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Malaria Journal Oct 2023
PubMed: 37858164
DOI: 10.1186/s12936-023-04732-x -
ELife May 2024Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host a... (Meta-Analysis)
Meta-Analysis
Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.
Topics: Animals; Humans; Asia, Southeastern; Ecosystem; Malaria; Plasmodium knowlesi; Prevalence; Primate Diseases; Primates; Zoonoses
PubMed: 38753426
DOI: 10.7554/eLife.88616 -
MedRxiv : the Preprint Server For... May 2024The emergence of the zoonotic monkey parasite as the dominant cause of malaria in Malaysia has disrupted current national WHO elimination goals. Malaysia has free...
BACKGROUND
The emergence of the zoonotic monkey parasite as the dominant cause of malaria in Malaysia has disrupted current national WHO elimination goals. Malaysia has free universal access to malaria care; however, out-of-pocket costs are unknown. This study estimated household costs of illness attributable to malaria due to against other non-zoonotic species infections in Sabah, Malaysia.
METHODOLOGY/PRINCIPAL FINDINGS
Household costs were estimated from patient-level surveys collected from four hospitals between 2013 and 2016. Direct costs including medical and associated travel costs, and indirect costs due to lost productivity were included. One hundred and fifty-two malaria cases were enrolled: (n=108), (n=22), (n=16), and (n=6). Costs were inflated to 2022 Malaysian Ringgits and reported in United States dollars (US$). Across all cases, the mean total costs were US$138 (SD=108), with productivity losses accounting for 58% of costs (US$80; SD=73). had the highest mean total household cost at US$210, followed by (US$127), (US$126), and (US$105). Most patients (80%) experienced direct health costs above 10% of monthly income, with 58 (38%) patients experiencing health spending over 25% of monthly income, consistent with catastrophic health expenditure.
CONCLUSIONS/SIGNIFICANCE
Despite Malaysia's free health-system care for malaria, patients and families face other related medical, travel, and indirect costs. Household out-of-pocket costs were driven by productivity losses; primarily attributed to infections in working-aged males in rural agricultural-based occupations. Costs for were comparable to and lower than The higher costs related to direct health facility costs for repeat monitoring visits given the liver-stage treatment required.
AUTHOR SUMMARY
Knowlesi malaria is due to infection with a parasite transmitted by mosquitos from monkeys to humans. Most people who are infected work or live near the forest. It is now the major type of malaria affecting humans in Malaysia. The recent increase of knowlesi malaria cases in humans has impacted individuals, families, and health systems in Southeast Asia. Although the region has made substantial progress towards eliminating human-only malaria species, knowlesi malaria threatens elimination targets as traditional control measures do not address the parasite reservoir in monkeys. The economic burden of illness due to knowlesi malaria has not previously been estimated or subsequently compared with other malaria species. We collected data on the cost of illness to households in Sabah, Malaysia, to estimate their related total economic burden. Medical costs and time off work and usual activities were substantial in patients with the four species of malaria diagnosed during the time of this study. This research highlights the financial burden which households face when seeking care for malaria in Malaysia, despite the free treatment provided by the government.
