The Latin American Zika virus (ZIKV) outbreak had a major impact on reproductive health worldwide. The reasons for the massively increased reports of neonatal microcephaly in northeastern Brazil are still unclear. Beyond the technical limitations of laboratory diagnostics, unambiguous diagnosis of ZIKV as the cause of congenital malformations is hampered by similar clinical pictures elicited by other pathogens known as TORCH pathogens. We performed a case-control study comparing mothers of children with congenital malformations to age-matched controls from Salvador, Brazil, one of the areas most extensively affected by the ZIKV outbreak. The ZIKV and Chikungunya virus seroprevalence rates differed significantly, whereas the levels of maternal exposure to TORCH pathogens were similar between cases and controls. Our data support a link between maternal ZIKV infection and congenital malformations and suggest the occurrence of predominantly vector-borne ZIKV transmission in these cases. In addition, some highly prevalent TORCH pathogens may be misinterpreted as representative of ongoing ZIKV activity in the absence of exhaustive diagnostics in northeastern Brazil.
The first cluster of patients suffering from coronavirus disease 2019 (COVID-19) was identified on December 21, 2019, and as of July 29, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been linked with 664,333 deaths and number at least 16,932,996 worldwide. Unprecedented in global societal impact, the COVID-19 pandemic has tested local, national, and international preparedness for viral outbreaks to the limits. Just as it will be vital to identify missed opportunities and improve contingency planning for future outbreaks, we must also highlight key successes and build on them. Concomitant to the emergence of a novel viral disease, there is a 'research and development gap' that poses a threat to the overall pace and quality of outbreak response during its most crucial early phase. Here, we outline key components of an adequate research response to novel viral outbreaks using the example of SARS-CoV-2. We highlight the exceptional recent progress made in fundamental science, resulting in the fastest scientific response to a major infectious disease outbreak or pandemic. We underline the vital role of the international research community, from the implementation of diagnostics and contact tracing procedures to the collective search for vaccines and antiviral therapies, sustained by unique information sharing efforts.
Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014–2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5–2 years after the 2015–2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7–66.7%), and decreased to 38.6% (56/144, CI 31.3–47.0%) 1.5–2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals that remained positive in both timepoints significantly decreased from a ratio of 4.4 (95% CI 3.8–5.0) to 1.6 (95% CI 1.6–1.9) over the 2-year interval (Z: − 6.1; p < 0.001) irrespective of the subpopulation analyzed. Initial 2016 DENV antibody response was non-significant between groups, suggesting comparable DENV background. The high 20.6% seroreversion suggest that widely used serologic tests may fail to account a considerable proportion of past ZIKV infections in flavivirus endemic countries. In addition, ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.
Although essential for control strategies, knowledge about transmission cycles is limited for Venezuelan equine encephalitis complex alphaviruses (VEEVs). After testing 1,398 bats from French Guiana for alphaviruses, we identified and isolated a new strain of the encephalitogenic VEEV species Tonate virus (TONV). Bats may contribute to TONV spread in Latin America.
Decades after its discovery in East Africa, Zika virus (ZIKV) emerged in Brazil in 2013 and infected millions of people during intense urban transmission. Whether vertebrates other than humans are involved in ZIKV transmission cycles remained unclear. Here, we investigate the role of different animals as ZIKV reservoirs by testing 1723 sera of pets, peri-domestic animals and African non-human primates (NHP) sampled during 2013–2018 in Brazil and 2006–2016 in Côte d'Ivoire. Exhaustive neutralization testing substantiated co-circulation of multiple flaviviruses and failed to confirm ZIKV infection in pets or peri-domestic animals in Côte d'Ivoire (n=259) and Brazil (n=1416). In contrast, ZIKV seroprevalence was 22.2% (2/9, 95% CI, 2.8–60.1) in West African chimpanzees (Pan troglodytes verus) and 11.1% (1/9, 95% CI, 0.3–48.3) in king colobus (Colobus polycomos). Our results indicate that while NHP may represent ZIKV reservoirs in Africa, pets or peri-domestic animals likely do not play a role in ZIKV transmission cycles.
The hepatitis C virus genotype 2 (HCV2) is endemic in Western and Central Africa. The HCV2 evolutionary origins remain uncertain due to the paucity of available genomes from African settings. In this study, we investigated the molecular epidemiology of HCV infections in rural Guinea, Western Africa, during 2004 and 2014. Broadly reactive nested RT-PCR-based screening of sera from 1,571 asymptomatic adults resulted in the detection of 25 (1.5%, 95% CI 0.9-2.3) positive samples, with a median viral load of 2.54E+05 IU/mL (IQR 6.72E+05). HCV-infected persons had a median age of 47 years and 62.5% were male and 37.5% female. The full polyprotein-encoding genes were retrieved by a combination of high throughput and Sanger sequencing from 17 samples showing sufficiently high viral loads. Phylogenetic analysis and sequence distances ≥13% averaged over the polyprotein genes compared to other HCV2 subtypes revealed 9 previously unknown HCV2 subtypes. The time to the most recent common ancestor of the Guinean HCV2 strains inferred in a Bayesian framework was 493 years (95% HPD 453-532). Most of the Guinean strains clustered poorly by location both on the level of sampling sites within Guinea and the level of countries in the phylogenetic reconstructions. Ancestral state reconstruction provided decisive support (Bayes factor >100) for an origin of HCV2 in Western Africa. Phylogeographic reconstructions in a Bayesian framework pointed to a radial diffusion of HCV2 from Western African regions encompassing today’s countries like Ghana, Guinea Bissau, or Burkina Faso, to Central and Northern African regions that took place from the 16th century onwards. The spread of HCV2 coincided in time and space with the main historic slave trade and commerce routes, supported by Bayesian tip-association significance testing (p = 0.01). Our study confirms the evolutionary origins of HCV2 in Western Africa and provides a potential link between historic human movements and HCV2 dispersion.
Genomic surveillance during ebolavirus outbreaks to elucidate transmission chains and develop diagnostic tests is delayed by the laborious development of variant-specific laboratory assays. We developed a new protocol combining 31 parallel PCR assays with Illumina/MinION-based sequencing, allowing generic ebolavirus genomic surveillance, validated using cell culture-derived Ebola, Reston, Sudan and Taï Forest virus at concentrations compatible with patient viral loads. Our approach enables pre-emptive genomic surveillance of ongoing and future ebolavirus outbreaks irrespective of variant divergence.
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