Project description:Arthropod-borne viruses (arboviruses) represent a threat to global public health, especially in the tropical and subtropical regions of the world. More than 150 arboviruses can infect humans; they cause mainly febrile illness, although hemorrhagic complications and diseases affecting the central nervous system (SNC) can also be observed. Arboviruses represent a threat to Brazil and, therefore, a permanent surveillance of these viruses is required to timely reduce the risk of epidemic outbreaks. The Brazilian Amazon region is where the highest number of arboviruses has been detected in the world. Besides, malaria is also endemic in the Amazon region, with a significant predominance of Plasmodium vivax. It is often difficult to differentiate between malaria and arboviral diseases, as they share similar clinical features and laboratory findings, mainly undifferentiated fever. This study aimed to estimate possible viral etiology in patients with febrile syndrome negative for Plasmodium infection, in the Brazilian Amazon. We initially analyzed serum samples of 124 participants with a DNA microarray platform designed for the detection of arboviruses and viruses transmitted by small mammals, but no virus was detected. Then, the serum samples of 76 participants were analyzed with a deep New Generation Sequencing, which showed evidence of the presence of only one arbovirus, the Zika virus in only one pool of 9 serum samples. This result is in contrast with our hypothesis, showing that arboviruses are not frequent in suspected malaria cases in Manaus, Brazil. Other viruses instead of arboviruses were found in this study. Primate erythrovirus 1 was the virus most frequently found virus in the suspected malaria patients, followed by Enterobacteria phage lambda. Besides, we detected, in a lower frequency, the Pegivirus C. In addition to the exogenous viruses, we also detected human endogenous retrovirus in all pools. Due to the high number of viruses that are important in the differential diagnosis of malaria, cost-effective and simple high throughput methods are required, helping molecular surveillance of misdiagnosed viral infections. Further studies with more robust sample sizes in other areas in the Amazon are needed.

Project description: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.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.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.

Project description:BackgroundIn 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.MethodsTime-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.ResultsA 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.ConclusionThe 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.

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Screening of virus infection in suspected malaria patients in the city of Manaus in the Amazon region of Brazil

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