Human Infections with Plasmodium knowlesi, the Philippines.

Five human cases of infection with the simian malaria parasite Plasmodium knowlesi from Palawan, the Philippines, were confirmed by nested PCR. This study suggests that this zoonotic infection is found across a relatively wide area in Palawan and documents autochthonous cases in the country

Characterising the spatial dynamics of sympatric Aedes Aegypti and Aedes Albopictus populations in the Philippines

Entomological surveillance and control are essential to the management of dengue fever (DF). Hence, understanding the spatial and temporal patterns of DF vectors, Aedes (Stegomyia) aegypti (L.) and Ae. (Stegomyia) albopictus (Skuse), is paramount. In th

Estimating dengue vector abundance in the wet and dry season : implications for targeted vector control in urban and peri-urban Asia

Background: Research has shown that the classical Stegomyia indices (or ‘‘larval indices’’) of the dengue vector Aedes aegypti reflect the absence or presence of the vector but do not provide accurate measures of adult mosquito density. In contrast, pupal indices as collected in pupal productivity surveys are a much better proxy indicator for adult vector abundance. However, it is unknown when it is most optimal to conduct pupal productivity surveys, in the wet or in the dry season or in both, to inform control services about the most productive water container types and if this pattern varies among different ecological settings. Methods: A multi-country study in randomly selected twelve to twenty urban and peri-urban neighborhoods (‘‘clusters’’) of six Asian countries, in which all water holding containers were examined for larvae and pupae of Aedes aegypti during the dry season and the wet season and their productivity was characterized by water container types. In addition, meteorological data and information on reported dengue cases were collected. Findings: The study reconfirmed the association between rainfall and dengue cases (‘‘dengue season’’) and underlined the importance of determining through pupal productivity surveys the ‘‘most productive containers types’’, responsible for the majority (.70%) of adult dengue vectors. The variety of productive container types was greater during the wet than during the dry season, but included practically all container types productive in the dry season. Container types producing pupae were usually different from those infested by larvae indicating that containers with larval infestations do not necessarily foster pupal development and thus the production of adult Aedes mosquitoes. Conclusion: Pupal productivity surveys conducted during the wet season will identify almost all of the most productive container types for both the dry and wet seasons and will therefore facilitate cost-effective targeted interventions

Community-based dengue vector control : experiences in behavior change in Metropolitan Manila, Philippines

Dengue is the most important mosquito-borne disease in the Philippines, especially in Metropolitan Manila where communities are socially and economically diverse, and city governments struggle to provide basic services such as continuously available, piped water supply to residents. We examined responses to introducing water container management to control dengue vectors in two diverse communities in Masagana City: Village A (gated community) and Village B (informal settlers community). The roll out of the intervention was carried out by the study team, dengue control personnel and local health workers (BHWs). A behavioural change framework was used to describe the community responses to the introduction of a new vector control intervention - household water containermanagement. Although, the desired outcome was not achieved during the study’s timeline, observation on processes of behaviour change underscored the importance of understanding the social nature of the urban communities, often overlooked structures when dengue control program and researchers introduce new dengue control interventions

Use of mobile technology-based participatory mapping approaches to geolocate health facility attendees for disease surveillance in low resource settings.

BACKGROUND: Identifying fine-scale spatial patterns of disease is essential for effective disease control and elimination programmes. In low resource areas without formal addresses, novel strategies are needed to locate residences of individuals attending health facilities in order to efficiently map disease patterns. We aimed to assess the use of Android tablet-based applications containing high resolution maps to geolocate individual residences, whilst comparing the functionality, usability and cost of three software packages designed to collect spatial information. RESULTS: Using Open Data Kit GeoODK, we designed and piloted an electronic questionnaire for rolling cross sectional surveys of health facility attendees as part of a malaria elimination campaign in two predominantly rural sites in the Rizal, Palawan, the Philippines and Kulon Progo Regency, Yogyakarta, Indonesia. The majority of health workers were able to use the tablets effectively, including locating participant households on electronic maps. For all households sampled (n = 603), health facility workers were able to retrospectively find the participant household using the Global Positioning System (GPS) coordinates and data collected by tablet computers. Median distance between actual house locations and points collected on the tablet was 116 m (IQR 42-368) in Rizal and 493 m (IQR 258-886) in Kulon Progo Regency. Accuracy varied between health facilities and decreased in less populated areas with fewer prominent landmarks. CONCLUSIONS: Results demonstrate the utility of this approach to develop real-time high-resolution maps of disease in resource-poor environments. This method provides an attractive approach for quickly obtaining spatial information on individuals presenting at health facilities in resource poor areas where formal addresses are unavailable and internet connectivity is limited. Further research is needed on how to integrate these with other health data management systems and implement in a wider operational context

Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report.

