Understanding the clinical spectrum of complicated Plasmodium vivax malaria: a systematic review on the contributions of the Brazilian literature

The resurgence of the malaria eradication agenda and the increasing number of severe manifestation reports has contributed to a renewed interested in the Plasmodium vivax infection. It is the most geographically widespread parasite causing human malaria, with around 2.85 billion people living under risk of infection. The Brazilian Amazon region reports more than 50% of the malaria cases in Latin America and since 1990 there is a marked predominance of this species, responsible for 85% of cases in 2009. However, only a few complicated cases of P. vivax have been reported from this region. A systematic review of the Brazilian indexed and non-indexed literature on complicated cases of vivax malaria was performed including published articles, masters' dissertations, doctoral theses and national congresses' abstracts. The following information was retrieved: patient characteristics (demographic, presence of co-morbidities and, whenever possible, associated genetic disorders); description of each major clinical manifestation. As a result, 27 articles, 28 abstracts from scientific events' annals and 13 theses/dissertations were found, only after 1987. Most of the reported information was described in small case series and case reports of patients from all the Amazonian states, and also in travellers from Brazilian non-endemic areas. The more relevant clinical complications were anaemia, thrombocytopaenia, jaundice and acute respiratory distress syndrome, present in all age groups, in addition to other more rare clinical pictures. Complications in pregnant women were also reported. Acute and chronic co-morbidities were frequent, however death was occasional. Clinical atypical cases of malaria are more frequent than published in the indexed literature, probably due to a publication bias. In the Brazilian Amazon (considered to be a low to moderate intensity area of transmission), clinical data are in accordance with the recent findings of severity described in diverse P. vivax endemic areas (especially anaemia in Southeast Asia), however in this region both children and adults are affected. Finally, gaps of knowledge and areas for future research are opportunely pointed out

Correlation between TH1 response standard cytokines as biomarkers in patients with the delta virus in the western Brazilian Amazon

Hepatitis D virus (HDV) is endemic in the Amazon Region and its pathophysiology is the most severe among viral hepatitis. Treatment is performed with pegylated interferon and the immune response appears to be important for infection control. HDV patients were studied: untreated and polymerase chain reaction (PCR) positive (n = 9), anti-HDV positive and PCR negative (n = 8), and responders to treatment (n = 12). The cytokines, interleukin (IL)-2 (p = 0.0008) and IL-12 (p = 0.02) were differentially expressed among the groups and were also correlated (p = 0.0143). Future studies will be conducted with patients at different stages of treatment, associating the viral load with serum cytokines produced, thereby attempting to establish a prognostic indicator of the infection

Development of cost-effective real-time PCR test: to detect a wide range of HBV DNA concentrations in the western amazon region of Brazil

Submitted by EMERSON LEAL ([email protected]) on 2016-04-04T13:48:06Z No. of bitstreams: 1 Development of cost-effective.pdf: 268008 bytes, checksum: 97a9f9602cf50350dc69a9b2ca0b2367 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2016-04-13T14:19:19Z (GMT) No. of bitstreams: 1 Development of cost-effective.pdf: 268008 bytes, checksum: 97a9f9602cf50350dc69a9b2ca0b2367 (MD5)Made available in DSpace on 2016-04-13T14:19:19Z (GMT). No. of bitstreams: 1 Development of cost-effective.pdf: 268008 bytes, checksum: 97a9f9602cf50350dc69a9b2ca0b2367 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Porto Velho, RO, Brazil.Background: Currently there is a significant risk of infection with hepatitis B virus (HBV) during blood transfusion in high epidemic area. This is due to the pre-seroconversion window period, immunovariant viral strains and the presence of occult HBV infection (OBI). The aim of this study was to develop an in-house real-time PCR-based method, which was both ultra-sensitive and efficient offering an alternative method for nucleic acid testing (NAT). Methods: A precore fragment with 109 bp was cloned and serial diluted to standard curve construction. The calibration of the HBV - DNA values was performed against OptiQuant® HBV-DNA Quantification Panel, Acrometrix Europe B.V.). Results: From our in-house plasmid we prepared serial dilutions ranging from 2 × 103 – 2 × 109 copies/ml. The threshold was adjusted automatically during analysis and the data collected were analyzed by linear regression (r2 = 0.99). The limit of detection for the assay with pHBVRO standards was 2000/ml in a total reaction volume of 30 μl. We found a strong correlation between the two methods (r2 = 0.9965 and p < 0.0001). The regression line give us the following equation: Log 10 (IU/mL) = 0.9038Log 10 (copies/mL) − 1.0643, suggesting that 1 IU/mL = 15 copies/mL. Conclusions: Therefore, we can affirm that the qHBVRO PCR can detect HBV DNA in individuals with hepatitis B at any stage of the disease showing high capacity for NAT screening in hepatitis b donors. This results of sensitivity could provide an advance for automation in blood banks and increasing safety of patients who receive blood transfusions

