Displaying publications 1 - 20 of 163 in total

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  1. Srisawat N, Gubler DJ, Pangestu T, Limothai U, Thisyakorn U, Ismail Z, et al.
    PLoS Negl Trop Dis, 2024 Mar;18(3):e0012060.
    PMID: 38551892 DOI: 10.1371/journal.pntd.0012060
    The 6th Asia Dengue Summit (ADS) themed "Road Map to Zero Dengue Death" was held in Thailand from 15th-16th June 2023. The summit was hosted by Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand in conjunction with Queen Saovabha Memorial Institute, The Thai Red Cross Society; Faculty of Tropical Medicine, Mahidol University; and the Ministry of Public Health. The 6th ADS was convened by Asia Dengue Voice and Action (ADVA); Global Dengue and Aedes Transmitted Diseases Consortium (GDAC); Southeast Asian Ministers of Education Tropical Medicine and Public Health Network (SEAMEO TROPMED); Fondation Mérieux (FMx) and the International Society for Neglected Tropical Diseases (ISNTD). Dengue experts from academia and research, and representatives from the Ministries of Health, Regional and Global World Health Organization (WHO) and International Vaccine Institute (IVI) participated in the three-day summit. With more than 51 speakers and 451 delegates from over 24 countries, 10 symposiums, and 2 full days, the 6th ADS highlighted the growing threat of dengue and its antigenic evolution, flagged the urgent need to overcome vaccine hesitancy and misinformation crisis, and focused on dengue control policies, newer diagnostics, therapeutics and vaccines, travel-associated dengue, and strategies to improve community involvement.
  2. 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.

  3. Idrus NL, Md Jamal S, Abu Bakar A, Embong H, Ahmad NS
    PLoS Negl Trop Dis, 2023 Dec;17(12):e0011839.
    PMID: 38113250 DOI: 10.1371/journal.pntd.0011839
    BACKGROUND: The timely identification of severe dengue in peadiatric patients is of utmost importance, as any delay in diagnosis could lead to an irreversible state of shock potentially leading to fatal consequences. The primary aim of our study was to characterize dengue severity in paediatric patients based on initial symptoms, signs, and laboratory investigation of their presentation in the emergency department.

    METHODOLOGY: We conducted a retrospective data retrieval from the medical records of 254 paediatric patients who had been diagnosed with confirmed cases of dengue fever. The clinical characteristics were compared between severe and non-severe dengue. Multiple logistic regression analysis was utilised to elucidate the variables that exhibited associations with severe dengue.

    RESULTS: A total of 254 paediatric patients were included, among whom 15.4% (n = 39) were diagnosed with severe dengue. Multiple logistic regression analysis identified lethargy, systolic blood pressure (SBP) below 90 mmHg, capillary refilled time (CRT) longer than 2 seconds, ascites, and hepatomegaly were independently associated with severe dengue.

    CONCLUSION: In paediatric patients, severe dengue is associated with specific clinical indicators, including lethargy, low systolic blood pressure, prolonged capillary refill time (CRT), and the presence of ascites and hepatomegaly. Identifying these clinical features early is crucial for primary care physicians, as it enables accurate diagnosis and timely intervention to manage severe dengue effectively.

  4. Hussin A, Nor Rahim MY, Dalusim F, Shahidan MA, Nathan S, Ibrahim N
    PLoS Negl Trop Dis, 2023 Oct;17(10):e0011696.
    PMID: 37844130 DOI: 10.1371/journal.pntd.0011696
    INTRODUCTION: Melioidosis is a deadly endemic disease in northern Australia and Southeast Asia, including Sabah, Malaysia, which is caused by the bacterium Burkholderia pseudomallei. It contributes to high fatality rates, mainly due to misdiagnosis leading to the wrong treatment being administered to the patients. Local epidemiology and data on clinical features could assist clinicians during diagnosis and treatment. However, these details are still scarce, particularly in Sabah.

    METHODS: A retrospective study of 246 culture-confirmed melioidosis cases in Queen Elizabeth Hospital, Sabah, Malaysia was performed between 2016 and 2018. The epidemiological data and clinical and laboratory findings were extracted and analysed.

