The ongoing value of first few X studies for COVID-19 in the Western Pacific Region

First few ‘X’ (FFX) studies for COVID-19 involve data collection from confirmed cases and their close contacts. They remain relevant especially as many remain susceptible to infection, and as they can provide detailed insight into vaccine effectiveness and the epidemiology of variants of concern, helping to inform a proportionate health response

Multidrug resistance plasmids underlie clonal expansions and international spread of Salmonella enterica serotype 1,4,[5],12:i:- ST34 in Southeast Asia

Salmonella enterica serotype 1,4,[5],12:i:- (Typhimurium monophasic variant) of sequence type (ST) 34 has emerged as the predominant pandemic genotype in recent decades. Despite increasing reports of resistance to antimicrobials in Southeast Asia, Salmonella ST34 population structure and evolution remained understudied in the region. Here we performed detailed genomic investigations on 454 ST34 genomes collected from Vietnam and diverse geographical sources to elucidate the pathogen’s epidemiology, evolution and antimicrobial resistance. We showed that ST34 has been introduced into Vietnam in at least nine occasions since 2000, forming five co-circulating major clones responsible for paediatric diarrhoea and bloodstream infection. Most expansion events were associated with acquisitions of large multidrug resistance plasmids of IncHI2 or IncA/C2. Particularly, the self-conjugative IncA/C2 pST34VN2 (co-transferring blaCTX-M-55, mcr-3.1, and qnrS1) underlies local expansion and intercontinental spread in two separate ST34 clones. At the global scale, Southeast Asia was identified as a potential hub for the emergence and dissemination of multidrug resistant Salmonella ST34, and mutation analysis suggests of selection in antimicrobial responses and key virulence factors

Sustaining effective COVID-19 control in Malaysia through large-scale vaccination

Introduction: As of 3rd June 2021, Malaysia is experiencing a resurgence of COVID-19 cases. In response, the federal government has implemented various non-pharmaceutical interventions (NPIs) under a series of Movement Control Orders and, more recently, a vaccination campaign to regain epidemic control. In this study, we assessed the potential for the vaccination campaign to control the epidemic in Malaysia and four high-burden regions of interest, under various public health response scenarios. Methods: A modified susceptible-exposed-infectious-recovered compartmental model was developed that included two sequential incubation and infectious periods, with stratification by clinical state. The model was further stratified by age and incorporated population mobility to capture NPIs and micro-distancing (behaviour changes not captured through population mobility). Emerging variants of concern (VoC) were included as an additional strain competing with the existing wild-type strain. Several scenarios that included different vaccination strategies (i.e. vaccines that reduce disease severity and/or prevent infection, vaccination coverage) and mobility restrictions were implemented. Results: The national model and the regional models all fit well to notification data but underestimated ICU occupancy and deaths in recent weeks, which may be attributable to increased severity of VoC or saturation of case detection. However, the true case detection proportion showed wide credible intervals, highlighting incomplete understanding of the true epidemic size. The scenario projections suggested that under current vaccination rates complete relaxation of all NPIs would trigger a major epidemic. The results emphasise the importance of micro-distancing, maintaining mobility restrictions during vaccination roll-out and accelerating the pace of vaccination for future control. Malaysia is particularly susceptible to a major COVID-19 resurgence resulting from its limited population immunity due to the country's historical success in maintaining control throughout much of 2020

Understanding COVID-19 Dynamics and the Effects of Interventions in the Philippines: A Mathematical Modelling Study

Background COVID-19 initially caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with many high-income countries; possibly because of differing demographics; socioeconomics; surveillance; and policy responses. Here; we investigate the role of multiple factors on COVID-19 dynamics in the Philippines; a LMIC that has had a relatively severe COVID-19 outbreak. Methods We applied an age-structured compartmental model that incorporated time-varying mobility; testing; and personal protective behaviors (through a “Minimum Health Standards” policy; MHS) to represent the first wave of the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon; Central Visayas; and the National Capital Region). We estimated effects of control measures; key epidemiological parameters; and interventions. Findings Population age structure; contact rates; mobility; testing; and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases; hospitalisations; and deaths. The model indicated that MHS reduced the probability of transmission per contact by 13-27%. The February 2021 case detection rate was estimated at ~8%; population recovered at ~9%; and scenario projections indicated high sensitivity to MHS adherence. Interpretation COVID-19 dynamics in the Philippines are driven by age; contact structure; mobility; and MHS adherence. Continued compliance with low-cost MHS should help the Philippines control the epidemic until vaccines are widely distributed; but disease resurgence may be occurring due to a combination of low population immunity and detection rates and new variants of concern

COVID-19 collaborative modelling for policy response in the Philippines, Malaysia and Vietnam

Mathematical models that capture COVID-19 dynamics have supported public health responses and policy development since the beginning of the pandemic, yet there is limited discourse to describe features of an optimal modelling platform to support policy decisions or how modellers and policy makers have engaged with each other. Here, we outline how we used a modelling software platform to support public health decision making for the COVID-19 response in the Western Pacific Region (WPR) countries of the Philippines, Malaysia and Viet Nam. This perspective describes an approach to support evidence-based public health decisions and policy, which may help inform other responses to similar outbreak events. The platform we describe formed the basis for one of the inaugural World Health Organization (WHO) Western Pacific (WPRO) Innovation Challenge awards, and was backed by collaboration between epidemiological modellers, those providing public health advice, and policy makers