Development of a reverse transcription quantitative real-time PCR-based system for rapid detection and quantitation of hepatitis delta virus in the western Amazon region of Brazil

Submitted by EMERSON LEAL ([email protected]) on 2016-06-22T14:49:46Z No. of bitstreams: 1 Development of a reverse transcription.pdf: 1097165 bytes, checksum: f7c63b478041c080da932ce62e0a3115 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2016-07-14T15:34:41Z (GMT) No. of bitstreams: 1 Development of a reverse transcription.pdf: 1097165 bytes, checksum: f7c63b478041c080da932ce62e0a3115 (MD5)Made available in DSpace on 2016-07-14T15:34:41Z (GMT). No. of bitstreams: 1 Development of a reverse transcription.pdf: 1097165 bytes, checksum: f7c63b478041c080da932ce62e0a3115 (MD5) Previous issue date: 2013Made available in DSpace on 2016-07-15T18:40:34Z (GMT). No. of bitstreams: 3 Development of a reverse transcription.pdf.txt: 35171 bytes, checksum: 66954954a32e342f185d534363acf5f8 (MD5) Development of a reverse transcription.pdf: 1097165 bytes, checksum: f7c63b478041c080da932ce62e0a3115 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório Plataforma Técnica. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Departamento de Medicina. Núcleo de Saúde. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório Plataforma Técnica. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Departamento de Medicina. Núcleo de Saúde. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brazil.Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório Plataforma Técnica. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Departamento de Medicina. Núcleo de Saúde. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brazil.Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório Plataforma Técnica. Porto Velho, RO, Brazil / Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil / Universidade Federal de Rondônia. Departamento de Medicina. Núcleo de Saúde. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brazil.The hepatitis delta virus (HDV) is a pathogen that causes a severe and rapidly progressive disease ofhepatocytes. The measurement of viral load in the peripheral blood of patients with HDV infections isimportant for diagnosis, treatment monitoring, and support for follow-up studies of viral replication dur-ing the course of the disease. This study reports the development of an assay capable of detecting andquantifying the abundance of HDV particles in serum samples, based on reverse-transcription quantita-tive PCR (RT-qPCR). Two standards for calibration were produced for determining the viral load of HDV:a cDNA cloned into a linear plasmid and a transcribed RNA. For validating this assay, 140 clinical samplesof sera were used, comprising 100 samples from patients who tested positive for anti-HDV and hepatitisB virus surface antigen (HBsAg) by ELISA; 30 samples from blood donors; 5 samples monoinfected withhepatitis B virus (HBV); and 5 samples monoinfected with hepatitis C virus (HCV). The HDV RT-qPCR assayperformed better when calibrated using the standard based on HDV cDNA cloned into a linear plasmid,yielding an efficiency of 99.8% and a specificity of 100% in the in vitro assays. This study represents thefirst HDV RT-qPCR assay developed with clinical samples from Brazil and offers great potential for newclinical efficacy studies of antiviral therapeutics for use in patients with hepatitis delta in the western Amazon region

Treatment of hepatitis delta virus genotype 3 infection with peg-interferon and entecavir