The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency is a crucial aspect in the current phases of malaria control and elimination, which will require the wider use of 8-aminoquinolines for both reducing Plasmodium falciparum transmission and achieving the radical cure of Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe haemolysis in G6PD-deficient individuals, potentially creating significant morbidity and undermining confidence in 8-aminoquinoline prescription. On the other hand, erring on the side of safety and excluding large numbers of people with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity is the most direct, accessible, and reliable assessment of the phenotype and remains the gold standard for the diagnosis of patients who could be harmed by the administration of primaquine. Genotyping seems an unambiguous technique, but its use is limited by cost and the large range of recognized G6PD genotypes. A number of enzyme activity assays diagnose G6PD deficiency, but they require a cold chain, specialized equipment, and laboratory skills. These assays are impractical for care delivery where most patients with malaria live. Improvements to the diagnosis of G6PD deficiency are required for the broader and safer use of 8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be safely used to kill gametocytes without testing. The discussions and conclusions of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge gaps in G6PD deficiency are reported here

Disentangling fine-scale effects of environment on malaria detection and infection to design risk-based disease surveillance systems in changing landscapes

AbstractLandscape changes have complex effects on malaria transmission, disrupting social and ecological systems determining the spatial distribution of risk. Within Southeast Asia, forested landscapes are associated with both increased malaria transmission and reduced healthcare access. Here, we adapt an ecological modelling framework to identify how local environmental factors influence the spatial distributions of malaria infections, diagnostic sensitivity and detection probabilities in the Philippines. Using convenience sampling of health facility attendees and Bayesian latent process models, we demonstrate how risk-based surveillance incorporating forest data increases the probability of detecting malaria foci over three-fold and enables estimation of underlying distributions of malaria infections. We show the sensitivity of routine diagnostics varies spatially, with the decreased sensitivity in closed canopy forest areas limiting the utility of passive reporting to identify spatial patterns of transmission. By adjusting for diagnostic sensitivity and targeting spatial coverage of health systems, we develop a model approach for how to use landscape data within disease surveillance systems. Together, this illustrates the essential role of environmental data in designing risk-based surveillance to provide an operationally feasible and cost-effective method to characterise malaria transmission while accounting for imperfect detection.</jats:p

Analytical approaches for antimalarial antibody responses to confirm historical and recent malaria transmission: an example from the Philippines

Background: Assessing the status of malaria transmission in endemic areas becomes increasingly challenging as countries approach elimination. Serology can provide robust estimates of malaria transmission intensities, and multiplex serological assays allow for simultaneous assessment of markers of recent and historical malaria exposure. Methods: Here, we evaluated different statistical and machine learning methods for analyzing multiplex malaria-specific antibody response data to classify recent and historical exposure to Plasmodium falciparum and Plasmodium vivax. To assess these methods, we utilized samples from a health-facility based survey (n = 9132) in the Philippines, where we quantified antibody responses against 8 P. falciparum and 6 P. vivax-specific antigens from 3 sites with varying transmission intensity. Findings: Measurements of antibody responses and seroprevalence were consistent with the 3 sites’ known endemicity status. Among the models tested, a machine learning (ML) approach (Random Forest model) using 4 serological markers (PfGLURP R2, Etramp5.Ag1, GEXP18, and PfMSP119) gave better predictions for P. falciparum recent infection in Palawan (AUC: 0.9591, CI 0.9497–0.9684) than individual antigen seropositivity. Although the ML approach did not improve P. vivax infection predictions, ML classifications confirmed the absence of recent exposure to P. falciparum and P. vivax in both Occidental Mindoro and Bataan. For predicting historical P. falciparum and P. vivax transmission, seroprevalence and seroconversion rates based on cumulative exposure markers AMA1 and MSP119 showed reliable trends in the 3 sites. Interpretation: Our study emphasizes the utility of serological markers in predicting recent and historical exposure in a sub-national elimination setting, and also highlights the potential use of machine learning models using multiplex antibody responses to improve assessment of the malaria transmission status of countries aiming for elimination. This work also provides baseline antibody data for monitoring risk in malaria-endemic areas in the Philippines. Funding: Newton Fund, Philippine Council for Health Research and Development, UK Medical Research Council

The seasonal dynamics and biting behavior of potential Anopheles vectors of Plasmodium knowlesi in Palawan, Philippines.

