Edessa Negera

Background The host immune responses associated with the clinical phenotypes of Mycobacterium leprae infection are not fully understood. The inflammatory complications of leprosy, leprosy reactions, particularly erythema nodosum leprosum (ENL), present therapeutic challenges. Thalidomide is an effective drug for ENL but is not widely available due to teratogenicity. Thalidomide binds cereblon (CRBN), a substrate receptor for the E3 ligase complex, promoting ubiquitination. Thus, we investigated the CRBN expression in human peripheral blood mononuclear cells (PBMCs) in response to in vitro stimulation with M. leprae with/without CRBN blockade peptide. Methods Blood samples were obtained from apparently BCG-vaccinated and BCG-unvaccinated healthy volunteers. PBMC was isolated and stimulated with irradiated M. leprae with or without CRBN blockade peptide. CRBN, NF-kB, and PARK2 proteins were determined by ELISA, and their gene expression by qPCR. Results Stimulation with M. leprae significantly increased CRBN gene expression and protein production. Incubation of PBMCs with M. leprae with CRBN blockade significantly increased NF-kB expression. In a subgroup analysis, CRBN and NF-kB gene expression following stimulation with M. leprae (p ≤ 0.05) was significantly higher in PBMCs from Mycobacterium bovis bacillus Calmette–Guérin (BCG)-vaccinated individuals compared to those from unvaccinated participants. PARK2 gene expression and parkin protein were significantly decreased in PBMCs stimulated with M. leprae compared to unstimulated PBMCs (p ≤ 0.05). In a subgroup analysis, PARK2 gene expression and parkin protein were decreased in the PBMCs from BCG-unvaccinated individuals following incubation with M. leprae compared to those from BCG-vaccinated individuals. Stimulation of the PBMCs with M. leprae with CRBN blockade increased PARK2 gene expression and parkin protein production (p ≤ 0.05). Conclusion The findings are evidence that CRBN may have a role in modulating PARK2 and NF-kB gene expression in response to M. leprae infection. This needs further investigation in individuals with leprosy. The differential gene expression of CRBN and PARK2 in BCG-vaccinated and BCG-unvaccinated individuals could be further explored to understand the mechanism of BCG protection against leprosy.

Background: The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions.Methods: A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses toMycobacterium leprae (M.leprae)stimulation before and after depletion of CD25⁺cells.Results: 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25⁺cells from PBMCs was associated with enhanced TNFα and IFNγ responses toM.lepraestimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25⁺cells to CD25⁺depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25⁺cells either before or after treatment. Depleting CD25⁺cells did not affect the IL-10 response toM.lepraebefore and after 24 weeks of MDT in participants with LL. However, depletion of CD25⁺cells was associated with an enhanced IL-10 response on stimulation withM.lepraein untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25⁺cells.Conclusion: The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL isM.lepraeantigen specific and the unresponsiveness can be reversed by depleting CD25⁺cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25⁺depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25⁺cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.

The coronavirus disease 2019 (COVID-19) pandemic has led to governments implementing a variety of public health measures to control transmission and has affected health services. Leprosy is a communicable neglected tropical disease caused by Mycobacterium leprae and is an important health problem in low- and middle-income countries. The natural history of leprosy means that affected individuals need long-term follow-up. The measures recommended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can create barriers to health services. We evaluated the impact of the COVID-19 epidemic response on leprosy services and disease management. We conducted a cross-sectional online survey with healthcare professionals in leprosy referral centres. Eighty percent of leprosy diagnostic services were reduced. All respondents reported that multidrug therapy (MDT) was available but two reported a reduced stock. Clinicians used alternative strategies such as telephone consultations to maintain contact with patients. However, patients were not able to travel to the referral centres. This study highlights the effects of the initial phase of the SARS-CoV-2 pandemic on leprosy services in a range of leprosy-endemic countries. Many services remained open, providing leprosy diagnosis, MDT and leprosy reaction medications. Centres developed innovative measures to counter the negative impacts of the COVID-19 pandemic.

Influenza virus infections affect millions of people annually, and current available vaccines provide varying rates of protection. However, the way in which the nasal microbiota, particularly established pneumococcal colonization, shape the response to influenza vaccination is not yet fully understood. In this study, we inoculated healthy adults with live Streptococcus pneumoniae and vaccinated them 3 days later with either tetravalent-inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). Vaccine-induced immune responses were assessed in nose, blood, and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, experimentally induced pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared with either the TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S . pneumoniae . Therefore, nasopharyngeal pneumococcal colonization may affect LAIV efficacy.

