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Abstract Cases of H5 highly pathogenic avian influenzas (HPAI) are on the rise. Although mammalian spillover events are rare, H5N1 viruses have an estimated mortality rate in humans of 60%. No human cases of H5 infection have been reported in Malaysian Borneo, but HPAI has circulated in poultry and migratory avian species transiting through the region. Recent deforestation in coastal habitats in Malaysian Borneo may increase the proximity between humans and migratory birds. We hypothesise that higher rates of human-animal contact, caused by this habitat destruction, will increase the likelihood of potential zoonotic spillover events. In 2015, an environmentally stratified cross-sectional survey was conducted collecting geolocated questionnaire data in 10,100 individuals. A serological survey of these individuals reveals evidence of H5 neutralisation that persisted following depletion of seasonal H1/H3 HA binding antibodies from the plasma. The presence of these antibodies suggests that some individuals living near migratory sites may have been exposed to H5 HA. There is a spatial and environmental overlap between individuals displaying high H5 HA binding and the distribution of migratory birds. We have developed a novel surveillance approach including both spatial and serological data to detect potential spillover events, highlighting the urgent need to study cross-species pathogen transmission in migratory zones.

Objective: The objective of this study was to investigate the prevalence and seasonal distribution of rotavirus and enteric adenovirus in patients with acute gastroenteritis. Methods: The results of 2960 patients admitted to Ankara Training and Research Hospital with gastroenteritis between March 2018 and August 2019 were investigated retrospectively. A chromatographic immunoassay (Rotavirus and Adenovirus Combo Rapid Test, General Diagnostica Inc., Rancho Cucamonga, CA, USA), detecting both viruses simultaneously, was used according to the manufacturer’s instructions. Results: Of the 2960 patients, 1286 (43.4%) were female, 1674 (56.6%) were male, and 2873 (97.7%) and 87 (2.3%) were under 18 years old and 18 years and older, respectively. The number of Turkish and refugee patients was 2590 (87.5%) and 370 (12.5%), respectively. Viral antigens of 281/2960 (9.5%) were positive for rotavirus, and 54/2960 (1.8%) were positive for adenovirus. Of the Turkish patients, 243/2590 (9.4%) were rotavirus positive, and 51/2590 (1.9%) were adenovirus positive. Among the refugee patients, 38/370 (10.3%) were rotavirus positive, and 3/370 (0.8%) were adenovirus positive. The highest prevalence of rotavirus and adenovirus, according to age groups, was determined at 12-36 months of age (25.3%) and 49-59 months of age (3.2%), respectively. The highest prevalence of rotavirus and adenovirus positivity was in spring (17.8%) and in autumn (2.9%), respectively. Conclusion: Rotavirus is the most common cause of gastroenteritis during infancy and childhood. Additionally, enteric adenovirus is an important cause of gastroenteritis during this period. Since these viral infections may have serious complications, rapid diagnosis is important, and detection of both viruses among various populations may be useful for epidemiological purposes.

Abstract Background Zoonotic malaria is a growing public health threat in the WHO Southeast Asia (SEA) and Western Pacific (WP) regions. Despite vector-control measures, the distribution of Macaque fascicularis and M. nemestrina, and Anopheles mosquitoes carrying non-human simian malaria parasites poses challenges to malaria elimination. The systematic review assesses the literature on knowledge and malaria-preventive practices in zoonotic malaria-affected areas across the WHO SEA and WP, aiming to identify challenges for malaria control. Methods Peer-reviewed articles published in English, Malay and Indonesian between January 2010 and December 2022 were searched in OVID Medline, Scopus, Web of Science, and Google Scholar. Studies of any design—excluding reviews, conference proceedings, and reports from all WHO SEA and WP countries vulnerable to zoonotic malaria—were included. Backwards-reference screening and thematic analysis were conducted. Results Among 4,174 initially searched articles, 22 peer-reviewed articles met the inclusion criteria. An additional seven articles were identified through backwards-reference screening, resulting in a total of 29 articles for this review. Half of these studies were conducted in Cambodia, Myanmar, Malaysia, and Thailand, mainly in forests and remote communities. The review highlighted inconsistencies in the operationalization of knowledge, and five major themes were identified related to knowledge: causation and transmission, symptoms, treatment, severity and complications, and malaria prevention. While participants generally had some understanding of malaria causation/transmission, minority and indigenous ethnic groups demonstrated limited knowledge and held misconceptions, such as attributing malaria to drinking dirty water. Preventive practices included traditional and non-traditional or modern methods—with a preference for traditional approaches to avoid mosquito bites. Challenges to malaria control included feasibility, cost, and access to healthcare services. Conclusion This review provides insights into knowledge, local understandings, and preventive practices related to malaria in the WHO SEA and WP regions. The findings highlight the need for future research to explore the knowledge of at-risk communities regarding zoonotic malaria, their perceive threat of the disease and factors exposing them to zoonotic malaria. New strategies must be developed for zoonotic malaria programs tailored to local contexts, emphasizing the significance of community participation, health education, and socio-behavioural change initiatives. It is important to consider the interconnectedness of human health, environmental and non-human primates conservation. Socio-cultural nuances should also be carefully considered in the design and implementation of these programs to ensure their effect tailored to local contexts.

Spinal tuberculosis, also referred to as Pott's disease, presents a significant risk of severe paralysis if not promptly detected and treated, owing to complications such as spinal cord compression and deformity. This article presents the genetic analysis of a Mycobacterium tuberculosis STB-T1A strain, isolated from the spine of a 29-year-old female diagnosed with spinal tuberculosis. Genomic DNA was extracted from pure culture and subjected to sequencing using the Illumina NovaSeq 6000 sequencing system. The genome of the M. tuberculosis STB-T1A strain spans 4,367,616 base pairs with a G+C content of 65.56 % and 4174 protein-coding genes. Comparative genomic analysis, conducted via single nucleotide polymorphism (SNP)-based phylogenetic analysis using the Maximum Likelihood method, revealed that the strain falls within the Indo-Oceanic lineage (Lineage 1). It clusters with the M. tuberculosis 43-16836 strain, which was isolated from the cerebrospinal fluid of a patient with tuberculous meningitis in Thailand. The complete genome sequence has been deposited at the National Center for Biotechnology Information (NCBI) GenBank database with the accession number JBBMVZ000000000.

