Dengue virus serotype 2 (DENV-2) is responsible for dengue epidemics on a global scale and is associated with severe cases of the disease. This study conducted a phylogenetic investigation of DENV-2 isolates from 2017 to 2021 originating from the northern states of Brazil. A total of 32 samples from DENV-2 isolates were analyzed, including 12 from Acre, 19 from Roraima, and one from Tocantins. Only one lineage of the Asian-American genotype and one lineage of the cosmopolitan genotype were observed: Lineage 1, Asian-American genotype (connection to Puerto Rico); Lineage 5, cosmopolitan genotype (connection to Peru). Our results provide important data regarding the study of DENV genotypes and lineage distribution and open up possibilities for probable introduction and dissemination routes. Full article

Dengue virus serotype 4 (DENV-4) has been the rarest circulating serotype in Malaysia, resulting in it being an understudied area. A recent observation from institutional surveillance data indicated a rapid increase in DENV-4-infected cases. The present study aimed to investigate the resurgence of DENV-4 in relation to the demographic, clinical and genomic profiles of 75 retrospective dengue samples. First, the demographic and clinical profiles obtained between 2017 and July 2022 were statistically assessed. Samples with good quality were subjected to full genome sequencing on the Illumina Next Seq 500 platform and the genome data were analysed for the presence of mutations. The effect of the mutations of interest was studied via an in silico computational approach using SWISS-MODEL and AlphaFold2 programs. The predominance of DENV-4 was discovered from 2021 to 2022, with a prevalence of 64.3% (n = 9/14) and 89.2% (n = 33/37), respectively. Two clades with a genetic divergence of 2.8% were observed within the dominant genotype IIa. The majority of DENV-4-infected patients presented with gastrointestinal symptoms, such as vomiting (46.7%), persistent diarrhoea (30.7%) and abdominal pain (13.3%). Two mutations, His50Tyr and Pro144Ser, located at the wing domain of the NS1 protein were discovered to be unique to the recently sequenced DENV-4. Full article

Dengue virus 2 (DENV-2) seriously contributes to dengue-related mortality. It includes five nonsylvatic genotypes, with cosmopolitan being the most widespread with a significant contribution to the total number of DENV-2 cases globally. In South America, the cosmopolitan genotype was first recorded in 2019 in Madre de Dios, Peru, and then in Goiás (Midwest Brazil) in November 2021. In this study, we tested 163 human serum samples from Acre (Northern Brazil) collected during a DENV outbreak between 2020 and 2021 for all DENV genotypes by RT-qPCR. Of the 163 samples, 139 were positive for DENV-2, and 5 were positive for DENV-1. Five DENV-2-positive samples from early 2021 were sequenced, and the sequences clustered with the three other DENV-2 cosmopolitan genotype sequences already recorded on the continent. These results create a geographical link, suggesting the possible route of introduction of the DENV-2 cosmopolitan genotype into Brazil through the border with Peru, from which it may have dispersed to Midwest Brazil. Full article

Background: Dengue has become one of the major vector-borne diseases, which has been an important public health concern. We aimed to estimate the disease burden of dengue in major endemic regions from 1990 to 2019, and explore the impact pattern of the socioeconomic factors on the burden of dengue based on the global burden of diseases, injuries, and risk factors study 2019 (GBD 2019). Methods: Using the analytical strategies and data from the GBD 2019, we described the incidence and disability-adjusted life years (DALYs) of dengue in major endemic regions from 1990 to 2019. Furthermore, we estimated the correlation between dengue burden and socioeconomic factors, and then established an autoregressive integrated moving average (ARIMA) model to predict the epidemic trends of dengue in endemic regions. All estimates were proposed as numbers and age-standardized rates (ASR) per 100,000 population, with uncertainty intervals (UIs). The ASRs of dengue incidence were compared geographically and five regions were stratified by a sociodemographic index (SDI). Results: A significant rise was observed on a global scale between 1990 and 2019, with the overall age-standardized rate (ASR) increasing from 557.15 (95% UI 243.32–1212.53) per 100,000 in 1990 to 740.4 (95% UI 478.2–1323.1) per 100,000 in 2019. In 2019, the Oceania region had the highest age-standardized incidence rates per 100,000 population (3173.48 (95% UI 762.33–6161.18)), followed by the South Asia region (1740.79 (95% UI 660.93–4287.12)), and then the Southeast Asia region (1153.57 (95% UI 1049.49–1281.59)). In Oceania, South Asia, and Southeast Asia, increase trends were found in the burden of dengue fever measured by ASRs of DALY which were consistent with ASRs of dengue incidence at the national level. Most of the countries with the heaviest burden of dengue fever occurred in areas with low and medium SDI regions. However, the burden in high-middle and high-SDI countries is relatively low, especially the Solomon Islands and Tonga in Oceania, the Maldives in South Asia and Indonesia in Southeast Asia. The age distribution results of the incidence rate and disease burden of dengue fever of major endemic regions showed that the higher risk and disease burden are mainly concentrated in people under 14 or over 70 years old. The prediction by ARIMA showed that the risk of dengue fever in South and Southeast Asia is on the rise, and further prevention and control is warranted. Conclusions: In view of the rapid population growth and urbanization in many dengue-endemic countries, our research results are of great significance for presenting the future trend in dengue fever. It is recommended to policy makers that specific attention needs to be paid to the negative impact of urbanization on dengue incidence and allocate more resources to the low-SDI areas and people under 14 or over 70 years old to reduce the burden of dengue fever. Full article

Congenital microcephaly is caused by a multitude of drivers affecting maternal–fetal health during pregnancy. It is a rare outcome in high-income industrial countries where microcephaly rates are in the range of 0.3–0.9 per 1000 newborns. Prevalence of microcephaly varies considerably across developing countries and can go as high as 58 cases per 1000 live births in pregnancies exposed to infection by Zika virus (ZIKV). Not only ZIKV-infected pregnancies, but other drivers can modulate the occurrence and severity of this outcome. Here, we sought to test the ZIKV–microcephaly association vs. competing hypotheses using a meta-analysis with 8341 microcephaly cases pooled from 10,250,994 newborns in the Americas, Africa, and Asia. Analysis of risk ratios (RR) showed teratogens the most likely microcephaly-associated risk factor (RR = 3.43; 95%-CI 2.69–4.38; p-value < 0.0001), while the statistical significance of the ZIKV–microcephaly association was marginal (RR = 2.12; 95%-CI 1.01–4.48; p-value = 0.048). Other congenital infections showed strong but variable associations with microcephaly (RR = 15.24; 95%-CI 1.74–133.70; p-value = 0.014). Microcephaly cases were associated with impoverished socioeconomic settings, but this association was statistically non-significant (RR = 2.75; 95%-CI 0.55–13.78; p-value = 0.22). The marginal ZIKV–microcephaly association and statistical significance of the competing hypotheses suggest maternal ZIKV infection might not be a cause of microcephaly alone. Full article