Evidence for immune activation in pathogenesis of the HLA class II associated disease, podoconiosis.

Available evidences suggest that podoconiosis is triggered by long term exposure of bare feet to volcanic red clay soil particles. Previous genome-wide studies in Ethiopia showed association between the HLA class II region and disease susceptibility. However, functional relationships between the soil trigger, immunogenetic risk factors and the immunological basis of the disease are uncharted. Therefore, we aimed to characterise the immune profile and gene expression of podoconiosis patients relative to endemic healthy controls. Peripheral blood immunophenotyping of T cells indicated podoconiosis patients had significantly higher CD4 and CD8 T cell surface HLA-DR expression compared to healthy controls while CD62L expression was significantly lower. The levels of the activation markers CD40 and CD86 were significantly higher on monocytes and dendritic cell subsets in patients compared to the controls. RNA sequencing gene expression data indicated higher transcript levels for activation, scavenger receptors, and apoptosis markers while levels were lower for histones, T cell receptors, variable, and constant immunoglobulin chain in podoconiosis patients compared to healthy controls. Our finding provides evidence that podoconiosis is associated with high levels of immune activation and inflammation with over-expression of genes within the pro-inflammatory axis. This offers further support to a working hypothesis of podoconiosis as soil particle-driven, HLA-associated disease of immunopathogenic aetiology.

Impairment of health-related quality of life and its determinants among patients with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia: institutional-based cross-sectional study.

OBJECTIVE: This study aimed to assess the impairment of health-related quality of life (HRQoL) and its determinants among patients diagnosed with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia. METHODS: An institutional-based cross-sectional study design was used in the setting of primary healthcare facilities to assess impaired HRQoL among patients with podoconiosis in the East Wollega Zone from 1 March 2023 to 30 April 2023, using the Dermatologic Life Quality Index (DLQI). Data was collected from 494 patients with podoconiosis, and a multistage sampling technique was employed. The data was entered into EpiData V.4.6 and exported to SPSS V.27 for analysis. A linear regression model with a 95% cofidence interval (CI) was used to estimate level of HRQoL and to identify its determinants estimating beta (ß) coefficient declaring the significance level at p<0.05. RESULTS: The quality of life among patients was impaired on average by 9.6±6.1 with the lowest DLQI Score in the domain of treatment (0.8±0.97) and the highest in the domain of daily activity (2.3±1.72). The identified significant determinants of impairment of HRQoL associated with DLQI scores were duration of disease (95% CI, ß=0.11 (0.08 to 0.15)), acute dermato-lymphangio-adenitis (ADLA) (95% CI, ß=0.08 (0.01 to 0.16)), comorbidity (95% CI, ß=1.26 (0.37 to 2.16)), consistently wearing shoes (95% CI, ß=-0.06 (-0.09 to -0.03)), feeling of stigmatised (95% CI, ß=0.21 (0.16 to 0.25)) and psychological distress (95% CI, ß=0.17 (0.14 to 0.21)) and being female (95% CI, ß=1.16 (0.19 to 2.12)). CONCLUSION: Overall, HRQoL among patients with podoconiosis was moderately impaired. The duration of disease, ADLA, comorbidity, stigma, psychological distress and being female in sex significantly impaired HRQoL, whereas consistently wearing shoes significantly improved HRQoL among the patients with podoconiosis. Therefore, healthcare providers and public health experts should work on educating communities and counselling patients to avoid stigma and psychological distress, wearing shoes consistently and treating podoconiosis and other comorbidities among these patients.

Public perceptions of genomic studies and hereditary diseases in Aari community, South Omo Zone, Ethiopia.

BACKGROUND: Genetic and genomic research is revolutionizing precision medicine; however, addressing ethical and cultural aspects is crucial to ensure ethical conduct and respect for community values and beliefs. This study explored the beliefs, perceptions and concerns of the Aari community in South Ethiopia regarding genetic concepts, hereditary diseases and ethical research practices related to sample collection, storage and sharing. METHODS: In-depth interviews and focus group discussions were conducted with community elders, health officials, tuberculosis patients and apparently healthy individuals. Data were thematically analysed using MAXQDA software. RESULTS: Participants identified diseases such as podoconiosis, leprosy, goitre and epilepsy as hereditary and perceived some as 'curses' due to generational impact and social stigma. Disease susceptibility was attributed to divine intervention or factors such as malnutrition and sanitation. Although hereditary diseases were considered unavoidable, in some cases environmental factors were acknowledged. Participants shared personal examples to demonstrate inheritance concepts. Blood held cultural significance, and concerns about its potential misuse resulted in scepticism towards giving samples. CONCLUSIONS: This study emphasizes the significance of comprehending local beliefs and perceptions and stresses the need to establish effective communication, build trust and address underlying causes of hesitancy to improve recruitment and ensure ethical conduct.

