Delayed gametocyte clearance in Plasmodium vivax malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR).

Primaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytocidal activity in 100 subjects with P. vivax malaria. To determine gametocyte density, we measured the levels of pvs25 transcripts in samples taken before treatment (D0) and 72 hours after treatment (D3). Generalized estimating equations (GEEs) were used to examine the effects of enzyme variants on gametocyte densities, adjusting for potential confounding factors. Linear regression models were adjusted to explore the predictors of PQ blood levels measured on D3. Individuals with the CPR mutation showed a smaller decrease in gametocyte transcript levels on D3 compared to those without the mutation (P = 0.02, by GEE). Consistent with this, higher PQ blood levels on D3 were associated with a lower reduction in pvs25 transcripts. Based on our findings, the CPR variant plays a role in the persistence of gametocyte density in P. vivax malaria. Conceptually, our work points to pharmacogenetics as a non-negligible factor to define potential host reservoirs with the propensity to contribute to transmission in the first days of CQ-PQ treatment, particularly in settings and seasons of high Anopheles human-biting rates.

A redução de risco de desastres, a agenda dos Objetivos Sustentáveis e os princípios do SUS, no contexto da pandemia de COVID-19 / Disaster risk reduction, the Sustainable Goals agenda and the principles of the SUS, in the context of the COVID-19 pandemic

Resumo O objetivo foi analisar os nexos entre o Marco de Sendai para a Redução do Risco de Desastres, os Objetivos de Desenvolvimento Sustentável (ODS) e os princípios do Sistema Único de Saúde (SUS), no contexto da emergência de saúde pública da pandemia de COVID-19, e suas potenciais implicações para a saúde da população. O estudo é qualitativo, transversal, exploratório, com dados coletados junto a profissionais de saúde com experiência em práticas assistenciais e de gestão de risco de emergências e desastres, e tratados pelo software Iramuteq para análise lexical. O corpus textual foi apresentado através da classificação hierárquica descendente, que originou sete classes aglutinadas em três categorias denominadas: resposta a desastres no contexto do SUS; prevenção de futuros riscos de desastres; e ações de preparação e recuperação a partir do Marco de Sendai e dos ODS. Ressaltou-se aspectos sobre os efeitos diretos e indiretos da pandemia de COVID-19 e os desafios relacionados à redução do risco de desastres preconizados no Marco de Sendai, apontando a necessidade de fortalecer a cultura de segurança e sustentabilidade no âmbito do SUS, o que se coaduna com os ODS, bem como aos determinantes sociais da saúde.

Abstract The aim of this study was to analyze the connections between the Sendai Framework for Disaster Risk Reduction, the Sustainable Development Goals (SDGs), and the principles of Brazil's Unified Health System (SUS) in the context of the public health emergency caused by the COVID-19 pandemic and its potential implications for population health. This qualitative, cross-sectional, exploratory study collected data from health professionals with experience in emergency and disaster risk management and treatment practices, which were then processed using the Iramuteq software for lexical analysis. The textual corpus was presented through a descending hierarchical classification that resulted in seven classes grouped into three categories: disaster response in the context of SUS; prevention of future disaster risks; and preparedness and recovery actions based on the Sendai Framework and the SDGs. The study highlighted aspects related to the direct and indirect effects of the COVID-19 pandemic and the challenges related to disaster risk reduction as advocated by the Sendai Framework, emphasizing the need to strengthen the culture of safety and sustainability within the SUS, which aligns with the ODS and social determinants of health.

Disaster risk reduction, the Sustainable Goals agenda and the principles of the SUS, in the context of the COVID-19 pandemic. / A redução de risco de desastres, a agenda dos Objetivos Sustentáveis e os princípios do SUS, no contexto da pandemia de COVID-19.

