Prolonged viral excretion in faeces among patients with hepatitis A
Published: 19.04.11 Updated: 27.04.2011 12:01:50
N. Vatev¹, M. Stoycheva², A. Petrov², C. Venchev², M. Troyancheva³
¹ Medical University, Dept. Hygiene, Ecology and Epidemiology, Plovdiv, Bulgaria
² Medical University, Dept. Infectious Diseases, Parasitology and Tropical medicine, Plovdiv, Bulgaria
³ Regional Inspectorate for Protection and Control of Public Health, Plovdiv, Bulgaria
Citation: Vatev N, Stoycheva M, Petrov A, Venchev C, Troyancheva MG. Prolonged viral excretion in faeces among patients with hepatits A. EpiNorth 2010; 11: 137-40.
Patients with hepatitis A excrete the virus in faeces from 1-3 weeks before to 2 weeks after the onset of disease. According to some recent investigations the viral excretion is longer. Faecal samples from 86 patients collected between the 40th to 50th day (6-7 weeks) after the onset of disease were examined. Five patients (5.8%) were positive. The results indicate prolonged viral faecal excretion in some of the cases. We recommend that preventive measures be extended for a longer period especially when children and food handlers are infected.
Viral hepatitis A (VHA) is an acute infectious disease that is transmitted primarily by the faecal-oral route (1, 2). The infection is most spread by person to person contact (3, 4). Results from numerous investigations indicate that virus excretion in patients’ faeces occurs from 1 – 3 weeks before until 2 weeks after the onset of disease (5, 6). The majority of authors believe that patients are contagious only during this period. Studies performed during last ten years suggest prolonged viral faecal excretion (7, 8, 9). The aim of this study is to establish if viral faecal excretion continues from the 40th to 50th day after the onset of disease. The study was performed in Plovdiv region of Bulgaria. The incidence rate of VHA in Bulgaria is several times higher than in the other EU countries. From 1997-2007 the incidence varied from 37/100,000 to 93/100,000. In Plovdiv region a large outbreak of HAV with more than 1000 patients involved was registered in 2006. An additional 43 smaller outbreaks were registered in Plovdiv and the incidence for the region reached 426/100,000.
Faecal samples were obtained from patients with VHA at the Clinic for Infectious Diseases, Medical University in Plovdiv, from November 15, 2008 until May 30, 2009. Samples were collected at the first control examination after the patients were discharged from hospital (between the 40th to 50th day after the onset of disease). The VHA diagnosis was confirmed by the presence of anti-hepatitis A virus (HAV) IgM. Faecal samples were examined for HAV antigen (HAV Ag) using the Mediagnost (Germany) HAV-antigen enzyme immunoassay (EIA). The cut-off value was set at 0.173. Every sample with an optical density value over or equal to the cut-off was considered positive and samples with an optical density value below the cut-off were considered negative. The positive results were confirmed by neutralizing the samples with anti-HAV serum to discriminate false positive reactions that occasionally occur in stools.
The following epidemiological investigations were performed; epidemiological history and tests directed at identifying the source of infection, determining the type of isolation (home or infectious disease department), regular clinical examination of the patient after discharge, detecting the contacts of patients and conducting the necessary measures, clinical supervision, immunoprophylaxis, disinfection where the outbreak occurred, and analysis of survey data in regard to the effectiveness of measures taken for prevention and control. Clinical analyses used to define prolonged viral excretion in faeces included diagnosis based on clinically overt symptoms, etiological confirmation by positive anti-HAV IgM serological test results, assessment of the severity of the clinical course and biochemical tests (blood bilirubin, alanine transaminase (ALT), aspartate transaminase, fibrinogen and blood count).
Faecal samples were obtained from 86 patients aged from 2 to 70 years. The median age was 23.7 ± 15.9 years, IQR (interquartile range) = 25.00. The male to female ratio was 1.15:1. Patients were mostly from the Plovdiv region. The results are presented in Figure 1. Samples with an optical density value greater than 0.173 were positive and those under 0.173 were negative.
Fig. 1. Viral faecal excretion of 86 hepatitis A patients 6-7 weeks after the onset of the disease, Plovdiv, Bulgaria
Five (5.8%) samples were positive. Three of the patients with positive results were children (4, 7 and 13 years old) and two were young people (27 and 38 years old). The course of the disease was mild in 3 and moderate in 2 of the cases. At the time of the sample collection one patient had an elevated ALT, 168 IU/L, and the other four had normal ALT levels (less than 40 IU/L) with a reference value of 40 IU/L.
Due to the acute and self-limiting nature of HAV infection, sequential sample collection combined with clinical data is uncommon. Information on the duration of HAV excretion in faeces is therefore limited despite its importance for disease control. Prolonged excretion of HAV in faeces extends the contagious period and poses a risk for the occurrence of secondary cases.
Based on the pathogenesis of VHA, most authors agree that patients excrete the virus in faeces up to 2 weeks after the onset of disease (2, 5, 6). Measures for prevention and control around the focus of infection are provided during this period. We conducted a large study to establish the epidemiological characteristics of VHA in Plovdiv region, Bulgaria, during 2005 to 2008 (10). The investigation included 3,911 patients and their contacts. Several cases were revealed in the same family more than 60 days after the initial patient was discharged from hospital. Among the secondary cases there were no data about contacts with persons with other diseases than VHA. Meaning that the secondary cases have been probably infected themselves from the other persons of their family with VHA who have been discharged before more than 60 days. Several similar cases were found among children attending kindergartens. We suggest that this may be due to a prolonged viral faecal excretion from the initial VHA case.
We have performed this study to shed light on the matter under question. Faecal samples were tested for HAV antigen using an HAV antigen EIA. This method was used rather than RT-PCR as described by Polish et al. (11) because specimens that are HAV-antigen positive are known to be more contagious than samples in which HAV RNA is detected by RT-PCR. While the sensitivity of the test is very high, EIA-negative samples can contain HAV particles. According to the manufacturer, 91% of ELISA-positive samples are also HAV RT-PCR positive. Cross reactivity is not known.
The results show that the faecal excretion of HAV continued for more than 40 days after the onset of disease in 5.8% of the patients included in this study. No correlation between the severity of clinical disease and the duration of HAV excretion in faeces or age was found. The findings suggest that patients may be infectious for a longer period than currently assumed. It is necessary to provide preventive measures for a longer period, especially at infection foci and among people at risk including children and food handlers. Timely preventive measures will limit secondary cases of VHA. Literature on this subject is sparse and further studies are warranted.
The authors thank the Medical University of Plovdiv for providing the immunoassay kits and the Regional Inspectorate for Protection and Control of Public Health in Plovdiv for conducting the laboratory analyses.
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