Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon

ABSTRACT Objective: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. Methods: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. Results: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. Conclusion: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study

ABSTRACT Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials.

Effect of weekly versus daily primaquine on Plasmodium vivax malaria recurrences: A real-life cohort study

ABSTRACT Background: Although primaquine (PQ) is indicated for G6PD-deficient patients, data on weekly PQ use in Brazil are limited. Methods: We aimed to investigate malaria recurrences among participants receiving daily and weekly PQ treatments in a real-life setting of two municipalities in the Amazon between 2019 and 2020. Results: Patients receiving weekly PQ treatment had a lower risk of recurrence than those receiving daily PQ treatment (risk ratio: 0.62, 95% confidence interval: 0.41-0.94), using a model adjusted for study site. Conclusions: Weekly PQ use did not increase the risk of malaria recurrence. Further studies with larger populations are warranted.

Prevalence and force of Plasmodium vivax blood-stage infection and associated clinical malaria burden in the Brazilian Amazon

BACKGROUND Understanding the epidemiology of malaria through the molecular force of the blood-stage infection of Plasmodium vivax (molFOB) may provide a detailed assessment of malaria transmission. OBJECTIVES In this study, we investigated risk factors and spatial-temporal patterns of incidence of Plasmodium infection and clinical malaria episodes in three peri-urban communities of Manaus, Western Brazilian Amazon. METHODS Monthly samples were collected in a cohort of 1,274 individuals between April 2013 and March 2014. DNA samples were subject to Plasmodium species. molFOB was calculated by counting the number of genotypes observed on each visit, which had not been present in the preceding two visits and adjusting these counts by the respective times-at-risk. FINDINGS Respectively, 77.8% and 97.2% of the population remained free of P. vivax and P. falciparum infection. Expected heterozygosity for P. vivax was 0.69 for MSP1_F3 and 0.86 for MS2. Multiplicity of infection in P. vivax was close to the value of 1. The season was associated with P. vivax positivity [adjusted hazard ratio (aHR) 2.6 (1.9-5.7)] and clinical disease [aHR 10.6 (2.4-47.2)]. P. falciparum infection was associated with previous malarial episodes [HR 9.7 (4.5-20.9)]. Subjects who reported possession of a bed net [incidence rate ratio (IRR) 1.6 (1.2-2.2)] or previous malaria episodes [IRR 3.0 (2.0-4.5)] were found to have significantly higher P. vivax molFOB. MAIN CONCLUSIONS Overall, P. vivax infection prevailed in the area and infections were mostly observed as monoclonal. Previous malaria episodes were associated with significantly higher P. vivax molFOB.

Prediction of malaria using deep learning models: A case study on city clusters in the state of Amazonas, Brazil, from 2003 to 2018

ABSTRACT Background: Malaria is curable. Nonetheless, over 229 million cases of malaria were recorded in 2019, along with 409,000 deaths. Although over 42 million Brazilians are at risk of contracting malaria, 99% percent of all malaria cases in Brazil are located in or around the Amazon rainforest. Despite declining cases and deaths, malaria remains a major public health issue in Brazil. Accurate spatiotemporal prediction of malaria propagation may enable improved resource allocation to support efforts to eradicate the disease. Methods: In response to calls for novel research on malaria elimination strategies that suit local conditions, in this study, we propose machine learning (ML) and deep learning (DL) models to predict the probability of malaria cases in the state of Amazonas. Using a dataset of approximately 6 million records (January 2003 to December 2018), we applied k-means clustering to group cities based on their similarity of malaria incidence. We evaluated random forest, long-short term memory (LSTM) and dated recurrent unit (GRU) models and compared their performance. Results: The LSTM architecture achieved better performance in clusters with less variability in the number of cases, whereas the GRU presents better results in clusters with high variability. Although Diebold-Mariano testing suggested that both the LSTM and GRU performed comparably, GRU can be trained significantly faster, which could prove advantageous in practice. Conclusions: All models showed satisfactory accuracy and strong performance in predicting new cases of malaria, and each could serve as a supplemental tool to support regional policies and strategies.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Fatores associados à mortalidade por causas inespecíficas e mal definidas no estado do Amazonas, Brasil, de 2006 a 2012 / Factors associated with unspecified and ill-defined causes of death in the State of Amazonas, Brazil, from 2006 to 2012

