BackgroundThe Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.MethodsSolidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.InterpretationRemdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).FundingWHO.

BACKGROUND:Asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections are well documented. Healthcare workers (HCW) are at increased risk of infection due to occupational exposure to infected patients. We aim to determine the prevalence of SARS-CoV-2 antibodies among HCW who did not come to medical attention.METHODS:We prospectively recruited 400 HCW from the National Public Health Laboratory and two COVID-19 designated public hospitals in Klang Valley, Malaysia between 13/4/2020 and 12/5/2020. Quota sampling was used to ensure representativeness of HCW involved in direct and indirect patient care. All participants answered a self-administered questionnaire and blood samples were taken to test for SARS-CoV-2 antibodies by surrogate virus neutralization test.FINDINGS:The study population comprised 154 (38.5%) nurses, 103 (25.8%) medical doctors, 47 (11.8%) laboratory technologists and others (23.9%). A majority (68.9%) reported exposure to SARS-CoV-2 in the past month within their respective workplaces. Adherence to personal protection equipment (PPE) guidelines and hand hygiene were good, ranging from 91-100% compliance. None (95% CI: 0, 0.0095) of the participants had SARS-CoV-2 antibodies detected, despite 182 (45.5%) reporting some symptoms one month prior to study recruitment. One hundred and fifteen (29%) of participants claimed to have had contact with known COVID-19 persons outside of their workplace.INTERPRETATION:Zero seroprevalence among HCW suggests a low incidence of undiagnosed COVID-19 infection in our healthcare setting during the first local wave of SARS-CoV-2 infection. The occupational risk of SARS-CoV-2 transmission within healthcare facilities can be prevented by adherence to infection control measures and appropriate use of PPE.

Rapid diagnosis is an important intervention in managing the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak. Real time reverse transcription polymerase chain reaction (RT-qPCR) remains the primary means for diagnosing the new virus strain but it is time consuming and costly. Recombinase polymerase amplification (RPA) is an isothermal amplification assay that does not require a PCR machine. It is an affordable, rapid, and simple assay. In this study, we developed and optimized a sensitive reverse transcription (RT)-RPA assay for the rapid detection of SARS-CoV-2 using SYBR Green I and/or lateral flow (LF) strip. The analytical sensitivity and specificity of the RT-RPA assay were tested by using 10-fold serial diluted synthetic RNA and genomic RNA of similar viruses, respectively. Clinical sensitivity and specificity of the RT-RPA assay were carried out using 78 positive and 35 negative nasopharyngeal samples. The detection limit of both RPA and RT-qPCR assays was 7.659 and 5 copies/μL RNA, respectively with no cross reactivity with other viruses. The clinical sensitivity and specificity of RT-RPA were 98% and 100%, respectively. Our study showed that RT-RPA represents a viable alternative to RT-qPCR for the detection of SARS-CoV-2, especially in areas with limited infrastructure.

Background Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men. Method This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire. Results The median age at enrolment was 40 years old (IQR: 31-50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections. Conclusion Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.

The susceptible-infectious-removed (SIR) model offers the simplest framework to study transmission dynamics of COVID-19, however, it does not factor in its early depleting trend observed during a lockdown. We modified the SIR model to specifically simulate the early depleting transmission dynamics of COVID-19 to better predict its temporal trend in Malaysia. The classical SIR model was fitted to observed total (I total), active (I), and removed (R) cases of COVID-19 before lockdown to estimate the basic reproduction number. Next, the model was modified with a partial time-varying force of infection, given by a proportionally depleting transmission coefficient, β t , and a fractional term, z . The modified SIR model was then fitted to observed data over 6 weeks during the lockdown. Model fitting and projection were validated using the mean absolute percent error (MAPE). The transmission dynamics of COVID-19 was interrupted immediately by the lockdown. The modified SIR model projected the depleting temporal trends with lowest MAPE for I total, followed by I, I daily, and R. During lockdown, the dynamics of COVID-19 depleted at a rate of 4·7% each day with a decreased capacity of 40%. For 7–day and 14–day projections, the modified SIR model accurately predicted I total, I, and R. The depleting transmission dynamics for COVID-19 during lockdown can be accurately captured by time-varying SIR model. Projection generated based on observed data is useful for future planning and control of COVID-19.

Abstract The susceptible-infectious-removed (SIR) model offers the simplest framework to study transmission dynamics of COVID-19, however, it does not factor in its early depleting trend observed during a lockdown. We modified the SIR model to specifically simulate the early depleting transmission dynamics of COVID-19 to better predict its temporal trend in Malaysia. The classical SIR model was fitted to observed total (I total), active (I) and removed (R) cases of COVID-19 before lockdown to estimate the basic reproduction number. Next, the model was modified with a partial time-varying force of infection, given by a proportionally depleting transmission coefficient, $$\beta_{t}$$ β t and a fractional term, z. The modified SIR model was then fitted to observed data over 6 weeks during the lockdown. Model fitting and projection were validated using the mean absolute percent error (MAPE). The transmission dynamics of COVID-19 was interrupted immediately by the lockdown. The modified SIR model projected the depleting temporal trends with lowest MAPE for I total, followed by I, I daily and R. During lockdown, the dynamics of COVID-19 depleted at a rate of 4.7% each day with a decreased capacity of 40%. For 7-day and 14-day projections, the modified SIR model accurately predicted I total, I and R. The depleting transmission dynamics for COVID-19 during lockdown can be accurately captured by time-varying SIR model. Projection generated based on observed data is useful for future planning and control of COVID-19.

