Prevalence and predictors of asymptomatic malaria infection in Boricha District, Sidama Region, Ethiopia: implications for elimination strategies.

BACKGROUND: Malaria remains a major public health threat in Ethiopia despite the tremendous progress made towards the 2030 elimination targets. The silent transmission of asymptomatic infection is one of the factors that enhance the persistence of the disease as a public health issue and impedes efforts to eliminate malaria. Thus, this study aimed at investigating the prevalence and risk factors of asymptomatic malaria infection in Boricha district, Sidama region of Ethiopia. METHODS: A community-based cross-sectional study was conducted in eight selected kebeles (smallest administrative unit) in Boricha district. Representative households were chosen using a multi-stage sampling technique. A total of 573 participants were included in the study. Malaria diagnosis was performed using rapid diagnostic test (RDT) and microscopy. A structured questionnaire was administered to collect socio-demographic information. Epi data 3.1 was employed for data entry, and SPSS version 25 was used for analysis. RESULTS: Of the 573 asymptomatic participants tested, 6.1% were found to be positive by RDT and 4.0% by microscopy. Participants aged under 5 years (AOR = 1.57, 95% CI 0.46-5.39) and 5-14 years old (AOR = 2.42, 95% CI 1.08-5.40), Insecticide-treated net utilization (AOR = 8.41; 95% CI 1.09-65.08), travel history (AOR = 6.85, 95% CI 2.32-20.26) and living in a house with windows (AOR = 2.11, 95% CI 1.02-4.36) were significantly associated with the asymptomatic malaria infection. CONCLUSION: The findings of this study revealed that prevalence of asymptomatic malaria infection was higher in the study area. As a result, rigorous implementation of existing interventions, such as vector control and anti-malaria drugs, is strongly recommended. In addition, devising new ones that are suited to the contextual situations is highly suggested.

Adapting international clinical trials during COVID-19 and beyond.

BACKGROUND: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. THE NEW WORKING MODEL: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice-compliant antimalarial trials and foster cross-country and cross-study site collaboration. CONCLUSION: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research.

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data.

BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185.

COVID-19 vaccine acceptability among healthcare workers in Ethiopia: Do we practice what we preach?

OBJECTIVE: We assessed healthcare workers (HCWs) COVID-19 vaccine acceptability in Ethiopia. METHODS: We carried out a cross-sectional survey from February to April 2021 in HCWs from five teaching hospitals. HCWs were selected using convenient sampling, and data were collected through a survey link. Descriptive analysis and mixed-effect logistic regression were performed. A total of 1,314 HCWs participated in the study. RESULTS: We found that 25.5% (n = 332) of the HCWs would not accept a COVID-19 vaccine and 20.2% (n = 264) were not willing to recommend COVID-19 vaccination to others. Factors associated with vaccine non-acceptance were female sex (AOR = 1.8; 95% CI: 1.3-2.5), the perception that vaccines are unsafe (AOR = 15.0; 95% CI: 8.7-25.9), not considering COVID-19 as health risk (AOR = 4.4; 95% CI: 2.0-9.5) and being unconcerned about contracting COVID-19 at work (AOR = 3.5; 95% CI: 1.5-8.4). Physicians were more willing to accept vaccination than other HCWs. Higher vaccine acceptability was also noted with increasing age. Participants most often indicated safety concerns as the determining factor on their decision to get vaccinated or not. CONCLUSION: Overall, a quarter of HCWs would not accept a COVID-19 vaccine. Communications and training should address vaccine safety concerns. Additionally, emphasis should be given to showing current and future impact of COVID-19 on the personal, public and country level unless control efforts are improved. Interventions aimed to increase vaccine uptake should focus their efforts on younger and non-physician HCWs.

Predictors of glucose metabolism and blood pressure among Ethiopian individuals with HIV/AIDS after one-year of antiretroviral therapy.

