A safe and effective rotavirus vaccine is urgently needed, particularly in developing countries. Critical to vaccine development and implementation is a knowledge base concerning the epidemiology of rotavirus G and P serotypes/genotypes throughout the world. The temporal and geographical distribution of human rotavirus G and P types was reviewed by analysing a total of 45571 strains collected globally from 124 studies reported from 52 countries on five continents published between 1989 and 2004. Four common G types (G1, G2, G3 and G4) in conjunction with P[8] or P[4] represented over 88% of the strains analysed worldwide. In addition, serotype G9 viruses associated with P[8] or P[6] were shown to have emerged as the fourth globally important G type with the relative frequency of 4.1%. When the global G and/or P type distributions were divided into five continents/subcontinents, several characteristic features emerged. For example, the P[8]G1 represented over 70% of rotavirus infections in North America, Europe and Australia, but only about 30% of the infections in South America and Asia, and 23% in Africa. In addition, in Africa (i) the relative frequency of G8 was as high as that of the globally common G3 or G4, (ii) P[6] represented almost one-third of all P types identified and (iii) 27% of the infections were associated with rotavirus strains bearing unusual combinations such as P[6]G8 or P[4]G8. Furthermore, in South America, uncommon G5 virus appeared to increase its epidemiological importance among children with diarrhea. Such findings have (i) confirmed the importance of continued active rotavirus strain surveillance in a variety of geographical settings and (ii) provided important considerations for the development and implementation of an effective rotavirus vaccine (e.g. a geographical P-G type adjustment in the formulation of next generation multivalent vaccines).

Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine.

The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.

Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs.

https://hal.archives-ouvertes.fr/hal-00556058/document

Zoonotic aspects of rotaviruses

Rotavirus genotyping: keeping up with an evolving population of human rotaviruses

Temporal and spatial fluctuations in the genotype distribution of human rotaviruses are continuously observed in surveillance studies. New genotypes, such as G9 and G12, have emerged and spread worldwide in a very short time span. In addition, reassortment events have the potential to contribute substantially to genetic diversity among human and animal rotaviruses. With the recent introduction of the two rotavirus vaccines, RotaTeq and Rotarix, in many countries, it appears that the total number of hospitalizations due to rotavirus infections is being reduced, at least in developed countries that implemented a universal immunization program. However, continued surveillance is warranted, especially regarding the long-term effects of the vaccines. No data analyses are available to clarify whether rotavirus vaccine introduction would allow other rotavirus P and G genotypes, which are not covered by the current vaccines, to emerge into the human population and fill the apparent gap. This kind of data analysis is essential, but its interpretation is hampered by natural and cyclical genotype fluctuations.

Rotavirus disease and vaccination: impact on genotype diversity.

Rotavirus serotype G5 in fecal specimens of 38 Brazilian children with diarrhea was identified by PCR and enzyme immunoassays The strains exhibited long RNA electropherotypes and either subgroup II or nonsubgroup I-nonsubgroup II specificities Serotype G5 has been found in piglets and horses but not yet in humans Images

Rotavirus serotype G5 associated with diarrhea in Brazilian children.

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A virus with bi-segmented double-stranded RNA genome in guinea pig intestines.

