Mosquitoes and transmission of malaria parasites – not just vectors

The regional malaria epidemics of the early 1900s provided the basis for much of our current understanding of malaria epidemiology. Colonel Gill, an eminent malariologist of that time, suggested that the explosive nature of the regional epidemics was due to a sudden increased infectiousness of the adult population. His pertinent observations underlying this suggestion have, however, gone unheeded. Here, the literature on Plasmodium seasonal behaviour is reviewed and three historical data sets, concerning seasonal transmission of Plasmodium falciparum, are examined. It is proposed that the dramatic seasonal increase in the density of uninfected mosquito bites results in an increased infectiousness of the human reservoir of infection and, therefore, plays a key role in "kick-starting" malaria parasite transmission

Risk of exposure to potential vector mosquitoes for rural workers in Northern Lao PDR

Background One major consequence of economic development in South-East Asia has been a rapid expansion of rubber plantations, in which outbreaks of dengue and malaria have occurred. Here we explored the difference in risk of exposure to potential dengue, Japanese encephalitis (JE), and malaria vectors between rubber workers and those engaged in traditional forest activities in northern Laos PDR. Methodology/Principal findings Adult mosquitoes were collected for nine months in secondary forests, mature and immature rubber plantations, and villages. Human behavior data were collected using rapid participatory rural appraisals and surveys. Exposure risk was assessed by combining vector and human behavior and calculating the basic reproduction number (R0) in different typologies. Compared to those that stayed in the village, the risk of dengue vector exposure was higher for those that visited the secondary forests during the day (odds ratio (OR) 36.0), for those living and working in rubber plantations (OR 16.2) and for those that tapped rubber (OR 3.2). Exposure to JE vectors was also higher in the forest (OR 1.4) and, similar when working (OR 1.0) and living in the plantations (OR 0.8). Exposure to malaria vectors was greater in the forest (OR 1.3), similar when working in the plantations (OR 0.9) and lower when living in the plantations (OR 0.6). R0 for dengue was >2.8 for all habitats surveyed, except villages where R0≤0.06. The main malaria vector in all habitats was Anopheles maculatus s.l. in the rainy season and An. minimus s.l. in the dry season. Conclusions/Significance The highest risk of exposure to vector mosquitoes occurred when people visit natural forests. However, since rubber workers spend long periods in the rubber plantations, their risk of exposure is increased greatly compared to those who temporarily enter natural forests or remain in the village. This study highlights the necessity of broadening mosquito control to include rubber plantations

Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

BACKGROUND: Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. RESULTS: Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio) that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density) or with increased transmission. CONCLUSIONS: We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality) and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical research and adds support to the prediction that partially effective vaccines may select for increasingly virulent malaria parasite strains. By contrast, there was no consistent correlation between transmission and sub-lethal anaemia, a more common outcome of malaria infection. However, overall, the data are not inconsistent with the recent proposal that sub-lethal effects may impose an upper limit on virulence. Moreover, clone specific differences in transmission phenotypes linked to anaemia do suggest that there is considerable adaptive potential relating anaemia and transmission that may lead to uncertain consequences following intervention strategies

Risk factors for mosquito house entry in the Lao PDR.

BACKGROUND: Construction of the Nam Theun 2 hydroelectric project and flooding of a 450 km(2) area of mountain plateau in south-central Lao PDR resulted in the resettlement of 6,300 people to newly built homes. We examined whether new houses would have altered risk of house entry by mosquitoes compared with traditional homes built from poorer construction materials. METHODOLOGY/PRINCIPAL FINDINGS: Surveys were carried out in the Nam Theun 2 resettlement area and a nearby traditional rice farming area in 2010. Mosquitoes were sampled in bedrooms using CDC light traps in 96 resettlement houses and 96 traditional houses and potential risk factors for mosquito house entry were recorded. Risk of mosquito house entry was more than twice as high in traditional bamboo houses compared with those newly constructed from wood (Putative Japanese Encephalitis (JE) vector incidence rate ratio (IRR) = 2.26, 95% CI 1.38-3.70, P = 0.001; Anopheline IRR = 2.35, 95% CI: 1.30-4.23, P = 0.005). Anophelines were more common in homes with cattle compared against those without (IRR = 2.32, 95% CI: 1.29-4.17, P = 0.005).Wood smoke from cooking fires located under the house or indoors was found to be protective against house entry by both groups of mosquito, compared with cooking in a separate room beside the house (Putative JE vector IRR = 0.43, 95% CI: 0.26-0.73, P = 0.002; Anopheline IRR = 0.22, 95% CI: 0.10-0.51, P<0.001). CONCLUSIONS/SIGNIFICANCE: Construction of modern wooden homes should help reduce human-mosquito contact in the Lao PDR. Reduced mosquito contact rates could lead to reduced transmission of diseases such as JE and malaria. Cattle ownership was associated with increased anopheline house entry, so zooprophylaxis for malaria control is not recommended in this area. Whilst wood smoke was protective against putative JE vector and anopheline house entry we do not recommend indoor cooking since smoke inhalation can enhance respiratory disease