OBJECTIVE: Better understanding of glucose metabolism in patients with HIV after initiating antiretroviral therapy (ART) is important to target treatment and follow-up for diabetes risk and other non-communicable diseases in resource-limited settings. The aim of this study was to assess the changes and predictors of glucose metabolism and blood pressure among patients with HIV on ART for 12 months. METHODS: One-year follow-up of Ethiopian patients with HIV after initiation of ART was done. Outcomes were changes in fasting plasma glucose (FPG), and 30-minute (30mPG) and 2-hour plasma glucose (2hPG) after oral glucose tolerance test, glycated haemoglobin (HbA1c), fasting plasma insulin (p-insulin), homeostatic model assessment index for insulin resistance (HOMA-IR) and blood pressure.   RESULTS: The mean age was 33 years, and the majority were women. During the first 12 months, levels of all plasma glucose parameters decreased, while p-insulin (10B 3.1; 95% CI2.4, 4.0), HOMA-IR (10B 3.1; 95% CI2.3, 4.0) and systolic blood pressure (B 4.0; 95% CI2.5, 5.5) increased. Fat-free mass at baseline predicted higher increments in p-insulin, HOMA-IR and blood pressure; whereas, fat mass predicted higher increment in HbA1c. CONCLUSIONS: Among Ethiopian patients with HIV, blood pressure and insulin increased, and all glucose parameters declined during 12-month of ART. Only longer-term follow-up will tell us whether insulin increase is due to insulin resistance or from recovering ß-cells.

Efficacy and safety of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Regular monitoring of anti-malarial drug efficacy is vital for establishing rational malaria treatment guidelines and ensuring adequate treatment outcomes. This study aimed to synthesize the available evidence on the efficacy of artemether-lumefantrine for the management of uncomplicated falciparum malaria in Ethiopia. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant published studies were searched from the databases (PubMed, Google Scholar and Clinical trial registry) on published artemether-lumefantrine therapeutic efficacy studies conducted in Ethiopia from 2004 to 2020. The retrieved studies were assessed for quality using the modified Newcastle Ottawa Scale for observational studies and modified Jadad scale for interventional studies. Risk of bias was also assessed by using ROBINS-I tool. OpenMeta-Analyst software was used for the statistical analysis. The review protocol is registered in PROSPERO, number CRD42020201859. RESULTS: Fifteen studies (1523 participants) were included in the final analysis. The overall PCR-uncorrected pooled proportion of treatment success of artemether-lumefantrine therapy for uncomplicated falciparum malaria was 98.4% (95%CI 97.6-99.1). A random-effects model was used because of considerable heterogeneity [χ2 = 20.48, df (14), P = 0.011 and I2 = 31.65]. PCR-corrected pooled proportion of treatment success of artemether-lumefantrine therapy was 98.7% (95% CI 97.7-99.6). A random-effects model was used [χ2 = 7.37, df(6), P = 0.287 and I2 = 18.69]. Most studies included in the present review achieved a rapid reduction of fevers and parasitaemia between D0 and D3 of assessment. Adverse events were mostly mild and only two cases were reported as serious, but were not directly attributed to the drug. CONCLUSION: The present meta-analysis suggests that artemether-lumefantrine therapy is efficacious and safe in treating uncomplicated falciparum malaria in Ethiopia. However, owing to the high risk of bias in the included studies, strong conclusions cannot be drawn. Further high-quality RCTs assessing anti-malarial efficacy and safety should be performed to demonstrates strong evidence of changes in parasite sensitivity to artemether-lumefantrine in Ethiopia.

Usability of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency: a multi-country assessment of test label comprehension and results interpretation.

