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Nature Communications Jun 2023Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission...
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 R, 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 (R < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (R > 1) was estimated historically for P. falciparum and P. vivax, with declines in R 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.
Topics: Humans; Plasmodium knowlesi; Malaysia; Malaria; Malaria, Falciparum; Malaria, Vivax
PubMed: 37263994
DOI: 10.1038/s41467-023-38476-8 -
Malaria Journal May 2023Many rural communities in Malaysian Borneo and Southeast Asia are at risk of Plasmodium knowlesi malaria. Multiple factors contribute to infection, however, a deep...
Seeing malaria through the eyes of affected communities: using photovoice to document local knowledge on zoonotic malaria causation and prevention practices among rural communities exposed to Plasmodium knowlesi malaria in Northern Borneo Island.
BACKGROUND
Many rural communities in Malaysian Borneo and Southeast Asia are at risk of Plasmodium knowlesi malaria. Multiple factors contribute to infection, however, a deep understanding of illness causation and prevention practices among at-risk communities remains limited. This study aims to document local knowledge on malaria causation and preventive practices of rural communities in Sabah, Malaysia, using photovoice-a participatory research method.
METHODS
From January to June 2022, a photovoice study was conducted with rural communities in Matunggong subdistrict, Malaysia, to explore their experiences with and local knowledge of non-human primate malaria and prevention practices. The study included (1) an introductory phase in which participants were introduced to the photovoice method; (2) a documentation phase in which participants captured and narrated photos from their communities; (3) a discussion phase in which participants discussed photos and relevant topics through a series of three focus group discussions (FGDs) per village; and (4) a dissemination phase where selected photos were shared with key stakeholders through a photo exhibition. A purposively selected sample of 26 participants (adults > 18 years old, male, and female) from four villages participated in all phases of the study. The study activities were conducted in Sabah Malay dialect. Participants and the research team contributed to data review and analyses.
RESULTS
Rural communities in Sabah, Malaysia possess local knowledge that attributes non-human primate malaria to natural factors related to the presence of mosquitoes that bite humans and which carry "kuman-malaria" or malaria parasite. Participants revealed various preventive practises ranging from traditional practises, including burning dried leaves and using plants that produce foul odours, to non-traditional approaches such as aerosols and mosquito repellents. By engaging with researchers and policymakers, the participants or termed as co-researchers in this study, showcased their ability to learn and appreciate new knowledge and perspectives and valued the opportunity to share their voices with policymakers. The study successfully fostered a balance of power dynamics between the co-researchers, research team members and policymakers.
CONCLUSION
There were no misconceptions about malaria causation among study participants. The insights from study participants are relevant because of their living experience with the non-human malaria. It is critical to incorporate rural community perspectives in designing locally effective and feasible malaria interventions in rural Sabah, Malaysia. Future research can consider adapting the photovoice methodology for further research with the community toward building locally tailored-malaria strategies.
Topics: Adult; Animals; Humans; Plasmodium knowlesi; Rural Population; Borneo; Malaria; Asia, Southeastern; Malaysia
PubMed: 37237418
DOI: 10.1186/s12936-023-04603-5 -
Tropical Medicine and Infectious Disease May 2023The genetic diversity of of Malaysian isolates was studied recently. However, the study only included three relatively older strains from Peninsular Malaysia and...
The genetic diversity of of Malaysian isolates was studied recently. However, the study only included three relatively older strains from Peninsular Malaysia and focused mainly on the conserved blocks of this gene. In this study, the full-length sequence of recent isolates from Peninsular Malaysia was characterized, along with Malaysian Borneo and Thailand sequences that were retrieved from GenBank. Genomic DNA of was extracted from human blood specimens and the gene was PCR-amplified, cloned, and sequenced. The sequences were analysed for genetic diversity, departure from neutrality, and geographical clustering. The gene was found to be under purifying/negative selection and grouped into three clusters via a neighbour-joining tree and neighbour net inferences. Of the four polymorphic blocks in , block IV, was most polymorphic, with the highest insertion-deletion (indel) sites. Two allelic families were identified in block IV, thereby highlighting the importance of this block as a promising genotyping marker for the multiplicity of infection study of malaria. A single locus marker may provide an alternate, simpler method to type in a population.
PubMed: 37235333
DOI: 10.3390/tropicalmed8050285 -
Microbiology Spectrum Jun 2023Human malaria is a life-threatening parasitic disease with high impact in the sub-Saharan Africa region, where 95% of global cases occurred in 2021. While most malaria...
