Saleem Kamili

Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area

Aim:  To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally.

Serologic Assays Specific to Immunoglobulin M Antibodies against Hepatitis E Virus: Pangenotypic Evaluation of Performances

Six immunoassays for detecting immunoglobulin M antibodies to hepatitis E virus were evaluated. Serum samples representing acute infection by each of the 4 viral genotypes as well as nonacute hepatitis E virus infection constituted the test panels. Diagnostic sensitivities and specificities as well as interassay agreement varied widely. Analytical sensitivity limits also were determined and were found to be particularly disparate.

Evidence of Person-to-Person Transmission of Hepatitis E Virus during a Large Outbreak in Northern Uganda

BACKGROUND Outbreaks of infection with hepatitis E virus (HEV) are frequently attributed to contaminated drinking water, even if direct evidence for this is lacking. METHODS We conducted several epidemiologic investigations during a large HEV infection outbreak in Uganda. RESULTS Of 10,535 residents, 3218 had HEV infection; of these, 2531 lived in households with >1 case. HEV was not detected in drinking water or zoonotic sources. Twenty-five percent of cases occurred > or = 8 weeks after onset of hepatitis in an index case in the household. Households with > or = 2 cases were more likely to have a member(s) who attended a funeral, had close contact with a jaundiced person, or washed hands in a common basin with others (P < .05 for all). CONCLUSIONS A high attack rate in households, lack of a common source of infection, and poor hygienic practices in households with > or = 2 cases suggest person-to-person transmission of HEV during this outbreak.

Serological diagnostics of hepatitis E virus infection

Development of accurate diagnostic assays for the detection of serological markers of hepatitis E virus (HEV) infection remains challenging. In the course of nearly 20 years after the discovery of HEV, significant progress has been made in characterizing the antigenic structure of HEV proteins, engineering highly immunoreactive diagnostic antigens, and devising efficient serological assays. However, many outstanding issues related to sensitivity and specificity of these assays in clinical and epidemiological settings remain to be resolved. Complexity of antigenic composition, viral genetic heterogeneity and varying epidemiological patterns of hepatitis E in different parts of the world present challenges to the refinement of HEV serological diagnostic assays. Development of antigens specially designed for the identification of serological markers specific to acute infection and of IgG anti-HEV specific to the convalescent phase of infection would greatly facilitate accurate identification of active, recent and past HEV infections.

Infectivity of Hepatitis C Virus in Plasma After Drying and Storing at Room Temperature

OBJECTIVE To determine effect of environmental exposure on the survival and infectivity of hepatitis C virus (HCV). METHODS Three aliquots of chimpanzee plasma containing HCV and proven infectious HCV inoculum were dried and stored at room temperature, 1 aliquot for 16 hours, 1 for 4 days, and 1 for 7 days. A chimpanzee (CH247) was sequentially inoculated intravenously with each of these experimental inocula, beginning with the material stored for 7 days. Each inoculation was separated by at least 18 weeks of follow-up to monitor for infection. The concentration of HCV RNA was measured and quasi species were sequenced for each experimental inoculum and in serum samples from CH247. RESULTS Evidence of HCV infection developed in CH247 only after inoculation with the material stored for 16 hours. No infection occurred after inoculation with the material stored for 7 days or 4 days. Compared with the original infectious chimpanzee plasma, the concentration of HCV RNA was 1 log lower in all 3 experimental inocula. The same predominant sequences were found in similar proportions in the original chimpanzee plasma and in the experimental inocula, as well as in serum samples from CH247. CONCLUSION HCV in plasma can survive drying and environmental exposure to room temperature for at least 16 hours, which supports the results of recent epidemiologic investigations that implicated blood-contaminated inanimate surfaces, objects, and/or devices as reservoirs for patient-to-patient transmission of HCV. Healthcare professionals in all settings should review their aseptic techniques and infection control practices to ensure that they are being performed in a manner that prevents cross-contamination from such reservoirs.

Hepatitis E Epidemic, Uganda

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths.