The aim of this study was to analyze the connections between the Sendai Framework for Disaster Risk Reduction, the Sustainable Development Goals (SDGs), and the principles of Brazil's Unified Health System (SUS) in the context of the public health emergency caused by the COVID-19 pandemic and its potential implications for population health. This qualitative, cross-sectional, exploratory study collected data from health professionals with experience in emergency and disaster risk management and treatment practices, which were then processed using the Iramuteq software for lexical analysis. The textual corpus was presented through a descending hierarchical classification that resulted in seven classes grouped into three categories: disaster response in the context of SUS; prevention of future disaster risks; and preparedness and recovery actions based on the Sendai Framework and the SDGs. The study highlighted aspects related to the direct and indirect effects of the COVID-19 pandemic and the challenges related to disaster risk reduction as advocated by the Sendai Framework, emphasizing the need to strengthen the culture of safety and sustainability within the SUS, which aligns with the ODS and social determinants of health.

O objetivo foi analisar os nexos entre o Marco de Sendai para a Redução do Risco de Desastres, os Objetivos de Desenvolvimento Sustentável (ODS) e os princípios do Sistema Único de Saúde (SUS), no contexto da emergência de saúde pública da pandemia de COVID-19, e suas potenciais implicações para a saúde da população. O estudo é qualitativo, transversal, exploratório, com dados coletados junto a profissionais de saúde com experiência em práticas assistenciais e de gestão de risco de emergências e desastres, e tratados pelo software Iramuteq para análise lexical. O corpus textual foi apresentado através da classificação hierárquica descendente, que originou sete classes aglutinadas em três categorias denominadas: resposta a desastres no contexto do SUS; prevenção de futuros riscos de desastres; e ações de preparação e recuperação a partir do Marco de Sendai e dos ODS. Ressaltou-se aspectos sobre os efeitos diretos e indiretos da pandemia de COVID-19 e os desafios relacionados à redução do risco de desastres preconizados no Marco de Sendai, apontando a necessidade de fortalecer a cultura de segurança e sustentabilidade no âmbito do SUS, o que se coaduna com os ODS, bem como aos determinantes sociais da saúde.

Challenges of acute febrile illness diagnosis in a national infectious diseases center in Rio de Janeiro: 16-year experience of syndromic surveillance.

INTRODUCTION: Acute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. Understanding the distribution of causes of AFI can improve patient outcomes. This study aims to describe the most common etiologies diagnosed over a 16-years period in a national reference center for tropical diseases in a large urban center in Rio de Janeiro, Brazil. METHODS: From August 2004-December 2019, 3591 patients > 12 years old, with AFI and/or rash were eligible. Complementary exams for etiological investigation were requested using syndromic classification as a decision guide. Results. Among the 3591 patients included, endemic arboviruses such as chikungunya (21%), dengue (15%) and zika (6%) were the most common laboratory-confirmed diagnosis, together with travel-related malaria (11%). Clinical presumptive diagnosis lacked sensitivity for emerging diseases such as zika (31%). Rickettsia disease and leptospirosis were rarely investigated and an infrequent finding when based purely on clinical features. Respiratory symptoms increased the odds for the diagnostic remaining inconclusive. CONCLUSIONS: Numerous patients did not have a conclusive etiologic diagnosis. Since syndromic classification used for standardization of etiological investigation and presumptive clinical diagnosis had moderate accuracy, it is necessary to incorporate new diagnostic technologies to improve diagnostic accuracy and surveillance capacity.

Serum biomarkers associated with SARS-CoV-2 severity.

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

Correction: Vertical transmission of chikungunya virus: A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0249166.].

COVID-19 seroepidemiological survey among healthcare workers in the City of Ribeirão Preto, São Paulo, Brazil.

BACKGROUND: Coronavirus disease (COVID-19) serology testing evaluates the prevalence of COVID-19 cases. METHODS: A seroepidemiological survey of COVID-19 among healthcare workers was performed (June 2020 to November 2020) in Ribeirão Preto, São Paulo, Brazil. Overall, 10,172 and 2,129 workers participated in the first and second phases, respectively. RESULTS: First phase: 12.7% tested positive for COVID-19 (73.5% females and 35.2% aged 30-39 years), and 29.6% were nursing technicians. Second phase: 12.1% tested positive for COVID-19 (65.5% females and 33.3% aged 40-49 years), and 24.8% were nursing assistants. CONCLUSIONS: In 2020, healthcare workers in Ribeirão Preto had COVID-19 in a similar way.

