Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon.

OBJECTIVE: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. METHODS: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. RESULTS: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. CONCLUSION: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox: A Randomized Clinical Trial.

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage. Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations. Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022. Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point. Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction. Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed. Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon

ABSTRACT Objective: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. Methods: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. Results: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. Conclusion: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Inflammatory Profile Associated with Secondary Infection from Bothrops atrox Snakebites in the Brazilian Amazon.

Bothrops snakebite envenomation (SBE) is consider an important health problem in Brazil, where Bothrops atrox is mainly responsible in the Brazilian Amazon. Local effects represent a relevant clinical issue, in which inflammatory signs and symptoms in the bite site represent a potential risk for short and long-term disabilities. Among local complications, secondary infections (SIs) are a common clinical finding during Bothrops atrox SBE and are described by the appearance of signs such as abscess, cellulitis or necrotizing fasciitis in the affected site. However, the influence of SI in the local events is still poorly understood. Therefore, the present study describes for the first time the impact of SBE wound infection on local manifestations and inflammatory response from patients of Bothrops atrox SBE in the Brazilian Amazon. This was an observational study carried out at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus (Brazil), involving victims of Bothrops SBE. Clinical and laboratorial data were collected along with blood samples for the quantification of circulating cytokines and chemokines before antivenom administrations (T0) and 24 h (T1), 48 h (T2), 72 h (T3) and 7 days after (T4). From the 94 patients included in this study, 42 presented SI (44.7%) and 52 were without SI (NSI, 55.3%). Patients classified as moderate envenoming presented an increased risk of developing SI (OR = 2.69; CI 95% = 1.08-6.66, p = 0.033), while patients with bites in hands showed a lower risk (OR = 0.20; CI 95% = 0.04-0.96, p = 0.045). During follow-up, SI patients presented a worsening of local temperature along with a sustained profile of edema and pain, while NSI patients showed a tendency to restore and were highlighted in patients where SI was diagnosed at T2. As for laboratorial parameters, leukocytes, erythrocyte sedimentation ratio, fibrinogen and C-reactive protein were found increased in patients with SI and more frequently in patients diagnosed with SI at T3. Higher levels of circulating IL-2, IL-10, IL-6, TNF, INF-γ and CXCL-10 were observed in SI patients along with marked correlations between these mediators and IL-4 and IL-17, showing a plurality in the profile with a mix of Th1/Th2/Th17 response. The present study reports for the first time the synergistic effects of local infection and envenoming on the inflammatory response represented by local manifestations, which reflected on laboratorial parameters and inflammatory mediators and thus help improve the clinical management of SI associated to Bothrops SBE.

Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone.

Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1ß) were quantified using cytometric bead array. Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1ß and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.

Antigen-Specific Antibody Signature Is Associated with COVID-19 Outcome.

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.

Pediatric central nervous system infections in the Amazon: clinical and laboratory profiles.

Background: Central nervous system (CNS) infections are important causes of mortality and morbidity in children, and they are related to severe problems such as hearing loss, neurological sequelae, and death. The objective was to describe clinical and laboratory exam profiles of children who were diagnosed with CNS infections. Methods: We conducted a cross-sectional study based on medical records, which included pediatric patients aged from 3 months to 15 years, with a clinical suspicion of CNS infection between January 2014 to December 2019. The pathogens were confirmed in cerebrospinal fluid (CSF) samples using Gram staining, cell culture, molecular diagnostics (PCR and qPCR), and serology. Results: Out of the 689 enrolled patients, 108 (15.6%) had laboratory-confirmed infections in CSF. The most common bacterial pathogens isolated from the culture were Neisseria meningitidis serogroup C in 19, Streptococcus pneumoniae in 11, and Haemophilus influenzae in seven samples. The viruses identified were Enterovirus, Cytomegalovirus, Varicella-zoster virus, Epstein-Barr virus, and arbovirus. No patient was found to be positive for Herpes simplex virus 1 and 2. Patients with viral infections showed altered levels of consciousness (p = 0.001) when compared to bacterial infections. Conclusion: This study shows the presence of important vaccine-preventable pathogens, and different families of viruses causing CNS infections in the pediatric patients of Manaus.

Prediction of malaria using deep learning models: A case study on city clusters in the state of Amazonas, Brazil, from 2003 to 2018.

