Norovirus infection among HIV patients in Abuja, Nigeria: impact of Highly Active Antiretroviral therapy status

doi:10.21203/rs.3.rs-3142055/v1

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Norovirus infection among HIV patients in Abuja, Nigeria: impact of Highly Active Antiretroviral therapy status

https://doi.org/10.21203/rs.3.rs-3142055/v1

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Journal Publication

published 21 Sep, 2023

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Background

Norovirus is now recognized to be major cause of gastroenteritis worldwide, with significantly higher disease burden among immunocompromised patients. This study aimed to determine the prevalence of Norovirus among HIV patients and to evaluate the impact of Highly active antiretroviral therapy (HAART) status on Norovirus prevalence in a sub-urban area of Abuja, Nigeria.

Methods

This study included a total of Two hundred and fifteen subjects (85 HAART-naïve and 130 HAART-exposed) HIV patients. Age range of study participants was 18 to 60 years. Faecal specimens where collected in screw capped containers and analyzed for Norovirus using Accupower Norovirus real-time PCR Test kit. CD4 cell count was determined using flow cytometry.

Results

The prevalence of Norovirus among HAART-naïve HIV patients was 10.6%. Age and gender was not associated with norovirus infection. HAART –naïve HIV patients with CD4 cell count < 200 was significantly more infected with Norovirus as compared to those with CD4 count ≥ 200 (OR: 28.000, 95% CI 3.2237, 243.2007, P = 0.0025). Norovirus was also found to be significantly higher in HAART-naïve HIV patients than amongst HAART-exposed counterparts (OR: 6.882, 95% CI: 1.4514, 32.6343, P = 0.015).

Conclusions

The prevalence of Norovirus among HAART-naïve HIV patients was high; and was significantly higher in subjects with low CD4 counts. Screening for Norovirus among HAART-naïve HIV patients is however emphasized to allow for effective Norovirus disease management.

Norovirus

HAART

HIV

CD4

Norovirus continues to be a major etiologic agent of diarrhea worldwide, and it causes about 18% of all cases of acute gastroenteritis worldwide [1]. Norovirus also called the winter vomiting bug is characterized by non-bloody diarrhea, vomiting and stomach pain and in some cases dehydration [2]. Norovirus infection in severe cases results in norovirus-associated enteropathy, intestinal villous atrophy, and malabsorption [2].

Norovirus is capable of establishing a long term infection in people who are immunocompromised, such as those with common variable immunodeficiency, Human Immunodeficiency virus (HIV) or with a suppressed immune system after organ transplantation [3]. Characteristically, norovirus infection in HIV patients lasts from weeks to years with concomitant difficulty in clinical management [4]. To the best of our knowledge, there is dearth of information on the proportion of norovirus infection among HIV patients with diarrhea in Nigeria. This study thus aimed to determine the prevalence of Norovirus among HIV patients in Abuja, Nigeria.

Study design and setting

This study was a one-year longitudinal cross-sectional study among HIV patients presenting at three ART clinics in Yangoji, Abaji and Kwali communities of Abaji and Kwali Local Government areas of Abuja, Federal Capital Territory (FCT), Nigeria. This Study was carried out in the period February 2022 to January, 2023. The study area is mainly sub-urban, and it’s the farthest local area from the FCT city Centre.

Ethical approval

was received from Local health authority (HEC/LHA:130A5) before commencement of study. Within the study period, Eighty-Five (85) HAART –naïve recently diagnosed HIV patients both male and female with diarrhea were recruited after receiving verbal or written consent for inclusion. One hundred and thirty (130) HAART exposed patients were also screened for Norovirus. Age range of study participants was 18 to 60 years.

Sample collection and Processing

About 5 ml of blood was collected into EDTA vacutainer aseptically. Participants were tested for HIV using two different immunochromatographic methods: Determine 1 & 2 (Inverness Medical Japan Co, Ltd) and STAT-PAK (Chembio Diagnostic System, New York, USA) the tie breaker employed was Unigold HIV test kit.

Faecal specimens where collected by participants into well screw-capped universal containers and where safely transported to the laboratory within thirty minutes of collection. Screening for Norovirus was performed using AccuPower Norovirus Real-Time RT-PCR Kit (Bioneer, South Korea), an in vitro diagnostic kit designed for the detection of norovirus (GI, GII) RNA in human samples such as stool and rectal swab through real-time PCR. The PCR protocol was a one-step premix type with a vacuum dried premix. All PCR protocol was carried out on a Exicycler 96 PCR platform (Bioneer, South Korea). AccuPower Norovirus Real-Time RT-PCR Kit includes Positive Control (PC), No Template Control (NTC) and Internal Positive Control (IPC) for accurate and reliable diagnosis of norovirus. ExiDiagnosis software was used to analyze the test results based upon the Ct (threshold cycle) value. CD4 cell counts were measured among HAART naïve HIV patients by flow cytometry (FACS scan, Beckton Dickinson, USA).

