Abstract

In the battle to quickly identify potential yellow fever arbovirus outbreaks in the Democratic Republic of the Congo, active syndromic surveillance of acute febrile jaundice patients across the country is a powerful tool. However, patients who test negative for yellow fever virus infection are too often left without a diagnosis. By retroactively screening samples for other potential viral infections, we can both try to find sources of patient disease and gain information on how commonly they may occur and co-occur. Several human arboviruses have previously been identified, but there remain many other viral families that could be responsible for acute febrile jaundice. Here, we assessed the prevalence of human herpes viruses (HHVs) in these acute febrile jaundice disease samples. Total viral DNA was extracted from serum of 451 patients with acute febrile jaundice. We used real-time quantitative PCR to test all specimens for cytomegalovirus (CMV), herpes simplex virus (HSV), human herpes virus type 6 (HHV-6) and varicella-zoster virus (VZV). We found 21.3% had active HHV replication (13.1%, 2.4%, 6.2% and 2.4% were positive for CMV, HSV, HHV-6 and VZV, respectively), and that nearly half (45.8%) of these infections were characterized by co-infection either among HHVs or between HHVs and other viral infection, sometimes associated with acute febrile jaundice previously identified. Our results show that the role of HHV primary infection or reactivation in contributing to acute febrile jaundice disease identified through the yellow fever surveillance program should be routinely considered in diagnosing these patients.

Highlights

  • Due to the severity and the high risk of re-emergence of yellow fever, a disease caused by an arthropod-borne virus, the Democratic Republic of the Congo (DRC) has implemented an active syndromic surveillance program throughout the country since 2003 based on the involvement of healthcare structures located in its health areas

  • Clinical manifestations are diverse: herpes simplex virus (HSV)-1 causes blisters on the lips and HSV-2 is associated with similar blisters or sores on the genitals, CMV induces pneumonia and meningitis, varicella-zoster virus (VZV) is responsible for Varicella or herpes zoster after reactivation, and human herpes viruses (HHVs)-6 is the cause of the common childhood illness exanthema subitum [11,12]

  • Diagnosis of acute febrile jaundice remains a challenge in yellow fever surveillance

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Summary

Introduction

Due to the severity and the high risk of re-emergence of yellow fever, a disease caused by an arthropod-borne virus, the Democratic Republic of the Congo (DRC) has implemented an active syndromic surveillance program throughout the country since 2003 based on the involvement of healthcare structures located in its health areas. In order to investigate other causative pathogens, we previously investigated other viral pathogens, sometimes associated with acute febrile jaundice, retrospectively in available samples [1,2] These target viruses included two transmitted by arthropods ( known as arboviruses: Chikungunya virus and dengue virus), as well as hepatitis (A, B, C and E) virus infections which are characterized by hepatic disease and which can occur at high frequencies in the study population. We found 3.5% (n = 16/453), 0.4% (n = 2/453), 16.7% (72/432), 22.3% (n = 105/470), 2.3% (n = 9/379) and 10.4% (n = 38/365) tested positive for Chikungunya virus, Dengue virus, HAV, HBV, HCV and HEV, respectively Though these investigations associated 224 suspected yellow fever cases with a potential causative pathogen, many remained unidentified. Clinical manifestations are diverse: HSV-1 causes blisters on the lips and HSV-2 is associated with similar blisters or sores on the genitals, CMV induces pneumonia and meningitis, VZV is responsible for Varicella (chickenpox) or herpes zoster (shingles) after reactivation, and HHV-6 is the cause of the common childhood illness exanthema subitum ( known as roseola infantum) [11,12]

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