Laboratory Diagnostics for Hepatitis C Virus Infection

Identification of prevalent infection by hepatitis C virus (HCV) is based serologically on detecting anti-HCV immunoglobulin G, using immunoassays, immunoblot assays, and, more recently, immunochromatography-based rapid tests. None discriminate between active and resolved HCV infection. Tests for detecting HCV RNA identify active HCV infection but are costly. Serologic assays for HCV antigens have been developed and show potential for diagnosis of active HCV infection, and their performance characteristics are undergoing evaluation. The diagnosis of acute HCV infection without the demonstration of seroconversion remains elusive.

Aetiology and prognostic factors in acute liver failure in India

Summary.  The early prognostic indicators for acute liver failure in endemic zones for hepatitis E virus have not been determined. All consecutive patients with acute liver failure from a geographically defined region endemic for hepatitis E virus were studied over the period April 1989–April 1996. Demographic, clinical and biochemical parameters were recorded at presentation and serum samples were analysed for known viral hepatitis (A–E) markers. Multiple parameters were compared in survivors and non‐survivors in a univariate analysis. All significant factors on univariate analysis were entered into a stepwise logistic regression analysis to identify independent variables of prognosis. The sensitivity and specificity of significant prognostic factors was then assessed.

Experimental Studies on Subclinical Hepatitis E Virus Infection in Cynomolgus Macaques

Serial subclinical transmission among susceptible humans may serve as a reservoir of hepatitis E virus (HEV) in areas in which HEV is endemic. This hypothesis was investigated in an experimental primate model. Four groups of 4 cynomolgus macaques each were inoculated intravenously with 10(4)-10(5) (group 1), 10-100 (group 2), and 1-10 (group 3) cynomolgus macaque HEV infectious doses. All 4 animals in group 1 had clinical disease marked by alanine aminotransferase (ALT) elevation, fecal virus excretion, viremia, and seroconversion. Of the animals in groups 2 and 3, only 1 had evidence of biochemical hepatitis, although most had virus excretion and viremia (3 animals each in groups 2 and 3), and evidence of seroconversion (1 animal in group 2 and 3 animals in group 3). Viral genomic titers in stool specimens of animals with or without ALT elevation were similar. Infectivity studies confirmed the viability and transmission potential of the virus excreted by animals without ALT elevation. These data suggest that subclinical HEV infection may represent an HEV reservoir.

Efficacy of hepatitis B vaccine against antiviral drug‐resistant hepatitis B virus mutants in the chimpanzee model

Hepatitis B virus (HBV) mutants resistant to treatment with nucleoside or nucleotide analogs and those with the ability to escape from HBV‐neutralizing antibody have the potential to infect HBV‐vaccinated individuals. To address this potential serious public health challenge, we tested the efficacy of immunity induced by a commercial hepatitis B vaccine against a tissue culture‐derived, clonal HBV polymerase mutant in HBV seronegative chimpanzees. The polymerase gene mutant contained a combination of three mutations (rtV173L, rtL180M, rtM204V), two of which resulted in changes to the overlapping viral envelope of the hepatitis B surface antigen (sE164D, sI195M). Prior to the HBV mutant challenge of vaccinated chimpanzees, we established virologic, serologic, and pathologic characteristics of infections resulting from intravenous inoculation of the HBV polymerase gene mutant and the sG145R vaccine‐escape surface gene mutant. Cloning and sequencing experiments determined that the three mutations in the polymerase gene mutant remained stable and that the single mutation in the surface gene mutant reverted to the wild‐type sequence. Immunological evidence of HBV replication was observed in the vaccinated chimpanzees after challenge with the polymerase gene mutant as well as after rechallenge with serum‐derived wild‐type HBV (5,000 chimpanzee infectious doses administered intravenously), despite robust humoral and cellular anti‐HBV immune responses after hepatitis B vaccination. Conclusion: Our data showing successful experimental infection by HBV mutants despite the presence of high anti‐HBs levels considered protective in the vaccinated host are consistent with clinical reports on breakthrough infection in anti‐HBs‐positive patients infected with HBV mutants. In the absence of a protective humoral immunity, adaptive cellular immune responses elicited by infection may limit HBV replication and persistence. (HEPATOLOGY 2009.)