Diabetic foot disease in Ethiopian patients: A hospital based study

Background: Ulcers of the foot are one of the most feared and common complications of diabetes. It is a major cause of disability, morbidity and mortality among diabetic patients and about 15% develop foot ulcers in their lifetime. So far, there are few published data in relation to the high-risk diabetic foot in Ethiopian subjects. Methods: A retrospective study was done to determine the various risks as well as antecedent factors, other long term complications, treatment profile and subsequent follow up of 196 patients with diabetic foot disease admitted to the Tikur Anbessa Specialized Referral Hospital from Jan 1999 to Dec 2003. Patients’ medical records were reviewed using pre-prepared formats and relevant data were abstracted. The data were analyzed using Epi info version 3.4.3 statistical soft ware. Results: A total of 196 patients were included in this study. The male to female ratio was 3 to 1. The median age was 60 years (IQR, 47-65). Median duration of symptoms before presentation was 21 days (IQR, 14-30) and the median duration of diabetes mellitus was144 months (IQR, 60-216). More than two thirds had type 2 diabetes mellitus. Among 109 patients with identified antecedent risk factors for their foot problem, ill fitting or new shoes attributed in 48(44%). Neuro-ischaemic ulcers were seen in 113 (58%) of the cases and neuropathic ulcer in 63 (32%). Ulcer with cellulitis or gangrene was the most common mode of presentation seen in 92 (47%) of the patients. Ninety two (47%) patients had amputations. Re-amputation was necessary in 24 (26%) of these cases. Less than 40% of the total cases had a regular follow up either at a clinic or hospital. Diabetes was diagnosed for the first time in 7 cases (4%) on presentation with foot ulcer. The mean glycemic level was poorly controlled in over 80% of the cases. The overall mortality rate was 21% and sepsis was the most identified cause. Conclusion: Lack of regular patient follow up and diabetes education on foot care, poor glycemic control, delay in patient presentation and surgical intervention as well as patients’ refusal to undergo surgical interventions were the reported contributing factors for the observed high mortality. Recommendation: Diabetic education on foot care, emphasis on metabolic control of diabetes, early presentation and surgical intervention when appropriate has to be highlighted in the management of diabetic patients. More studies have to be done in relation to the high-risk diabetic foot particularly in the Ethiopian setting emphasizing on preventive aspects

Pattern of skin disease in Ethiopian HIV‐infected patients on combination antiretroviral therapy: A cross‐sectional study in a dermatology referral hospital

Abstract Background More than 90% of human immunodeficiency virus (HIV)‐infected patients will develop at least one type of skin disorder during the course of the disease. The prevalence and severity of skin disease commonly seen in HIV‐infected patients has decreased in the era of combination antiretroviral therapy (cART). Few studies in Ethiopia have shown the magnitude of skin problems among adult patients on cART. The aim of this study is to describe the pattern of skin disease among adult patients who are on cART. Methods Cross‐sectional observational study at ALERT Hospital from April 2018 to November 2018. Patterns of clinically diagnosed skin diseases were summarized descriptively. Result A total of 572 patients were evaluated. In total, 412 (72%) were female and the mean age of study participants was 40 (SD = 10.4). The median CD4 count at the time of diagnosis and start of cART were 178 (R 5‐2000) and 168 cells/μl (R 5‐1327), respectively. The mean duration of cART was 8 (SD = 3) years. 89.3% of patients were on first line and 7% on second line of cART regimen. Noninfectious inflammatory skin disorders (40.9%) were the most common concomitant diagnosis followed by infectious diseases (34.9%), infestation (7.7%), pigmentary disorders (6.3%) and cutaneous drug eruption (0.7%), respectively. Among the inflammatory skin disorders, 56.5% presented with eczema. One patient had Kaposi sarcoma. Conclusion Noninfectious inflammatory skin disorders are the most common concomitant skin disease in HIV‐infected patients, with eczema being most prevalent. Infectious skin diseases were also common presentations. In our study, AIDS‐defining skin conditions were rare

MWCNTs/Ag-ZnO nanocomposite for efficient photocatalytic degradation of congo red

Three nanomaterials namely, zinc oxide (ZC), silver-doped zinc oxide (AZ) and multi-walled carbon nanotubes coupled with silver doped zinc oxide nanocomposite (MWAZ) were synthesized, characterized and employed for photo degradation of an organic pollutant, congo red (CR). The photocatalytic activity study showed efficient degradation of CR upon irradiation with UV and visible light in the order of MWAZ > AZ > ZC > Commercial ZnO (ZCO). Percentage photodegradation of 99% and a pseudo 1st order rate constant of 2.3 x 10-2 min-1 were achieved by MWAZ as a catalyst under visible light irradiation, implying photo- sensitizing ability of MWCNTs and the capability of MWCNTs to hinder recombination of photogenerated holes and electrons. The control experiment in the dark condition gave only 7.9% of degradation efficiency and 5.56 x 10-4 min-1 rate constant, implying the significant role of light source for catalytic degradation of CR.   Bull. Chem. Soc. Ethiop. 2020, 34(1), 55-66. DOI: https://dx.doi.org/10.4314/bcse.v34i1.

