Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions.

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions.

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

Comparing the performance of dengue virus IgG and IgG-capture enzyme-linked immunosorbent assays in seroprevalence study.

BACKGROUND: Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. Currently Dengvaxia, the first dengue vaccine licensed in 20 countries, was recommended for DENV seropositive individuals aged 9-45 years. Studying dengue seroprevalence can improve our understanding of the epidemiology and transmission dynamics of DENV, and facilitate future intervention strategies and assessment of vaccine efficacy. Several DENV envelope protein-based serological tests including IgG and IgG-capture enzyme-linked immunosorbent assays (ELISAs) have been employed in seroprevalence studies. Previously DENV IgG-capture ELISA was reported to distinguish primary and secondary DENV infections during early convalescence, however, its performance over time and in seroprevalence study remains understudied. METHODS: In this study, we used well-documented neutralization test- or reverse-transcription-polymerase-chain reaction-confirmed serum/plasma samples including DENV-naïve, primary and secondary DENV, primary West Nile virus, primary Zika virus, and Zika with previous DENV infection panels to compare the performance of three ELISAs. RESULTS: The sensitivity of the InBios IgG ELISA was higher than that of InBios IgG-capture and SD IgG-capture ELISAs. The sensitivity of IgG-capture ELISAs was higher for secondary than primary DENV infection panel. Within the secondary DENV infection panel, the sensitivity of InBios IgG-capture ELISA decreased from 77.8% at < 6 months to 41.7% at 1-1.5 years, 28.6% at 2-15 years and 0% at > 20 years (p < 0.001, Cochran-Armitage test for trend), whereas that of IgG ELISA remains 100%. A similar trend was observed for SD IgG-capture ELISA. CONCLUSIONS: Our findings demonstrate higher sensitivity of DENV IgG ELISA than IgG-capture ELISA in seroprevalence study and interpretation of DENV IgG-capture ELISA should take sampling time and primary or secondary DENV infection into consideration.

A Simplified Sanger Sequencing Method for Detection of Relevant SARS-CoV-2 Variants.

Molecular surveillance of the new coronavirus through new genomic sequencing technologies revealed the circulation of important variants of SARS-CoV-2. Sanger sequencing has been useful in identifying important variants of SARS-CoV-2 without the need for whole-genome sequencing. A sequencing protocol was constructed to cover a region of 1000 base pairs, from a 1120 bp product generated after a two-step RT-PCR assay in samples positive for SARS-CoV-2. Consensus sequence construction and mutation identification were performed. Of all 103 samples sequenced, 69 contained relevant variants represented by 20 BA.1, 13 delta, 22 gamma, and 14 zeta, identified between June 2020 and February 2022. All sequences found were aligned with representative sequences of the variants. Using the Sanger sequencing methodology, we were able to develop a more accessible protocol to assist viral surveillance with a more accessible platform.

SARS-CoV-2 Incidence, signs and symptoms and main risk factors for COVID-19 infection in Health Care Workers: A hospital-wide survey in Salvador, Brazil.

BACKGROUND: Brazil is the third country most affected by Coronavirus Disease 2019 (COVID-19) in the world. Health care workers (HCWs) are at higher risk of infection. Despite the increasing numbers of studies on the topic, There are gaps in the knowledge of characteristics and risk factors for infection of HCWS. This information is important to design preventive strategies and to mitigate the disease impact. The objective of this study was to estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to identify factors associated, and to describe symptoms reported by healthcare workers at a tertiary hospital in Salvador, Brazil. METHODS: All HCWs were evaluated in a cross-sectional study conducted between May and September 2020, using self-administered questionnaires, and screening all participants for SARS-COV-2 IgG and IgM antibodies by rapid tests. Reactive IgG samples were retested by ELISA and IgM-positive test had a saliva sample retest by RT-PCR. Univariate associations were estimated by a non-adjusted incidence proportion ratio. Variables associated with COVID-19 incidence at p < 0.20 were selected for inclusion in a binary logistic regression model. RESULTS: A total of 2083 HCWs were included, mean age 41±10 years, 71.8% women, and 77.8% non-white. Of these, 271 (13.0%) and 25 (1.2%) HCWs tested positive for IgG and IgM SARS-CoV-2 antibodies, respectively, and three had a positive RT-PCR. Ancillary work [Odds Ratio (OR): 4.96], elementary education (OR: 2.91), high school education (OR: 2.89), and catholic religion (OR: 2.16) were associated with an increased likelihood of a positive IgG antibodies against SARS-CoV-2. Anosmia [Incidence Proportion Ratio (IPR): 7.41] and ageusia (IPR:8.51) were the most frequent associated symptoms. CONCLUSION: HCWs with low mean family income, lower level of schooling, ancillary workor being black had a significantly higher likelihood of testing positive for SARS-CoV-2 antibodies. Social vulnerability was an important risk factor for COVID-19 infection.