BACKGROUND: Malaria is curable. Nonetheless, over 229 million cases of malaria were recorded in 2019, along with 409,000 deaths. Although over 42 million Brazilians are at risk of contracting malaria, 99% percent of all malaria cases in Brazil are located in or around the Amazon rainforest. Despite declining cases and deaths, malaria remains a major public health issue in Brazil. Accurate spatiotemporal prediction of malaria propagation may enable improved resource allocation to support efforts to eradicate the disease. METHODS: In response to calls for novel research on malaria elimination strategies that suit local conditions, in this study, we propose machine learning (ML) and deep learning (DL) models to predict the probability of malaria cases in the state of Amazonas. Using a dataset of approximately 6 million records (January 2003 to December 2018), we applied k-means clustering to group cities based on their similarity of malaria incidence. We evaluated random forest, long-short term memory (LSTM) and dated recurrent unit (GRU) models and compared their performance. RESULTS: The LSTM architecture achieved better performance in clusters with less variability in the number of cases, whereas the GRU presents better results in clusters with high variability. Although Diebold-Mariano testing suggested that both the LSTM and GRU performed comparably, GRU can be trained significantly faster, which could prove advantageous in practice. CONCLUSIONS: All models showed satisfactory accuracy and strong performance in predicting new cases of malaria, and each could serve as a supplemental tool to support regional policies and strategies.

Metabolomic Profiling of Plasma Reveals Differential Disease Severity Markers in COVID-19 Patients.

The severity, disabilities, and lethality caused by the coronavirus 2019 (COVID-19) disease have dumbfounded the entire world on an unprecedented scale. The multifactorial aspect of the infection has generated interest in understanding the clinical history of COVID-19, particularly the classification of severity and early prediction on prognosis. Metabolomics is a powerful tool for identifying metabolite signatures when profiling parasitic, metabolic, and microbial diseases. This study undertook a metabolomic approach to identify potential metabolic signatures to discriminate severe COVID-19 from non-severe COVID-19. The secondary aim was to determine whether the clinical and laboratory data from the severe and non-severe COVID-19 patients were compatible with the metabolomic findings. Metabolomic analysis of samples revealed that 43 metabolites from 9 classes indicated COVID-19 severity: 29 metabolites for non-severe and 14 metabolites for severe disease. The metabolites from porphyrin and purine pathways were significantly elevated in the severe disease group, suggesting that they could be potential prognostic biomarkers. Elevated levels of the cholesteryl ester CE (18:3) in non-severe patients matched the significantly different blood cholesterol components (total cholesterol and HDL, both p < 0.001) that were detected. Pathway analysis identified 8 metabolomic pathways associated with the 43 discriminating metabolites. Metabolomic pathway analysis revealed that COVID-19 affected glycerophospholipid and porphyrin metabolism but significantly affected the glycerophospholipid and linoleic acid metabolism pathways (p = 0.025 and p = 0.035, respectively). Our results indicate that these metabolomics-based markers could have prognostic and diagnostic potential when managing and understanding the evolution of COVID-19.

Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil.

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we did not find an increased incidence of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sublineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting more infectious variants or antibody evasion mutations is expected to increase. IMPORTANCE The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress. Our results showed that the answer behind that was a new generation of Gamma-like viruses, which emerged locally carrying mutations that made it more transmissible and more capable of spreading, partially evading prior immunity triggered by natural infections or vaccines. With thousands of new cases daily, the current pandemics scenario suggests that SARS-CoV-2 will continue to evolve and efforts to reduce the number of infected subjects, including global equitable access to COVID-19 vaccines, are mandatory. Thus, until the end of pandemics, the SARS-CoV-2 genomic surveillance will be an essential tool to better understand the drivers of the viral evolutionary process.

Prediction of malaria using deep learning models: A case study on city clusters in the state of Amazonas, Brazil, from 2003 to 2018

ABSTRACT Background: Malaria is curable. Nonetheless, over 229 million cases of malaria were recorded in 2019, along with 409,000 deaths. Although over 42 million Brazilians are at risk of contracting malaria, 99% percent of all malaria cases in Brazil are located in or around the Amazon rainforest. Despite declining cases and deaths, malaria remains a major public health issue in Brazil. Accurate spatiotemporal prediction of malaria propagation may enable improved resource allocation to support efforts to eradicate the disease. Methods: In response to calls for novel research on malaria elimination strategies that suit local conditions, in this study, we propose machine learning (ML) and deep learning (DL) models to predict the probability of malaria cases in the state of Amazonas. Using a dataset of approximately 6 million records (January 2003 to December 2018), we applied k-means clustering to group cities based on their similarity of malaria incidence. We evaluated random forest, long-short term memory (LSTM) and dated recurrent unit (GRU) models and compared their performance. Results: The LSTM architecture achieved better performance in clusters with less variability in the number of cases, whereas the GRU presents better results in clusters with high variability. Although Diebold-Mariano testing suggested that both the LSTM and GRU performed comparably, GRU can be trained significantly faster, which could prove advantageous in practice. Conclusions: All models showed satisfactory accuracy and strong performance in predicting new cases of malaria, and each could serve as a supplemental tool to support regional policies and strategies.

Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series.

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.

Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with comorbidities associated with severe COVID-19 display higher levels of ACE2 in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of ACE2. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of ACE2 in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased ACE2 expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.

Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. METHODS: We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. FINDINGS: For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. INTERPRETATION: Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. FUNDING: Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas.

#StayHome: Monitoring and benchmarking social isolation trends in Caruaru and the Região Metropolitana do Recife during the COVID-19 pandemic.

This technical report presents information related to the Social Isolation Index (SII) of the city of Caruaru, Pernambuco, Brazil. The data was provided by In Loco, a technology startup that has collected the movement of around 60 million Brazilians through cell phone location.

Correction: Social, demographic, health care and co-morbidity predictors of tuberculosis mortality in Amazonas, Brazil: a multiple cause of death approach.

[This corrects the article DOI: 10.1371/journal.pone.0218359.].

Social, demographic, health care and co-morbidity predictors of tuberculosis mortality in Amazonas, Brazil: a multiple cause of death approach.

OBJECTIVES: Estimate TB mortality rates, catalogue multiple causes on death certificates in which TB was reported and identify predictors of TB from reporting on death certificates in the State of Amazonas, Brazil, based on a multiple cause of death approach. METHODS: The death records of residents in the Amazonas state between 2006-2014 were analyzed and separated into three categories: TB not reported on the death certificate (TBNoR), TB reported as the underlying cause of death (TBUC) and TB reported as an associated cause of death (TBAC). Age standardized annual mortality rates for TBUC, TBAC and with TB reported (TBUC plus TBAC) were estimated for the State of Amazonas using the direct standardization method and World Health Organization 2000-2025 standard population. Mortality odds ratios (OR) for reporting of TBUC and TBAC were estimated using multinomial logistic regression. RESULTS: Age standardized annual TBUC and TBAC mortality rates ranged between 5.9-7.8/105 and 2.7-4.0/105, respectively. TBUC was associated with being a resident in the State capital (OR = 0.66), of female gender (OR = 0.87), having an education level of 8 to 11, or 12 or more school years (OR = 0.67 and 0.50 respectively), non-white race/skin color (OR = 1.38) and place of death reported as in the State capital (OR = 1.69). TBAC was related to the triennium in which death occurred (OR = 1.21 and 1.22 for the years 2009-2011 and 2012-2014 respectively), age (OR = 36.1 and 16.5 for ages 15-39 and 40-64 years respectively) and when death occurred in the State capital (OR = 5.8). CONCLUSIONS: TBUC was predominantly associated with predictors of unfavorable socioeconomic conditions and health care access constraints, whereas TBAC was mainly related to ages which were typical of high HIV disease incidence.

Fatores associados à mortalidade por causas inespecíficas e mal definidas no estado do Amazonas, Brasil, de 2006 a 2012 / Factors associated with unspecified and ill-defined causes of death in the State of Amazonas, Brazil, from 2006 to 2012

Resumo Objetivou-se investigar fatores associados à mortalidade por causas inespecíficas e mal definidas no estado do Amazonas (AM). Desenvolveu-se um estudo seccional incluindo 90.439 registros de óbitos não fetais, com residência e ocorrência no AM entre 2006 e 2012. Foram estimadas razões de chances de causas inespecíficas e mal definidas por meio de regressão logística multinomial hierárquica. A proporção de causas mal definidas e inespecíficas foi, respectivamente, 16,6% e 9,1%. A ocorrência de causas mal definidas diminuiu ao longo dos anos e a de causas inespecíficas somente no último biênio. As causas inespecíficas associaram-se com residência e ocorrência do óbito fora da capital, via pública, sexo feminino, dos 10 aos 49 anos, cor parda e quando atestadas por legistas. As causas mal definidas associaram-se com residência e ocorrência fora da capital, em domicílios, a partir de 40 anos, cor não branca, não ser solteiro, baixa escolaridade, assistência médica e falta de informação sobre o atestante. A mortalidade por causas mal definidas e inespecíficas no AM declinou entre 2006 e 2012, associando-se às dimensões espacial e temporal, fatores demográficos, socioeconômicos e à assistência médica na ocasião do óbito.