Genital elephantiasis in men.

Penoscrotal elephantiasis (PSE) is defined as an increase, sometimes considerable, in the volume of the external genitalia, which will be responsible for an unsightly appearance, a sexological impact and a psychological harm. The cause may be primary or secondary to a parasitic disease (filarsiosis) or to intrinsic or extrinsic lymphatic obstruction. The diagnosis is essentially clinical, with penoscrotal involvement being the most frequent. The etiological research implies the realization of certain complementary examinations according to the circumstances. Surgical treatment ideally consists of excising the mass. followed by reconstruction using grafts or local flaps of healthy skin, which is an important way of restoring comfort to the patient. We report two cases of penoscrotal elephantiasis treated surgically with good functional and aesthetic results. We update, through our own experience, aspects of the diagnostic and therapeutic care of penoscrotal elephantiasis.

Genital elephantiasis: Surgical treatment and reconstruction.

Genital elephantiasis is a severe form of lymphedema of the groin. It is characterized by progressive enlargement and distortion of the genitals, presenting significant physical, psychological, and social challenges to the affected individuals. Although pharmacological treatment of filariasis is well-established in the medical field, the surgical management of genital elephantiasis can be varied and confusing. This review article provides an in-depth analysis of the etiology, classification, severity grading, and various effective surgical treatment and reconstructive modalities commonly employed by surgeons since the early twentieth century. We also discuss how a combination approach of ablation, soft tissue coverage, and lymphatic reconstruction is viable for treating genital elephantiasis. By examining the literature, we hope to provide insights into how surgery plays a role in the holistic management of genital elephantiasis.

Podoconiosis.

This case report describes a woman with the appearance of elephantine skin tumors predominantly on her left foot.

Elephantiasis mimicry in recurrent lower limb skin infections in a diabetic patient: a case report.

BACKGROUND: Chronic edema as a complication of systemic diseases or infections can mimic filarial lymphedema (also known as elephantiasis) and considered so. We describe a case of chronic lymphedema that mimicked elephantiasis in a diabetic man. CASE PRESENTATION: The patient was a 70-year-old black man, bed-bound at the time of admission following a diagnosis of stroke and hypertension in the previous 5 years. He had been diabetic for 20 years with poorly controlled diabetes mellitus. He suffered recurrent bilateral lower limb skin infections for 5 years prior to admission that culminated into progressive lowerlimb edema. The infections eventually complicated into skin edema, hardening, fissuring, and hyperkeratotic plaques. The physical examination revealed Tinea pedis and bilateral non-pitting edema of lowerlimbs to the level of the knees. Investigations confirmed non-filarial lymphedema-related skin changes. The absence of the classic pebbly/cobblestone skin changes ruled out elephantiasis nostra verrucosa (ENV), with a possibility of it being in the early stages of evolution. The patient's skin fissuring and infections were successfully treated with antibiotics and antifungals while compression stockings helped to relieve the edema. CONCLUSIONS: Chronic lymphedema can complicate repeated non-filarial infections of lower limbs. Its fissures are a risk factor for cellulitis, prompting early identification and management of both infections and lymphedema to halt their vicious cycle, especially in at risk populations like diabetics.

Determinants of podoconiosis among residents of Machakle District East Gojjam Zone Amhara Region Ethiopia.

