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Background: A better knowledge of the burden and risk factors associated with severity due to spider bites would lead to improved management with a reduction of sequelae usually seen for this neglected health problem, and would ensure proper use of antivenoms in remote localities in the Brazilian Amazon. The aim of this study was to analyze the profile of spider bites reported in the state of Amazonas in the Western Brazilian Amazon, and to investigate potential risk factors associated with severity of envenomation. Methodology/Principal Findings: We used a case-control study in order to identify factors associated with spider bite severity in the Western Brazilian Amazon from 2007 to 2014. Patients evolving to any severity criteria were considered cases and those with non-severe bites were included in the control group. All variables were retrieved from the official Brazilian reporting systems. Socioeconomical and environmental components were also included in a multivariable analysis in order to identify ecological determinants of incidence and severity. A total of 1,181 spider bites were recorded, resulting in an incidence of 4 cases per 100,000 person/year. Most of the spider bites occurred in males (65.8%). Bites mostly occurred in rural areas (59.5%). The most affected age group was between 16 and 45 years old (50.9%). A proportion of 39.7% of the bites were related to work activities. Antivenom was prescribed to 39% of the patients. Envenomings recorded from urban areas [Odds ratio (OR) = 0.40 (95%CI = 0.30–0.71; p<0.001)] and living in a municipality with a mean health system performance index (MHSPI >median [OR = 0.64 (95%CI = 0.39–0.75; p<0.001)] were independently associated with decreased risk of severity. Work related accidents [OR = 2.09 (95%CI = 1.49–2.94; p<0.001)], Indigenous status [OR = 2.15 (95%CI = 1.19–3.86; p = 0.011)] and living in a municipality located >300 km away from the state capital Manaus [OR = 1.90 (95%CI = 1.28–2.40; p<0.001)] were independently associated with a risk of severity. Living in a municipality located >300 km away from the state capital Manaus [OR = 1.53 (95%CI = 1.15–2.02; p = 0.003)] and living in a municipality with a MHSPI 300 km away from the state capital Manaus could be contributing factors to higher severity of spider envenomings in this area, as well as to antivenom underdosage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute Kidney Injury (AKI) is the main systemic complication and cause of death in viperid envenomation. Although there are hypotheses for the development of AKI, the mechanisms involved are still not established. The aim of this study was to evaluate the clinical-laboratorial-epidemiological factors associated with AKI in victims of Bothrops sp envenomation. This is an observational study carried out at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. AKI was defined according to the guidelines of the Acute Kidney Injury Network (AKIN). Among the 186 patients evaluated, AKI was observed in 24 (12.9%) after 48 hours of admission. Stage I was present in 17 (70.8%) patients, II in 3 (12.5%) and III in 4 (16.7%). Epidemiological characterization showed predominance of men, occurrence in rural areas, aged between 16–60 years, feet as the most affected anatomical region, and time to medical assistance less than 3 hours. Hypertension and diabetes were the comorbidities identified. Most of the accidents were classified as moderate, and clinical manifestations included severe pain, mild edema, local bleeding and headache. Laboratory results showed blood uncoagulability, hypofibrinogenemia, leukocytosis, increase of creatine kinase, and high lactate dehydrogenase levels. Multivariate analysis showed an association with high LDH levels [AOR = 1.01 (95% CI = 1.01–1.01, p<0.002)], local bleeding [AOR = 0.13 (95%CI = 0.027–0.59, p<0.009)], and the presence of comorbidities [AOR = 60.96 (95%CI = 9.69–383.30; p<0.000)]. Herein, laboratory markers such as high LDH levels along with local bleeding and comorbidities may aid in the diagnosis of AKI. