Biology subjects

Brasil, P.

Publications and source records attributed to Brasil, P..

5 recordsLinked to original sources

bioRxiv2020

A systematic evaluation of IgM and IgG antibody assay accuracy in diagnosing acute Zika Virus infection in Brazil; lessons relevant to emerging infections

Accurate diagnostics underpin effective public health responses to emerging viruses. For viruses, such as Zika virus (ZIKV), where the viremia clears quickly, antibody-based (IgM or IgG) diagnostics are recommended for patients who present seven days after symptom onset. However, cross-reactive antibody responses can complicate test interpretation among populations where closely related viruses circulate. We examined the accuracy (proportion of samples correctly categorized as Zika-positive or negative) for antibody-based diagnostics among Brazilian residents (Rio de Janeiro) during the ZIKV outbreak. Four ZIKV ELISAs (IgM and IgG Euroimmun, IgM Novagnost and CDC MAC), two dengue ELISAs (IgM and IgG Panbio), and the ZIKV plaque reduction neutralization test (PRNT) were evaluated. Positive samples were ZIKV PCR confirmed clinical cases collected in 2015-2016 (n=169); Negative samples (n=236) were collected before ZIKV was present in Brazil ([≤]2013). Among serum samples collected [≥]7 days from symptom onset, PRNT exhibited the highest accuracy (93.7%), followed by the Euroimmun IgG ELISA (77.9%). All IgM assays exhibited lower accuracy (<74%). IgG was detected more consistently than IgM among ZIKV cases using Euroimmun ELISAs (68% versus 22%). Anti-DENV IgM ELISA was positive in 41.1% of confirmed ZIKV samples tested. The Euroimmun IgG assay, although misdiagnosing 22% of samples, provided the most accurate ELISA. Anti-ZIKV IgG was detected more reliably than IgM among ZIKV patients, suggesting a secondary antibody response to assay antigens following ZIKV infection. Antibody ELISAs need careful evaluation in their target population to optimise use and minimise misdiagnosis, prior to widespread deployment, particularly where related viruses co-circulate.

microbiology↗

bioRxiv2019

The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptions to host-switching

BackgroundPlasmodium simium, a malaria parasite of non-human primates (NHP) was recently shown to cause zoonotic infections in humans in Brazil. We sequenced the P. simium genome to investigate its evolutionary history and to identify any genetic adaptions that may underlie the ability of this parasite to switch between host species. ResultsPhylogenetic analyses based on whole genome sequences of P. simium from humans and NHPs reveals that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, suggesting P. simium first infected NHPs as a result of a host-switch of P. vivax from humans. The P. simium isolates show the closest relationship to Mexican P. vivax isolates. Analysis of erythrocyte invasion genes reveals differences between P. vivax and P. simium, including large deletions in the Duffy Binding Protein 1 (DBP1) and Reticulocyte Binding Protein 2a genes of P. simium. Analysis of P. simium isolated from NHPs and humans revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic. ConclusionsAnalysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.

genomics↗

bioRxiv2019

Howler monkeys are the reservoir of malaria parasites causing zoonotic infections in the Atlantic forest of Rio de Janeiro

