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Background: The city of Manaus, Brazil, has seen two collapses of the health system due to the COVID-19 pandemic. We report anti-SARS-CoV-2 nucleocapsid IgG antibody seroconversion rates and associated risk factors in Manaus residents before the second wave of the epidemic in Brazil. Methods: A convenience sample of adult (aged ≥18 years) residents of Manaus was recruited through online and university website advertising into the DETECTCoV-19 study cohort. The current analysis of seroconversion included a subgroup of DETECTCoV-19 participants who had at least two serum sample collections separated by at least 4 weeks between Aug 19 and Oct 2, 2020 (visit 1), and Oct 19 and Nov 27, 2020 (visit 2). Those who reported (or had no data on) having a COVID-19 diagnosis before visit 1, and who were positive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at visit 1 were excluded. Using an in-house ELISA, the reactivity index (RI; calculated as the optical density ratio of the sample to the negative control) for serum anti-SARS-CoV-2 nucleocapsid IgG antibodies was measured at both visits. We calculated the incidence of seroconversion (defined as RI values ≤1·5 at visit 1 and ≥1·5 at visit 2, and a ratio >2 between the visit 2 and visit 1 RI values) during the study period, as well as incidence rate ratios (IRRs) through cluster-corrected and adjusted Poisson regression models to analyse associations between seroconversion and variables related to sociodemographic characteristics, health access, comorbidities, COVID-19 exposure, protective behaviours, and symptoms. Findings: 2496 DETECTCoV-19 cohort participants returned for a follow-up visit between Oct 19 and Nov 27, 2020, of whom 204 reported having COVID-19 before the first visit and 24 had no data regarding previous disease status. 559 participants were seropositive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at baseline. Of the remaining 1709 participants who were seronegative at baseline, 71 did not meet the criteria for seroconversion and were excluded from the analyses. Among the remaining 1638 participants who were seronegative at baseline, 214 showed seroconversion at visit 2. The seroconversion incidence was 13·06% (95% CI 11·52–14·79) overall and 6·78% (5·61–8·10) for symptomatic seroconversion, over a median follow-up period of 57 days (IQR 54–61). 48·1% of seroconversion events were estimated to be asymptomatic. The sample had higher proportions of affluent and higher-educated people than those reported for the Manaus city population. In the fully adjusted and corrected model, risk factors for seroconversion before visit 2 were having a COVID-19 case in the household (IRR 1·49 [95% CI 1·21–1·83]), not wearing a mask during contact with a person with COVID-19 (1·25 [1·09–1·45]), relaxation of physical distancing (1·31 [1·05–1·64]), and having flu-like symptoms (1·79 [1·23–2·59]) or a COVID-19 diagnosis (3·57 [2·27–5·63]) between the first and second visits, whereas working remotely was associated with lower incidence (0·74 [0·56–0·97]). Interpretation: An intense infection transmission period preceded the second wave of COVID-19 in Manaus. Several modifiable behaviours increased the risk of seroconversion, including non-compliance with non-pharmaceutical interventions measures such as not wearing a mask during contact, relaxation of protective measures, and non-remote working. Increased testing in high-transmission areas is needed to provide timely information about ongoing transmission and aid appropriate implementation of transmission mitigation measures. Funding: Ministry of Education, Brazil; Fundação de Amparo à Pesquisa do Estado do Amazonas; Pan American Health Organization (PAHO)/WHO. World Health Organization Revisión por pares

Background: Twice city of Manaus located in the Brazilian rainforest, has experienced a health system collapse due to the SARS-CoV-2 pandemic. However, little is known about which groups among the general population have been more affected. In this report, we present the overall prevalence of SARS-CoV-2 infection and associated factors from the DETECTCoV-19 cohort. Methods: A convenience sampling strategy via online advertising recruited 3046 adults. Sociodemographic characteristics, COVID-19-related symptoms, COVID-19 testing, self-medication and prescribed medications were recorded. Serum anti-SARS-CoV-2 nucleocapsid IgG antibodies were measured with an in-house ELISA. Prevalence ratios (PR) were obtained using cluster-corrected and adjusted Poisson’s regression models. Findings: A crude positivity rate among asymptomatic and symptomatic individuals, was estimated at 29·10%, with a maximum seroprevalence of 41·53% corrected by test characteristics and an antibody decay rate of 27%. Regression models demonstrated a strong association towards marginalized low-income and vulnerable residents with limited health access. Presence of a COVID-19 case (PR 1·39, 1·24-1·57) or death (PR 2·14, 1·74-2·62) in a household increased greatly the risk of other household members acquiring infection. SARS-CoV-2 seroprevalence was higher among those who self-medicated to prevent infection (PR 1·36, 1·27-1·46). Interpretation: High SARS-CoV-2 seropositivity reveals a much burdensome scenario than estimations based on confirmed COVID-19 cases in Manaus. Overall, prevalence of SARS-CoV-2 antibody response demonstrated a disproportionate social and economic disparity among the study participants. The syndemic nature of COVID-19 in the Amazon region needs differential policies and urgent solutions to control the pandemic. Funding: Research was funded by Ministry of Education (MEC), Brazil. BBS, IVPF, ROS, ARCB and WBSS received scholarship from CAPES. DSSS, TBNM, MFF and NOC received scholarship from FAPEAM Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The research ethics committee of Federal University of Amazonas (UFAM) approved this study (CAAE:34906920·4·0000·5020) in accordance with Brazilian law