Diversity of Mosquitoes (Diptera: Culicidae) Attracted to Human Subjects in Rubber Plantations, Secondary Forests, and Villages in Luang Prabang Province, Northern Lao PDR

The impact of the rapid expansion of rubber plantations in South-East Asia on mosquito populations is uncertain. We compared the abundance and diversity of adult mosquitoes using human-baited traps in four typical rural habitats in northern Lao PDR: secondary forests, immature rubber plantations, mature rubber plantations, and villages. Generalized estimating equations were used to explore differences in mosquito abundance between habitats, and Simpson’s diversity index was used to measure species diversity. Over nine months, 24,927 female mosquitoes were collected, including 51 species newly recorded in Lao PDR. A list of the 114 mosquito species identified is included. More mosquitoes, including vector species, were collected in the secondary forest than immature rubber plantations (rainy season, odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31–0.36; dry season, 0.46, 95% CI 0.41–0.51), mature rubber plantations (rainy season, OR 0.25, 95% CI 0.23–0.27; dry season, OR 0.25, 95% CI 0.22–0.28), and villages (rainy season, OR 0.13, 95% CI 0.12–0.14; dry season, 0.20, 95% CI 0.18–0.23). All habitats showed high species diversity (Simpson’s indexes between 0.82–0.86) with vectors of dengue, Japanese encephalitis (JE), lymphatic filariasis, and malaria. In the secondary forests and rubber plantations, Aedes albopictus (Skuse), a dengue vector, was the dominant mosquito species, while in the villages, Culex vishnui (Theobald), a JE vector, was most common. This study has increased the overall knowledge of mosquito fauna in Lao PDR. The high abundance of Ae. albopictus in natural and man-made forests warrants concern, with vector control measures currently only implemented in cities and villages

Impact of mosquito bites on asexual parasite density and gametocyte prevalence in asymptomatic chronic Plasmodium falciparum infections and correlation with IgE and IgG titers.

International audienceAn immunomodulatory role of arthropod saliva has been well documented, but evidence for an effect on Plasmodium sp. infectiousness remains controversial. Mosquito saliva may orient the immune response toward a Th2 profile, thereby priming a Th2 response against subsequent antigens, including Plasmodium. Orientation toward a Th1 versus a Th2 profile promotes IgG and IgE proliferation, respectively, where the former is crucial for the development of an efficient antiparasite immune response. Here we assessed the direct effect of mosquito bites on the density of Plasmodium falciparum asexual parasites and the prevalence of gametocytes in chronic, asymptomatic infections in a longitudinal cohort study of seasonal transmission. We additionally correlated these parasitological measures with IgE and IgG antiparasite and anti-salivary gland extract titers. The mosquito biting density was positively correlated with the asexual parasite density but not asexual parasite prevalence and was negatively correlated with gametocyte prevalence. Individual anti-salivary gland IgE titers were also negatively correlated with gametocyte carriage and were strongly positively correlated with antiparasite IgE titers, consistent with the hypothesis that mosquito bites predispose individuals to develop an IgE antiparasite response. We provide evidence that mosquito bites have an impact on asymptomatic infections and differentially so for the production of asexual and sexual parasites. An increased research focus on the immunological impact of mosquito bites during asymptomatic infections is warranted, to establish whether strategies targeting the immune response to saliva can reduce the duration of infection and the onward transmission of the parasite

Pilot Anopheles gambiae full-length cDNA study: sequencing and initial characterization of 35,575 clones

