Health-Related Quality of Life after Dengue Fever, Morelos, Mexico, 2016-2017.

We adapted the EQ-5D-3L questionnaire and visual analog scale to assess health-related quality of life (HRQOL) and persistent symptoms in 79 patients with laboratory-confirmed dengue in Morelos, Mexico. The lowest HRQOLs were 0.53 and 38.1 (febrile phase). Patients recovered baseline HRQOL in ≈2 months.

Seroprevalence of dengue in school children in Mexico ages 6-17 years, 2016.

Background: Dengue is the most important arboviral disease in the world. Seroprevalence has been proposed as a marker of endemicity, however, studies are scarce. Methods: We conducted a cross-sectional, stratified cluster, random sample study to measure the seroprevalence of antibodies to dengue virus (DENV) in Mexico. The target population was school children ages 6-17 y from 22 endemic states in Mexico, clustered in four regions: Pacific, South-Central, Southeast and Low. Results: A total of 2134 subjects provided blood samples for immunoglobulin G antibody detection in serum by enzyme-linked immunosorbent assay. Overall, the seroprevalence of antibodies against DENV was 33.5% (95% confidence interval [CI] 27.5 to 40.1). The Southeast had the highest regional seroprevalence, reaching 70.9% (95% CI 60.3 to 79.7). Seroprevalence was higher in older children in the Southeast region: 62.1% (95% CI 46.9 to 75.2) in children 6-8 y and 82.6% (95% CI 73.8 to 88.9) in 13-17 years old (y). However, this was not consistent in all regions. Seroprevalence was associated with dengue incidence. Conclusions: DENV seroprevalence in Mexico was found to be heterogeneous at the country, regional and state levels. Seroprevalence was linked to long-term exposure and did not adequately reflect recent patterns of transmission, suggesting that utilization of a single epidemiological indicator to define endemic regions should be avoided.

Seroprevalence of neutralizing antibodies against dengue virus in two localities in the state of Morelos, Mexico.

Humoral immune response against dengue virus (DENV) is an important component in dengue-endemic transmission. We conducted a cross-sectional nested cohort study to determine the seroprevalence and frequency of neutralizing antibodies against DENV serotypes in two endemic localities in the state of Morelos, Mexico. The cohort participants (N = 1,196) were screened to determine previous exposure to DENV. Overall seroprevalence was 76.6% (95% confidence interval [95% CI] = 73.6-79.2), and prevalence of neutralizing antibodies in the 5- to 9-year-old group was 82.5% (95% CI = 67.2-92.7), 45% (95% CI = 29.3-61.5), and 65% (95% CI = 48.3-79.4) for DENV-1, DENV-2, and DENV-3, respectively. For participants older than 10 years, the observed seroprevalence was above 60% for each serotype, except DENV-4 in the 10- to 25-year-old group (42.9%); 81% of humoral responses were multitypic. The outcomes of our study contribute to understanding the immune component of dengue transmission and provide focal information for the evaluation of vaccine candidates under development.

Contrasting associations of polymorphisms in FcγRIIa and DC-SIGN with the clinical presentation of dengue infection in a Mexican population.

Dengue virus (DENV) causes a spectrum of illness from asymptomatic infection, to a mild febrile illness, to occasional more severe complications including hemorrhage and shock. Dengue is endemic in the state of Morelos, Mexico. Two single nucleotide polymorphisms (SNPs), rs1801274 of FcγRIIa and rs4804803 of DC-SIGN, have been associated with protection from or susceptibility to severe dengue infection. Both of these polymorphisms are located in genes for receptors with important roles in dengue pathogenesis, and their relationship with the clinical presentation of dengue infection in Mexican populations is unknown. In this study, real-time PCR was used to characterize the distribution of rs1801274 and rs4804803 in subjects with asymptomatic dengue infection (n=145), uncomplicated dengue (n=67), and severe dengue (n=36) in Morelos. In contrast with previous studies, the histidine (A) variant of rs1801274 was associated with more mild infection: carrying the histidine allele (either homozygous or heterozygous) was associated with protection from symptomatic infection compared with asymptomatic (OR 0.51, p=0.038). Histidine homozygotes were also less likely to present severe dengue (OR 0.34, p=0.05). Logistic regression models confirm this association (OR 0.48, p=0.04) and also indicate that the G allele of rs4804803 is associated with symptomatic dengue (OR 2.3, p=0.08), after accounting for other biological factors including history of infection. This variant was rare in this study population, with a frequency of 5.4%. These findings reflect the complexity of influences on the development of severe dengue infection. The inclusion of asymptomatic infections and adjusted case definitions likely do not explain the entire disparity with previous findings. Interactions with other polymorphisms may explain why the association of rs1801274 is reversed in this population compared to others. This study demonstrates the importance of genetic association studies in multiple genetically distinct populations.

Emergence potential of sylvatic dengue virus type 4 in the urban transmission cycle is restrained by vaccination and homotypic immunity.

Sylvatic dengue viruses (DENV) are both evolutionarily and ecologically distinct from human DENV and are maintained in an enzootic transmission cycle. Evidence of sylvatic human infections from West Africa and Southeast Asia suggests that sylvatic DENV come into regular contact with humans. Thus, this potential of emergence into the human transmission cycle could limit the potential for eradicating this cycle with vaccines currently in late stages of development. We assessed the likelihood of sylvatic DENV-4 emergence in the face of natural immunity to current human strains and vaccination with two DENV-4 vaccine candidates. Our data indicate homotypic neutralization of sylvatic and human DENV-4 strains by human primary convalescent and vaccinee sera but limited heterotypic immunity. These results suggest that emergence of sylvatic strains into the human cycle would be limited by homotypic immunity mediated by virus neutralizing antibodies produced by natural infection or vaccination.