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Worldwide, millions of children are estimated to have been infected with HIV through mother to child transmission (MTCT). However, in some settings, antenatal screening for HIV infection, proper management with antiretroviral drugs, obstetrical interventions, and avoidance of breastfeeding have reduced the risk of MTCT to less than 2%. In Brazil, pregnant women have been offered HIV testing since 1996. Those found to be HIV seropositive have been offered perinatal transmission prophylaxis with zidovudine according to the ACTG 076 protocol.

Background: There is interest in the public health impact of Long COVID, defined as symptoms that persist or begin after SARS-CoV-2 infection. We aimed to identify demographic and clinical risk factors associated with Long COVID over time in an Upper Middle-Income Country (UMIC) and potential biomarkers predictive of symptom trajectory., Methods: Prospective cohort study of adults with mild SARS-COV-2 during the Omicron period. We tracked symptom persistence and IgG antibody titers against the spike S1 subunit., Results: Of 383 participants, 276 had confirmed SARS-CoV-2 infection. Long COVID persisted for ≥ two months in 21 % and ≥ 12 months in 5 %. The most common symptoms were fatigue, upper respiratory symptoms, and myalgia/arthralgia: 15 % had fatigue for ≥ one month, 10 % for ≥ two months, and 5 % ≥ three months. Upper respiratory symptoms lasted ≥ one month in 17 %, ≥ two months in 7 %, and ≥ three months in 3 %. Fully 9 % reported myalgia/arthralgia lasting ≥ one month, 6 % ≥ two months, and 4 % ≥ three months. Risk factors for symptom persistence included female sex, not being fully vaccinated, and comorbidities. Participants experiencing persistent fatigue had lower anti-S1 IgG titers., Conclusions: In this population, symptom persistence declined after the acute phase, but 5 % of participants did not fully recover. Even in a population that was almost fully vaccinated, women, individuals with comorbidities, and the few remaining people who were unvaccinated were at greater risk for Long COVID. Immunoglobulins may have utility as a biomarker of Long COVID fatigue in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Infectious disease (ID) cohorts are key to advancing public health surveillance, public policies, and pandemic responses. Unfortunately, ID cohorts often lack funding to store and share clinical-epidemiological (CE) data and high-dimensional laboratory (HDL) data long term, which is evident when the link between these data elements is not kept up to date. This becomes particularly apparent when smaller cohorts fail to successfully address the initial scientific objectives due to limited case numbers, which also limits the potential to pool these studies to monitor long-term cross-disease interactions within and across populations. CE data from 9 arbovirus (arthropod-borne viruses) cohorts in Latin America were retrospectively harmonized using the Maelstrom Research methodology and standardized to Clinical Data Interchange Standards Consortium (CDISC). We created a harmonized and standardized meta-cohort that contains CE and HDL data from 9 arbovirus studies from Latin America. To facilitate advancements in cross-population inference and reuse of cohort data, the Reconciliation of Cohort Data for Infectious Diseases (ReCoDID) Consortium harmonized and standardized CE and HDL from 9 arbovirus cohorts into 1 meta-cohort. Interested parties will be able to access data dictionaries that include information on variables across the data sets via Bio Studies. After consultation with each cohort, linked harmonized and curated human cohort data (CE and HDL) will be made accessible through the European Genome-phenome Archive platform to data users after their requests are evaluated by the ReCoDID Data Access Committee. This meta-cohort can facilitate various joint research projects (eg, on immunological interactions between sequential flavivirus infections and for the evaluation of potential biomarkers for severe arboviral disease)., (©Gustavo Gómez, Heather Hufstedler, Carlos Montenegro Morales, Yannik Roell, Anyela Lozano-Parra, Adriana Tami, Tereza Magalhaes, Ernesto T A Marques, Angel Balmaseda, Guilherme Calvet, Eva Harris, Patricia Brasil, Victor Herrera, Luis Villar, Lauren Maxwell, Thomas Jaenisch, ReCoDID Arbovirus harmonization study group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 23.07.2024.)