Multidrug resistance plasmids underlie clonal expansions and international spread of Salmonella enterica serotype 1,4,[5],12:i:- ST34 in Southeast Asia

Salmonella enterica serotype 1,4,[5],12:i:- (Typhimurium monophasic variant) of sequence type (ST) 34 has emerged as the predominant pandemic genotype in recent decades. Despite increasing reports of resistance to antimicrobials in Southeast Asia, Salmonella ST34 population structure and evolution remained understudied in the region. Here we performed detailed genomic investigations on 454 ST34 genomes collected from Vietnam and diverse geographical sources to elucidate the pathogen’s epidemiology, evolution and antimicrobial resistance. We showed that ST34 has been introduced into Vietnam in at least nine occasions since 2000, forming five co-circulating major clones responsible for paediatric diarrhoea and bloodstream infection. Most expansion events were associated with acquisitions of large multidrug resistance plasmids of IncHI2 or IncA/C2. Particularly, the self-conjugative IncA/C2 pST34VN2 (co-transferring bla CTX-M-55, mcr-3.1, and qnrS1) underlies local expansion and intercontinental spread in two separate ST34 clones. At the global scale, Southeast Asia was identified as a potential hub for the emergence and dissemination of multidrug resistant Salmonella ST34, and mutation analysis suggests of selection in antimicrobial responses and key virulence factors

The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam : a study protocol for an open single-arm interventional trial [awaiting peer review]

Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018

Evaluating and informing programs fro the control of HIV and hepatitis C infection among female sex workers in Viet Nam

In the early 2000s, HIV surveillance in Viet Nam indicated that female sex workers (FSW) were among key populations with highest HIV infection rates. However, data on risk factors for HIV infection to inform prevention programs were limited. Data on HCV prevalence among FSW were scarce but suggested elevated burden in some regions of the country. Between 2004 and 2010, efforts were intensified nationwide to control HIV infection among FSW, and a series of cross-section surveys were conducted; in 2015 a national response was initiated to address high hepatitis C virus (HCV) burden. This thesis aimed to evaluate and inform HIV and HCV prevention among FSW in Viet Nam using empirical data from surveys and integrated analysis with program data. In Chapters 3 and 4, we report high HIV and HCV prevalence and up to 14% active HIV and HCV co-infection in urban settings. Strong associations between injection and non-injection drug use with both infections support the need for a comprehensive HIV and HCV prevention package addressing substance use risks among FSW. Inconsistent condom use was identified as an additional risk factor for HIV in provinces with HIV prevalence ≥10%, but not in provinces with <10% prevalence among street- and venue-based FSW, where only injection drug use was a significant behavioral risk factor. In Chapter 6, we synthesized four surveys conducted across 13 years and programmatic data collected over 23 years in Ho Chi Minh City, where HIV burden is highest. The scale and intensity of program coverage was low by global standards, even during peak funding and intervention coverage, and there was a clear lack of attention to substance use risks. Condom use and HIV testing uptake levels remained low across all years. Only knowledge about HIV transmission risks and perceived risk of infection reflected the scale of these interventions. The key behavioral determinants of consistent condom use were related to substance use, specifically daily alcohol intake and receptive syringe sharing in the last month. These findings indicated an on-going need for comprehensive interventions to address both HIV and HCV risks among FSW, specifically their dual sexual and drug use related risks

Investigating the traditional medicine shoulder pain (Jian Tong) characteristics in patients with ischaemic stroke in the early rehabilitation phase

Introduction: Ischaemic stroke often leaves serious sequelae affecting patients' daily activities and quality of life, especially shoulder pain. Shoulder pain after stroke often occurs in the first 3 months with an occurrence rate of 25–72% due to the strong natural neurological mechanism during the time, interferes with the recovery of motor function, increases hospital stay, is associated with depression, and limits mobility as well as inhibits treatment results. In Vietnam, Traditional Medicine (TM) has played an essential role in treating and rehabilitating shoulder pain after stroke for quite a long time. Studies on the pathology of shoulder pain (Jian Tong) after stroke in TM in Vietnam are still inadequate. Therefore, this study evaluated the severity and characteristics of post-stroke Jian Tong in patients with ischaemic stroke. Methods: The study was conducted from January 1, 2023–May 1, 2023. The study consisted of two phases: Phase 1: Searching TM documents and selecting the characteristics that appear in the documents as components for the questionnaire of phase 2. Phase 2: Conduct a cross-sectional study to investigate the characteristics of Jian Tong in 65 patients after ischaemic stroke in the early rehabilitation phase. Results: In phase 1, the study encoded 17 features of Jian Tong from 10 literary documents. In phase 2, we surveyed over 65 patients, and the result was that shoulder pain aggravated by exertion had the highest rate, whereas shoulder pain alleviated by cold and distended shoulder had the fewest. Pain level measured by Number Rating Scale (NRS) points and gender was significantly related to the characteristics of TM shoulder pain – Jian Tong (p < 0.05). Conclusion: The study demonstrated the pain level and the characteristics of Jian Tong in patients with ischaemic stroke in the early rehabilitation phase to contribute to the process of personalized diagnosing and treating Jian Tong after stroke for each patient, especially based on the theoretical basis and reasoning methods of Traditional Medicine