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Simian malaria from wild non-human primate populations is increasingly recognised as a public health threat and is now the main cause of human malaria in Malaysia and some regions of Brazil. In 2022, Malaysia became the first country not to achieve malaria elimination due to zoonotic simian malaria. We review the global distribution and drivers of simian malaria and identify priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and human malaria parasites spilling back into wild non-human primate populations. These complex transmission cycles require new molecular and epidemiological approaches to track parasite spread. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally. [ABSTRACT FROM AUTHOR]

Background: The increasing incidence of Plasmodium knowlesi malaria poses a significant challenge to efforts to eliminate malaria from Malaysia. Macaque reservoirs, outdoors-biting mosquitoes, human activities, and agricultural work are key factors associated with the transmission of this zoonotic pathogen. However, gaps in knowledge regarding reasons that drive malaria persistence in rural Kudat, Sabah, Northern Borneo remain. This study was conducted to address this knowledge gap, to better understand the complexities of these entangled problems, and to initiate discussion regarding new countermeasures to address them. This study aims to highlight rural community members' perspectives regarding inequities to health relating to P. knowlesi malaria exposure. Methods: From January to October 2022, a study using qualitative methods was conducted in four rural villages in Kudat district of Sabah, Malaysia. A total of nine in-depth interviews were conducted with community and faith leaders, after the completion of twelve focus group discussions with 26 photovoice participants. The interviews were conducted using the Sabah Malay dialect, audio-recorded, transcribed, and translated into English. The research team led the discussion and analysis, which was approved by participants through member checking at the community level. Results: Participants identified disparity in health as a key issue affecting their health and livelihoods. Injustice in the social environment was also identified as a significant challenge, including the importance of listening to the voices of affected communities in disentangling the social and economic phenomena that can impact malaria control. Specific concerns included inadequate access to health-related resources and degradation of the environment. Participants recommended improving access to water and other necessities, increasing the availability of malaria control commodities in healthcare facilities, and developing sustainable programs to reduce socioeconomic disparities. Conclusion: Inequities to health emerged as a key concern for malaria control in rural Kudat, Sabah. A locally targeted malaria programme cantered on improving the social and economic disparities associated with health outcomes, could be a potential strategy for malaria prevention in such areas. Community-level perspectives gathered from this study can be used as a foundation for future discussions and dialogues among policymakers and community members for achieving greater transparency, improving social equity, and interoperability in addressing P. knowlesi malaria control. [ABSTRACT FROM AUTHOR]

Background: Since 2018, no indigenous human malaria cases has been reported in Malaysia. However, during the recent COVID-19 pandemic the World Health Organization is concerned that the pandemic might erode the success of malaria control as there are reports of increase malaria cases in resource limited countries. Little is known how the COVID-19 pandemic has impacted malaria in middle-income countries like Malaysia. Here the public health response to a Plasmodium malariae outbreak occurred in a village in Sabah state, Malaysia, during a COVID-19 movement control order is reported. Methods: An outbreak was declared following the detection of P. malariae in July 2020 and active case detection for malaria was performed by collecting blood samples from residents residing within 2 km radius of Moyog village. Vector prevalence and the efficacy of residual insecticides were determined. Health awareness programmes were implemented to prevent future outbreaks. A survey was conducted among villagers to understand risk behaviour and beliefs concerning malaria. Results: A total of 5254 blood samples collected from 19 villages. Among them, 19 P. malariae cases were identified, including the index case, which originated from a man who returned from Indonesia. His return from Indonesia and healthcare facilities visit coincided with the movement control order during COVID-19 pandemic when the healthcare facilities stretched its capacity and only serious cases were given priority. Despite the index case being a returnee from a malaria endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. All cases were symptomatic and uncomplicated except for a pregnant woman with severe malaria. There were no deaths; all patients recovered following treatment with artemether-lumefantrine combination therapy. Anopheles balabacensis and Anopheles barbirostris were detected in ponds, puddles and riverbeds. The survey revealed that fishing and hunting during night, and self-treatment for mild symptoms contributed to the outbreak. Despite the index case being a returnee from a malaria-endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. Conclusion: The outbreak occurred during a COVID-19 movement control order, which strained healthcare facilities, prioritizing only serious cases. Healthcare workers need to be more aware of the risk of malaria from individuals who return from malaria endemic areas. To achieve malaria elimination and prevention of disease reintroduction, new strategies that include multisectoral agencies and active community participation are essential for a more sustainable malaria control programme. [ABSTRACT FROM AUTHOR]

