Uncommon Variants in FLG2 and NOD2 Are Associated with Atopic Dermatitis in the Ethiopian Population.

Loss-of-function variants in the FLG gene have been identified as the strongest cause of susceptibility to atopic dermatitis (AD) in Europeans and Asians. However, very little is known about the genetic etiology behind AD in African populations, where the prevalence of AD is notably high. We sought to investigate the genetic origins of AD by performing whole-genome sequencing in an Ethiopian family with 12 individuals and several affected in different generations. We identified 2 variants within FLG2 (p.D13Y) and NOD2 (p.A918S) genes cosegregating with AD in the affected individuals. Further genotyping analyses in both Ethiopian and Swedish AD cases and controls revealed a significant association with the FLG2 variant (p.D13Y, P < .0013) only in the Ethiopian cohort. However, the NOD2 variant (p.A918S) did not show any association in our Ethiopian cohort. Instead, 2 previously recognized NOD2 variants (p.A849V, P < .0085 and p.G908R, P < .0036) were significantly associated with AD in our Ethiopian cohort. Our study indicates that the FLG2 and NOD2 genes might be important in the etiology of AD in Ethiopians. Additional genetic and functional studies are needed to confirm the role of these genes and the associated variants into the development of AD.

Severe Immediate and Delayed Hypersensitivity Reactions to Biologics in a Toddler With Systemic Juvenile Idiopathic Arthritis.

Many pediatric rheumatic diseases can be safely managed with biologic therapy. Severe allergic reactions to these medications are uncommon. We report the case of a 2-year-old male with systemic-onset juvenile idiopathic arthritis and secondary macrophage activation syndrome (MAS), whose treatment was complicated by severe allergic reactions to biologics, including drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity reaction (DIHR) likely due to anakinra, and anaphylactoid reaction to intravenous tocilizumab. These required transition to canakinumab, cyclosporine, and corticosteroids, with later development of interstitial lung disease and MAS flare needing transition from canakinumab to tofacitinib, which led to disease control. Whether lung disease is a manifestation of DRESS/DIHR to canakinumab remains unclear. High index of suspicion of hypersensitivity reactions for timely diagnosis and drug discontinuation is critical, especially in patients with active disease who might be at increased risk of these adverse events.

Free online dermatology course for medical trainees in Ethiopia: A pilot study.

BACKGROUND: The effectiveness of virtual dermatology curricula in developing countries remains unclear despite an urgent need due to the pandemic and other factors. OBJECTIVE: To compare a virtual dermatology curriculum deployed in Gondar, Ethiopia with a traditional in-person course. METHODS: We developed a free, on-line dermatology course. 104 trainees from the University of Gondar, Ethiopia, completed the course. Pre- and post-course surveys measuring self-reported proficiency were administered. End-of-Course surveys were distributed to elicit feedback on the course. Performance on final examinations was compared to a historical control group, which did not participate in the course but received standard in-person training. RESULTS: Compared to historical controls (n = 236), the pilot cohort (n = 104) averaged over 4 points higher on the final exam (P < .0001). Most participants were satisfied with all aspects of the on-line course and desire at least a component of virtual learning in the future. LIMITATIONS: This pilot study was performed at a single institution, and the participants were not randomized. Further studies in demographically diverse cohorts are needed to validate the results. CONCLUSION: This dermatology curriculum is a free, innovative platform that can be adapted for dermatology trainees in resource-limited settings.

Undernutrition, food insecurity, and leprosy in North Gondar Zone, Ethiopia: A case-control study to identify infection risk factors associated with poverty.