Correction: Netto et al. Hypovitaminosis D Is Associated with Higher Levels of Inflammatory Cytokines and with HAM/TSP in HTLV-Infected Patients. Viruses 2021, 13, 2223.

In the original publication [...].

Frequent Infection of Cats With SARS-CoV-2 Irrespective of Pre-Existing Enzootic Coronavirus Immunity, Brazil 2020.

Carnivores such as cats and minks are highly susceptible to SARS-CoV-2. Brazil is a global COVID-19 hot spot and several cases of human-to-cat transmission have been documented. We investigated the spread of SARS-CoV-2 by testing 547 domestic cats sampled between July-November 2020 from seven states in southern, southeastern, and northeastern Brazil. Moreover, we investigated whether immune responses elicited by enzootic coronaviruses affect SARS-CoV-2 infection in cats. We found infection with significantly higher neutralizing antibody titers against the Gamma variant of concern, endemic in Brazil during 2020, than against an early SARS-CoV-2 B.1 isolate (p<0.0001), validating the use of Gamma for further testing. The overall SARS-CoV-2 seroprevalence in Brazilian cats during late 2020 validated by plaque reduction neutralization test (PRNT90) was 7.3% (95% CI, 5.3-9.8). There was no significant difference in SARS-CoV-2 seroprevalence in cats between Brazilian states, suggesting homogeneous infection levels ranging from 4.6% (95% CI, 2.2-8.4) to 11.4% (95% CI, 6.7-17.4; p=0.4438). Seroprevalence of the prototypic cat coronavirus Feline coronavirus (FCoV) in a PRNT90 was high at 33.3% (95% CI, 24.9-42.5) and seroprevalence of Bovine coronavirus (BCoV) was low at 1.7% (95% CI, 0.2-5.9) in a PRNT90. Neutralizing antibody titers were significantly lower for FCoV than for SARS-CoV-2 (p=0.0001), consistent with relatively more recent infection of cats with SARS-CoV-2. Neither the magnitude of SARS-CoV-2 antibody titers (p=0.6390), nor SARS-CoV-2 infection status were affected by FCoV serostatus (p=0.8863). Our data suggest that pre-existing immunity against enzootic coronaviruses neither prevents, nor enhances SARS-CoV-2 infection in cats. High SARS-CoV-2 seroprevalence already during the first year of the pandemic substantiates frequent infection of domestic cats and raises concerns on potential SARS-CoV-2 mutations escaping human immunity upon spillback.

SARS-CoV-2 Incidence, signs and symptoms and main risk factors for COVID-19 infection in Health Care Workers: A hospital-wide survey in Salvador, Brazil

ABSTRACT Background: Brazil is the third country most affected by Coronavirus Disease 2019 (COVID-19) in the world. Health care workers (HCWs) are at higher risk of infection. Despite the increasing numbers of studies on the topic, There are gaps in the knowledge of characteristics and risk factors for infection of HCWS. This information is important to design preventive strategies and to mitigate the disease impact. The objective of this study was to estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to identify factors associated, and to describe symptoms reported by healthcare workers at a tertiary hospital in Salvador, Brazil. Methods: All HCWs were evaluated in a cross-sectional study conducted between May and September 2020, using self-administered questionnaires, and screening all participants for SARS-COV-2 IgG and IgM antibodies by rapid tests. Reactive IgG samples were retested by ELISA and IgM-positive test had a saliva sample retest by RT-PCR. Univariate associations were estimated by a non-adjusted incidence proportion ratio. Variables associated with COVID-19 incidence at p < 0.20 were selected for inclusion in a binary logistic regression model. Results: A total of 2083 HCWs were included, mean age 41±10 years, 71.8% women, and 77.8% non-white. Of these, 271 (13.0%) and 25 (1.2%) HCWs tested positive for IgG and IgM SARS-CoV-2 antibodies, respectively, and three had a positive RT-PCR. Ancillary work [Odds Ratio (OR): 4.96], elementary education (OR: 2.91), high school education (OR: 2.89), and catholic religion (OR: 2.16) were associated with an increased likelihood of a positive IgG antibodies against SARS-CoV-2. Anosmia [Incidence Proportion Ratio (IPR): 7.41] and ageusia (IPR:8.51) were the most frequent associated symptoms. Conclusion: HCWs with low mean family income, lower level of schooling, ancillary workor being black had a significantly higher likelihood of testing positive for SARS-CoV-2 antibodies. Social vulnerability was an important risk factor for COVID-19 infection.