Apresentar um diagnóstico e constituir uma memória sobre a evolução da pandemia no Brasil, a partir de registros e análises de dados, sistemas de monitoramento e vigilância em saúde. É com esse intuito que o Observatório Covid-19 Fiocruz e a Editora Fiocruz publicam, em coedição, mais um e-book gratuito. Em três partes, que englobam um total de 25 capítulos, o título agrega os muitos desafios da comunidade científica brasileira - especialmente das equipes técnicas da Fiocruz - para a avaliação de cenários epidemiológicos diante da chegada do vírus Sars-CoV-2 ao país. Em um contexto que inclui dados reportados nos sistemas de vigilância epidemiológica, uso de modelos matemáticos e estatísticos, painéis de acompanhamento dos dados e sistemas de informação em saúde, o volume detalha os esforços e contribuições para a formulação de estratégias de mitigação e supressão da transmissão da doença. Este é o terceiro livro da série "Informação para Ação na Covid-19", que tem como objetivo reunir o conjunto de respostas, pesquisas e ações técnicas produzidas pela Fiocruz durante a pandemia. Com apoio da rede SciELO Livros, a iniciativa disponibiliza as obras exclusivamente em formato digital e acesso aberto.

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 Fundacao Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundacao de Vigilância em Saude do Amazonas

BackgroundSevere 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.MethodsWe 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.FindingsFor 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.InterpretationEvidence 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.FundingFundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of ManausResearch in ContextEvidence before this studyWe searched PubMed for articles published from inception of the pandemic until April 3, 2021, with no language restrictions, using the search terms “P.1” AND “vaccine” AND “SARS-CoV-2”. Additionally, we searched for “CoronaVac” AND “SARS-CoV-2”. Early studies have found plasma from convalescent COVID-19 patients and sera from vaccinated individuals have reduced neutralisation of the SARS-CoV-2 variant, Gamma or P.1, compared with strains isolated earlier in the pandemic. Pfizer BNT162b2 mRNA, Oxford-AstraZeneca ChAdOx1, and CoronaVac are the only vaccines for which such data has been published to date.No studies reported effectiveness of any vaccine on reducing the risk of infection or disease among individuals exposed to P.1 or in settings of high P.1 transmission.Added value of this studyThis study finds that vaccination with CoronaVac was 49.4% (95% CI 13.2 to 71.9) effective at preventing COVID-19 in a setting with likely high prevalence of the Gamma Variant of Concern. However, an analysis of effectiveness by dose was underpowered and failed to find significant effectiveness of the two-dose schedule of CoronaVac (estimated VE 37.1%, 95% CI -53.3 to 74.2).Implications of all the available evidenceThese findings are suggestive for the effectiveness of CoronaVac in healthcare workers in the setting of widespread P.1 transmission but must be strengthened by observational studies in other settings and populations. Based on this evidence, there is a need to implement sustained non-pharmaceutical interventions even as vaccination campaigns continue.

Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04323527

SummaryBackgroundThere is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19). Recent publications have drawn attention to the possible benefit of chloroquine (CQ). Our study aimed to comprehensively evaluate the safety and efficacy of two different CQ dosages in patients with established severe COVID-19.MethodsWe performed a parallel, double-blinded, randomized, phase IIb clinical trial, aiming to assess safety and efficacy of two different CQ dosages as adjunctive therapy of hospitalized patients with SARS in Manaus, Brazilian Amazon. Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600mg CQ twice daily for 10 days or total dose 12g); or low dose CQ (450mg for 5 days, twice daily only on the first day, or total dose 2.7g). In addition, all patients received ceftriaxone and azithromycin. This study was registered with ClinicalTrials.gov, number NCT04323527.FindingsOut of a pre-defined 440 patients sample size, 81 patients were enrolled. The high dosage CQ arm presented more QTc>500ms (18.9%), and a trend toward higher lethality (39%) than the lower dosage. Fatality rate until day 13 was 27% (95%CI=17.9-38.2%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). In 27 patients with paired samples, respiratory secretion at day 4 was negative in only six patients (22%).InterpretationPreliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm. Given the enormous global push for the use of CQ for COVID-19, results such as the ones found in this trial can provide robust evidence for updated COVID-19 patient management recommendations.FundingThis study was funded by the Government of the Amazonas State, Farmanguinhos (Fiocruz), SUFRAMA, CAPES, FAPEAM, and federal funds granted by a coalition of Brazilian senators.Research in contextEvidence before this studyBefore the CloroCovid-19 trial began, to our knowledge, there were no published reports of robust clinical studies on the safety and/or efficacy of chloroquine (CQ) and/or hydroxychloroquine (HCQ) for the treatment of COVID-19 during the recent 2020 pandemic. We searched PubMed and also MedRxiv.org (pre-print server for health sciences, without peer review), without any language restrictions and including Chinese publications, for studies published between Dec 2019 and April 5, 2020, using the search terms ‘COVID-19, coronavirus, SARS-Cov-2’. We found three non-randomized studies with limited sample sizes in which (1) HCQ use led to a decrease in SARS-Cov-2 detected in respiratory secretions five days after treatment, together with azithromycin (France, 36 patients); (2) HCQ use shortened time to clinical recovery (China, 62 patients); and (3) CQ was superior to control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, and promoting virus-negative conversion and shortening the disease course (China, 100 patients). We found no published studies comparing different dosages of CQ/HCQ and their thorough safety assessment.Added value of this studyIn a larger patient population, we found that a higher dosage of CQ for 10 days presented toxicity red flags, particularly affecting QTc prolongation. The limited sample size recruited so far does not allow to show any benefit regarding treatment efficacy, however the higher fatality associated with the higher dosage by day 13 of follow-up resulted in a premature halting of this arm. This is the first double-blinded, randomized clinical trial addressing different dosages of CQ for the treatment of severe patients with COVID-19 in the absence of a control group using placebo. Due to the impossibility of not using the drug recommended at the national level, we used historical data from the literature to infer comparisons for lethality endpoints. Follow-up until day 28 is ongoing with a larger sample size, in which long-term lethality will be better estimated.Implications of all the available evidenceThe preliminary findings from CloroCovid-19 trial suggest that the higher dosage of CQ (12 g total dose over 10 days) in COVID-19 should not be recommended because of safety concerns regarding QTc prolongation and increased lethality, in the Brazilian population, and more often in older patients in use of drugs such as azithromycin and oseltamivir, which also prolong QTc interval. Among patients randomized to the lower dosage group (5 days of treatment, total dose 2.7 g), given the limited number of patients so far enrolled, it is still not possible to estimate a clear benefit of CQ in patients with severe ARDS. Preliminary data on viral clearance in respiratory secretions in our confirmed cases are also indicative of little effect of the drug at high dosage. More studies initiating CQ prior to the onset of the severe phase of the disease are urgently needed.

BACKGROUND: The aim of this study is to describe the molecular epidemiology of Neisseria meningitidis invasive disease before the introduction of serogroup C conjugate vaccine in Amazonas State in 2010. METHODS: Meningococcal disease reported cases were investigated in Amazonas State during the period 2000 to 2010. N. meningitidis isolates (n = 196) recovered from patients were genotyped by multilocus sequence typing (MLST) and sequencing of porB, porA, fetA, fHbp, and penA. Antimicrobial susceptibility was determined using E-test. RESULTS: In the study period, 948 cases were reported; the incidence was 2.8 for the entire state and 4.8 per 100,000 in the capital of Manaus. Most meningococcal disease was caused by N. meningitidis belonging to ST-32 (72%; 141/196) or ST-103 (21%; 41/196) clonal complexes. Capsular switching (B→C) was suggested within clonal complex (cc) 32. There were 6 (3%; 6/196) strains with intermediate susceptibility to penicillin and a single strain was resistant to rifampicin. Since 2007, serogroup C strains belonging to the cc103 have predominated and case-fatality has increased. CONCLUSIONS: We demonstrate a high rate of meningococcal disease in Amazonas State, where, like other parts of Brazil, serogroup C replaced serogroup B during 2000s. These data serve as a baseline to measure impact of serogroup C conjugate vaccine introduction in 2010. This study emphasizes the need for enhanced surveillance to monitor changes in meningococcal disease trends following the introduction of meningococcal vaccines.

Background Long-lasting insecticidal nets (LLINs) are one of the main vector control strategies recommended by the World Health Organization for the control and elimination of malaria. This study aimed to evaluate the use and retention of LLINs during the 5 years of implementing an integrated control strategy in a malaria-endemic area in the Brazilian Amazon. Methods This intervention study was conducted in localities of the municipality of Barcelos, Amazonas, from 2008 to 2014. Four rural localities situated along the Padauiri River were the object of this study. Two localities (Bacabal-rio Aracá and the São Sebastião district) were used as controls. LLINs were distributed to all residents of the Padauiri River; assessments were made regarding their use and retention via a semistructured questionnaire, a household register, and direct observation during 5 years. Results Overall, 208 individuals participated in the study. In the baseline pilot study (2008), 9.9% of the subjects in the intervention group had slept with mosquito nets the previous night compared with 37.8% of the subjects in the control group. In 2010, this percentage was 43.2% in the intervention group and 50.9% in the control group. Therefore, 1 year after the implementation of the strategy, although there was an increase in the use of mosquito nets in both groups, this increase was significantly higher in the intervention group. This increase in LLINs use did not persist after 5 years of intervention. The households’ evaluation in 2014 showed that 80% of the houses in the intervention group owned at least one LLIN compared with 66% in the control group (p = 0.11); 76% of households in the intervention group owned sufficient LLINs for all family members compared with 50% in the control group (p = 0.007). Conclusions High ownership and retention of the LLINs was observed in the intervention group. At 1 year after the distribution of these LLINs, there was a significant increase in their use that was not maintained over the long term. Control strategies must be permanent; however, exploring new strategies is necessary to ensure that the knowledge acquired further modifies the attitudes and behaviours.