    RESULTS: The annual incidence of culture-confirmed melioidosis cases was estimated to be 4.97 per 100,000 people. The mean age of the patients was 50±15 years. Males and members of the Kadazan-Dusun ethnic group accounted for the majority of the melioidosis cases. The odds ratio analysis indicated that bacteraemic melioidosis in this region was significantly associated with fever (76%), and patients having at least one underlying illness (43%), including diabetes mellitus (32%). Sixty-eight patients (28%) succumbed to melioidosis. Contrary to what is known regarding factors that promote bacteraemic melioidosis, neither patients with fever nor patients with at least one comorbid disease, including diabetes mellitus, were significantly associated with death from melioidosis. There was no statistically significant difference between patients without comorbidities (24, 27%) and those with at least one comorbid disease (26, 25%), including diabetes mellitus (18, 23%). The odds ratios indicate that melioidosis mortality in this region is related to patients showing respiratory organ-associated symptoms (29%), bacteraemia (30%), and septic shock (47%). Burkholderia pseudomallei isolates in this study were highly susceptible to ceftazidime (100%), imipenem (100%), and trimethoprim-sulfamethoxazole (98%).

    CONCLUSIONS: Information obtained from this study can be used by clinicians to recognise individuals with the highest risk of acquiring melioidosis, estimate an accurate prognosis, and provide effective treatment for melioidosis patients to reduce death from melioidosis.

  5. Shettima A, Ishak IH, Lau B, Abu Hasan H, Miswan N, Othman N
    PLoS Negl Trop Dis, 2023 Sep;17(9):e0011604.
    PMID: 37721966 DOI: 10.1371/journal.pntd.0011604
    Synthetic insecticides are the primary vector control method used globally. However, the widespread use of insecticides is a major cause of insecticide-resistance in mosquitoes. Hence, this study aimed at elucidating permethrin and temephos-resistant protein expression profiles in Ae. aegypti using quantitative proteomics. In this study, we evaluated the susceptibility of Ae. aegypti from Penang Island dengue hotspot and non-hotspot against 0.75% permethrin and 31.25 mg/l temephos using WHO bioassay method. Protein extracts from the mosquitoes were then analysed using LC-ESI-MS/MS for protein identification and quantification via label-free quantitative proteomics (LFQ). Next, Perseus 1.6.14.0 statistical software was used to perform differential protein expression analysis using ANOVA and Student's t-test. The t-test selected proteins with≥2.0-fold change (FC) and ≥2 unique peptides for gene expression validation via qPCR. Finally, STRING software was used for functional ontology enrichment and protein-protein interactions (PPI). The WHO bioassay showed resistance with 28% and 53% mortalities in adult mosquitoes exposed to permethrin from the hotspot and non-hotspot areas. Meanwhile, the susceptibility of Ae. aegypti larvae revealed high resistance to temephos in hotspot and non-hotspot regions with 80% and 91% mortalities. The LFQ analyses revealed 501 and 557 (q-value <0.05) differentially expressed proteins in adults and larvae Ae. aegypti. The t-test showed 114 upregulated and 74 downregulated proteins in adult resistant versus laboratory strains exposed to permethrin. Meanwhile, 13 upregulated and 105 downregulated proteins were observed in larvae resistant versus laboratory strains exposed to temephos. The t-test revealed the upregulation of sodium/potassium-dependent ATPase β2 in adult permethrin resistant strain, H15 domain-containing protein, 60S ribosomal protein, and PB protein in larvae temephos resistant strain. The downregulation of troponin I, enolase phosphatase E1, glucosidase 2β was observed in adult permethrin resistant strain and tubulin β chain in larvae temephos resistant strain. Furthermore, the gene expression by qPCR revealed similar gene expression patterns in the above eight differentially expressed proteins. The PPI of differentially expressed proteins showed a p-value at <1.0 x 10-16 in permethrin and temephos resistant Ae. aegypti. Significantly enriched pathways in differentially expressed proteins revealed metabolic pathways, oxidative phosphorylation, carbon metabolism, biosynthesis of amino acids, glycolysis, and citrate cycle. In conclusion, this study has shown differentially expressed proteins and highlighted upregulated and downregulated proteins associated with insecticide resistance in Ae. aegypti. The validated differentially expressed proteins merit further investigation as a potential protein marker to monitor and predict insecticide resistance in field Ae. aegypti. The LC-MS/MS data were submitted into the MASSIVE database with identifier no: MSV000089259.
  6. Qamruddin RM, Safferi RS, Mohamed Ismail Z, Salleh MS, Abd Hamid MNH, Frederic Ng VER, et al.
    PLoS Negl Trop Dis, 2023 Aug;17(8):e0011569.
    PMID: 37585486 DOI: 10.1371/journal.pntd.0011569
    Not all pit viper species are present in every state of Malaysia and their distribution varies according to altitude. There is limited information on pit viper bite incidence and its geographical distribution. This was a cross-sectional study of confirmed pit viper bite cases referred to Remote Envenomation Consultancy Services (RECS) from January 2017 to December 2020. Data was collected following the approval of institutional research ethics committee. Universal sampling methods were used. Confirmed pit viper bite cases in each state, geographical location and the antivenom used were reported. A total of 523 confirmed pit viper bite injuries occurred over the 4-year study period. The majority were Malaysians, male and young adults. Most were non-occupational related (83.9%) and involved the upper limbs (46.8%). The commonest pit viper species involved was Trimeresurus purpureomaculatus (23.7%). Green pit viper antivenom (GPAV) was the most frequent antivenom used (n = 51) with the majority of patients requiring only one dose (3 vials). This study provides a better appreciation of indigenous pit viper species distribution for each state and reflects the requirement of appropriate antivenom to be stocked in each state or district hospital.
  7. Fu JYL, Chua CL, Abu Bakar AS, Vythilingam I, Wan Sulaiman WY, Alphey L, et al.
    PLoS Negl Trop Dis, 2023 Jun;17(6):e0011423.
    PMID: 37307291 DOI: 10.1371/journal.pntd.0011423
    BACKGROUND: Emerging arboviruses such as chikungunya and Zika viruses have unexpectedly caused widespread outbreaks in tropical and subtropical regions recently. Ross River virus (RRV) is endemic in Australia and has epidemic potential. In Malaysia, Aedes mosquitoes are abundant and drive dengue and chikungunya outbreaks. We assessed risk of an RRV outbreak in Kuala Lumpur, Malaysia by determining vector competence of local Aedes mosquitoes and local seroprevalence as a proxy of human population susceptibility.