PubMed: 38746350
DOI: 10.1101/2024.05.02.24306734 -
Acta Tropica Jun 2024Malaria continues to be a global public health problem although it has been eliminated from many countries. Sri Lanka and China are two countries that recently achieved... (Review)
Review
Malaria continues to be a global public health problem although it has been eliminated from many countries. Sri Lanka and China are two countries that recently achieved malaria elimination status, and many countries in Southeast Asia are currently in the pipeline for achieving the same goal by 2030. However, Plasmodium knowlesi, a non-human primate malaria parasite continues to pose a threat to public health in this region, infecting many humans in all countries in Southeast Asia except for Timor-Leste. Besides, other non-human primate malaria parasite such as Plasmodium cynomolgi and Plasmodium inui are infecting humans in the region. The non-human primates, the long-tailed and pig-tailed macaques which harbour these parasites are now increasingly prevalent in farms and forest fringes close by to the villages. Additionally, the Anopheles mosquitoes belonging to the Lecuosphyrus Group are also present in these areas which makes them ideal for transmitting the non-human primate malaria parasites. With changing landscape and deforestation, non-human primate malaria parasites will affect more humans in the coming years with the elimination of human malaria. Perhaps due to loss of immunity, more humans will be infected as currently being demonstrated in Malaysia. Thus, control measures need to be instituted rapidly to achieve the malaria elimination status by 2030. However, the zoonotic origin of the parasite and the changes of the vectors behaviour to early biting seems to be the stumbling block to the malaria elimination efforts in this region. In this review, we discuss the challenges faced in malaria elimination due to deforestation and the serious threat posed by non-human primate malaria parasites.
PubMed: 38908421
DOI: 10.1016/j.actatropica.2024.107280 -
The American Journal of Tropical... Aug 2023Severe malaria after splenectomy has been reported with infections with Plasmodium falciparum, Plasmodium knowlesi, and Plasmodium malariae, but is less...
Severe malaria after splenectomy has been reported with infections with Plasmodium falciparum, Plasmodium knowlesi, and Plasmodium malariae, but is less well-characterized with Plasmodium vivax. We describe a case of severe P. vivax malaria with hypotension, prostration, and acute kidney injury occurring 2 months after splenectomy in Papua, Indonesia. The patient was treated successfully with intravenous artesunate.
Topics: Humans; Malaria, Vivax; Splenectomy; Malaria; Artesunate; Plasmodium vivax; Plasmodium falciparum
PubMed: 37339765
DOI: 10.4269/ajtmh.23-0147 -
The American Journal of Tropical... Apr 2024Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that can amplify specific nucleic acids at a constant temperature (63-65°C)...
Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that can amplify specific nucleic acids at a constant temperature (63-65°C) within a short period (<1 hour). In this study, we report the utilization of recombinase-aided LAMP to specifically amplify the 18S sRNA of Plasmodium knowlesi. The method was built on a conventional LAMP assay by inclusion of an extra enzyme, namely recombinase, into the master mixture. With the addition of recombinase into the LAMP assay, the assay speed was executed within a time frame of less than 28 minutes at 65°C. We screened 55 P. knowlesi samples and 47 non-P. knowlesi samples. No cross-reactivity was observed for non-P. knowlesi samples, and the detection limit for recombinase-aided LAMP was one copy for P. knowlesi after LAMP amplification. It has been reported elsewhere that LAMP can be detected through fluorescent readout systems. Although such systems result in considerable limits of detection, the need for sophisticated equipment limits their use. Hence, we used here a colorimetric detection platform for the evaluation of the LAMP assay's performance. This malachite green-based recombinase-aided LAMP assay enabled visualization of results with the naked eye. Negative samples were observed by a change in color from green to colorless, whereas positive samples remained green. Our results demonstrate that the LAMP assay developed here is a convenient, sensitive, and useful diagnostic tool for the rapid detection of knowlesi malaria parasites. This method is suitable for implementation in remote healthcare settings, where centralized laboratory facilities, funds, and clinicians are in short supply.
Topics: Humans; Plasmodium knowlesi; Malaria; Recombinases; Sensitivity and Specificity; Nucleic Acid Amplification Techniques; Molecular Diagnostic Techniques
PubMed: 38412548
DOI: 10.4269/ajtmh.23-0572 -
Frontiers in Cellular and Infection... 2023The zoonotic malaria parasite is an important public health concern in Southeast Asia. Invasion of host erythrocytes is essential for parasite growth, and thus,...
