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Despite the considerable advances in the last years, the health information systems for health surveillance still need to overcome some critical issues so that epidemic detection can be performed in real time. For instance, despite the efforts of the Brazilian Ministry of Health (MoH) to make COVID-19 data available during the pandemic, delays due to data entry and data availability posed an additional threat to disease monitoring. Here, we propose a complementary approach by using electronic medical records (EMRs) data collected in real time to generate a system to enable insights from the local health surveillance system personnel. As a proof of concept, we assessed data from São Caetano do Sul City (SCS), São Paulo, Brazil. We used the "fever" term as a sentinel event. Regular expression techniques were applied to detect febrile diseases. Other specific terms such as "malaria," "dengue," "Zika," or any infectious disease were included in the dictionary and mapped to "fever." Additionally, after "tokenizing," we assessed the frequencies of most mentioned terms when fever was also mentioned in the patient complaint. The findings allowed us to detect the overlapping outbreaks of both COVID-19 Omicron BA.1 subvariant and Influenza A virus, which were confirmed by our team by analyzing data from private laboratories and another COVID-19 public monitoring system. Timely information generated from EMRs will be a very important tool to the decision-making process as well as research in epidemiology. Quality and security on the data produced is of paramount importance to allow the use by health surveillance systems.

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IMPORTANCE: The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family.

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Snakebite envenomations (SBEs) in pregnant women can result in adverse maternal or neonatal effects, such as abortion, placental abruption, preterm labor, fetal malformations, and maternal, fetal or neonatal deaths. Despite the high incidence of SBEs in the Brazilian Amazon, there is no literature on the impact of SBEs on pregnancy outcomes. The objective of this study was to describe clinical epidemiology and outcomes associated with SBEs in women of childbearing age and pregnant women in the state of Amazonas, Western Brazilian Amazon, from 2007 to 2021. Information on the population was obtained from the Reporting Information System (SINAN), Mortality Information System (SIM) and Live Birth Information System (SINASC) for the period from 2007 to 2021. A total of 36,786 SBEs were reported, of which 3,297 (9%) involved women of childbearing age, and 274 (8.3%) involved pregnant women. Severity (7.9% in pregnant versus 8.7% in non-pregnant women) (P = 0.87) and case-fatality (0.4% in pregnant versus 0.3% in non-pregnant women) rates were similar between groups (P = 0.76). Pregnant women who suffered snakebites were at higher risk for fetal death (OR: 2.17, 95%CI: 1.74-2.67) and neonatal death (OR = 2.79, 95%CI: 2.26-3.40). This study had major limitations related to the completeness of the information on the pregnancy outcomes. Although SBE incidence in pregnant women is low in the Brazilian Amazon, SBEs increased the risk of fetal and neonatal deaths.

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The exact path leading to cognitive impairment that goes beyond malaria is unclear, but it appears to be the result of interactive factors. Time of exposure to disease and recurrences are potentially major determinant variables. Cognitive impairment is described mainly in children, rarely in adults. The disease in high endemic areas usually does not affect elderlies, because of acquired immunity over time. However, this population is relatively more frequently sick in lower endemic areas, such as in the Amazon. This study assessed the effect of Plasmodium vivax malaria on the executive and cognitive functions of elderlies, in the Brazilian Amazon. A cohort study was conducted to evaluate executive and cognitive functions one week (T0), two months (T2) and eight months (T8) after the malaria episode. Mini-Mental State Examination (MMSE), Beck Depression Inventory II (BDI-II), Clock Drawing Test (CDT), Wechsler adult intelligence scale (WAIS-III), and Wisconsin Card Sorting Test (WCST) were used to assess executive and cognitive functions. One hundred-forty elderlies were enrolled (70 with P. vivax malaria and 70 without malaria). P. vivax malaria was associated with impairment of the executive and cognitive functions in elderlies for up to 8 months after acute P. vivax malaria. Prior history of malaria, recurrences and higher parasitemia were independently associated with various surrogates of executive and cognitive impairment. With the increase in life expectancy, elderlies living in malaria endemic areas will deserve more attention from health authorities, to guarantee improvement of their quality of life in the tropics.