Introduction Vector borne diseases (VBDs) present significant public health challenges in Southeast Asia (SEA), and the increasing number of cases threatens vulnerable communities. Inadequate vector control and management have been linked to the spread of VBDs. To address these issues, community participation has been proposed as a promising approach to enhance health programmes and control of VBDs. This article outlines a protocol for a scoping review of the published literature on community-participation approaches to control VBDs in the SEA region. The primary research question is ‘How does community participation complement the control of VBDs in SEA?’ This review aims to provide an overview of various approaches and identify barriers and facilitators to effective implementation.Methods and analysis The research questions will guide the scoping review. In stage 1, peer-reviewed publications from PubMed, Web of Science and Scopus will be searched using predefined search terms related to community-based approaches and VBDs in the SEA region, English, Indonesian and Malay published between 2012 and 2022. In stage 2, the references from relevant articles will be screened for eligibility. In stage 3, eligible articles will be charted in Microsoft Excel to facilitate the review process, and studies will be characterised based on the investigated diseases; this review will also highlight the methodological context of these studies. In stage 4, a thematic analysis will be conducted to derive meaningful findings from the dataset relevant to the research inquiry, followed by writing the results in stage 5. This scoping review aims to be the first to explore community participation in VBD control in the SEA population, providing valuable insights for future research and stakeholders involved in disease control.Ethics and dissemination This scoping review does not require ethical approval because the methodology synthesises information from available articles. This review is planned for dissemination in academic journals, conference presentations and shared with stakeholders as part of knowledge sharing among those involved in VBD control.

Abstract Among zoonotic infections, leptospirosis has a worldwide distribution and high prevalence in tropical regions. It has a broad clinical presentation from mild to severe, life-threatening infection. Leptospires, the etiological agent of leptospirosis, are found in varied ecological niches and animal species, providing a significant source of human infection. This review aims to provide the current status of leptospirosis in Malaysia and the direction for future studies. The literature search for this review was performed using PubMed, Web of Sciences, and Google Scholar databases. The incidence of leptospirosis in Malaysia from 2004 to 2020 varied; however, a large number of cases occurred during floods. Leptospira has been isolated from wild and domestic animals as well as from the environment; among them, several novel species have been identified. In Malaysia, leptospirosis infection and death were mostly associated with recreational and non-recreational water activities. Despite the endemicity of leptospirosis, the public’s knowledge, attitude, and practice level are relatively low in this country. More studies are needed in Malaysia to explore the extent of leptospirosis in different settings and locations.

Abstract Background The increasing incidence of Plasmodium knowlesi malaria poses a significant challenge to efforts to eliminate malaria from Malaysia. Macaque reservoirs, outdoors-biting mosquitoes, human activities, and agricultural work are key factors associated with the transmission of this zoonotic pathogen. However, gaps in knowledge regarding reasons that drive malaria persistence in rural Kudat, Sabah, Northern Borneo remain. This study was conducted to address this knowledge gap, to better understand the complexities of these entangled problems, and to initiate discussion regarding new countermeasures to address them. This study aims to highlight rural community members’ perspectives regarding inequities to health relating to P. knowlesi malaria exposure. Methods From January to October 2022, a study using qualitative methods was conducted in four rural villages in Kudat district of Sabah, Malaysia. A total of nine in-depth interviews were conducted with community and faith leaders, after the completion of twelve focus group discussions with 26 photovoice participants. The interviews were conducted using the Sabah Malay dialect, audio-recorded, transcribed, and translated into English. The research team led the discussion and analysis, which was approved by participants through member checking at the community level. Results Participants identified disparity in health as a key issue affecting their health and livelihoods. Injustice in the social environment was also identified as a significant challenge, including the importance of listening to the voices of affected communities in disentangling the social and economic phenomena that can impact malaria control. Specific concerns included inadequate access to health-related resources and degradation of the environment. Participants recommended improving access to water and other necessities, increasing the availability of malaria control commodities in healthcare facilities, and developing sustainable programs to reduce socioeconomic disparities. Conclusion Inequities to health emerged as a key concern for malaria control in rural Kudat, Sabah. A locally targeted malaria programme cantered on improving the social and economic disparities associated with health outcomes, could be a potential strategy for malaria prevention in such areas. Community-level perspectives gathered from this study can be used as a foundation for future discussions and dialogues among policymakers and community members for achieving greater transparency, improving social equity, and interoperability in addressing P. knowlesi malaria control.

Abstract Background Since 2018, no indigenous human malaria cases has been reported in Malaysia. However, during the recent COVID-19 pandemic the World Health Organization is concerned that the pandemic might erode the success of malaria control as there are reports of increase malaria cases in resource limited countries. Little is known how the COVID-19 pandemic has impacted malaria in middle-income countries like Malaysia. Here the public health response to a Plasmodium malariae outbreak occurred in a village in Sabah state, Malaysia, during a COVID-19 movement control order is reported. Methods An outbreak was declared following the detection of P. malariae in July 2020 and active case detection for malaria was performed by collecting blood samples from residents residing within 2 km radius of Moyog village. Vector prevalence and the efficacy of residual insecticides were determined. Health awareness programmes were implemented to prevent future outbreaks. A survey was conducted among villagers to understand risk behaviour and beliefs concerning malaria. Results A total of 5254 blood samples collected from 19 villages. Among them, 19 P. malariae cases were identified, including the index case, which originated from a man who returned from Indonesia. His return from Indonesia and healthcare facilities visit coincided with the movement control order during COVID-19 pandemic when the healthcare facilities stretched its capacity and only serious cases were given priority. Despite the index case being a returnee from a malaria endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. All cases were symptomatic and uncomplicated except for a pregnant woman with severe malaria. There were no deaths; all patients recovered following treatment with artemether-lumefantrine combination therapy. Anopheles balabacensis and Anopheles barbirostris were detected in ponds, puddles and riverbeds. The survey revealed that fishing and hunting during night, and self-treatment for mild symptoms contributed to the outbreak. Despite the index case being a returnee from a malaria-endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. Conclusion The outbreak occurred during a COVID-19 movement control order, which strained healthcare facilities, prioritizing only serious cases. Healthcare workers need to be more aware of the risk of malaria from individuals who return from malaria endemic areas. To achieve malaria elimination and prevention of disease reintroduction, new strategies that include multisectoral agencies and active community participation are essential for a more sustainable malaria control programme.

