Philippe Colson

Pig Liver Sausage as a Source of Hepatitis E Virus Transmission to Humans

BACKGROUND The source and route of autochthonous hepatitis E virus (HEV) infections are not clearly established in industrialized countries despite evidence that it is a zoonosis in pigs. We investigated the role of figatellu, a traditional pig liver sausage widely eaten in France and commonly consumed raw, as a source of HEV infection. METHODS A case-control study was conducted of 3 patients who presented autochthonous hepatitis E and 15 members of their 3 different families. Anti-HEV immunoglobulin G and immunoglobulin M antibody testing was performed with commercial assays. HEV RNA was detected in serum samples of patients and in pig liver sausages by means of real-time polymerase chain reaction and sequenced by means of in-house sequencing assays. Genetic links between HEV sequences were analyzed. RESULTS Acute or recent HEV infection, defined by detection of anti-HEV immunoglobulin M antibodies and/or HEV RNA, was observed in 7 of 13 individuals who ate raw figatellu and 0 of 5 individuals who did not eat raw figatellu (P=.041). Moreover, HEV RNA of genotype 3 was recovered from 7 of 12 figatelli purchased in supermarkets, and statistically significant genetic links were found between these sequences and those recovered from patients who ate raw figatellu. CONCLUSION Our findings strongly support the hypothesis of HEV infection through ingestion of raw figatellu.

Chronic Hepatitis E with Cirrhosis in a Kidney-Transplant Recipient

The authors report a rapidly progressing case of cirrhosis in a renal-transplant recipient with chronic hepatitis E virus infection.

Modern clinical microbiology: new challenges and solutions

In the twenty-first century, the clinical microbiology laboratory plays a central part in optimizing the management of infectious diseases and surveying local and global epidemiology. This pivotal role is made possible by the adoption of rational sampling, point-of-care tests, extended automation and new technologies, including mass spectrometry for colony identification, real-time genomics for isolate characterization, and versatile and permissive culture systems. When balanced with cost, these developments can improve the workflow and output of clinical microbiology laboratories and, by identifying and characterizing microbial pathogens, provide significant input to scientific discovery.

Treatment of severe acute hepatitis E by ribavirin

BACKGROUND Acute hepatitis E is associated with a higher rate of mortality as compared to hepatitis A or B infections in some series. To date no treatment has been recommended for acute hepatitis E. However, ribavirin has been recently reported to be highly effective to treat solid-organ-transplant recipients chronically infected with hepatitis E virus (HEV). OBJECTIVE AND STUDY DESIGN We report here on the use of ribavirin to treat severe acute HEV infection in a non-immunocompromized patient. This 61-year-old-man presented with acute hepatitis with HEV genotype 3. Seven days after admission, prothrombin index was 38%, bilirubinaemia was 550 μmol/L and alanine aminotransferases level was still increasing, reaching 4565IU/L. No hepatic encephalopathy was noted. Ribavirin (1200 mg/day) was introduced. RESULTS Liver biological tests showed rapid improvement concurrently with a decrease in HEV RNA levels in serum samples. Therapy was interrupted after 21 days. At that time, ALT had normalized, bilirubinemia was 138 μmol/L, and HEV RNA was almost undetectable in the serum. CONCLUSION Ribavirin therapy could be an effective treatment of severe acute hepatitis E.

Hepatitis E virus as an emerging cause of chronic liver disease in organ transplant recipients.

et al. Histopathological features of hepatitis C in renal transplant candidates. Transplantation 2000;69:1479–1484. [6] Samonakis DN, Cholongitas E, Triantos CK, Griffiths P, Dhillon AP, Thalheimer U, et al. Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantation for HCV cirrhosis. J Hepatol 2005;43:1091–1093. [7] Roche B, Samuel D. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat 2007;14 (Suppl. 1): 89–96. [8] Cholongitas E, Quaglia A, Samonakis DN, Papatheodoridis G, Senzolo M, Triantos C, et al. Patients with recurrent HCV infection and renal dysfunction after liver transplantation have slower fibrosis progression. J Hepatol 2006;44:S58. Evangelos Cholongitas Pinelopi Manousou Dimitrios Samonakis Andrew K. Burroughs * The Royal Free Sheila Sherlock Liver Centre and Department of Surgery, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK * Tel.: +44 20 74726229; fax: +44 20 74726226. E-mail address: Andrew.Burroughs@royalfree.nhs.uk (A.K. Burroughs).

Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century

Abstract Chloroquine (CQ) and its hydroxyl analogue hydroxychloroquine (HCQ) are weak bases with a half-century long use as antimalarial agents. Apart from this antimalarial activity, CQ and HCQ have gained interest in the field of other infectious diseases. One of the most interesting mechanisms of action is that CQ leads to alkalinisation of acid vesicles that inhibit the growth of several intracellular bacteria and fungi. The proof of concept of this effect was first used to restore intracellular pH allowing antibiotic efficacy for Coxiella burnetii, the agent of Q fever, and doxycycline plus HCQ is now the reference treatment for chronic Q fever. There is also strong evidence of a similar effect in vitro against Tropheryma whipplei, the agent of Whipples disease, and a clinical trial is in progress. Other bacteria and fungi multiply in an acidic environment and encouraging in vitro data suggest that this concept may be generalised for all intracellular organisms that multiply in an acidic environment. For viruses, CQ led to inhibition of uncoating and/or alteration of post-translational modifications of newly synthesised proteins, especially inhibition of glycosylation. These effects have been well described in vitro for many viruses, with human immunodeficiency virus (HIV) being the most studied. Preliminary in vivo clinical trials suggest that CQ alone or in combination with antiretroviral drugs might represent an interesting way to treat HIV infection. In conclusion, our review re-emphasises the paradigm that activities mediated by lysosomotropic agents may offer an interesting weapon to face present and future infectious diseases worldwide.

