Displaying publications 1 - 20 of 162 in total

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  1. Cardosa J, Ooi MH, Tio PH, Perera D, Holmes EC, Bibi K, et al.
    PLoS Negl Trop Dis, 2009;3(4):e423.
    PMID: 19399166 DOI: 10.1371/journal.pntd.0000423
    Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.
  2. Sam SS, Omar SF, Teoh BT, Abd-Jamil J, AbuBakar S
    PLoS Negl Trop Dis, 2013;7(5):e2194.
    PMID: 23658849 DOI: 10.1371/journal.pntd.0002194
    Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The disease affects mainly children, but in recent years it is becoming more of an adult disease. Malaysia experienced a large dengue outbreak in 2006 to 2007, involving mostly adults, with a high number of deaths.
  3. Chandren JR, Wong LP, AbuBakar S
    PLoS Negl Trop Dis, 2015;9(8):e0003954.
    PMID: 26267905 DOI: 10.1371/journal.pntd.0003954
    BACKGROUND: Dengue is prevalent among Malaysia's indigenous peoples, known as the Orang Asli, and it poses a serious health threat to them. The study aims to look at the socio-demographic factors, health beliefs, and knowledge about dengue and its association to dengue prevention practices among Orang Asli communities in Peninsular Malaysia.

    METHODS: A cross-sectional survey was conducted in 16 randomly selected Orang Asli villages from eight states in Peninsular Malaysia from April 2012 until February 2013.

    RESULTS: A total of 560 Orang Asli were interviewed and 505 completed the survey. Slightly above half of the participants (n = 280, 55.4%) had a total dengue prevention score of 51-100 (of a possible score of 0-100). Multivariate analysis findings showed dengue knowledge, perceived barriers to perform dengue prevention, fogging frequency, and perceived susceptibility to dengue fever as significant factors associated to dengue prevention practices. Participants with a lower dengue knowledge score (score 0-18) were less likely (OR = 0.63, 95%CI = 0.44-0.92 vs. score 19-36, P = 0.015) to practice dengue prevention. Participants with low perceived barriers to prevent dengue (score of 1-5) were more likely (OR = 2.06, 95%CI = 1.21-3.53, vs. score of 6-10, P = 0.008) to practice dengue prevention. Villages that were not fogged (OR = 0.49, 95%CI = 0.24-0.99, P = 0.045) or rarely fogged (OR = 0.40, 95%CI = 0.22-0.75, P = 0.004) had lower dengue prevention practices than villages that were fogged often. Participants with low perceived susceptibility of acquiring dengue (score of 1-5) were less likely (OR = 0.54, 95%CI = 0.33-0.89 vs. score of 6-10, P = 0.018) to practice dengue prevention measures.

    CONCLUSION: Findings imply that educational and health programmes should focus on enhancing dengue knowledge and perceived susceptibility of acquiring dengue and reducing perceived barriers to performing dengue prevention practices among the Orang Asli. More outreach on mosquito control campaigns should be carried out especially in villages where mosquito fogging is frequent.

  4. Hotez PJ, Bottazzi ME, Strych U, Chang LY, Lim YA, Goodenow MM, et al.
    PLoS Negl Trop Dis, 2015 Apr;9(4):e0003575.
    PMID: 25880767 DOI: 10.1371/journal.pntd.0003575
    The ten member states of the Association of Southeast Asian Nations (ASEAN) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs). Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF). Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection) causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation provides a policy framework for the development of new control and elimination tools. Together with prominent research institutions and universities, the World Health Organization (WHO), and its regional offices, these organizations could implement important public health improvements through NTD control and elimination in the coming decade.
  5. Wong LP, AbuBakar S
    PLoS Negl Trop Dis, 2013;7(7):e2310.
    PMID: 23875045 DOI: 10.1371/journal.pntd.0002310
    BACKGROUND: This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF) amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours.

    METHODS: A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16(th) December, 2011 and 12(th) May, 2012.

    RESULTS: The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i) lack of self-efficacy, ii) lack of perceived benefit, iii) low perceived susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF.

    CONCLUSION: Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments.