We describe the preliminary analysis of over 35,000 clones from a full-length enriched cDNA library from the malaria mosquito vector Anopheles gambiae. The clones define nearly 3,700 genes, of which around 2,600 significantly improve current gene definitions. An additional 17% of the genes were not previously annotated, suggesting that an equal percentage may be missing from the current Anopheles genome annotation

Validation of Mesocyclops (Copepoda) and community participation as an effective combination for Dengue control in Northern Vietnam

The “Programme Meso-Vietnam” was implemented in Vietnam from October 2007 to December 2010 to reduce dengue and dengue hemorrhagic fever incidence and to improve the quality of life in the four project communes. This dengue control project was based on biological control using Mesocyclops, a larvivorous micro-crustacean, as well as on the establishment of a strong community involvement to educate the population on dengue transmission and to reduce Aedes breeding by removal of containers. During three years, a network of collaborators was responsible for introducing Mesocyclops in all the containers defined as key breeding-sites, and regular activities such as community training workshops, school programmes, clean-up campaigns and health promotion through IEC programmess were performed. To make this programme sustainable, local leadership has been strengthened as well. The use of these larvivorous micro-crustaceans as a biological control strategy against dengue over the medium and long term, when combined with community participation and effective health promotion, demonstrated a significant reduction in dengue vector populations and dengue cases.  In Vietnam, this study reconfirms that there is an ecological alternative to systematic use of insecticides to control dengue vector population. (Abstract word count: 186)Le " Programme Meso-Vietnam " a été mis en œuvre au Vietnam entre octobre 2007 et décembre 2010. Ce programme vise à réduire l'incidence de la dengue et de la fièvre hémorragique de la dengue et à améliorer la qualité de vie dans les quatre communes sélectionnées pour le projet. Ce projet de lutte contre la dengue était basé sur un contrôle biologique assuré par des Mésocyclopes, micro-crustacés larvivores, et sur l'établissement d'une forte implication de la communauté pour éduquer la population sur la transmission de la dengue et pour réduire la reproduction des moustiques Aedes par élimination des conteneurs leur servant de site de ponte. Pendant trois ans, un réseau de collaborateurs a été chargé d'introduire des Mésocyclopes dans tous les conteneurs définis comme des sites de reproduction clés, et des activités régulières telles que des ateliers de formation communautaires, des programmes scolaires, des campagnes de nettoyage et des activités de promotion de la santé via les programmes IEC ont été mises en place. En outre, pour assurer la pérennité de ce programme, le leadership local a été renforcé. L'utilisation de ces micro-crustacés larvivores comme stratégie de contrôle biologique de la dengue à moyen et long terme, associée à une participation communautaire et à une promotion efficace de la santé, a permis d'aboutir à une réduction significative des populations vecteurs de la dengue et des cas de dengue. Au Vietnam, cette étude confirme une fois de plus qu'il existe une alternative écologique à l'utilisation systématique d'insecticides pour lutter contre les vecteurs de la dengue.El “Programa Meso-Vietnam” se implementó en Vietnam desde octubre de 2007 hasta diciembre de 2010 para reducir la incidencia del dengue y la fiebre hemorrágica del dengue y para mejorar la calidad de vida en los cuatro municipios del proyecto. Este proyecto de control del dengue se basaba en el control biológico usando Mesocyclops, un microcrustáceo larvívoro, así como en el establecimiento de una fuerte implicación comunitaria para educar a la población sobre la transmisión del dengue y para reducir la cría de Aedes mediante la eliminación de recipientes. Durante tres años, una red de colaboradores fue responsable de la introducción de Mesocyclops en todos los recipientes definidos como sitios clave para la cría, y se realizaron actividades regulares tales como talleres de formación comunitaria, programas escolares, campañas de limpieza y promoción de la salud a través de programas de IEC. Para hacer sostenible este programa, también se reforzó el liderazgo local. El uso de estos microcrustáceos larvívoros como estrategia de control biológico contra el dengue a medio y largo plazo demostró una reducción significativa de las poblaciones de vectores del dengue y los casos de dengue cuando se combinaba con la participación comunitaria y la promoción eficaz de la salud. En Vietnam, este estudio vuelve a confirmar que existe una alternativa ecológica al uso sistemático de insecticidas para controlar la población de vectores del dengue

Low seroprevalence of COVID-19 in Lao PDR, late 2020

Background In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure. Methods Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex. Findings In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative). Interpretation We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses. Funding Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs (“PaReCIDS II”)