Identification of malaria transmission and epidemic hotspots in the western Kenya highlands: its application to malaria epidemic prediction

<p>Abstract</p> <p>Background</p> <p>Malaria in the western Kenya highlands is characterized by unstable and high transmission variability which results in epidemics during periods of suitable climatic conditions. The sensitivity of a site to malaria epidemics depends on the level of immunity of the human population. This study examined how terrain in the highlands affects exposure and sensitivity of a site to malaria.</p> <p>Methods</p> <p>The study was conducted in five sites in the western Kenya highlands, two U-shaped valleys (Iguhu, Emutete), two V-shaped valleys (Marani, Fort-Ternan) and one plateau (Shikondi) for 16 months among 6-15 years old children. Exposure to malaria was tested using circum-sporozoite protein (CSP) and merozoite surface protein (MSP) immunochromatographic antibody tests; malaria infections were tested by microscopic examination of thick and thin smears, the children's homes were georeferenced using a global positioning system. Paired t-test was used to compare the mean prevalence rates of the sites, K-function was use to determine if the clustering of malaria infections was significant.</p> <p>Results and Discussion</p> <p>The mean antibody prevalence was 22.6% in Iguhu, 24% in Emutete, 11.5% in Shikondi, 8.3% in Fort-Ternan and 9.3% in Marani. The mean malaria infection prevalence was 23.3% in Iguhu, 21.9% in Emutete, 4.7% in Shikondi, 2.9% in Fort-Ternan and 2.4% in Marani. There was a significant difference in the antibodies and malaria infection prevalence between the two valley systems, and between the two valley systems and the plateau (P < 0.05). There was no significant difference in the antibodies and malaria infection prevalence in the two U-shaped valleys (Iguhu and Emutete) and in the V-shaped valleys (Marani and Fort Ternan) (P > 0.05). There was 8.5- fold and a 2-fold greater parasite and antibody prevalence respectively, in the U-shaped compared to the V-shaped valleys. The plateau antibody and parasite prevalence was similar to that of the V-shaped valleys. There was clustering of malaria antibodies and infections around flat areas in the U-shaped valleys, the infections were randomly distributed in the V-shaped valleys and less clustered at the plateau.</p> <p>Conclusion</p> <p>This study showed that the V-shaped ecosystems have very low malaria prevalence and few individuals with an immune response to two major malaria antigens and they can be considered as epidemic hotspots. These populations are at higher risk of severe forms of malaria during hyper-transmission seasons. The plateau ecosystem has a similar infection and immune response to the V-shaped ecosystems. The U-shaped ecosystems are transmission hotspots.</p

Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Surveillance of malaria vector population density and biting behaviour in western Kenya

BACKGROUND: Malaria is a great public health burden and Africa suffers the largest share of malaria-attributed deaths. Despite control efforts targeting indoor malaria transmission, such as insecticide-treated bed nets (ITNs) and deployment of indoor residual spraying, transmission of the parasite in western Kenya is still maintained. This study was carried out to determine the impact of ITNs on indoor vector densities and biting behaviour in western Kenya. METHODS: Indoor collection of adult mosquitoes was done monthly in six study sites in western Kenya using pyrethrum spray collections from 2012 to 2014. The rotator trap collections were done in July–August in 2013 and May–June in 2014. Mosquitoes were collected every 2 h between 18.00 and 08.00 h. Human behaviour study was conducted via questionnaire surveys. Species within Anopheles gambiae complex was differentiated by PCR and sporozoite infectivity was determined by ELISA. Species distribution was determined and bed net coverage in the study sites was recorded. RESULTS: During the study a total of 5,469 mosquito vectors were collected from both PSC and Rotator traps comprising 3,181 (58.2%) Anopheles gambiae and 2,288 (41.8%) Anopheles funestus. Compared to all the study sites, Rae had the highest density of An. gambiae with a mean of 1.2 (P < 0.001) while Kombewa had the highest density of An. funestus with a mean of 1.08 (P < 0.001). Marani had the lowest density of vectors with 0.06 An. gambiae and 0.17 An. funestus (P < 0.001). Among the 700 PCR confirmed An. gambiaes.l. individuals, An. gambiaes.s. accounted for 49% and An. arabiensis 51%. Over 50% of the study population stayed outdoors between 18.00 and 20.00 and 06.00 and 08.00 which was the time when highest densities of blood fed vectors were collected. Anopheles gambies.s. was the main malaria parasite vector in the highland sites and An. arabiensis in the lowland sites. Bed net ownership in 2012 averaged 87% across the study sites. CONCLUSIONS: This study suggests that mass distribution of ITNs has had a significant impact on vector densities, species distribution and sporozoite rate. However, shift of biting time poses significant threats to the current malaria vector control strategies which heavily rely on indoor controls

Entomological aspects and the role of human behaviour in malaria transmission in a highland region of the Republic of Yemen

© 2016 Al-Eryani et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus

Shady business: understanding the spatial ecology of exophilic Anopheles mosquitoes

