When fever is not malaria in Latin America: a systematic review

In malaria-endemic countries, febrile episodes caused by diseases other than malaria are a growing concern. However, limited knowledge of the prevalent etiologic agents and their geographic distributions restrict the ability of health services to address non-malarial morbidity and mortality through effective case management. Here, we review the etiology of fever in Latin America (LA) between 1980 and 2015 and map significant pathogens commonly implicated in febrile infectious diseases.; A literature search was conducted, without language restrictions, in three distinct databases in order to identify fever etiology studies that report laboratory-confirmed fever-causing pathogens that were isolated from usually sterile body sites. Data analyses and mapping was conducted with Tableau Desktop (version 2018.2.3).; Inclusion criteria were met by 625 publications corresponding to data relative to 34 countries. Studies using serology (n = 339) predominated for viral infections, culture (n = 131) for bacteria, and microscopy (n = 62) for fungi and parasites. The pathogen groups most frequently reported were viral infections (n = 277), bacterial infections (n = 265), parasitic infections (n = 59), fungal infections (n = 47), and more than one pathogen group (n = 24). The most frequently reported virus was dengue virus (n = 171), followed by other arboviruses (n = 55), and hantavirus (n = 18). For bacteria, Staphylococcus spp. (n = 82), Rickettsia spp. (n = 70), and Leptospira spp. (n = 55) were frequently reported. Areas with biggest gaps on etiology of fever were apparent.; This review provides a landscape of pathogens causing febrile illness other than malaria in LA for over 30 years. Our findings highlight the need to standardize protocols and report guidelines for fever etiology studies for better comparability of results and improved interpretation. Lastly, we should improve existing national laboratory surveillance systems, especially from low- to middle-income countries, to inform global fever policy priorities and timely identify emerging infections threats.; PROSPERO systematic review registration number: CRD42016049281

A emergência da nova variante P.1 do SARS-CoV-2 no Amazonas (Brasil) foi temporalmente associada a uma mudança no perfil da mortalidade devido a COVID-19, segundo sexo e idade

Background Since the end of 2020, there has been a great deal of international concern about the variants of SARS-COV-2 B.1.1.7, identified in the United Kingdom; B.1.351 discovered in South Africa and P.1, originating from the Brazilian state of Amazonas. The three variants were associated with an increase in transmissibility and worsening of the epidemiological situation in the places where they expanded. The lineage B.1.1.7 was associated with the increase in case fatality rate in the United Kingdom. There are still no studies on the case fatality rate of the other two variants. The aim of this study was to analyze the mortality profile before and after the emergence of the P.1 strain in the Amazonas state. Methods We analyzed data from the Influenza Epidemiological Surveillance Information System, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), comparing two distinct epidemiological periods: during the peak of the first wave, between April and May 2020, and in January 2021 (the second wave), the month in which the new variant came to predominate. We calculated mortality rates, overall case fatality rate and case fatality rate among hospitalized patients; all rates were calculated by age and gender and 95% confidence intervals (95% CI) were determined. Findings We observed that in the second wave there were a higher incidence and an increase in the proportion of cases of COVID-19 in the younger age groups. There was also an increase in the proportion of women among Severe Acute Respiratory Infection (SARI) cases from 40% (2,709) in the first wave to 47% (2,898) in the second wave and in the proportion of deaths due to COVID-19 between the two periods varying from 34% (1,051) to 47% (1,724), respectively. In addition, the proportion of deaths among people between 20 and 59 years old has increased in both sexes. The case fatality rate among those hospitalized in the population between 20 and 39 years old during the second wave was 2.7 times the rate observed in the first wave (female rate ratio = 2.71; 95% CI: 1.9-3.9], p <0.0001; male rate ratio = 2.70, 95%CI:2.0-3.7), and in the general population the rate ratios were 1.15 (95% CI: 1.1-1.2) in females and 0.78 (95% CI: 0.7-0.8) in males]. Interpretation Based on this prompt analysis of the epidemiological scenario in the Amazonas state, the observed changes in the pattern of mortality due to COVID-19 between age groups and gender simultaneously with the emergence of the P.1 strain suggest changes in the pathogenicity and virulence profile of this new variant. Further studies are needed to better understanding of SARS-CoV-2 variants profile and their impact for the health population.Introdução Desde o final de 2020 tem havido grande preocupação internacional com as variantes do SARS-COV-2: B.1.1.7, identificada no Reino Unido; B.1.351, descoberta na África do Sul e P.1, que emergiu inicialmente estado brasileiro do Amazonas. As três variantes foram associadas a aumento na transmissibilidade e piora da situação epidemiológica nos locais onde se expandiram. A linhagem B.1.1.7 foi associada ao aumento da taxa de letalidade no Reino Unido. Ainda não existem estudos conclusivos sobre letalidade das outras duas variantes. O objetivo deste estudo foi analisar o perfil de mortalidade antes e depois da emergência da linhagem P.1 no Amazonas. Métodos Analisamos os dados do sistema nacional de vigilância epidemiológica, comparando dois momentos epidemiológicos distintos: durante o pico da primeira onda, entre abril e maio de 2020, e em janeiro de 2021, mês em que a nova variante passou a predominar. Calculamos as taxas de mortalidade, letalidade e letalidade entre pacientes internados, todas as taxas foram calculadas por idade e por sexo e determinados os intervalos de confiança de 95%. Achados Observamos que na segunda onda houve maior incidência e aumento na proporção de casos de COVID-19 nas faixas etárias mais jovens. Observou-se, também, um aumento na proporção de mulheres entre os casos de SARI de 40% (2.709) na primeira onda para 47% (2.898) na segunda onda e entre mortes por COVID-19 de 34% (1,051) para 47% (1.724), respectivamente. Além disso, a proporção de mortes entre 20 e 59 anos aumentou em ambos os sexos. A letalidade entre os hospitalizados na população entre 20 e 39 anos durante a segunda onda foi 2.7 vezes a primeira onda [razão de taxas sexo feminino=2,71; CI(95%)=1,9-3,9], p<0.0001; razão de taxas sexo masculino=2.70(2.0-3.7)), na população geral as razões de taxa foram 1,15(1,1-1,2) no sexo feminino e 0,78(0,7-0,8) no sexo masculino. Interpretação Observamos mudanças no padrão de mortalidade por COVID-19 entre as faixas etárias e sexo simultaneamente à emergência da linhagem P.1, sugerindo mudanças nos perfis de patogenicidade e virulência, novos estudos são necessários para melhor compreensão das variantes do SARS-CoV-2 e suas consequências na saúde da população

Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities

Background: The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. Methods: Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. Results: In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Bra- zil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. Conclusion: The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diag- nostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement

Genomic analysis and immune response in a murine mastitis model of vB_EcoM-UFV13, a potential biocontrol agent for use in dairy cows

Bovine mastitis remains the main cause of economic losses for dairy farmers. Mammary pathogenic Escherichia coli (MPEC) is related to an acute mastitis and its treatment is still based on the use of antibiotics. In the era of antimicrobial resistance (AMR), bacterial viruses (bacteriophages) present as an efficient treatment or prophylactic option. However, this makes it essential that its genetic structure, stability and interaction with the host immune system be thoroughly characterized. The present study analyzed a novel, broad host-range anti-mastitis agent, the T4virus vB-EcoM-UFV13 in genomic terms, and its activity against a MPEC strain in an experimental E. coli-induced mastitis mouse model. 4,975 Single Nucleotide Polymorphisms (SNPs) were assigned between vB-EcoM-UFV13 and E. coli phage T4 genomes with high impact on coding sequences (CDS) (37.60%) for virion proteins. Phylogenetic trees and genome analysis supported a recent infection mix between vB-EcoM-UFV13 and Shigella phage Shfl2. After a viral stability evaluation (e.g pH and temperature), intramammary administration (MOI 10) resulted in a 10-fold reduction in bacterial load. Furthermore, pro-inflammatory cytokines, such as IL-6 and TNF-\u3b1, were observed after viral treatment. This work brings the whole characterization and immune response to vB-EcoM-UFV13, a biocontrol candidate for bovine mastitis

Integrated vector management targeting Anopheles darlingi populations decreases malaria incidence in an unstable transmission area, in the rural Brazilian Amazon