This study aims to analyze factors related to the occurrence of American Tegumentary Leishmaniasis in the Purus Region, based on the reporting of cases between 2001 and 2013, correlating them with livelihoods and subsistence farming in the region, and analyzing them in regards to sex, age, clinical form, occupation, diagnostic methods and seasonality. The analysis parameter which was used included all cases of American Tegumentary Leishmaniasis in each sub-region by municipality. The Purus Region, between the states of Amazonas and Acre, consists of three sub-regions: Upper, Middle, and Lower Purus. We observed that socio-environmental impacts influenced the livelihoods of the human population and that the interaction with extractive activities, especially latex and Brazil nut collecting, where the labor regime implies a long stay in the jungle, leads to socio-environmental conditions that are favorable to the contraction of American Tegumentary Leishmaniasis. During the referred period, there were 13,971 cases of American Tegumentary Leishmaniasis distributed among the sub-regions: High (12611 cases = 90.27%), Middle (1225 cases = 8.77%) and Lower (135 cases = 0.96%). Among the 22 municipalities that were studied, Rio Branco stands out with 31.6% of cases, followed by Xapuri with 12.6% and Sena Madureira with 12.5%. In the results, we highlight the high percentage (20.8%) of mucous forms; the age group from 11 to 50 (70.2%), however, 20.2% were in the age group of 1 month to 10 years of age; cases in males were 69.8%, and, in the reports examined, 43.7%. cited their occupation as extractivism. A statistically significant negative association was demonstrated between cutaneous leishmaniasis and rainfall between Purus municipalities. However, in regards to the association of cutaneous leishmaniasis for both, temperature and Municipal Human Development Index-MHDI, no significant associations were found in Purus. We concluded that American Tegumentary Leishmaniasis occurring in the Purus Region is related to two distinct aspects: the development of enterprises that extend the agricultural frontier, and a change in lifestyle, namely the extraction of wood as an occupation, which has, as a consequence, an environmental impact and creates difficulties in accessing treatment.

We report an ongoing measles outbreak in Manaus, Amazonas state, Brazil. As at 3 November 2018, 1,631 cases were confirmed corresponding to an incidence of 75.3 per 100,000 inhabitants; all five sanitary districts presented confirmed cases. Reintroduction of measles virus in Manaus is likely related to the current outbreak in Venezuela and due to recent decline in measles vaccine coverage. Given the current scenario, prevention and control measures should target individuals aged 15–29 years.

In the Brazilian Amazon, the suspected source of infection in an outbreak of acute Chagas disease involving 10 patients was Euterpe oleracea (açaí berry) juice. Patient blood and juice samples contained Trypanosoma cruzi TcIV, indicating oral transmission of the Chagas disease agent. publishersversion published

OBJECTIVES To analyze the relationship between the occurrence of dengue and ovitrap positivity and dengue egg density in two Amazonas municipalities (Brazil) in 2016. METHODS We performed a case-control study using secondary data from the dengue fever surveillance system. Ovitraps distributed regularly in the urban area of two cities were used to monitor the presence of the vector. The relationship between egg positivity, egg density and the location of dengue cases was evaluated using two approaches as follows: (i) based on the result of the nearest neighbour ovitrap and (ii) based on the results of the set of ovitraps within the influence area of 300 m from the location of each case and control. RESULTS During the study period, 229 confirmed cases of dengue fever were reported in Tabatinga and 89 cases in Itacoatiara. In this study, we found that the positivity of ovitraps was related to the occurrence of dengue in Tabatinga and Itacoatiara. An association between egg density of Ae. aegypti and dengue occurrence was also observed in Itacoatiara. The temporal lags for ovitrap positivity measurements were predominantly 15 or 30 days. A dengue association for egg density for a 15-day time lag was detected for one of the case-control approaches. CONCLUSIONS The location of dengue cases is related to ovitrap egg positivity, while a less evident possible association may exist for egg density. This indicates that these traps could be used to improve vector control actions.

Background In Latin America, where Plasmodium vivax malaria is more prevalent, it is known that this species plays an important role in the sustainability of transmission, and can have an impact on morbidity in terms of anaemia, nutritional status, and cognitive development in children. Methods The present study aimed to assess the impact of malaria infection on cognition of children in a peri-urban community in the Brazilian Amazon with moderate endemicity by applying Home Inventory and WPPSI-IV. A non-concurrent cohort study was designed and the cognitive, haematological, and nutritional profiles of the children were assessed. Children with documented malaria history were identified from official reported data. Results A total of 219 children aged between 2 and 7 years were enrolled. Although 205 (95%) children had normal birth weight, 177 (81%) were malnourished, and 35 (16%) had anaemia. Among the 100 (46%) children who experienced at least one episode of malaria, 89 (89%) children demonstrated low level of cognitive development. The findings showed that Plasmodium vivax malaria was an independent risk factor for low cognitive development. Conclusions In addition to the known economic impact of malaria in the Amazon region, the study highlights the deleterious effects P. vivax malaria has on the socio-cultural development of the population.

Background Dengue is the most prevalent arboviral disease affecting humans. The frequency and magnitude of dengue epidemic have significantly increased over recent decades. This study aimed to identify dengue epidemic types and risk factors for the extensive epidemics that occurred in 2010–2011, across the municipalities of Amazonas state, Brazil. Methods Using an ecological approach, secondary data were obtained from the dengue fever surveillance system. Epidemic waves were classified according to three indices: duration, intensity, and coverage. A hierarchical model of multiple logistic regression was used for the identification of risk factors, with the occurrence of extensive dengue epidemic. Results During the study period, dengue virus affected 49 of the 62 Amazonas municipalities. In 22 of these, the epidemics were of high intensity, wide range, and long time span, and therefore categorized as “extensive epidemics”. The final multivariable model revealed a significant association between extensive dengue epidemics occurrence and the average number of days with precipitation (adjusted OR = 1.40, 95% CI: 1.01–1.94) and the number of years with infestation (adjusted OR = 1.53, 95% CI: 1.18–1.98). Conclusions Our results indicate that it is crucial to integrate vector control, case management, epidemiological investigation, and health education, in order to respond to the growing threat of multiple mosquito-borne diseases, such as dengue, Zika and chikungunya, which are highly prevalent in the South America region. Electronic supplementary material The online version of this article (10.1186/s12889-018-5251-x) contains supplementary material, which is available to authorized users.

Despite the availability of tuberculosis prevention and control services throughout Amazonas, high rates of morbidity and mortality from tuberculosis remain in the region. Knowledge of the social determinants of tuberculosis in Amazonas is important for the establishment of public policies and the planning of effective preventive and control measures for the disease. To analyze the relationship of the spatial distribution of the incidence of tuberculosis in municipalities and regions of Amazonas to the socioeconomic factors and indigenous tuberculosis component, from 2007 to 2013. An ecological study was conducted based on secondary data from the epidemiological surveillance of tuberculosis. A linear regression model was used to analyze the relationship of the annual incidence of tuberculosis to the socioeconomic factors, performance indicators of health services, and indigenous tuberculosis component. The distribution of the incidence of tuberculosis in the municipalities of Amazonas was positively associated with the Gini index and the population attributable fraction of tuberculosis in the indigenous peoples, but negatively associated with the proportion of the poor and the unemployment rate. The spatial distribution of tuberculosis in the different regions of Amazonas was heterogeneous and closely related with the socioeconomic factors and indigenous component of tuberculosis.

INTRODUCTION: In the State of Amazonas, particularly in the capital Manaus, meningitis has affected populations of different cultures and social strata over the years. Bacterial meningitis is caused by several different species and represents a major issue of public health importance. The present study reports the meningitis case numbers with different etiologies in Amazonas from January 1976 to December 2012. METHODS: Since the 1970s, the (currently named) Tropical Medicine Foundation of Doutor Heitor Vieira Dourado [Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD)] has remained a reference center in Amazonas for the treatment of meningitis through the diagnosis and notification of cases and the confirmation of such cases using specific laboratory tests. RESULTS: The foundation has achieved coverage of over 90% of the state medical records for many years. Between 1990 and 2012, meningitis cases caused by Haemophilus influenzae decreased with the introduction of the H. influenzae vaccine. Meningococcal disease previously had a higher frequency of serogroup B disease, but starting in 2008, the detection of serogroup C increased gradually and has outpaced the detection of serogroup B. Recently, surveillance has improved the etiological definition of viral meningitis at FMT-HVD, with enteroviruses, Epstein-Barr virus (EBV) and varicella zoster virus (VZV) prevailing in this group of pathogens. With the advent of acquired immunodeficiency syndrome (AIDS), cryptococcal meningitis has become an important disease in Amazonas. Additionally, infectious meningitis is an important burden in the State of Amazonas. CONCLUSIONS: Changes in the epidemiological profile for the different etiology-defined cases are the result of continuous epidemiological surveillance and laboratory capacity improvements and control measures, such as Haemophilus influenzae vaccination.

