H. Triki

Multiple Diverse Circoviruses Infect Farm Animals and Are Commonly Found in Human and Chimpanzee Feces

ABSTRACT Circoviruses are known to infect birds and pigs and can cause a wide range of severe symptoms with significant economic impact. Using viral metagenomics, we identified circovirus-like DNA sequences and characterized 15 circular viral DNA genomes in stool samples from humans in Pakistan, Nigeria, Tunisia, and the United States and from wild chimpanzees. Distinct genomic features and phylogenetic analysis indicate that some viral genomes were part of a previously unrecognized genus in the Circoviridae family we tentatively named “Cyclovirus” whose genetic diversity is comparable to that of all the known species in the Circovirus genus. Circoviridae detection in the stools of U.S. adults was limited to porcine circoviruses which were also found in most U.S. pork products. To determine whether the divergent cycloviruses found in non-U.S. human stools were of dietary origin, we genetically compared them to the cycloviruses in muscle tissue samples of commonly eaten farm animals in Pakistan and Nigeria. Limited genetic overlap between cycloviruses in human stool samples and local cow, goat, sheep, camel, and chicken meat samples indicated that the majority of the 25 Cyclovirus species identified might be human viruses. We show that the genetic diversity of small circular DNA viral genomes in various mammals, including humans, is significantly larger than previously recognized, and frequent exposure through meat consumption and contact with animal or human feces provides ample opportunities for cyclovirus transmission. Determining the role of cycloviruses, found in 7 to 17% of non-U.S. human stools and 3 to 55% of non-U.S. meat samples tested, in both human and animal diseases is now facilitated by knowledge of their genomes.

A Novel Picornavirus Associated with Gastroenteritis

ABSTRACT A novel picornavirus genome was sequenced, showing 42.6%, 35.2%, and 44.6% of deduced amino acid identities corresponding to the P1, P2, and P3 regions, respectively, of the Aichi virus. Divergent strains of this new virus, which we named salivirus, were detected in 18 stool samples from Nigeria, Tunisia, Nepal, and the United States. A statistical association was seen between virus shedding and unexplained cases of gastroenteritis in Nepal (P = 0.0056). Viruses with approximately 90% nucleotide similarity, named klassevirus, were also recently reported in three cases of unexplained diarrhea from the United States and Australia and in sewage from Spain, reflecting a global distribution and supporting a pathogenic role for this new group of picornaviruses.

Seroepidemiology of hepatitis B, C and delta viruses in Tunisia

Serum samples from 33,363 healthy people in Tunisia have been tested for serological markers of hepatitis B, C and delta viruses (HBV, HCV and HDV). Hepatitis B surface antigen (HBsAg) was detected in 6.5% of sera. The overall seroprevalence of HBV was 37.5%. Vertical and perinatal transmission of HBV in the first 3 months of life occurred in only 0.4% of 177 mother and child pairs. HBV seroprevalence was 10.7% in infants under 5 years old and increased with age rapidly till 25 years of age and then more slowly in adulthood, reaching 54% for people aged over 40 years. HBsAg seropositivity varied throughout the country, ranging from 3% to 13% with higher prevalences in the south and central-west regions. Overall seroprevalences for HDV and HCV were 17.7% and 0.4%, respectively. HDV superinfection occurred later than HBV and increased with age in parallel with HBV. Overall, HCV and HBV infections had different geographical distributions throughout the country. The study confirmed the high prevalence of HBV infection in Tunisia; it occurs mainly in children and teenagers, and vertical and perinatal transmission of HBV does not appear to be significant. HDV superinfection is quite common in Tunisia and occurs in almost 44% of individuals infected with HBV. In contrast, seroprevalence of HCV in the Tunisian general population was low (0.4%). These results indicate differences in the distribution of the viruses and/or different routes of transmission.

Influence of host related factors on the antibody response to trivalent oral polio vaccine in Tunisian infants

The low efficiency of trivalent oral polio vaccine (TOPV) in inducing protective antibody titres to polio3 is a problem of great importance in many regions of the world. A prospective study was conducted in 121 Tunisian infants aged 3 months during routine immunization with TOPV under carefully controlled conditions. Seroconversion rates to polio1, polio2 and polio3, one month after the third dose, were 94.7, 100 and 89.5%, respectively. The kinetics of the antibody response showed delayed and more difficult responses to polio3 compared to polio2 and polio1. The following host related factors, previously suggested to interfere with the immune response, were assessed: maternal antibodies; breast-feeding; concurrent enteric infections; and other illnesses. The main factor associated with the lack of seroconversion was concurrent infection with non-polio enteroviruses (NPE) which was found in 50% of non-responders to polio1 and/or to polio3 during the vaccination protocol whereas no NPE was isolated in vaccine responders. The other studied factors seemed not to interfere in the infants according to the locally adopted vaccination schedule and to the specific socio-economic conditions.