Keywords: adverse event, drug related, genetic polymorphisms, pharmacogeneticsSUMMARYWhat is known and Objective: Anti-tuberculosis drugs (ATD),although highly effective, often cause liver injury. GlutathioneS-transferases (GST) play a crucial protective role in the detoxi-fying mechanisms of drugs. Several studies have investigatedthe genetic null variants of GSTM1 and GSTT1 as possible riskfactors for ATD-induced liver injury; however, those ﬁndingsare inconsistent. We investigated GSTM1 and GSTT1 null geno-types in Brazilian patients with tuberculosis (TB), adjusting forother possible predictors of ATD-induced liver injury.Methods: This was a prospective cohort study with patientswho were treated for TB from 2006 to 2011. GSTM1 and GSTT1gene deletions were analysed from genomic DNA by polymer-ase chain reaction (PCR). Demographic, clinical and laboratorydata were extracted from medical records and possible predic-tors of liver injury were evaluated.Results and Discussion: This study enrolled 177 patients. Anti-tuberculosis drugs-induced liver injury incidence was 33AE3%.Hepatitis B infection (HBV) and increased alanine amino-transferase (ALT) baseline were signiﬁcant predictors. NeitherGSTM1 nor GSTT1 null genotypes were associated with ATD-induced liver injury; nevertheless, the comparison among fourdifferent liver toxicity grades showed that GSTM1 non-nullgenotype was signiﬁcant more frequent among the highergrades of liver toxicity.What is new and Conclusion: GSTM1 and GSTT1 null geno-types do not seem to play important roles in ATD-inducedliver injury in Brazilians. However, there was evidence thatGSTM1 polymorphisms were possibly related to the intensityof toxicity. Active HBV and initial high ALT could predictATD-induced liver injury.WHAT IS KNOWN AND OBJECTIVEStandard tuberculosis (TB) treatment with rifampicin (R), isonia-zid (H), pyrazinamide (Z) and ethambutol (E) is highly effec-tive; however, the multi-drug regimen for TB often causesadverse events. Hepatotoxicity is one of the most frequent andmost serious adverse effects observed during TB treatment.

/pdf/the-roles-of-gstm1-and-gstt1-null-genotypes-and-other-4p8cq1uzgf.pdf

The roles of GSTM1 and GSTT1 null genotypes and other predictors in anti-tuberculosis drug-induced liver injury.

A method for genotyping hepatitis B virus (HBV) strains, based on restriction fragment length polymorphism (RFLP) analysis of four different amplified fragments of the HBV genome, was used to investigate nosocomial infections that occurred in two Brazilian hemodialysis centers. Viral isolates from hepatitis B surface antigen (HBsAg)-positive serum samples from 27 hemodialysis patients and 39 HBV-positive unrelated control patients were grouped according to their RFLP patterns. Strains isolated from the control patients were divided into nine RFLP patterns: A1, A2, A3 (genotype A), D1, D2, D3, D4 (genotype D), F1, and F2 (genotype F). In hemodialysis unit A (Rio de Janeiro), 14 HBV isolates were grouped into five different RFLP patterns: A1, A2, A3, D3, and D4. Pattern A2, present at a relatively low prevalence (18%) in the control group, was observed in the majority (53%) of the hemodialysis patients. Notably, all five patients who seroconverted to HBsAg positivity in 1995 carried the strain A2. In hemodialysis unit B (state of Sao Paulo), where an outbreak of HBV infection occurred in 1996–1997, RFLP analysis showed that all 13 patients who seroconverted were infected with HBV isolates of genotype D. Coinfection with strain A1 was detected in seven of them. The results demonstrate the value of RFLP analysis in establishing common sources of infection in hemodialysis centers.

Nosocomial Spread of Hepatitis B Virus in Two Hemodialysis Units, Investigated by Restriction Fragment Length Polymorphism Analysis

Summary
Oral inoculation of newborn mice with the MET strain of human rotavirus produced transient diarrhoeal disease. Light and scanning electron microscopy showed typical rotavirus-induced morphological lesions in the villous epithelium of the small intestine consisting of extensive cytoplasmic vacuolation, villous necrosis and atrophy. Virus recovered from intestinal suspensions of infected mice showed the typical electrophoretic profile of the genome of the inoculated strain. Rotavirus antibody appeared in infected mice 10 to 20 days after inoculation but not in controls or nursing dams. The availability of a small animal model for experimental infection with human rotaviruses should prove useful for virulence and protection studies.

L. de Castro

Papers

Rotavirus serotype G5 associated with diarrhea in Brazilian children.

A virus with bi-segmented double-stranded RNA genome in guinea pig intestines.

The roles of GSTM1 and GSTT1 null genotypes and other predictors in anti-tuberculosis drug-induced liver injury.

Nosocomial Spread of Hepatitis B Virus in Two Hemodialysis Units, Investigated by Restriction Fragment Length Polymorphism Analysis

Diarrhoea in mice infected with a human rotavirus.