Fekadu Abebe

Background Traditional Healers (THs) hold significant roles in many developing countries, often sought for ailments like tuberculosis (TB). However, their knowledge, attitude, and practice (KAP) regarding TB, particularly in Ethiopia’s pastoralist areas, remains unexamined. This study evaluates THs’ KAP on TB and their perceptions to collaborate with conventional health systems on TB control. Method A cross-sectional survey was conducted among THs in Kereyu, Ethiopia from September 2014 to January 2015. Using a semi-structured questionnaire, 268 THs were interviewed. Health Extension workers helped identify the THs. Results Of the 268 participants, 80.6% were male. 97.4% were aware of TB (locally “dukubba soombaa”), with 80.2% associating its cause to proximity with a TB patient. Coughing for over two weeks was identified as a primary TB symptom by 87.35%. However, 66.4% displayed limited biomedical knowledge on TB. A notable 38.4% associated TB with sadness and hopelessness, while 47.8% utilized plant-based remedies for treatment. Impressively, 86.2% expressed willingness to collaborate with conventional health services for TB control. Conclusion The THs had limited biomedical knowledge and some misconceptions about TB. Despite providing traditional medicine to treat TB, their readiness to collaborate with established health systems is promising. Thus, Ethiopian TB control initiatives should consider integrating THs via targeted training and health education interventions.

Tuberculosis kills more people than any other single infectious disease globally. Despite decades of research, there is no vaccine to prevent TB transmission. Bacille Calmette‐Guerin (BCG) vaccine developed a century ago, is effective against childhood (disseminated and miliary) TB. However, its protective efficacy against pulmonary TB varies from 0‐80% in different populations. One of the main reasons for lack of an effective vaccine against TB is lack of complete understanding about correlates of protective immunity on which to base vaccine design and development. However, some household contacts who are extensively exposed to Mtb infection remain persistently negative to tuberculin skin test and interferon‐gamma assay. These individuals called “resisters” clear Mtb infection early before the development of acquired immunity. The immunological basis of early Mtb clearance is yet to be established, however, innate lymphocytes such as monocytes/macrophages, dendritic cells, neutrophils and natural killer cells, and innate like T cells such as mucosal associated invariant T cells, invariant natural killer T cells and gamma‐delta (γδ) T cells have been implicated in this early protection. In recent years, NK cells have attracted increasing attention because of their role in controlling Mtb infection. Emerging data from animal and epidemiological studies indicate that NK cells play a significant role in the fight against Mtb. NK cells express various surface markers to recognize and kill both Mtb and Mtb‐infected cells. This review presents recent advances in our understanding of NK cells in the fight against Mtb early during infection, with emphasis on cohort studies.

Background: Despite the potential foetal and maternal risks of self-medication, studies on self-medication and safety profile of medicines used during pregnancy are scarce. This study determined the prevalence, predictors and safety profile of medicines used for self-medication during pregnancy at Jimma University Medical Centre (JUMC) in Ethiopia. Methods: A hospital-based cross sectional study was conducted on 1117 hospitalized pregnant women or postpartum women in the maternity and gynaecology wards at JUMC between February and June 2017. Data were collected using an interviewer-administered structured questionnaire and by reviewing patient medical records. Data were analysed using descriptive statistics and logistic regression. Result: Nearly 3 out of 10 women reported taking at least one type of conventional medicine for self-medication, mainly analgesics 92.3%. Almost 75.0% of the self-medicated women used medicines classified as probably safe and 13.6% as potentially risky to use during pregnancy. Medicinal plant use, religion and access to a health facility near their residency were significantly associated with self-medication during pregnancy. Conclusions: Self-medication is common among pregnant women at JUMC. Most women used medicines classified as safe to use during pregnancy. There is need for enlightenment of pregnant women on the potential dangers of self-medication during pregnancy to prevent foetal and maternal risks.

Induction of Th1 (cell-mediated) immunity and associated production of IFN-γ by CD4+ T cells has been widely used as a marker of protective immunity against tuberculosis (TB). This is based on two assumptions. The first is the widely accepted view that Mycobacterium tuberculosis (Mtb), the causative agent of TB is an obligate intracellular pathogen, and the second is based on the Th1/Th2 paradigm, which posits that polarization of CD4+ T cells into type1 (cell-mediated) and type 2 (humoral) is central for proper induction of protective immunity against pathogens. However, almost all licensed vaccines currently in use are primarily anti-body based whether intracellular or extra-cellular. In addition, converging data from both animal models and humans indicate that the production of IFN-γ alone is not sufficient to confer protection against TB. In addition, a substantial body of the literature suggests that, in addition to Th1 cells, antibody classes and sub-classes are protective against TB. In a recent study, we have shown that there is a synergy between IFN-γ (cell-mediated) and IgA (humoral) in human population in an endemic setting. In this review, current data from both animal and human studies that support mixed Th1 and Th2 responses that are protective against Mtb and other pathogens are presented.