Human malaria is a life-threatening parasitic disease with high impact in the sub-Saharan Africa region, where 95% of global cases occurred in 2021. While most malaria diagnostic tools are focused on Plasmodium falciparum, there is a current lack of testing non-P. falciparum cases, which may be underreported and, if undiagnosed or untreated, may lead to severe consequences. In this work, seven species-specific loop-mediated isothermal amplification (LAMP) assays were designed and evaluated against TaqMan quantitative PCR (qPCR), microscopy, and enzyme-linked immunosorbent assays (ELISAs). Their clinical performance was assessed with a cohort of 164 samples of symptomatic and asymptomatic patients from Ghana. All asymptomatic samples with a parasite load above 80 genomic DNA (gDNA) copies per μL of extracted sample were detected with the Plasmodium falciparum LAMP assay, reporting 95.6% (95% confidence interval [95% CI] of 89.9 to 98.5) sensitivity and 100% (95% CI of 87.2 to 100) specificity. This assay showed higher sensitivity than microscopy and ELISA, which were 52.7% (95% CI of 39.7 to 67%) and 67.3% (95% CI of 53.3 to 79.3%), respectively. Nine samples were positive for , indicating coinfections with P. falciparum, which represented 5.5% of the tested population. No samples were detected as positive for P. vivax, , P. knowlesi, or P. cynomolgi by any method. Furthermore, translation to the point-of-care was demonstrated with a subcohort of 18 samples tested locally in Ghana using our handheld lab-on-chip platform, Lacewing, showing comparable results to a conventional fluorescence-based instrument. The developed molecular diagnostic test could detect asymptomatic malaria cases, including submicroscopic parasitemia, and it has the potential to be used for point-of-care applications. The spread of Plasmodium falciparum parasites with / gene deletions presents a major threat to reliable point-of-care diagnosis with current rapid diagnostic tests (RDTs). Novel molecular diagnostics based on nucleic acid amplification are needed to address this liability. In this work, we overcome this challenge by developing sensitive tools for the detection of Plasmodium falciparum and non-P. falciparum species. Furthermore, we evaluate these tools with a cohort of symptomatic and asymptomatic malaria patients and test a subcohort locally in Ghana. The findings of this work could lead to the implementation of DNA-based diagnostics to fight against the spread of malaria and provide reliable, sensitive, and specific diagnostics at the point of care.
Topics: Humans; Animals; Parasites; Point-of-Care Systems; Sensitivity and Specificity; Malaria; Malaria, Vivax; Malaria, Falciparum; Plasmodium falciparum
PubMed: 37158750
DOI: 10.1128/spectrum.05222-22 -
Tropical Medicine and Infectious Disease Mar 2023We propose a protocol suitable for point-of-care diagnosis of malaria utilizing a simple and purification-free DNA extraction method with the combination of...
We propose a protocol suitable for point-of-care diagnosis of malaria utilizing a simple and purification-free DNA extraction method with the combination of loop-mediated isothermal amplification assay and lateral flow (LAMP-LF). The multiplex LAMP-LF platform developed here can simultaneously detect and genus (for and ). Through the capillary effect, the results can be observed by the red band signal on the test and control lines within 5 min. The developed multiplex LAMP-LF was tested with 86 clinical blood samples on-site at Hospital Kapit, Sarawak, Malaysia. By using microscopy as the reference method, the multiplex LAMP-LF showed 100% sensitivity (95% confidence interval (CI): 91.4 to 100.00%) and 97.8% specificity (95% CI: 88.2% to 99.9%). The high sensitivity and specificity of multiplex LAMP-LF make it ideal for use as a point-of-care diagnostic tool. The simple and purification-free DNA extraction protocol can be employed as an alternative DNA extraction method for malaria diagnosis in resource-limited settings. By combining the simple DNA extraction protocol and multiplex LAMP-LF approach, we aim to develop a simple-to-handle and easy-to-read molecular diagnostic tool for malaria in both laboratory and on-site settings.
PubMed: 37104326
DOI: 10.3390/tropicalmed8040199 -
Travel Medicine and Infectious Disease 2023Plasmodium knowlesi has been reported as an emerging infection throughout the Southeast Asian region, especially in the Malaysian state of Sabah, where it accounts for...
Plasmodium knowlesi has been reported as an emerging infection throughout the Southeast Asian region, especially in the Malaysian state of Sabah, where it accounts for the majority of the malaria cases reported. This is in contrast to Europe, where imported P. knowlesi is a rarely reported infection. We present a case of P. knowlesi infection in a Danish woman returning from a short trip to Malaysian Borneo. Microscopy of blood smears revealed 0.8% infected erythrocytes, but due to the atypical morphological presentation, a conclusive species identification was made by molecular methods. Plasmodium knowlesi is a potentially fatal infection and taking the increasing travel activity into consideration after the coronavirus disease 2019 (COVID-19) pandemic, P. knowlesi should be a differential diagnosis in patients with travel-associated illness returning from highly endemic Southeast Asian areas.
