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Fulltext Contribution of Plasmodium knowlesi to Multispecies Human Malaria Infections in North Sumatera, Indonesia

Lubis IND, Wijaya H, Lubis M, Lubis CP, Divis PCS, Beshir KB, et al.

J Infect Dis, 2017 Apr 01;215(7):1148-1155.
PMID: 28201638 DOI: 10.1093/infdis/jix091

Background: As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province.
Methods: A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi.
Results: Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%).
Conclusions: Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities.
Fulltext Emergence of Undetectable Malaria Parasites: A Threat under the Radar amid the COVID-19 Pandemic?

Beshir KB, Grignard L, Hajissa K, Mohammed A, Nurhussein AM, Ishengoma DS, et al.

Am J Trop Med Hyg, 2020 08;103(2):558-560.
PMID: 32553046 DOI: 10.4269/ajtmh.20-0467

Rapid diagnostic tests (RDTs) play a critical role in malaria diagnosis and control. The emergence of Plasmodium falciparum parasites that can evade detection by RDTs threatens control and elimination efforts. These parasites lack or have altered genes encoding histidine-rich proteins (HRPs) 2 and 3, the antigens recognized by HRP2-based RDTs. Surveillance of such parasites is dependent on identifying false-negative RDT results among suspected malaria cases, a task made more challenging during the current pandemic because of the overlap of symptoms between malaria and COVID-19, particularly in areas of low malaria transmission. Here, we share our perspective on the emergence of P. falciparum parasites lacking HRP2 and HRP3, and the surveillance needed to identify them amid the COVID-19 pandemic.
Fulltext Use of saliva as an alternative diagnostic method for diagnosis of COVID-19

Ganie MW, Nainggolan IRA, Bestari R, Hazidar AH, Hasibuan M, Siregar J, et al.

IJID Reg, 2023 May 04.
PMID: 37363193 DOI: 10.1016/j.ijregi.2023.03.011

BACKGROUND: Mass population testing has been recommended to contain the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the use of nasopharyngeal swab specimens has caused many logistic challenges. This study investigated the sensitivity and specificity of saliva as a non-invasively-obtained specimen for molecular detection of SARS-CoV-2 RNA.
METHODS: In total, 153 patients with confirmed coronavirus disease 2019 (COVID-19) who had been admitted to the regional referral hospital or who self-isolated at home were included in this study. Nasopharyngeal swab specimens and saliva samples were collected on the same day, and were tested for SARS-CoV-2 infection using reverse transcriptase polymerase chain reaction.
RESULTS: The sensitivity and specificity of saliva samples were 81.5% and 76.4%, respectively, in cases that had been confirmed as COVID-19 using nasopharyngeal swab samples. Positive predictive values and negative predictive values were 92.3% and 54.1%, respectively. The highest detection rates were found among samples collected 4-7 days since symptom onset.
CONCLUSION: Saliva samples showed comparable performance to nasopharyngeal swab specimens for the diagnosis of COVID-19 in adults. The performance of saliva as a diagnostic specimen for COVID-19 testing is particularly significant during the first week of symptoms.
Fulltext Perceptions and prevention practices on malaria among the indigenous Orang Asli community in Kelantan, Peninsular Malaysia

Munajat MB, Rahim MAFA, Wahid W, Seri Rakna MIM, Divis PCS, Chuangchaiya S, et al.