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an RNA flavivirus (Flaviviridae family) endemic in tropical and subtropical regions that is transmitted to humans by Aedes (Stegomyia) species mosquitoes. The two main urban vectors of ZIKV are Aedes aegypti and Aedes albopictus, which can be found throughout Brazil. This study investigated ZIKV infection in mosquito species sampled from urban forest fragments in Manaus (Brazilian Amazon). A total of 905 non-engorged female Ae. aegypti (22 specimens) and Ae. albopictus (883 specimens) were collected using BG-Sentinel traps, entomological hand nets, and Prokopack aspirators during the rainy and dry seasons between 2018 and 2021. All pools were macerated and used to inoculate C6/36 culture cells. Overall, 3/20 (15%) Ae. aegypti and 5/241 (2%) Ae. albopictus pools screened using RT-qPCR were positive for ZIKV. No supernatants from Ae. aegypti were positive for ZIKV (0%), and 15 out of 241 (6.2%) Ae. albopictus pools were positive. In this study, we provide the first-ever evidence of Ae. albopictus naturally infected with ZIKV in the Amazon region. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is currently considered a neglected tropical disease, which affects over 5 million people worldwide, and causes almost 150 000 deaths every year, as well as severe injuries, amputations and other sequelae. Snakebite envenoming in children, although proportionally less frequent, is generally more severe, and represents an important challenge for pediatric medicine, since they often result in worse outcomes. In Brazil, given its ecological, geographic and socioeconomic characteristics, snakebites are considered an important health problem, presenting approximately 30 000 victims per year, approximately 15% of them in children. Even with low snakebite incidence, children tend to have higher snakebite severity and complications due to the small body mass and same venom volume inoculated in comparison to adults, even though, due to the lack of epidemiological information about pediatric snakebites and induced injuries, it is difficult to measure the treatment effectiveness, outcomes and quality of emergency medical services for snakebites in children. In this review, we report how Brazilian children are affected by snakebites, describing the characteristics of this affected population, clinical aspects, management, outcomes and main challenges. [ABSTRACT FROM AUTHOR]

Globally, malaria and human immunodeficiency virus (HIV) are both independently associated with a massive burden of disease and death. While their co-infection has been well studied for Plasmodium falciparum, scarce data exist regarding the association of P. vivax and HIV. In this cohort study, we assessed the effect of HIV on the risk of vivax malaria infection and recurrence during a 4-year follow-up period in an endemic area of the Brazilian Amazon. For the purpose of this study, we obtained clinical information from January 2012 to December 2016 from two databases. HIV screening data were acquired from the clinical information system at the tropical hospital Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD). The National Malaria Surveillance database (SIVEP malaria) was utilized to identify malaria infections during a 4-year follow-up period after diagnosis of HIV. Both datasets were combined via data linkage. Between 2012 and 2016, a total of 42,121 people were screened for HIV, with 1569 testing positive (3.7%). Out of all the patients diagnosed with HIV, 198 had at least one episode of P. vivax malaria in the follow-up. In the HIV-negative group, 711 participants had at least one P. vivax malaria episode. When comparing both groups, HIV patients had a 6.48 [(5.37–7.83); P < 0.0001] (adjusted relative risk) greater chance of acquiring P. vivax malaria. Moreover, being of the male gender [ARR = 1.41 (1.17–1.71); P < 0.0001], Amerindian ethnicity [ARR = 2.77 (1.46–5.28); P < 0.0001], and a resident in a municipality of the Metropolitan region of Manaus [ARR = 1.48 (1.02–2.15); P = 0.038] were independent risk factors associated with an increased risk of clinical malaria. Education ≥ 8 years [ARR = 0.41 (0.26–0.64); P < 0.0001] and living in the urban area [ARR = 0.44 (0.24–0.80); P = 0.007] were associated to a lower risk of P. vivax malaria. A total of 28 (14.1%) and 180 (25.3%) recurrences (at least a second clinical malaria episode) were reported in the HIV-positive and HIV-negative groups, respectively. After adjusting for sex and education, HIV-positive status was associated with a tendency towards protection from P. vivax malaria recurrences [ARR = 0.55 (0.27–1.10); P = 0.090]. HIV status was not associated with hospitalizations due to P. vivax malaria. CD4 + counts and viral load were not associated with recurrences of P. vivax malaria. No significant differences were found in the distribution of parasitemia between HIV-negative and HIV-positive P. vivax malaria patients. Our results suggest that HIV-positive status is a risk factor for vivax malaria infection, which represents an additional challenge that should be addressed during elimination efforts. [ABSTRACT FROM AUTHOR]

