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Observational Study
. 2025 Dec 12;13(4):316.
doi: 10.3390/medsci13040316.

Determinants of Entero-Invasive and Non-Entero-Invasive Diarrheagenic Bacteria Among HIV-Positive and HIV-Negative Adults in Ghana

Hagen Frickmann  1   2 , Fred Stephen Sarfo  3   4 , Betty Roberta Norman  3   4 , Albert Dompreh  5 , Shadrack Osei Asibey  3 , Richard Boateng  5 , Veronica Di Cristanziano  6 , Tafese Beyene Tufa  7   8   9 , Ulrike Loderstädt  10 , Ramona Binder  11 , Andreas Erich Zautner  12   13 , Tom Luedde  9 , Torsten Feldt  8   9 , Kirsten Alexandra Eberhardt  9   14   15
Affiliations
Observational Study

Determinants of Entero-Invasive and Non-Entero-Invasive Diarrheagenic Bacteria Among HIV-Positive and HIV-Negative Adults in Ghana

Hagen Frickmann et al. Med Sci (Basel). .

Abstract

Objectives: This observational and cross-sectional study investigated differential associations between entero-invasive and non-entero-invasive enteric pathogens and HIV infection, considering socioeconomic, clinical and immunological aspects. In a Ghanaian population with a high prevalence of enteric pathogens, stool samples from people living with HIV (PLWH) were screened for Salmonella spp., Shigella spp./EIEC (enteroinvasive Escherichia coli), and Campylobacter jejuni as entero-invasive bacteria, for enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), and enteroaggregative E. coli (EAEC) as non-entero-invasive bacteria. Arcobacter butzleri, with uncertain enteropathogenicity, was also included.

Methods: Stool samples from PLWH (with and without antiretroviral therapy) and HIV-negative controls were analyzed by real-time PCR for the presence and quantity of the selected enteropathogens. Results were correlated with socioeconomic, clinical, and immunological parameters.

Results: The presence of Shigella spp. /EIEC in stool was both qualitatively and quantitatively associated with reduced CD4+ T lymphocyte counts and was qualitatively associated with clinically apparent diarrhea. EAEC showed a weak positive association with HIV infection, supported by a negative correlation between EAEC DNA quantity and CD4+ T lymphocyte counts. EPEC colonization was associated with HIV negativity, higher CD4+ T lymphocyte counts, and lower socioeconomic status. Abundance of Salmonella enterica was associated with clinically apparent diarrhea.

Conclusions: This explorative, hypothesis-forming study suggests species- or pathovar-specific associations between enteric bacterial pathogens and HIV-related immunosuppression. Observed relationships with clinically apparent diarrhea largely align with findings from sub-Saharan African children, except for a more pronounced association between diarrhea and Salmonella in this cohort.

Keywords: Arcobacter butzleri; Campylobacter; Escherichia coli; HIV; Salmonella; Shigella; enteroaggregative; enteropathogenic; enterotoxigenic; immunosuppression.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
DNA-detection-based prevalence and absolute numbers of coinfections with enteropathogenic bacteria by HIV status in the study population. (a) Prevalence of detected enteric pathogens in stool samples, stratified by HIV-negative and HIV-positive groups. (b) Distribution of the number of concurrent detected enteric bacterial infections according to HIV status.
Figure 2
Figure 2
Pathogens associated with CD4+ T-lymphocyte counts in the study population. (a) Random forest variable importance analysis for HIV-positive individuals identifying bacterial enteropathogens ranked by their predictive contribution to CD4+ T-lymphocyte counts. (b) Corresponding random forest analysis for HIV-negative individuals. (c) Multivariable linear regression results for the combined cohort showing estimated associations between pathogens and CD4+ T-lymphocyte counts.
Figure 3
Figure 3
Pathogens associated with diarrheal disease in the study population. (a) Random forest variable importance analysis for HIV-positive individuals identifying enteropathogenic bacteria ranked by their predictive contribution to the clinical symptom of diarrhea. (b) Corresponding random forest analysis for HIV-negative individuals. (c) Multivariable logistic regression results for the entire study population showing estimated associations between pathogens and diarrheal disease.
Figure 4
Figure 4
Pathogens associated with socioeconomic status index in the study population. (a) Random forest variable importance analysis for HIV-positive individuals identifying bacterial enteropathogens ranked by their predictive contribution to the binary socioeconomic status. (b) Corresponding random forest analysis for HIV-negative individuals. (c) Multivariable logistic regression results for the entire study population showing estimated associations between detected enteropathogens and socioeconomic status index.
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