Abstract Background The control of Plasmodium knowlesi malaria remains challenging due to the presence of macaque monkeys and predominantly outdoor-biting Anopheles mosquitoes around human settlements. This study aims to explore the barriers and facilitators related to prevention of mosquito bites among rural communities living in Sabah, Malaysia using the participatory visual method, photovoice. Methods From January through June 2022, 26 participants were recruited from four villages in Kudat, Sabah, using purposive sampling. Participants were male and female villagers, aged > 18 years old. After photovoice training in the villages, participants documented facilitators of and barriers related to avoiding mosquito bites using their own smartphone cameras, and provided narratives for their photos. Twelve Focus Group Discussions (FGDs) sessions in three rounds were held to share and discuss the photos, and to address challenges to the avoidance of mosquito bites. All discussions were conducted in the Sabah Malay dialect, and were video and audio recorded, transcribed, and analyzed using reflexive thematic analysis. The Ideation Model, a meta-theoretical model of behaviour change, underpinned this study. Results The most common types of barriers identified by participants included (I) intrapersonal factors such as low perceived threat of malaria, (II) livelihood and lifestyle activities consisting of the local economy and socio-cultural activities, and (III) physical and social environment. The facilitators were categorized into (I) intrapersonal reasons, including having the opportunity to stay indoors, especially women who are housewives, (II) social support by the households, neaighbours and healthcare workers, and (III) support from healthcare services and malaria awareness program. Participants emphasized the importance of stakeholder's support in implementing feasible and affordable approaches to P. knowlesi malaria control. Conclusion Results provided insights regarding the challenges to preventing P. knowlesi malaria in rural Kudat, Sabah. The participation of communities in research was valuable in expanding knowledge of local challenges and highlighting possible ways to overcome barriers. These findings may be used to improve strategies for zoonotic malaria control, which is critical for advancing social change and minimizing health disparities in malaria prevention.

Vibrio cholerae remains a notable public health challenge across Malaysia. Although the Malaysian state of Sabah is considered a cholera-affected area, gaps remain in understanding the epidemiological trends and spatial distribution of outbreaks. Therefore, to determine longitudinal and spatial trends in cholera cases data were obtained from the Sabah State Health Department for all notified cases of cholera between 2005-2020. A cholera outbreak is defined as one or more confirmed cases in a single locality with the evidence of local transmission. All records were geolocated to village level. Satellite-derived data and generalised linearized models were used to assess potential risk factors, including population density, elevation, and distance to the sea. Spatiotemporal clustering of reported cholera cases and zones of increased cholera risk were evaluated using the tau statistic (τ) at 550m, 5km and 10km distances. Over a 15-year period between 2005-2020, 2865 cholera cases were recorded in Sabah, with a mean incidence rate of 5.6 cases per 100,000 (95% CI: 3.4-7.9). From 2015-2020, 705 symptomatic cases and 727 asymptomatic cases were reported. Symptomatic cases primarily occurred in local Malaysian populations (62.6%, 441/705) and in children and adolescents under 15-years old (49.4%, 348/705). On average, cases were reported in areas with low population density (19.45 persons/km2), low elevations (19.45m) and near coastal areas. Spatiotemporal clustering of cholera cases was identified up to 3.5km, with increased village-level cholera risk within 500m and 5 days of initial case presentation to a health facility (Risk Ratio = 9.7, 95% CI: 7.5-12.4). Cholera incidence has high spatial and temporal heterogeneity within Sabah, with some districts experiencing repeated outbreaks. Cholera cases clustered across space and time, with village-level risk of cholera highest within 5 days and within close proximity to primary case villages, suggesting local transmission.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasia associated with human T-cell leukemia virus type 1 (HTLV-1) infection and has an extremely poor prognosis. Lenalidomide (LEN; a second-generation immunomodulatory drug [IMiD]) has been employed as an additional therapeutic option for ATL since 2017, but its mechanism of action has not been fully proven, and recent studies reported emerging concerns about the development of second primary malignancies in patients treated with long-term IMiD therapy. Our purpose in this study was to elucidate the IMiD-mediated anti-ATL mechanisms. Thirteen ATL-related cell lines were divided into LEN-sensitive or LEN-resistant groups. CRBN knockdown (KD) led to a loss of LEN efficacy and IKZF2-KD-induced LEN efficacy in resistant cells. DNA microarray analysis demonstrated distinct transcriptional alteration after LEN treatment between LEN-sensitive and LEN-resistant ATL cell lines. Oral treatment of LEN for ATL cell-transplanted severe combined immunodeficiency (SCID) mice also indicated clear suppressive effects on tumor growth. Finally, a novel cereblon modulator (CELMoD), iberdomide (IBE), exhibited a broader and deeper spectrum of growth suppression to ATL cells with efficient IKZF2 degradation, which was not observed in other IMiD treatments. Based on these findings, our study strongly supports the novel therapeutic advantages of IBE against aggressive and relapsed ATL.

Abstract Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate R C , individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (R C 1) was estimated historically for P. falciparum and P. vivax, with declines in R C estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.