Submitted by EMERSON LEAL ([email protected]) on 2018-08-15T12:55:49Z No. of bitstreams: 1 Treatment of hepatitis delta virus genotype 3 infection with peg-interferon and entecavir.pdf: 640164 bytes, checksum: eb2dc45fe4928bedd19a2bf93c05444d (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2018-08-16T21:18:01Z (GMT) No. of bitstreams: 1 Treatment of hepatitis delta virus genotype 3 infection with peg-interferon and entecavir.pdf: 640164 bytes, checksum: eb2dc45fe4928bedd19a2bf93c05444d (MD5)Made available in DSpace on 2018-08-16T21:18:01Z (GMT). No. of bitstreams: 1 Treatment of hepatitis delta virus genotype 3 infection with peg-interferon and entecavir.pdf: 640164 bytes, checksum: eb2dc45fe4928bedd19a2bf93c05444d (MD5) Previous issue date: 2016Federal University of Rondônia. Research Center for Tropical Medicine of Rondônia. Porto Velho, RO, Brasil.Federal University of Rondônia. Research Center for Tropical Medicine of Rondônia. Porto Velho, RO, Brasil.Federal University of Rondônia. Research Center for Tropical Medicine of Rondônia. Porto Velho, RO, Brasil.Federal University of Rondônia. Research Center for Tropical Medicine of Rondônia. Porto Velho, RO, Brasil.Federal University of Rondônia. Research Center for Tropical Medicine of Rondônia. Porto Velho, RO, Brasil.Federal University of Rondônia. Research Center for Tropical Medicine of Rondônia. Porto Velho, RO, Brasil.Objectives: Hepatitis delta virus (HDV) is recognized as the most pathogenic and infectious among the hepatotropic viruses. Studies on the treatment of HDV have predominantly included European patients and carriers of genotype 1 (HDV-1) in their clinical protocols. For the Amazon region, data show that infected individuals have mainly Native American ancestry and that >90% of HDV carriers have the genotype 3 (HDV-3). Thus combined therapy clinical protocols do not adequately address the treatment of these patients. Methods: A prospective, non-randomized study was conducted in which 22 patients received 180 mg of pegylated interferon alpha 2a (PEG-IFN) plus entecavir at a dose of 0.5 mg for 48 weeks, with a subsequent 24-week follow-up. Throughout treatment, the patients were monitored for biochemical responses and the kinetics of hepatitis B virus (HBV) and HDV viral loads. Results: Of the 22 patients treated, 15 presented normal alanine aminotransferase values at the end of treatment (p = 0.002). At week 24 of treatment, 86.4% of the patients did not present detectable HDV- RNA; at week 48, the rate of negative patients increased to >95% and remained the same after 6 months. With regard to HBV, only two patients (9%) still presented detectable HBV genetic material at the end of treatment, suggesting the effectiveness of combined therapy in combating the two viruses. Conclusions: These findings support the use of this effective therapeutic protocol for HDV-3 in patients of non-European ethnicity and suggest a possible ‘easy to treat’ variant when compared to HDV-1

Clinical and virological heterogeneity of hepatitis delta in different regions world‐wide: The Hepatitis Delta International Network (HDIN)

Background & Aims: Chronic hepatitis D (delta) is a major global health burden. Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined. Methods: The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America. Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis. The primary aim was to investigate if the region of origin was associated with HDV replication and clinical outcome. Results: The majority of patients was male (n = 979, 62%) and the mean age was 36.7 years (range 1-79, with 9% of patients younger than 20 years). Most patients were HBeAg-negative (77%) and HDV-RNA positive (85%). Cirrhosis was reported in 48.7% of cases which included 13% of patients with previous or ongoing liver decompensation. Hepatocellular carcinoma (HCC) developed in 30 patients (2.5%) and 44 (3.6%) underwent liver transplantation. Regions of origin were independently associated with clinical endpoints and detectability of HDV RNA. Antiviral therapy was administered to 356 patients with different treatment uptakes in different regions. Of these, 264 patients were treated with interferon-a and 92 were treated with HBV-Nucs only. Conclusion: The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions. There is an urgent need for novel treatment options for HDV infection

Genomic Variability of Hepatitis B Virus Circulating in Brazilian Western Amazon

The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host&rsquo;s immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rond&ocirc;nia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease