Inter-Epidemic Transmission of Rift Valley Fever in\ud Livestock in the Kilombero River Valley, Tanzania:\ud A Cross-Sectional Survey

In recent years, evidence of Rift Valley fever (RVF) transmission during inter-epidemic periods in parts of Africa has increasingly been reported. The inter-epidemic transmissions generally pass undetected where there is no surveillance in the livestock or human populations. We studied the presence of and the determinants for inter-epidemic RVF transmission in an area experiencing annual flooding in southern Tanzania. A cross-sectional sero-survey was conducted in randomly selected cattle, sheep and goats in the Kilombero river valley from May to August 2011, approximately four years after the 2006/07 RVF outbreak in Tanzania. The exposure status to RVF virus (RVFV) was determined using two commercial ELISA kits, detecting IgM and IgG antibodies in serum. Information about determinants was obtained through structured interviews with herd owners. An overall seroprevalence of 11.3% (n = 1680) was recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in animals present during the outbreak. There was a linear increase in prevalence in the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were also positive for RVFV IgM antibodies indicating a recent infection. The spatial distribution of seroprevalence exhibited a few hotspots. The sex difference in seroprevalence in animals born after the previous epidemic was not significant (6.1% vs. 4.6% for females and males respectively, p = 0.158) whereas it was significant in animals present during the outbreak (26.0% vs. 7.8% for females and males respectively, p,0.001). Animals living .15 km from the flood plain were more likely to have antibodies than those living ,5 km (OR 1.92; 95% CI 1.04–3.56). Species, breed, herd composition, grazing practices and altitude were not associated with seropositivity. These findings indicate post-epidemic transmission of RVFV in the study area. The linear increase in seroprevalence in the post-epidemic annual cohorts implies a constant exposure and presence of active foci transmission preceding the survey

A Geographical Location Model for Targeted Implementation of Lure-and-Kill Strategies Against Disease-Transmitting Mosquitoes in Rural Areas

Outdoor devices for luring and killing disease-transmitting mosquitoes have been proposed as potential com- plementary interventions alongside existing intra-domiciliary methods namely insecticide treated nets and house spraying with residual insecticides. To enhance effectiveness of such outdoor interventions, it is essential to optimally locate them in such a way that they target most of the outdoor mosquitoes. Using odour-baited lure and kill stations (OBS) as an example, we describe a map model derived from: 1) com-munity participatory mapping conducted to identify mosquito breeding habitats, 2) entomological field studies conducted to estimate outdoor mosquito densities and to determine safe distances of the OBS from human dwellings, and 3) field surveys conducted to map households, roads, outdoor human aggregations and landmarks. The resulting data were combined in a Ge- ographical Information Systems (GIS) environment and analysed to determine optimal locations for the OBS. Separately, a GIS-interpolated map produced by asking community members to rank different zones of the study area and show where they expected to find most mosquitoes, was visually compared to another map interpolated from the entomological survey of outdoor mosquito densities. An easy-to-interpret suitability map showing optimal sites for placing OBS was produced, which clearly depicted areas least suitable and areas most suitable for locating the devices. Comparative visual interpretation of maps derived from interpolating the community knowledge and entomological data revealed major similarities between the two maps. Using distribution patterns of human and mosquito populations as well as characteristics of candidate outdoor interventions, it is possible to readily determine suitable areas for targeted positioning of the interventions, thus improve effectiveness. This study also highlights possibilities of relying on community knowledge to approximate areas where mosquitoes are most abundant and where to locate outdoor complementary interventions such as odour-baited lure and kill stations for controlling disease-transmitting mosquitoes.\u

Outdoor Mosquito Control Using Odour-Baited Devices: Development and Evaluation of a Potential New Strategy to Complement Indoor Malaria Prevention Methods

A considerable effort is currently underway to develop a malaria vaccine based on live Plasmodium falciparum sporozoites. The first requisite of a sporozoite vaccine is the guarantee of parasite arrest prior to the onset of the pathogenic blood stage. Immunisation with genetically attenuated parasites (GAP) that arrest in the liver forms a promising approach. Work in this thesis describes the development and characterisation of a P. berghei Δb9Δslarp GAP that fully arrests in the liver. Immunisation of multiple mouse strains with low numbers of Δb9Δslarp GAP resulted in sterile protection. The Δb9Δslarp GAP is there- fore the leading GAP vaccine candidate. Work in this the- sis further describes the effect of varying the parameters of sporozoite inoculation on parasite liver load. These findings provide a rationale for the design of clinical trials aimed at the administration of live attenuated P. falciparum sporozoites

Inter-epidemic Acquisition of Rift Valley Fever Virus in Humans in Tanzania.