Hypovitaminosis D Is Associated with Higher Levels of Inflammatory Cytokines and with HAM/TSP in HTLV-Infected Patients.

Recent studies have shown the effects of vitamin D on host response to infectious diseases. Some studies detected a high prevalence of hypovitaminosis D in HIV-infected patients, but scarce information exists for HTLV-1 infection. We conducted a cross-sectional study to evaluate the frequency of hypovitaminosis D in HTLV-1 patients and its relationship with their immune response in HTLV-infected patients and in age- and gender-matched controls at a Brazilian rehabilitation hospital. We compared vitamin D, interleukin-6 (IL-6), tumoral necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) levels across groups. Logistic regression was utilized to assess the association between hypovitaminosis D and cytokine levels. We enrolled 161 HTLV-infected subjects (129 HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 32 asymptomatic HTLV carriers) and equal number of HTLV-negative controls. We observed a significantly higher prevalence of hypovitaminosis D in patients with HAM/TSP than in HTLV asymptomatic carriers (p < 0.001), or controls (p < 0.001). HAM/TSP patients also had higher levels of IL-6 and IFN-γ than asymptomatic carriers. Patients with HAM/TSP and hypovitaminosis D had higher levels of TNF-α than asymptomatic HTLV carriers. These findings suggest hypovitaminosis D plays a role in HAM/TSP pathogenesis, and it needs to be evaluated in further studies.

Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response.

BACKGROUND: Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common, despite the lack of evidence on its clinical efficacy. OBJECTIVE: To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers (HCW) diagnosed with COVID-19 and of Th1/Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort (PBMCs). METHODS: This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universitário Professor Edgard Santos (Salvador, Brazil), diagnosed with COVID-19 from May to July, 2020, as well as in vitro production of antibody against SARS-CoV-2 and Th1/Th2 cytokines. Analyses were performed between December 2020 and February 2021. Participants were stratified according to the use of ivermectin (≤ 1 dose vs. multiple doses) for treatment of COVID-19. RESULTS: 45 HCW were included (62% women). Mean age was 39 years, and disease severity was similar across groups. Neutralizing antibodies were detected less frequently in multiple doses (70%) vs. ≤ 1 dose (97%) groups, p = 0.02). PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following in vitro stimulation with purified spike protein in comparison with patients in ≤ 1 dose group (p < 0.001). PBMC´s production of Th1/Th2 cytokines levels was similar across groups. Abdominal pain (15% vs 46%, p = 0.04), diarrhea (21% vs. 55%, p = 0.05) and taste perversion (0% vs. 18%, p = 0.05) were more frequently reported by participants that used multiple doses of ivermectin. CONCLUSIONS: Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production, in a dose dependent manner. This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects.

Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response

ABSTRACT Background: Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common, despite the lack of evidence on its clinical efficacy. Objective: To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers (HCW) diagnosed with COVID-19 and of Th1/Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort (PBMCs). Methods: This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universitário Professor Edgard Santos (Salvador, Brazil), diagnosed with COVID-19 from May to July, 2020, as well as in vitro production of antibody against SARS-CoV-2 and Th1/Th2 cytokines. Analyses were performed between December 2020 and February 2021. Participants were stratified according to the use of ivermectin (≤ 1 dose vs. multiple doses) for treatment of COVID-19. Results: 45 HCW were included (62% women). Mean age was 39 years, and disease severity was similar across groups. Neutralizing antibodies were detected less frequently in multiple doses (70%) vs. ≤ 1 dose (97%) groups, p = 0.02). PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following in vitro stimulation with purified spike protein in comparison with patients in ≤ 1 dose group (p < 0.001). PBMC's production of Th1/Th2 cytokines levels was similar across groups. Abdominal pain (15% vs 46%, p = 0.04), diarrhea (21% vs. 55%, p = 0.05) and taste perversion (0% vs. 18%, p = 0.05) were more frequently reported by participants that used multiple doses of ivermectin. Conclusions: Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production, in a dose dependent manner. This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects.