Background: Highly sensitive real-time reverse transcription polymerase chain reaction (qRT-PCR) methods have been developed for the detection of SARS-CoV2. However, they are costly. Loop-mediated isothermal amplification (LAMP) assay has emerged as a novel alternative isothermal amplification method for the detection of nucleic acid. Methods: A rapid, sensitive and specific real-time reverse transcription LAMP (RT-LAMP) assay was developed for SARS-CoV2 detection. Results: This assay detected one copy of SARS-CoV2 RNA in 30 min. Both the clinical sensitivity and specificity of this assay were 100%. The RT-LAMP showed comparable performance with real-time qRT-PCR. Combining simplicity and cost-effectiveness, this assay is therefore recommended for use in resource limiting settings. Subjects Virology, Drugs and Devices, Emergency and Critical Care, Global Health, Infectious Diseases

Background: COVID-19 emerged as a major public health outbreak in China in late 2019. Malaysia reported its first imported case on 25 January 2020, and adopted a policy of extensive contact tracing and hospitalizing of all patients, regardless of severity. We describe clinical characteristics of COVID-19 patients nationwide and determine the risk factors associated with disease severity.Method: Clinical records of all RT-PCR confirmed COVID-19 patients admitted to 18 designated hospitals in Malaysia between 1 February and 30 April 2020 with complete outcomes were retrieved. Epidemiological history, co-morbidities, clinical features, investigations, management and complications were captured using REDCap database. Variables were compared among patients with mild and severe diseases. Univariate and multivariate regression analyses were used to identify determinants for disease severity.Findings:The sample comprised of 5889 cases (median age 34 years, male 71·7%). Majority were mild (92%) and 3·3% required intensive care with 80% admitted within the first 5 days. Older age (> 51 years), fever, cough, diarrhoea, breathlessness, tachypnoea, abnormal chest radiographs and high serum CRP (≥5mg/dL) on admission were significant determinants for disease severity (p < 0·05). The case fatality rate was 1·2% and the three commonest complications were liver injuries (6·7%), kidney injuries (4%), and acute respiratory distress syndrome (2·3%).Interpretations: Lower case fatality rate was contributed by young patients with mild presenting COVID-19 and early hospitalisation. Abnormal chest radiographic findings in symptomatic elderly with tachypnoea require close monitoring in first 5 days to detect early deterioration.Funding Statement: Supported by NIH, MalaysiaDeclaration of Interests: None to declare.Ethics Approval Statement: The study was registered with the National Medical Research Register (NMRR-20-580- 54339) and approved by the Medical Research and Ethics Committee, Ministry of Health, Malaysia (KKM/NIHSEC/P20-706).

A simple and rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of SARS-CoV-2. The RT-LAMP assay was highly specific for SARS-CoV-2 and was able to detect one copy of transcribed SARS-CoV-2 RNA within 24 minutes. Assay validation performed using 50 positive and 32 negative clinical samples showed 100% sensitivity and specificity. The RT-LAMP would be valuable for clinical diagnosis and epidemiological surveillance of SARS-CoV-2 infection in resource-limited areas as it does not require the use of sophisticated and costly equipment.

Background To date, most of the recent publications on malaria in Malaysia were conducted in Sabah, East Malaysia focusing on the emergence of Plasmodium knowlesi . This analysis aims to describe the incidence, mortality and case fatality rate of malaria caused by all Plasmodium species between Peninsular Malaysia and East Malaysia (Sabah and Sarawak) over a 5-year period (2013–2017). Methods This is a secondary data review of all diagnosed and reported malaria confirmed cases notified to the Ministry of Health, Malaysia between January 2013 and December 2017. Results From 2013 to 2017, a total of 16,500 malaria cases were notified in Malaysia. The cases were mainly contributed from Sabah (7150; 43.3%) and Sarawak (5684; 34.4%). Majority of the patients were male (13,552; 82.1%). The most common age group in Peninsular Malaysia was 20 to 29 years (1286; 35.1%), while Sabah and Sarawak reported highest number of malaria cases in age group of 30 to 39 years (2776; 21.6%). The top two races with malaria in Sabah and Sarawak were Bumiputera Sabah (5613; 43.7%) and Bumiputera Sarawak (4512; 35.1%), whereas other ethnic group (1232; 33.6%) and Malays (1025; 28.0%) were the two most common races in Peninsular Malaysia. Plasmodium knowlesi was the commonest species in Sabah and Sarawak (9902; 77.1%), while there were more Plasmodium vivax cases (1548; 42.2%) in Peninsular Malaysia. The overall average incidence rate, mortality rate and case fatality rates for malaria from 2013 to 2017 in Malaysia were 0.106/1000, 0.030/100,000 and 0.27%, respectively. Sarawak reported the highest average incidence rate of 0.420/1000 population followed by Sabah (0.383/1000). Other states in Peninsular Malaysia reported below the national average incidence rate with less than 0.100/1000. Conclusions There were different trends and characteristics of notified malaria cases in Peninsular Malaysia and Sabah and Sarawak. They provide useful information to modify current prevention and control measures so that they are customised to the peculiarities of disease patterns in the two regions in order to successfully achieve the pre-elimination of human-only species in the near future.

