Analyzing the Local Epidemiological Profile of Malaria Transmission in the Brazilian Amazon Between 2010 and 2015

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Introduction: Malaria still is a public health problem in the Americas. In 2015, Brazil accounted for 37% of all cases in the Americas, and of these cases, 99.5% were located in the Brazilian Amazon. Despite the mobilization of resources from the Brazilian National Plan for Malaria Control, too many municipalities have high transmission levels. The objective of this study is to evaluate the local epidemiological profile of malaria and its trend between 2010 and 2015 in the Brazilian Amazon. This study also aims to recognize the epidemiological differences in the local temporo-spatial dynamics of malaria.

Methods: Malaria data were stratified by the annual parasite incidence (API) over the six-year period and by municipality. We used the method of seasonal decomposition by Loess smoothing to capture trend, seasonal and irregular components. A generalized linear model was applied to quantify trends, and the Kruskal-Wallis Rank Sum was applied to test for seasonality significance.

Results: The malaria API declined by 61% from 2010 to 2015, and there was a 40% reduction of municipalities with high transmission (determined as an API higher than 50). In 2015, 9.4% of municipalities had high transmission and included 62.8% of the total cases. The time-series analyses showed different incidence patterns by region after 2012; several states have minimized the effect of the seasonality in their incidence rates, thus achieving low rates of incidence. There were 13 municipalities with sustained high transmission that have become the principal focus of malaria control; these municipalities contained 40% of the cases between 2013 and 2015.

Discussion: Brazil has achieved advances, but more sustained efforts are necessary to contain malaria resurgence. The use of malaria stratification has been demonstrated as a relevant tool to plan malaria programs more efficiently, and spatiotemporal analysis corroborates the idea that implementing any intervention in malaria should be stratified by time to interpret tendencies and by space to understand the local dynamics of the disease.

Human Orthobunyavirus Infections, Tefé, Amazonas, Brazil

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Introduction: Several orthobunyaviruses are important arthropod-borne pathogens, responsible for a variety of diseases in humans, from acute febrile illness to encephalitis.

Methods: We collected serum samples from a series of dengue suspected cases in Tefé, a mid-size city located in the interior of the Amazonas state, Brazil. Viral RNA extraction was performed, and specimens were tested for dengue virus using RT-PCR. Thirty dengue negative samples were further tested for Mayaro virus (MAYV) and Oropouche virus (OROV) using an RT-qPCR protocol previously described. Positive samples were characterized by MegaBLAST analysis over the entire nucleotide collection of the main public databases, and also by maximum likelihood phylogenetic reconstruction of the S genome segment.

Results: We detected nine OROV or OROV-like positive cases among 30 patients reporting fever and headache, as the most common symptoms. The closest nucleotide sequence returned from the MegaBLAST analysis belongs to an OROV isolated in Peru 2008. Moreover, all Tefé samples grouped in the same clade with the OROV reference sequence and other closely-related OROV-like viruses.

Discussion: Dengue viruses are still the most important arbovirus worldwide, causing hundreds of millions of infections every year. Nonetheless, other arboviruses like chikungunya virus, Zika virus, and yellow fever virus have emerged in the last few years and are now a public health concern in several countries. OROV is believed to have caused more than 500,000 febrile infections in Brazil over recent decades. Therefore, the results described in this study strengthen that this arbovirus, and its closely-related recombinants, should be under continuous surveillance, at least in the endemic countries of Latin America.

A Possible Link Between Pyriproxyfen and Microcephaly

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The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus’s role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented—it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about molecular mechanisms and toxicological evidence, we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further.

First Report of the East-Central South African Genotype of Chikungunya Virus in Rio de Janeiro, Brazil

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Background: Chikungunya virus (CHIKV) is an arbovirus that causes an acute febrile syndrome with a severe and debilitating arthralgia. In Brazil, the Asian and East-Central South African (ECSA) genotypes are circulating in the north and northeast of the country, respectively. In 2015, the first autochthonous cases in Rio de Janeiro, Brazil were reported but until now the circulating strains have not been characterized. Therefore, we aimed here to perform the molecular characterization and phylogenetic analysis of CHIKV strains circulating in the 2016 outbreak occurred in the municipality of Rio de Janeiro.