Outbreak caused by the SARS-CoV-2 Omicron variant in the psychiatric ward of a general hospital in Brazil.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. METHODS: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. RESULTS: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. CONCLUSIONS: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.

Malaria time series in the extra-Amazon region of Brazil: epidemiological scenario and a two-year prediction model.

BACKGROUND: In Brazil, malaria is caused mainly by the Plasmodium vivax and Plasmodium falciparum species. Its transmission occurs in endemic and non-endemic areas. Malaria geography in Brazil has retracted and is now concentrated in the North region. The Brazilian Amazon region accounts for 99% of Brazil's cases. Brazil's extra-Amazon region has a high frequency of imported cases and in 2019 presented a mortality rate 123 times higher than the Amazon region. Extra-Amazon cases present risks of reintroduction. This study aims to characterize the epidemiological scenario for malaria in the extra-Amazon region of Brazil from 2011 to 2020 with a two-year forecast. METHODS: Time-series study with description of malaria cases and deaths registered in Brazilian extra-Amazon region from 2011 to 2020. Public data from the Notifiable Diseases Information System (Sinan) and the Mortality Information System (SIM) were used. Descriptive analysis, incidence, and notification rates were calculated. Flow charts analysed the flux between Places of Probable Infection (PI) and places of notification. The prediction model utilized a multiplicative Holt-winters model for trend and seasonality components. RESULTS: A total of 6849 cases were registered. Cases were predominantly white males with 9 to 11 years of education, mostly between 30 and 39 years old. Imported cases accounted for 78.9% of cases. Most frequent occupations for imported cases are related to travelling and tourism activities. Among autochthonous cases, there is a higher frequency of agriculture and domestic economic activities. In the period there were 118 deaths due to malaria, of which 34.7% were caused by P. falciparum infections and 48.3% were not specified. The most intense flows of imported cases are from Amazonas and Rondônia to São Paulo, Rio de Janeiro, and Paraná. The prediction estimates around 611 cases for each of the following two years. CONCLUSION: The time series allows a vast epidemiological visualization with a short-term prediction analysis that supports public health planning. Government actions need to be better directed in the extra-Amazon region so the objective of eliminating malaria in Brazil is achieved. Carrying out quality assessments for information systems and qualifying personnel is advisable. Malaria outside the Amazon region is mainly due to imported cases and delay in diagnosis is associated with a higher fatality rate. Better strategies to diagnose and treat suspected cases can lead to lower risk of deaths and local outbreaks that will be important for achieving malaria elimination in Brazil.

Outbreak caused by the SARS-CoV-2 Omicron variant in the psychiatric ward of a general hospital in Brazil

ABSTRACT Background: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. Methods: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. Results: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. Conclusions: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.

COVID-19 seroepidemiological survey among healthcare workers in the City of Ribeirão Preto, São Paulo, Brazil

ABSTRACT Background: Coronavirus disease (COVID-19) serology testing evaluates the prevalence of COVID-19 cases. Methods: A seroepidemiological survey of COVID-19 among healthcare workers was performed (June 2020 to November 2020) in Ribeirão Preto, São Paulo, Brazil. Overall, 10,172 and 2,129 workers participated in the first and second phases, respectively. Results: First phase: 12.7% tested positive for COVID-19 (73.5% females and 35.2% aged 30-39 years), and 29.6% were nursing technicians. Second phase: 12.1% tested positive for COVID-19 (65.5% females and 33.3% aged 40-49 years), and 24.8% were nursing assistants. Conclusions: In 2020, healthcare workers in Ribeirão Preto had COVID-19 in a similar way.