Te world has been grappling with the outbreak of COVID-19 for the past few months. Te coronavirus, which was frst reported in Wuhan, China has now spread to 82 countries and infected more than 95000 individuals. As of March 5, 2020, there have been 55 confrmed cases of COVID-19 in Malaysia.

BACKGROUND:Highly sensitive real-time reverse transcription polymerase chain reaction (RT-qPCR) methods have been developed for the detection of SARS-CoV-2. However, they are costly. Loop-mediated isothermal amplification (LAMP) assay has emerged as a novel alternative isothermal amplification method for the detection of nucleic acid.METHODS:A rapid, sensitive and specific real-time reverse transcription LAMP (RT-LAMP) assay was developed for SARS-CoV-2 detection.RESULTS:This assay detected one copy/reaction of SARS-CoV-2 RNA in 30 min. Both the clinical sensitivity and specificity of this assay were 100%. The RT-LAMP showed comparable performance with RT-qPCR. Combining simplicity and cost-effectiveness, this assay is therefore recommended for use in resource resource-limited settings.

BACKGROUND Financial toxicity negatively affects the well-being of cancer survivors. We examined the incidence, cost drivers, and factors associated with financial toxicity after cancer in an upper-middle-income country with universal health coverage. METHODS Through the Association of Southeast Asian Nations Costs in Oncology study, 1,294 newly diagnosed patients with cancer (Ministry of Health [MOH] hospitals [n = 577], a public university hospital [n = 642], private hospitals [n = 75]) were observed in Malaysia. Cost diaries and questionnaires were used to measure incidence of financial toxicity, encompassing financial catastrophe (FC; out-of-pocket costs ≥ 30% of annual household income), medical impoverishment (decrease in household income from above the national poverty line to below that line after subtraction of cancer-related costs), and economic hardship (inability to make necessary household payments). Predictors of financial toxicity were determined using multivariable analyses. RESULTS One fifth of patients had private health insurance. Incidence of FC at 1 year was 51% (MOH hospitals, 33%; public university hospital, 65%; private hospitals, 72%). Thirty-three percent of households were impoverished at 1 year. Economic hardship was reported by 47% of families. Risk of FC attributed to conventional medical care alone was 18% (MOH hospitals, 5%; public university hospital, 24%; private hospitals, 67%). Inclusion of expenditures on nonmedical goods and services inflated the risk of financial toxicity in public hospitals. Low-income status, type of hospital, and lack of health insurance were strong predictors of FC. CONCLUSION Patients with cancer may not be fully protected against financial hardships, even in settings with universal health coverage. Nonmedical costs also contribute as important drivers of financial toxicity in these settings.

Background Epidemiologic measures of the dengue burden such as prevalence and incidence are important for policy-making and monitoring the progress of disease control. It is a common practice where epidemiologic and economic research estimate dengue burden based on notification data. However, a basic challenge in estimating the incidence of dengue is that a significant proportion of infected population are asymptomatic. It can be overcome by using mathematical models that relate observed prevalence and mortality to incidence. In this study, we estimate the trend of dengue incidence and hospitalization in Malaysia. Methods This study is based entirely on the available secondary data sources on dengue in Malaysia. The age-specific incidence of dengue between 2001 and 2013 was estimated using the prevalence and mortality estimates in an incidence-prevalence-mortality (IPM) model. Data on dengue prevalence were extracted from six sero-surveys conducted in Malaysia between 2001 and 2013; while statistics on dengue notification and Case Fatality Rate were derived from National Dengue Surveillance System. Dengue hospitalization data for the years 2009 to 2013 were extracted from the Health Informatics Centre and the volumes of dengue hospitalization for hospitals with missing data were estimated with Poisson models. Results The dengue incidence in Malaysia varied from 69.9 to 93.4 per 1000 population (pkp) between 2001 and 2013.The temporal trend in incidence rate was decreasing since 2001. It has been reducing at an average rate of 2.57 pkp per year from 2001 to 2013 ( p = 0.011). The age-specific incidence of dengue decreased steadily with dengue incidence reaching zero by age > 70 years. Dengue notification rate has remained stable since 2001 and the number of notified cases each year was only a small fraction of the incident cases (0.7 to 2.3%). Similarly, the dengue hospitalization was larger but still a small fraction of the incident cases (3.0 to 5.6%). Conclusion Dengue incidence can be estimated with the use of sero-prevalence surveys and mortality data. This study highlights a reducing trend of dengue incidence in Malaysia and demonstrates the discrepancy between true dengue disease burden and cases reported by national surveillance system. Sero-prevalence studies with representative samples should be conducted regularly to allow better estimation of dengue burden in Malaysia.