Entomological Risk Assessment for Dengue Virus Transmission during 2016-2020 in Kamphaeng Phet, Thailand.

Individual houses with high risks of dengue virus (DENV) transmission might be a source of virus transmission within the neighborhood. We conducted an entomological risk assessment for DENV transmission at the household level, comprising family cohort members residing in the same location, to assess the risk for dengue virus transmitted by mosquito vectors. The studies were conducted in Kamphaeng Phet Province, Thailand, during 2016-2020. Entomological investigations were performed in 35 cohort families on day 1 and day 14 after receiving dengue case reports. DENV was found in 22 Aedes samples (4.9%) out of 451 tested samples. A significantly higher DENV infection rate was detected in vectors collected on day 1 (6.64%) compared to those collected on day 14 (1.82%). Annual vector surveillance was carried out in 732 houses, with 1002 traps catching 3653 Aedes females. The majority of the 13,228 water containers examined were made from plastic and clay, with used tires serving as a primary container, with 59.55% larval abundance. Larval indices, as indicators of dengue epidemics and to evaluate disease and vector control approaches, were calculated. As a result, high values of larval indices indicated the considerably high risk of dengue transmission in these communities.

A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain.

BACKGROUND: Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. METHODS: A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. RESULTS: Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. CONCLUSIONS: We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. CLINICAL TRIALS REGISTRATION: NCT02372175.

Prospective cohort studies of dengue viral transmission and severity of disease.

As the four serotypes of dengue virus (DENV) systematically spread throughout the tropical and subtropical regions globally, dengue is increasingly contributing to the overall morbidity and mortality sustained by populations and thereby challenging the health infrastructures of most endemic countries. DENV-human host-mosquito vector interactions are complex and cause in humans either asymptomatic or subclinical DENV infection, mild to severe dengue fever (DF), severe dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Over the past decade, we have seen an increase in research funding and public health efforts to offset the effects of this pandemic. Though multiple vaccine development efforts are underway, the need remains to further characterize the determinants of varying severities of clinical outcomes. Several long-term prospective studies on DENV transmission and dengue severity have sought to define the epidemiology and pathogenesis of this disease. Yet, more studies are required to quantify the disease burden on different populations, explore the impact of DENV serotype-specific transmission on host-responses and dengue severity and measure the economic impact of dengue on a population. In this section, we will review the critical past and recent findings of dengue prospective studies on our understanding of the disease and the potential role of future prospective cohort studies in advancing issues required for vaccine field evaluations.

Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study.

BACKGROUND: Dengue viruses are a major cause of morbidity and mortality in tropical and subtropical areas. Our aim was to assess prospectively the burden of dengue-related illness in children in Thailand. METHODS: We did a prospective study in a cohort of children at primary school in northern Thailand from 1998 to 2002. We assessed the burden of dengue illness as disability-adjusted life years (DALYs) and patient costs per illness. FINDINGS: Dengue accounted for 328 (11%) of the 3056 febrile cases identified in 2114 children during the study period. The mean burden of dengue was 465.3 (SD 358.0; range 76.5-954.0) DALYs per million population per year, accounting for about 15% of DALYs lost to all febrile illnesses (3213.1 [SD 2624.2] DALYs per million per year). Non-hospitalised patients with dengue illnesses represented a substantial proportion of the overall burden of disease, with 44-73% of the total DALYs lost to dengue each year due to such illness. The infecting dengue serotype was an important determinant of DALYs lost: DEN4 was responsible for 1% of total DALYs lost, DEN1 for 9%, DEN2 for 30%, and DEN3 for 29%. INTERPRETATION: Use of prospective data to estimate the burden of disease shows that most DALYs lost to dengue illness were the result of non-hospitalised illnesses of long duration. Thus, inclusion of non-hospitalised cases is critical to accurately assess the total burden of dengue illness.

Economic impact of dengue fever/dengue hemorrhagic fever in Thailand at the family and population levels.

Dengue fever and dengue hemorrhagic fever constitute a substantial health burden on the population in Thailand. In this study, the impact of symptomatic dengue virus infection on the families of patients hospitalized at the Kamphaeng Phet Provincial Hospital with laboratory-confirmed dengue in 2001 was assessed, and the disability-adjusted life years (DALYs) lost for fatal and non-fatal cases of dengue were calculated using population level data for Thailand. When we accounted for the direct cost of hospitalization, indirect costs due to loss of productivity, and the average number of persons infected per family, we observed a financial loss of approximately US$61 per family, which is more than the average monthly income in Thailand. The DALYs were calculated using select results from a family level survey, and resulted in an estimated 427 DALYs/million population in 2001. This figure is of the same order of magnitude as the impact of several diseases currently given priority in southeast Asia, such as the tropical cluster (trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, and onchocerciasis), malaria, meningitis, and hepatitis. These results indicate that dengue prevention, control, and research should be considered equally important as that of diseases currently given priority.

Assessment of body fluid compartment volumes by multifrequency bioelectrical impedance spectroscopy in children with dengue.

Dengue haemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage and a period of increased microvascular permeability. Monitoring of plasma volume and body fluid compartment shifts is an integral part of the clinical management of DHF, and is crucial to the performance of clinical research studies on DHF pathogenesis. Multifrequency bioelectrical impedance spectroscopy (BIS) was assessed as a non-invasive method to monitor body fluid compartment shifts in children participating in a prospective, hospital-based, study of dengue virus infections in Thailand. Over the 48 h surrounding defervescence, the extracellular water/intracellular water ratio (ECW/ICW) rose in children with dengue virus infections and correlated with increasing disease severity [DHF > intermediate dengue fever (DF)/DHF > DF]. Plasma leakage remained within the ECW compartment and was not directly measured by multifrequency BIS. Expansion of the ECW space in DHF appeared to be primarily due to diminished renal water clearance. During the course of dengue illness, multifrequency BIS did not improve on serial haematocrit and bodyweight determinations for monitoring plasma volume contraction and ECW expansion, respectively.