Hantavirus pulmonary syndrome (HPS) is an acute, severe, frequently fatal disease associated with cardiopulmonary failure; it is caused by hantaviruses naturally hosted by wild rodents. Rio Mamore virus (RIOMV) was first described in 1996 in Bolivia; it was associated with the small-eared pygmy rice rat, Oligoryzomys microtis (1). Subsequently, 1 strain of RIOMV was isolated from O. microtis rats in Peru, designated HTN-007 (2); and 2 strains were recovered in the Brazilian Amazon from O. microtis rats (RIOMV-3) and uncharacterized species of rodents of the genus Oligoryzomys (RIOMV-4) (3). Recently, HPS cases associated with RIOMV have been reported: 2 cases in Peru (4) and 1 case in French Guiana (caused by a variant named Maripa virus) (5). We report isolation of a strain of RIOMV from a patient with fatal HPS in Brazil....

In Brazil, more than 99% of malaria cases are reported in the Amazon, and the State of Amazonas accounts for 40% of this total. However, the accumulated experience and challenges in controlling malaria in this region in recent decades have not been reported. Throughout the first economic cycle during the rubber boom (1879 to 1912), malaria was recorded in the entire state, with the highest incidence in the villages near the Madeira River in the Southern part of the State of Amazonas. In the 1970s, during the second economic development cycle, the economy turned to the industrial sector and demanded a large labor force, resulting in a large migratory influx to the capital Manaus. Over time, a gradual increase in malaria transmission was observed in peri-urban areas. In the 1990s, the stimulation of agroforestry, particularly fish farming, led to the formation of permanent Anopheline breeding sites and increased malaria in settlements. The estimation of environmental impacts and the planning of measures to mitigate them, as seen in the construction of the Coari-Manaus gas pipeline, proved effective. Considering the changes occurred since the Amsterdam Conference in 1992, disease control has been based on early diagnosis and treatment, but the development of parasites that are resistant to major antimalarial drugs in Brazilian Amazon has posed a new challenge. Despite the decreased lethality and the gradual decrease in the number of malaria cases, disease elimination, which should be associated with government programs for economic development in the region, continues to be a challenge.

1 Western General Hospital, Edinburgh, United Kingdom, 2Fundac¸a˜o de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil, 3Universidade do Estadodo Amazonas, Programa de Po´s-Graduac¸a˜o em Medicina Tropical, Manaus, Amazonas, Brazil, 4 Universidade Federal de Sa˜oJoa˜o Del Rei, Campus Centro Oeste,Divino´polis, Minas Gerais, Brazil, 5 Fundac¸a˜o de Vigilaˆncia em Sau´de, Manaus, Amazonas, Brazil