Malar J, 2021 Apr 27;20(1):202.
PMID: 33906645 DOI: 10.1186/s12936-021-03741-y

BACKGROUND: Malaysia is on track towards malaria elimination. However, several cases of malaria still occur in the country. Contributing factors and communal aspects have noteworthy effects on any malaria elimination activities. Thus, assessing the community's knowledge, attitudes and practices (KAP) towards malaria is essential. This study was performed to evaluate KAP regarding malaria among the indigenous people (i.e. Orang Asli) in Peninsular Malaysia.
METHODS: A household-based cross-sectional study was conducted in five remote villages (clusters) of Orang Asli located in the State of Kelantan, a central region of the country. Community members aged six years and above were interviewed. Demographic, socio-economic and KAP data on malaria were collected using a structured questionnaire and analysed using descriptive statistics.
RESULTS: Overall, 536 individuals from 208 households were interviewed. Household indoor residual spraying (IRS) coverage and bed net ownership were 100% and 89.2%, respectively. A majority of respondents used mosquito bed nets every night (95.1%), but only 50.2% were aware that bed nets were used to prevent malaria. Nevertheless, almost all of the respondents (97.9%) were aware that malaria is transmitted by mosquitoes. Regarding practice for managing malaria, the most common practice adopted by the respondents was seeking treatment at the health facilities (70.9%), followed by self-purchase of medication from a local shop (12.7%), seeking treatment from a traditional healer (10.5%) and self-healing (5.9%). Concerning potential zoonotic malaria, about half of the respondents (47.2%) reported seeing monkeys from their houses and 20.1% reported entering nearby forests within the last 6 months.
CONCLUSION: This study found that most populations living in the villages have an acceptable level of knowledge and awareness about malaria. However, positive attitudes and practices concerning managing malaria require marked improvement.
Fulltext The presence of Plasmodium malariae and Plasmodium knowlesi in near malaria elimination setting in western Indonesia

Nainggolan IRA, Syafutri RD, Sinambela MN, Devina C, Handayani, Hasibuan BS, et al.

Malar J, 2022 Nov 05;21(1):316.
PMID: 36333701 DOI: 10.1186/s12936-022-04335-y

BACKGROUND: Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive control measures and surveillance programmes must be intensified. This study aims to determine the prevalence of microscopic and submicroscopic malaria in Langkat district, North Sumatera Province, Indonesia.
METHODS: A cross-sectional survey was conducted in six villages in Langkat district, North Sumatera Province in June 2019. Data were recorded using a standardized questionnaire. Finger pricked blood samples were obtained for malaria examination using rapid diagnostic test, thick and thin blood smears, and polymerase chain reaction.
RESULTS: A total of 342 individuals were included in the study. Of them, one (0.3%) had a microscopic Plasmodium malariae infection, no positive RDT examination, and three (0.9%) were positive for P. malariae (n = 1) and Plasmodium knowlesi (n = 2). The distribution of bed net ownership was owned by 40% of the study participants. The participants had a house within a radius of 100-500 m from the forest (86.3%) and had the housing material of cement floor (56.1%), a tin roof (82.2%), wooden wall (35.7%), bamboo wall (28.1%), and brick wall (21.6%).
CONCLUSION: Malaria incidence has substantially decreased in Langkat, North Sumatera, Indonesia. However, submicroscopic infection remains in the population and may contribute to further transmission. Surveillance should include the detection of microscopic undetected parasites, to enable the achievement of malaria elimination.
Fulltext Updating estimates of Plasmodium knowlesi malaria risk in response to changing land use patterns across Southeast Asia

Tobin RJ, Harrison LE, Tully MK, Lubis IND, Noviyanti R, Anstey NM, et al.

PLoS Negl Trop Dis, 2024 Jan;18(1):e0011570.
PMID: 38252650 DOI: 10.1371/journal.pntd.0011570

BACKGROUND: Plasmodium knowlesi is a zoonotic parasite that causes malaria in humans. The pathogen has a natural host reservoir in certain macaque species and is transmitted to humans via mosquitoes of the Anopheles Leucosphyrus Group. The risk of human P. knowlesi infection varies across Southeast Asia and is dependent upon environmental factors. Understanding this geographic variation in risk is important both for enabling appropriate diagnosis and treatment of the disease and for improving the planning and evaluation of malaria elimination. However, the data available on P. knowlesi occurrence are biased towards regions with greater surveillance and sampling effort. Predicting the spatial variation in risk of P. knowlesi malaria requires methods that can both incorporate environmental risk factors and account for spatial bias in detection.
METHODS & RESULTS: We extend and apply an environmental niche modelling framework as implemented by a previous mapping study of P. knowlesi transmission risk which included data up to 2015. We reviewed the literature from October 2015 through to March 2020 and identified 264 new records of P. knowlesi, with a total of 524 occurrences included in the current study following consolidation with the 2015 study. The modelling framework used in the 2015 study was extended, with changes including the addition of new covariates to capture the effect of deforestation and urbanisation on P. knowlesi transmission.
DISCUSSION: Our map of P. knowlesi relative transmission suitability estimates that the risk posed by the pathogen is highest in Malaysia and Indonesia, with localised areas of high risk also predicted in the Greater Mekong Subregion, The Philippines and Northeast India. These results highlight areas of priority for P. knowlesi surveillance and prospective sampling to address the challenge the disease poses to malaria elimination planning.
Fulltext Updating estimates of Plasmodium knowlesi malaria risk in response to changing land use patterns across Southeast Asia

