We described and quantified epidemiologic trends in dengue disease burden in 5 Asian countries (Indonesia, Thailand, Malaysia, Philippines, and Vietnam) and identified and estimated outbreaks impact over the last 3 decades. Dengue surveillance data from 1980 to 2010 were retrieved from DengueNet and from World Health Organization sources. Trends in incidence, mortality, and case fatality rate (CFR) were systematically analyzed using annual average percent change (AAPC), and the contribution of epidemic years identified over the observation period was quantified. Over the 30-year period, incidence increased in all countries (AAPC 1980-2010: 6.7% in Thailand, 10.4% in Vietnam, 12.0% in Indonesia, 18.1% in Malaysia, 24.4% in Philippines). Mortality also increased in Indonesia, Malaysia, and Philippines (AAPC: 6.8%, 7.0%, and 29.2%, respectively), but slightly decreased in Thailand and Vietnam (AAPC: -1.3% and -2.5%), and CFR decreased in all countries (AAPC: -4.2% to -8.3%). Epidemic years, despite representing less than a third of the observation period, contributed from 1 to 3 times more cases versus nonepidemic years. Implementation of more sensitive surveillance methods over the study period may have contributed to a reporting or ascertainment bias in some countries. Nonetheless, these data support the urgent need for novel, integrated, or otherwise effective dengue prevention and control tools and approaches.
Pinpointing environmental antibiotic resistance (AR) hot spots in low-and middle-income countries (LMICs) is hindered by a lack of available and comparable AR monitoring data relevant to such settings. Addressing this problem, we performed a comprehensive spatial and seasonal assessment of water quality and AR conditions in a Malaysian river catchment to identify potential "simple" surrogates that mirror elevated AR. We screened for resistant coliforms, 22 antibiotics, 287 AR genes and integrons, and routine water quality parameters, covering absolute concentrations and mass loadings. To understand relationships, we introduced standardized "effect sizes" (Cohen's D) for AR monitoring to improve comparability of field studies. Overall, water quality generally declined and environmental AR levels increased as one moved down the catchment without major seasonal variations, except total antibiotic concentrations that were higher in the dry season (Cohen's D > 0.8, P < 0.05). Among simple surrogates, dissolved oxygen (DO) most strongly correlated (inversely) with total AR gene concentrations (Spearman's ρ 0.81, P < 0.05). We suspect this results from minimally treated sewage inputs, which also contain AR bacteria and genes, depleting DO in the most impacted reaches. Thus, although DO is not a measure of AR, lower DO levels reflect wastewater inputs, flagging possible AR hot spots. DO measurement is inexpensive, already monitored in many catchments, and exists in many numerical water quality models (e.g., oxygen sag curves). Therefore, we propose combining DO data and prospective modeling to guide local interventions, especially in LMIC rivers with limited data.
Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.
An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children.