To the Editor: Since hantavirus pulmonary syndrome (HPS) caused by Sin Nombre virus (SNV) was identified in the southwestern United States in 1993, cases have been diagnosed in many Latin American countries, and an increasing number of hantaviruses and their rodent reservoirs have been reported (1). The first evidence of hantavirus circulation in the western Brazilian Amazon region was documented in 1991 (2). Vasconcelos et al., by using antigens from the Old World hantavirus, found evidence of hantavirus antibodies in 45.2% of serum samples acquired from contacts of patients who died with undiagnosed hemorrhagic fever in Manaus. The first human cases of symptomatic infection by hantaviruses were reported from Brazil in 1993, in Juquitiba (Sao Paulo State). HPS developed in 3 young brothers, who lived in a forested region along the Atlantic Coast, after they had cleared trees on their land, and 2 of them died. These patients were living in poor conditions, without appropriate storage spaces for human food or for animal feed, and their dwelling was constantly invaded by wild rodents who were looking for food (3). Since then, many other HPS cases have been reported, especially from the southern and southeastern regions of Brazil where agricultural activities are prominent; the mean case-fatality ratio is 48% (3). In the Brazilian Amazon, HPS has been frequently reported in Mato Grosso and sporadically in Maranhao and Para states, which indicates an endemic circulation of hantaviruses (4,5) We report here the first human cases of HPS in the state of Amazonas in the western part of the Brazilian Amazon. All 4 patients belonged to the same family cluster and came from a rural area near the town of Itacoatiara, on the edge of an important industrial waterway for soybean transport (the Itacoatiara soybean terminal). This family (patients 1, 2, and 3) had cleared a forested area on their farm and killed many rodents found in the bases of trees and near the house from May 25 to June 5, 2004. They also reported that wild rodents were inside their house. All serologic tests were performed in the Arbovirology and Hemorrhagic Fever Department, at the Evandro Chagas Institute (Para, Brazil), with antigens provided by the Centers for Disease Control and Prevention (Atlanta, GA, USA). An enzyme-linked immunosorbent assay (ELISA) was performed by using cellular fluid and Laguna Negra virus antigens for immunoglobulin M (IgM) detection (MAC-ELISA), and recombinant SNV antigens for IgG detection. Samples were considered positive with an optical density >0.2 in 1:100 (IgM) and 1:400 (IgG) dilutions (6,7). Viral isolation or polymerase chain reaction (PCR) for hantavirus were not attempted in human or rodent samples. In the index patient, symptoms developed 15 days after she had killed 20 rodents with hot water during the tree-clearing process on the farm. She was a 25-year-old woman who sought treatment with an acute syndrome of high fever, dry cough, and dyspnea. She was admitted to the Itacoatiara general hospital; her condition was diagnosed as bacterial pneumonia and treated with intravenous penicillin. She died within 5 days because of respiratory failure; since no laboratory tests were conducted, she does not fulfill the case definition criteria for HPS. This was the only case in this series not confirmed with laboratory tests. The second case was in the first patient's 31-year-old husband. Symptoms developed 2 weeks after the wife's death, starting with a 5-day febrile syndrome, which progressed to a dry cough and then respiratory distress, with a petechial rash, hemoconcentration, and thrombocytopenia (53,000 platelets/μL) over the next 2 days. He exhibited a diffuse, alveolar infiltrate on chest radiograph and a mild cardiomyopathy on echocardiogram. He was admitted to an intensive care unit and required mechanical ventilation for 10 days; he made a gradual recovery. Results of his laboratory tests ruled out malaria, dengue fever, and leptospirosis. Three consecutive blood culture samples were negative for bacterial growth. The IgG and IgM ELISA results for hantavirus were positive in both acute- and convalescent-phase serum samples. The third case was in the second patient's brother, a 43-year-old man, who exhibited a self-limited, acute febrile syndrome 1 month after the index patient. He did not live on the same farm but visited there often and had actively participated in removing the trees on his brother's farm. He had no respiratory complaints, and results of his chest radiographs were normal, but the complete blood count showed hemoconcentration and mild thrombocytopenia (130,000 platelets/μL). He was hospitalized for 3 days and recovered completely. An IgM ELISA result was positive for hantavirus in 2 consecutive blood samples, and an IgG ELISA result was positive in convalescent-phase serum. The fourth patient was a 67-year-old farmer, the uncle of the last 2 patients. He visited his nephew's farm regularly and was present during the deforestation process. He presented for medical assistance after a 15-day febrile syndrome, with a dry cough and mild dyspnea, 5 weeks after the index patient. He was hospitalized for 3 days and also had an uneventful recovery. The IgM ELISA result in this patient was also positive for hantavirus in 2 consecutive blood samples as was the IgG ELISA result for convalescent-phase serum. Shortly after the report of the first 3 cases, the Brazilian Health Surveillance Secretary (Ministry of Health) performed an epidemiologic field study to seek the probable site of infection, collect sylvatic rodents, and conduct a serologic survey of human contacts. No areas for soybean cultivation or seed storage were found, but local farmers commonly store dry corn for feeding their domestic fowl. Eighty-two blood samples were collected from asymptomatic persons and were all negative for hantavirus IgG antibodies by ELISA. Eleven sylvatic rodents were captured in 3 days of trapping (270 traps/night) on the farm, on neighboring farms, and in the nearby forest. Two species were identified, Proechimys sp. (2 animals) and Oligoryzomys microtis (9 animals). This finding is very similar to reports of rodents in other regions of Brazil (8). Four Oligoryzomys microtis had positive IgG results for hantavirus (9). Identification of human and rodent hantavirus infection in the Amazonas State adds this emergent disease to our differential diagnoses of febrile tropical diseases and to our syndromic surveillance approach for febrile respiratory diseases. Further research is needed to identify the viral genotype that circulates in this area and to determine the real prevalence of human infection and the epidemiologic scenario of HPS in the western Brazilian Amazon region.

SETTING: Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. OBJECTIVE: This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. DESIGN: Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as 'cases' and those completing treatment as 'controls'. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. RESULTS: Treatment default was observed to be associated to previous default (aOR 3.20; p

