Unexplained diarrhoea in HIV-1 infected individuals.

Bas B Oude Munnink,Cees Ja Sol,Richard Molenkamp,Formijn J Van Hemert,Sjoerd Rebers,Michel De Vries,Matthew Cotten,Marta Canuti,Maarten F Jebbink,Kevin Chung,Lia Van Der Hoek,Fransje Snijders,Martin Deijs

doi:10.1186/1471-2334-14-22

Abstract

BackgroundGastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics.MethodsIn this study stool samples of 196 HIV-1 infected persons, including 29 persons with diarrhoea, were examined for enteropathogens and HIV-1. A search for unknown and unexpected viruses was performed using virus discovery cDNA-AFLP combined with Roche-454 sequencing (VIDISCA-454).ResultsHIV-1 RNA was detected in stool of 19 patients with diarrhoea (66%) compared to 75 patients (45%) without diarrhoea. In 19 of the 29 diarrhoea cases a known enteropathogen could be identified (66%). Next to these known causative agents, a range of recently identified viruses was identified via VIDISCA-454: cosavirus, Aichi virus, human gyrovirus, and non-A non-B hepatitis virus. Moreover, a novel virus was detected which was named immunodeficiency-associated stool virus (IASvirus). However, PCR based screening for these viruses showed that none of these novel viruses was associated with diarrhoea. Notably, among the 34% enteropathogen-negative cases, HIV-1 RNA shedding in stool was more frequently observed (80%) compared to enteropathogen-positive cases (47%), indicating that HIV-1 itself is the most likely candidate to be involved in diarrhoea.ConclusionUnexplained diarrhoea in HIV-1 infected patients is probably not caused by recently described or previously unknown pathogens, but it is more likely that HIV-1 itself plays a role in intestinal mucosal abnormalities which leads to diarrhoea.

Highlights

Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated human immunodeficiency virus (HIV)-1 infected individuals
Known enteropathogens To investigate how many diarrhoea cases of HIV-1 infected individuals could be explained by infections with known pathogens, real time PCR, bacteria culture and microscopy was performed on stool samples of 196 HIV-1 infected patients of whom 29 had severe diarrhoea
Sapovirus was found in 3 patients with diarrhoea (10%) and once in the control group, whereas norovirus was present in 10 patients with diarrhoea (34%) compared to 13 controls (7.8%)

Summary

Introduction

Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. One of the most affected sites in untreated human immunodeficiency virus (HIV)-infected persons is the gastrointestinal tract [1,2,3,4,5] In these patients diarrhoea occurs frequently, especially in HIV-1 patients who are not treated with anti-retroviral therapy. Its link with diarrhoea has not been established and a recent study in HIV-infected individuals detected cosavirus in a substantial number of patients without diarrhoea [16]. Aichi virus is another recently described picornavirus which was identified in fecal samples of patients with gastroenteritis [17]. The virus is genetically very closely related to gyroviruses found in chicken meat [22] and it remains uncertain whether human gyrovirus in stool is a sign of gastrointestinal infection or a virus which is digested with food and shed in feces, like many food related viruses [23]

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