  6. 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.
  7. 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.

  8. 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.

  9. Naserrudin NA, Abdul Aziz EI, Aljet E, Mangunji G, Tojo B, Jeffree MS, et al.
    PLoS Negl Trop Dis, 2021 06;15(6):e0009450.
    PMID: 34081725 DOI: 10.1371/journal.pntd.0009450
    An outbreak of Plasmodium malariae occurred in Sonsogon Paliu village in the remote area of Ulu Bengkoka sub-district of Kota Marudu, Northern Sabah, Malaysian Borneo from July through August 2019. This was the first outbreak of malaria in this village since 2014. On 11th July 2019 the Kota Kinabalu Public Health Laboratory notified the Kota Marudu District Health Office of a Polymerase Chain Reaction (PCR) positive case of P. malariae. This index case was a male from Sulawesi, Indonesia working for a logging company operating in Sonsogon Paliu. During the resulting outbreak, a total of 14 symptomatic cases were detected. All of these cases were positive by thick and thin blood smear examination, and also by PCR. During the outbreak, a mass blood survey screening was performed by light-microscopy and PCR. A total of 94 asymptomatic villagers 31 (33.0%) were PCR positive but thick and thin blood smear negative for P. malariae. Both symptomatic and asymptomatic cases received treatment at the district hospital. When symptomatic and asymptomatic cases were considered together, males (29/45. 64.5%) were infected more than females (16/45, 35.6%), the male:female ratio being 1.8:1. Adults were the predominant age group infected (22/45, 48.9%) followed by adolescents (19/45, 42.2%) and children under five years of age (4/45, 8.9%). This report illustrates that symptomatic and submicroscopic cases pose a challenge during P. malariae outbreaks and that PCR is a valuable tool for their identification. The rapid identification and control of imported malaria is crucial for the continued control of malaria in Malaysia.
  10. Silver ZA, Kaliappan SP, Samuel P, Venugopal S, Kang G, Sarkar R, et al.
    PLoS Negl Trop Dis, 2018 01;12(1):e0006153.
    PMID: 29346440 DOI: 10.1371/journal.pntd.0006153
    BACKGROUND: Soil-transmitted helminth (STH) infections are among the most prevalent neglected tropical diseases (NTD) worldwide. Since the publication of the WHO road map to combat NTD in 2012, there has been a renewed commitment to control STH. In this study, we analysed the geographical distribution and effect of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia and south east Asia.

    METHODOLOGY: We conducted a systematic review of open-access literature published in PubMed Central and the Global Atlas of Helminth Infection. A total of 4182 articles were available and after applying selection criteria, 174 studies from the region were retained for analysis.

    PRINCIPAL FINDINGS: Ascaris was the commonest STH identified with an overall prevalence of 18% (95% CI, 14-23%) followed by Trichuris (14%, 9-19%) and hookworm (12%, 9-15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a geographical overlap in countries with high prevalence rates for Trichuris and Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect of community type was examined, prevalence rates of hookworm was comparable in rural (19%, 14-24%) and tribal communities (14%, 10-19%). Tribal communities, however, showed higher prevalence of Trichuris (38%, 18-63%) and Ascaris (32%, 23-43%) than rural communities (13%, 9-20% and 14%, 9-20% respectively). Considerable between and within country heterogeneity in the distribution of STH (I2 >90%) was also noted. When available data from school aged children (SAC) were analysed, prevalence of Ascaris (25% 16-31%) and Trichuris (22%, 14-34%) were higher than among the general population while that of hookworm (10%, 7-16%) was comparable.

    CONCLUSIONS/SIGNIFICANCE: Our analysis showed significant variation in prevalence rates between and within countries in the region. Highlighting the importance of community type in prevalence and species mix, we showed that tribal and rural communities had higher hookworm infections than urban communities and for ascariasis and trichuriasis, tribal populations had higher levels of infection than rural populations. We also found a higher prevalence of ascariasis and trichuriasis in SAC compared to the general population but comparable levels of hookworm infections. These key findings need to be taken into account in planning future MDA and other interventions.

