Enhancing ethics review of social and behavioral research : developing a review template in Ethiopia

CITATION: Wassie, L. et al. 2019. Enhancing ethics review of social and behavioral research : developing a review template in Ethiopia. Research Ethics, 15(3-4):1–23, doi:10.1177/1747016119865731.The original publication is available at https://journals.sagepub.com/home/reaBackground: Africa is increasingly becoming an important region for health research, mainly due to its heavy burden of disease, socioeconomic challenges, and inadequate health facilities. Regulatory capacities, in terms of ethical review processes, are also generally weak. The ethical assessment of social and behavioral research is relatively neglected compared to the review of biomedical and clinical studies, which led us to develop an ethics review assessment tool for use in the review of social and behavioral research in Ethiopia, which could potentially be of value in low- and middle-income settings. Methods: Initially, we did a comprehensive literature review on principles, guidelines, and practices of research ethics, on social and behavioral studies, from which we extracted query terms to explore the opinions of selected key informants and focus groups in Ethiopia. The discussants and informants were selected using a convenience sampling method to evaluate an ethics review template, which integrated issues that commonly arise in social and behavioral studies. Finally, we directly solicited opinions from the discussants about the desirability, feasibility, acceptability, and relevance of the ethics review assessment tool and used the resulting data to refine our initial draft. Results and conclusion: Although the same basic ethics principles govern all research studies, social and behavioral research have some disciplinary particularities that may require reviewers to exercise a different orientation of ethical attention in some cases. Using a qualitative approach, we developed a review assessment tool that could potentially be useful to raise awareness, focus attention, and strengthen the review of social and behavioral studies by ethics review committees, particularly in settings without a long-standing tradition of reviewing such research. This process also exposed some areas where further capacity building and discussion of ethical issues may be necessary among stakeholders in the review of social and behavioral research.Fogarty International Center of the National Institute of Health, USA (grant number R25 TW 008981)https://journals.sagepub.com/doi/full/10.1177/1747016119865731Publisher's versio

Ex vivo cytokine mRNA levels correlate with changing clinical status of ethiopian TB patients and their contacts over time.

There is an increasing body of evidence which suggests that IL-4 plays a role in the pathogenesis of TB, but a general consensus on its role remains elusive. We have previously published data from a cohort of Ethiopian TB patients, their contacts, and community controls suggesting that enhanced IL-4 production is associated with infection with M. tuberculosis, rather than overt disease and that long-term protection in infected community controls is associated with co-production of the IL-4 antagonist IL-4d2, alongside elevated IL-4. Here, for the first time, we compare data on expression of IFN-gamma, IL-4 and IL-4delta2 over time in TB patients and their household contacts. During the follow-up period, the TB patients completed therapy and ceased to display TB-like symptoms. This correlated with a decrease in the relative amount of IL-4 expressed. Over the same period, the clinical status of some of their contacts also changed, with a number developing TB-like symptoms or clinically apparent TB. IL-4 expression was disproportionately increased in this group. The findings support the hypothesis that elevated IL-4 production is generally associated with infection, but that TB disease is associated with a relatively increased expression of IL-4 compared to IFN-gamma and IL-4delta2. However, the data also suggest that there are no clear-cut differences between groups: the immune response over time appears to include changes in the expression of IFN-gamma, IL-4 and IL-4delta2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status

Phenotypic and functional heterogeneity of peripheral γδ T cells in pulmonary TB and HIV patients in Addis Ababa, Ethiopia

Abstract Background Previous studies reported HIV infection alters the distribution and function of γδ T cells and their subsets. γδ T phenotypes in healthy and diseased individuals has received little attention in Ethiopia. We conducted this study to analyze the distribution of γδ T cells, the subsets and levels of expression of activation (CD38), exhaustion or anergy (CD95, PD1), adhesion (N-CAM/CD56 and CD103), among HIV and TB infected patients. Method The distributions of total γδ T cells, Vδ1 and Vδ2 T cells subsets were analyzed in clinical samples collected from asymptomatic HIV, pulmonary TB patients and apparently healthy controls. Multicolor flow cytometry and IFN-γ ELISA were used to assess surface markers and functional responses of Vδ2 T cells to isopentenyl pyrophosphate stimulation, respectively. Result A total of 52 study participants were enrolled in this study, 22 HIV + TB-, 10 HIV-TB+ and 20 healthy controls. No significant differences were observed in the distribution of total γδ T cells and in the proportion of Vδ1 subsets in all study groups, though slightly higher proportions were observed in HIV + TB- patients for the latter, of borderline statistical significance (p = 0.07). However, the proportion of Vδ2 T cells, as well as the IFN-γ response to IPP stimulation, was significantly reduced in HIV + TB- patients compared to healthy controls (p < 0.002). Expression of the activation marker CD38 (p < 0.001) and adhesion marker CD103 (αEβ7) were significantly higher in the Vδ1 T cell subset among both HIV + TB- (p = 0.013) and HIV-TB+ (p = 0.006) patients compared to healthy controls. Similarly, exhaustion markers, CD95 and PD1, were significantly higher in these two T cell subsets among both HIV + TB- and HIV-TB+ patients (p < 0.01). Interestingly, we also observed an increased proportion of effector memory (CD45RA-CD27-) and effector cytotoxic (CD45RA + CD27-) Vδ2 T cell subsets in HIV negative pulmonary TB patients. Conclusion In sum, HIV infection was associated with an increase in Vδ1 and a decrease in the function and frequencies of Vδ2 T cells. Moreover, increased effector Vδ2 T cells were observed among HIV negative pulmonary TB patients suggesting a potential role of these T cells in the host response to TB

Diabetes mellitus is associated with an increased risk of unsuccessful treatment outcomes among drug-susceptible tuberculosis patients in Ethiopia: A prospective health facility-based study

Background: The impact of diabetes mellitus on tuberculosis (TB) treatment outcomes has not been well investigated in most sub-Saharan countries including Ethiopia. The current study aimed to determine the association between diabetes mellitus and unsuccessful TB treatment outcomes among drug-susceptible TB patients treated at selected health facilities in Addis Ababa, Ethiopia. Methods: This health facility-based prospective cohort study was conducted at six randomly selected public health centers in Addis Ababa, from August 2020 until November 2021. Clinically diagnosed adult pulmonary and extra pulmonary TB patients were recruited at the time of treatment initiation. A multivariable logistic regression analysis was used to estimate the association between diabetes and unsuccessful TB treatment outcomes. Results: Among the total 267 enrolled participants, 9.7% of patients with TB were identified to have diabetes comorbidity. Of patients with diabetes and TB, 9 (34.6%) were newly diagnosed based on glucose test results. Despite an overall high TB treatment success rate (94.0%), more than one-fourth (26.9%) of patients with diabetes had a poor TB treatment outcome (26.9%), which was remarkably higher compared to patients without diabetes (3.7%). In multivariable regression, the adjusted odds of poor TB treatment outcome among those with diabetes was 14.8 (95% CI 3.5 – 62.7) times the odds of poor outcome patients without diabetes. Conclusion: Diabetes was significantly associated with increased odds of poor TB treatment outcomes among patients in Addis Ababa, Ethiopia

Clinical and Imaging Characteristics of Smear Negative Pulmonary Tuberculosis Patients: A Comparative Study

Background. Prevalence surveys in Ethiopia indicate smear negative pulmonary tuberculosis (SNPTB) taking the major share of the overall TB burden. It has also been a diagnostic dilemma worldwide leading to diagnostic delays and difficulty in monitoring treatment outcomes. This study determines and compares the clinical and imaging findings in SNPTB and smear positive PTB (SPPTB). Methodology. A case-control study was conducted on 313 PTB (173 SNPTB) patients. Data and sputum samples were collected from consented patients. Smear microscopy, GeneXpert, and culture analyses were performed on sputum samples. Data were analyzed using Stata version 17; a P value < 0.05 was considered statistically significant. Results. Of the 173 SNPTB patients, 42% were culture positive with discordances between test results reported by health facilities and Armauer Hansen Research Institute laboratory using concentrated smear microscopy. A previous history of TB and fewer cavitary lesions were significantly associated with SNPTB. Conclusions. Though overall clinical presentations of SNPTB patients resemble those seen in SPPTB patients, a prior history of TB was strongly associated with SNPTB. Subject to further investigations, the relatively higher discrepancies seen in TB diagnoses reflect the posed diagnostic challenges in SNPTB patients, as a higher proportion of these patients are also seen in Ethiopia