Background: It is important to understand the dynamics of SARS-CoV-2 transmission in close-contact settings such as households. We hypothesized that children would most often acquire SARS-CoV-2 from a symptomatic adult caregiver., Methods: This prospective cohort study was conducted from April 2020 to July 2022 in a low-resource, urban settlement in Brazil. We recruited families who brought their children to a public clinic. We collected nasopharyngeal and oral swabs from household members and tracked symptoms and vaccination., Results: In total, 1256 participants in 298 households were tested for SARS-CoV-2. A total of 4073 RT-PCR tests were run with 893 SARS-CoV-2 positive results (21.9%). SARS-CoV-2 cases were defined as isolated cases (N = 158) or well-defined transmission events (N = 175). The risk of household transmission was lower if the index case was a child (OR: 0.3 [95% CI: 0.16-0.55], P < .001) or was vaccinated (OR: 0.29 [95% CI: 0.1-0.85], P = .024), and higher if the index was symptomatic (OR: 2.53 [95% CI: 1.51-4.26], P < .001). The secondary attack rate for child index cases to child contacts was 0.29, whereas the secondary attack rate for adult index cases to child contacts was 0.47 (P = .08)., Conclusions: In this community, children were significantly less infectious to their household contacts than adolescents or adults. Most children were infected by a symptomatic adult, usually their mother. There was a double benefit of vaccination as it protected the vaccine from severe illness and prevented onward transmission to household contacts. Our findings may also be valid for similar populations throughout Latin America., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted., (© 2023. The Author(s).)

Background: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening., Methods: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance., Results: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91)., Conclusions: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant., (© 2023. The Author(s).)

Background: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management., Methods: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values., Findings: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only., Interpretation: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook., Funding: EU's Seventh Framework Programme., Translations: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests TJ reports personal fees from the Roche Severe Dengue Advisory Board, Takeda Pharmaceutical Company, Merck Pharmaceuticals, and Emergent Biosolutions, as a member of advisory boards, outside the submitted work. BAW reports personal fees from Takeda Pharmaceutical Company and from the Roche Severe Dengue Advisory Board, outside the submitted work. SY reports personal fees from Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) is a treatment modality with curative intent for oligometastatic cancer patients, commonly defined by a low-burden metastatic disease with 1-5 systemic metastases. Better knowledge of the clinical profile and prognostic factors in oligometastatic cancer patients could help to improve the selection of candidates who may obtain most benefits from SBRT. The objective of this study was to describe the clinical data and outcome in term of overall survival (OS) of patients with oligometastatic disease treated with SBRT over a 6-year period., Methods: From 2013 to 2018, 284 solid tumor cancer patients with 1-5 oligometastases underwent SBRT at a large university-affiliated oncological center in Barcelona, Spain. Variables related to the patient profile, tumor, oligometastatic disease, and treatment were evaluated., Results: A total of 327 metastatic tumors were treated with SBRT. In 65.5% of cases, metachronous tumors were diagnosed at least 1 year after diagnosis of the primary tumor. The median age of the patients was 73.9 years and 66.5% were males. The median follow-up was 37.5 months. The most common primary tumors were lung and colorectal cancer, with lung and bone as the most commonly treated metastatic sites. Ninety-three percent of patients showed a Karnofsky score (KPS) between 80 and 100. Adenocarcinoma was the most common histological type. The median overall survival was 53.4 months, with 1-, 2- and 5-year survival rates of 90.5%, 73.9% and 43.4%, respectively. Overall survival rates of breast (67.6 months, 95% CI 56.4-78.9), urological (63.3 months, 95% CI 55.8-70.8), and colorectal (50.8 months, 95% CI 44.2-57.4) tumors were higher as compared with other malignancies (20 months, 95% CI 11.2-28.8 months) (p < 0.001). Patients with Karnofsky score (KPS) of 90 and 100 showed a significantly better survival than those with impaired performance status (p = 0.001)., Conclusion: SBRT appears to be well tolerated and safe approach in oligometastatic patients. Patients with good performance status and with primary breast, urological and colorectal cancer have higher OS compared with other malignancies. More studies are necessary to evaluate the prognostic factors in oligometastatic disease (OMD) in order to select patients who could benefit more from this therapeutic approach., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Incidence rates of SARS-CoV-2 infections in low-resource communities can inform vaccination strategies and non-pharmaceutical interventions (NPIs). Our objective was to estimate incidence over four epidemic waves in a slum in Rio de Janeiro, a proxy for economically deprived areas in the Global South., Methods: Prospective cohort of children and household contacts screened for SARS-CoV-2 by PCR and serology (IgG). The incidence density of PCR positive infections estimated for each wave - the first wave, Zeta, Gamma and Delta - was compared to an index combining NPIs and vaccination coverage., Findings: 718 families and 2501 individuals were enrolled, from May 2020 to November 2021. The incidence density of SARS-CoV-2 infection due to the first wave was 2, 3 times that of the other waves. The incidence among children was lower than that of older participants, except in later waves, when vaccination of the elderly reached 90%. Household agglomeration was significantly associated with incidence only during the first wave., Interpretation: The incidence of infection greatly exceeded rates reported in similar cohorts. The observed reduction in incidence in the elderly during the Delta variant wave, in spite of the rollback of NPIs, can be attributed to increased vaccine coverage. The high incidence in young people reinforces the importance of vaccination in this age group, a policy that has yet to receive the full support of some sectors of society., Funding: UK Medical Research Council, Foundation for the Advancement of Science of the State of Rio de Janeiro, National Council for Scientific and Technological Development., Competing Interests: None declared., (© 2022 Published by Elsevier Ltd.)