Saliva is a reliable, non-invasive specimen for SARS-CoV-2 detection.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease 2019 (COVID-19). Although Real Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) of respiratory specimens is the gold standard test for detection of SARS-CoV-2 infection, collecting nasopharyngeal swabs causes discomfort to patients and may represent considerable risk for healthcare workers. The use of saliva as a diagnostic sample has several advantages. OBJECTIVES: The aim of this study was to validate the use of saliva as a biological sample for diagnosis of COVID-19. METHODS: This study was conducted at Infectious Diseases Research Laboratory (LAPI), in Salvador, Brazil. Participants presenting with signs/symptoms suggesting SARS-CoV-2 infection underwent a nasopharyngeal swab (NPS) and/or oropharyngeal swab (OPS), and saliva collection. Saliva samples were diluted in PBS, followed by RNA isolation and RT-Real Time PCR for SARS-CoV-2. Results of conventional vs saliva samples testing were compared. Statistical analyses were performed using Statistical Package for the Social Sciences software (SPSS) version 18.0. RESULTS: One hundred fifty-five participants were recruited and samples pairs of NPS/OPS and saliva were collected. The sensitivity and specificity of RT-PCR using saliva samples were 94.4% (95% CI 86.4-97.8) and 97.62% (95% CI 91.7-99.3), respectively. There was an overall high agreement (96.1%) between the two tests. CONCLUSIONS: Use of self-collected saliva samples is an easy, convenient, and low-cost alternative to conventional NP swab-based molecular tests. These results may allow a broader use of molecular tests for management of COVID19 pandemic, especially in resources-limited settings.

Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil.

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.

Robustness of Serologic Investigations for Chikungunya and Mayaro Viruses following Coemergence.

Since 2013, the arthropod-borne Chikungunya virus (CHIKV) has cocirculated with the autochthonous Mayaro virus (MAYV) in Latin America. Both belong to the same alphavirus serocomplex, termed the Semliki Forest serocomplex. The extent of antibody cross-reactivity due to the antigenic relatedness of CHIKV and MAYV in commonly used serologic tests remains unclear. By testing 64 CHIKV- and 37 MAYV-specific sera from cohort studies conducted in Peru and Brazil, we demonstrate about 50% false-positive test results using commercially available enzyme-linked immunosorbent assays (ELISAs) based on structural antigens. In contrast, combining ELISAs for CHIKV and MAYV significantly increased positive predictive values (PPV) among all cohorts from 35.3% to 88.2% for IgM and from 61.3% to 96.8% for IgG (P < 0.0001). Testing of longitudinally collected CHIKV-specific patient sera indicated that ELISA specificity is highest for IgM testing at 5 to 9 days post-onset of symptoms (dpo) and for IgG testing at 10 to 14 dpo. IgG cross-reactivity in ELISA was asymmetric, occurring in 57.9% of MAYV-specific sera compared to 29.5% of CHIKV-specific sera. Parallel plaque reduction neutralization testing (PRNT) for CHIKV and MAYV increased the PPV from 80.0% to 100% (P = 0.0053). However, labor-intense procedures and delayed seroconversion limit PRNT for patient diagnostics. In sum, individual testing for CHIKV or MAYV only is prone to misclassifications that dramatically impact patient diagnostics and sero-epidemiologic investigation. Parallel ELISAs for both CHIKV and MAYV provide an easy and efficient solution to differentiate CHIKV from MAYV infections. This approach may provide a template globally for settings in which alphavirus coemergence imposes similar problems.IMPORTANCE Geographically overlapping transmission of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in Latin America challenges serologic diagnostics and epidemiologic surveillance, as antibodies against the antigenically related viruses can be cross-reactive, potentially causing false-positive test results. We examined whether widely used ELISAs and plaque reduction neutralization testing allow specific antibody detection in the scenario of CHIKV and MAYV coemergence. For this purpose, we used 37 patient-derived MAYV-specific sera from Peru and 64 patient-derived CHIKV-specific sera from Brazil, including longitudinally collected samples. Extensive testing of those samples revealed strong antibody cross-reactivity in ELISAs, particularly for IgM, which is commonly used for patient diagnostics. Cross-neutralization was also observed, albeit at lower frequencies. Parallel testing for both viruses and comparison of ELISA reactivities and neutralizing antibody titers significantly increased diagnostic specificity. Our data provide a convenient and practicable solution to ensure robust differentiation of CHIKV- and MAYV-specific antibodies.

HLA-B*14 allele predicts HIV-1 mother-to-child-transmission, in Salvador, Brazil.