Abstract This study aimed to investigate factors associated with unspecified and ill-defined causes of death in the State of Amazonas (AM), Brazil. This is a cross-sectional study on 90,439 non-fetal deaths of residents in AM from 2006 to 2012. The hierarchical multinomial logistic model estimated odds ratios of unspecified and ill-defined causes of death. Ill-defined and unspecified causes of death proportional mortality was, respectively, 16.6% and 9.1%. Ill-defined causes showed a decreasing trend over the years, while unspecified causes only decreased in the last two years. Unspecified causes of death were associated with residence and death outside the capital, public roads, female gender, age group 10-49 years, brown skin color and when certified by forensic doctors. Ill-defined causes of death were associated with residence and occurrence outside capital, at home, ages 40 years and older, non-whites, not being single, low schooling, under medical care and when examiner was unknown. Ill-defined and unspecified cause mortality in the State of Amazonas decreased between 2006 and 2012 in AM and was associated with space and time, demographic and socioeconomic factors and medical care at the moment of death.

Factors associated with unspecified and ill-defined causes of death in the State of Amazonas, Brazil, from 2006 to 2012. / Fatores associados à mortalidade por causas inespecíficas e mal definidas no estado do Amazonas, Brasil, de 2006 a 2012.

This study aimed to investigate factors associated with unspecified and ill-defined causes of death in the State of Amazonas (AM), Brazil. This is a cross-sectional study on 90,439 non-fetal deaths of residents in AM from 2006 to 2012. The hierarchical multinomial logistic model estimated odds ratios of unspecified and ill-defined causes of death. Ill-defined and unspecified causes of death proportional mortality was, respectively, 16.6% and 9.1%. Ill-defined causes showed a decreasing trend over the years, while unspecified causes only decreased in the last two years. Unspecified causes of death were associated with residence and death outside the capital, public roads, female gender, age group 10-49 years, brown skin color and when certified by forensic doctors. Ill-defined causes of death were associated with residence and occurrence outside capital, at home, ages 40 years and older, non-whites, not being single, low schooling, under medical care and when examiner was unknown. Ill-defined and unspecified cause mortality in the State of Amazonas decreased between 2006 and 2012 in AM and was associated with space and time, demographic and socioeconomic factors and medical care at the moment of death.

Objetivou-se investigar fatores associados à mortalidade por causas inespecíficas e mal definidas no estado do Amazonas (AM). Desenvolveu-se um estudo seccional incluindo 90.439 registros de óbitos não fetais, com residência e ocorrência no AM entre 2006 e 2012. Foram estimadas razões de chances de causas inespecíficas e mal definidas por meio de regressão logística multinomial hierárquica. A proporção de causas mal definidas e inespecíficas foi, respectivamente, 16,6% e 9,1%. A ocorrência de causas mal definidas diminuiu ao longo dos anos e a de causas inespecíficas somente no último biênio. As causas inespecíficas associaram-se com residência e ocorrência do óbito fora da capital, via pública, sexo feminino, dos 10 aos 49 anos, cor parda e quando atestadas por legistas. As causas mal definidas associaram-se com residência e ocorrência fora da capital, em domicílios, a partir de 40 anos, cor não branca, não ser solteiro, baixa escolaridade, assistência médica e falta de informação sobre o atestante. A mortalidade por causas mal definidas e inespecíficas no AM declinou entre 2006 e 2012, associando-se às dimensões espacial e temporal, fatores demográficos, socioeconômicos e à assistência médica na ocasião do óbito.

Do climate changes alter the distribution and transmission of malaria? Evidence assessment and recommendations for future studies.

Malaria, a mosquito-borne infectious disease, is considered a significant global health burden. Climate changes or different weather conditions may impact infectious diseases, specifically those transmitted by insect vectors and contaminated water. Based on the current predictions for climate change associated with the increase in carbon dioxide concentrations in the atmosphere and the increase in atmospheric temperature, the Intergovernmental Panel on Climate Change predicts that in 2050, malaria may threaten some previously unexposed areas worldwide and cause a 50% higher probability of malaria cases. Climate-based distribution models of malaria depict an increase in the geographic distribution of the disease as global environmental temperatures and conditions worsen. Researchers have studied the influence of changes in climate on the prevalence of malaria using different mathematical models that consider different variables and predict the conditions for malaria distribution. In this context, we conducted a mini-review to elucidate the important aspects described in the literature on the influence of climate change in the distribution and transmission of malaria. It is important to develop possible risk management strategies and enhance the surveillance system enhanced even in currently malaria-free areas predicted to experience malaria in the future.