Abstract Background Many rural communities in Malaysian Borneo and Southeast Asia are at risk of Plasmodium knowlesi malaria. Multiple factors contribute to infection, however, a deep understanding of illness causation and prevention practices among at-risk communities remains limited. This study aims to document local knowledge on malaria causation and preventive practices of rural communities in Sabah, Malaysia, using photovoice—a participatory research method. Methods From January to June 2022, a photovoice study was conducted with rural communities in Matunggong subdistrict, Malaysia, to explore their experiences with and local knowledge of non-human primate malaria and prevention practices. The study included (1) an introductory phase in which participants were introduced to the photovoice method; (2) a documentation phase in which participants captured and narrated photos from their communities; (3) a discussion phase in which participants discussed photos and relevant topics through a series of three focus group discussions (FGDs) per village; and (4) a dissemination phase where selected photos were shared with key stakeholders through a photo exhibition. A purposively selected sample of 26 participants (adults > 18 years old, male, and female) from four villages participated in all phases of the study. The study activities were conducted in Sabah Malay dialect. Participants and the research team contributed to data review and analyses. Results Rural communities in Sabah, Malaysia possess local knowledge that attributes non-human primate malaria to natural factors related to the presence of mosquitoes that bite humans and which carry “kuman-malaria” or malaria parasite. Participants revealed various preventive practises ranging from traditional practises, including burning dried leaves and using plants that produce foul odours, to non-traditional approaches such as aerosols and mosquito repellents. By engaging with researchers and policymakers, the participants or termed as co-researchers in this study, showcased their ability to learn and appreciate new knowledge and perspectives and valued the opportunity to share their voices with policymakers. The study successfully fostered a balance of power dynamics between the co-researchers, research team members and policymakers. Conclusion There were no misconceptions about malaria causation among study participants. The insights from study participants are relevant because of their living experience with the non-human malaria. It is critical to incorporate rural community perspectives in designing locally effective and feasible malaria interventions in rural Sabah, Malaysia. Future research can consider adapting the photovoice methodology for further research with the community toward building locally tailored-malaria strategies.

Increasing numbers of human zoonotic malaria cases are reported globally. Current malaria control measures cannot eliminate transmission from wildlife reservoirs, leaving many countries with no pathway to malaria elimination certification. New policies are needed to redefine elimination goals and certification.

Abstract Background In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those performing forest-related work. Furthermore, asymptomatic cases of P. knowlesi malaria have been reported including among women and children. Methods Pubmed, Scopus and the Web of Science databases for literature describing asymptomatic P. knowlesi malaria published between 2010 and 2020 were searched. A systematic literature review was conducted to identify studies reporting the prevalence and incidence of laboratory confirmed asymptomatic P. knowlesi cases in humans, their clinical and demographic characteristics, and methods used to diagnose these cases. Results By analysing over 102 papers, thirteen were eligible for this review. Asymptomatic P. knowlesi infections have been detected in 0.03%–4.0% of the population depending on region, and infections have been described in children as young as 2 years old. Various different diagnostic methods were used to detect P. knowlesi cases and there were differing definitions of asymptomatic cases in these studies. The literature indicates that regionally-differing immune-related mechanisms may play a part on the prevalence of asymptomatic P. knowlesi. Conclusion Differing epidemiological characteristics of asymptomatic P. knowlesi malaria in different regions reinforces the need to further investigate disease transmission mechanics. Effective public health responses to changes in P. knowlesi epidemiology require proactive intervention and multisectoral collaboration.

Abstract Background The Indonesian Republic plans to relocate its capital from Jakarta to East Kalimantan, Borneo Island, in the next few years. This relocation may be associated with deforestation, decreased biodiversity, and an increased risk of emerging zoonotic infections, including Plasmodium knowlesi malaria. The Malaysian part of Borneo Island is one of the main hotspots of P. knowlesi malaria. Methods Considering this risk, we evaluated the transmission dynamics of P. knowlesi in the Indonesian Archipelago based on a literature search and extensive review of data from the Indonesian Ministry of Health. Results We report that 545 P. knowlesi cases were documented in Indonesia, mainly in the Aceh and North Sumatra provinces, with 95% of these occurring in the last 4 years. Conclusions The main P. knowlesi vectors are present in the area of the future capital, requiring strengthened surveillance to reduce the risk of emerging cases in a rapidly growing population.

Abstract Plasmodium knowlesi malaria infection in humans has been reported throughout southeast Asia. The communities at risk are those living in areas where Macaque monkeys and Anopheles mosquito are present. Zoonotic malaria control is challenging due to the presence of the reservoir host and the possibility of human-vector-human transmission. Current control measures, including insecticide-treated nets (ITNs) and indoor residual spraying (IRS), are insufficient to address this threat due to gaps in protection associated with outdoor and early evening vector biting and social and economic activities, such as agricultural and forest work. Understanding the challenges faced by affected communities in preventing mosquito bites is important for reducing disease transmission. This opinion paper discusses opportunities to improve P. knowlesi malaria control through understanding the challenges faced by communities at risk and increasing community engagement and ownership of control measures. The paper highlights this issue by describing how the concept of reimagining malaria can be adapted to zoonotic malaria control measures including identifying current gaps in vector control, understanding interactions between environmental, economic, and human behavioral factors, and increasing community participation in and ownership of control measures.