BACKGROUND: Point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing has the potential to make the use of radical treatment for vivax malaria safer and more effective. Widespread use of G6PD tests as part of malaria case management has been limited, in part due to due concerns regarding product usability, user training, and supervision. This study seeks to assess how well end users can understand the Standard™ G6PD Test (SD Biosensor, Suwon, South Korea) workflow, result output, and label after training. This will ultimately help inform test registration and introduction. METHODS: Potential G6PD test users who provide malaria case management at three sites in Brazil, Ethiopia, and India were trained on the use of the SD Biosensor Standard G6PD Test and assessed based on their ability to understand the test workflow and interpret results. The assessment was done through a questionnaire, designed to assess product usability against key technical product specifications and fulfill regulatory evidence requirements. Any participant who obtained 85% or above correct responses to the questionnaire was considered to adequately comprehend how to use and interpret the test. RESULTS: Forty-five participants, including malaria microscopists, laboratory staff, nurses, and community health workers took part in the study. Seventy-eight percent of all participants in the study (35/45) obtained passing scores on the assessment with minimal training. Responses to the multiple-choice questions indicate that most participants understood well the test intended use, safety claims, and warnings. The greatest source of error regarding the test was around the correct operating temperature. Most test results were also read and interpreted correctly, with the haemoglobin measurement being a more problematic output to interpret than the G6PD measurement. CONCLUSIONS: These data results show how a standardized tool can be used to assess a user's ability to run a point-of-care diagnostic and interpret results. When applied to the SD Biosensor Standard G6PD Test, this tool demonstrates that a range of users across multiple contexts can use the test and suggests improvements to the test instructions and training that can improve product usability, increase user comprehension, and ultimately contribute to more widespread effective use of point-of-care G6PD tests. TRIAL REGISTRATION: NCT04033640.

Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria.

Plasmodium vivax has the largest geographic range of human malaria species and is challenging to manage and eradicate due to its ability to establish a dormant liver stage, the hypnozoite, which can reactivate leading to relapse. Until recently, the only treatment approved to kill hypnozoites was the 8-aminoquinoline, primaquine, requiring daily treatment for 14 days. Tafenoquine, an 8-aminoquinoline single-dose treatment with activity against P. vivax hypnozoites, has recently been approved by the US Food and Drug Administration and Australian Therapeutic Goods Administration for the radical cure of P. vivax malaria in patients 16 years and older. We conducted an exploratory pharmacogenetic analysis (GSK Study 208099) to assess the role of host genome-wide variation on tafenoquine efficacy in patients with P. vivax malaria using data from three GSK clinical trials, GATHER and DETECTIVE Part 1 and Part 2. Recurrence-free efficacy at 6 and 4 months and time to recurrence up to 6 months postdosing were analyzed in 438 P. vivax malaria patients treated with tafenoquine. Among the approximately 10.6 million host genetic variants analyzed, two signals reached genome-wide significance (P value ≤ 5 × 10). rs62103056, and variants in a chromosome 12 intergenic region, were associated with recurrence-free efficacy at 6 and 4 months, respectively. Neither of the signals has an obvious biological rationale and would need replication in an independent population. This is the first genome-wide association study to evaluate genetic influence on response to tafenoquine in P. vivax malaria.

Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Chewaka District, Ethiopia.

BACKGROUND: The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia. METHODS: The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum. A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection. RESULTS: Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1-98.5) and 96% (95% CI 88.8-99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8-99.2). Based on Kaplan-Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3-11.4). Only three participants 3.8% (95% CI 0.8-10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL. CONCLUSIONS: The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.

Genetic diversity and genotype multiplicity of Plasmodium falciparum infection in patients with uncomplicated malaria in Chewaka district, Ethiopia.