Globally, malaria and human immunodeficiency virus (HIV) are both independently associated with a massive burden of disease and death. While their co-infection has been well studied for Plasmodium falciparum, scarce data exist regarding the association of P. vivax and HIV. In this cohort study, we assessed the effect of HIV on the risk of vivax malaria infection and recurrence during a 4-year follow-up period in an endemic area of the Brazilian Amazon. For the purpose of this study, we obtained clinical information from January 2012 to December 2016 from two databases. HIV screening data were acquired from the clinical information system at the tropical hospital Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD). The National Malaria Surveillance database (SIVEP malaria) was utilized to identify malaria infections during a 4-year follow-up period after diagnosis of HIV. Both datasets were combined via data linkage. Between 2012 and 2016, a total of 42,121 people were screened for HIV, with 1569 testing positive (3.7%). Out of all the patients diagnosed with HIV, 198 had at least one episode of P. vivax malaria in the follow-up. In the HIV-negative group, 711 participants had at least one P. vivax malaria episode. When comparing both groups, HIV patients had a 6.48 [(5.37–7.83); P < 0.0001] (adjusted relative risk) greater chance of acquiring P. vivax malaria. Moreover, being of the male gender [ARR = 1.41 (1.17–1.71); P < 0.0001], Amerindian ethnicity [ARR = 2.77 (1.46–5.28); P < 0.0001], and a resident in a municipality of the Metropolitan region of Manaus [ARR = 1.48 (1.02–2.15); P = 0.038] were independent risk factors associated with an increased risk of clinical malaria. Education ≥ 8 years [ARR = 0.41 (0.26–0.64); P < 0.0001] and living in the urban area [ARR = 0.44 (0.24–0.80); P = 0.007] were associated to a lower risk of P. vivax malaria. A total of 28 (14.1%) and 180 (25.3%) recurrences (at least a second clinical malaria episode) were reported in the HIV-positive and HIV-negative groups, respectively. After adjusting for sex and education, HIV-positive status was associated with a tendency towards protection from P. vivax malaria recurrences [ARR = 0.55 (0.27–1.10); P = 0.090]. HIV status was not associated with hospitalizations due to P. vivax malaria. CD4 + counts and viral load were not associated with recurrences of P. vivax malaria. No significant differences were found in the distribution of parasitemia between HIV-negative and HIV-positive P. vivax malaria patients. Our results suggest that HIV-positive status is a risk factor for vivax malaria infection, which represents an additional challenge that should be addressed during elimination efforts. [ABSTRACT FROM AUTHOR]

Background: Although considerable success in reducing the incidence of malaria has been achieved in Brazil in recent years, an increase in the proportion of cases caused by the harder-to-eliminate Plasmodium vivax parasite can be noted. Recurrences in P. vivax malaria cases are due to new mosquito-bite infections, drug resistance or especially from relapses arising from hypnozoites. As such, new innovative surveillance strategies are needed. The aim of this study was to develop an infographic visualization tool to improve individual-level malaria surveillance focused on malaria elimination in the Brazilian Amazon. Methods: Action Research methodology was employed to deal with the complex malaria surveillance problem in the Amazon region. Iterative cycles were used, totalling four cycles with a formal validation of an operational version of the Malaria Trigram tool at the end of the process. Further probabilistic data linkage was carried out so that information on the same patients could be linked, allowing for follow-up analysis since the official system was not planned in such way that includes this purpose. Results: An infographic user interface was developed for the Malaria Trigram that incorporates all the visual and descriptive power of the Trigram concept. It is a multidimensional and interactive historical representation of malaria cases per patient over time and provides visual input to decision-makers on recurrences of malaria. Conclusions: The Malaria Trigram is aimed to help public health professionals and policy makers to recognise and analyse different types of patterns in malaria events, including recurrences and reinfections, based on the current Brazilian health surveillance system, the SIVEP-Malária system, with no additional primary data collection or change in the current process. By using the Malaria Trigram, it is possible to plan and coordinate interventions for malaria elimination that are integrated with other parallel actions in the Brazilian Amazon region, such as vector control management, effective drug and vaccine deployment strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. Methods A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. Results From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. Conclusions The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. Clinical Trials Registration NCT04343729. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite the availability of effective antimicrobials, tuberculosis (TB) is still a serious health threat. Mortality is even higher in people living with HIV who are diagnosed with TB. New therapies are needed to shorten the time required to cure TB and decrease fatality rates in this population. N-acetylcysteine (NAC) is a glutathione precursor and has shown recently in experimental setting to present in vitro and in vivo anti-mycobacterial activity. We test the hypothesis that NAC is safe, well tolerated and secondarily efficacious as adjunctive anti-TB therapy in hospitalized individuals with HIV-associated TB. Patients were enrolled sequentially in a tertiary care center, in the Brazilian Amazon. We performed a randomized, parallel group, single-center, open study trial of two arms, in hospitalized patients over 18 years of age, with microbiologically confirmed pulmonary TB in HIV: one with rifampicin, isoniazid, pyrazinamide and ethambutol at standard doses (Control Group), and a second in which NAC 600 mg bid for eight weeks was added (NAC Group). A total of 21 and 18 patients were enrolled to the Control Group and NAC Group, respectively. Adverse event rates were similar in the two arms. Our findings suggest that in the more critical population of hospitalized patients with HIV-associated TB, the use of NAC was not unsafe, despite the low sample size, and a potential impact on faster negative cultures needs to be further explored in larger studies. [ABSTRACT FROM AUTHOR]

Background: Brazil has considerably reduced the number of cases of malaria in recent years and aims to eradicate the disease completely, however, vivax malaria continues to be a major challenge for the health system. In this context, the key to building a successful elimination programme may lie in the knowledge and the perceptions of the health agents, the patients affected by the disease and the personnel responsible for malaria diagnosis, treatment and control at the local level. Methods: A qualitative study was undertaken in Manaus, capital of the state of Amazonas, Western Brazilian Amazon, using a sample of 33 patients who were being treated for malaria and 22 health agents who were working in malaria diagnosis, treatment and control at the local level. A semi-structured interview with a further thematic analysis was performed. Results: There are still many myths regarding malaria transmission and treatment that may hinder the sensitization of the population of this region in relation to the use of current control tools and elimination strategies, such as mass drug administration (MDA). Most health professionals reported that the abandonment of treatment for malaria by the patient is related to poor social conditions, the high incidence of alcoholism and the low level of schooling of the affected population. One negative perception, observed in both groups with regard to the use of insecticide-treated nets, is that they may cause skin irritations and allergies. Most patients and health professionals have described malaria as an impossible disease to eliminate because it is intrinsically associated with forest landscapes, and according to them, elimination would only be possible if there were a vaccine against malaria. Conclusion: In the Amazon, cultural perceptions about the etiology of this disease can influence the behaviour and practices that social groups adopt in relation to the different forms of living in a malaria-endemic context. Negative perceptions about malaria elimination can act as a barrier when trying to reach proper coverage for control strategies such as mosquito nets and MDA. [ABSTRACT FROM AUTHOR]