Abstract Background Children are at higher risk of influenza virus infection, and it is difficult to diagnose. They are also responsible for the transmission of influenza because of their longer viral shedding compared to adults. In Malaysia, studies on influenza in children are scarce, and as a result, policy decisions cannot be formulated to control the infection. Hence, the objective of this study is to determine the prevalence and epidemiological characteristics of influenza among children with upper respiratory symptoms in the Sabah state of Malaysia. Methods A cross-sectional study with a simple random sampling was conducted among children with upper respiratory symptoms in Sabah from 1 March 2019 to 29 February 2020. Patients admitted to a pediatric ward of Sabah Women and Children’s Hospital who presented with a fever >38 °C and cough within 48 h of admission were enrolled in this study. A nasopharyngeal swab was taken, and influenza was diagnosed by lateral flow test. Clinical features of influenza-positive children were compared with children whose results were negative. Results A total of 323 nasopharyngeal samples were collected, and 66 (20.4%) of them were positive for influenza. Fifty-six (85%) were infected by influenza A whereas ten (15%) were by influenza B virus. Higher temperature (aOR 2.03, 95% CI 1.296–3.181), less activity (aOR 2.07, 95% CI 1.158–3.693), and seizure (aOR 4.2, 95% CI 1.614–10.978) on admission were significant risk factors associated with influenza in children. Meteorology parameters such as humidity and rainfall amount were statistically significant at 95% CI [1.133 (1.024–1.255)] and 95% CI [0.946 (0.907–0.986)]. Conclusion The prevalence of influenza was high among children with upper respiratory symptoms, and they were infected predominantly with the influenza A virus. Children presented with seizures, less activity, and fever were the significant risk factors for influenza. Influenza vaccination should be prioritized as preventive measures for children.

Abstract Background In October 2016, a mumps outbreak occurred among the students living in the on-campus dormitory of a public university located in Kota Kinabalu, Sabah, Malaysia. This study aimed to investigate the outbreak and identify the genotype of the mumps virus (MuV) strain that was involved in the outbreak. Main body During the outbreak, one 21-year-old and four 20-year-old males staying in the same dormitory building were reported to have developed symptoms of mumps. Of these, two students were available during the investigation for sample collection to detect MuV by reverse transcription polymerase chain reaction (RT-PCR) of the 639-bp fragment encompassing the entire small hydrophobic (SH) gene. Nucleotide sequencing of the amplicon and phylogenetic analysis using the neighbor-joining method was performed to determine the MuV genotype. Of the two buccal swab samples, one was positive for MuV. The MuV strain in this sample belonged to genotype F and it was clustered together with genotype F strains from China with 96.84–99.68% nucleotide identity. Conclusions Genotype F has limited circulation and is endemic in mainland China. Genotype F strains occasionally reported from other countries were epidemiologically linked to China. This study is the first to report a case of genotype F MuV in Malaysia and no epidemiological link could be established with mainland China. The results provide important information that can assist in strategic planning to improve the prevention and control of mumps infection in Malaysia.

Introduction Plasmodium knowlesi malaria is a non-human simian malaria that threatens Southeast Asian rural communities. Studies indicate that non-compliant bednet usage, travelling into the forest and working as farmers and rubber tappers put communities at risk for infection. Despite guidelines, malaria incidence increases yearly and has become a public health concern. In addition to research gaps addressing factors that influence malaria prevention behaviour in these communities, there are no specific guidelines to facilitate strategies against the threat of P. knowlesi malaria.Method To examine potential factors that influence malaria-prevention behaviour in communities exposed to P. knowlesi malaria, 12 malaria experts participated in a modified Delphi study; every participant maintained their anonymity throughout the study. Three Delphi rounds were conducted via different online platforms between 15 November 2021 and 26 February 2022, and consensus was achieved when 70% of the participants agreed on a particular point with a 4–5 median. The results from the open-ended questions were then subjected to thematic analysis, and the dataset generated by this study was analysed using a deductive and inductive approach.Results After a systematic, iterative process, knowledge and belief, social support, cognitive and environmental factors, past experience as a malaria patient, and the affordability and feasibility of a given intervention were critical contributors to malaria-prevention behaviour.Conclusion Future research on P. knowlesi malaria could adapt this study’s findings for a more nuanced understanding of factors that influence malaria-prevention behaviour and improve P. knowlesi malaria programmes based on the expert consensus.

Abstract Hand, foot, and mouth disease (HFMD) is endemic in Malaysia, with the number of cases increasing. Sabah has experienced several HFMD outbreaks, but information on the epidemiology and molecular characteristics of responsible viruses is scarce. In this study, data of 17,574 reports of HFMD cases in Sabah from 2015 to 2019 were extracted from a public health disease surveillance system and analyzed. Twenty-one swab samples from 13 children were collected from Beaufort, Sabah, during an outbreak in August 2018 for detection and serotyping of causative viruses by semi-nested reverse transcription-polymerase chain reaction (snRT-PCR) of the VP4–VP2 region and consensus degenerate hybrid oligonucleotide primer PCR of the VP1 region, respectively. Nucleotide sequencing and phylogenetic analysis were conducted by the neighbor-joining method. The average annual incidence of HFMD was 94.3 per 100,000 people, with the greatest yearly increase between 2017 and 2018. Swabs from six children were tested positive for enterovirus, of which five were positive for CVA16 and one for EV71. All CVA16 strains belonged to sub-genotype B1a, and the EV71 strain belonged to sub-genotype B5. Phylogenetic analyses indicate that enterovirus genotype shift might be responsible for the increasing trend of HFMD in Sabah, however, further study is needed.

Abstract Background Malaysia recorded the highest number of dengue cases between 2014 and 2017. There are 13 states and three federal territories in Malaysia, and each area varies in their prevalence of dengue. Sabah is one of the states situated in Borneo, Malaysia. Although dengue has been increasing for the last several years, no study was being done to understand the burden and serotype distribution of the dengue virus (DENV) in Sabah. Therefore, the present study was carried out to understand the epidemiology of the dengue infection and the factors responsible for severe dengue in Sabah. Methods Data on dengue infection were extracted from the dengue database of the state of Sabah from 2013 through 2018. DENV NS-1-positive serum samples from multiple sites throughout Sabah were sent to the state public health laboratory, Kota Kinabalu Public Health Laboratory, for serotype determination. The analysis of factors associated with severe dengue was determined from the data of 2018 only. Results In 2013, there were 724 dengue cases; however, from 2014, dengue cases increased exponentially and resulted in 3423 cases in 2018. Increasing dengue cases also led to increased dengue mortality. The number of dengue deaths in 2013 was only five which then gradually increased, and in 2018, 29 patients died. This is an increase of 580% from 2013 to 2018. Deaths were considerably more in the districts of the east coast of Sabah compared with districts in the west coast. During the study period, all DENV serotypes could be identified as serotypes circulating in Sabah. In 2018, the predominant serotype was DENV-3. The monthly peak of dengue infection varied in different years. In the logistic regression analysis, it was identified that children were 6.5 times, patients infected with mixed serotype of DENV were 13 times, and cases from the districts of the east coast were 5.2 times more likely to develop severe dengue. Conclusions An increasing trend of dengue infection has been observed in Sabah. The burden of dengue, severe dengue, and mortality was noted especially in the districts of the east coast of Sabah. Severe dengue was most likely developed in children, cases from the east coast, and patients infected with mixed serotype of DENV.