The zoonotic malaria parasite is an important public health concern in Southeast Asia. Invasion of host erythrocytes is essential for parasite growth, and thus, understanding the repertoire of parasite proteins that enable this process is vital for identifying vaccine candidates and how some species are able to cause zoonotic infection. Merozoite surface protein 1 (MSP1) is found in all malaria parasite species and is perhaps the most well-studied as a potential vaccine candidate. While MSP1 is encoded by a single gene in , all other human infective species (, , , and ) additionally encode a divergent paralogue known as MSP1P, and little is known about its role or potential functional redundancy with MSP1. We, therefore, studied the function of merozoite surface protein 1 paralog (PkMSP1P), using both recombinant protein and CRISPR-Cas9 genome editing. The recombinant 19-kDa C-terminus of PkMSP1P (PkMSP1P-19) was shown to bind specifically to human reticulocytes. However, immunoblotting data suggested that PkMSP1P-19-induced antibodies can recognize PkMSP1-19 and vice versa, confounding our ability to separate the properties of these two proteins. Targeted disruption of the gene profoundly impacts parasite growth, demonstrating for the first time that PkMSP1P is important in growth of and likely plays a distinct role from PkMSP1. Importantly, the MSP1P KO also enabled functional characterization of the PkMSP1P-19 antibodies, revealing clear immune cross-reactivity between the two paralogues, highlighting the vital importance of genetic studies in contextualizing recombinant protein studies.
Topics: Humans; Merozoite Surface Protein 1; Plasmodium knowlesi; Malaria; Erythrocytes; Malaria, Vivax; Antibodies; Malaria, Falciparum; Recombinant Proteins; Vaccines
PubMed: 38111629
DOI: 10.3389/fcimb.2023.1314533 -
Malaria Journal Jan 2024A major challenge to malaria elimination is identifying and targeting populations that are harbouring residual infections and contributing to persistent transmission. In...
BACKGROUND
A major challenge to malaria elimination is identifying and targeting populations that are harbouring residual infections and contributing to persistent transmission. In many near-elimination settings in Southeast Asia, it is known that forest-goers are at higher risk for malaria infection, but detailed information on their behaviours and exposures is not available.
METHODS
In Aceh Province, Indonesia, a near-elimination setting where a growing proportion of malaria is due to Plasmodium knowlesi, a case-control study was conducted to identify risk factors for symptomatic malaria, characteristics of forest-goers, and key intervention points. From April 2017 to September 2018, cases and controls were recruited and enrolled in a 1:3 ratio. Cases had confirmed malaria infection by rapid diagnostic test or microscopy detected at a health facility (HF). Gender-matched controls were recruited from passive case detection among individuals with suspected malaria who tested negative at a health facility (HF controls), and community-matched controls were recruited among those testing negative during active case detection. Multivariable logistic regression (unconditional for HF controls and conditional for community controls) was used to identify risk factors for symptomatic malaria infection.
RESULTS
There were 45 cases, of which 27 were P. knowlesi, 17 were Plasmodium vivax, and one was not determined. For controls, 509 and 599 participants were recruited from health facilities and the community, respectively. Forest exposures were associated with high odds of malaria; in particular, working and sleeping in the forest (HF controls: adjusted odds ratio (aOR) 21.66, 95% CI 5.09-92.26; community controls: aOR 16.78, 95% CI 2.19-128.7) and having a second residence in the forest (aOR 6.29, 95% CI 2.29-17.31 and 13.53, 95% CI 2.10-87.12). Male forest-goers were a diverse population employed in a variety of occupations including logging, farming, and mining, sleeping in settings, such as huts, tents, and barracks, and working in a wide range of group sizes. Reported use of protective measures, such as nets, hammock nets, mosquito coils, and repellents was low among forest-goers and interventions at forest residences were absent.
CONCLUSIONS
Second residences in the forest and gaps in use of protective measures point to key malaria interventions to improve coverage in forest-going populations at risk for P. knowlesi and P. vivax in Aceh, Indonesia. Intensified strategies tailored to specific sub-populations will be essential to achieve elimination.
