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Background Domesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure. Methods Eight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO ® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3–5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan–Meier survival estimates, and log-logistic regression on cumulative mortality. Results Both formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4–5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC 50 ) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations. Conclusions This long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity. Graphical Abstract

African great apes are susceptible to infections with several species of Plasmodium, including the predecessor of Plasmodium falciparum. Little is known about the ecology of these pathogens in gorillas. A total of 131 gorilla fecal samples were collected from Dzanga-Sangha Protected Areas to study the diversity and prevalence of Plasmodium species. The effects of sex and age as factors influencing levels of infection with Plasmodium in habituated gorilla groups were assessed. Ninety-five human blood samples from the same locality were also analysed to test for cross-transmission between humans and gorillas. According to a cytB PCR assay 32% of gorilla's fecal samples and 43·1% human individuals were infected with Plasmodium spp. All Laverania species, Plasmodium vivax, and for the first time Plasmodium ovale were identified from gorilla samples. Plasmodium praefalciparum was present only from habituated individuals and P. falciparum was detected from human samples. Although few P. vivax and P. ovale sequences were obtained from gorillas, the evidence for cross-species transmission between humans and gorillas requires more in depth analysis. No association was found between malaria infection and sex, however, younger individuals aged ≤6 years were more susceptible. Switching between two different Plasmodium spp. was observed in three individuals. Prolonged monitoring of Plasmodium infection during various seasons and recording behavioural data is necessary to draw a precise picture about the infection dynamics.

Background Zoonotic infections with epidemic potential, as non-human primate malaria and yellow fever (YF), can overlap geographically. Optimizing a small blood sample for diagnosis and surveillance is of great importance. Blood are routinely collected for YF diagnosis and blood clots usually discarded after serum obtention. Aiming to take sample advantage, the sensitivity of a PCR using extracted DNA from long-term frozen clots from human and non-human primates for detection of Plasmodium spp. in low parasitaemia conditions was assayed. Results Malaria diagnosis with DNA extracted from blood clots generated results in agreement with samples obtained with whole blood, including mixed Plasmodium vivax/simium and Plasmodium malariae/brasilianum infections. Conclusion Blood clots from human and non-human primates may be an important and low cost source of DNA for malaria surveillance in the Atlantic Forest.

Disease transmission prediction across wildlife is crucial for risk assessment of emerging infectious diseases. Susceptibility of host species to pathogens is influenced by the geographic, environmental, and phylogenetic context of the specific system under study. We used machine learning to analyze how such variables influence pathogen incidence for multihost pathogen assemblages, including one of direct transmission (coronaviruses and bats) and two vector-borne systems (West Nile Virus [WNV] and birds, and malaria and birds). Here we show that this methodology is able to provide reliable global spatial susceptibility predictions for the studied host–pathogen systems, even when using a small amount of incidence information (i.e., <20% of information in a database). We found that avian malaria was mostly affected by environmental factors and by an interaction between phylogeny and geography, and WNV susceptibility was mostly influenced by phylogeny and by the interaction between geographic and environmental distances, whereas coronavirus susceptibility was mostly affected by geography. This approach will help to direct surveillance and field efforts providing cost-effective decisions on where to invest limited resources.

Plasmodium knowlesi , a simian malaria parasite, has been in the limelight since a large focus of human P . knowlesi infection was reported from Sarawak (Malaysian Borneo) in 2004. Although this infection is transmitted across Southeast Asia, the largest number of cases has been reported from Malaysia. The increasing number of knowlesi malaria cases has been attributed to the use of molecular tools for detection, but environmental changes including deforestation likely play a major role by increasing human exposure to vector mosquitoes, which coexist with the macaque host. In addition, with the reduction in human malaria transmission in Southeast Asia, it is possible that human populations are at a greater risk of P . knowlesi infection due to diminishing cross-species immunity. Furthermore, the possibility of increasing exposure of humans to other simian Plasmodium parasites such as Plasmodium cynomolgi and Plasmodium inui should not be ignored. We here review the current status of these parasites in humans, macaques, and mosquitoes to support necessary reorientation of malaria control and elimination in the affected areas.