BACKGROUND: Podoconiosis (endemic non-filarial elephantiasis) is a chronic disease characterized by the development of persistent swelling of plantar foot initially; which progresses to the dorsal foot and lower leg slowly or in a number of acute episodes to reach the knee. About 4 million people are said to be affected by the disease worldwide and it is deemed a serious public health problem in at least 10 African countries including Ethiopia. Therefore this study aimed to identify the determinants of podoconiosis among residence in Machakel district. METHOD: Unmatched case control study design was conducted at Machakel district from August 30 to September 30, 2022. The sample size calculated using Epi-info software yielded 211 controls and 106 cases (317 study participants). Simple random sampling technique was used to select the cases using registration books of the district. Data were entered to Epi info version 7 and exported to SPSS version 22 for statistical analysis. Binary logistic regression was used to identify explanatory variables. RESULT: A total of 312 study participants (104 cases and 208 controls) were included giving a response rate of 98.42%. Bare foot (AOR, 5.83 [95% CI: 2.34-14.50]), female sex (AOR, 4.25 [95% CI: 2.22-8.14]), family history of podoconiosis (AOR: 3.01(95% CI: 1.41-6.42) and age group 41-60 (AOR: 5.05(95% CI: 2.35-10.83), and 61-80 AOR 15.74 95% CI: (5.56-44.55) were determinants of Podoconiosis. CONCLUSION AND RECOMMENDATION: Barefoot, sex, family history of podoconiosis and age were determinants of Podoconiosis. District health office should encourage at risk populations especially older people and individuals with family history of podoconiosis about shoe wearing practice all the time and not to expose their skin and feet.

The cross-cultural validation of the Beach Center Family Quality of Life Scale among persons affected by leprosy or podoconiosis in Northwest Ethiopia.

BACKGROUND: The Beach Center Family Quality of Life Scale has been developed and validated in different languages in different countries. However, this scale has not been validated in the Ethiopian Amharic language context. Therefore, this study aimed to investigate the cross-cultural validity of the Beach Center Family Quality of Life Scale, among Ethiopian families of persons affected by leprosy and podoconiosis. METHODOLOGY: We explored the semantic equivalence, internal consistency, reproducibility, floor and ceiling effects, and interpretability of the Beach Center Family Quality of Life Scale in Amharic. A cross-sectional study was conducted after the translation and back-translation of the instrument. A total of 302 adult persons affected by leprosy or podoconiosis was asked about their level of satisfaction with their family life, using the Beach Center Family Quality of Life Scale. In addition, 50 participants were re-interviewed two weeks after the initial assessment to test the reproducibility of the scale. Participants were recruited in the East Gojjam zone of Northwest Ethiopia. RESULTS: The findings of this study showed that the Beach Center Family Quality of Life Scale had high internal consistency (Cronbach's alpha of 0.913) and reproducibility (intra-class correlation coefficient of 0.857). The standard error of measurement was 3.01, which is 2.4% of the total score range. The smallest detectable change was 8.34. Confirmatory factor analysis showed adequate factor loadings and model fit indices like the original scale. The composite reliability and average variance extracted from the scale were acceptable. No floor and ceiling effects were found. CONCLUSIONS: Our findings indicate that the Amharic version of the Beach Center Family Quality of Life Scale has adequate cultural validity to assess the family quality of life in Ethiopian families of persons affected by leprosy and podoconiosis.

Determinants of Podoconiosis in Bensa District, Sidama Region, Ethiopia: A case control study.

BACKGROUND: Podoconiosis is one of the neglected tropical diseases (NTD) with the greatest potential for elimination. Despite its public health importance, podoconiosis is a poorly understood disease which led to a widespread misconception about its cause, prevention, and treatment. Even though the exact global burden is still to be measured, it is estimated that at least 4 million people are affected with podoconiosis worldwide, of which more than 1.5 million people are in Ethiopia. The objective of this study was to identify the determinants of podoconiosis in Bensa District, Sidama Regional State, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: A community-based unmatched case-control study was used to identify the determinants of podoconiosis. The sample size was estimated using the double population proportion formula. An interviewer-administered structured questionnaire was used for data collection. Blood specimens collected from cases were tested by Filariasis Test Strip to exclude lymphatic filariasis. Data were checked for completeness, coded and entered into Epi-data Version 4.6, and exported to the SPSS version 22 software. Variables with a p<0.2 in the bivariate analysis were further analyzed using multivariable binary logistic regression. Multivariable logistic regression analysis was used to examine determinants that could be associated with podoconiosis with a 95% confidence interval. A total of 459 (153 cases and 306 controls) participants were included with a response rate of 100%. Factors such as the age of participant [AOR = 0.34, 95% CI (0.13-0.87)], being female [AOR = 2.90, 95% CI (1.40-6.10)], age at which shoe wearing started [AOR = 0.7, 95% CI (0.03-0.16)], not wearing shoe daily [AOR = 2.26, 95% CI (1.05-4.86)], wearing hard plastic shoe [AOR = 3.38, 95% CI (1.31-10.89)], and family history with a similar disease (leg swelling) [AOR = 10.2, 95% CI (3.97-26.37)] were significantly associated with the occurrence of podoconiosis. CONCLUSIONS/SIGNIFICANCE: The age of the participants, gender, the age at which shoe wearing started, type of shoe the participants' wear, frequency of shoe wearing, traveling barefoot, and family history with similar disease (leg swelling) were significantly associated with the occurrence of podoconiosis. Sidama regional health bureau along with non-governmental organizations working on the neglected tropical disease should plan modalities on awareness creation and comprehensive health education on shoe wearing and foot hygiene.