Background: Studies on vector behaviour should be conducted in order to evaluate the effectiveness of vector control measures on malaria protection in endemic areas of Latin America, where P. vivax predominates. This work aims to investigate the fauna of anopheline mosquitoes and verify the impact of integrated vector management in two colonization projects in the Careiro Municipality, Western Brazilian Amazon. Methods. Four mosquitoes captures were carried out from August 2008 to March 2010, with an interval of six months between each collection. Since September 2009 a large programme to reduce the burden of malaria has started in the two communities by distribution of insecticide-treated bed nets (ITN) and intensification of indoor residual spraying (IRS). Human biting rates (HBRs), entomological inoculation rates (EIRs), malaria incidence rate (MIR) and Plasmodium carriers prevalence were used as outcomes to estimate the impact of the control measures. Results: A total of 3,189 anophelines were collected, belonging to 13 species. Anopheles darlingi was the predominant species in the period (42.6%), followed by Anopheles albitarsis (38.4%). An. darlingi HBRs showed a notable decreasing trend from the start to the end of the study. Conversely, An. albitarsis increased its contribution to overall HBRs throughout the study. For An. darlingi there was a significant positive correlation between HBRs and MIR (p=0.002). Anopheles albitarsis HBRs showed a significant negative correlation with the corresponding MIR (p=0.045). EIR from total anophelines and from An. darlingi and An. albitarsis presented decreasing patterns in the successive collections. Four species of anophelines (An. darlingi, An. albitarsis, Anopheles braziliensis and Anopheles nuneztovari) were naturally infected with Plasmodium, albeit at very low infection rates. There were a decrease in the MIR for both vivax and falciparum malaria and in the prevalence of Plasmodium vivax and Plasmodium falciparum carriers during the period of study. Conclusions: There is strong evidence of association between the density of An. darlingi and the incidence of malaria in the studies sites, further highlighting the importance of this vector in malaria transmission in this region. An. darlingi susceptibility to control using ITN and IRS is likely to be high in the rural settlements studied. © 2012 Martins-Campos et al

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazili an centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome83289298CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL - FAPERGSSem informaçãoSem informação2006/60402-1; 2010/51547-1; 2013/01476-9; 2014/06570-6; 2009/50575-4; 2010/51546-5; 2012/21942-116/2551-0000482-

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil

<p>Abstract</p> <p>Background/Aim</p> <p>Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (<it>MTHFR</it>) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of <it>MTHFR </it>gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil.</p> <p>Method</p> <p>One hundred seven-four untreated patients with CHC were genotyped for the C677T <it>MTHFR</it>. Genomic DNA was extracted from peripheral blood cells and the C677T <it>MTHFR </it>polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week.</p> <p>Results</p> <p>Among subjects infected with CHC genotype non-1 the frequency of <it>MTHFR </it>genotypes TT was 9.8% <it>versus </it>4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the <it>MTHFR </it>genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03).</p> <p>Conclusion</p> <p>Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of <it>MTHFR </it>C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of <it>MTHFR </it>C677T polymorphism should be confirmed in a large population.</p

Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells

<p>Abstract</p> <p>Findings</p> <p>We set out to analyse the gene expression profile of pre-osteoblastic C2C12 cells during osteodifferentiation induced by both rhBMP2 and rhBMP7 using DNA microarrays. Induced and repressed genes were intercepted, resulting in 1,318 induced genes and 704 repressed genes by both rhBMP2 and rhBMP7. We selected and validated, by RT-qPCR, 24 genes which were upregulated by rhBMP2 and rhBMP7; of these, 13 are related to transcription (<it>Runx2, Dlx1, Dlx2, Dlx5, Id1, Id2, Id3, Fkhr1, Osx, Hoxc8, Glis1, Glis3 </it>and <it>Cfdp1</it>), four are associated with cell signalling pathways (<it>Lrp6, Dvl1, Ecsit </it>and <it>PKCδ</it>) and seven are associated with the extracellular matrix (<it>Ltbp2, Grn, Postn, Plod1, BMP1, Htra1 </it>and <it>IGFBP-rP10</it>). The novel identified genes include: <it>Hoxc8, Glis1, Glis3, Ecsit, PKCδ, LrP6, Dvl1, Grn, BMP1, Ltbp2, Plod1, Htra1 </it>and <it>IGFBP-rP10</it>.</p> <p>Background</p> <p>BMPs (bone morphogenetic proteins) are members of the TGFβ (transforming growth factor-β) super-family of proteins, which regulate growth and differentiation of different cell types in various tissues, and play a critical role in the differentiation of mesenchymal cells into osteoblasts. In particular, rhBMP2 and rhBMP7 promote osteoinduction <it>in vitro </it>and <it>in vivo</it>, and both proteins are therapeutically applied in orthopaedics and dentistry.</p> <p>Conclusion</p> <p>Using DNA microarrays and RT-qPCR, we identified both previously known and novel genes which are upregulated by rhBMP2 and rhBMP7 during the onset of osteoblastic transdifferentiation of pre-myoblastic C2C12 cells. Subsequent studies of these genes in C2C12 and mesenchymal or pre-osteoblastic cells should reveal more details about their role during this type of cellular differentiation induced by BMP2 or BMP7. These studies are relevant to better understanding the molecular mechanisms underlying osteoblastic differentiation and bone repair.</p

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016