Haff disease, first reported along the Baltic coast in 1924, is unexplained rhabdomyolysis in a person who ate fish in the 24 hours before onset of illness (1). Outbreaks resembling Haff disease were described in Sweden and the Soviet Union between 1934 and 1984 (2, 3). In the United States, only three reports have been published to date (4). Haff disease remains a rare clinical syndrome for which there is no physiologic explanation. Outbreaks of Haff disease have never been reported in Brazil. But in June 2008, a 39-year-old female medical doctor was admitted by the emergency service of a public hospital in Manaus, Amazonas State, Brazil, with diffuse myalgia and chest pain. The plasma creatine kinase (CK) activity levels were 6 252 units per liter (U/L) and no history of classic risk factors for rhabdomyolysis was detected. Her mother had been admitted 1 week before, presenting the same symptoms. Both women reported eating fish 24 hours before the onset of symptoms; further inquiry revealed that two residents from the same household who had not eaten fish did not become sick. The attending physician at the hospital was intrigued by the diagnosis of the two familial cases of Haff disease and began an epidemiologic investigation, looking for similar cases and potential risk factors. A case report form was designed and distributed along with a technical note to all hospitals in Manaus, instructions on how to report suspected cases, and suggestions for their management. The cases were defined as those who were hospitalized on or after 1 June 2008 with a diffuse myalgia of sudden onset who ate fish in the 24 hours before onset of illness and CK serum activity that exceeded five times the upper limit of normal. Patients with a classic risk factor for rhabdomyolysis were not included. The results of the investigation are reported here. Twenty-five cases of Haff disease were identified in Manaus between June and September 2008. All reported consumption of fried or roasted pacu—silver dollars (Mylossoma spp.), tambaqui—black-finned colossoma (Colossoma macropomum), or pirapitinga—freshwater pompano (Piaractus brachypomus), three river fishes of the region, within 24 hours before the onset of symptoms. All patients were older than 13 years of age (range 13–80 years); there were a similar number of males and females (59% and 41%, respectively). Three patients came from rural areas surrounding Manaus and nine patients were clustered in four families: the initial mother–daughter pair, a brother–sister pair, a husband–wife pair, and a family of three (husband, wife, and daughter). Five other members of these four families, who did not eat fish, did not fall ill. All patients were hospitalized (range 3–6 days) with myalgia of sudden onset, mostly localized at the beginning of symptoms and followed by generalized spreading within a few hours. Nineteen patients reported chest pain, among other symptoms (see Table 1). No fever or kidney damage was observed. TABLE 1 Symptoms of Haff disease cases, Amazon, Brazil, 2008 Predominant laboratory abnormalities were elevated CK serum activity (mean = 12 795 U/L, range 1 444–36 896 U/L). Serum activities of transaminases and lactate dehydrogenase were also elevated. In two patients, myoglobin was measured and found to be higher than 700 U/L. Serology for leptospirosis and hepatitis A and B was negative. Patients were treated with intravenous fluid hydration and bicarbonate infusion. No deaths were observed. In only 4 months, 27 cases of Haff disease were reported in Manaus and surrounding municipalities of the Brazilian Amazon. The diagnosis of Haff disease was made based on the fact that none of the cases could be explained by classic causes of rhabdomyolysis; all patients reported consumption of fish within 24 hours before the onset of symptoms; some cases occurred in family clusters and no cases were observed after the beginning of the period of prohibition of fishing in the region that occurs every year from October to March. This possible association between fish eating and rhabdomyolysis in the Amazon region may have an important impact, as fish is a major source of protein in the Brazilian Amazon (5). Active surveillance of this supposedly uncommon condition is necessary to corroborate its frequency in the region and enhance our understanding of this elusive disease. This paper is part of the doctoral thesis of Marcelo Cordeiro dos Santos of Amazonas State University, Amazonas State Tropical Medicine Foundation. The views expressed here are those of the authors and do not necessarily reflect the official policy or position of the Brazilian Government, the U.S. Government, Department of the Navy, or Department of Defense.

Introduction : Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. Methods : We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. Results : There were 15 males (average age, 31.3 years), all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. Conclusions : All patients had consumed acai products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil. Keywords : Chagas disease. Acute outbreak. State of Amazonas.Several outbreaks of acute Chagas disease in the Amazon region 1 have been associated with oral consumption of acai. The most accepted transmission mechanism is contamination due to triatomine feces in the fruit or by insects that are inadvertently crushed while the fruit is being processed. In this process

Dois casos de lactentes atendidos na Fundação de Medicina Tropical do Amazonas, com síndrome febril exantemática aguda, extravasamento capilar e manifestações hemorrágicas de pequena magnitude, caracterizando quadro de febre hemorrágica do dengue. O diagnóstico etiológico foi confirmado pelo MAC-ELISA e pelo ELISA de inibição para IgG, realizados nos lactentes e nas respectivas mães.

Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

Background Malaria is a major public health problem worldwide. In Brazil, an average of 420,000 cases of malaria have been reported annually in the last 12 years, of which 99.7 % occurred in the Amazon region. This study aimed to analyse the distribution of malaria in the State of Amazonas and the influence of indigenous malaria in this scenario, to evaluate the correlation between incidence rates and socio-economic and environmental factors, and to evaluate the performance of health surveillance services. Methods This ecological study used secondary data obtained from the SIVEP-MALARIA malaria surveillance programme. The relationship between demographic, socio-economic and environmental factors, the performance of health surveillance services and the incidence of malaria in Amazonas, a multiple linear regression model was used. Results The crude rate of malaria in Amazonas was 4142.72 cases per 100,000 inhabitants between 2003 and 2012. The incidence rates for the indigenous and non-indigenous populations were 12,976.02 and 3749.82, respectively, with an indigenous population attributable fraction of only 8 %. The results of the linear regression analysis indicated a negative correlation between the two socio-economic indicators (municipal human development index (MHDI) and poverty rate) and the incidence of malaria in the period. With regard to the environmental indicators (average annual deforestation rate and percentage of areas under the influence of watercourses), the correlation with the incidence rate was positive. Conclusions The findings underscore the importance of implementing economic and social development policies articulated with strategic actions of environmental protection and health care for the population.