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BACKGROUND: As quantitative glucose 6-phosphate dehydrogenase deficiency (G6PDd) screening tools are evaluated in operational studies, questions remain as to whether they are cost-effective. Here, a cost-effectiveness analysis (CEA) was performed to estimate the Incremental Cost-effectiveness Ratio (ICER) of the introduction of quantitative screening test to detect G6PDd among P. vivax carriers in two municipalities in the Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: This cost-effectiveness analysis evaluated the use of the Standard G6PD quantitative screening test in vivax malaria treatment units in two municipalities of the Brazilian Amazon. Using the perspective of the Brazilian public health system, the analysis was performed for the outcome 'PQ-associated hospitalization avoided', based on a decision tree model. The results indicated that the G6PDd screening strategy compared with the routine strategy was highly cost-effective, with an ICER of US$495 per additional hospitalization avoided, which represented less than 8% of one Brazilian gross domestic product per capita (US$6,822). The uncertainties evaluated in the sensitivity analysis did not significantly affect the ICER identified in the base-case. CONCLUSIONS/SIGNIFICANCE: This cost-effectiveness analysis showed the quantitative G6PD testing was effective in avoiding PQ-associated hospitalizations. The incorporation of G6PD screening is of paramount importance towards P. vivax malaria elimination in the Amazon to promote the safe use of primaquine and tafenoquine.

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In Brazil, malaria caused by Plasmodium vivax presents control challenges due to several reasons, among them the increasing possibility of failure of P. vivax treatment due to chloroquine-resistance (CQR). Despite limited reports of CQR, more extensive studies on the actual magnitude of resistance are still needed. Short-time recurrences of malaria cases were analyzed in different transmission scenarios over three years (2005, 2010, and 2015), selected according to malaria incidence. Multilevel models (binomial) were used to evaluate association of short-time recurrences with variables such as age. The zero-inflated Poisson scan model (scanZIP) was used to detect spatial clusters of recurrences up to 28 days. Recurrences compose less than 5% of overall infection, being more frequent in the age group under four years. Recurrences slightly increased incidence. No fixed clusters were detected throughout the period, although there are clustering sites, spatially varying over the years. This is the most extensive analysis of short-time recurrences worldwide which addresses the occurrence of P. vivax CQR. As an important step forward in malaria elimination, policymakers should focus their efforts on young children, with an eventual shift in the first line of malaria treatment to P. vivax.

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BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. Although the deleterious health effects of primaquine in G6PD deficient individuals have been known for over 50 years, G6PD testing is not routinely performed before primaquine treatment in most P. vivax endemic areas. METHOD/PRINCIPAL FINDINGS: The qualitative CareStart G6PD screening test was implemented in 12 malaria treatment units (MTUs) in the municipality of Rio Preto da Eva, Western Brazilian Amazon, a malaria endemic area, between February 2019 and early January 2020. Training materials were developed and validated; evaluations were conducted on the effectiveness of training health care professionals (HCPs) to perform the test, the interpretation and reliability of routine testing performed by HCPs, and perceptions of HCPs and patients. Most HCPs were unaware of G6PD deficiency and primaquine-related adverse effects. Most of 110 HCPs trained (86/110, 78%) were able to correctly perform the G6PD test after a single 4-hour training session. The test performed by HCPs during implementation showed 100.0% (4/4) sensitivity and 68.1% (62/91) specificity in identifying G6PD deficient patients as compared to a point-of-care quantitative test (Standard G6PD). CONCLUSIONS/SIGNIFICANCE: G6PD screening using the qualitative CareStart G6PD test performed by HCPs in MTUs of an endemic area showed high sensitivity and concerning low specificity. The amount of false G6PD deficiency detected led to substantial loss of opportunities for radical cure.

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Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit Mycobacterium tuberculosis infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology.

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Bothrops snakebites usually present systemic bleeding, and the clinical⁻epidemiological and laboratorial factors associated with the development of this manifestation are not well established. In this study, we assessed the prevalence of Bothrops snakebites with systemic bleeding reported at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, in Manaus, Amazonas State, Brazil, and the clinical⁻epidemiological and laboratorial factors associated with systemic bleeding. This is an observational, cross-sectional study carried out between August, 2013 and July, 2016. Patients who developed systemic bleeding on admission or during hospitalization were considered cases, and those with non-systemic bleeding were included in the control group. Systemic bleeding was observed in 63 (15.3%) of the 442 Bothrops snakebites evaluated. Bothrops snakebites mostly occurred in males (78.2%), in rural areas (89.0%) and in the age group of 11 to 30 years old (40.4%). It took most of the patients (59.8%) less than 3 h to receive medical assistance. Unclottable blood (AOR = 3.11 (95% CI = 1.53 to 6.31; p = 0.002)) and thrombocytopenia (AOR = 4.52 (95% CI = 2.03 to 10.09; p < 0.001)) on admission were independently associated with systemic bleeding during hospitalization. These hemostatic disorders on admission increase the chances of systemic bleeding during hospitalization. Prospective studies are needed to clarify the pathophysiology of systemic bleeding in Bothrops snakebites in the Amazon region.

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