Evaluation of the effect of supervised anti-malarial treatment on recurrences of Plasmodium vivax malaria.

BACKGROUND: Relapses in vivax malaria have posed great challenges for malaria control, and they also account for a great proportion of reported cases. Knowing the real effectiveness of a 7-day primaquine (PQ) scheme is crucial in order to evaluate not only the cost-effectiveness of implementing new anti-hypnozoite drugs, but also how health education strategies can guarantee better compliance and be reinforced. This study aimed to evaluate the effect of daily treatment with chloroquine and PQ supervised by health workers versus prescription without supervision. METHODS: The outcome was the passive detection of new positive thick blood smears up to 180 days, based on the official data records from the National Malaria Control Programme. The recurrences seen in the real life were, therefore, used as a surrogate for true relapses. RESULTS: Patients under supervised treatment had a lower risk of recurrence up to day 180 when compared to the unsupervised treatment (17.9% vs. 36.1%; p = 0.027). CONCLUSIONS: The lack of supervision in the non-supervised group (which followed standard of care in the real life) enabled proper comparison, as consent itself would have lead to greater compliance in this group. Future studies should scale such an analysis to different settings in the Brazilian Amazon.

Vertical transmission of chikungunya virus: A systematic review.

OBJECTIVES: To describe and estimate the frequency of pregnancy outcomes, clinical and laboratory characteristics of vertical transmission of CHIKV in the neonate. STUDY DESIGN: We performed a systematic review evaluating the clinical presentation of perinatally-acquired CHIKV infection in neonates. The search was performed using Medline (via PubMed), LILACS, Web of Science, Scielo, Google Scholar and Open grey to identify studies assessing vertical transmission of CHIKV up to November 3, 2020. There were no search restrictions regarding the study type, the publication date or language. Studies with no documented evidence of CHIKV infection in neonates (negative RT-PCR or absence of IgM) were excluded. RESULTS: From the 227 studies initially identified, 42 were selected as follows: 28 case reports, 7 case series, 2 cross-sectional studies and 5 cohort studies, for a total of 266 CHIKV infected neonates confirmed by serological and/or molecular tests. The vertical transmission rate was 50% in the Reunion Island outbreak, which was the subject of the majority of the studies; the premature delivery were reported in 19 (45.2%) studies; the rate of fetal distress was 19.6% of infected babies and fetal loss occurred in 2% of the cases. Approximately 68.7% of newborns were diagnosed with encephalopathy or encephalitis after perinatally acquired CHIKV. Most of the infected neonates were born healthy, developing CHIKV sepsis clinical syndrome within the first week of life. CONCLUSIONS: We alert neonatologists to the late manifestations of neonatal CHIKV infection, relevant to the management and reduction of morbidity. A limitation of our review was that it was not possible to carry out meta-analysis due to differences in study design and the small number of participants.

Should we care about Plasmodium vivax and HIV co-infection? A systematic review and a cases series from the Brazilian Amazon.

BACKGROUND: Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available information related to Plasmodium falciparum on the African continent. It is unclear whether HIV can change the clinical course of vivax malaria and increase the risk of complications. In this study, a systematic review of HIV/PvCo studies was performed, and recent cases from the Brazilian Amazon were included. METHODS: Medical records from a tertiary care centre in the Western Brazilian Amazon (2009-2018) were reviewed to identify HIV/PvCo hospitalized patients. Demographic, clinical and laboratory characteristics and outcomes are reported. Also, a systematic review of published studies on HIV/PvCo was conducted. Metadata, number of HIV/PvCo cases, demographic, clinical, and outcome data were extracted. RESULTS: A total of 1,048 vivax malaria patients were hospitalized in the 10-year period; 21 (2.0%) were HIV/PvCo cases, of which 9 (42.9%) had AIDS-defining illnesses. This was the first malaria episode in 11 (52.4%) patients. Seven (33.3%) patients were unaware of their HIV status and were diagnosed on hospitalization. Severe malaria was diagnosed in 5 (23.8%) patients. One patient died. The systematic review search provided 17 articles (12 cross-sectional or longitudinal studies and 5 case report studies). A higher prevalence of studies involved cases in African and Asian countries (35.3 and 29.4%, respectively), and the prevalence of reported co-infections ranged from 0.1 to 60%. CONCLUSION: Reports of HIV/PvCo are scarce in the literature, with only a few studies describing clinical and laboratory outcomes. Systematic screening for both co-infections is not routinely performed, and therefore the real prevalence of HIV/PvCo is unknown. This study showed a low prevalence of HIV/PvCo despite the high prevalence of malaria and HIV locally. Even though relatively small, this is the largest case series to describe HIV/PvCo.