BACKGROUND: A small number of human cases of the zoonotic malaria Plasmodium knowlesi have been reported in Palawan Island, the Philippines. Identification of potential vector species and their bionomics is crucial for understanding human exposure risk in this setting. Here, we combined longitudinal surveillance with a trap-evaluation study to address knowledge gaps about the ecology and potential for zoonotic spillover of this macaque malaria in Palawan Island. METHODS: The abundance, diversity and biting behavior of human-biting Anopheles mosquitoes were assessed through monthly outdoor human landing catches (HLC) in three ecotypes representing different land use (forest edge, forest and agricultural area) across 8 months. Additionally, the host preference and biting activity of potential Anopheles vectors were assessed through comparison of their abundance and capture time in traps baited with humans (HLC, human-baited electrocuting net-HEN) or macaques (monkey-baited trap-MBT, monkey-baited electrocuting net-MEN). All female Anopheles mosquitoes were tested for the presence of Plasmodium parasites by PCR. RESULTS: Previously incriminated vectors Anopheles balabacensis and An. flavirostris accounted for > 95% of anophelines caught in longitudinal surveillance. However, human biting densities were relatively low (An. balabacensis: 0.34-1.20 per night, An. flavirostris: 0-2 bites per night). Biting densities of An. balabacensis were highest in the forest edge, while An. flavirostris was most abundant in the agricultural area. The abundance of An. balabacensis and An. flavirostris was significantly higher in HLC than in MBT. None of the 357 female Anopheles mosquitoes tested for Plasmodium infection were positive. CONCLUSIONS: The relatively low density and lack of malaria infection in Anopheles mosquitoes sampled here indicates that exposure to P. knowlesi in this setting is considerably lower than in neighboring countries (i.e. Malaysia), where it is now the primary cause of malaria in humans. Although anophelines had lower abundance in MBTs than in HLCs, An. balabacensis and An. flavirostris were caught by both methods, suggesting they could act as bridge vectors between humans and macaques. These species bite primarily outdoors during the early evening, confirming that insecticide-treated nets are unlikely to provide protection against P. knowlesi vectors

Exposure and infection to Plasmodium knowlesi in case study communities in Northern Sabah, Malaysia and Palawan, The Philippines.

BACKGROUND: Primarily impacting poor, rural populations, the zoonotic malaria Plasmodium knowlesi is now the main cause of human malaria within Malaysian Borneo. While data is increasingly available on symptomatic cases, little is known about community-level patterns of exposure and infection. Understanding the true burden of disease and associated risk factors within endemic communities is critical for informing evidence-based control measures. METHODOLOGY/PRINCIPAL FINDINGS: We conducted comprehensive surveys in three areas where P. knowlesi transmission is reported: Limbuak, Pulau Banggi and Matunggung, Kudat, Sabah, Malaysia and Bacungan, Palawan, the Philippines. Infection prevalence was low with parasites detected by PCR in only 0.2% (4/2503) of the population. P. knowlesi PkSERA3 ag1 antibody responses were detected in 7.1% (95% CI: 6.2-8.2%) of the population, compared with 16.1% (14.6-17.7%) and 12.6% (11.2-14.1%) for P. falciparum and P. vivax. Sero-prevalence was low in individuals <10 years old for P. falciparum and P. vivax consistent with decreased transmission of non-zoonotic malaria species. Results indicated marked heterogeneity in transmission intensity between sites and P. knowlesi exposure was associated with agricultural work (OR 1.63; 95% CI 1.07-2.48) and higher levels of forest cover (OR 2.40; 95% CI 1.29-4.46) and clearing (OR 2.14; 95% CI 1.35-3.40) around houses. Spatial patterns of P. knowlesi exposure differed from exposure to non-zoonotic malaria and P. knowlesi exposed individuals were younger on average than individuals exposed to non-zoonotic malaria. CONCLUSIONS/SIGNIFICANCE: This is the first study to describe serological exposure to P. knowlesi and associated risk factors within endemic communities. Results indicate community-level patterns of infection and exposure differ markedly from demographics of reported cases, with higher levels of exposure among women and children. Further work is needed to understand these variations in risk across a wider population and spatial scale