Introduction: Leukemia is the most common cancer in children and has the highest rates of incidence in industrialized countries, followed by developing countries. This epidemiologic profile can mainly be attributed to the availability of diagnostic resources. In Brazil, leukemia diagnosis is a challenge due to financial viability, lack of hemovigilance services in isolated regions and the vast size of the territory. Its incidence in the state of Amazonas has been increasing since 2010. Therefore, this study aims to describe the epidemiological pattern and spatial distribution of patients with acute lymphoid leukemia and acute myeloid leukemia in Amazonas and identify the predictors of comorbidity and death. Materials and methods: A retrospective cross-sectional study was carried out based on patients’ data which was obtained from the database of a referral center for the period of 2005 to 2015. Variables included age, gender, ethnicity, civil status, schooling, income, location of residence, subtype of leukemia, comorbidities, and date of death. The spatial distribution was performed using QGIS v.2.18. Stata software was used for univariable and multivariable logistic regression to evaluate the association between both comorbidities and death for all characteristic groups of ALL and AML. Results: The group that was studied was composed of 577 ALL and 266 AML patients. For both, most patients were male, with a schooling period of 1–4 years, received<1 minimum wage, and lived mostly in Manaus, followed by the municipality of Tefé. There was no association between the development of comorbidities and analyzed variables in patients with ALL. AML patients that were >60 years old and with family history of the disease had the highest risk of developing comorbidities (OR = 5.06, p = 0.038; OR = 2.44, p = 0.041, respectively). Furthermore, patients with ALL and in the 41-50-year age group had a higher risk of death (OR = 31.12; p = 0.001). No association between death and explanatory variables were found in patients with AML. In addition, significant difference was observed in time to death (chi2 = 4,098.32, p = 0.000), with 50% of patients with AML dying within two years after diagnosis, whereas in ALL, this percentual of death only is reached in approximately 5 years. Conclusion: Our study describes the data of patients with acute leukemia in Amazonas, a remote region in the north of Brazil. In addition, it highlights the importance of hemovigilance in an Amazon region state, while focusing on peripheral areas which don't have prevention, diagnosis and treatment tools for this disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax malaria (Pv-malaria) is still considered a neglected disease despite an alarming number of individuals being infected annually. Malaria pathogenesis occurs with the onset of the vector-parasite-host interaction through the binding of pathogen-associated molecular patterns (PAMPs) and receptors of innate immunity, such as toll-like receptors (TLRs). The triggering of the signaling cascade produces an elevated inflammatory response. Genetic polymorphisms in TLRs are involved in susceptibility or resistance to infection, and the identification of genes involved with Pv-malaria response is important to elucidate the pathogenesis of the disease and may contribute to the formulation of control and elimination tools. Methodology/Principal findings: A retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the state of Amazonas, Brazil. Genetic polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 325 patients infected with P. vivax and 274 healthy individuals without malaria history in the prior 12 months from the same endemic area. Parasite load was determined by qPCR. Simple and multiple logistic/linear regressions were performed to investigate association between the polymorphisms and the occurrence of Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T (TLR9 -1486C/T) genotypes appear to be risk factors for infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI: 1.054–4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI: 1.159–3.177, p = 0.010]; respectively). Fever (COEF = 7599.46, 95% CI = 3063.80–12135.12, p = 0.001) and the C/C genotype of TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83–30540.44, p = 0.014) were independently associated with increased parasitemia in patients with Pv-malaria. Conclusions: Variants of TLRs may predispose individuals to infection by P. vivax. The TLR5 R392StopCodon and TLR9 -1486C/T variants are associated with susceptibility to Pv-malaria. Furthermore, the TLR9 variant -1237C/C correlates with high parasitemia. [ABSTRACT FROM AUTHOR]

The article explores clinical observations about our randomized METCOVID clinical trial on the efficacy of methylprednisolone (MP) in the adjuvant treatment of coronavirus disease 2019 (COVID-19). As the benefit of MP for 5 days was estimated to be 50%, it is likely that the overall final analysis was not powered to estimate such a difference.