  11. Chong NS, Smith SR, Werkman M, Anderson RM
    PLoS Negl Trop Dis, 2021 08;15(8):e0009625.
    PMID: 34339450 DOI: 10.1371/journal.pntd.0009625
    The World Health Organization has recommended the application of mass drug administration (MDA) in treating high prevalence neglected tropical diseases such as soil-transmitted helminths (STHs), schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. MDA-which is safe, effective and inexpensive-has been widely applied to eliminate or interrupt the transmission of STHs in particular and has been offered to people in endemic regions without requiring individual diagnosis. We propose two mathematical models to investigate the impact of MDA on the mean number of worms in both treated and untreated human subpopulations. By varying the efficay of drugs, initial conditions of the models, coverage and frequency of MDA (both annual and biannual), we examine the dynamic behaviour of both models and the possibility of interruption of transmission. Both models predict that the interruption of transmission is possible if the drug efficacy is sufficiently high, but STH infection remains endemic if the drug efficacy is sufficiently low. In between these two critical values, the two models produce different predictions. By applying an additional round of biannual and annual MDA, we find that interruption of transmission is likely to happen in both cases with lower drug efficacy. In order to interrupt the transmission of STH or eliminate the infection efficiently and effectively, it is crucial to identify the appropriate efficacy of drug, coverage, frequency, timing and number of rounds of MDA.
  12. Azlan A, Obeidat SM, Theva Das K, Yunus MA, Azzam G
    PLoS Negl Trop Dis, 2021 01;15(1):e0008351.
    PMID: 33481791 DOI: 10.1371/journal.pntd.0008351
    The Asian tiger mosquito, Aedes albopictus (Ae. albopictus), is an important vector that transmits arboviruses such as dengue (DENV), Zika (ZIKV) and Chikungunya virus (CHIKV). Long noncoding RNAs (lncRNAs) are known to regulate various biological processes. Knowledge on Ae. albopictus lncRNAs and their functional role in virus-host interactions are still limited. Here, we identified and characterized the lncRNAs in the genome of an arbovirus vector, Ae. albopictus, and evaluated their potential involvement in DENV and ZIKV infection. We used 148 public datasets, and identified a total of 10, 867 novel lncRNA transcripts, of which 5,809, 4,139, and 919 were intergenic, intronic and antisense respectively. The Ae. albopictus lncRNAs shared many characteristics with other species such as short length, low GC content, and low sequence conservation. RNA-sequencing of Ae. albopictus cells infected with DENV and ZIKV showed that the expression of lncRNAs was altered upon virus infection. Target prediction analysis revealed that Ae. albopictus lncRNAs may regulate the expression of genes involved in immunity and other metabolic and cellular processes. To verify the role of lncRNAs in virus infection, we generated mutations in lncRNA loci using CRISPR-Cas9, and discovered that two lncRNA loci mutations, namely XLOC_029733 (novel lncRNA transcript id: lncRNA_27639.2) and LOC115270134 (known lncRNA transcript id: XR_003899061.1) resulted in enhancement of DENV and ZIKV replication. The results presented here provide an important foundation for future studies of lncRNAs and their relationship with virus infection in Ae. albopictus.
  13. William T, Rahman HA, Jelip J, Ibrahim MY, Menon J, Grigg MJ, et al.
    PLoS Negl Trop Dis, 2013;7(1):e2026.
    PMID: 23359830 DOI: 10.1371/journal.pntd.0002026
    BACKGROUND: The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time.

    METHODS: Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992-2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity.

    RESULTS: From 1992-2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈ 100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly.

    CONCLUSIONS: A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence.

  14. Maynard AJ, Ambrose L, Cooper RD, Chow WK, Davis JB, Muzari MO, et al.
    PLoS Negl Trop Dis, 2017 04;11(4):e0005546.
    PMID: 28410388 DOI: 10.1371/journal.pntd.0005546
    BACKGROUND: Within the last century, increases in human movement and globalization of trade have facilitated the establishment of several highly invasive mosquito species in new geographic locations with concurrent major environmental, economic and health consequences. The Asian tiger mosquito, Aedes albopictus, is an extremely invasive and aggressive daytime-biting mosquito that is a major public health threat throughout its expanding range.