Status of Global Virologic Surveillance for Rubella Viruses

The suspected measles case definition captures rubella cases. Therefore, measles surveillance will be improved in the course of the control and eventual elimination of rubella transmission. One aspect of rubella control, virologic surveillance, is reviewed here. A systematic nomenclature for rubella viruses (RVs) based on 13 genotypes has been established and is updated when warranted by increases in information about RVs. From 2005 through 2010, the genotypes of RVs most frequently reported were 1E, 1G, and 2B, and genotypes 1a, 1B, 1C, 1h, 1j, and 2C were less frequently reported. Virologic surveillance can support rubella control and elimination. Synopses of rubella virologic surveillance in various countries, regions, and globally are given, including characterization of viruses from imported cases in a country that has eliminated rubella and studies of endemic viruses circulating in countries without rubella control objectives. Current challenges are discussed.

Association of interleukin‐18 polymorphisms and plasma level with the outcome of chronic HCV infection

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease throughout the world, and may progress to cirrhosis and hepatocellular carcinoma (HCC). Immunological factors, especially cytokines and some host genetic variations, rather than direct HCV action, seem to play an important role in the pathogenesis of HCV infection. Elevated levels of interleukin‐18 (IL‐18) were described previously for chronically (HCV)‐infected patients. This study is aimed at investigating IL‐18 promoter polymorphisms (−607C/A and −137G/C) in HCV‐infected patients with different disease severities (chronic hepatitis C, liver cirrhosis and HCC) and establishing an association between these polymorphisms and IL‐18 plasma concentration with the outcome of chronic HCV infection. The carriage of at least one C allele at position −607 (CC + CA) was associated with a higher risk of cirrhosis and HCC (P = 0.032). Compared with controls, HCV‐infected patients had significantly higher levels of IL‐18 (P = 0.0001) that correlate with disease severity (P = 0.01, P = 0.001, P = 0.0006, respectively). In conclusion, we supposed a possible implication of IL‐18 promoter polymorphisms in the pathogenesis of chronic HCV infection. J. Med. Virol. 80:607–614, 2008.

First multicenter study for risk factors for hepatocellular carcinoma development in North Africa

AIM To assess the role of the major risk factors for hepatocellular carcinoma (HCC) development in the western part of North Africa. METHODS A multicenter case control study was conducted in Tunisia, Morocco and Algeria in collaboration with Pasteur Institutes in these countries. A total of 164 patients with HCC and 250 control subjects without hepatic diseases were included. Prevalences of HBsAg, anti-hepatitis C virus (HCV) and diabetes were assessed. HCV and HBV genotyping were performed for anti-HCV and HBsAg positive patients. RESULTS The mean age of patients was 62 ± 10 years old for a 1.5 M:F sex ratio. Sixty percent of HCC patients were positive for anti-HCV and 17.9% for HBsAg. Diabetes was detected in 18% of cases. Odd ratio (OR) and 95% confidence intervals (CI) were 32.0 (15.8 - 65.0), 7.2 (3.2 - 16.1) and 8.0 (3.1 - 20.0) for anti-HCV, HBsAg and diabetes respectively. Multivariate analysis indicated that the three studied factors were independent. 1b HCV genotype and D HBV genotype were predominant in HCC patients. HCV was the only risk factor significantly associated with an excess of cirrhosis (90% vs 68% for all other risk factors collectively, P = 0.00168). Excessive alcohol consumption was reliably established for 19 (17.6%) cases among the 108 HCC patients for whom data is available. CONCLUSION HCV and HBV infections and diabetes are the main determinants of HCC development in North Africa. An active surveillance and secondary prevention programs for patients with chronic hepatitis and nutrition-associated metabolic liver diseases are the most important steps to reduce the risk of HCC in the region.