Malaysia has reported no indigenous cases of P. falciparum and P. vivax for over 3 years. When transmission reaches such low levels, it is important to understand the individuals and locations where exposure risks are high, as they may be at greater risk in the case of a resurgence of transmission. Serology is a useful tool in low transmission settings, providing insight into exposure over longer durations than PCR or RDT. We ran blood samples from a 2015 population-based survey in northern Sabah, Malaysian Borneo on a multiplex bead assay. Using supervised machine learning methods, we characterised recent and historic exposure to Plasmodium falciparum and P. vivax and found recent exposure to P. falciparum to be very low, with exposure to both species increasing with age. We performed a risk-factor assessment on environmental, behavioural, demographic and household factors, and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to P. falciparum and P. vivax. In addition, we used remote-sensing derived data and geostatistical models to assess environmental and spatial associations with exposure. We created predictive maps of exposure to recent P. falciparum in the study area and showed 3 clear foci of exposure. This study provides useful insight into the environmental, spatial and demographic risk factors for P. falciparum and P. vivax at a period of low transmission in Malaysian Borneo. The findings would be valuable in the case of resurgence of human malarias in the region. [ABSTRACT FROM AUTHOR]

Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate RC, individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (RC < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (RC > 1) was estimated historically for P. falciparum and P. vivax, with declines in RC estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks. Plasmodium knowlesi is a zoonotic malaria parasite that can infect humans, but whether human-mosquito-human transmission occurs is not known. Here, the authors use data from Malaysia and show, through mathematical modelling, that sustained non-zoonotic transmission is unlikely to be occurring in this setting. [ABSTRACT FROM AUTHOR]

Increasing numbers of human zoonotic malaria cases are reported globally. Current malaria control measures cannot eliminate transmission from wildlife reservoirs, leaving many countries with no pathway to malaria elimination certification. New policies are needed to redefine elimination goals and certification. WHO guidelines for classification of malaria elimination in a country require that the risk of human infection from zoonotic, as well as nonzoonotic, malaria parasites is negligible. In this Comment, the authors discuss the implications of this policy for countries, such as Malaysia, with no recent reported nonzoonotic cases but ongoing zoonotic transmission. [ABSTRACT FROM AUTHOR]

To determine the presence and species composition of malaria infections, we screened a subset of samples collected during a cross-sectional survey in Northern Sabah, Malaysia using highly sensitive molecular techniques. Results identified 54 asymptomatic submicroscopic malaria infections, including a large cluster of Plasmodium falciparum and 3 P. knowlesi infections. We additionally identified 2 monoinfections with the zoonotic malaria Plasmodium cynomolgi, both in individuals reporting no history of forest activities or contact with macaques. Results highlight the need for improved surveillance strategies to detect these infections and determine public health impacts. [ABSTRACT FROM AUTHOR]

Land-use changes can impact infectious disease transmission by increasing spatial overlap between people and wildlife disease reservoirs. In Malaysian Borneo, increases in human infections by the zoonotic malaria Plasmodium knowlesi are hypothesised to be due to increasing contact between people and macaques due to deforestation. To explore how macaque responses to environmental change impact disease risks, we analysed movement of a GPS-collared long-tailed macaque in a knowlesi-endemic area in Sabah, Malaysia, during a deforestation event. Land-cover maps were derived from satellite-based and aerial remote sensing data and models of macaque occurrence were developed to evaluate how macaque habitat use was influenced by land-use change. During deforestation, changes were observed in macaque troop home range size, movement speeds and use of different habitat types. Results of models were consistent with the hypothesis that macaque ranging behaviour is disturbed by deforestation events but begins to equilibrate after seeking and occupying a new habitat, potentially impacting human disease risks. Further research is required to explore how these changes in macaque movement affect knowlesi epidemiology on a wider spatial scale. [ABSTRACT FROM AUTHOR]