Resumo Objetivou-se investigar fatores associados à mortalidade por causas inespecíficas e mal definidas no estado do Amazonas (AM). Desenvolveu-se um estudo seccional incluindo 90.439 registros de óbitos não fetais, com residência e ocorrência no AM entre 2006 e 2012. Foram estimadas razões de chances de causas inespecíficas e mal definidas por meio de regressão logística multinomial hierárquica. A proporção de causas mal definidas e inespecíficas foi, respectivamente, 16,6% e 9,1%. A ocorrência de causas mal definidas diminuiu ao longo dos anos e a de causas inespecíficas somente no último biênio. As causas inespecíficas associaram-se com residência e ocorrência do óbito fora da capital, via pública, sexo feminino, dos 10 aos 49 anos, cor parda e quando atestadas por legistas. As causas mal definidas associaram-se com residência e ocorrência fora da capital, em domicílios, a partir de 40 anos, cor não branca, não ser solteiro, baixa escolaridade, assistência médica e falta de informação sobre o atestante. A mortalidade por causas mal definidas e inespecíficas no AM declinou entre 2006 e 2012, associando-se às dimensões espacial e temporal, fatores demográficos, socioeconômicos e à assistência médica na ocasião do óbito.

Abstract This study aimed to investigate factors associated with unspecified and ill-defined causes of death in the State of Amazonas (AM), Brazil. This is a cross-sectional study on 90,439 non-fetal deaths of residents in AM from 2006 to 2012. The hierarchical multinomial logistic model estimated odds ratios of unspecified and ill-defined causes of death. Ill-defined and unspecified causes of death proportional mortality was, respectively, 16.6% and 9.1%. Ill-defined causes showed a decreasing trend over the years, while unspecified causes only decreased in the last two years. Unspecified causes of death were associated with residence and death outside the capital, public roads, female gender, age group 10-49 years, brown skin color and when certified by forensic doctors. Ill-defined causes of death were associated with residence and occurrence outside capital, at home, ages 40 years and older, non-whites, not being single, low schooling, under medical care and when examiner was unknown. Ill-defined and unspecified cause mortality in the State of Amazonas decreased between 2006 and 2012 in AM and was associated with space and time, demographic and socioeconomic factors and medical care at the moment of death.

Do climate changes alter the distribution and transmission of malaria? Evidence assessment and recommendations for future studies

Abstract Malaria, a mosquito-borne infectious disease, is considered a significant global health burden. Climate changes or different weather conditions may impact infectious diseases, specifically those transmitted by insect vectors and contaminated water. Based on the current predictions for climate change associated with the increase in carbon dioxide concentrations in the atmosphere and the increase in atmospheric temperature, the Intergovernmental Panel on Climate Change predicts that in 2050, malaria may threaten some previously unexposed areas worldwide and cause a 50% higher probability of malaria cases. Climate-based distribution models of malaria depict an increase in the geographic distribution of the disease as global environmental temperatures and conditions worsen. Researchers have studied the influence of changes in climate on the prevalence of malaria using different mathematical models that consider different variables and predict the conditions for malaria distribution. In this context, we conducted a mini-review to elucidate the important aspects described in the literature on the influence of climate change in the distribution and transmission of malaria. It is important to develop possible risk management strategies and enhance the surveillance system enhanced even in currently malaria-free areas predicted to experience malaria in the future.

Overview of artemisinin effectiveness during outset years of its implementation in the western Brazilian Amazon

BACKGROUND The elimination of malaria depends on the blocking of transmission and of an effective treatment. In Brazil, artemisinin therapy was introduced in 1991, and here we present a performance overview during implementation outset years. METHODS It is a retrospective cohort (1991 to 2002) of patients treated in a tertiary centre of Manaus, with positive microscopic diagnosis of Plasmodium falciparum malaria, under treatment with using injectable or rectal artemisinin derivatives, and followed over 35-days to evaluate parasite clearance, death and recurrence. FINDINGS This cohort outcome resulted 97.6% (1554/1593) of patients who completed the 35-day follow-up, 0.6% (10/1593) of death and 1.8% (29/1593) of follow-up loss. All patients that died and those that presented parasitaemia recurrence had pure P. falciparum infections and received monotherapy. Considering patients who completed 35-day treatment, 98.2% (1527/1554) presented asexual parasitaemia clearance until D4 and 1.8% (27/1554) between D5-D10. It is important to highlight that had no correlation between the five treatment schemes and the sexual parasite clearance. Finally, it is noteworthy that we were able to observe also gametocytes carriage during all follow-up (D0-D35). MAIN CONCLUSIONS Artemisinin derivatives remained effective in the treatment of falciparum malaria during first 12-years of use in north area of Brazil.