Prevalence of drug resistant mutants and virological response to combination therapy in patients with primary HIV-1 infection.

Baseline genotype resistance analysis was carried out in 48 adults with primary HIV‐1 infection between 1995 and 1998 before starting early combination therapy. Seventeen percent (8/48) of the isolates displayed key mutations conferring resistance to reverse transcriptase (RT) inhibitors such as amino acid substitutions 215Y/F (5/48,10%), 70R (3/48, 6%), 184V (2%). Two percent (1/48) had a major mutation associated with resistance to protease inhibitors (D30N). Other mutations at positions 10, 15, 20, 33, 36, 46, 63, 71, 77, 82, 93 of the protease gene were frequent (73%). Among the 46 patients who were given antiretroviral combination therapy and who responded durably to treatment after 6 and 12 months, there was no significant difference between those harboring RT mutant strains (Group I) and those with wild‐type isolates (Group II). No significant difference was found at months 6 and 12 between the two groups in terms of CD4+ cell counts. These findings suggest that the presence of drug‐resistant strains at the time of primary HIV‐1 infection does not necessarily predict drug failure. Other factors, such as adherence to treatment, tolerance and pharmacokinetics parameters are probably major determinants of virological response in patients with early therapeutic intervention. J. Med. Virol. 61:181–186, 2000.

Autochthonous Infections with Hepatitis E Virus Genotype 4, France

During January–March 2011, diagnoses of hepatitis E virus (HEV) infection increased in Marseille University hospitals in southeastern France. HEV genotype 4, which is described almost exclusively in Asia, was recovered from 2 persons who ate uncooked pork liver sausage. Genetic sequences were 96.7% identical to those recently described in swine in Europe.

Pepper mild mottle virus, a plant virus associated with specific immune responses, Fever, abdominal pains, and pruritus in humans.

Background Recently, metagenomic studies have identified viable Pepper mild mottle virus (PMMoV), a plant virus, in the stool of healthy subjects. However, its source and role as pathogen have not been determined. Methods and Findings 21 commercialized food products containing peppers, 357 stool samples from 304 adults and 208 stool samples from 137 children were tested for PMMoV using real-time PCR, sequencing, and electron microscopy. Anti-PMMoV IgM antibody testing was concurrently performed. A case-control study tested the association of biological and clinical symptoms with the presence of PMMoV in the stool. Twelve (57%) food products were positive for PMMoV RNA sequencing. Stool samples from twenty-two (7.2%) adults and one child (0.7%) were positive for PMMoV by real-time PCR. Positive cases were significantly more likely to have been sampled in Dermatology Units (p<10−6), to be seropositive for anti-PMMoV IgM antibodies (p = 0.026) and to be patients who exhibited fever, abdominal pains, and pruritus (p = 0.045, 0.038 and 0.046, respectively). Conclusions Our study identified a local source of PMMoV and linked the presence of PMMoV RNA in stool with a specific immune response and clinical symptoms. Although clinical symptoms may be imputable to another cofactor, including spicy food, our data suggest the possibility of a direct or indirect pathogenic role of plant viruses in humans.

Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients

IntroductionReactivation of hepatitis B virus (HBV) infection in patients with past infection has been described in 5% to 10% of individuals undergoing immunosuppressive therapies. No data are available to date on the outcome of patients treated by tumour necrosis factor-alpha (TNFα) inhibitors for chronic arthritis with a serological pattern of past HBV infection. The aim of our study was to monitor HBV markers in HBV surface antigen (HBsAg)-negative/anti-HBcAb-positive patients treated with a TNFα inhibitor for inflammatory arthritides.MethodsTwenty-one HBsAg-negative/anti-HBcAb-positive patients were included. HBV serological patterns were compared with those determined before starting TNFα inhibitors. Serum HBV DNA testing by polymerase chain reaction was additionally performed. Spearman correlation analysis was used and P < 0.05 was chosen as the significance threshold.ResultsBefore starting therapy, mean anti-HBsAb titre was 725 IU/L, no patient had an anti-HBsAb titre <10 IU/L, and 18 patients had an anti-HBsAb >100 IU/L. At a mean time of 27.2 months following therapy introduction, mean anti-HBsAb titre was 675 IU/L and anti-HBsAb titre remained >100 IU/L in 17 patients. There was a strong correlation between the first and second anti-HBsAb titres (r = 0.98, P = 0.013). Moreover, no patient had an anti-HBsAb titre below 10 IU/L or HBV reactivation (HBsAg seroreversion or positive HBV DNA detection). However, the anti-HBsAb titre decreased by more than 30% in 6 patients. The mean anti-HBsAb titre at baseline was significantly lower (P = 0.006) and the mean duration of anti-TNFα therapy, although non-significant (P = 0.09), was longer in these six patients as compared to patients without a decrease in anti-HBsAb titre.ConclusionsAnti-TNFα treatments are likely to be safe in patients with past hepatitis B serological pattern. However, the significant decrease of anti-HBsAb titre observed in a proportion of patients deserves HBV virological follow-up in these patients, especially in those with a low anti-HBsAb titre at baseline.