Early or deferred initiation of efavirenz during rifampicin‐based TB therapy has no significant effect on CYP3A induction in TB‐HIV infected patients

Background and Purpose: In TB‐HIV co‐infection, prompt initiation of TB therapy is recommended but anti‐retroviral treatment (ART) is often delayed due to potential drug–drug interactions between rifampicin and efavirenz. In a longitudinal cohort study, we evaluated the effects of efavirenz/rifampicin co‐treatment and time of ART initiation on CYP3A induction. / Experimental Approach: Treatment‐naïve TB‐HIV co‐infected patients (n = 102) were randomized to efavirenz‐based‐ART after 4 (n = 69) or 8 weeks (n = 33) of commencing rifampicin‐based anti‐TB therapy. HIV patients without TB (n = 94) receiving efavirenz‐based‐ART only were enrolled as control. Plasma 4β‐hydroxycholesterol/cholesterol (4β‐OHC/Chol) ratio, an endogenous biomarker for CYP3A activity, was determined at baseline, at 4 and 16 weeks of ART. / Key Results: In patients treated with efavirenz only, median 4β‐OHC/Chol ratios increased from baseline by 269% and 275% after 4 and 16 weeks of ART, respectively. In TB‐HIV patients, rifampicin only therapy for 4 and 8 weeks increased median 4β‐OHC/Chol ratios from baseline by 378% and 576% respectively. After efavirenz/rifampicin co‐treatment, 4β‐OHC/Chol ratios increased by 560% of baseline (4 weeks) and 456% of baseline (16 weeks). Neither time of ART initiation, sex, genotype nor efavirenz plasma concentration were significant predictors of 4β‐OHC/Chol ratios after 4 weeks of efavirenz/rifampicin co‐treatment. / Conclusion and Implications: Rifampicin induced CYP3A more potently than efavirenz, with maximum induction occurring within the first 4 weeks of rifampicin therapy. We provide pharmacological evidence that early (4 weeks) or deferred (8 weeks) ART initiation during anti‐TB therapy has no significant effect on CYP3A induction

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur

Spectral, electrochemical and DFT studies of a trimetallic Cu II Derivative: Antimycobacterial and cytotoxic activity

The trimetallic Cu II derivative, [Cu 3 (L) 2 (ClO 4 ) 2 ] (1) [where H 2 L = N,N′-bis(salicylidene)-1,3-propanediamine] has been synthesized and characterized by different spectral techniques. In 1, the two terminal Cu II atoms are linked to the central Cu II atom by perchlorato anions and doubly phenoxido bridging. Both the square-pyramidal and octahedral geometries are observed in the two different types of Cu II centers which form the linear trimetallic unit. The EPR spectra in solid state reveal that there exists an exchange coupling among the Cu(II) atoms in the trinuclear unit having the two absorptions at g z = 2.204 and g x = g y = 2.032. We also conduct the DFT computational study which is in good accordance with EPR experimental data. The cyclic voltammogram of 1 shows a redox couple in the negative potential region, which is assigned to the possible reduction of Cu(II) to Cu(I) and further reduction of Cu(I) to Cu(0). Complex 1 exhibits anti-mycobacterial activity and considerable efficacy on M. tuberculosis H 37 Ra (ATCC 25177) and M. tuberculosis H 37 Rv (ATCC 25618) strains. The biological effect of 1 on the viability of human carcinoma cells has been evaluated using the MTT assay and the results indicate that the Cu(II) complex induces a decrease in cell-population growth with apoptosis

Current Efavirenz (EFV) or Ritonavir-Boosted Lopinavir (LPV/r) Use Correlates with Elevate Markers of Atherosclerosis in HIV-Infected Subjects in Addis Ababa, Ethiopia

<div><p>Background</p><p>HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa.</p><p>Methods</p><p>Adult HIV-negative (<i>n</i> = 36), treatment naïve (<i>n</i> = 51), efavirenz (EFV)-treated (<i>n</i> = 91), nevirapine (NVP)-treated (<i>n</i> = 95), or ritonavir-boosted lopinavir (LPV/r)-treated (<i>n</i>=44) subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV) were measured via applanation tonometry and carotid intima-media thickness (cIMT) and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD) were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR), skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured.</p><p>Results</p><p>PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure.</p><p>Conclusions</p><p>Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors.</p></div