Asymptomatic dengue carriers a potential epidemic reservoir
Individuals carrying the dengue virus (DENV) and showing little to no outward symptoms of the disease may play a larger role in dengue fever epidemics than previously expected, says an expert.
According to Dr. Yu-Wen Chien, assistant professor of infectious disease at the Department of Public Health of National Cheng Kung University College of Medicine, Taiwan, asymptomatic and subclinical carriers of DENV have been demonstrated to not only be infectious to mosquito vectors, but also capable of transmitting the disease more effectively than symptomatic patients.
“Asymptomatic infection” can be defined as a serologically confirmed DENV infection in the absence of reported or detected symptoms, while “subclinical infection” can be defined as a confirmed DENV infection with insufficient symptoms to be detected by existing healthcare surveillance systems.
“The majority of dengue cases are asymptomatic, [although] the percentage varies from study to study due to differences in study design, participant age group and dengue serotype,” said Chien. She referred to a 2014 literature review of 48 serological studies of dengue epidemics across multiple countries, which estimated that hidden carriers of DENV accounted to 50% to 90% of the population in epidemic zones. [Front Immunol 2014;5:280]
Speaking at the recent National Dengue and Arboviruses Conference 2017 in Kuala Lumpur recently, Chien noted that people with asymptomatic or subclinical infections generally have a lower average level of DENV viraemia (presence of virus in the blood) compared to those with visible symptoms; this was previously thought to be associated with a shorter time window of infectiousness and less efficiency in transmission.
However, she highlighted a key study published two years ago which established that “not only did a larger proportion of mosquitoes became infected when they fed on the blood of participants without symptoms, but mosquitoes that became infected had significantly more viral genome copies in their bodies than those infected by feeding on the blood of symptomatic participants.” [Proc Natl Acad Sci USA 2015;112;14688–14693]
The study examined 181 participants who were either confirmed DENV-infected at point of mosquito feeding (n=176) or had no detectable viraemia at feeding, but still found to be infectious to mosquitoes (n=5). Of these, 126 were symptomatic for dengue when feeding occurred; 42 developed symptoms post-feeding; and 13 had no symptoms throughout the study.
According to the study’s researchers, asymptomatic and pre-symptomatic infections were found to be more infectious to mosquitoes than symptomatic infections at any given viremia level. With uninfected mosquitoes fed directly on participants, the 50% oral infectious dose—defined as viral concentration necessary to infect 50% of mosquitoes in a feeding—was found to be 7.21 (95% CI, 7.05–7.36) log10 viral cDNA copies per mL plasma in symptomatic patients, but only 5.31 (95% CI, 4.81–5.80) in asymptomatic patients, and 5.68 (95% CI, 5.30–6.00) in presymptomatic patients.
“Apart from being more infectious, people without symptoms may [also] be more likely to visit multiple locations during their daily routines, where they are cumulatively bitten by more mosquitoes than people who are hospitalized or stay at home, and are [therefore] exposed to only their resident mosquitoes,” said Chien. “In addition to traditional transmission route of mosquito bites, there is evidence of other avenues of dengue transmission through blood transfusions, transplants and nosocomial infections.”
Chien noted that the first case of transfusion-mediated dengue infection was reported in 2002 in Hong Kong, with 8 other individual cases reported in Singapore, Puerto Rico and Brazil between 2007 and 2014. In addition to these, Chien highlighted a prospective study in Brazil which found that of 16 recipients of blood which tested positive for DENV, evidence of transfusion-transmitted infection was found in 6 recipients, with viral loads ranging from 36 to 84,400 copies/mL in the six infection cases. [J Infect Dis 2016;213(5):694–702]