BACKGROUND: Class I human leukocyte antigens, especially the molecules encoded at the B locus (HLA-B), are associated with AIDS progression risk. Different groups of HLA-B alleles have been associated to a protective effect or increasing susceptibility to HIV infection and are expressed from the earliest stages of gestation. OBJECTIVE: The aim of this study was to evaluate which variants of HLA-B are associated with the risk of HIV vertical transmission in infected pregnant women and in their offspring, in a referral center in Salvador Bahia. METHODS: We performed HLA-B genotyping in 52 HIV-infected mothers and their children exposed to HIV-1 during pregnancy (N=65) in Salvador, Brazil. We compared the HLA-B alleles frequency in mothers, uninfected and infected children, according to the use of antiretroviral prophylaxis. RESULTS: Absence of antiretroviral antenatal and postnatal prophylaxis was significantly associated with vertical transmission of HIV-1 (p=<0.01, and p=<0.01 respectively). Frequency of HLA-B*14 (29.2%, p=0.002), HLA-B*18 (16.7%, p=0.04) or HLA-B*14:1 (20.8%, p=0.01) alleles subgroups were significantly higher in HIV-1 infected children and persisted (HLA-B*14, p=0.04) even after adjusting for use of antiretroviral prophylaxis. No significant difference in expression of HLA-B alleles was observed among mothers who transmitted the virus compared to those who did not. CONCLUSIONS: Expression of HLA-B*14 allele in children exposed to HIV-1 is predictive of vertical transmission and reinforces the important role of genetics in mother-to-child transmission.

Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil.

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

HLA-B*14 allele predicts HIV-1 mother-to-child-transmission, in Salvador, Brazil

ABSTRACT Background: Class I human leukocyte antigens, especially the molecules encoded at the B locus (HLA-B), are associated with AIDS progression risk. Different groups of HLA-B alleles have been associated to a protective effect or increasing susceptibility to HIV infection and are expressed from the earliest stages of gestation. Objective: The aim of this study was to evaluate which variants of HLA-B are associated with the risk of HIV vertical transmission in infected pregnant women and in their offspring, in a referral center in Salvador Bahia. Methods: We performed HLA-B genotyping in 52 HIV-infected mothers and their children exposed to HIV-1 during pregnancy (N = 65) in Salvador, Brazil. We compared the HLA-B alleles frequency in mothers, uninfected and infected children, according to the use of antiretroviral prophylaxis. Results: Absence of antiretroviral antenatal and postnatal prophylaxis was significantly associated with vertical transmission of HIV-1 (p = <0.01, and p = <0.01 respectively). Frequency of HLA-B*14 (29.2%, p = 0.002), HLA-B*18 (16.7%, p = 0.04) or HLA-B*14:1 (20.8%, p = 0.01) alleles subgroups were significantly higher in HIV-1 infected children and persisted (HLA-B*14, p = 0.04) even after adjusting for use of antiretroviral prophylaxis. No significant difference in expression of HLA-B alleles was observed among mothers who transmitted the virus compared to those who did not. Conclusions: Expression of HLA-B*14 allele in children exposed to HIV-1 is predictive of vertical transmission and reinforces the important role of genetics in mother-to-child transmission.

A SYSTEMATIC REVIEW ON THE INFLUENCE OF HLA-B POLYMORPHISMS ON HIV-1 MOTHER-TO-CHILD-TRANSMISSION.

BACKGROUND: Mother-to-child-transmission (MTCT) is the main route of HIV-1 infection in children. Genetic studies suggest HLA-B alleles play an important role on HIV-1 transmission, progression, and control of HIV-1 infection. OBJECTIVE: To evaluate which polymorphisms of HLA-B are involved in HIV-1 MTCT. METHODS: Two independent reviewers performed a systematic review on search engines PubMed, Europe PMC, Cochrane, Scientific Electronic Library Online (SciELO), and Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs), using the following key terms: "HIV infection", "HIV newborn", "HLA polymorphisms", "HLA-B", and "Mother to child transmission". All studies focusing on evaluation of HIV-1 MTCT, HIV infection evolution, and molecular analyses of HLA-B in children were selected. RESULTS: Nine studies fulfilled the inclusion criteria. Sixteen HLA-B alleles groups were associated with HIV-1 infection; seven of them (43.8%) were related to slow disease progression or reduced risk of MTCT, while six (37.5%) alleles groups were linked to a faster progression of HIV infection in children and to increased risk of MTCT. The available evidence suggest that HLA-B*57 group allele is associated with slow disease progression, while HLA-B*35 group allele is associated to increased risk of MTCT and rapid disease progression in infected children. The role of HLA-B*18, B*58 and B*44 are still controversial because they were associated to both, protection against MTCT, and to higher HIV replicative capacity, in different studies. CONCLUSION: HLA-B*57 group allele can be protective against MTCT while HLA-B*35 groups alleles are consistently associated with HIV-1 MTCT.