The ability to culture pathogenic organisms substantially enhances the quest for fundamental knowledge and the development of vaccines and drugs. Thus, the elaboration of a protocol for the in vitro cultivation of the erythrocytic stages of Plasmodium falciparum revolutionized research on this important parasite. However, for P. vivax , the most widely distributed and difficult to treat malaria parasite, a strict preference for reticulocytes thwarts efforts to maintain it in vitro. Cultivation of P. cynomolgi , a macaque-infecting species phylogenetically close to P. vivax , was briefly reported in the early 1980s, but not pursued further. Here, we define the conditions under which P. cynomolgi can be adapted to long term in vitro culture to yield parasites that share many of the morphological and phenotypic features of P. vivax . We further validate the potential of this culture system for high-throughput screening to prime and accelerate anti- P. vivax drug discovery efforts. Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi , which shares morphological and phenotypic similarities with P. vivax , initiating a new phase in vivax research.

The human parasite Plasmodium malariae has relatives infecting African apes ( Plasmodium rodhaini ) and New World monkeys ( Plasmodium brasilianum ), but its origins remain unknown. Using a novel approach to characterise P. malariae -related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa. A second ape-derived lineage is much more closely related to the third, human-infective lineage P. malariae , but exhibits little evidence of genetic exchange with it, and so likely represents a separate species. Moreover, the levels and nature of genetic polymorphisms in P. malariae indicate that it resulted from the zoonotic transmission of an African ape parasite, reminiscent of the origin of P. falciparum . In contrast, P. brasilianum falls within the radiation of human P. malariae , and thus reflects a recent anthroponosis. Plasmodium malariae is a cause of malaria in humans and related species have been identified in non-human primates. Here, the authors use genomic analyses to establish that human P. malariae arose from a host switch of an ape parasite whilst a species infecting New World monkeys can be traced to a reverse zoonosis.

Background Plasmodium knowlesi , a non-human primate (NHP) malaria parasite, has become a major public health concern in Malaysia and is now the leading cause of human malaria infections in the country. The transmission of P. knowlesi involves a complex cycle among humans, non-human primates and vectors. Numerous studies have focused on these hosts individually, but comprehensive research that integrates field data from all three hosts is lacking. This study aims to integrate multi-pronged surveillance data from macaques, vectors and human blood samples to better understand the epidemiology of P. knowlesi malaria in Peninsular Malaysia. Methods Field sampling data (both previously published and unpublished) collected from humans, macaques and mosquito vectors by this research group in Peninsular Malaysia between 2019 and 2022 were integrated. The data collected for each host type within the same site and month were aggregated as a single sampling event. Partial correlations of outcomes between different host sampling sites were analysed by controlling for inter-host sampling site proximity and temporal difference. Spatiotemporal correlations were analysed between the sampling outcomes and historical human P.   knowlesi malaria cases reported within defined distances (up to 20 km) from the sampling sites across different time lead windows (range from −12 to 12 months). Results Partial correlation analysis, controlled for inter-host sampling-site spatial proximity and temporal difference, showed a statistically significant positive partial correlation between the proportion of field-sampled human P. knowlesi -positive cases and the average number of Anopheles Leucosphyrus-group mosquitoes sampled per night within a 10-km proximity constraint ( rs  = 0.228, P  = 0.042). A consistently statistically significant positive correlation was found between the proportion of P. knowlesi -positive macaques and the number of historical human P. knowlesi cases reported in defined spatial proximity to macaque sampling sites, particularly within spatial radii of 6 km and beyond, across both backward and forward time leads. Other NHP malaria parasites, P. cynomolgi , P. inui , P. coatneyi and P. fieldi , exhibited heterogeneous patterns in macaques and vectors, particularly in terms of geographical distribution and mixed-species infection. The proportions of macaque samples positive for P. knowlesi , P. inui and P. coatneyi were statistically higher in the peridomestic–agriculture area as compared with the urban area. Conclusions A key finding from this study is that the proportion of P. knowlesi infection in macaques may serve as a useful proxy for persistent transmission in an area, potentially indicating increased risk of human infection in nearby communities. This highlights the value of wildlife surveillance in predicting and managing zoonotic malaria risk. Integrating insights from epidemiology, ecology, veterinary science and public health is essential for effectively controlling zoonotic diseases such as P. knowlesi malaria and reducing their impact on both human and animal populations. Graphical abstract

