design and implementation of control efforts underway in Uganda.