Introduction. Landscape changes disrupt environmental, social and biological systems, altering pathogen spillover and transmission risks. This study aims to quantify the impact of specific land management practices on spillover and transmission rates of zoonotic and vector-borne diseases within Malaysian Borneo. This protocol describes a cohort study with integrated ecological sampling to assess how deforestation and agricultural practices impact pathogen flow from wildlife and vector populations to human infection and detection by health facilities. This will focus on malaria, dengue and emerging arboviruses (Chikungunya and Zika), vector-borne diseases with varying contributions of simian reservoirs within this setting. Methods. A prospective longitudinal observational cohort study will be established in communities residing or working within the vicinity of the Stability of Altered Forest Ecosystems (SAFE) Project, a landscape gradient within Malaysian Borneo encompassing different plantation and forest types. The primary outcome of this study will be transmission intensity of selected zoonotic and vector-borne diseases, as quantified by changes in pathogen-specific antibody levels. Exposure will be measured using paired population-based serological surveys conducted at the beginning and end of the two-year cohort study. Secondary outcomes will include the distribution and infection rates of Aedes and Anopheles mosquito vectors, human risk behaviours and clinical cases reported to health facilities. Longitudinal data on human behaviour, contact with wildlife and GPS tracking of mobility patterns will be collected throughout the study period. This will be integrated with entomological surveillance to monitor densities and pathogen infection rates of Aedes and Anopheles mosquitoes relative to land cover. Within surrounding health clinics, continuous health facility surveillance will be used to monitor reported infections and febrile illnesses. Models will be developed to assess spillover and transmission rates relative to specific land management practices and evaluate abilities of surveillance systems to capture these risks.

The severity of childhood diarrhoea is linked with poor socioeconomic status, unhygienic living environment, and caregiver’s behaviour. This study is to determine the risk factors and economic burden associated with diarrhoea in children under 5 years of age. A case-control study using convenience sampling method with 105 cases and 105 controls was performed in Menggatal health clinic, Kota Kinabalu, Sabah between March-June 2017. Younger caregivers, without formal education, poor knowledge, practice handwashing with water only and stopped breastfeeding were associated with diarrhoea. Household with poor economic status, a family of five and more, crowded, with a pet, unsafe drinking water, no sanitary toilet, unsanitary garbage disposal and consuming street vendor food also associated with diarrhoea. The mean of total direct costs, total indirect costs and total incurred costs were (Ringgit Malaysia) RM 9.70, RM 59.40, and RM 14.30, respectively. As a conclusion, the risk factors for diarrhoea under 5 years of age still presents in Sabah. Environmental factors and hygienic practice are needed to control under 5 diarrhoea.

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.

BackgroundIn the Malaysian state of Sabah, P. knowlesi notifications increased from 2% (59/2,741) of total malaria notifications in 2004 to 98% (2030/2,078) in 2017. There was a gap regarding P. knowlesi acquisition risk factors related to practice specifically in working age group. The main objective of this study was to identify the risk factors for acquiring P. knowlesi infection in Sabah among the working age group.Methods and methodsThis retrospective population-based case-control study was conducted in Ranau district to assess sociodemographic, behavioural and medical history risk factors using a pretested questionnaire. The data were entered and analyzed using IBM SPSS version 23. Bivariate analysis was conducted using binary logistic regression whereas multivariate analysis was conducted using multivariable logistic regression. We set a statistical significance at p-value less than or equal to 0.05.ResultsA total of 266 cases and 532 controls were included in the study. Male gender (AOR = 2.71; 95% CI: 1.63-4.50), spending overnight in forest (AOR = 1.92; 95% CI: 1.20-3.06), not using mosquito repellent (AOR = 2.49; 95% CI: 1.36-4.56) and history of previous malaria infection (AOR = 49.34; 95% CI: 39.09-78.32) were found to be independent predictors of P. knowlesi infection.ConclusionsThis study showed the need to strengthen the strategies in preventing and controlling P. knowlesi infection specifically in changing the practice of spending overnight in forest and increasing the usage of personal mosquito repellent.