Topics: Animals; Female; Humans; Borneo; Plasmodium knowlesi; Parasites; Travel; COVID-19; Malaria; Denmark
PubMed: 37088361
DOI: 10.1016/j.tmaid.2023.102580 -
Tropical Medicine & International... Jun 2023Malaysia has achieved the status of zero indigenous human malaria cases. Nevertheless, imported human malaria has increasingly been reported in Sarawak, Malaysian...
OBJECTIVES
Malaysia has achieved the status of zero indigenous human malaria cases. Nevertheless, imported human malaria has increasingly been reported in Sarawak, Malaysian Borneo. As zoonotic malaria caused by Plasmodium knowlesi remains a major public health problem in Sarawak, the threat of imported malaria must be addressed as it can cause human malaria reintroduction, sustain transmission, and lead to complications. The objectives of this study were to investigate the epidemiological characteristics of imported malaria cases reported in Sarawak and to underline the challenge posed by imported malaria towards malaria elimination efforts.
METHODS
Imported malaria cases reported in Sarawak from 2011 to 2019 were collected from Sarawak State Health Department and analysed in this longitudinal retrospective study.
RESULTS
A total of 2058 imported malaria cases were registered in all districts in Sarawak. Highest number of cases were reported in Kapit (n = 559; 27.16%), followed by Sibu (n = 424; 20.6%), and Miri (n = 166; 8.07%). Based on the demographic profile, most of the patients constituted of either male sex (98.49%), age group of 40-49 years (39.6%), Iban ethnic (57.92%), worked in logging industry (88.58%), Malaysian nationals (91.84%), contracted malaria in Papua New Guinea (46.11%), uncomplicated disease (77.89%), or hospitalised cases (97.86%). The most prominent Plasmodium species diagnosed were P. vivax (52.67%) and P. falciparum (35.81%).
CONCLUSIONS
Surveillance, disease detection, and medical follow-up must be carried out thoroughly for individuals who returned from malaria-endemic countries. It is also necessary to promote pre-travel preventive education as well as chemoprophylaxis to travellers heading to endemic areas.
Topics: Humans; Male; Adult; Middle Aged; Malaysia; Retrospective Studies; Malaria; Malaria, Vivax; Malaria, Falciparum; Plasmodium knowlesi
PubMed: 37042251
DOI: 10.1111/tmi.13875 -
Frontiers in Microbiology 2023[This corrects the article DOI: 10.3389/fmicb.2023.1126418.].
[This corrects the article DOI: 10.3389/fmicb.2023.1126418.].
PubMed: 37007492
DOI: 10.3389/fmicb.2023.1178864 -
Scientific Reports Mar 2023Plasmodium knowlesi is the major cause of zoonotic malaria in Southeast Asia. Rapid and accurate diagnosis enables effective clinical management. A novel malaria...
Plasmodium knowlesi is the major cause of zoonotic malaria in Southeast Asia. Rapid and accurate diagnosis enables effective clinical management. A novel malaria diagnostic tool, Gazelle (Hemex Health, USA) detects haemozoin, a by-product of haem metabolism found in all Plasmodium infections. A pilot phase refined the Gazelle haemozoin identification algorithm, with the algorithm then tested against reference PCR in a larger cohort of patients with P. knowlesi mono-infections and febrile malaria-negative controls. Limit-of-detection analysis was conducted on a subset of P. knowlesi samples serially diluted with non-infected whole blood. The pilot phase of 40 P. knowlesi samples demonstrated 92.5% test sensitivity. P. knowlesi-infected patients (n = 203) and febrile controls (n = 44) were subsequently enrolled. Sensitivity and specificity of the Gazelle against reference PCR were 94.6% (95% CI 90.5-97.3%) and 100% (95% CI 92.0-100%) respectively. Positive and negative predictive values were 100% and 98.8%, respectively. In those tested before antimalarial treatment (n = 143), test sensitivity was 96.5% (95% CI 92.0-98.9%). Sensitivity for samples with ≤ 200 parasites/µL (n = 26) was 84.6% (95% CI 65.1-95.6%), with the lowest parasitaemia detected at 18/µL. Limit-of-detection (n = 20) was 33 parasites/µL (95% CI 16-65%). The Gazelle device has the potential for rapid, sensitive detection of P. knowlesi infections in endemic areas.
Topics: Animals; Humans; Plasmodium knowlesi; Antelopes; Point-of-Care Systems; Malaria; Parasites
PubMed: 36959462
DOI: 10.1038/s41598-023-31839-7