BACKGROUND: Ethiopia has over 3,200 new cases of leprosy diagnosed every year. Prevention remains a challenge as transmission pathways are poorly understood. Susceptibility and disease manifestations are highly dependent on individual host-immune response. Nutritional deficiencies, such as protein-energy malnutrition, have been linked to reduced cell-mediated immunity, which in the case of leprosy, could lead to a higher chance of active leprosy and thus an increased reservoir of transmissible infection. METHODOLOGY/PRINCIPAL FINDINGS: Between June and August 2018, recently diagnosed patients with leprosy and individuals without known contact with cases were enrolled as controls in North Gondar regional health centers. Participants answered survey questions on biometric data, demographics, socioeconomic situation, and dietary habits. Descriptive statistics, univariate, and multivariate logisitic regression examined associations between undernutrition, specifically body mass index (BMI), middle upper arm circumference (MUAC), and leprosy. Eighty-one participants (40 cases of leprosy, 41 controls) were enrolled (75% male) with an average age of 38.6 years (SD 18.3). The majority of cases were multibacillary (MB) (90%). There was a high prevalence of undernutrition with 24 (29.6%) participants underweight (BMI <18.5) and 17 (21%) having a low MUAC. On multivariate analysis, underweight was significantly associated with leprosy (aOR = 9.25, 95% CI 2.77, 30.81). Also found to be associated with leprosy was cutting the size of meals/skipping meals (OR = 2.9, 95% CI 1.0, 8.32) or not having enough money for food (OR = 10, 95% CI 3.44 29.06). CONCLUSIONS/SIGNIFICANCE: The results suggest a strong association between leprosy and undernutrition, while also supporting the framework that food insecurity may lead to undernutrition that then could increase susceptibility to leprosy. In conclusion, this study highlights the need to study the interplay of undernutrition, food insecurity, and the manifestations of leprosy.

Poor WASH (Water, Sanitation, and Hygiene) Conditions Are Associated with Leprosy in North Gondar, Ethiopia.

Access to safe water, sanitation, and hygiene (WASH) is critical for preventing the spread of neglected tropical diseases (NTDs) including leprosy. WASH-related transmission factors remain largely unexplored in the leprosy transmission cycle. The aim of this project is to better understand WASH exposures among leprosy cases through a case-control study in North Gondar, Ethiopia. We hypothesized that leprosy cases were more likely to have inadequate WASH access and were more likely to have concurrent schistosomiasis, as schistosomiasis immune consequences may facilitate leprosy infection. Forty leprosy cases (forty-one controls) were enrolled, tested for Schistosomamansoni, administered a demographic and WASH survey, and assigned a WASH index score. WASH factors significantly associated with leprosy on adjusted analyses included open defecation (aOR = 19.9, 95% CI 2.2, 176.3) and lack of access to soap (aOR = 7.3, 95% CI 1.1, 49.9). S. mansoni was detected in 26% of participants and in stratified analysis those with leprosy had a 3.6 (95% CI (0.8, 15.9)) greater odds of schistosomiasis in districts bordering the lake, compared to 0.33 lower odds of schistosomiasis in districts not bordering the lake (95% CI (0.09, 1.2)). Overall, results suggest that leprosy transmission may be related to WASH adequacy and access as well as to schistosomiasis co-infection.

Intragenic Copy Number Variation in the Filaggrin Gene in Ethiopian Patients with Atopic Dermatitis.

Genetic variants in filaggrin (FLG) involving truncating mutations or intragenic copy number variation are strongly associated with the risk of developing atopic dermatitis (AD) in European and Asian populations. Few loss-of-function mutations have been identified in Africans, although an association between FLG copy number variation and AD severity in a small African American cohort has been proposed. We studied the association between FLG copy number and AD in 132 Ethiopians and found no association between AD severity and FLG copy number, suggesting that other, still unidentified genetic factors are of more importance in predisposing Ethiopians to AD.

Borrelia recurrentis in head lice, Ethiopia.

Since the 1800s, the only known vector of Borrelia recurrentis has been the body louse. In 2011, we found B. recurrentis DNA in 23% of head lice from patients with louse-borne relapsing fever in Ethiopia. Whether head lice can transmit these bacteria from one person to another remains to be determined.

Multispacer sequence typing relapsing fever Borreliae in Africa.

BACKGROUND: In Africa, relapsing fevers are neglected arthropod-borne infections caused by closely related Borrelia species. They cause mild to deadly undifferentiated fever particularly severe in pregnant women. Lack of a tool to genotype these Borrelia organisms limits knowledge regarding their reservoirs and their epidemiology. METHODOLOGY/PRINCIPAL FINDINGS: Genome sequence analysis of Borrelia crocidurae, Borrelia duttonii and Borrelia recurrentis yielded 5 intergenic spacers scattered between 10 chromosomal genes that were incorporated into a multispacer sequence typing (MST) approach. Sequencing these spacers directly from human blood specimens previously found to be infected by B. recurrentis (30 specimens), B. duttonii (17 specimens) and B. crocidurae (13 specimens) resolved these 60 strains and the 3 type strains into 13 species-specific spacer types in the presence of negative controls. B. crocidurae comprised of 8 spacer types, B. duttonii of 3 spacer types and B. recurrentis of 2 spacer types. CONCLUSIONS/SIGNIFICANCE: Phylogenetic analyses of MST data suggested that B. duttonii, B. crocidurae and B. recurrentis are variants of a unique ancestral Borrelia species. MST proved to be a suitable approach for identifying and genotyping relapsing fever borreliae in Africa. It could be applied to both vectors and clinical specimens.

Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in Ethiopia.

BACKGROUND: Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We have recently shown in an experimental model of cutaneous leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneous leishmaniasis as compared with controls. Furthermore, we found that the expression levels of CD3ζ, CD4 and CD8 molecules were considerably lower at the site of pathology as compared to those observed in paired PBMCs. CONCLUSION: Our results suggest that increased arginase in lesions of patients with cutaneous leishmaniasis might play a role in the pathogenesis of the disease by impairing T cell effector functions.

Patch testing and contact allergens in Ethiopia--results of 514 contact dermatitis patients using the European baseline series.

BACKGROUND: Patch testing is essential to diagnose allergic contact dermatitis. Dermatologists in many countries use a baseline (standard) series covering the major allergens responsible for allergic contact dermatitis in their population, with the addition of relevant allergens for the individual patient. However, a baseline series has not yet been developed for Ethiopia. Our objective in this study is to identify common contact allergens to form the basis of a future baseline series in Ethiopia. METHODOLOGY: We patch tested 514 subjects with dermatitis according to the recommended procedure using the European baseline series for 1 year. RESULTS: 52.7% of the tested subjects showed positive reaction for at least one allergen tested. The top five contact allergens identified were nickel sulfate, fragrance mix I, cobalt chloride, p-tert-butylphenolformaldehyde (PTBP) resin and potassium dichromate. Positive reactions to nickel and PTBP were commoner in females. PTBP positivity was strongly associated with foot eczema. Positive test reactions were commoner in cement workers, notably to potassium dichromate, which was also a commoner allergen in patients presenting with hand dermatitis. There were no reactions to several allergens, including neomycin, benzocaine, budesonide, primin and quaternium-15. CONCLUSION: Comparable patch test results with other countries have been shown and the European baseline series can be used as a baseline series in Ethiopia with some modification.

Community dermatology in Debre Markos: an attempt to define children's dermatological needs in a rural area of Ethiopia.

BACKGROUND: Skin diseases are very common in rural and urban areas in developing countries. Knowledge of the real frequency of the dermatological problems of Ethiopian children could help plan future intervention for early diagnosis and low cost "good practice" therapies. METHODS: We involved in the project two primary Ethiopian schools, attended by 1765 children from grade 1 to grade 4, who were screened to assess their general skin health conditions. All children were examined naked in good day light. To record data we used an EPIinfo questionnaire. RESULTS: A total of 1104 children were screened. We registered a total number of 1086 dermatological problems, 876 of them were of infective origin mainly represented by fungal infections (36.1%). Tinea capitis represented 76% of the cases, tinea corporis 27% and tinea unguium 8%. Head lice affected 345 children. Viral infections accounted for 12%, most of them were warts. CONCLUSIONS: We think our work highlights the general health and living conditions of Ethiopian school children. The dermatological problems affecting most of the children could improve just by better skin hygiene conditions. The presence at the community level of health workers trained to perform a correct and early diagnosis and distribute efficacious, low-cost therapies would be a relevant step forward. We think this project could help draw attention and interest to these issues.

Patch test reaction on Ethiopian subjects with eczema.

BACKGROUND: Allergic contact dermatitis is a common condition with an incidence of 1-10% in the general population. An increasing number of allergens in the environment are responsible for the condition. These allergens can be identified using patch testing. Many countries have a standard series of common allergens used for patch testing. There is no standard series of allergens in Ethiopia, and our objective was to obtain baseline data for common allergens for future standardization. METHODS: One hundred and eighty-one subjects with eczema were patch tested using 17 selected allergens from Chemotechnique Diagnostics AB employing a standard procedure. RESULTS: Positive patch test reactions were detected in more than 60% of subjects, the most common allergen being nickel, followed by fragrance mix and butylphenolformaldehyde. A higher incidence of positive reactions was seen in females. CONCLUSIONS: A high incidence of positive patch test reactions was identified in the study population, and the introduction of patch testing in Ethiopia is essential for the management of allergic contact dermatitis.