BACKGROUND COVID-19 has a potential to cause chaos in Ethiopia due to the country’s already daunting economic and social challenges. Living and working conditions are highly conducive for transmission, as people live in crowded inter-generational households that often lack running water and other basic sanitary facilities. OBJECTIVE The objective of this study was to investigate the knowledge, attitudes and practices (KAP) of Ethiopians toward COVID-19 following the introduction of state of emergency by the Ethiopian government to curb the spread of the disease. METHODS A cross-sectional study design was conducted in nine regional states and two chartered cities. Data for demographic, knowledge, attitude and practice toward COVID-19 were collected through telephone interview from 1570 participants. Descriptive and bivariate analyses using chi-square test, t-test or analysis of variance were performed as appropriate. Binary and multiple logistic regression analysis were used to measure the relationship between the categorical dependent variables and one or more socio-demographic independent variables with two-tailed at α=0.05 significance level and 95% of confidence interval. RESULTS The level of good knowledge, favourable attitude and good practice among the respondents were 42%, 53.8% and 24.3% respectively. Being rural resident, older than 50 years, having at least primary education, being resident of Amhara and Oromia regions were independent predictors of knowledge level. While being rural resident, married, employed, having at least basic education, being residents of Afar, Amhara, Gambela, Oromia and Somali regions were found to be the best predictors of the attitude, being rural resident, government employee, having at least basic education, and living outside of the capital were the independent predictors of practice level of the respondents CONCLUSIONS The finding revealed that Ethiopians have inadequate level of knowledge and are generally have a mixed outlook on overcoming the pandemic with poor adherence to COVID-19 prevention practice. Reinforcing preventive measures and intensifying sensitization campaigns to fill the knowledge gap and persuading people to follow the preventive measures set by the government with concurrent evaluation of the impacts of these measures on knowledge and practice is highly recommended to mitigate the disease.

COVID-19 has a potential to cause chaos in Ethiopia due to the country’s already daunting economic and social challenges. Living and working conditions are highly conducive for transmission, as people live in crowded inter-generational households that often lack running water and other basic sanitary facilities. Thus, the aim of this study was to investigate the knowledge, attitudes and practices (KAP) of Ethiopians toward COVID-19 following the introduction of state of emergency by the Ethiopian government to curb the spread of the disease. A cross-sectional study design was conducted in nine reginal states and two chartered cities. Data for demographic, Knowledge, attitude and practice toward COVID-19 were collected through telephone interview from 1570 participants. Descriptive and bivariate analyses using chi-square test, t-test or analysis of variance were performed as appropriate. Binary and multiple logistic regression analysis were used to measure the relationship between the categorical dependent variables and one or more socio-demographic independent variables with two-tailed at α=0.05 significance level and 95% of confidence interval. The level of good knowledge, favourable attitude and good practice among the respondents were 42%, 53.8% and 24.3% respectively. Being rural resident, older than 50 years, having at least primary education, being resident of Amhara and Oromia regions were independent predictors of knowledge level. While being rural resident, married, employed, having at least basic education, being residents of Afar, Amhara, Gambela, Oromia and Somali regions were found to be the best predictors of the attitude, being rural resident, government employee, having at least basic education, and living outside of the capital were the independent predictors of practice level of the respondents. The finding revealed that Ethiopians have inadequate level of knowledge and are generally have a mixed outlook on overcoming the pandemic with poor adherence to COVID-19 prevention practice. reinforcing preventive measures and intensifying sensitization campaigns to fill the knowledge gap and persuading people to follow the preventive measures set by the government with concurrent evaluation of the impacts of these measures on knowledge and practice is highly recommended to mitigate the disease.

Influenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae . This important confounder should be considered when assessing LAIV efficacy.