Although asymptomatic carriage of human malaria species has been widely reported, the extent of asymptomatic, submicroscopic Plasmodium knowlesi parasitemia is unknown. In this study, samples were obtained from individuals residing in households or villages of symptomatic malaria cases with the aim of detecting submicroscopic P. knowlesi in this population. Four published molecular assays were used to confirm the presence of P. knowlesi. Latent class analysis revealed that the estimated proportion of asymptomatic individuals was 6.9% (95% confidence interval, 5.6%-8.4%). This study confirms the presence of a substantial number of asymptomatic monoinfections across all age groups; further work is needed to estimate prevalence in the wider community. [ABSTRACT FROM AUTHOR]

The zoonotic malaria species Plasmodium knowlesi has become the main cause of human malaria in Malaysian Borneo. Deforestation and associated environmental and population changes have been hypothesized as main drivers of this apparent emergence. We gathered village-level data for P. knowlesi incidence for the districts of Kudat and Kota Marudu in Sabah state, Malaysia, for 2008-2012. We adjusted malaria records from routine reporting systems to reflect the diagnostic uncertainty of microscopy for P. knowlesi. We also developed negative binomial spatial autoregressive models to assess potential associations between P. knowlesi incidence and environmental variables derived from satellite-based remote-sensing data. Marked spatial heterogeneity in P. knowlesi incidence was observed, and village-level numbers of P. knowlesi cases were positively associated with forest cover and historical forest loss in surrounding areas. These results suggest the likelihood that deforestation and associated environmental changes are key drivers in P. knowlesi transmission in these areas. [ABSTRACT FROM AUTHOR]

Background: The control of Plasmodium knowlesi malaria remains challenging due to the presence of macaque monkeys and predominantly outdoor-biting Anopheles mosquitoes around human settlements. This study aims to explore the barriers and facilitators related to prevention of mosquito bites among rural communities living in Sabah, Malaysia using the participatory visual method, photovoice., Methods: From January through June 2022, 26 participants were recruited from four villages in Kudat, Sabah, using purposive sampling. Participants were male and female villagers, aged > 18 years old. After photovoice training in the villages, participants documented facilitators of and barriers related to avoiding mosquito bites using their own smartphone cameras, and provided narratives for their photos. Twelve Focus Group Discussions (FGDs) sessions in three rounds were held to share and discuss the photos, and to address challenges to the avoidance of mosquito bites. All discussions were conducted in the Sabah Malay dialect, and were video and audio recorded, transcribed, and analyzed using reflexive thematic analysis. The Ideation Model, a meta-theoretical model of behaviour change, underpinned this study., Results: The most common types of barriers identified by participants included (I) intrapersonal factors such as low perceived threat of malaria, (II) livelihood and lifestyle activities consisting of the local economy and socio-cultural activities, and (III) physical and social environment. The facilitators were categorized into (I) intrapersonal reasons, including having the opportunity to stay indoors, especially women who are housewives, (II) social support by the households, neaighbours and healthcare workers, and (III) support from healthcare services and malaria awareness program. Participants emphasized the importance of stakeholder's support in implementing feasible and affordable approaches to P. knowlesi malaria control., Conclusion: Results provided insights regarding the challenges to preventing P. knowlesi malaria in rural Kudat, Sabah. The participation of communities in research was valuable in expanding knowledge of local challenges and highlighting possible ways to overcome barriers. These findings may be used to improve strategies for zoonotic malaria control, which is critical for advancing social change and minimizing health disparities in malaria prevention., (© 2023. The Author(s).)

