High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behaviour measures: results from the prospective DETECTCoV-19 cohort

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 OrganizationRevisión por pare

In vitro and in vivo anti‑malarial activity of plants from the Brazilian Amazon

Submitted by Nuzia Santos ([email protected]) on 2016-07-08T18:45:22Z No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2016-07-08T19:00:53Z (GMT) No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5)Made available in DSpace on 2016-07-08T19:00:53Z (GMT). No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5) Previous issue date: 2015Made available in DSpace on 2016-07-22T13:23:06Z (GMT). No. of bitstreams: 3 ve_Lima_Renata_INVitro_CPqRR_2015.pdf.txt: 78136 bytes, checksum: 163d252edb75adfcdde79e41ea296080 (MD5) ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2015Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil / Centro Universitário Lima do Norte. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil / Centro Universitário Lima do Norte. Manaus, AM, Brasil.Universidade Estadual do Amazonas. Escola Superior de Ciências da Saúde. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.Embrapa Amazônia Ocidental. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Instituto Nacional de Pesquisas da Amazônia Laboratório de Malária e Dengue, Coordenação de Sociedade, Ambiente. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.BACKGROUND: The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. METHODS: Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice. RESULTS: High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71% suppression of P. berghei parasitaemia versus untreated controls). CONCLUSIONS: Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present