Health is fundamental to human development. All people, regardless of social status, consistently rank good health as a top priority, and healthy people are critical to sustaining societies. It is therefore not surprising that four of the eight Millennium Development Goals (MDGs) directly relate to health.

Ensure healthy lives and promote well-being for all at all ages

Knowledge on the extent, distribution and mechanisms of insecticide resistance is essential for successful insecticide-based dengue control interventions. Here, we report an extensive resistance profiling of the dengue vectors Aedes aegypti and Aedes albopictus across Malaysia and establish the contribution of knockdown resistance mechanism revealing significant contrast between both species. Aedes mosquitoes were collected from four states in Malaysia in 2010 using ovitraps and tested against six major insecticides using WHO bioassays. Knockdown resistance (kdr) was investigated in both species. A moderate resistance to temephos was detected from samples collected in 2010 in Penang, Kuala Lumpur, Johor Bharu and Kota Bharu (1.5 < RR < 3.3). A widespread and multiple resistances was observed in Ae. aegypti particularly against pyrethroids, DDT and bendiocarb. Mosquitoes from Kuala Lumpur consistently had the highest resistance levels and was the only population showing a moderate resistance to malathion (91% mortality). The resistance profile of Ae. albopictus contrasted to Ae. aegypti with full susceptibility to pyrethroids except in Kuala Lumpur where moderate resistance is observed. PBO synergist assays suggest metabolic resistance mechanisms play a major role in resistance in both species. Two kdr mutations, F1534C and V1016G, were detected in Ae. aegypti across Malaysia but neither of these mutations were found in Ae. albopictus. Additionally, signatures of selection were detected on the Voltage-gated sodium channel gene in Ae. aegypti but not in Ae. albopictus. The presence of the 1534C allele was significantly associated with pyrethroid resistance and an additive effect to pyrethroid resistance was observed in individuals containing both kdr alleles. Findings from this study will help to design and implement successful insecticide-based interventions against Ae. aegypti and Ae. albopictus to improve dengue control across Malaysia.

/pdf/contrasting-patterns-of-insecticide-resistance-and-knockdown-4amyfb7zwo.pdf

Contrasting patterns of insecticide resistance and knockdown resistance (kdr) in the dengue vectors Aedes aegypti and Aedes albopictus from Malaysia

BackgroundThe control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic. MethodsWe monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase–polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria. ResultsApproximately 10% of the febrile...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1503877

Symptomatic Dengue in Children in 10 Asian and Latin American Countries.

The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 – 2013) was performed. Patient’s demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. A total 667 dengue patients (30.69 ± 16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P   40 years (OR: 4.1, P < 0.001), secondary infection (OR: 2.7, P = 0.042), diabetes mellitus (OR: 2.8, P = 0.041), lethargy (OR: 3.1, P = 0.005), thick gallbladder (OR: 1.7, P = 0.029) and delayed hospitalization (OR: 2.3, P = 0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected clinical profile and predictors of DHF/DSS development would provide information to identify individuals at higher risk and on the other hand, give sufficient time to clinicians for reducing dengue related morbidity and mortality.

/pdf/clinico-laboratory-spectrum-of-dengue-viral-infection-and-1di4gcou90.pdf

Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study

Dengue fever is caused by infection with one of four dengue virus (DENV) serotypes (DENV-1–4), necessitating tetravalent dengue vaccines that can induce protection against all four DENV. Takeda’s live attenuated tetravalent dengue vaccine candidate (TDV) comprises an attenuated DENV-2 strain plus chimeric viruses containing the prM and E genes of DENV-1, -3 and -4 cloned into the attenuated DENV-2 ‘backbone’. In Phase 1 and 2 studies, TDV was well tolerated by children and adults aged 1.5–45 years, irrespective of prior dengue exposure; mild injection-site symptoms were the most common adverse events. TDV induced neutralizing antibody responses and seroconversion to all four DENV as well as cross-reactive T cell-mediated responses that may be necessary for broad protection against dengue fever.

A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone

A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions.

/pdf/epidemiology-of-dengue-disease-in-malaysia-2000-2012-a-4podoh569g.pdf

Ellyana Ismail

Papers

Epidemiology of Dengue Disease in Malaysia (2000-2012): A Systematic Literature Review