Erythema nodosum leprosum (ENL) is a systemic inflammatory complication occurring mainly in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL). Prednisolone is widely used for treatment of ENL reactions. However, it has been reported that prolonged treatment with prednisolone increases the risk for prednisolone-induced complications such as osteoporosis, diabetes, cataract and arteriosclerosis. It has been speculated that perhaps these complications result from lipid profile alterations by prednisolone. The effects of extended prednisolone treatment on lipid profiles in ENL patients have not been studied in leprosy patients with ENL reactions. Therefore, in this study we conducted a case-control study to investigate the changes in lipid profiles and serological responses in Ethiopian patients with ENL reaction after prednisolone treatment. A prospective matched case–control study was employed to recruit 30 patients with ENL and 30 non-reactional LL patient controls at ALERT Hospital, Ethiopia. Blood samples were obtained from each patient with ENL reaction before and after prednisolone treatment as well as from LL controls. The serological host responses to PGL-1, LAM and Ag85 M. leprae antigens were measured by ELISA. Total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured by spectrophotometric method. The host antibody response to M. leprae PGL-1, LAM and Ag85 antigens were significantly reduced in patients with ENL reactions compared to LL controls after treatment. Comparison between patients with acute and chronic ENL showed that host-response to PGL-1 was significantly reduced in chronic ENL after prednisolone treatment. Untreated patients with ENL reactions had low lipid concentration compared to LL controls. However, after treatment, both groups had comparable lipid profiles except for LDL, which was significantly higher in patients with ENL reaction. Comparison within the ENL group before and after treatment showed that prednisolone significantly increased LDL and HDL levels in ENL patients and this was more prominent in chronic ENL than in acute patients with ENL. The significantly increased prednisolone-induced LDL and TG levels, particularly in patients with chronic ENL reactions, is a concern in the use of prednisolone for extended periods in ENL patients. The findings highlight the importance of monitoring lipid profiles during treatment of patients to minimize the long-term risk of prednisolone-induced complications. Erythema Nodosum Leprosum (ENL) reaction is a severe multisystem immune-mediated complication of lepromatous and borderline leprosy. It causes high morbidity and mortality and usually requires urgent medical attention. Although thalidomide is an effective drug for ENL treatment, it is not available in many leprosy endemic countries including Ethiopia. Prednisolone is widely used for treatment of ENL reactions but its efficacy is less than 40%. As a result, patients with ENL reactions receive Prednisolone for prolonged periods. However, it has been reported that prolonged treatment with prednisolone increases the risk for prednisolone-induced complications such as osteoporosis, diabetes, cataract and arteriosclerosis. It has been hypothesized that perhaps these complications result from changes in lipid concentration due to prednisolone. Therefore, this study was aimed to determine changes in lipid profiles in patients with ENL reactions. We found that prednisolone treatment not only alters lipid concentrations in patients with ENL reactions but also reduced the antibody responses to M. leprae antigens. Our result has shown that prednisolone treatment has increased low and high lipoproteins in patients with ENL reactions. We also found that use of prednisolone for prolonged time in chronic ENL was correlated with increased triglycerides (TG) and low density lipoproteins (LDL) showing the need for monitoring lipid profiles during prednisolone treatment of these patients to avoid the risks associated with increased TG and HDL such as diabetes and hypertension.

Background Leprosy is a chronic infectious disease of public health importance and one of the leading causes of permanent physical disability. The integration of leprosy service to the general health system in Ethiopia made leprosy patients to be seen by non-leprosy specialists which could lead to misdiagnosis and delay in treatment. In addition to the multi-drug treatment, patient self - care practice is crucial for the successful treatment of the disease. This study was aimed to assess the knowledge and self-care practices of leprosy patients and associated factors at ALERT leprosy referral Hospital in Ethiopia. Method A cross-sectional study was conducted ALERT leprosy referral Hospital, Addis Ababa, Ethiopia. A total of 424 leprosy patients were interviewed using pre-tested structured questionnaires. The questionnaires included core points such as socio-demographic characteristics, knowledge of leprosy and self-care practices. Bloom’s cut off point was used to describe the knowledge and self-care practice of the respondents and statistical significance was assessed at 95% confidence interval with 5% of level of significance. Result The knowledge score of the respondents was poor for 276 (65.1%) and good for 148 (34.9%). The level of knowledge was significantly varied within age groups (P= 000), sex (P=000), marital status (p=0.003), educational status (p=000) and income (p-000). More than three-fourth (77.4%) of interviewed patients had poor self-care practice and only less than a quarter (22.6%) of patients had good self-care practice score (P=000). Age (p=0.002), Previous disability due to leprosy (P=000), Knowledge of leprosy (p=0.038) and income (P=0.028) significantly associated with poor self-care practice. On the other hand, educational status, sex, marital status and health education did not associated with leprosy self-care practice. Conclusion Although, leprosy treatment, disability prevention and rehabilitation program run in the country under general public health care service for decades, poor leprosy self-care practice and poor leprosy knowledge had been confirmed in this study. Therefore, the leprosy service program should re-visit its strategy and mode of delivery to improve the leprosy knowledge and leprosy self-care practices of patients. Author summary Leprosy is an infectious bacterial disease. It is a curable disease if treated early before disability occurs with the correct regimen. However, treatment cannot reverse disability once occurred. in addition to chemotherapeutic treatment, lack of social and psychological treatment may expose patients to disability as they may not adhere to treatment. To prevent disability it is vital to empower leprosy patients through promoting self-confidence, providing knowledge and self-care skills. In the present study, we investigated the knowledge and self-care practice of 424 leprosy patients at ALERT hospital through face-to face guided interview. It was found that majority of patients had poor knowledge about leprosy. Some factors such as sex, income status, age and educational status of the patient significantly affected the level of leprosy knowledge. Similarly, it was found that 77% of patients had poor self-care practice which significantly varied with income status, knowledge of leprosy, age and having previous disability. Therefore, it is very important to improve the leprosy knowledge and self-care skills of patients. This can be achieved through dealing with issues such as the physical, emotional, intellectual and social aspects of the patients in addition to the chemotherapeutic treatment.