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.

Evidence for hidden leprosy in a high leprosy-endemic setting, Eastern Ethiopia: The application of active case-finding and contact screening.

Leprosy or Hansen's disease is a disabling infectious disease caused by Mycobacterium leprae. Reliance on the self-presentation of patients to the health services results in many numbers of leprosy cases remaining hidden in the community, which in turn results in a longer delay of presentation and therefore leading to more patients with disabilities. Although studies in Ethiopia show pockets of endemic leprosy, the extent of hidden leprosy in such pockets remains unexplored. This study determined the magnitude of hidden leprosy among the general population in Fedis District, eastern Ethiopia. A community-based cross-sectional study was conducted in six randomly selected leprosy-endemic villages in 2019. Health extension workers identified study participants from the selected villages through active case findings and household contact screening. All consenting individuals were enrolled and underwent a standardized physical examination for diagnosis of leprosy. Overall, 262 individuals (214 with skin lesions suspected for leprosy and 48 household contacts of newly diagnosed leprosy cases) were identified for confirmatory investigation. The slit skin smear technique was employed to perform a bacteriological examination. Data on socio-demographic characteristics and clinical profiles were obtained through a structured questionnaire. Descriptive statistics and binary logistic regression were used to assess the association between the outcome variable and predictor variables, and the P-value was set at 0.05. From the 268 individuals identified in the survey, 6 declined consent and 262 (97.8%) were investigated for leprosy. Fifteen cases were confirmed as leprosy, giving a detection rate of 5.7% (95%, CI: 3%, 9%). The prevalence of hidden leprosy cases was 9.3 per 10,000 of the population (15/16107). The majority (93.3%) of the cases were of the multi-bacillary type, and three cases were under 15 years of age. Three cases presented with grade II disability at initial diagnosis. The extent of hidden leprosy was not statistically different based on their sex and contact history difference (p > 0.05). High numbers of leprosy cases were hidden in the community. Active cases findings, and contact screening strategies, play an important role in discovering hidden leprosy. Therefore, targeting all populations living in leprosy pocket areas is required for achieving the leprosy elimination target.

Knowledge of and Attitude Toward Leprosy in a Leprosy Endemic District, Eastern Ethiopia: A Community-Based Study.

INTRODUCTION: Leprosy or Hansen's disease is a potentially disabling disease that results in discrimination and self-stigma. A delay in case detection among leprosy patients is one of the factors resulting in disability. Although poor insights of the community toward leprosy lead to delays in case detection, studies on such matters are neglected in Ethiopia. OBJECTIVE: To assess the level of community knowledge and attitudes toward leprosy in Fedis District, Eastern Ethiopia. METHODS: A community-based cross-sectional study was carried out among 728 randomly selected households from July to August 2019. Each participant was interviewed using a pretested structured questionnaire consisting of participants' socio-demographic background, questions related to knowledge of and attitudes toward leprosy. The collected data were entered using EpiData 3.1 and analyzed using STATA version 13. Chi-squared test, binary, and multivariable logistic regressions were applied as appropriate to assess the association between outcome and independent variables. RESULTS: Among 728 study participants, 608 (83.52%) of them had heard about leprosy. Among the study participants who had heard of leprosy, 346 (56.91%) of them had high knowledge of leprosy. Multivariable logistic regression revealed that study participants who completed grade 1-8 (AOR=1.68, 95% CI=1.09-2.58, P=0.017) and government employees (AOR=7.56, 95% CI=2.23-25.63, P=0.001) were significantly associated with high level of knowledge of leprosy. Out of 608 study participants who had heard of leprosy, only 248 (40.79%) had a favorable attitude toward leprosy. Study participants who completed grade 1-8 (AOR= 2.72, 95% CI=1.76-4.19, P= 0.000) and urban inhabitants (AOR=0.49, 95% CI=0.31-0.75, P= 0.032) were significantly associated with favorable attitude toward leprosy. Having high knowledge of leprosy was significantly associated with favorable attitudes toward leprosy. CONCLUSION: This study revealed unfavorable attitudes toward leprosy among the community. Having a high overall knowledge level on leprosy has been shown to support a favorable attitude toward leprosy.

New Insight into the Pathogenesis of Erythema Nodosum Leprosum: The Role of Activated Memory T-Cells.

Memory T-cells, particularly, effector memory T cells are implicated in the pathogenesis of inflammatory diseases and may contribute to tissue injury and disease progression. Although erythema nodosum leprosum (ENL) is an inflammatory complication of leprosy, the role of memory T cell subsets has never been studied in this patient group. The aim of this study was at investigate the kinetics of memory T cell subsets in patients with ENL before and after prednisolone treatment. A case-control study design was used to recruit 35 untreated patients with ENL and 25 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Venous blood samples were obtained before, during, and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of T cell activation and memory T-cell subsets by flow cytometry. The kinetics of these immune cells in patients with ENL before and after treatment were compared with LL patient controls as well as within ENL cases at different time points. The median percentage of CD3+, CD4+, and CD8+ T-cells expressing activated T-cells were significantly higher in the PBMCs from patients with ENL than from LL patient controls before treatment. The median percentage of central and activated memory T-cells was significantly increased in patients with ENL compared to LL patient controls before treatment. Interestingly, patients with ENL had a lower percentage of naïve T cells (27.7%) compared to LL patient controls (59.5%) (P < 0.0001) before treatment. However, after prednisolone treatment, patients with ENL had a higher median percentage of naïve T-cells (43.0%) than LL controls (33.0%) (P < 0.001). The median percentage of activated T-cells (effector memory and effector T-cells) was significantly increased in patients with ENL (59.2%) before treatment compared to after treatment with prednisolone (33.9%) (P < 0.005). This is the first work which has shown T-cell activation and the different subsets of memory T cells in untreated patients with ENL. Consequently, this study delineates the role of T-cell activation in the pathogenesis of ENL reaction and challenges the long-standing dogma of immune complex as a sole etiology of ENL reaction.

T-cell regulation in Erythema Nodosum Leprosum.

Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL.

Growth and development of children of mothers with leprosy and healthy controls.

INTRODUCTION: In the pre-sulphone and early sulphone years children of leprous parents had been followed in a few prospective studies to observe the development of leprosy. No studies were made of the growth and development of these children. METHODS: A prospective, open-ended, cohort study began in 1975 with follow-up of both mothers and their children until 2003. 156 pregnancies were studied consisting of 36 non-leprous (NL), 25 tuberculoid and borderline tuberculoid leprosy (TT&BT) (released-from-treatment), 18 with TT&BT (active), 42 borderline lepromatous leprosy (BL) and 35 lepromatous leprosy (LL). RESULTS: Babies of mothers with leprosy had lower birth weight, smaller placentae, grew more slowly, had more infections and higher infant mortality than those of non-leprous mothers. The findings were most marked in babies of LL mothers. Growth in childhood was uneventful, infants of LL mothers catching up by age 3.6 years. Childhood infections were common in all groups but more serious for children of lepromatous mothers. The puberty skeletal growth spurt, and, for the girls, menarche was delayed for children studied compared with a new healthy control group, with catch-up by late teens. These findings were most marked in children of lepromatous, especially LL, mothers. CONCLUSION: Impaired growth in utero and infancy is probably due to immunological factors but we could find no explanation for the delayed growth in adolescent children of LL mothers.