Pastoralists rely on traditional healers (THs) for general health problems. However, some studies indicate that such practices result in delays in the diagnosis and treatment of tuberculosis (TB) cases. This study aims to assess the role of traditional healers in the detection and referral of active TB cases in a pastoralist community. We identified 22 traditional healers from 7 villages of Kereyu pastoralist community in the Fentale district in Ethiopia in January 2015. We trained these THs in identifying presumptive TB symptoms and early referral to the nearby healthcare facilities. The training was held during a 1 week period that included a visit to their villages and follow-up. A 1 day meeting was held with the traditional healers, the district TB care and prevention coordinator and health extension workers from the selected sub-district to discuss the referral link between THs and the nearby healthcare facilities. Health providers working at the TB units in the selected healthcare facilities were oriented about the training given and planned involvement of THs in referring presumptive TB case. In addition, documentation of the presumptive TB cases was discussed. We succeeded in tracing and interviewing 8 of the 22 THs. The rest were on seasonal migration. According to the THs report for the 1 year period, these 8 THs had referred 24 TB suspects to the healthcare facilities. Sputum smear microscopy confirmed 13 of the 24 suspects as having TB cases. Among those confirmed, 10 completed treatment and three were on treatment. Five presumptive TB cases were confirmed non TB cases through further evaluation at the healthcare facilities and six of the presumptive TB cases were lost to follow up by the THs. Whereas, four of the presumptive TB cases were lost to follow up to the healthcare facility. Results of the present study indicate that THs can contribute to the detection of undiagnosed active TB cases in a pastoralist community, provided they are given appropriate training and support.

Tuberculosis (TB) remains the prime killer disease among infectious diseases. TB control depends on early case detection and treatment in a directly observed treatment short course (DOTS) programme. The success of DOTS depends on the ability of the health care system to identify and properly manage TB cases. The present study aims to assess healthcare provider (HCP) knowledge, attitude and perceived stigma regarding TB and perception about traditional healers. A descriptive cross sectional study was conducted among 108 HCPs using a semi-structured, self-administered questionnaire from September 2014 to January 2015. The study district has a high TB burden area with one district hospital, 4 health centres, and 18 health posts. All health facilities and HCPs available during the study period in the district were included in the study. Statistical software for social science (SPSS) version 22 and STATA version 14 were used to enter and analyse data, respectively. The majority (64%) of the HCPs had poor overall knowledge regarding TB, and 67.6 and 57.6% had poor knowledge regarding TB diagnosis and nature of the disease, respectively. Moreover, most 66.7 and 55.6% of the HCPs had an unfavourable attitude towards TB and TB control systems, respectively. Slightly under half (49.1%) of the HCPs had a favourable attitude towards TB patients, and the majority (88.9%) had low perceived stigma. The majority (87.0%) of the HCPs indicated the importance of community involvement in TB control activity. Moreover, most (60.2%) of the HCPs showed willingness to collaborate with traditional healers (THs) on TB control activity. Healthcare workers’ knowledge gap and unfavourable attitude towards TB control systems reported in this study may cause poor TB care delivery. HCPs’ perception of the importance of community involvement in TB control and willingness to collaborate with THs on TB management could be an opportunity to strengthen the World Health Organization’s (WHO’s) component of End TB strategy through community engagement. Training and workshops could be used to address the knowledge gap and the unfavourable attitude regarding TB among HCPs.

As part of a major project to investigate protective and diagnostic immune markers against tuberculosis (TB), we measured antibody isotype responses to Mycobacterium tuberculosis (Mtb) antigens (LAM, Rv2031, and HBHA) in cohorts of 149 pulmonary tuberculosis patients (PTBP), 148 household contacts (HHCs), and 68 community controls (CCs) in an endemic setting. ELISA was used to measure levels of IgA, IgG, and IgM from sera of cohorts at baseline, and at 6 and 12 months from entry. The results show that there were significant differences in IgA, IgG, and IgM responses to the different antigens and in the three cohorts. At baseline, the level of IgM against RV2031 and LAM did not vary between cohorts, but the levels of IgA and IgG against Rv2031 were significantly higher in PTB patients than HHCs and CCs, followed by HHCs, and the lowest in CCs. In patients, there was a significant variation in antibody responses before and after chemotherapy. The levels of IgA and IgG against HBHA, and IgA against Rv2031 decreased significantly and remained low, while IgA and IgG against LAM increased significantly and remained high following chemotherapy. However, the levels of IgM against Rv2031 and LAM increased at 6 months but decreased again at 12 months. IgM against HBHA did not show any significant variation before and after chemotherapy. Similarly, there were also significant variations in antibody responses in HHCs over time. Our results show that there are significant variations in IgA, IgG and IgM responses to the different antigens and in the three cohorts, implying that not all antibody isotype responses are markers of clinical TB. In addition, the current and previous studies consistently show that IgA and IgG against Rv2031 discriminate between clinical disease, Mtb-infected and non-infected individuals.