Background: Infectious diseases continue to burden populations in Malaysia, especially among rural communities where resources are limited and access to health care is difficult. Current epidemiological trends of several neglected tropical diseases in these populations are at present absent due to the lack of habitual and efficient surveillance. To date, various studies have explored the utility of serological multiplex beads to monitor numerous diseases simultaneously. We therefore applied this platform to assess population level exposure to six infectious diseases in Sabah, Malaysia. Furthermore, we concurrently investigated demographic and spatial risk factors that may be associated with exposure for each disease., Methods: This study was conducted in four districts of Northern Sabah in Malaysian Borneo, using an environmentally stratified, population-based cross-sectional serological survey targeted to determine risk factors for malaria. Samples were collected between September to December 2015, from 919 villages totaling 10,100 persons. IgG responses to twelve antigens of six diseases (lymphatic filariasis- Bm33, Bm14, BmR1, Wb123; strongyloides- NIE; toxoplasmosis-SAG2A; yaws- Rp17 and TmpA; trachoma- Pgp3, Ct694; and giardiasis- VSP3, VSP5) were measured using serological multiplex bead assays. Eight demographic risk factors and twelve environmental covariates were included in this study to better understand transmission in this community., Results: Seroprevalence of LF antigens included Bm33 (10.9%), Bm14+ BmR1 (3.5%), and Wb123 (1.7%). Seroprevalence of Strongyloides antigen NIE was 16.8%, for Toxoplasma antigen SAG2A was 29.9%, and Giardia antigens GVSP3 + GVSP5 was 23.2%. Seroprevalence estimates for yaws Rp17 was 4.91%, for TmpA was 4.81%, and for combined seropositivity to both antigens was 1.2%. Seroprevalence estimates for trachoma Pgp3 + Ct694 were 4.5%. Age was a significant risk factors consistent among all antigens assessed, while other risk factors varied among the different antigens. Spatial heterogeneity of seroprevalence was observed more prominently in lymphatic filariasis and toxoplasmosis., Conclusions: Multiplex bead assays can be used to assess serological responses to numerous pathogens simultaneously to support infectious disease surveillance in rural communities, especially where prevalences estimates are lacking for neglected tropical diseases. Demographic and spatial data collected alongside serosurveys can prove useful in identifying risk factors associated with exposure and geographic distribution of transmission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Patterson, Priest, Stresman, William, Chua, Tetteh, Lammie, Drakeley and Fornace.)

Land-use changes, such as deforestation and agriculture, can influence mosquito vector populations and malaria transmission. These land-use changes have been linked to increased incidence in human cases of the zoonotic malaria Plasmodium knowlesi in Sabah, Malaysian Borneo. This study investigates whether these associations are partially driven by fine-scale land-use changes creating more favourable aquatic breeding habitats for P. knowlesi anopheline vectors. Using aerial remote sensing data, we developed a sampling frame representative of all land use types within a major focus of P. knowlesi transmission. From 2015 to 2016 monthly longitudinal surveys of larval habitats were collected in randomly selected areas stratified by land use type. Additional remote sensing data on environmental variables, land cover and landscape configuration were assembled for the study site. Risk factor analyses were performed over multiple spatial scales to determine associations between environmental and spatial variables and anopheline larval presence. Habitat fragmentation (300 m), aspect (350 m), distance to rubber plantations (100 m) and Culex larval presence were identified as risk factors for Anopheles breeding. Additionally, models were fit to determine the presence of potential larval habitats within the areas surveyed and used to generate a time-series of monthly predictive maps. These results indicate that land-use change and topography influence the suitability of larval habitats, and may partially explain the link between P. knowlesi incidence and deforestation. The predictive maps, and identification of the spatial scales at which risk factors are most influential may aid spatio-temporally targeted vector control interventions.