    METHODOLOGY/PRINCIPAL FINDINGS: We assessed oral susceptibility of Malaysian Ae. aegypti and Ae. albopictus by real-time PCR to an Australian RRV strain SW2089. Replication kinetics in midgut, head and saliva were determined at 3 and 10 days post-infection (dpi). With a 3 log10 PFU/ml blood meal, infection rate was higher in Ae. albopictus (60%) than Ae. aegypti (15%; p<0.05). Despite similar infection rates at 5 and 7 log10 PFU/ml blood meals, Ae. albopictus had significantly higher viral loads and required a significantly lower median oral infectious dose (2.7 log10 PFU/ml) than Ae. aegypti (4.2 log10 PFU/ml). Ae. albopictus showed higher vector competence, with higher viral loads in heads and saliva, and higher transmission rate (RRV present in saliva) of 100% at 10 dpi, than Ae. aegypti (41%). Ae. aegypti demonstrated greater barriers at either midgut escape or salivary gland infection, and salivary gland escape. We then assessed seropositivity against RRV among 240 Kuala Lumpur inpatients using plaque reduction neutralization, and found a low rate of 0.8%.

    CONCLUSIONS/SIGNIFICANCE: Both Ae. aegypti and Ae. albopictus are susceptible to RRV, but Ae. albopictus displays greater vector competence. Extensive travel links with Australia, abundant Aedes vectors, and low population immunity places Kuala Lumpur, Malaysia at risk of an imported RRV outbreak. Surveillance and increased diagnostic awareness and capacity are imperative to prevent establishment of new arboviruses in Malaysia.