Objectives: To investigate the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a vulnerable population of children and their household contacts., Methods: SARS-CoV-2 reverse transcription polymerase chain reaction assays and coronavirus disease 2019 (COVID-19) immunoglobulin G serology tests were performed in children and their household contacts after enrollment during primary health care clinic visits. Participants were followed prospectively with subsequent specimens collected through household visits in Manguinhos, an impoverished urban slum (a favela) in Rio de Janeiro at 1, 2, and 4 weeks and quarterly post study enrollment., Results: Six hundred sixty-seven participants from 259 households were enrolled from May to September 2020. This included 323 children (0-13 years), 54 adolescents (14-19 years), and 290 adults. Forty-five (13.9%) children had positive test results for SARS-CoV-2 polymerase chain reaction. SARS-CoV-2 infection was most frequent in children aged <1 year (25%) and children aged 11 to 13 years (21%). No child had severe COVID-19 symptoms. Asymptomatic infection was more prevalent in children aged <14 years than in those aged ≥14 years (74.3% and 51.1%, respectively). All children ( n = 45) diagnosed with SARS-CoV-2 infection had an adult contact with evidence of recent infection., Conclusions: In our setting, children do not seem to be the source of SARS-CoV-2 infection and most frequently acquire the virus from adults. Our findings suggest that, in settings such as ours, schools and child care potentially may be reopened safely if adequate COVID-19 mitigation measures are in place and staff are appropriately immunized., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: Accurate serological assays are urgently needed to support public health responses to Zika virus (ZIKV) infection with its potential to cause foetal damage during pregnancy. Current flavivirus serology for ZIKV infections lacks specificity due to cross-reacting antibodies from closely related other flaviviruses. In this study, we evaluated novel serological tests for accurate ZIKV IgG detection., Methods: Our ELISAs are based on immune complex binding. The high specificity is achieved by the simultaneous incubation of labelled ZIKV antigen and unlabelled flavivirus homolog protein competitors. Two assays were validated with a panel of 406 human samples from PCR-confirmed ZIKV patients collected in Brazil (n = 154), healthy blood donors and other infections from Brazil, Europe, Canada and Colombia (n = 252)., Results: The highest specificity (100% [252/252, 95% confidence interval (CI) 98.5-100.0]) was shown by the ZIKV ED3 ICB ELISA using the ED3 antigen of the ZIKV envelope. A similar test using the NS1 antigen (ZIKV NS1 ICB ELISA) was slightly less specific (92.1% [232/252, 95% CI 88.0-95.1]). The commercial Euroimmun ZIKV ELISA had a specificity of only 82.1% (207/252, 95% CI 76.8-86.7). Sensitivity was high (93-100%) from day 12 after onset of symptoms in all three tests. Seroprevalence of ZIKV IgG was analysed in 87 samples from Laos (Asia) confirming that the ED3 ELISA showed specific reactions in other populations., Conclusions: The novel ED3 ICB ELISA will be useful for ZIKV-specific IgG detection for seroepidemiological studies and serological diagnosis for case management in travellers and in countries where other flavivirus infections are co-circulating., (© 2020 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