Background: Understanding the ecology of exophilic anophelines is a key step toward developing outdoor control strategies to complement existing indoor control tools against malaria vectors. This study was conducted to assess the movement pattern of exophilic Anopheles mosquitoes between blood meal sources and resting habitats, and the landscape factors dictating their resting habitat choice. Results: Resting clay pots were placed at 5 m, 25 m, 50 m, 75 m and 100 m away from isolated focal houses, radiating from them in four directions. The locations of the clay pots represent heterogeneous land cover types at a relatively fine spatial scale in the landscape. The effect of the landscape characters on the number of both female and male anophelines caught was modelled using zero-inflated negative binomial regression with a log link function. A total of 420 Anopheles mosquitoes (353 females and 67 males) belonging to three species; Anopheles arabiensis, Anopheles pharoensis, and Anopheles tenebrosus were caught in the resting clay pots, with An. arabiensis being the dominant species. Canopy cover, distance from the house, and land cover type were the significant landscape characters influencing the aggregation of resting mosquitoes. Both the count and binary models showed that canopy cover was the strongest predictor variable on the counts and the presence of Anopheles mosquitoes in the clay pots. Female Anopheles were most frequently found resting in the pots placed in banana plantations, and at sampling points that were at the greater distances (75 m and 100 m) from the focal house. Conclusions: This study showed that exophilic Anopheles mosquitoes tend to rest in shaded areas some distance away from human habitation. These findings are important when targeting mosquitoes outdoors, complementing the existing effort being made to control malaria vectors indoors

Clinical malaria case definition and malaria attributable fraction in the highlands of western Kenya

BACKGROUND: In African highland areas where endemicity of malaria varies greatly according to altitude and topography, parasitaemia accompanied by fever may not be sufficient to define an episode of clinical malaria in endemic areas. To evaluate the effectiveness of malaria interventions, age-specific case definitions of clinical malaria needs to be determined. Cases of clinical malaria through active case surveillance were quantified in a highland area in Kenya and defined clinical malaria for different age groups. METHODS: A cohort of over 1,800 participants from all age groups was selected randomly from over 350 houses in 10 villages stratified by topography and followed for two-and-a-half years. Participants were visited every two weeks and screened for clinical malaria, defined as an individual with malaria-related symptoms (fever [axillary temperature ≥ 37.5°C], chills, severe malaise, headache or vomiting) at the time of examination or 1–2 days prior to the examination in the presence of a Plasmodium falciparum positive blood smear. Individuals in the same cohort were screened for asymptomatic malaria infection during the low and high malaria transmission seasons. Parasite densities and temperature were used to define clinical malaria by age in the population. The proportion of fevers attributable to malaria was calculated using logistic regression models. RESULTS: Incidence of clinical malaria was highest in valley bottom population (5.0% cases per 1,000 population per year) compared to mid-hill (2.2% cases per 1,000 population per year) and up-hill (1.1% cases per 1,000 population per year) populations. The optimum cut-off parasite densities through the determination of the sensitivity and specificity showed that in children less than five years of age, 500 parasites per μl of blood could be used to define the malaria attributable fever cases for this age group. In children between the ages of 5–14, a parasite density of 1,000 parasites per μl of blood could be used to define the malaria attributable fever cases. For individuals older than 14 years, the cut-off parasite density was 3,000 parasites per μl of blood. CONCLUSION: Clinical malaria case definitions are affected by age and endemicity, which needs to be taken into consideration during evaluation of interventions

Topography and malaria transmission heterogeneity in western Kenya highlands: prospects for focal vector control

BACKGROUND: Recent resurgence of malaria in the highlands of Western Kenya has called for a more comprehensive understanding of the previously neglected complex highland vector ecology. Besides other drivers of malaria epidemiology, topography is likely to have a major effect on spatial vector and parasite distribution. The aim of this study was to determine the effects of topography on malaria spatial vector distribution and parasite prevalence. METHODOLOGY: Indoor resting adult malaria vectors and blood parasites were collected in three villages along a 4 km transect originating from the valley bottom and ending at the hilltop for 13 months. Members of the Anopheles gambiae complex were identified by PCR. Blood parasites were collected from children 6–13 years old and densities categorized by site of home location and age of the children. RESULTS: Ninety eight percent (98%) of An. gambiae s.s. and (99%) Anopheles funestus were collected in houses located at the edge of the valley bottom, whereas 1% of An. gambiae s.s. were collected at mid hill and at the hilltop respectively. No An. funestus were collected at the hilltop. Malaria prevalence was 68% at the valley bottom, 40.2% at mid hill and 26.7% at the hilltop. Children aged six years and living at the edge of the valley bottom had an annual geometric mean number of 66.1 trophozoites for every 200 white blood cells, while those living at mid-hill had a mean of 84.8, and those living at hilltop had 199.5 trophozoites. CONCLUSION: Malaria transmission in this area is mainly confined to the valley bottom. Effective vector control could be targeted at the foci. However, the few vectors observed at mid-hill maintained a relatively high prevalence rate. The higher variability in blood parasite densities and their low correlation with age in children living at the hilltop suggests a lower stability of transmission than at the mid-hill and valley bottom

The role of anti-malarial drugs in eliminating malaria

Abstract Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and transmissibility coincides with peak asexual parasite densities. Mature Plasmodium falciparum gametocytes are more drug resistant and affected only by artemisinins and 8-aminoquinolines. The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection. Radical treatment with primaquine plays a key role in the eradication of vivax and ovale malaria. More evidence is needed on the safety of primaquine when administered without screening for G6PD deficiency to inform individual and mass treatment approaches in the context of malaria elimination programmes.</p