Plasmodium knowlesi and Wuchereria bancrofti: Their Vectors and Challenges for the Future

Malaria and filariasis still continue to pose public health problems in developing countries of the tropics. Although plans are in progress for the elimination of both these parasitic vector borne diseases, we are now faced with a daunting challenge as we have a fifth species, Plasmodium knowlesi a simian malaria parasite affecting humans. Similarly in peninsular Malaysia, filariasis was mainly due to Brugia malayi. However, we now see cases of Wuchereria bancrofti in immigrant workers coming into the country. In order to successfully eliminate both these diseases we need to know the vectors involved and introduce appropriate control measures to prevent the diseases occurring in the future. As for knowlesi malaria it is still uncertain if human to human transmission through mosquito bites is occurring. However, P. knowlesi in human is not a rare occurrence anymore and has all the characteristics of a pathogen spreading due to changes in the ecosystem, international travel, and cross border migration. This has created a more complex situation. In order to overcome these challenges we need to revamp our control measures. This paper reviews the vectors of malaria and filariasis in Southeast Asia with special emphasis on P. knowlesi and W. bancrofti in Malaysia and their control strategies

Human and Simian Malaria in the Greater Mekong Subregion and Challenges for Elimination

In recent years malaria initiatives have increasingly shifted from malaria control to a focus on achieving malaria elimination in the Southeast Asia region. However, this region experiences unique challenges in this transition due to its distinctive malaria ecosystem (mainly related to forests) and high volume of population movement (both within and between countries). These bioenvironmental factors increase the exposure of populations at higher risk due to their close association with forest, and contributes to outdoor and residual transmission. Given that this region has also historically been the source of resistance to anti-malarial drugs, the potential spread of artemisinin resistance via global transportation routes would pose a major threat to malaria control and elimination efforts worldwide. In addition, other factors also hinder the malaria elimination goal such as importation of parasite infection, uncontrolled monkey malaria (Plasmodium knowlesi), or the fact that many countries in this region experience mixed infections where P. vivax becomes a more predominant species as overall malaria transmission decreases. This chapter addresses these challenges in detail and provide recommendations and key priorities to overcome these obstacles to accelerate efforts for achieving malaria elimination

Choosing the lesser of two evils, the better of two goods: Specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning

Seasonal and spatial dynamics of the primary vector of plasmodium knowlesi within a major transmission focus in Sabah, Malaysia

Background The simian malaria parasite Plasmodium knowlesi is emerging as a public health problem in Southeast Asia, particularly in Malaysian Borneo where it now accounts for the greatest burden of malaria cases and deaths. Control is hindered by limited understanding of the ecology of potential vector species. Methodology/Principal Findings We conducted a one year longitudinal study of P. knowlesi vectors in three sites within an endemic area of Sabah, Malaysia. All mosquitoes were captured using human landing catch. Anopheles mosquitoes were dissected to determine, oocyst, sporozoites and parous rate. Anopheles balabacensis is confirmed as the primary vector of. P. knowlesi (using nested PCR) in Sabah for the first time. Vector densities were significantly higher and more seasonally variable in the village than forest or small scale farming site. However An. balabacensis survival and P. knowlesi infection rates were highest in forest and small scale farm sites. Anopheles balabacensis mostly bites humans outdoors in the early evening between 1800 to 2000hrs. Conclusions/Significance This study indicates transmission is unlikely to be prevented by bednets. This combined with its high vectorial capacity poses a threat to malaria elimination programmes within the region. Author Summary The first natural infection of Plasmodium knowlesi was reported 40 years ago. At that time it was perceived that the infection would not affect humans. However, now P. knowlesi is the predominant malaria species (38% of the cases) infecting people in Malaysia and is a notable obstacle to malaria elimination in the country. Plasmodium knowlesi has also been reported from all countries in Southeast Asia with the exception of Lao PDR and Timor Leste. In Sabah, Malaysian Borneo cases of human P. knowlesi are increasing. Thus, a comprehensive understanding of the bionomics of the vectors is required so as to enable proper control strategies. Here, we conducted a longitudinal study in Kudat district, Sabah, to determine and characterize the vectors of P. knowlesi within this transmission foci. Anopheles balabacensis was the predominant mosquito in all study sites and is confirmed as vector for P. knowlesi and other simian malaria parasites. The peak biting time was in the early part of the evening between1800 to 2000. Thus, breaking the chain of transmission is an extremely challenging task for the malaria elimination programme

Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

<p>Abstract</p> <p>Background</p> <p>A large focus of human infections with <it>Plasmodium knowlesi</it>, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit.</p> <p>Methods</p> <p>Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites.</p> <p>Results and Discussions</p> <p>Over an 11-month period, a total of 2,504 <it>Anopheles </it>mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. <it>Anopheles latens </it>(62.3%) and <it>Anopheles watsonii </it>(30.6%) were the predominant species caught in the forested ecotypes, while in the farm <it>Anopheles donaldi </it>(49.9%) and <it>An. latens </it>(35.6%) predominated. In the long house, <it>An. latens </it>(29.6%) and <it>An. donaldi </it>(22.8%) were the major Anopheline species. However, <it>An. latens </it>was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. <it>An. latens </it>was found biting early as 18.00 hours.</p> <p>Conclusion</p> <p><it>Anopheles latens </it>is the main vector for <it>P</it>. <it>knowlesi </it>malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of <it>An. latens </it>makes it an efficient vector for the transmission of <it>P. knowlesi </it>parasites to both human and monkey hosts.</p

Vertical stratification of adult mosquitoes (Diptera: Culicidae) within a tropical rainforest in Sabah, Malaysia.

BACKGROUND: Malaria cases caused by Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques, are increasing rapidly in Sabah, Malaysia. One hypothesis is that this increase is associated with changes in land use. A study was carried out to identify the anopheline vectors present in different forest types and to observe the human landing behaviour of mosquitoes. METHODS: Mosquito collections were carried out using human landing catches at ground and canopy levels in the Tawau Division of Sabah. Collections were conducted along an anthropogenic disturbance gradient (primary forest, lightly logged virgin jungle reserve and salvage logged forest) between 18:00 and 22:00 h. RESULTS: Anopheles balabacensis, a vector of P. knowlesi, was the predominant species in all collection areas, accounting for 70 % of the total catch, with a peak landing time of 18:30-20:00 h. Anopheles balabacensis had a preference for landing on humans at ground level compared to the canopy (p < 0.0001). A greater abundance of mosquitoes were landing in the logged forest compared to the primary forest (p < 0.0001). There was no difference between mosquito abundance in the logged forest and lightly logged forest (p = 0.554). A higher evening temperature (p < 0.0001) and rainfall (p < 0.0001) significantly decreased mosquito abundance during collection nights. CONCLUSIONS: This study demonstrates the potential ability of An. balabacensis to transmit P. knowlesi between canopy-dwelling simian hosts and ground-dwelling humans, and that forest disturbance increases the abundance of this disease vector. These results, in combination with regional patterns of land use change, may partly explain the rapid rise in P. knowlesi cases in Sabah. This study provides essential data on anthropophily for the principal vector of P. knowlesi which is important for the planning of vector control strategies

Human exposure to zoonotic malaria vectors in village, farm and forest habitats in Sabah, Malaysian Borneo.

The zoonotic malaria parasite, Plasmodium knowlesi, is now a substantial public health problem in Malaysian Borneo. Current understanding of P. knowlesi vector bionomics and ecology in Sabah comes from a few studies near the epicentre of human cases in one district, Kudat. These have incriminated Anopheles balabacensis as the primary vector, and suggest that human exposure to vector biting is peri-domestic as well as in forest environments. To address the limited understanding of vector ecology and human exposure risk outside of Kudat, we performed wider scale surveillance across four districts in Sabah with confirmed transmission to investigate spatial heterogeneity in vector abundance, diversity and infection rate. Entomological surveillance was carried out six months after a cross-sectional survey of P. knowlesi prevalence in humans throughout the study area; providing an opportunity to investigate associations between entomological indicators and infection. Human-landing catches were performed in peri-domestic, farm and forest sites in 11 villages (3-4 per district) and paired with estimates of human P. knowlesi exposure based on sero-prevalence. Anopheles balabacensis was present in all districts but only 6/11 villages. The mean density of An. balabacensis was relatively low, but significantly higher in farm (0.094/night) and forest (0.082/night) than peri-domestic areas (0.007/night). Only one An. balabacensis (n = 32) was infected with P. knowlesi. Plasmodium knowlesi sero-positivity in people was not associated with An. balabacensis density at the village-level however post hoc analyses indicated the study had limited power to detect a statistical association due low vector density. Wider scale sampling revealed substantial heterogeneity in vector density and distribution between villages and districts. Vector-habitat associations predicted from this larger-scale surveillance differed from those inferred from smaller-scale studies in Kudat; highlighting the importance of local ecological context. Findings highlight potential trade-offs between maximizing temporal versus spatial breadth when designing entomological surveillance; and provide baseline entomological and epidemiological data to inform future studies of entomological risk factors for human P. knowlesi infection