Rotavirus infection is a dilemma for developing countries, including Malaysia. Although commercial rotavirus vaccines are available, these are not included in Malaysia's national immunization program. A scarcity of data about rotavirus genotype distribution could be partially to blame for this policy decision, because there are no data for rotavirus genotype distribution in Malaysia over the past 20 years. From January 2018 to March 2019, we conducted a study to elucidate the rotavirus burden and genotype distribution in the Kota Kinabalu and Kunak districts of the state of Sabah. Stool specimens were collected from children under 5 years of age, and rotavirus antigen in these samples was detected using commercially available kit. Electropherotypes were determined by polyacrylamide gel electrophoresis of genomic RNA. G and P genotypes were determined by RT-PCR using type specific primers. The nucleotide sequence of the amplicons was determined by Sanger sequencing and phylogenetic analysis was performed by neighbor-joining method. Rotavirus was identified in 43 (15.1%) children with watery diarrhea. The male:female ratio (1.9:1) of the rotavirus-infected children clearly showed that it affected predominantly boys, and children 12-23 months of age. The genotypes identified were G3P[8] (74% n = 31), followed by G1P[8] (14% n = 6), G12P[6](7% n = 3), G8P[8](3% n = 1), and GxP[8] (3% n = 1). The predominant rotavirus circulating among the children was the equine-like G3P[8] (59.5% n = 25) with a short electropherotype. Eleven electropherotypes were identified among 34 strains, indicating substantial diversity among the circulating strains. The circulating genotypes were also phylogenetically diverse and related to strains from several different countries. The antigenic epitopes present on VP7 and VP4 of Sabahan G3 and equine-like G3 differed considerably from that of the RotaTeq vaccine strain. Our results also indicate that considerable genetic exchange is occurring in Sabahan strains. Sabah is home to a number of different ethnic groups, some of which culturally are in close contact with animals, which might contribute to the evolution of diverse rotavirus strains. Sabah is also a popular tourist destination, and a large number of tourists from different countries possibly contributes to the diversity of circulating rotavirus genotypes. Considering all these factors which are contributing rotavirus genotype diversity, continuous surveillance of rotavirus strains is of utmost importance to monitor the pre- and post-vaccination efficacy of rotavirus vaccines in Sabah.

In 2019, 10 million new cases of tuberculosis have been reported worldwide. Our data reports genetic analyses of a Mycobacterium tuberculosis strain SBH321 isolated from a 31-year-old female with pulmonary tuberculosis. The genomic DNA of the strain was extracted from pure culture and subjected to sequencing using Illumina platform. M. tuberculosis strain SBH321 consists of 4,374,895 bp with G+C content of 65.59%. The comparative analysis by SNP-based phylogenetic analysis using maximum-likelihood method showed that our strain belonging to sublineage of the Ural family of Europe–America–Africa lineage (Lineage 4) and clustered with M. tuberculosis strain OFXR-4 from Taiwan. The whole genome sequence is deposited at DDBJ/ENA/GenBank under the accession WCJH00000000 (SRR10230353).

Empowering marginalised urban islanders with limited heatlh accessibility for controlling pulmonary tuberculosis (PTB) requires a specific training module. Developing a training module for knowledge transfer to empower these marginalised islanders in high PTB occurrence region can be adapted based on IMCI framework. Structuring knowledge and skills for PTB control is based on the National Strategic Plan for Tuberculosis Control 2016-2020 and the Integrated Management of Childhood Illness (IMCI) framework is adapted for developing the training module. A total of five knowledge and skills were structured: 1) PTB disease and diagnosis, 2) PTB treatment, 3) preventive PTB measures, 4) prevention of malnutrion, and 5) psychosocial discrimination. The IMCI framework was adapted in 3 ways: 1) identifying signs and symptoms of PTB, 2) emphasising 5 steps: assess, diagnose, treat, counsel and detect, as the integrated management, and 3) counseling on BCG immunisation, malnutrition, environmental modifications and stigma on PTB.

Objectives: In this study we investigated an outbreak of Vibrio cholera O1 Ogawa serotype, occurred during December 2014 in Kudat district, situated in Sabah state of the Malaysian part of Borneo. Methods: Active case detection and contact tracing were done at respective localities by house to house survey. Passive case detection was done among acute gastroenteritis patients attended at various health facilities. To determine the source, samples from food, water and environment were taken. A case control study was also done to determine the risk factors. Results: A total of 44 symptomatic and 34 asymptomatic cases from 19 localities were investigated. 39 cases were detected through passive case detection. Median age of cases was 23 years. All cases belonged to serogroup O1 and Ogawa serotype. The epidemiological investigation of time, place, and person identified that V. cholerae cross-transmission might have occurred in two fish markets and the fish-loading port. Circumstantial evidences indicated that cholera was possibly transmitted through contaminated sea foods. Conclusions: We concluded that the life-style of Sea Gypsies is a challenge in cholera control; therefore vaccination might be an effective way to mitigate cholera in an outbreak prone area like Kudat. Keywords: Cholera, Kudat, Sabah, Malaysia, Sea Gypsy, Outbreak, Fish

A Mycobacterium tuberculosis strain SBH162 was isolated from a 49-year-old male with pulmonary tuberculosis. GeneXpert MDR/RIF identified the strain as rifampicin-resistant M. tuberculosis. The whole genome sequencing was performed using Illumina HiSeq 4000 system to further investigate and verify the mutation sites of the strain through genetic analyses namely variant calling using bioinformatics tools. The de novo assembly of genome generated 100 contigs with N50 of 156,381bp. The whole genome size was 4,343,911 bp with G + C content of 65.58% and consisted of 4,306 predicted genes. The mutation site, S450L, for rifampicin resistance was detected in the rpoB gene. Based on the phylogenetic analysis using the Maximum Likelihood method, the strain was identified as belonging to the Europe America Africa lineage (Lineage 4). The genome dataset has been deposited at DDBJ/ENA/GenBank under the accession number SMOE00000000. Keywords: M. tuberculosis, Whole genome sequencing, Next generation sequencing, Rifampicin resistant, Sabah, Malaysia