The overall prevalence of Norovirus among HAART naïve HIV patients in this study was 10.6 % (9/85). Age and gender were not significant prevalence determinants of norovirus among study participants. HAART-naïve patients with CD4 counts <200 were significantly more infected with norovirus as compared to subjects with CD4 counts ≥200 (OR: 28.000, 95% CI 3.2237 to 243.2007, P =0.0025) Table 1.

Table 1: Prevalence of Norovirus among HAART Naïve HIV patients

Norovirus was also found to be significantly higher in HAART-naïve HIV patients when compared to the HAART exposed counterparts (Table 2).

Table 2: Proportion of Norovirus among HAART naïve and HAART exposed subjects

The most commonly encountered norovirus genotypes among HAART-naïve patients in our study area was Nov GII (Figure 1).

Norovirus is now recognized as the major cause of gastroenteritis world over [5]. Norovirus is known to have high prevalence among immunocompromised patients with concomitant chronic diarrhea rather than acute illness [ 6], our study reports a high prevalence of Norovirus among HAART-naïve HIV patients in Abuja, Nigeria. Our finding further provides strength to the growing body of knowledge incriminating Norovirus as one of the major infectious disease causing diarrhea in HIV patients [7] and immunocompromised subjects [8].

Immunocompromised hosts have defective mechanisms to fight infections as compared to healthy individuals [9]. Immunocompromised hosts include patients with immunologic disorders, organ transplant recipients, patients on immunosuppressive therapies, cancer patients, patients with neutropenia and diabetic patients etc. [10]. Immunocompromised subjects are at higher odds of infection with Norovirus as compared to healthy individuals [11]. Norovirus infection in HIV patients have been documented to produce more adverse outcomes than in non-HIV patients [12]. Norovirus disease in HIV patients causes profound and persistent diarrhea, with excessive weight loss [12].

A recent study identified Norovirus as the most common encountered viral enteropathogen among HIV patients [13], further analysis showed that there was a significant association between Norovirus and onset and degree of diarrhea. Screening for Norovirus amongst HIV patients is valuable, early detection and management is pivotal.

inclusion of norovirus screening in the work up for HAART –naïve patients in our study area should be encouraged. Evaluation of immune status might provide better insights for patient segregation and care.

ART: Anti-retroviral therapy

HAART: Highly active anti-retroviral therapy

Nov: Norovirus

PCR: Polymerase chain reaction

HIV: Human Immunodeficiency Virus

OR: Odds Ratio

CI: Confidence Interval

CD4: Cluster of Differentiation 4

EDTA: Ethylene diamine tetra acetic acid

Data Availability

The data and materials supporting the conclusions of the study are available from the corresponding author on reasonable request.

Acknowledgements

Study participants are highly appreciated for being part of this study. Thanks to all Nurses and Community health care works at the ART clinic for their cooperation and assistance with sample collection and participant’s education.

Funding

First author received gifts of test kits and laboratory space from MDS Molecular services and Biotech Africa Genomics to execute this research (BTM: F001:234DER)

Authors Information

Department of Medical Laboratory Sciences, University of Benin, Benin City, Nigeria

Biotech Africa Genomics, Sub-Sahara African Office, Abuja, Nigeria.

MDS Molecular Services, Abuja, Nigeria.

Author Contribution

FO designed the study, data collection, collected the specimens and performed sample analysis.

WOJ performed statistical analysis and validation of test report and manuscript review. HSG performed critical review of manuscript and result validation. All authors reviewed and approved the manuscript

Corresponding author: Dr. Favour Osazuwa

Ethics declaration

All components of this study were approved by the Local Health authority of Abaji Local Government area (HEC/LHA:130A5). All procedures were performed in accordance with the ethical guidelines and regulations. Informed consent was obtained from all participants/legal guardians.

Consent for Publication

Not applicable.

Competing Interests

Authors declare no conflicts of interest.

Foot notes

Not applicable

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No competing interests reported.

Download PDF

Journal Publication

published 21 Sep, 2023

Read the published version in BMC Infectious Diseases →

Editorial decision: Major revision
21 Aug, 2023
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Reviewers agreed at journal
01 Aug, 2023
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29 Jul, 2023
Editor assigned by journal
29 Jul, 2023
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25 Jul, 2023
Submission checks completed at journal
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You are reading this latest preprint version

Norovirus infection among HIV patients in Abuja, Nigeria: impact of Highly Active Antiretroviral therapy status

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Study design and setting

Sample collection and Processing

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1