  8. Jeyaprakasam NK, Low VL, Pramasivan S, Liew JWK, Wan-Sulaiman WY, Vythilingam I
    PLoS Negl Trop Dis, 2023 Jun;17(6):e0011438.
    PMID: 37384790 DOI: 10.1371/journal.pntd.0011438
    BACKGROUND: The elimination of malaria in Southeast Asia has become more challenging as a result of rising knowlesi malaria cases. In addition, naturally occurring human infections with other zoonotic simian malaria caused by Plasmodium cynomolgi and Plasmodium inui adds another level of complexity in malaria elimination in this region. Unfortunately, data on vectors which are responsible for transmitting this zoonotic disease is very limited.

    METHODOLOGY/PRINCIPAL FINDINGS: We conducted longitudinal studies to investigate the entomological parameters of the simian malaria vectors and to examine the genetic diversity and evolutionary pattern of their simian Plasmodium. All the captured Anopheles mosquitoes were dissected to examine for the presence of oocysts, sporozoites and to determine the parous rate. Our study revealed that the Anopheles Leucosphyrus Group mosquitoes are highly potential competent vectors, as evidenced by their high rate of parity, survival and sporozoite infections in these mosquitoes. Thus, these mosquitoes represent a risk of human infection with zoonotic simian malaria in this region. Haplotype analysis on P. cynomolgi and P. inui, found in high prevalence in the Anopheles mosquitoes from this study, had shown close relationship between simian Plasmodium from the Anopheles mosquitoes with its vertebrate hosts. This directly signifies the ongoing transmission between the vector, macaques, and humans. Furthermore, population genetic analysis showed significant negative values which suggest that both Plasmodium species are undergoing population expansion.

    CONCLUSIONS/SIGNIFICANCE: With constant microevolutionary processes, there are potential for both P. inui and P. cynomolgi to emerge and spread as a major public health problem, following the similar trend of P. knowlesi. Therefore, concerted vector studies in other parts of Southeast Asia are warranted to better comprehend the transmission dynamics of this zoonotic simian malaria which eventually would aid in the implementation of effective control measures in a rapidly changing environment.

  9. Wang G, Fu R, Zhang L, Xue L, Al-Mahdi AY, Xie X, et al.
    PLoS Negl Trop Dis, 2023 Apr 21;17(4):e0011243.
    PMID: 37083859 DOI: 10.1371/journal.pntd.0011243
    Scrub typhus, caused by mite-borne Orientia tsutsugamushi (O. tsutsugamushi), is a major febrile disease in the Asia-Pacific region. The DNA load of O. tsutsugamushi in the blood was previously found to be significantly higher in patients with fatal disease than those with non-fatal disease and correlated with the duration of illness, presence of eschar, and hepatic enzyme levels. In this prospective observation study, we analyzed the association of bacterial DNA load with clinical features, disease severity, and genotype using real-time PCR targeting the 56 kDa TSA gene of O. tsutsugamushi in the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment. The median O. tsutsugamushi DNA load was 3.11×103 copies/mL (range, 44 to 3.3×106 copies/mL). The severity of patients was categorized as mild, moderate, and severe based on the number of dysfunctional organs, and no significant difference in O. tsutsugamushi DNA load was found among these groups. Patients infected with the Karp group showed a significantly higher O. tsutsugamushi DNA load than those in the Gilliam (P 
  10. Natasha JA, Yasmin AR, Sharma RSK, Nur-Fazila SH, Nur-Mahiza MI, Arshad SS, et al.
    PLoS Negl Trop Dis, 2023 Apr;17(4):e0011255.
    PMID: 37023172 DOI: 10.1371/journal.pntd.0011255
    Being a tropical country with a conducive environment for mosquitoes, mosquito-borne illnesses such as dengue, chikungunya, lymphatic filariasis, malaria, and Japanese encephalitis are prevalent in Malaysia. Recent studies reported asymptomatic infection of West Nile virus (WNV) in animals and humans, but none of the studies included mosquitoes, except for one report made half a century ago. Considering the scarcity of information, our study sampled mosquitoes near migratory bird stopover wetland areas of West Coast Malaysia located in the Kuala Gula Bird Sanctuary and Kapar Energy Venture, during the southward migration period in October 2017 and September 2018. Our previous publication reported that migratory birds were positive for WNV antibody and RNA. Using a nested RT-PCR analysis, WNV RNA was detected in 35 (12.8%) out of 285 mosquito pools consisting of 2,635 mosquitoes, most of which were Culex spp. (species). Sanger sequencing and phylogenetic analysis revealed that the sequences grouped within lineage 2 and shared 90.12%-97.01% similarity with sequences found locally as well as those from Africa, Germany, Romania, Italy, and Israel. Evidence of WNV in the mosquitoes substantiates the need for continued surveillance of WNV in Malaysia.
  11. Nwameme A, Dako-Gyeke P, Asampong E, Allotey P, Reidpath DD, Certain E, et al.
    PLoS Negl Trop Dis, 2023 Mar;17(3):e0011139.
    PMID: 36961830 DOI: 10.1371/journal.pntd.0011139
    The Special Programme for Research and Training in Tropical Diseases developed a massive open online course (MOOC) on implementation research with a focus on infectious diseases of poverty (IDPs) to reinforce the explanation of implementation research concepts through real case studies. The target MOOC participant group included public health officers, researchers and students. By reshaping institutions and building resilience in communities and systems, implementation research will allow progress towards universal health coverage and sustainable development goals. This study evaluates learners' knowledge in implementation research after completing the MOOC using anonymous exit survey responses. Of the almost 4000 enrolled in the two sessions of the MOOC in 2018, about 30% completed all five modules and the assessments, and were awarded certificates. The majority of the participants were early to mid-career professionals, under the age of 40, and from low- and middle-income countries. They were slightly more likely to be men (56%) with a Bachelor or a Master's degree. Participants were public health researchers (45%), public health officers (11%) or students (11%). On completion of the course, an exit survey revealed that 80.9% of respondents indicated significant improvement to strong and very strong implementation research knowledge. This evaluation clearly shows the usefulness of the MOOC on implementation research for reaching out to field researchers and public health practitioners who are facing problems in the implementation of control programmes in low- and middle-income countries.
  12. Rajamanikam A, Isa MNM, Samudi C, Devaraj S, Govind SK
    PLoS Negl Trop Dis, 2023 Mar;17(3):e0011170.
    PMID: 36989208 DOI: 10.1371/journal.pntd.0011170
    Whilst the influence of intestinal microbiota has been shown in many diseases such as irritable bowel syndrome, colorectal cancer, and aging, investigations are still scarce on its role in altering the nature of other infective organisms. Here we studied the association and interaction of Blastocystis sp. and human intestinal microbiota. In this study, we investigated the gut microbiome of Blastocystis sp.-free and Blastocystis sp. ST3-infected individuals who are symptomatic and asymptomatic. We tested if the expression of phenotype and pathogenic characteristics of Blastocystis sp. ST3 was influenced by the alteration of its accompanying microbiota. Blastocystis sp. ST3 infection alters bacterial composition. Its presence in asymptomatic individuals showed a significant effect on microbial richness compared to symptomatic ones. Inferred metagenomic findings suggest that colonization of Blastocystis sp. ST3 could contribute to the alteration of microbial functions. For the first time, we demonstrate the influence of bacteria on Blastocystis sp. pathogenicity. When Blastocystis sp. isolated from a symptomatic individual was co-cultured with bacterial suspension of Blastocystis sp. from an asymptomatic individual, the parasite demonstrated increased growth and reduced potential pathogenic expressions. This study also reveals that Blastocystis sp. infection could influence microbial functions without much effect on the microbiota diversity itself. Our results also demonstrate evidence on the influential role of gut microbiota in altering the characteristics of the parasite, which becomes the basis for the contradictory findings on the parasite's pathogenic role seen across different studies. Our study provides evidence that asymptomatic Blastocystis sp. in a human gut can be triggered to show pathogenic characteristics when influenced by the intestinal microbiota.
  13. Ismail AK, Abd Hamid MNH, Ariff NA, Frederic Ng VER, Goh WC, Abdul Samat NS, et al.
    PLoS Negl Trop Dis, 2023 Jan;17(1):e0010983.
    PMID: 36598885 DOI: 10.1371/journal.pntd.0010983
    Pit vipers from the genus Tropidolaemus are identified as one of the common causes of snake bite from venomous species in Malaysia. All Tropidolaemus species bite cases referred to the Remote Envenomation Consultation Services (RECS) between 2015-2021 were included. A total of 4,718 snake-related injuries cases consulted to RECS with 310 (6.6%) involved Tropidolaemus species; of these 190 (61.3%) were T. subannulatus and 120 (38.7%) T. wagleri. All the T. subannulatus cases occurred in Sabah and Sarawak while all cases of T. wagleri occurred in Peninsular Malaysia. The majority of patients were male (74.8%) and adults between 18-59 years old (61.2%). The upper limb (56.6%) was the most frequent anatomical region involved. Most cases were non-occupationally related (75.4%). Bites from both species caused local pain (77.1%) and swelling (27.2%). Most patients complained of mild pain (48.0%). Paracetamol (40.0%) was the most common analgesic prescribed. Antivenom was not indicated in all cases. Two patients were given antivenom inappropriately before RECS consultation. Most patients (54.7%) needed hospital observation for less than 24 hours. No deaths occurred in the group studied.
  14. Jamil H, Din MFU, Tahir MJ, Saqlain M, Hassan Z, Khan MA, et al.
    PLoS Negl Trop Dis, 2022 Dec;16(12):e0010988.
    PMID: 36480553 DOI: 10.1371/journal.pntd.0010988
    BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) continues to pose a serious threat to the fragile healthcare system of Pakistan with a continuous increase of morbidity and mortality. The present study aimed to assess the knowledge, attitudes, and practices regarding CCHF among general people who resided in Pakistan.

    METHODS: An online cross-sectional survey design was applied, and a convenience sampling technique was used to recruit 1039 adult people from Pakistan. Data were collected from September 08 to October 12, 2021. The questionnaire consisted of a total of 32 questions in four parts assessing socio-demographics, as well as knowledge, attitudes, and practices regarding CCHF. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), and logistic regression analyses were performed to determine the factors associated with good knowledge, positive attitudes, and good practices.

    RESULTS: Alarmingly, 51.5% of participants heard about CCHF infection before administering the survey. Among these, 20.2%, 33.3%, and 48.2% of the study participants had demonstrated good knowledge, positive attitudes, and good practices, respectively. Binary logistic regression analysis revealed that education and income status had a significant impact on knowledge and attitudes (p<0.05). Similarly, the mean attitude scores differed significantly by age, education, and income status (p<0.05).

    CONCLUSIONS: The findings reflected inadequate levels of knowledge, attitudes, and practices regarding CCHF among general people in Pakistan which may regard as lower than expected. As CCHF is a highly contagious disease, it's urgent to initiate a comprehensive approach to handle the situation before it spreads further in Pakistan.

  15. Chamchoy K, Sudsumrit S, Thita T, Krudsood S, Patrapuvich R, Boonyuen U
    PLoS Negl Trop Dis, 2022 Dec;16(12):e0010986.
    PMID: 36508454 DOI: 10.1371/journal.pntd.0010986
    BACKGROUND: Primaquine and tafenoquine are the only licensed drugs that effectively kill the hypnozoite stage and are used to prevent Plasmodium vivax malaria relapse. However, both primaquine and tafenoquine can cause acute hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient people with varying degrees of severity depending on G6PD variants. Additionally, primaquine efficacy against malaria parasites was decreased in individuals with impaired cytochrome P450 2D6 (CYP2D6) activity due to genetic polymorphisms. This study aimed to characterize G6PD and CYP2D6 genetic variations in vivax malaria patients from Yala province, a malaria-endemic area along the Thai-Malaysian border, and determine the biochemical properties of identified G6PD variants.

    METHODOLOGY/PRINCIPLE FINDINGS: Multiplexed high-resolution melting assay and DNA sequencing detected five G6PD variants, including G6PD Kaiping, G6PD Vanua Lava, G6PD Coimbra, G6PD Mahidol, and G6PD Kerala-Kalyan. Biochemical and structural characterization revealed that G6PD Coimbra markedly reduced catalytic activity and structural stability, indicating a high susceptibility to drug-induced hemolysis. While Kerala-Kalyan had minor effects, it is possible to develop mild adverse effects when receiving radical treatment. CYP2D6 genotyping was performed using long-range PCR and DNA sequencing, and the phenotypes were predicted using the combination of allelic variants. Decreased and no-function alleles were detected at frequencies of 53.4% and 14.2%, respectively. The most common alleles were CYP2D6*36+*10 (25.6%), *10 (23.9%), and *1 (22.2%). Additionally, 51.1% of the intermediate metabolizers showed CYP2D6*10/*36+*10 as the predominant genotype (15.9%).

    CONCLUSIONS/SIGNIFICANCE: Our findings provide insights about genetic variations of G6PD and CYP2D6 in 88 vivax malaria patients from Yala, which may influence the safety and effectiveness of radical treatment. Optimization of 8-aminoquinoline administration may be required for safe and effective treatment in the studied population, which could be a significant challenge in achieving the goal of eliminating malaria.

  16. Patikorn C, Ismail AK, Zainal Abidin SA, Othman I, Chaiyakunapruk N, Taychakhoonavudh S
    PLoS Negl Trop Dis, 2022 Nov;16(11):e0010915.
    PMID: 36383562 DOI: 10.1371/journal.pntd.0010915
    BACKGROUND: Despite domestic production of antivenoms in the Association of Southeast Asian Nations (ASEAN) countries, not all victims with snakebite envenomings indicated for antivenom received the appropriate or adequate effective dose of antivenom due to insufficient supply and inadequate access to antivenoms. We aimed to conduct a cost-effectiveness analysis to project the potential economic and clinical impact of improving access to antivenoms when all snakebite envenomings in ASEAN countries were hypothetically treated with geographically appropriate antivenoms.

    METHODOLOGY: Using a decision analytic model with input parameters from published literature, local data, and expert opinion, we projected the impact of "full access" (100%) to antivenom, compared to "current access" in five most impacted ASEAN countries, including Indonesia (10%), Philippines (26%), Vietnam (37%), Lao PDR (4%), and Myanmar (64%), from a societal perspective with a lifetime time horizon. Sensitivity analyses were performed.

    PRINCIPAL FINDINGS: In base-case analyses, full access compared to current access to snake antivenom in the five countries resulted in a total of 9,362 deaths averted (-59%), 230,075 disability-adjusted life years (DALYs) averted (-59%), and cost savings of 1.3 billion USD (-53%). Incremental cost-effectiveness ratios (ICERs) of improving access to antivenom found higher outcomes but lower costs in all countries. Probabilistic sensitivity analyses of 1,000 iterations found that 98.1-100% of ICERs were cost-saving.

    CONCLUSION/SIGNIFICANCE: Improving access to snake antivenom will result in cost-saving for ASEAN countries. Our findings emphasized the importance of further strengthening regional cooperation, investment, and funding to improve the situation of snakebite victims in ASEAN countries.

  17. Jayaraj VJ, Ng CW, Bulgiba A, Appannan MR, Rampal S
    PLoS Negl Trop Dis, 2022 Nov;16(11):e0010887.
    PMID: 36346816 DOI: 10.1371/journal.pntd.0010887
    Malaysia has reported 2.75 million cases and 31,485 deaths as of 30 December 2021. Underestimation remains an issue due to the underdiagnosis of mild and asymptomatic cases. We aimed to estimate the burden of COVID-19 cases in Malaysia based on an adjusted case fatality rate (aCFR). Data on reported cases and mortalities were collated from the Ministry of Health official GitHub between 1 March 2020 and 30 December 2021. We estimated the total and age-stratified monthly incidence rates, mortality rates, and aCFR. Estimated new infections were inferred from the age-stratified aCFR. The total estimated infections between 1 March 2020 and 30 December 2021 was 9,955,000-cases (95% CI: 6,626,000-18,985,000). The proportion of COVID-19 infections in ages 0-11, 12-17, 18-50, 51-65, and above 65 years were 19.9% (n = 1,982,000), 2.4% (n = 236,000), 66.1% (n = 6,577,000), 9.1% (n = 901,000), 2.6% (n = 256,000), respectively. Approximately 32.8% of the total population in Malaysia was estimated to have been infected with COVID-19 by the end of December 2021. These estimations highlight a more accurate infection burden in Malaysia. It provides the first national-level prevalence estimates in Malaysia that adjusted for underdiagnosis. Naturally acquired community immunity has increased, but approximately 68.1% of the population remains susceptible. Population estimates of the infection burden are critical to determine the need for booster doses and calibration of public health measures.
  18. Park JH, Kim MH, Sutanto E, Na SW, Kim MJ, Yeom JS, et al.
    PLoS Negl Trop Dis, 2022 Jun;16(6):e0010492.
    PMID: 35737709 DOI: 10.1371/journal.pntd.0010492
    Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152-625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157-560 aa.) and PvRBP1a-C (606-962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels.
  19. Hajissa K, Islam MA, Sanyang AM, Mohamed Z
    PLoS Negl Trop Dis, 2022 Feb 11;16(2):e0009971.
    PMID: 35148325 DOI: 10.1371/journal.pntd.0009971
    INTRODUCTION: Parasitic infections, especially intestinal protozoan parasites (IPPs) remain a significant public health issue in Africa, where many conditions favour the transmission and children are the primary victims. This systematic review and meta-analysis was carried out with the objective of assessing the prevalence of IPPs among school children in Africa.