Diarrhea is a major cause of morbidity and mortality among Bhutanese children. The etiology of diarrhea is not well known due to the challenges of conducting routine surveillance with Bhutan's modest research facilities. Establishing an etiology is crucial toward generating evidence that will contribute to policy discussions on a diarrheal disease control program. Our previous study, during 2010-2012, revealed that norovirus (NoV) is an important cause of diarrhea among Bhutanese children, and that GII.21 was the major genotype circulating at that time. In other countries, GII.4 is the major genotype responsible for NoV infections. In this update report, we provide new prevalence data to describe the progression of the transformation and distribution of the NoV genotype among Bhutanese children.From June 2013 through May 2014, diarrheal stool samples were collected at one national referral hospital in Thimphu, two regional referral hospitals in the eastern and central regions, and one general hospital in the western region of Bhutan. NoV was detected by reverse transcription-polymerase chain reaction (RT-PCR), by amplifying the capsid gene. The RT-PCR results were confirmed by nucleotide sequencing of the amplicons.The proportion of NoV-positive stool samples was 23.6% (147/623), of which 76.9% were NoV GII and the remainders were NoV GI. The median age of infected children was 15.5 months, with a fairly balanced female: male ratio. NoV GII was most prevalent in the colder months (late November-mid April) and NoV GI had the highest prevalence in the summer (mid April-late September). Nucleotide sequencing was successful in 99 samples of GII strains. The most common genotypes were GII.3 (42.6%), GII.4 Sydney 2012 (15.8%), and GII.4 unassigned (11.9%). No GII.21 was found in any child in the present study. Phylogenetic analysis showed that GII.3 strains in the present study belonged to an independent cluster in lineage B. These strains shared an ancestor with those from different countries and Bhutanese strains circulating during 2010.NoV remains an important cause of diarrhea among Bhutanese children. Genotype GII.3 from a single ancestor strain has spread, replacing the previously circulating GII.21. Current NoV genotypes are similar to the strains circulating worldwide but are primarily related to those in neighboring countries. NoV GII is prevalent during the cold season, while GI is prevalent during the summer. To develop a NoV infection control policy, further studies are needed.

We identified human bocavirus (HBoV) DNA by PCR in cerebrospinal fluid from adults and children with encephalitis in Sri Lanka. HBoV types 1, 2, and 3 were identified among these cases. Phylogenetic analysis of HBoV1 strain sequences found no subclustering with strains previously identified among encephalitis cases in Bangladesh.

Arctic/Arctic-like rabies virus group 2 spread into Bangladesh ≈32 years ago. Because rabies is endemic to and a major public health problem in this country, we characterized this virus group. Its glycoprotein has 3 potential N-glycosylation sites that affect viral pathogenesis. Diversity of rabies virus might have public health implications in Bangladesh.

Information is scarce about sylvatic rabies virus in Asia and about rabies in palm civets. We report a novel sylvatic rabies virus variant detected in a golden palm civet in Sri Lanka. Evolutionary analysis suggests the virus diverged from canine rabies viruses in Sri Lanka in ≈1933 (range 1886–1963).

We identified a new genotype of bufavirus, BuV3, in fecal samples (0.8%) collected to determine the etiology of diarrhea in children in Bhutan. Norovirus GII.6 was detected in 1 sample; no other viral diarrheal pathogens were detected, suggesting BuV3 as a cause of diarrhea. This study investigates genetic diversity of circulating BuVs.

Although rabies is endemic in Laos, genetic characterization of the viruses in this country is limited. There are growing concerns that development in the region may have increased transport of dog through Laos for regional dog meat consumption, and that this may cause spillover of the viruses from dogs brought here from other countries. This study was therefore undertaken to evaluate the current rabies situation and the genetic characteristics of rabies viruses currently circulating in Laos.We determined the rate of rabies-positive samples by analyzing data from animal samples submitted to the Lao Ministry of Agriculture and Forestry's National Animal Health Centre rabies laboratory from 2004 through 2011. Twenty-three rabies-positive samples were used for viral genetic characterization. Full genome sequencing was performed on two rabies viruses.Rabies-positive samples increased substantially from 40.5% in 2004 to 60.2% in 2009 and continued at this level during the study period. More than 99% of the samples were from dogs, followed by cats and monkeys. Phylogenetic analyses showed that three rabies virus lineages belonging to the Southeast Asian cluster are currently circulating in Laos; these are closely related to viruses from Thailand, Cambodia and Vietnam. Lineages of the circulating Laos rabies viruses diverged from common ancestors as recently as 44.2 years and as much as 55.3 years ago, indicating periodic virus invasions.There is an increasing trend of rabies in Laotian animals. Similar to other rabies-endemic countries, dogs are the main viral reservoir. Three viral lineages closely related to viruses from neighboring countries are currently circulating in Laos. Data provide evidence of periodic historic exchanges of the viruses with neighboring countries, but no recent invasion.

Rabies is endemic in Sri Lanka, but little is known about the temporal and spatial trends of rabies in this country. Knowing these trends may provide insight into past control efforts and serve as the basis for future control measures. In this study, we analyzed distribution of rabies in humans and animals over a period of 12 years in Sri Lanka.Accumulated data from 1999 through 2010 compiled by the Department of Rabies Diagnosis and Research, Medical Research Institute (MRI), Colombo, were used in this study.The yearly mean percentage of rabies-positive sample was 62.4% (47.6-75.9%). Three-fourths of the rabies-positive samples were from the Colombo, Gampaha, and Kalutara districts in Western province, followed by Galle in Southern province. A high percentage of the rabies samples were from dogs (85.2%), followed by cats (7.9%), humans (3.8%), wild animals (2.0%), and livestock (1.1%). Among wild animals, mongooses were the main victims followed by civets. The number of suspect human rabies cases decreased gradually in Sri Lanka, although the number of human samples submitted for laboratory confirmation increased.The number of rabid dogs has remained relatively unchanged, but the number of suspect human rabies is decreasing gradually in Sri Lanka. These findings indicate successful use of postexposure prophylaxis (PEP) by animal bite victims and increased rabies awareness. PEP is free of charge and is supplied through government hospitals by the Ministry of Health, Sri Lanka. Our survey shows that most positive samples were received from Western and Southern provinces, possibly because of the ease of transporting samples to the laboratory. Submissions of wild animal and livestock samples should be increased by creating more awareness among the public. Better rabies surveillance will require introduction of molecular methods for detection and the establishment of more regional rabies diagnostic laboratories.

A prospective study was performed to determine the molecular characteristics of rotaviruses circulating among children aged

We detected rotavirus G5P[6] with a long RNA pattern in a Vietnamese child with diarrhea. Viral outer capsid protein VP7 and VP4 genes suggest that it likely originated from porcine rotavirus either by genetic reassortment or as whole virions. To our knowledge, this is the first report of human rotavirus G5 in Asia.