Persistent expression of activation markers on Mycobacterium tuberculosis-specific CD4 T cells in smear negative TB patients

BackgroundT cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB.MethodologyIn this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa.ResultLevels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month.ConclusionAfter six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context

Active tuberculosis case finding and detection of drug resistance among HIV-infected patients: A cross-sectional study in a TB endemic area, Gondar, Northwest Ethiopia

Background: Tuberculosis (TB) patients co-infected with human immunodeficiency virus (HIV) often lack the classic symptoms of pulmonary tuberculosis, making the diagnosis difficult. Current practices in resource-limited settings often indicate that these co-infected patients are diagnosed when they clinically manifest disease symptoms, resulting in a delayed diagnosis and despite continued transmission. The aim of this study is to determine the prevalence of undiagnosed pulmonary tuberculosis cases through active case finding and including multidrug-resistant TB (MDR-TB) among HIV-infected patients. Materials and methods: A total of 250 HIV-infected patients, aged 18 years and above were evaluated in a cross-sectional design between February 2012 and November 2012. Socio-demographic and clinical data were collected using a structured questionnaire. Sputum samples were collected from all participants for acid fast bacilli (AFB) direct smear microscopy and Mycobacteria culture. A PCR-based RD9 deletion and genus typing, as well as first-line anti-TB drug susceptibility testing, was performed for all culture-positive isolates. Results: Following active TB case finding, a total of 15/250 (6%) cases were diagnosed as TB cases, of whom 9/250 (3.6%) were detected by both smear microscopy and culture and the remaining 6/250 (2.4%) only by culture. All the 15 isolates were typed through RD9 typing of which 10 were Mycobacterium tuberculosis species; 1 belonged to Mycobacterium genus and 4 isolates were non-tuberculous mycobacteria. The prevalence of undiagnosed pulmonary TB disease among the study participants was 4.4%, which implies the possibility of identifying even more undiagnosed cases through active case finding. A multivariate logistic regression showed a statistically significant association between the presence of pneumonia infection and the occurrence of TB (OR = 4.81, 95% CI (1.08–21.43), p = 0.04). In addition, all the isolates were sensitive to all first-line anti-TB drugs, except for streptomycin, seen in only one newly diagnosed TB patient, and MDR-TB was not detected. Conclusion: The prevalence of undiagnosed pulmonary TB infection among HIV-infected patients in Gondar was 4.4%. Additionally, the possibility of these undiagnosed TB cases in the community could also pose a risk for the transmission of the disease, particularly among family members. Active screening of known HIV-infected individuals, with at least one TB symptom is recommended, even in persons with opportunistic infections

Epidemiology of tuberculous lymphadenitis in Africa: A systematic review and meta-analysis.

IntroductionTuberculous lymphadenitis is the most frequent form of extra-pulmonary TB (EPTB) and accounts for a considerable proportion of all EPTB cases. We conducted a systematic review of articles that described the epidemiological features of TBLN in Africa.MethodsAny article that characterized TBLN cases with respect to demographic, exposure and clinical features were included. Article search was restricted to African countries and those published in English language irrespective of publication year. The articles were retrieved from the electronic database of PubMed, Scopus, Cochrane library and Lens.org. Random effect pooled prevalence with 95% CI was computed based on Dersimonian and Laird method. To stabilize the variance, Freeman-Tukey double arcsine root transformation was done. The data were analyzed using Stata 14.ResultsOf the total 833 articles retrieved, twenty-eight articles from 12 African countries fulfilled the eligibility criteria. A total of 6746 TBLN cases were identified. The majority of the cases, 4762 (70.6%) were from Ethiopia. Over 77% and 88% of identified TBLN were cervical in type and naïve to TB drugs. Among the total number of TBLN cases, 53% were female, 68% were in the age range of 15-44 years, 52% had a history of livestock exposure, 46% had a history of consuming raw milk/meat and 24% had history of BCG vaccination. The proportion of TBLN/HIV co-infection was much lower in Ethiopia (21%) than in other African countries (73%) and the overall African estimate (52%). Fever was recorded in 45%, night sweating in 55%, weight loss in 62% and cough for longer than two weeks in 32% of the TBLN cases.ConclusionsTBLN was more common in females than in males. The high prevalence of TBLN in Ethiopia did not show directional correlation with HIV. Population based prospective studies are warranted to better define the risk factors of TBLN in Africa