Molecular characterisation of a coxsackievirus A24 that caused an outbreak of acute haemorrhagic conjunctivitis, Tunisia 2003

This study reports the genetic characteristics of coxsackievirus A24 isolates from Tunisia, including a coxsackievirus A24 variant (CVA24v) that caused an outbreak of acute haemorrhagic conjunctivitis (AHC) between September and November 2003. The virus genome was detected by PCR from conjunctival swabs obtained from patients with AHC. Four virus isolates were obtained from PCR-positive samples and were serotyped by sequence analysis of the VP1 and VP4 genomic region and by seroneutralisation. Phylogenetic analysis of the VP1, VP4 and 3C genomic regions was performed. Other Tunisian CVA24 isolates from paralytic cases and healthy individuals were also amplified, sequenced and included in the phylogenetic analysis. The epidemic strain belonged to the CVA24 serotype. Phylogenetic analysis of the 3C region of the genome revealed a strong relationship between the Tunisian epidemic strain and strains that caused outbreaks in Korea (2002) and Guadeloupe and French Guiana (2003). Phylogenetic analysis of the VP1 and VP4 regions showed a clear distinction between serotype CVA24 isolates from conjunctivitis and non-conjunctivitis cases. This is the first study to report an outbreak of AHC caused by CVA24v in the North African region.

Hépatite virale B chez les femmes enceintes tunisiennes : facteurs de risque et intérêt de l’étude de la réplication virale en cas d’antigène HBe négatif

OBJECTIVE To evaluate the seroprevalence and the risk factors of hepatitis B virus (HBV) infection in 2303 Tunisian pregnant women and to estimate the risk of perinatal transmission in women positive for hepatitis B surface antigen (HBsAg) but negative for hepatitis B e-antigen (HBeAg). MATERIAL AND METHODS Positive samples were tested for HBeAg and anti-HBe antibody using enzyme immunoassays. Serum HBV-DNA was determined by real time PCR assay. RESULTS Overall, 4% of women were HBsAg positive and for the majority of them (96.8%) this status was unknown. Only 1.4% of studied population were vaccinated previously against hepatitis B. Study of risk factors revealed association between the HBsAg status and presence of intrafamilial hepatitis cases (p<0.05). Only four women were positive for HBeAg. Among patients with HBeAg negative status, only 11% were negative for HBV DNA. For the others, DNA level ranged from 34 to 10(8)copies/ml; it was greater than 10(4)copies/ml in 26.5% of them. CONCLUSION Hepatitis B virus (HBV) prevalence in pregnant women is of intermediate endemicity in Tunisia. Universal vaccination before pregnancy and antenatal screening is recommended. Pregnant women who are found to be HBsAg positive and HBeAg negative should be tested systematically for DNA level to evaluate the risk of perinatal infection and to prevent it by sero-prophylactic for babies or by treatment during the third trimester of pregnancy.

NS5AISDR‐V3 region genetic variability of Tunisian HCV‐1b strains: Correlation with the response to the combined interferon/Ribavirin therapy

In the non‐structural protein 5A (NS5A) of hepatitis C virus (HCV), mutations within the interferon sensitivity‐determining region (ISDR), the PKR‐binding domain (PKR‐BD), the variable region 3 (V3), and the interferon/ribavirin resistance‐determining region (IRRDR) have been correlated with the IFN‐based therapy response. In Tunisia, where a high prevalence of HCV‐1b has been found, no data regarding the implication of NS5A in treatment response were available. The current study examined the relationship between the pre‐treatment mutation number within ISDR, PKR‐BD, V3, IRRDR, as well as in the entire ISDR‐V3 region of NS5A (aa 2209–2379) and the response to the 48‐week course of combined IFN plus ribavirin therapy in 15 HCV‐1b‐infected Tunisian patients. Referring to HCV‐J sequence, a significant high genetic variability was observed within PKR‐BD in the sustained virological responder patients compared to non‐responders (P = 0.040). More importantly, when considering the entire region from ISDR to V3, referred to as NS5AISDR‐V3, a clear difference in the mutation number was observed between sustained virological responders (19.6 ± 3.16) and non‐responders (15.0 ± 1.41) (P = 0.002). Additionally, a more detailed analysis of NS5AISDR‐V3 region revealed an elevated degree of mutation rate within the region located between amino acids 2282 and 2308 (P = 0.0006). Interestingly, an analysis of specific amino acid variations defined proline and serine at position 2300 as signature patterns for sensitive and resistant strains, respectively. The genetic variability within the NS5A region of HCV‐1b strains was associated with the response to the combined IFN plus ribavirin therapy in our Tunisian cohort. J. Med. Virol. 81:2021–2028, 2009.