Measuring the effectiveness of integrated vector management with targeted outdoor residual spraying and autodissemination devices on the incidence of dengue in urban Malaysia in the iDEM trial (intervention for Dengue Epidemiology in Malaysia): study protocol for a cluster randomized controlled trial

In common with many South East Asian countries, Malaysia is endemic for dengue. Dengue control in Malaysia is currently based on reactive vector management within 24 h of a dengue case being reported. Preventive rather than reactive vector control approaches, with combined interventions, are expected to improve the cost-effectiveness of dengue control programs. The principal objective of this cluster randomized controlled trial is to quantify the effectiveness of a preventive integrated vector management (IVM) strategy on the incidence of dengue as compared to routine vector control efforts

Targeted outdoor residual spraying, autodissemination devices and their combination against Aedes mosquitoes: field implementation in a Malaysian urban setting

Currently, dengue control relies largely on reactive vector control programmes. Proactive vector-control using a rational, well-balanced integrated vector management approach may prove more successful for dengue control. As part of the development of a cluster randomized controlled epidemiological trial, a study was conducted in Johor Bahru, Malaysia. The study included one control site (three buildings) and three intervention sites which were treated as follows: targeted outdoor residual spraying only (TORS site, two buildings); deployment of autodissemination devices only (ADD site, four buildings); and the previous two treatments combined (TORS + ADD site, three buildings). The primary entomological measurement was per cent of positive ovitraps—ovitrap index (OI). The effect of each intervention on OI was analyzed by a modified ordinary least squares regression model. Relative to the control site, the TORS and ADD sites showed a reduction in the Aedes OI (−6.5%, P = 0.04 and −8.3%, P = 0.10, respectively). Analysis by species showed that, relative to control, the Ae. aegypti OI was lower in ADD (−8.9%, P = 0.03) and in TORS (−10.4%, P = 0.02). No such effect was evident in the TORS + ADD site. The present study provides insights into the methods to be used for the main trial. The combination of multiple insecticides with different modes of action in one package is innovative, although we could not demonstrate the additive effect of TORS + ADD. Further work is required to strengthen our understanding of how these interventions impact dengue vector populations and dengue transmission

Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.

The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness

Evaluation of A Simple DNA Extraction Method and Its Combination with Loop-Mediated Isothermal Amplification Assays for Rapid <i>Plasmodium knowlesi</i> Diagnosis

The initial and vital stage in the diagnosis of malaria involves extracting DNA. The efficiency of malaria testing is restricted by the multiple steps involved in commercial DNA extraction kits. We attempted to improve an existing loop-mediated isothermal amplification (LAMP) for the detection of Plasmodium knowlesi by using a simple DNA extraction approach, making it a feasible option for mass screening. We utilized a simple nucleic acid extraction method directly from whole blood for the detection of P. knowlesi, taking only 5 min to complete. The extracted DNA was evaluated by two fluorescent-based LAMP and one colorimetric-based LAMP assay. The detection limit for both SYTO-LAMP and SYBR green-LAMP was 0.00001% and 0.0001% parasitemia, respectively. Meanwhile, neutral red-LAMP had a detection limit of 0.01% parasitemia. Combining this simple and inexpensive DNA extraction method, SYTO-LAMP could serve as an alternative molecular diagnosis for the detection of P. knowlesi and other human Plasmodium spp

Spatial and Temporal Analysis of Plasmodium knowlesi Infection in Peninsular Malaysia, 2011 to 2018

The life-threatening zoonotic malaria cases caused by Plasmodium knowlesi in Malaysia has recently been reported to be the highest among all malaria cases; however, previous studies have mainly focused on the transmission of P. knowlesi in Malaysian Borneo (East Malaysia). This study aimed to describe the transmission patterns of P. knowlesi infection in Peninsular Malaysia (West Malaysia). The spatial distribution of P. knowlesi was mapped across Peninsular Malaysia using Geographic Information System techniques. Local indicators of spatial associations were used to evaluate spatial patterns of P. knowlesi incidence. Seasonal autoregressive integrated moving average models were utilized to analyze the monthly incidence of knowlesi malaria in the hotspot region from 2012 to 2017 and to forecast subsequent incidence in 2018. Spatial analysis revealed that hotspots were clustered in the central-northern region of Peninsular Malaysia. Time series analysis revealed the strong seasonality of transmission from January to March. This study provides fundamental information on the spatial distribution and temporal dynamic of P. knowlesi in Peninsular Malaysia from 2011 to 2018. Current control policy should consider different strategies to prevent the transmission of both human and zoonotic malaria, particularly in the hotspot region, to ensure a successful elimination of malaria in the future

Zika virus infection in Malaysia: an epidemiological, clinical and virological analysis