Methods: The cases analyzed in this study were collected at a private Hospital, from April 2016 to May 2016, during the chikungunya outbreak in Rio de Janeiro, Brazil. All cases were submitted to the Real Time RT-PCR for CHIKV genome detection and to anti-CHIKV IgM ELISA. Chikungunya infection was laboratorially confirmed by at least one diagnostic method and, randomly selected positive cases (n=10), were partially sequenced (CHIKV E1 gene) and analyzed.

Results: The results showed that all the samples grouped in ECSA genotype branch and the molecular characterization of the fragment did not reveal the A226V mutation in the Rio de Janeiro strains analyzed, but a K211T amino acid substitution was observed for the first time in all samples and a V156A substitution in two of ten samples.

Conclusions: Phylogenetic analysis and molecular characterization reveals the circulation of the ECSA genotype of CHIKV in the city of Rio de Janeiro, Brazil and two amino acids substitutions (K211T and V156A) exclusive to the CHIKV strains obtained during the 2016 epidemic, were reported.

Social Media as a Sentinel for Disease Surveillance: What Does Sociodemographic Status Have to Do with It?

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Introduction: Data from social media have been shown to have utility in augmenting traditional approaches to public health surveillance. Quantifying the representativeness of these data is needed for making accurate public health inferences.

Methods: We applied machine-learning methods to explore spatial and temporal dengue event reporting trends on Twitter relative to confirmed cases, and quantified associations with sociodemographic factors across three Brazilian states (São Paulo, Rio de Janeiro, and Minas Gerais) at the municipality level.

Results: Education and income were positive predictors of dengue reporting on Twitter. In contrast, municipalities with a higher percentage of older adults, and males were less likely to report suspected dengue disease on Twitter. Overall, municipalities with dengue disease tweets had higher mean per capita income and lower proportion of individuals with no primary school education.

Conclusions: These observations highlight the need to understand population representation across locations, age, and racial/ethnic backgrounds in studies using social media data for public health research. Additional data is needed to assess and compare data representativeness across regions in Brazil.

Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases from 2015 Outbreak in Brazil

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Introduction: Brazil is facing, since October of 2015, an outbreak of microcephalic fetuses. This outbreak is correlated with the beginning of circulation of Zika virus (ZIKV) in the country. Although it is clear that the size of the head is diminished in these fetuses, the brain phenotype associated with these malformations is unknown.

Methods: We collected computed tomography images of the microcephaly cases from the region of Natal, Rio Grande do Norte, from September 2015 to February 2016.

Findings: The microcephalies derived from the current outbreak are associated with intracerebral calcifications, malformation of the ventricular system, migratory disorders in the telencephalon and, in a lower frequency, malformation of the cerebellum and brainstem.

Discussion: The characteristics described herein are not usually found in other types of microcephaly. We suggest that this work can be used as a guideline to identify microcephaly cases associated to the current outbreak.

Unintended Pregnancies in Brazil – A Challenge for the Recommendation to Delay Pregnancy Due to Zika

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Figure 2.

Because of the potential link between the ongoing Zika virus outbreak and a surge in the number of cases of congenital microcephaly, officials in Latin America have recommended that women postpone pregnancy until this association is firmly established or the outbreak subsides. However, in all these countries a large proportion of babies are still born out of unplanned pregnancies. Teenage girls are particularly at high risk, as they often lack access to preventive contraception methods, or the knowledge to use them appropriately. To gauge the magnitude of the barriers preventing the implementation of such a recommendation in Brazil, the country so far most affected by the Zika epidemic, we evaluated pregnancy rates in teenage girls, and their spatial heterogeneity in the country, in recent years (2012-2014). Nearly 20% of children born in Brazil today (~560,000 live births) are by teenage mothers. Birth incidence is far higher in the tropical and poorer northern states. However, in absolute terms most births occur in the populous southeastern states, matching to a large extent the geographic distribution of dengue (an indicator of suitable climatic and sociodemographic conditions for the circulation of Aedes mosquitoes). These findings indicate that recommendation to delay pregnancy will leave over half a million pregnant adolescents in Brazil vulnerable to infection every year if not accompanied by effective education and real access to prevention.