The Chikungunya virus infection in Brazil has raised several concerns due to the rapid dissemination of the virus and its association with several clinical complications. Nevertheless, there is limited information about the genomic epidemiology of CHIKV circulating in Brazil from surveillance studies. Thus, to better understand its dispersion dynamics in Rio de Janeiro (RJ), one of the most affected states during the 2016-2019 epidemic waves, we generated 23 near-complete genomes of CHIKV isolates from two main cities located in the metropolitan mesoregion, obtained directly from clinical samples. Our phylogenetic reconstructions suggest the 2019-CHIKV-ECSA epidemic in RJ state was characterized by the co-circulation of multiple clade (clade A and B), highlighting that two independent introduction events of CHIKV-ECSA into RJ state have occurred between 2016-2019, both mediated from the northeastern region. Interestingly, we identified that the two-clade displaying eighteen characteristic amino acids changes among structural and non-structural proteins. Our findings reinforce that genomic data can provide information about virus genetic diversity and transmission dynamics, which might assist in the arbovirus epidemics establishing of an effective surveillance framework.

Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I 2 =19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I 2 =0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I 2 =0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I 2 =0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I 2 =74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Counotte MJ et al.)

The emergence of chikungunya virus (CHIKV) has raised serious concerns due to the virus' rapid dissemination into new geographic areas and the clinical features associated with infection. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. Our phylogenetic reconstructions indicated the circulation of the East-Central-South-African (ECSA) lineage in Rio de Janeiro. Time-measured phylogenetic analysis combined with CHIKV notified case numbers revealed the ECSA lineage was introduced in Rio de Janeiro around June 2015 (95% Bayesian credible interval: May to July 2015) indicating the virus was circulating unnoticed for 5 months before the first reports of CHIKV autochthonous transmissions in Rio de Janeiro, in November 2015. These findings reinforce that continued genomic surveillance strategies are needed to assist in the monitoring and understanding of arbovirus epidemics, which might help to attenuate public health impact of infectious diseases., Competing Interests: The authors have declared that no competing interests exist.

Detection and sequencing of chikungunya virus (CHIKV) genome was performed using a combination of a modified reverse transcription loop-mediated isothermal amplification (RT-LAMP) method and a MinION sequencer. We developed the protocol for drying all the reagents for the RT-LAMP in a single reaction tube. Using this system, the CHIKV genome was effectively amplified under isothermal conditions, and used as a template for MinION sequencing with a laptop computer. Our in-house RT-LAMP method and MinION sequencing system were also validated with RNAs and serum samples from recent outbreaks of CHIKV patients in Brazil. The obtained sequence data confirmed the CHIKV outbreaks and identified the genotype. In summary, our established inexpensive on-site genome detection and sequencing system is applicable for both diagnosis of CHIKV infected patients and genotyping of the CHIKV virus in future outbreak in remote areas., Competing Interests: The authors have declared that no competing interests exist.