BACKGROUND: Genetic diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity of P. falciparum strains can be used to assess intensity of parasite transmission and identify potential deficiencies in malaria control programmes, which provides vital information to evaluating malaria elimination efforts. This study investigated the P. falciparum genetic diversity and genotype multiplicity of infection in parasite isolates from cases with uncomplicated P. falciparum malaria in Southwest Ethiopia. METHODS: A total of 80 P. falciparum microscopy and qPCR positive blood samples were collected from study participants aged 6 months to 60 years, who visited the health facilities during study evaluating the efficacy of artemether-lumefantrine from September-December, 2017. Polymorphic regions of the msp-1 and msp-2 were genotyped by nested polymerase chain reactions (nPCR) followed by gel electrophoresis for fragment analysis. RESULTS: Of 80 qPCR-positive samples analysed for polymorphisms on msp-1 and msp-2 genes, the efficiency of msp-1 and msp-2 gene amplification reactions with family-specific primers were 95% and 98.8%, respectively. Allelic variation of 90% (72/80) for msp-1 and 86.2% (69/80) for msp-2 were observed. K1 was the predominant msp-1 allelic family detected in 20.8% (15/72) of the samples followed by MAD20 and RO33. Within msp-2, allelic family FC27 showed a higher frequency (26.1%) compared to IC/3D7 (15.9%). Ten different alleles were observed in msp-1 with 6 alleles for K1, 3 alleles for MAD20 and 1 allele for RO33. In msp-2, 19 individual alleles were detected with 10 alleles for FC27 and 9 alleles for 3D7. Eighty percent (80%) of isolates had multiple genotypes and the overall mean multiplicity of infection was 3.2 (95% CI 2.87-3.46). The heterozygosity indices were 0.43 and 0.85 for msp-1 and msp-2, respectively. There was no significant association between multiplicity of infection and age or parasite density. CONCLUSIONS: The study revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations in Chewaka district, Ethiopia, suggesting that both endemicity level and malaria transmission remain high and that strengthened control efforts are needed in Ethiopia.

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir.

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

HIV and metabolic syndrome in an Ethiopian population.

BACKGROUND: The global prevalence of metabolic syndrome (MS) is increasing due to lifestyle changes. Studies have found that MS is associated with human immunodeficiency virus (HIV) and antiretroviral treatment (ART), but controversies still exist on associations between HIV and MS. AIMS: To assess associations between HIV and MS among ART-naïve HIV positive individuals compared to HIV negative individuals. SUBJECTS AND METHODS: A cross-sectional study among ART-naïve HIV positive and HIV negative individuals recruited from HIV treatment and testing facilities in Ethiopia. Information was collected on components of MS: waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure and fasting plasma glucose (FPG). Data were analysed using logistic and linear regression stratified by sex and adjusted for age, wealth and education. RESULTS: Data from 329 HIV positive and 100 HIV negative individuals were included. HIV positive status was associated with higher odds of MS in women (OR: 3.56, 95%CI: 1.25; 10.15) (n = 292), but not in men (OR: 0.98, 95%CI: 0.22; 4.30) (n = 137), interaction: p= .11. Associations between HIV and components of MS were strongest for HDL-C among women and for FPG among men. The most prevalent components of MS in HIV positive individuals were elevated triglycerides, reduced HDL-C and elevated FPG. CONCLUSIONS: HIV was associated with MS among ART-naïve women, suggesting that MS should be evaluated before initiating ART and monitored during treatment to identify those at risk of developing diabetes and cardiovascular disease (CVD).

The effect of nutritional supplementation on quality of life in people living with HIV: a randomised controlled trial.

OBJECTIVE: To determine the effects of lipid-based nutrient supplements (LNS) on the quality of life of people living with HIV (PLHIV) during the first 3 months of antiretroviral treatment (ART) and to investigate the effects of timing of supplementation by comparing with supplementation during the subsequent 3 months. METHODS: A randomised controlled trial was conducted in three ART clinics within public health facilities in Jimma, Ethiopia. Participants were PLHIV eligible to start ART with body mass index >17 kg/m(2) and given daily supplements of 200 g of LNS containing whey or soya either during the first 3 months or the subsequent months of ART. The outcome was measured in terms of total quality-of-life scores on the adapted version of the WHOQOL-HIV-BREF assessed at baseline, three and six months. RESULTS: Of the 282 participants, 186 (66.0%) were women. The mean age (SD) was 32.8 (±9.0) years, and the mean (SD) total quality-of-life score was 82.0 (±14.8) at baseline assessment. At 3 months, participants who received LNS showed better quality of life than those who only received ART without LNS (ß = 6.2, 95% CI: 2.9: 9.6). At 6 months, there was no difference in total quality-of-life score between the early and delayed supplementation groups (ß = 3.0, 95% CI: -0.4: 6.4). However, the early supplementation group showed higher scores on the social and spirituality domains than the delayed group. CONCLUSIONS: LNS given during the first three months of ART improves the quality of life of PLHIV.

Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults.

Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25(OH)D levels. A randomised nutritional supplementation trial was conducted at Jimma University Specialized Hospital, Ethiopia. The trial compared 200 g/d of lipid-based nutrient supplement (LNS) with no supplementation during the first 3 months of ART. The supplement provided twice the recommended daily allowance of vitamin D (10 µg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level was higher in HIV-positive than in HIV-negative persons (42·5 v. 35·3 nmol/l, P<0·001). In all, 282 HIV-positive persons with BMI>17 kg/m2 were randomised to either LNS supplementation (n 189) or no supplementation (n 93) during the first 3 months of ART. The supplemented group had a 4·1 (95 % CI 1·7, 6·4) nmol/l increase in serum 25(OH)D, whereas the non-supplemented group had a 10·8 (95 % CI 7·8, 13·9) nmol/l decrease in serum 25(OH)D level after 3 months of ART. Nutritional supplementation that contained vitamin D prevented a reduction in serum 25(OH)D levels in HIV-positive persons initiating ART. Vitamin D replenishment may be needed to prevent reduction in serum 25(OH)D levels during ART.

Food insecurity, mental health and quality of life among people living with HIV commencing antiretroviral treatment in Ethiopia: a cross-sectional study.

BACKGROUND: Studies from high-income settings show that both food insecurity and common mental disorders (CMDs) are associated with lower quality of life among people living with HIV (PLHIV). However, there is limited research among PLHIV in sub-Saharan Africa. In this study we tested the hypothesis that food insecurity and CMDs would be associated with poorer quality of life of PLHIV in Ethiopia. METHODS: A cross-sectional study was carried out with 348 PLHIV who were initiating antiretroviral therapy recruited from two primary care centers and a tertiary Hospital in southwest Ethiopia. Food insecurity, CMD, and quality of life were measured using instruments adapted and validated in Ethiopia (Household Food Insecurity Access Scale, Kessler-6, and WHOQOL-HIV-BREF-ETH, respectively). Multiple linear regression analysis was used to identify factors associated with quality of life after adjusting for confounders. RESULTS: The prevalence of severe household food insecurity among PLHIV was 38.7 %. After adjusting for confounders, severe food insecurity (ß = -3.24, 95 % CI: -6.19; -0.29) and higher levels of CMD symptoms (ß = -1.72 for each 1 point increase, 95 % CI: -1.94; -1.49) were associated with lower quality of life. Other factors associated with lower quality of life were advanced HIV disease (ß = -3.80, 95 % CI: -6.18; -1.42), and being underweight (BMI = 17.0 - 18.5 kg/m(2)) (ß = -3.45, 95 % CI: -6.18; -0.71). Owning more household assets was associated with higher quality of life (ß = 0.99 for owning one more asset, 95 % CI: 0.09; 1.89). CONCLUSION: Poor mental health and food insecurity are associated with lower quality of life in PLHIV. There is a need for longitudinal studies to elucidate the pathways linking CMD, food insecurity and quality of life.

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/µL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. RESULTS: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/µL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). CONCLUSIONS: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. TRIAL REGISTRATION: PACTR201106000300631, registered on 1st June 2011.

Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia.

BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months). RESULTS: Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS: Our data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART. However, the documented occurrence of transmitted resistance and accumulation of acquired HIVDR mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations.

Haematological Indices in Acute Coronary Syndrome Patients in Ethiopia: A Comparative Cross-Sectional Study.

Background: Numerous biomarkers are used as diagnostic, prognostic, and predictive indicators of myocardial ischemia. The most commonly used biomarkers are cardiac troponin I (Tn-I) and creatinine kinase (CK-MB). However, in developing nations, their availability in primary care settings is extremely limited. In such situations, easily available assays such as complete blood count (CBC) should be investigated as prognostic indicators in individuals with acute coronary syndrome (ACS). Objective: This study aimed to compare the pattern of haematological indices and blood cell ratios of ACS patients compared with apparently healthy controls. Methods: Patients diagnosed with ACS were recruited consecutively between 01 May 2022 and 31 October 2023 at Jimma Medical Center (JMC). Biochemical analyses and complete blood counts were performed. Analysis of variance was performed to compare the continuous variables. Spearman correlation coefficient tests were performed to correlate hematologic parameters with high sensitive troponin-I (hs-Tn-I) levels. Results: This study enrolled 220 participants (110 patients with ACS and age, sex, and place of residence matched 110 non-ACS controls). From ACS group 99 (90%) were diagnosed with ST-elevated myocardial infarction. The ACS group had a significantly greater mean platelet volume (MPV), white blood cell count, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. The RDW (r = 0.248, p = 0.009) and MPV (r = 0.245, p = 0.009) were significantly positively correlated with hs-Tn-I levels in the ACS group. MPV, RDW, and monocyte count were significantly higher in non-survivor ACS patients (p <0.05). Conclusion: The significant differences observed in haematological parameters between individuals with ACS and healthy controls suggest the potential utility of these easily accessible and cost-effective diagnostics in predicting future morbidity and ACS risk. Incorporating these routine evaluations into clinical practice could enhance risk assessment and improve patient outcomes.

Associations of early childhood body mass index trajectories with body composition and cardiometabolic markers at age 10 years: the Ethiopian infant anthropometry and body composition (iABC) birth cohort study.

BACKGROUND: Variability in body mass index (BMI) (kg/m2) trajectories is associated with body composition and cardiometabolic markers in early childhood, but it is unknown how these associations track to later childhood. OBJECTIVES: We aimed to assess associations of BMI trajectories from 0 to 5 y with body composition and cardiometabolic markers at 10 y. METHODS: In the Ethiopian infant anthropometry and body composition (iABC) birth cohort, we previously identified 4 distinct BMI trajectories from 0 to 5 y: stable low BMI (19.2%), normal BMI (48.8%), rapid growth to high BMI (17.9%), and slow growth to high BMI (14.1%). At 10 y, we obtained data from 320 children on anthropometry, body composition, abdominal subcutaneous and visceral fat, and cardiometabolic markers. Associations of BMI trajectories and 10-y outcomes were analyzed using multiple linear regression. RESULTS: Compared with children with the normal BMI trajectory, those with rapid growth to high BMI had 1.7 cm (95% CI: 0.1, 3.3) larger waist circumference and those with slow growth to high had 0.63 kg/m2 (95% CI: 0.09, 1.17) greater fat mass index and 0.19 cm (95% CI: 0.02, 0.37) greater abdominal subcutaneous fat, whereas those with stable low BMI had -0.28 kg/m2 (95% CI: -0.59, 0.03) lower fat-free mass at 10 y. Although the confidence bands were wide and included the null value, children with rapid growth to high BMI trajectory had 48.6% (95% CI: -1.4, 123.8) higher C-peptide concentration and those with slow growth to high BMI had 29.8% (95% CI: -0.8, 69.8) higher insulin and 30.3% (95% CI: -1.1, 71.6) higher homeostasis model assessment of insulin resistance, whereas those with rapid growth to high BMI had -0.23 mmol/L (95% CI: -0.47, 0.02) lower total cholesterol concentration. The trajectories were not associated with abdominal visceral fat, blood pressure, glucose, and other lipids at 10 y. CONCLUSIONS: Children with rapid and slow growth to high BMI trajectories before 5 y tend to show higher measures of adiposity and higher concentrations of markers related to glucose metabolism at 10 y. CLINICAL TRIAL REGISTRY: ISRCTN46718296 (https://www.isrctn.com/ISRCTN46718296).