In East Africa, epidemics of Rift Valley fever (RVF) occur in cycles of 5-15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP) generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection. Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression. RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71). Four of 16 (25.0%) IgM positives and 11/71 (15.5%) of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2-14.5) and risk was elevated with age (odds ratio (OR) 1.03 per year; 95% CI 1.01-1.04), among milkers (OR 2.19; 95% CI 1.23-3.91), and individuals eating raw meat (OR 4.17; 95% CI 1.18-14.66). Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42-6.48) than those that do not keep livestock. There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study's population. However, at least part of RVFV transmission appears to have occurred through bites of infected mosquitoes

Attracting, trapping and killing disease-transmitting mosquitoes using odor-baited stations - The Ifakara Odor-Baited Stations

BACKGROUND: To accelerate efforts towards control and possibly elimination of mosquito-borne diseases such as malaria and lymphatic filariasis, optimally located outdoor interventions could be used to complement existing intradomicilliary vector control methods such as house spraying with insecticides and insecticidal bednets. METHODS: We describe a new odor-baited station for trapping, contaminating and killing disease-transmitting mosquitoes. This device, named the 'Ifakara Odor-baited Station' (Ifakara OBS), is a 4 m3 hut-shaped canvas box with seven openings, two of which may be fitted with interception traps to catch exiting mosquitoes. It is baited with synthetic human odors and may be augmented with contaminants including toxic insecticides or biological agents. RESULTS: In field trials where panels of fabric were soaked in 1% pirimiphos-methyl solution and suspended inside the Ifakara OBS, at least 73.6% of Anopheles arabiensis, 78.7% of Culex and 60% of Mansonia mosquitoes sampled while exiting the OBS, died within 24 hours. When used simply as a trap and evaluated against two existing outdoor traps, Ifakara Tent trap and Mosquito Magnet-X(R), the OBS proved more efficacious than the Ifakara Tent trap in catching all mosquito species found (P < 0.001). Compared to the Mosquito Magnet-X(R), it was equally efficacious in catching An. arabiensis (P = 0.969), but was less efficacious against Culex (P < 0.001) or Mansonia species (P < 0.001). CONCLUSION: The Ifakara OBS is efficacious against disease-carrying mosquitoes including the malaria vector, An. arabiensis and Culicine vectors of filarial worms and arboviruses. It can be used simultaneously as a trap and as a contamination or killing station, meaning most mosquitoes which escape trapping would leave when already contaminated and die shortly afterwards. This technique has potential to complement current vector control methods, by targeting mosquitoes in places other than human dwellings, but its effectiveness in the field will require cheap, long-lasting and easy-to-use mosquito lures

Rift Valley fever : an open-source transmission dynamics simulation model

Rift Valley fever (RVF) is one of the major viral zoonoses in Africa, affecting humans and several domestic animal species. The epidemics in eastern Africa occur in a 5-15 year cycle coinciding with abnormally high rainfall generally associated to the warm phase of the El Niño event. However, recently, evidence has been gathered of inter-epidemic transmission. An open-source, easily applicable, accessible and modifiable model was built to simulate the transmission dynamics of RVF. The model was calibrated using data collected in the Kilombero Valley in Tanzania with people and cattle as host species and Ædes mcintoshi, Æ. ægypti and two Culex species as vectors. Simulations were run over a period of 27 years using standard parameter values derived from two previous studies in this region. Our model predicts low-level transmission of RVF, which is in line with epidemiological studies in this area. Emphasis in our simulation was put on both the dynamics and composition of vector populations in three ecological zones, in order to elucidate the respective roles played by different vector species: the model output did indicate the necessity of Culex involvement and also indicated that vertical transmission in Ædes mcintoshi may be underestimated. This model, being built with open-source software and with an easy-to-use interface, can be adapted by researchers and control program managers to their specific needs by plugging in new parameters relevant to their situation and locality