Abstract Background A major outbreak of the Zika virus (ZIKV) has been reported in Brazil in 2015. Since then, it spread further to other countries in the Americas and resulted in declaration of the Public Health Emergency of International Concern (PHEIC) by World Health Organization. In 2016, Singapore reported its first minor ZIKV epidemic. Malaysia shares similar ecological environment as Brazil and Singapore which may also favor ZIKV transmission. However, no ZIKV outbreak has been reported in Malaysia to date. This study aimed to discuss all confirmed ZIKV cases captured under Malaysia ZIKV surveillance system after declaration of the PHEIC; and explore why Malaysia did not suffer a similar ZIKV outbreak as the other two countries. Methods This was an observational study reviewing all confirmed ZIKV cases detected in Malaysia through the ZIKV clinical surveillance and Flavivirus laboratory surveillance between June 2015 and December 2017. All basic demographic characteristics, co-morbidities, clinical, laboratory and outcome data of the confirmed ZIKV cases were collected from the source documents. Results Only eight out of 4043 cases tested positive for ZIKV infection during that period. The median age of infected patients was 48.6 years and majority was Chinese. Two of the subjects were pregnant. The median interval between the onset of disease and the first detection of ZIKV Ribonucleic Acid (RNA) in body fluid was 3 days. Six cases had ZIKV RNA detected in both serum and urine samples. Phylogenetic analysis suggests that isolates from the 7 cases of ZIKV infection came from two clusters, both of which were local circulating strains. Conclusion Despite similar ecological background characteristics, Malaysia was not as affected by the recent ZIKV outbreak compared to Brazil and Singapore. This could be related to pre-existing immunity against ZIKV in this population, which developed after the first introduction of the ZIKV in Malaysia decades ago. A serosurvey to determine the seroprevalence of ZIKV in Malaysia was carried out in 2017. The differences in circulating ZIKV strains could be another reason as to why Malaysia seemed to be protected from an outbreak

Dengue in Malaysia: Factors Associated with Dengue Mortality from a National Registry.

BACKGROUND:The increasing incidence and geographical distribution of dengue has had significant impact on global healthcare services and resources. This study aimed to determine the factors associated with dengue-related mortality in a cohort of Malaysian patients. METHODS:This was a retrospective cohort study of patients in the Malaysian National Dengue Registry of 2013. The outcome measure was dengue-related mortality. Associations between sociodemographic and clinical variables with the outcome were analysed using multivariate analysis. RESULTS:There were 43 347 cases of which 13081 were serologically confirmed. The mean age was 30.0 years (SD 15.7); 60.2% were male. The incidence of dengue increased towards the later part of the calendar year. There were 92 probable dengue mortalities, of which 41 were serologically confirmed. Multivariate analysis in those with positive serology showed that increasing age (OR 1.03; CI:1.01-1.05), persistent vomiting (OR 13.34; CI: 1.92-92.95), bleeding (OR 5.84; CI 2.17-15.70) and severe plasma leakage (OR 66.68; CI: 9.13-487.23) were associated with mortality. Factors associated with probable dengue mortality were increasing age (OR 1.04; CI:1.03-1.06), female gender (OR 1.53; CI:1.01-2.33), nausea and/or vomiting (OR 1.80; CI:1.17-2.77), bleeding (OR 3.01; CI:1.29-7.04), lethargy and/or restlessness (OR 5.97; CI:2.26-15.78), severe plasma leakage (OR 14.72; CI:1.54-140.70), and shock (OR 1805.37; CI:125.44-25982.98), in the overall study population. CONCLUSIONS:Older persons and those with persistent vomiting, bleeding or severe plasma leakage, which were associated with mortality, at notification should be monitored closely and referred early if indicated. Doctors and primary care practitioners need to detect patients with dengue early before they develop these severe signs and symptoms

Approaches to Refining Estimates of Global Burden and Economics of Dengue

<div><p>Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host's immune status, age, pre-existing medical conditions, all contribute to the disease's complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools for diagnosis, vaccination, vector control, and treatment are being developed, these recommended steps should improve objective, systematic measures of dengue burden to strengthen health policy decisions.</p></div

Importance of Proactive Malaria Case Surveillance and Management in Malaysia

Although Plasmodium vivax infections in Malaysia are usually imported, a significant autochthonous outbreak of vivax malaria was detected in a remote indigenous (Orang Asli) settlement located in northern peninsular Malaysia. Between November 2016 and April 2017, 164 cases of P. vivax infection were detected. Although 83.5% of the vivax cases were identified through passive case detection and contact screening during the first 7 weeks, subsequent mass blood screening (combination of rapid diagnostic tests, blood films, and polymerase chain reaction [PCR]) of the entire settlement (N = 3,757) revealed another 27 P. vivax infections, 19 of which were asymptomatic. The mapped data from this active case detection program was used to direct control efforts resulting in the successful control of the outbreak in this region. This report highlights the importance of proactive case surveillance and timely management of malaria control in Malaysia as it nears malaria elimination