Current vector control challenges in the fight against malaria in Brazil

Abstract In Brazil, malaria is an important public health problem first reported in 1560. Historically, fluctuations in malaria cases in Brazil are attributed to waves of economic development; construction of railroads, highways, and hydroelectric dams; and population displacement and land occupation policies. Vector control measures have been widely used with an important role in reducing malaria cases. In this review article, we reviewed the vector control measures established in the Brazilian territory and aspects associated with such measures for malaria. Although some vector control measures are routinely used in Brazil, many entomological and effectiveness information still need better evidence in endemic areas where Plasmodium vivax predominates. Herein, we outlined some of the needs and priorities for future research: a) update of the cartography of malaria vectors in Brazil, adding molecular techniques for the correct identification of species and complexes of species; b) evaluation of vector competence of anophelines in Brazil; c) strengthening of local entomology teams to perform vector control measures and interpret results; d) evaluation of vector control measures, especially use of insecticide-treated nets and long-lasting insecticidal nets, estimating their effectiveness, cost-benefit, and population acceptance; e) establishment of colonies of malaria vectors in Brazil, i.e., Anopheles darlingi, to understand parasite-vector interactions better; f) study of new vector control strategies with impacts on non-endophilic vectors; g) estimation of the impact of insecticide resistance in different geographical areas; and h) identification of the relative contribution of natural and artificial breeding sites in different epidemiological contexts for transmission.

Delayed healthcare and secondary infections following freshwater stingray injuries: risk factors for a poorly understood health issue in the Amazon

Abstract INTRODUCTION This study aimed to describe the profile of freshwater stingray injuries in the State of Amazonas, Brazilian Amazon, and to identify the associated risk factors for secondary infections. METHODS This cross-sectional study used surveillance data from 2007 to 2014 to identify factors associated with secondary infections from stingray injuries. RESULTS A total of 476 freshwater stingray injuries were recorded, with an incidence rate of 1.7 cases/100,000 person/year. The majority of injuries were reported from rural areas (73.8%) and 26.1% were related to work activities. A total of 74.5% of patients received medical assistance within the first 3 hours of injury. Secondary infections and necrosis were observed in 8.9% and 3.8%, respectively. Work-related injuries [odds ratio (OR) 4.1, confidence interval (CI); 1.87-9.13] and >24 hours from a sting until receiving medical care (OR; 15.5, CI; 6.77-35.40) were independently associated with the risk of secondary bacterial infection. CONCLUSIONS: In this study, work-related injuries and >24 hours from being stung until receiving medical care were independently and significantly associated with the risk of secondary infection. The frequency of infection following sting injuries was 9%. The major factor associated with the risk of secondary bacterial infection was a time period of >24 hours from being stung until receiving medical care.

Hymenoptera stings in Brazil: a neglected health threat in Amazonas State

Abstract INTRODUCTION: Hymenoptera injuries are commonly caused by stinging insects. In Amazonas state, Brazil, there is no information regarding distribution, profile, and systemic manifestations associated with Hymenoptera injuries. METHODS: This study aimed to identify risk factors for systemic manifestation using the Brazilian Notifiable Diseases Surveillance System (2007 to 2015). RESULTS: Half of Hymenoptera injuries were caused by bee stings. Hymenoptera injuries were concentrated in Manaus, and 13.36% of cases displayed systemic signs. Delayed medical assistance (4 to 12 hours) presented four times more risk for systemic manifestations. CONCLUSIONS: Simple clinical observations and history of injury are critical information for prognostic improvement.

Snakebites as a largely neglected problem in the Brazilian Amazon: highlights of the epidemiological trends in the State of Amazonas

Envenoming snakebites are thought to be a particularly important threat to public health worldwide, especially in rural areas of tropical and subtropical countries. The true magnitude of the public health threat posed by snakebites is unknown, making it difficult for public health officials to optimize prevention and treatment. The objective of this work was to conduct a systematic review of the literature to gather data on snakebite epidemiology in the Amazon region and describe a case series of snakebites from epidemiological surveillance in the State of Amazonas (1974-2012). Only 11 articles regarding snakebites were found. In the State of Amazonas, information regarding incidents involving snakes is scarce. Historical trends show an increasing number of cases after the second half of the 1980s. Snakebites predominated among adults (20-39 years old; 38%), in the male gender (78.9%) and in those living in rural areas (85.6%). The predominant snake envenomation type was bothropic. The incidence reported by the epidemiological surveillance in the State of Amazonas, reaching up to 200 cases/100,000 inhabitants in some areas, is among the highest annual snakebite incidence rates of any region in the world. The majority of the cases were reported in the rainy season with a case-fatality rate of 0.6%. Snakebite envenomation is a great disease burden in the State of Amazonas, representing a challenge for future investigations, including approaches to estimating incidence under-notification and case-fatality rates as well as the factors related to severity and disabilities.

Malaria in the State of Amazonas: a typical Brazilian tropical disease influenced by waves of economic development

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.

G6PD deficiency in Latin America: systematic review on prevalence and variants

Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

Plasmodium vivax malaria elimination: should innovative ideas from the past be revisited?

In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis against malaria was considered to be a successful tool. However, with the development of Plasmodium resistance in the Brazilian Amazon, this control strategy was abandoned. More than 50 years later, asexual stage resistance can be avoided by screening for antimalarial drugs that have a selective action against gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old methods should be tested as complementary tools for the elimination of malaria.