Tobin RJ, Harrison LE, Tully MK, Lubis IND, Noviyanti R, Anstey NM, et al.

medRxiv, 2023 Aug 08.
PMID: 37609228 DOI: 10.1101/2023.08.04.23293633

BACKGROUND: Plasmodium knowlesi is a zoonotic parasite that causes malaria in humans. The pathogen has a natural host reservoir in certain macaque species and is transmitted to humans via mosquitoes of the Anopheles Leucosphyrus Group. The risk of human P. knowlesi infection varies across Southeast Asia and is dependent upon environmental factors. Understanding this geographic variation in risk is important both for enabling appropriate diagnosis and treatment of the disease and for improving the planning and evaluation of malaria elimination. However, the data available on P. knowlesi occurrence are biased towards regions with greater surveillance and sampling effort. Predicting the spatial variation in risk of P. knowlesi malaria requires methods that can both incorporate environmental risk factors and account for spatial bias in detection.
METHODS & RESULTS: We extend and apply an environmental niche modelling framework as implemented by a previous mapping study of P. knowlesi transmission risk which included data up to 2015. We reviewed the literature from October 2015 through to March 2020 and identified 264 new records of P. knowlesi, with a total of 524 occurrences included in the current study following consolidation with the 2015 study. The modelling framework used in the 2015 study was extended, with changes including the addition of new covariates to capture the effect of deforestation and urbanisation on P. knowlesi transmission.
DISCUSSION: Our map of P. knowlesi relative transmission suitability estimates that the risk posed by the pathogen is highest in Malaysia and Indonesia, with localised areas of high risk also predicted in the Greater Mekong Subregion, The Philippines and Northeast India. These results highlight areas of priority for P. knowlesi surveillance and prospective sampling to address the challenge the disease poses to malaria elimination planning.
Fulltext Evidence of Submicroscopic Plasmodium knowlesi Mono-Infection in Remote Indigenous Communities in Kelantan, Peninsular Malaysia

Dian ND, Muhammad AB, Azman EN, Eddie NA, Azmi NI, Yee VCT, et al.

Am J Trop Med Hyg, 2023 Nov 01;109(5):1081-1085.
PMID: 37748768 DOI: 10.4269/ajtmh.23-0184

Malaysia has maintained zero cases of indigenous human malaria since 2018. However, zoonotic malaria is still prevalent in underdeveloped areas and hard-to-reach populations. This study aimed to determine the prevalence of malaria among remote indigenous communities in Peninsular Malaysia. A cross-sectional survey was conducted in six settlements in Kelantan state, from June to October 2019. Blood samples were tested for malaria using microscopy and nested polymerase chain reaction (nPCR) targeting the Plasmodium cytochrome c oxidase subunit III (cox3) gene. Of the 1,954 individuals who appeared healthy, no malaria parasites were found using microscopy. However, nPCR revealed seven cases of Plasmodium knowlesi mono-infection (0.4%), and six out of seven infections were in the group of 19 to 40 years old (P = 0.026). No human malaria species were detected by nPCR. Analysis of the DNA sequences also showed high similarity that reflects common ancestry to other P. knowlesi isolates. These findings indicate low submicroscopic P. knowlesi infections among indigenous communities in Malaysia, requiring PCR-based surveillance to support malaria control activities in the country.
ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Mo Y, Ding Y, Cao Y, Hopkins J, Ashley EA, Waithira N, et al.

Wellcome Open Res, 2023;8:179.
PMID: 37854055 DOI: 10.12688/wellcomeopenres.19210.2

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.