Seroprevalence, spatial dispersion and factors associated with flavivirus and chikungunha infection in a risk area: a population-based seroprevalence study in Brazil.

BACKGROUND: The State of Ceará, in Northeastern Brazil, suffers from a triple burden of arboviruses (dengue, Zika and chikungunya). We measured the seroprevalence of chikungunya, dengue and Zika and its associated factors in the population of Juazeiro do Norte, Southern Ceará State, Brazil. METHODS: A cross-sectional study of analytical and spatial analysis was performed to estimate the seroprevalence of dengue, Zika and chikungunya, in the year 2018. Participants were tested for IgM and IgG against these three viruses. Those with IgM and/or IgG positive tests results were considered positive. Poisson regression was used to analyze the factors associated with positive cases, in the same way that the spatial analysis of positive cases was performed to verify whether the cases were grouped. RESULTS: Of the 404 participants, 25.0% (103/404) were positive for CHIKV, 92.0% (373/404) for flavivirus (dengue or Zika) and of these, 37.9% (153/404) samples were classified as probable dengue infection. Of those who reported having had an arbovirus in the past, positive CHIKV cases had 58.7% arthralgia (PR = 4.31; 95% CI: 2.06-9.03; p = 0.000) mainly in the hands, ankles and feet. Age over 60 years had a positive association with cases of flavivirus (PR = 1.29; 95% CI: 1.09-1.54; p = 0.000). Fever, muscle pain, joint pain and skin rash were the most reported symptoms (46.1, 41.0, 38.3 and 28.41%, respectively). The positive cases of chikungunya and dengue or Zika were grouped in space and the city center was most affected area. CONCLUSIONS: Four years after the introduction of CHIKV, where DENV has been in circulation for over 30 years, 1/4 of the population has already been exposed, showing the extent of the epidemic. The measured prevalence was much higher than that reported by local epidemiological surveillance.

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

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.

Chikungunya Case Classification after the Experience with Dengue Classification: How Much Time Will We Lose?

In 2013, cases of chikungunya virus (CHIKV) infection were first detected in the Caribbean. Chikungunya virus rapidly spread through Central and South America, causing explosive outbreaks in naive populations. Since its emergence in 2004, the number of case and series reports describing severe, atypical manifestations seen in chikungunya patients has increased substantially, calling into question whether clinicians and health services are failing to diagnose these atypical cases because of not only insufficient knowledge but also limitations in the case classification. Although this classification based on the duration of the musculoskeletal (acute, subacute, and chronic forms) complaints helped guide therapeutic approaches directed to these manifestations, patients presenting severe or complicated forms, which are less frequent but produce most of the fatal outcomes, were not properly addressed. In Brazil and the Caribbean, a clear temporal and spatial association between excess overall mortality and the occurrence of chikungunya epidemics has been shown, supporting the hypothesis that many of these excess deaths were a consequence of CHIKV infections. Thus, accumulated experience has highlighted that the current chikungunya case classification does not encompass the actual needs presented by certain cases with atypical features nor does it contribute to early detection and management of potentially severe cases. With continued CHIKV circulation in three continents and recent reemergence in Asia and Europe, we need a classification that is prospective and informed both by initial clinical presentation and by progression of signs and symptoms.