Tropical leg lymphedema caused by podoconiosis is associated with increased colonisation by anaerobic bacteria.

The non-filarial and non-communicable disease podoconiosis affects around 4 million people and is characterized by severe leg lymphedema accompanied with painful intermittent acute inflammatory episodes, called acute dermatolymphangioadenitis (ADLA) attacks. Risk factors have been associated with the disease but the mechanisms of pathophysiology remain uncertain. Lymphedema can lead to skin lesions, which can serve as entry points for bacteria that may cause ADLA attacks leading to progression of the lymphedema. However, the microbiome of the skin of affected legs from podoconiosis individuals remains unclear. Thus, we analysed the skin microbiome of podoconiosis legs using next generation sequencing. We revealed a positive correlation between increasing lymphedema severity and non-commensal anaerobic bacteria, especially Anaerococcus provencensis, as well as a negative correlation with the presence of Corynebacterium, a constituent of normal skin flora. Disease symptoms were generally linked to higher microbial diversity and richness, which deviated from the normal composition of the skin. These findings show an association of distinct bacterial taxa with lymphedema stages, highlighting the important role of bacteria for the pathogenesis of podoconiosis and might enable a selection of better treatment regimens to manage ADLA attacks and disease progression.

Phenotypical characterization, and antibiotics susceptibility patterns of skin bacteria found in podoconiosis patients in the North West Region of Cameroon.

BACKGROUND: Podoconiosis, a non-infectious disease originating from long-term exposure of bare feet to irritant red clay soil is a lifelong, disabling disease with no specific diagnostic tool, classified into 5 stages based on the severity of leg swelling (lymphoedema). Secondary bacterial infections have been suggested to cause acute dermatolymphangioadenitis (ADLA) attacks and drive disease progression. Although the North West Region of Cameroon has a proven history of podoconiosis endemicity, the bacterial composition of lymphoedema due to this condition has not been studied. Thus, this study investigated the leg bacterial diversity of patients who suffered from the lymphoedema and their susceptibility pattern to selected antibiotics. METHODS: A cross-sectional study was carried out in which podoconiosis affected and non-lymphoedema individuals living in the same community were purposively selected. Samples were collected by swabbing the skin between the toes and around the anklebone, then cultured and sub-cultured on nutrient agar to obtain pure isolates. The cultured isolates were then morphologically and biochemically classified using microscopy and analytic profile index test kits, respectively. The disk diffusion technique was used to determine antibiotic susceptibility. RESULTS: Thirty-three participants were recruited, and 249 bacterial isolates were characterized into 29 genera, 60 species; with 30 (50%) being gram positive rods, 19 (31.7%) gram positive cocci, and 11 (18.3%) gram negative rods. Thirteen gram positive rods, fifteen gram positive cocci, and eight gram negative rods of bacterial species were found only in podoconiosis individuals among which Cellulomonas spp / Microbacterium spp. (2.8%), Staphylococcus lentus (3.3%), and Burkholderia cepacia (4.0%) dominated. 90% (90%) of the bacterial isolates were sensitive to doxycycline, whereas ampicillin had a high level of intermediate resistance, and penicillin G had the greatest resistant profile. CONCLUSION: Our findings show that 94 (37.8%) out of 249 described bacterial isolates were exclusively found in the legs of podoconiosis individuals, and their susceptibility pattern to antibiotics was similar to that of others.

A geochemical and mineralogical characterization of soils associated with podoconiosis.

Podoconiosis is a disease that causes swelling and disfiguration of the lower legs found in several developing countries where shoes are not regularly worn. The current model for the etiology of the disease proposes that mineralogical agents enter the lymph system through the skin leading to inflammation that causes swelling of the feet and legs. We collected 125 soil samples from 21 towns associated with podoconiosis, 8 towns unassociated with Podoconiosis as controls, and 3 towns of unknown status. Data collected for each soil sample included color, particle size, mineralogy, and geochemistry to distinguish unique components within the podoconiosis-associated soils. Our results indicate podoconiosis-associated soils are more highly weathered than non-podoconiosis associated soils. The enrichment of kaolinite and gibbsite suggests that these minerals, their surface chemistry, and trace elements associated with them should be prioritized in future podoconiosis research. In addition, we found that color may be a valuable tool to identify soils at greater risk for inducing podoconiosis.