A number of primate census techniques have been developed over the past half-century, each of which have advantages and disadvantages in terms of resources required by researchers (e.g., time and costs), availability of technologies, and effectiveness in different habitat types. This study aims to explore the effectiveness of a thermal imaging technique to estimate the group size of different primate species populations in a degraded riparian forest in the Lower Kinabatangan Wildlife Sanctuary (LKWS), Sabah. We compared this survey technique to the conventional visual counting method along the riverbank. For 38 days, a total of 138 primate groups were observed by thermal camera and visually throughout the study. Optimal conditions for the thermal camera were clear weather, not more than 100 m distance from the observer to the targeted area, boat speed ranging between 5 and 12 km/h, and early morning between 04:30 and 05:30 am. The limitations of the thermal cameras include the inability to identify individual species, sexes, age classes, and also to discern between animals closely aggregated (i.e., mothers with attached infants). Despite these limitations with the thermal camera technique, 1.78 times more primates were detected than counting by eye (p < 0.001), showing the potential benefit of using thermal cameras as an important tool in primate surveys. Nevertheless, ground truthing must be conducted immediately after, or simultaneously during, the thermal survey to verify the species of animals observed on the thermal imagery.

Background: Land use changes disrupt ecosystems, altering the transmission of vector-borne diseases. These changes have been associated with increasing incidence of zoonotic malaria caused by Plasmodium knowlesi; however, the population-level distributions of infection and exposure remain unknown. We aimed to measure prevalence of serological exposure to P knowlesi and assess associated risk factors., Methods: We did an environmentally stratified, population-based, cross-sectional survey across households in the Kudat, Kota Marudu, Pitas, and Ranau districts in northern Sabah, Malaysia, encompassing a range of ecologies. Using blood samples, the transmission intensity of P knowlesi and other malaria species was measured by specific antibody prevalence and infection detected using molecular methods. Proportions and configurations of land types were extracted from maps derived from satellite images; a data-mining approach was used to select variables. A Bayesian hierarchical model for P knowlesi seropositivity was developed, incorporating questionnaire data about individual and household-level risk factors with selected landscape factors., Findings: Between Sept 17, 2015, and Dec 12, 2015, 10 100 individuals with a median age of 25 years (range 3 months to 105 years) were sampled from 2849 households in 180 villages. 5·1% (95% CI 4·8-5·4) were seropositive for P knowlesi, and marked historical decreases were observed in the transmission of Plasmodium falciparum and Plasmodium vivax. Nine Plasmodium spp infections were detected. Age, male sex, contact with macaques, forest use, and raised house construction were positively associated with P knowlesi exposure, whereas residing at higher geographical elevations and use of insecticide were protective. Agricultural and forest variables, such as proportions and fragmentation of land cover types, predicted exposure at different spatial scales from households., Interpretation: Although few infections were detected, P knowlesi exposure was observed in all demographic groups and was associated with occupational factors. Results suggest that agricultural expansion and forest fragmentation affect P knowlesi exposure, supporting linkages between land use change and P knowlesi transmission., Funding: UK Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The complex transmission ecologies of vector-borne and zoonotic diseases pose challenges to their control, especially in changing landscapes. Human incidence of zoonotic malaria ( Plasmodium knowlesi) is associated with deforestation although mechanisms are unknown. Here, a novel application of a method for predicting disease occurrence that combines machine learning and statistics is used to identify the key spatial scales that define the relationship between zoonotic malaria cases and environmental change. Using data from satellite imagery, a case-control study, and a cross-sectional survey, predictive models of household-level occurrence of P. knowlesi were fitted with 16 variables summarized at 11 spatial scales simultaneously. The method identified a strong and well-defined peak of predictive influence of the proportion of cleared land within 1 km of households on P. knowlesi occurrence. Aspect (1 and 2 km), slope (0.5 km) and canopy regrowth (0.5 km) were important at small scales. By contrast, fragmentation of deforested areas influenced P. knowlesi occurrence probability most strongly at large scales (4 and 5 km). The identification of these spatial scales narrows the field of plausible mechanisms that connect land use change and P. knowlesi, allowing for the refinement of disease occurrence predictions and the design of spatially-targeted interventions.