The burden of arboviruses in the Americas is high and may result in long-term sequelae with infants disabled by Zika virus infection (ZIKV) and arthritis caused by infection with Chikungunya virus (CHIKV). We aimed to identify environmental drivers of arbovirus epidemics to predict where the next epidemics will occur and prioritize municipalities for vector control and eventual vaccination. We screened sera and urine samples (n = 10,459) from residents of 48 municipalities in the state of Rio de Janeiro for CHIKV, dengue virus (DENV), and ZIKV by molecular PCR diagnostics. Further, we assessed the spatial pattern of arbovirus incidence at the municipal and neighborhood scales and the timing of epidemics and major rainfall events. Lab-confirmed cases included 1,717 infections with ZIKV (43.8%) and 2,170 with CHIKV (55.4%) and only 29 (<1%) with DENV. ZIKV incidence was greater in neighborhoods with little access to municipal water infrastructure (r = -0.47, p = 1.2x10-8). CHIKV incidence was weakly correlated with urbanization (r = 0.2, p = 0.02). Rains began in October 2015 and were followed one month later by the largest wave of ZIKV epidemic. ZIKV cases markedly declined in February 2016, which coincided with the start of a CHIKV outbreak. Rainfall predicted ZIKV and CHIKV with a lead time of 3 weeks each time. The association between rainfall and epidemics reflects vector ecology as the larval stages of Aedes aegypti require pools of water to develop. The temporal dynamics of ZIKV and CHIKV may be explained by the shorter incubation period of the viruses in the mosquito vector; 2 days for CHIKV versus 10 days for ZIKV.

Objective: Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected persons., Design: Prospective, randomized, and open-label noninferiority trial., Setting: The United States , Brazil, Spain, Peru, Canada, and Hong Kong., Participants: HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases., Intervention: 3HP versus 9H., Main Outcome Measures: The effectiveness endpoint was tuberculosis; the noninferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation because of adverse drug reaction., Results: Median baseline CD4 cell counts were 495 (IQR 389-675) and 538 (IQR 418-729) cells/μl in the 3HP and 9H arms, respectively (P = 0.09). In the modified intention-to-treat analysis, there were two tuberculosis cases among 206 persons [517 person-years (p-y) of follow-up] in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01 versus 3.50% in the 3HP and 9H arms, respectively (rate difference: -2.49%; upper bound of the 95% confidence interval of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P < 0.001), and drug discontinuation because of an adverse drug reaction was similar (3 vs. 4%; P = 0.79) in 3HP and 9H, respectively., Conclusion: Among HIV-infected persons with median CD4 cell count of approximately 500 cells/μl, 3HP was as effective and safe for treatment of latent Mycobacterium tuberculosis infection as 9H, and better tolerated.

Background: The incidence of microcephaly in Brazil in 2015 was 20 times higher than in previous years. Congenital microcephaly is associated with genetic factors and several causative agents. Epidemiological data suggest that microcephaly cases in Brazil might be associated with the introduction of Zika virus. We aimed to detect and sequence the Zika virus genome in amniotic fluid samples of two pregnant women in Brazil whose fetuses were diagnosed with microcephaly., Methods: In this case study, amniotic fluid samples from two pregnant women from the state of Paraíba in Brazil whose fetuses had been diagnosed with microcephaly were obtained, on the recommendation of the Brazilian health authorities, by ultrasound-guided transabdominal amniocentesis at 28 weeks' gestation. The women had presented at 18 weeks' and 10 weeks' gestation, respectively, with clinical manifestations that could have been symptoms of Zika virus infection, including fever, myalgia, and rash. After the amniotic fluid samples were centrifuged, DNA and RNA were extracted from the purified virus particles before the viral genome was identified by quantitative reverse transcription PCR and viral metagenomic next-generation sequencing. Phylogenetic reconstruction and investigation of recombination events were done by comparing the Brazilian Zika virus genome with sequences from other Zika strains and from flaviviruses that occur in similar regions in Brazil., Findings: We detected the Zika virus genome in the amniotic fluid of both pregnant women. The virus was not detected in their urine or serum. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, Treponema pallidum, and parvovirus B19 were all negative. After sequencing of the complete genome of the Brazilian Zika virus isolated from patient 1, phylogenetic analyses showed that the virus shares 97-100% of its genomic identity with lineages isolated during an outbreak in French Polynesia in 2013, and that in both envelope and NS5 genomic regions, it clustered with sequences from North and South America, southeast Asia, and the Pacific. After assessing the possibility of recombination events between the Zika virus and other flaviviruses, we ruled out the hypothesis that the Brazilian Zika virus genome is a recombinant strain with other mosquito-borne flaviviruses., Interpretation: These findings strengthen the putative association between Zika virus and cases of microcephaly in neonates in Brazil. Moreover, our results suggest that the virus can cross the placental barrier. As a result, Zika virus should be considered as a potential infectious agent for human fetuses. Pathogenesis studies that confirm the tropism of Zika virus for neuronal cells are warranted., Funding: Consellho Nacional de Desenvolvimento e Pesquisa (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To describe the access to the interventions for the prevention of Human Immunodeficiency Virus (HIV) mother to child transmission and mother to child transmission rates in the outskirts of Rio de Janeiro, from 1999 to 2009., Methods: This is a retrospective cohort study. Prevention of HIV mother to child transmission interventions were accessed and mother to child transmission rates were calculated., Results: The study population is young (median: 26 years; interquartile range: 22.0-31.0), with low monthly family income (40.4% up to one Brazilian minimum wage) and schooling (62.1% less than 8 years). Only 47.1% (n=469) knew the HIV status of their partner; of these women, 39.9% had an HIV-seronegative partner. Among the 1259 newborns evaluated, access to the antenatal, intrapartum and postpartum prevention of HIV mother to child transmission components occurred in 59.2%, 74.2%, and 97.5% respectively; 91.0% of the newborns were not breastfed. Overall 52.7% of the newborns have benefited from all the recommended interventions. In subsequent pregnancies (n=289), 67.8% of the newborns received the full package of interventions. The overall rate of HIV vertical transmission was 4.7% and the highest annual rate occurred in 2005 (7.4%), with no definite trend in the period., Conclusions: Access to the full package of interventions for the prevention of HIV vertical transmission was low, with no significant trend of improvement over the years. The vertical transmission rates observed were higher than those found in reference services in the municipality of Rio de Janeiro and in the richest regions of the country., (Copyright © 2014. Published by Elsevier Editora Ltda.)

