Chronic HDV/HBV co-infection: predictors of disease stage---a case series of HDV-3 patients.

BACKGROUND & AIMS: Chronic HDV/HBV co-infection is perhaps the most intriguing amongst all viral hepatitis. Only few studies focus deeply on this topic, particularly with patients infected with HDV-3. This study aimed to identify predictors of advanced disease, examining a cross-sectional data of 64 patients. METHODS: Histological grading was used to characterize the disease stages and viral loads were tested as predictors of necroinflammatory activity and fibrosis. RESULTS: We identified three HDV/HBV co-infection patterns: patients with predominant HDV replication (56.3%), patients with similar viral loads of both viruses (40.6%), and patients with predominant HBV replication (3.1%). Mean HDV-RNA showed a positive trend regarding inflammatory activity and grade of fibrosis. HDV viral load correlated positively with serum levels of liver enzymes and inversely with platelets count. HBV viral load showed no correlation with any of the above parameters. Advanced fibrosis was associated with age, splenomegaly, and HDV viral load of more than 2 log10. Multiple logistic regression confirmed the independent effect of HDV viral predominance. Advanced necroinflammatory activity was independently associated with HDV viral load and splenomegaly. CONCLUSIONS: HDV may possibly play an important and direct role in the establishment of necroinflammatory activity and fibrosis. Data show an indigenous HDV genotype, HDV-3, similar to those described in the Amazon region.

Arboviral diseases in the Western Brazilian Amazon: a perspective and analysis from a tertiary health & research center in Manaus, State of Amazonas.

The Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), located in Manaus, the capital of the State of Amazonas (Western Brazilian Amazon), is a pioneering institution in this region regarding the syndromic surveillance of acute febrile illness, including arboviral infections. Based on the data from patients at the FMT-HVD, we have detected recurrent outbreaks in Manaus by the four dengue serotypes in the past 15 years, with increasing severity of the disease. This endemicity has culminated in the simultaneous circulation of all four serotypes in 2011, the first time this has been reported in Brazil. Between 1996 and 2009, 42 cases of yellow fever (YF) were registered in the State of Amazonas, and 71.4% (30/42) were fatal. Since 2010, no cases have been reported. Because the introduction of the yellow fever virus into a large city such as Manaus, which is widely infested by Aedes mosquitoes, may pose a real risk of a yellow fever outbreak, efforts to maintain an appropriate immunization policy for the populace are critical. Manaus has also suffered silent outbreaks of Mayaro and Oropouche fevers lately, most of which were misdiagnosed as dengue fever. The tropical conditions of the State of Amazonas favor the existence of other arboviruses capable of producing human disease. Under this real threat, represented by at least 4 arboviruses producing human infections in Manaus and in other neighboring countries, it is important to develop an efficient public health surveillance strategy, including laboratories that are able to make proper diagnoses of arboviruses.

Epidemiology and molecular characterization of hepatitis B virus infection in isolated villages in the Western Brazilian Amazon.

Individuals from three isolated, rural communities in the western Brazilian Amazon were evaluated for serological markers of hepatitis B virus (HBV) infection, HBV genotype, and the presence of risk factors for infection and transmission. Of the 225 individuals studied, 79.1% had serological evidence of HBV infection; 10.2% individuals were chronic carriers for HBV surface antigen (HBsAg-positive). Analysis of risk factors indicates that HBV is transmitted mainly horizontally within the family from a chronic "active" carrier for hepatitis B "e" antigen (HBeAg-positive), though a strong possibility of vertical transmission remains. The predominance of HBV genotype F, with a higher genomic similarity between the isolates, indicated a relatively recent introduction of HBV, from a common source, to the area. This study sheds light on the HBV epidemiology in the Brazilian Amazon region and highlights the need for greater emphasis on HBV control and immunization programs.

Identification of Oropouche Orthobunyavirus in the cerebrospinal fluid of three patients in the Amazonas, Brazil.

Oropouche fever is the second most frequent arboviral infection in Brazil, surpassed only by dengue. Oropouche virus (OROV) causes large and explosive outbreaks of acute febrile illness in cities and villages in the Amazon and Central-Plateau regions. Cerebrospinal fluid (CSF) samples from 110 meningoencephalitis patients were analyzed. The RNA extracted from fluid was submitted to reverse transcription-polymerase chain reaction and sequencing to identify OROV. Three CSF samples showed the presence of OROV causing infection in the central nervous system (CNS). These patients are adults. Two of the patients had other diseases affecting CNS and immune systems: neurocysticercosis and acquired immunodeficiency syndrome, respectively. Nucleotide sequence analysis showed that the OROV from the CSF of these patients belonged to genotype I. We show here that severe Oropouche disease is occurring during outbreaks of this virus in Brazil.

Arboviral diseases in the Western Brazilian Amazon: a perspective and analysis from a tertiary health & research center in Manaus, State of Amazonas

The Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), located in Manaus, the capital of the State of Amazonas (Western Brazilian Amazon), is a pioneering institution in this region regarding the syndromic surveillance of acute febrile illness, including arboviral infections. Based on the data from patients at the FMT-HVD, we have detected recurrent outbreaks in Manaus by the four dengue serotypes in the past 15 years, with increasing severity of the disease. This endemicity has culminated in the simultaneous circulation of all four serotypes in 2011, the first time this has been reported in Brazil. Between 1996 and 2009, 42 cases of yellow fever (YF) were registered in the State of Amazonas, and 71.4% (30/42) were fatal. Since 2010, no cases have been reported. Because the introduction of the yellow fever virus into a large city such as Manaus, which is widely infested by Aedes mosquitoes, may pose a real risk of a yellow fever outbreak, efforts to maintain an appropriate immunization policy for the populace are critical. Manaus has also suffered silent outbreaks of Mayaro and Oropouche fevers lately, most of which were misdiagnosed as dengue fever. The tropical conditions of the State of Amazonas favor the existence of other arboviruses capable of producing human disease. Under this real threat, represented by at least 4 arboviruses producing human infections in Manaus and in other neighboring countries, it is important to develop an efficient public health surveillance strategy, including laboratories that are able to make proper diagnoses of arboviruses.