    METHODS: Relevant studies published between January 2000 and December 2020 were identified by systematic online search on PubMed, Web of Science, Embase and Scopus databases without language restriction. Pooled prevalence was estimated using a random-effects model. Heterogeneity of studies were assessed using Cochrane Q test and I2 test, while publication bias was evaluated using Egger's test.

    RESULTS: Of the 1,645 articles identified through our searches, 46 cross-sectional studies matched our inclusion criteria, reported data from 29,968 school children of Africa. The pooled prevalence of intestinal protozoan parasites amongst African school children was 25.8% (95% CI: 21.2%-30.3%) with E. histolytica/ dispar (13.3%; 95% CI: 10.9%-15.9%) and Giardia spp. (12%; 95% CI: 9.8%-14.3%) were the most predominant pathogenic parasites amongst the study participants. While E. coli was the most common non-pathogenic protozoa (17.1%; 95% CI: 10.9%-23.2%).

    CONCLUSIONS: This study revealed a relatively high prevalence of IPPs in school children, especially in northern and western Africa. Thus, poverty reduction, improvement of sanitation and hygiene and attention to preventive control measures will be the key to reducing protozoan parasite transmission.

  20. Andrew A, Navien TN, Yeoh TS, Citartan M, Mangantig E, Sum MSH, et al.
    PLoS Negl Trop Dis, 2022 Feb;16(2):e0010152.
    PMID: 35120141 DOI: 10.1371/journal.pntd.0010152
    BACKGROUND: Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV.

    METHODOLOGY AND PRINCIPAL FINDINGS: A literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1st December 2020 until 22nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses. Thirty-five studies were included in this meta-analysis; 72 index test data were extracted and analysed. Rapid and ELISA-based antigen tests had a pooled sensitivity of 85.8% and 82.2%, respectively, and a pooled specificity of 96.1% and 96.0%, respectively. According to our meta-analysis, antigen detection tests serve as a good diagnostic test for acute-phase samples. The IgM detection tests had more than 90% diagnostic accuracy for ELISA-based tests, immunofluorescence assays, in-house developed tests, and samples collected after seven days of symptom onset. Conversely, low sensitivity was found for the IgM rapid test (42.3%), commercial test (78.6%), and for samples collected less than seven of symptom onset (26.2%). Although IgM antibodies start to develop on day 2 of CHIKV infection, our meta-analysis revealed that the IgM detection test is not recommended for acute-phase samples. The diagnostic performance of the IgG detection tests was more than 93% regardless of the test formats and whether the test was commercially available or developed in-house. The use of samples collected after seven days of symptom onset for the IgG detection test suggests that IgG antibodies can be detected in the convalescent-phase samples. Additionally, we evaluated commercial IgM and IgG tests for CHIKV and found that ELISA-based and IFA commercial tests manufactured by Euroimmun (Lübeck, Germany), Abcam (Cambridge, UK), and Inbios (Seattle, WA) had diagnostic accuracy of above 90%, which was similar to the manufacturers' claim.

    CONCLUSION: Based on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections.

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