An extra-domiciliary method of delivering entomopathogenic fungus, Metharizium anisopliae IP 46 for controlling adult populations of the malaria vector, Anopheles arabiensis

Fungal biopesticides have the potential to significantly reduce densities of malaria vectors as well as associated malaria transmission. In previous field trials, entomopathogenic fungus was delivered from within human dwellings, where its efficacy was limited by low infection rates of target mosquitoes, high costs of spraying fungus inside houses, and potential public health concerns associated with introducing fungal conidia inside houses. Here we have demonstrated that Metarhizium anisopliae IP 46, delivered within an extra-domiciliary odor-baited station (OBS), can infect and slowly-kill a high proportion of the wild adult malaria vector, Anopheles arabiensis which entered and exited the OBS. This study, carried out in rural Tanzania, showed that by using a concentration of 3.9 × 1010 conidia/m2, more than 95% of mosquitoes that flew in and out of the OBS died within 14 days post-exposure. At least 86% infection of mosquito cadavers was recorded with a significant reduction in the probability of daily survival of exposed An. arabiensis in both treatments tested: low quantity of conidia (eave baffles plus one cotton panel; HR = 2.65, P < 0.0001) and high quantity of conidia (eave baffles plus two cotton panels; HR = 2.32, P < 0.0001). We conclude that high infection rates of entomopathogenic fungi on wild malaria vectors and possibly significant disruption of malaria transmission can be achieved if the fungus is delivered using optimally located outdoor odor-baited stations

Effects of a new outdoor mosquito control device, the mosquito landing box, on densities and survival of the malaria vector, Anopheles arabiensis, inside controlled semi-field settings

Background The significance of malaria transmission occurring outdoors has risen even in areas where indoor interventions such as long-lasting insecticidal nets and indoor residual spraying are common. The actual contamination rates and effectiveness of recently developed outdoor mosquito control device, the mosquito landing box (MLB), on densities and daily survival of host-seeking laboratory Anopheles arabiensis, which readily bites humans outdoors was demonstrated. Methods Experiments were conducted in large semi-field systems (SFS) with human volunteers inside, to mimic natural ecosystems, and using MLBs baited with natural or synthetic human odours and carbon dioxide. The MLBs were dusted with 10 % pyriproxyfen (PPF) or entomopathogenic fungi (Metarhizium anisopliae) spores to mark mosquitoes physically contacting the devices. Each night, 400 laboratory-reared An. arabiensis females were released in one SFS chamber with two MLBs, and another chamber without MLBs (control). Mosquitoes were individually recaptured while attempting to bite volunteers inside SFS or by aspiration from SFS walls. Mosquitoes from chambers with PPF-treated MLBs and respective controls were individually dipped in water-filled cups containing ten conspecific third-instar larvae, whose subsequent development was monitored. Mosquitoes recaptured from chambers with fungi-treated MLBs were observed for fungal hyphal growth on their cadavers. Separately, effects on daily survival were determined by exposing An. arabiensis in chambers having MLBs treated with 5 % pirimiphos methyl compared to chambers without MLBs (control), after which the mosquitoes were recaptured and monitored individually until they died. Results Up to 63 % (152/240) and 43 % (92/210) of mosquitoes recaptured inside treatment chambers were contaminated with pyriproxyfen and M. anisopliae, respectively, compared to 8 % (19/240) and 0 % (0/164) in controls. The mean number of larvae emerging from cups in which adults from chambers with PPF-treated MLBs were dipped was significantly lower [0.75 (0.50–1.01)], than in controls [28.79 (28.32–29.26)], P < 0.001). Daily survival of mosquitoes exposed to 5 % pirimiphos methyl was nearly two-fold lower than controls [hazard ratio (HR) = 1.748 (1.551–1.920), P < 0.001]. Conclusion High contamination rates in exposed mosquitoes even in presence of humans, demonstrates potential of MLBs for controlling outdoor-biting malaria vectors, either by reducing their survival or directly killing host-seeking mosquitoes. The MLBs also have potential for dispensing filial infanticides, such as PPF, which mosquitoes can transmit to their aquatic habitats for mosquito population control. Keywords: Mosquito landing box; Malaria; Elimination; Anopheles arabiensis ; Pirimiphos methyl; Outdoor biting; Pyriproxyfen; Metarhizium anisopliae ; Semi-field syste