A general and efficient procedure for the synthesis of 2,3-disubstituted 5-azaindoles through the palladium-catalyzed heteroannulation of 4-acetamido-3-iodopyridines and diaryl-, dialkyl-, or arylalkylalkynes is described along with a study of the reaction regioselectivity. The preparation of 2-monosubstituted 5-azaindoles via sila-Sonogashira/5-endo cyclization is also reported. These methods allowed us to prepare 36 diversely substituted 5-azaindoles in good yields.

A general and efficient procedure for the synthesis of functionalized 5-azaindoles through the catalyzed heteroannulation of 4-acetamido-3-iodopyridines and diarylalkynes is described. The reaction allows the preparation of a variety of substituted 2,3-diaryl-5-azaindoles in good to excellent yields.

The efficient cleavage of the N-O bond of some nitroso Diels-Alder cycloadducts has been achieved in mild conditions, mediated either by 2,2-dimethyl-1,3-dioxan-5-one or 1,3-dithiolane-2-carboxaldehyde. These new and purely organic conditions allow an excellent tolerance with respect to many functional groups that would have been affected by previous reductive cleavage conditions.

The crystal structures of 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl benzoate, C(13)H(15)NO(5), (I), 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate, C(13)H(14)ClNO(5), (II), and 5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate, C(11)H(11)NO(5), (III), have been determined in order to gain insight into the conformational preference of alpha-benzoyloxynitroso. Unfavourable 1,3-diaxial interactions force (I) and (II) to crystallize in the 2,5 twist-boat conformation, whereas compound (III), lacking this destabilizing interaction, crystallizes in the chair conformation.

[reaction: see text] Strained bicyclic 3,6-dihydro-1,2-oxazine is a reactive substrate in domino metathesis with an external alkene. This general transformation leads to isoxazolo[2,3-a]pyridin-7-one, a versatile scaffold combining chemical functions that could be selectively oxidized or reduced. The synthetic relevance of these domino metathesis products is demonstrated by a straightforward synthesis of a quinolizinone.

The Diels-Alder cycloadditions of the alpha-acetoxynitroso dienophile in water are reported. The rapid and high yielding synthesis of structurally diverse 3,6-dihydro-1,2-oxazines complements the straightforward elaboration of aminoalcohols obtained from the alpha-acetoxynitroso derivative in anhydrous medium. A rationale for this solvent-dependent product distribution is proposed.