    METHODOLOGY/PRINCIPAL FINDINGS: We used 13 nuclear microsatellite loci (on 911 individuals) and mitochondrial COI sequences to gain a better understanding of the historical and contemporary movements of Ae. albopictus in the Indo-Pacific region and to characterize its population structure. Approximate Bayesian computation (ABC) was employed to test competing historical routes of invasion of Ae. albopictus within the Southeast (SE) Asian/Australasian region. Our ABC results show that Ae. albopictus was most likely introduced to New Guinea via mainland Southeast Asia, before colonizing the Solomon Islands via either Papua New Guinea or SE Asia. The analysis also supported that the recent incursion into northern Australia's Torres Strait Islands was seeded chiefly from Indonesia. For the first time documented in this invasive species, we provide evidence of a recently colonized population (the Torres Strait Islands) that has undergone rapid temporal changes in its genetic makeup, which could be the result of genetic drift or represent a secondary invasion from an unknown source.

    CONCLUSIONS/SIGNIFICANCE: There appears to be high spatial genetic structure and high gene flow between some geographically distant populations. The species' genetic structure in the region tends to favour a dispersal pattern driven mostly by human movements. Importantly, this study provides a more widespread sampling distribution of the species' native range, revealing more spatial population structure than previously shown. Additionally, we present the most probable invasion history of this species in the Australasian region using ABC analysis.

  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. Nealon J, Taurel AF, Capeding MR, Tran NH, Hadinegoro SR, Chotpitayasunondh T, et al.
    PLoS Negl Trop Dis, 2016 Aug;10(8):e0004918.
    PMID: 27532617 DOI: 10.1371/journal.pntd.0004918
    Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.
  17. McDonald EM, Duggal NK, Brault AC
    PLoS Negl Trop Dis, 2017 Oct;11(10):e0005990.
    PMID: 28985234 DOI: 10.1371/journal.pntd.0005990
    The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon α/β and -γ receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60-72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV.
  18. Tappe D, Büttner DW
    PLoS Negl Trop Dis, 2009;3(2):e320.
    PMID: 19238218 DOI: 10.1371/journal.pntd.0000320
    Visceral pentastomiasis in humans is caused by the larval stages (nymphs) of the arthropod-related tongue worms Linguatula serrata, Armillifer armillatus, A. moniliformis, A. grandis, and Porocephalus crotali. The majority of cases has been reported from Africa, Malaysia, and the Middle East, where visceral pentastomiasis may be an incidental finding in autopsies, and less often from China and Latin America. In Europe and North America, the disease is only rarely encountered in immigrants and long-term travelers, and the parasitic lesions may be confused with malignancies, leading to a delay in the correct diagnosis. Since clinical symptoms are variable and serological tests are not readily available, the diagnosis often relies on histopathological examinations. This laboratory symposium focuses on the diagnosis of this unusual parasitic disease and presents its risk factors and epidemiology.
  19. Chaisakul J, Alsolaiss J, Charoenpitakchai M, Wiwatwarayos K, Sookprasert N, Harrison RA, et al.
    PLoS Negl Trop Dis, 2019 10;13(10):e0007338.
    PMID: 31644526 DOI: 10.1371/journal.pntd.0007338
    BACKGROUND: Daboia siamensis (Eastern Russell's viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell's viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand against D. siamensis venoms from four geographical locales: Myanmar, Taiwan, China and Thailand.

    METHODOLOGY/PRINCIPLE FINDINGS: The D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.

    CONCLUSIONS/SIGNIFICANCE: This study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell's viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.

  20. NikNadia N, Sam IC, Rampal S, WanNorAmalina W, NurAtifah G, Verasahib K, et al.
    PLoS Negl Trop Dis, 2016 Mar;10(3):e0004562.
    PMID: 27010319 DOI: 10.1371/journal.pntd.0004562
    Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2-3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance). A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24-1.69; P<0.001). Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01-1.34 P<0.034). In summary, the 2-3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs.
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