BackgroundAlthough malaria transmission was eradicated from southeast Brazil, a significant increase in the number of Plasmodium vivax-like autochthonous human cases has been reported in remote areas of the Atlantic Forest in the last decades in Rio de Janeiro (RJ) state, including an outbreak in 2015-2016. The singular clinical and epidemiological aspects of several human cases combined with molecular and genetic data revealed that they were due to the non-human primate (NHP) parasite P. simium. The full understanding of the epidemiology of the autochthonous malaria in southeastern Brazil depends, however, upon the knowledge on the circulation of NHP Plasmodium in the foci and the determination of its reservoirs.\n\nMethodologyA large sampling effort was carried out in the Atlantic forest of RJ and its bordering states (Minas Gerais, Sao Paulo, Espirito Santo) for capture and examination of free-living NHPs. Blood and/or viscera were analyzed for Plasmodia infections through molecular and microscopic techniques.\n\nPrincipal findingsIn total, 146 NHPs of six species, from 30 counties in four states were tested. Howler monkeys (A. guariba clamitans) were the only NHP species found infected. In RJ, 26% of howlers were positive, among them 17% were found to be infected with P. simium. Importantly, specific single nucleotide polymorphisms were detected in all P. simium infected howlers regardless geographical origin of malaria foci. Interestingly, 71% of P. simium infected NHP were from the coastal slope of a mountain chain (Serra do Mar), where most human cases have been occurring. P. brasilianum/malariae was detected for the first time in 14% free-living howlers in RJ as well as in 25% of those from the Espirito Santo state. Moreover, malarial pigment was detected in spleen fragments of 50% of a subsample composed of howler monkeys found dead in both RJ and ES. All NHPs were negative for P. falciparum.\n\nConclusions/SignificanceOur data indicate the howler monkeys as the main reservoir of the Atlantic forest human malaria in RJ and other sites in Southeast Brazil and reinforce its zoonotic nature.\n\nAuthor summaryThe present work consists of an unprecedented capture effort and large-scale field survey of plasmodial species in Non-human primates (NHPs) in RJ, a state recording a three-decade history of autochthonous human cases of benign tertian malaria pending epidemiological clarification of their origin. For the first time, we describe infection rates by Plasmodium sp.in free-living NHP, match the spatial distribution of P. simium in NHP with that of local human cases of benign tertian malaria due to this parasite, disclose howler monkeys as the only confirmed reservoir of this zoonotic malaria in the state and showed that specific single nucleotide polymorphisms were present in all P. simium infected howlers, regardless of the geographical origin of malaria foci. It is also the first time that P. brasilianum/malariae is recorded in free-living NHPs from Rio de Janeiro and the widespread distribution of this quartan-malaria parasite of zoonotic potential in the state is illustrated. Together, these findings increase the understanding about the simian malaria parasites in Atlantic Forests, as well as on the zoonotic character of autochthonous human malaria in Rio de Janeiro, providing subsidies for shaping surveillance and control.

ecology↗

bioRxiv2018

Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis

Background Zika virus (ZIKV) emerged in Latin America & the Caribbean (LAC) region in 2013, and has had serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and a lack of a comprehensive collation of data from affected countries.\n\nMethods Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 91 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vector capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.\n\nResults There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p<0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.\n\nConclusions The findings suggest that the ZIKV epidemic is by and large over, with incidence projected to be low in most cities in LAC in 2018. Local low levels of transmission are probable but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

epidemiology↗

bioRxiv2017

Plasmodium simium causing human malaria: a zoonosis with outbreak potential in the Rio de Janeiro Brazilian Atlantic forest

BackgroundMalaria was eliminated from Southern and Southeastern Brazil over 50 years ago. However, an increasing number of autochthonous episodes attributed to Plasmodium vivax have been recently reported in the Atlantic forest region of Rio de Janeiro State. As P. vivax-like non-human primate malaria parasite species Plasmodium simium is locally enzootic, we performed a molecular epidemiological investigation in order to determine whether zoonotic malaria transmission is occurring.\n\nMethodsBlood samples of humans presenting signs and/or symptoms suggestive of malaria as well as from local howler-monkeys were examined by microscopy and PCR. Additionally, a molecular assay based on sequencing of the parasite mitochondrial genome was developed to distinguish between P. vivax and P. simium, and applied to 33 cases from outbreaks occurred in 2015 and 2016.\n\nResultsOf 28 samples for which the assay was successfully performed, all were shown to be P. simium, indicating the zoonotic transmission of this species to humans in this region. Sequencing of the whole mitochondrial genome of three of these cases showed that P. simium is most closely related to P. vivax parasites from South American.\n\nFindingsThe explored malaria outbreaks were caused by P. simium, previously considered a monkey-specific malaria parasite, related to but distinct from P. vivax, and which has never conclusively been shown to infect humans before.\n\nInterpretationThis unequivocal demonstration of zoonotic transmission, 50 years after the only previous report of P. simium in man, leads to the possibility that this parasite has always infected humans in this region, but that it has been consistently misdiagnosed as P. vivax due to a lack of molecular typing techniques. Thorough screening of the local non-human primate and anophelines is required to evaluate the extent of this newly recognized zoonotic threat to public health and malaria eradication in Brazil.\n\nFundingFundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado de Rio de Janeiro (Faperj), The Brazilian National Council for Scientific and Technological Development (CNPq), JSPS Grant-in-Aid for scientific research, Secretary for Health Surveillance (SVS) of the Ministry of Health, Global Fund, and PRONEX Program of the CNPq.

genetics↗