Evaluating Rural Ethiopian Youths' Willingness and Competency to Promote Literacy Regarding G × E Influences on Podoconiosis.

INTRODUCTION: Engaging youth as peer educators has yet to be considered to promote literacy concerning conjoint genetic and environmental (G × E) influences on health conditions. Whether youth living in low- and middle-income countries (LMICs) could and would be willing to serve as lay educators of G × E education is unclear. METHODS: A cross-sectional survey of youth living in Southern Ethiopia was conducted from August to September 2017. Trained data collectors administered the survey on 377 randomly selected youth who ranged in age from 15 to 24; 52% were female and 95% reported having some formal education. Self-reported willingness and a constructed competency score were assessed. Bivariate analyses tested for factors associated with willingness and competency to serve as lay G × E literacy builders. RESULTS: Competency and willingness were significantly greater (p < 0.05) for youth who were male, had some formal education, and had civic or leadership experience. Differences in median willingness were significant for youth who scored as more competent versus those who scored as less competent (p < 0.001). There were no characteristics that moderated the association of competency with willingness. CONCLUSION: Youth peer educator programs hold promise for disseminating improved G Χ E literacy and reducing stigma associated with deterministic misunderstandings. Thoughtful recruitment and training strategies will be needed to ensure that the broadest representation of youth in LMIC contexts has the opportunity to serve in this role, particularly girls and those without formal education.

[Elephantiasis of the lower limb: Treatment of seven cases using the modified Charles technique]. / L'éléphantiasis du membre pelvien : traitement de sept cas selon la technique de Charles modifiée.

INTRODUCTION: Lymphedema is an obstructive dysfunction of the lymphatic system characterised by an inability of the lymphatic system to eliminate excess lymphatic load. It can be congenital or secondary. Untreated, it progresses in three stages, the final stage being elephantiasis. We report a short series of 7 cases of elephantiasis of the lower limb treated with the Charles technique. Our aim was to describe the results of the surgical treatment. METHOD: This was a retrospective descriptive and analytical study from January 2010 to December 2020. Patients with at least one lower limb elephantiasis of any aetiology of any age and gender who underwent excisional surgery with a complete medical record containing clinical and therapeutic data were included. RESULTS: During the study period, we received 710 patients with a prevalence of elephantiasis of 1.69%. The mean age was 43.3±14.5years with a male predominance. No etiology or co-morbidity factors (diabetes, hypertension, VRS) were found. In our mini-series, the average time between the two procedures was 34.3±9.6days. The mean time to healing was 82.3±15.1days. All patients healed with two excellent results. CONCLUSION: excisional surgery with two-stage repair combined with compression therapy gave satisfactory results.

Geostatistical modelling of the distribution, risk and burden of podoconiosis in Kenya.

BACKGROUND: Understanding and accurately predicting the environmental limits, population at risk and burden of podoconiosis are critical for delivering targeted and equitable prevention and treatment services, planning control and elimination programs and implementing tailored case finding and surveillance activities. METHODS: This is secondary analysis of a nationwide podoconiosis mapping survey in Kenya. We combined national representative prevalence survey data of podoconiosis with climate and environmental data, overlayed with population figures in a geostatistical modelling framework, to predict the environmental suitability, population living in at-risk areas and number of cases of podoconiosis in Kenya. RESULTS: In 2020, the number of people living with podoconiosis in Kenya was estimated to be 9344 (95% uncertainty interval 4222 to 17 962). The distribution of podoconiosis varies by geography and three regions (Eastern, Nyanza and Western) represent >90% of the absolute number of cases. High environmental suitability for podoconiosis was predicted in four regions of Kenya (Coastal, Eastern, Nyanza and Western). In total, 2.2 million people live in at-risk areas and 4.2% of the total landmass of Kenya is environmentally predisposed for podoconiosis. CONCLUSIONS: The burden of podoconiosis is relatively low in Kenya and is mostly restricted to certain small geographical areas. Our results will help guide targeted prevention and treatment approaches through local planning, spatial targeting and tailored surveillance activities.