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Introdução: A tuberculose (TB) é causada por uma das 07 espécies do complexo Mycobacterium tuberculosis. O tratamento para adultos com TB meningoencefálica tem duração 12 meses, sendo o tratamento intensivo por 2 meses com rifampicina, isoniazida, pirazinamina e etambutol (RHZE) e 10 meses de manutenção com RH. Porém, podem ocorrer reações adversas graves durante tratamento, sendo necessário alterar a composição do esquema inicial. Objetivo: Descrever a evolução de um caso de trombocitopenia induzida por etambutol em meningoencefalite tuberculosa e seu manejo terapêutico. Método: Homem, 55 anos, residente de Belém-PA. Em janeiro de 2023, evoluiu com cefaleia, febre e perda ponderal de 10 kg. Com piora da cefaleia, em 27.01.2023 foi atendido na referência de meningite, realizou punção lombar e tomografia computadorizada de tórax. O líquor era xantocrômico, com hiperproteinorraquia (175.2mg/dl), hipoglicorraquia (19mg/dl), aumento de citometria (130 células/mm3), 91% de mononucleares, baciloscopia positiva e teste rápido molecular para tuberculose, com resultado negativo. Na TC de tórax havia nódulos com aspecto miliar e linfonodos mediastinais aumentados de volume. Optou-se por internação e introdução do esquema RHZE para tuberculose meningoencefálica, associado à corticoterapia com dexametasona, na dose de 0.3 mg/kg/dia. Pesquisa de BAAR no escarro e infecção pelo HIV, tiveram resultados negativos. O paciente apresentava melhora clínica, porém, em 31.01.23 apresentou trombocitopenia (71.000/mm3), em queda progressiva - 55.000/mm3 em 03.02.23. No mielograma de 07.02.23, não havia alterações. Associou-se a causa da trombocitopenia ao esquema básico, optando-se por suspendê-lo, em 06.02.23. Após discussão do caso, decidiu-se por iniciar o tratamento em 10.02.23, com RH e Pirazinamida, excluindo Etambutol, associado como a principal causa da trombocitopenia. Resultados: Após isso, foram realizados hemogramas e observado aumento das plaquetas, apresentando valores de 49.000 e 66.000/mm3, em 12.02.23 e 16.02.23, respectivamente, corroborando com a hipótese inicial. O paciente recebeu alta e seguiu com manejo ambulatorial, com valores de plaquetas de 135.000 e 213.000/mm3 em 24.02.24 e 06.04.2024, respectivamente. Conclusão: Assim, quando há uma reação de hipersensibilidade grave, como trombocitopenia, o medicamento suspeito não deve ser reiniciado após suspensão, pois na sua reintrodução a reação adversa pode ser ainda mais grave. No caso relatado, foi optado iniciar um esquema especial, evoluindo com boa resposta.

BackgroundEpstein–Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients.MethodsWe recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO.ResultsThe DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection.ConclusionOur results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

A criptococose é uma infecção fúngica de natureza sistêmica que tem tido uma crescente importância nas últimas décadas, o agente etiológico é representado por fungos do complexo Cryptococcus. Objetivou-se identificar os principais fatores relacionados aos diferentes achados clínicos e laboratoriais de pacientes infectados pelo Cryptococcus spp., internados num hospital de referência de Belém. Foram analisados prontuários de 63 pacientes internados no período de 2015 a 2020. A maioria era do sexo masculino (n=39; 61,9%), residentes de áreas urbanas (n=32; 50,8%) e procedentes do estado do Pará (n=62; 98,4%). Não houve diferença estatística entre homens e mulheres no grupo dos imunocompetentes e no grupo dos imunodeprimidos. Na zona urbana houve predomínio de pacientes imunodeprimidos em relação aos imunocompetentes. A média do tempo de internação no grupo de pacientes imunocompetentes foi significativamente maior (p=0,003) em relação aos imunodeprimidos. Os pacientes do grupo imunocompetente apresentaram proporção significativamente maior de mialgia (p=0,005) em relação aos imunodeprimidos. Em relação as características do LCR, os pacientes do grupo imunodeprimido apresentaram valores significativamente menores de celularidade (p=0,001) e de linfócitos polimorfonucleares (p=0,004). Além disso, o grupo de imunodeprimidos possui significância em relação aos linfócitos mononucleares (P=0,005) quando comparados aos imunocompetentes. Quanto a dose acumulada dos fármacos, foi visto que o grupo dos imunocompetentes possui dose acumulada dos fármacos significativamente maior (p=0,01) do que o grupo imunossuprimido. Nas causas de suspensão, destacam-se a suspensão do tratamento por óbito, havendo significância (p=0,006) entre os grupos, com maior suspensão por óbito sendo do grupo dos imunodeprimidos. No desfecho clínico dos pacientes, analisou-se o óbito entre os grupos imunocompetente e imunodeprimidos, havendo diferença significante nesse desfecho, com uma quantidade significativamente maior de óbitos no grupo dos pacientes imunodeprimidos (p=0,023). Os aspectos epidemiológicos apresentados neste estudo apontam uma prevalência de pacientes imunocomprometidos pelo vírus da imunodeficiência humana e do sexo masculino, especialmente pela maior exposição a atividades laborais de maior risco para o desenvolvimento da criptococose. Além disso, essa mesma parcela de imunodeprimidos também é a que apresenta os maiores impactos na morbimortalidade que essa doença causa.