Background Zoonotic malaria is a growing public health concern in Southeast Asia, with Malaysia and Thailand accounting for 95.2% of the 3290 global cases reported in 2023. It is caused by Plasmodium species primarily adapted to long- and pig-tailed macaques, transmitted to humans via certain Anopheles mosquitoes. This meta-analysis quantifies its prevalence and risk factors in the Greater Mekong Subregion and Malaysia. Methods This meta-analysis was conducted following the PRISMA (Preferred Reporting Items for Systematic) guidelines. A comprehensive literature search was conducted in PubMed and Scopus databases (2000–2024) to identify studies on zoonotic malaria infection in humans and monkeys. Backward search was done using Google Scholar. Inclusion criteria were defined using the CoCoPop (Condition, Context, and Population) framework. Two reviewers independently extracted data, and study quality was assessed using appropriate risk-of-bias tools. A random-effects meta-analysis was conducted using the metafor package in R programme, with heterogeneity assessed via I 2 statistics and subgroup analyses. Meta-regression using a linear mixed-effects models estimated unadjusted odds ratios for transmission determinants. Results The overall pooled prevalence of malaria infection was 8.6% in humans and 35.0% in monkeys. The pooled prevalence was higher in Malaysia (22.8%) than GMS (1.2%). In GMS, Myanmar with a pooled prevalence of 4.9% contributes a higher burden of human zoonotic malaria than Thailand (1.8%). Significantly high heterogeneity between studies was recorded for both human ( I 2  = 99.7%, P < 0.0001) and monkey ( I 2  = 98.7%, P < 0.0001) infections. The major risk factors assessed were gender (males: OR = 4.3), age (adults 21–40 years: OR = 5.6), mobility, misdiagnosis, and Plasmodium knowlesi infection. Most cases (4773; 89.6%) were initially misdiagnosed by microscopy as non-zoonotic. Prevalence in monkeys was highest in Macaca nemestrina (63.3%) followed by Macaca fascicularis (31.4%) with Plasmodium inui and Plasmodium cynomolgi as the most frequent parasites. Conclusions This study contributes to the understanding of the transmission complexities of zoonotic malaria in the GMS countries and Malaysia, highlighting critical knowledge gaps and the need for a multidisciplinary approach to managing its further spread.

Sabah, Malaysia, has amongst the highest burden of human Plasmodium knowlesi infection in the world, associated with increasing encroachment on the parasite’s macaque host habitat. However, the genomic make-up of P. knowlesi in Sabah was previously poorly understood. To inform on local patterns of transmission and putative adaptive drivers, we conduct population-level genetic analyses of P. knowlesi human infections using 52 new whole genomes from Sabah, Malaysia, in combination with publicly available data. We identify the emergence of distinct geographical subpopulations within the macaque-associated clusters using identity-by-descent-based connectivity analysis. Secondly, we report on introgression events between the clusters, which may be linked to differentiation of the subpopulations, and that overlap genes critical for survival in human and mosquito hosts. Using village-level locations from P. knowlesi infections, we also identify associations between several introgressed regions and both intact forest perimeter-area ratio and mosquito vector habitat suitability. Our findings provide further evidence of the complex role of changing ecosystems and sympatric macaque hosts in Malaysia driving distinct genetic changes seen in P. knowlesi populations. Future expanded analyses of evolving P. knowlesi genetics and environmental drivers of transmission will be important to guide public health surveillance and control strategies.