Mycobacterium tuberculosis (Mtb) 38‐kDa antigen is an immunogenic lipoprotein that induces strong T‐cell responses in experimental animals. However, there is limited information on the role of this antigen in human population. In this article, we present the dynamics of pro‐inflammatory (IFN‐γ and TNF‐α) and anti‐inflammatory cytokine (IL‐10) against the 38 kDa in cohorts of pulmonary TB (PTB) patients, household contacts (HHCs), and community controls (CCs) in a high endemic setting. Whole blood assay was used to determine the levels of cytokines in 149 patients, 149 HHCs, and 68 CCs at baseline, 6 months, and 12 months. At baseline, the level of IFN‐γ was significantly (p < 0.0001) higher in CCs and HHCs than in untreated patients. CCs had significantly (p < 0.05) higher level of IFN‐γ than HHCs. There was no significant difference between treated and untreated patients, and there was no significant change in HHCs over 12 months. At baseline, the levels of IL‐10 and TNF‐α were significantly (p < 0.0001) higher in patients than in HHCs and CCs. No significant change was observed between treated patients and untreated patients and HHCs over time. The study shows that IFN‐γ against the 38 kDa discriminates clinical TB from infection and infection from exposure, suggesting its potential for immune protection and diagnosis.

Summary: Mycobacterium tuberculosis (Mtb) early secreted protein antigen 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are among candidate vaccines against tuberculosis (TB). Results of experimental animal models show that these antigens are associated with induction of strong T cell immunity [interferon (IFN)-γ production], while others report that these proteins as virulent factors involved in pathogenicity of Mtb infection. However, the role of ESAT-6/CFP-10 during natural Mtb infections in humans has not been established. In this paper we present results of a longitudinal study from an Mtb-infected human population from an endemic setting. Whole blood assay was used to determine levels of IFN-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 against rESAT-6/CFP-10 in TB patients, household contacts and community controls. The levels of IFN-γ, TNF-α and IL-10 against rESAT-6/CFP-10 at baseline were significantly higher in patients and community controls than in household contacts. In patients, no significant difference was observed in the level of these cytokines before and after chemotherapy whereas, in contacts, the level of these cytokines increased significantly and progressively over time. The study shows that the levels of IFN-γ, TNF-α and IL-10 against rESAT-6/CFP-10 are depressed during Mtb infection or exposure but are elevated during clinical TB. Our findings from a study of naturally infected human population suggest that IFN-γ, TNF-α and IL-10 against rESAT-6/CFP-10 are markers for clinical TB but not for protective immunity.

QuantiFERON-TB Gold In-Tube® (QFT-GIT) test is used for the diagnosis of latent tuberculosis (TB) infection. Besides, QFT-GIT test could allow tracking changes in immune response among TB patients and their contacts. In high TB burden settings, reports on QFT-GIT conversions and reversions among TB patients and their contacts are limited. As part of a major project to study immune responses to TB infection, we investigated QFT-GIT test conversions and reversions among smear positive pulmonary TB patients and their household contacts over 12 months. We followed a total of 107 HIV negative participants (33 patients and 74 contacts) in Addis Ababa. We did QFT-GIT test at baseline and 12 months later according to the manufacturer’s instructions. At baseline, 25/33 (75.8%) of the patients and 50/74 (67.6%) of the contacts were QFT-GIT positive. At 12 months, 2 more patients (1 test negative and 1 indeterminate) became test positive. Besides, 11/24 (45.8%) test negative contacts became positive. Only one patient and one contact who were test positive at baseline became test negative 12 months later. At 12 months, the proportions of QFT-GIT test positives for patients and contacts were, therefore, 78.8% and 81.1%, respectively. Among contacts, the proportion of QFT-GIT test positives at 12 months was significantly higher compared to the corresponding proportion at baseline (McNemar, p = 0.006); similarly, the median IFN-γ response significantly increased at 12 months compared with the baseline level (Wilcoxon matched-pairs signed rank test, p = 0.01). Patients, however, had comparable median IFN-γ levels at baseline and 12 months later (p = 0.56). Nearly half of QFT-GIT negative household contacts at baseline became positive at 12 months. This suggests that repeated screening of QFT-GIT negative contacts may be needed for epidemiological studies and interventions of latent TB in an endemic setting. A large longitudinal study may be needed to confirm our observations.