Introdução/objetivo: Popularmente conhecida como varíola dos macacos a monkeypox (MPOX) é uma zoonose ocasionada por um Orthopoxyvirus (OPXV) que teve seu primeiro caso descrito em humanos na República Democrática do Congo em 1970, tornando-se posteriormente endêmico em países da África Central e Ocidental. Em maio de 2022 foi relatada a detecção em vários países não endêmicos onde não se tinham ligações epidemiológicas conhecidas e o número de casos continuou a aumentar com a contínua transmissão em todo o mundo, no Brasil o primeiro caso foi confirmado em junho de 2022, logo após foi instituída a vigilância de rotina dos casos suspeitos. Diante disto, este estudo objetivou descrever a prevalência, as características epidemiológicas e clínicas dos casos confirmados de MPOX no Estado do Pará. Métodos: Para isso, foram analisadas amostras de swab de lesão coletadas de casos suspeitos e que deram entrada no Laboratório de Enterovírus (LEV) do Instituto Evandro Chagas (IEC) que atua como referência laboratorial para o Monkeypox no Estado do Pará no período de julho de 2022 a junho de 2023. Foi realizado o levantamento e tabulação das informações epidemiológicas e clínicas dos casos, após isso as amostras foram extraídas e testadas por Reação em Cadeia mediada pela Polimerase em tempo real (qPCR) utilizando oligonucleotídeos e sondas específicas para detecção de MPOX. Resultado: Das 284 amostras recebidas 45,8% (130) foram confirmadas, onde 95% (124) pertenciam a pacientes do sexo masculino tendo o grupo etário de 20 a 29 anos com 86% (61) dos casos. Os sintomas mais comuns relatados foram febre (78,4%), lesão cutânea (62,3%), cefaléia (60%) e adenomegalia (38,4%). Dos pacientes positivos 86% (112) se enquadram no grupo de homens que fazem sexo com homens, 52% (68) são pessoas que vivem com HIV e 18% (24) possuem alguma infecção sexualmente transmissível ativa, sendo a sífilis a mais prevalente com 91,6% (22) dos casos. Foi registrado a hospitalização e posterior óbito de um paciente que vivia com HIV e possuía sífilis ativa. Conclusão: Diante disto, pode-se avaliar que o perfil clínico e epidemiológico dos pacientes no Estado do Pará se assemelha com os descritos em literatura em todo o mundo, logo, torna-se fundamental a vigilância epidemiológica deste patógeno uma vez que atual e rápida disseminação e evolução do MPOX não têm precedentes e representa uma ameaça contínua à saúde pública.

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-ɣ, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.

IntroductionAfter three years since the beginning of the pandemic, the new coronavirus continues to raise several questions regarding its infectious process and host response. Several mutations occurred in different regions of the SARS-CoV-2 genome, such as in the spike gene, causing the emergence of variants of concern and interest (VOCs and VOIs), of which some present higher transmissibility and virulence, especially among patients with previous comorbidities. It is essential to understand its spread dynamics to prevent and control new biological threats that may occur in the future. In this population_based retrospective observational study, we generated data and used public databases to understand SARS-CoV-2 dynamics.MethodsWe sequenced 1,003 SARS-CoV-2 genomes from naso-oropharyngeal swabs and saliva samples from Pará from May 2020 to October 2022. To gather epidemiological data from Brazil and the world, we used FIOCRUZ and GISAID databases.ResultsRegarding our samples, 496 (49.45%) were derived from female participants and 507 (50.55%) from male participants, and the average age was 43 years old. The Gamma variant presented the highest number of cases, with 290 (28.91%) cases, followed by delta with 53 (5.28%). Moreover, we found seven (0.69%) Omicron cases and 651 (64.9%) non-VOC cases. A significant association was observed between sex and the clinical condition (female, p = 8.65e-08; male, p = 0.008961) and age (p = 3.6e-10).DiscussionAlthough gamma had been officially identified only in December 2020/January 2021, we identified a gamma case from Belém (capital of Pará State) dated May 2020 and three other cases in October 2020. This indicates that this variant was circulating in the North region of Brazil several months before its formal identification and that Gamma demonstrated its actual transmission capacity only at the end of 2020. Furthermore, the public data analysis showed that SARS-CoV-2 dispersion dynamics differed in Brazil as Gamma played an important role here, while most other countries reported a new infection caused by the Delta variant. The genetic and epidemiological information of this study reinforces the relevance of having a robust genomic surveillance service that allows better management of the pandemic and that provides efficient solutions to possible new disease-causing agents.

Abstract To identify the prevalence and risk factors for primary Epstein–Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51–15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01–2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12–2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79–1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22–3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1–10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.

Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1 + EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1 + EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1 + EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p

IntroductionImmune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the “classical” HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis.Materials and MethodsTreatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4+/CD8+ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4+ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3.ResultsOf the 270 patients monitored, 134 responded to treatment (CD4+ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4+ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis.ConclusionsThe allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon.

Introdução/objetivo: O início tardio do monitoramento específico após a aquisição do HIV-1 é multifatorial e está relacionado ao perfil social dos pacientes. Objetivamos identificar os fatores sóciodemográficos associados à apresentação tardia e as consequências clínicas resultantes em uma coorte de pacientes do Pará/Brasil. Métodos: O total de 402 pacientes HIV-1 + foram monitorados por 24 meses, estando todos livres de terapia na coleta inicial. Aspectos sóciodemográficos foram obtidos de prontuários clínicos e questionários epidemiológicos. A carga viral foi quantificada por PCR em tempo real. A concentração de linfócitos e de citocinas foi quantificada por citometria de fluxo. Os dados longitudinais do monitoramento foram obtidos do banco SISCEL. As mutações de resistência foram sequenciadas por Sanger e plataforma 3130Ix1 e analisadas em Standford HIV Drug Resistance Database. Os esquemas terapêuticos foram obtidos do banco SICLOM. Resultados: Cerca de 4% da coorte teve apresentação tardia entre 7 a mais de 12 meses do diagnóstico primário; a procura ocorreu por orientação de terceiros ou início dos sintomas. Renda familiar abaixo de 1 salário e relações com profissionais do sexo foram fatores associados. O atraso resultou em: Três ou mais coinfecções, a maioria viral e bacteriana; Polissintomatologia, com combinação específica de mialgia e febre; Carga viral elevada e CD4 + baixo nos 6 primeiros meses; Manutenção da terapia sem trocas ao longo dos 24 meses, porém, com maior representação de esquemas de 2ª escolha. Na pré-terapia, pacientes tardios tinham altas dosagens de citocinas TH1 e baixa dosagem de citocinas TH2 e TH17; mutações de resistência não foram frequentes. Conclusões: Poucos fatores sóciodemográficos e comportamentais foram associados à apresentação tardia, porém, as consequências deste atraso se mostraram adversas à progressão esperada com o início imediato da terapia, principalmente nos primeiros 6 meses de monitoramento.

(1) Background: Tropical spastic paraparesis (TSP/HAM) associated with the T cell lymphotropic virus in type I humans (HTLV-1) is a slow, chronic, and progressive disease that causes balance changes. TSP/HAM diagnosis can be classified as probable, possible, and definite. We compared the static balance control of HTLV-1-infected patients with different TSP/HAM diagnosis. (2) Methods: Our sample consisted of 13 participants infected with HTLV-1 and 16 healthy participants. The center of pressure was recorded using a force platform with open and closed eyes. We divided the recordings into three intervals, period T1 (corresponds to the first 10 s); period T2 (from 10 to 45 s); period T3 (from 45 to 55 s). (3) Results: Eight participants infected with HTLV-1 were classified as probable TSP/HAM and five participants infected with HTLV-1 were classified as definite TSP/HAM. There was a significant increase in postural instability in patients with definite PET/MAH considering the structural and global variables of body sway compared to the control and the probable TSP/HAM. (4) Conclusions: We concluded that the severity of balance is directly related to the degree of signs and symptoms of TSP/HAM.

Background: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein–Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. Materials and methods: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. Results: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. Conclusions: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed.

The Human T-cell Lymphotropic Virus (HTLV-1) is a Deltaretrovírus that was first isolated in the 1970s, and associated with Adult T-cell Leucemia-Lymphoma (ATLL), and subsequently to Tropical Spastic Paraparesis-Myelopathy (TSP/HAM). The genetic diversity of the virus varies among geographic regions, although its mutation rate is very low (approximately 1% per thousand years) in comparison with other viruses. The present study determined the genetic diversity of HTLV-1 in the metropolitan region of Belém, in northern Brazil. Blood samples were obtained from patients at the UFPA Tropical Medicine Nucleus between January 2010 and December 2013. The DNA was extracted and the PX region of the HTLV was amplified using nested PCR. The positive samples were then digested using the Taq1 enzyme for the identification and differentiation of the HTLV-1 and HTLV-2. The 5'LTR region of the positive HTLV-1 samples were amplified by nested PCR, and then sequenced genetically. The phylogenetic analysis of the samples was based on the maximum likelihood method and the evolutionary profile was analyzed by the Bayesian approach. Overall, 78 samples tested positive for HTLV-1, and 44 were analyzed here. The aA (cosmopolitan-transcontinental) subtype was recorded in all the samples. The following evolutionary rates were recorded for the different subtypes-a: 2.10-3, b: 2.69. 10-2, c: 6.23. 10-2, d: 3.08. 10-2, e: 6. 10-2, f: 1.78. 10-3, g: 2.2. 10-2 mutations per site per year. The positive HTLV-1 samples tested in the present study were characterized by their low genetic diversity and high degree of stability.

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

[This corrects the article DOI: 10.1371/journal.pone.0186055.].

Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.

Abstract INTRODUCTION: Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. METHODS: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. RESULTS: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. CONCLUSIONS: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.