Topics: Male; Humans; Indonesia; Case-Control Studies; Malaria; Malaria, Vivax; Forests
PubMed: 38291392
DOI: 10.1186/s12936-024-04856-8 -
PLoS Pathogens Dec 2023Malaria is caused by the rapid proliferation of Plasmodium parasites in patients and disease severity correlates with the number of infected red blood cells in...
Malaria is caused by the rapid proliferation of Plasmodium parasites in patients and disease severity correlates with the number of infected red blood cells in circulation. Parasite multiplication within red blood cells is called schizogony and occurs through an atypical multinucleated cell division mode. The mechanisms regulating the number of daughter cells produced by a single progenitor are poorly understood. We investigated underlying regulatory principles by quantifying nuclear multiplication dynamics in Plasmodium falciparum and knowlesi using super-resolution time-lapse microscopy. This confirmed that the number of daughter cells was consistent with a model in which a counter mechanism regulates multiplication yet incompatible with a timer mechanism. P. falciparum cell volume at the start of nuclear division correlated with the final number of daughter cells. As schizogony progressed, the nucleocytoplasmic volume ratio, which has been found to be constant in all eukaryotes characterized so far, increased significantly, possibly to accommodate the exponentially multiplying nuclei. Depleting nutrients by dilution of culture medium caused parasites to produce fewer merozoites and reduced proliferation but did not affect cell volume or total nuclear volume at the end of schizogony. Our findings suggest that the counter mechanism implicated in malaria parasite proliferation integrates extracellular resource status to modify progeny number during blood stage infection.
Topics: Animals; Humans; Parasites; Malaria, Falciparum; Malaria; Plasmodium falciparum; Merozoites; Erythrocytes
PubMed: 38051755
DOI: 10.1371/journal.ppat.1011807 -
Malaria Journal Aug 2023The recent deforestation for agricultural, mining, and human re-settlement has significantly reduced the habitat of many non-human primates (NHPs) in Indonesia and...
BACKGROUND
The recent deforestation for agricultural, mining, and human re-settlement has significantly reduced the habitat of many non-human primates (NHPs) in Indonesia and intensifies interaction between the NHPs and humans and thus opening the possibility of pathogen spill-over. The emergence of zoonotic malaria, such as Plasmodium knowlesi, poses an immense threat to the current malaria control and elimination that aims for the global elimination of malaria by 2030. As malaria in humans and NHPs is transmitted by the female Anopheles mosquito, malaria vector control is very important to mitigate the spill-over of the malaria parasite to humans. The present study aims to explore the Anopheles species diversity in human settlements adjacent to the wildlife sanctuary forest in Buton Utara Regency, Southeast Sulawesi, Indonesia, and identify the species that potentially transmit the pathogen from monkey to human in the area.
METHODS
Mosquito surveillance was conducted using larval and adult collection, and the collected mosquitoes were identified morphologically and molecularly using the barcoding markers, cytochrome oxidase subunit I (COI), and internal transcribed species 2 (ITS2) genes. Plasmodium sporozoite carriage was conducted on mosquitoes collected through human landing catch (HLC) and human-baited double net trap (HDNT).
RESULTS
The results revealed several Anopheles species, such as Anopheles flavirostris (16.6%), Anopheles sulawesi (3.3%), Anopheles maculatus (3.3%), Anopheles koliensis (1.2%), and Anopheles vagus (0.4%). Molecular analysis of the sporozoite carriage using the primate-specific malaria primers identified An. sulawesi, a member of the Leucosphyrus group, carrying Plasmodium inui sporozoite.
CONCLUSIONS
This study indicates that the transmission of zoonotic malaria in the area is possible and alerts to the need for mitigation efforts through a locally-tailored vector control intervention and NHPs habitat conservation.
Topics: Animals; Adult; Humans; Female; Malaria; Animals, Wild; Anopheles; Indonesia; Mosquito Vectors; Plasmodium knowlesi; Haplorhini
PubMed: 37528368
DOI: 10.1186/s12936-023-04647-7