‘Teaching corner’: Management of Diabetic Retinopathy

Sub-Saharan Africa faces an epidemic of diabetes. Visual loss from diabetic retinopathy (DR) is both preventable and treatable. This article reviews the epidemiology and clinical features of DR and current evidence based interventions in three areas: primary prevention of retinopathy by optimum medical management, early detection of pre-symptomatic disease and management of established retinopathy to prevent or mitigate visual loss. There are significant challenges to DR care in resource poor environments. Appropriate provision of effective interventions by health services can reduce social and economic costs associated with patien

Incremental cost-effectiveness of screening and laser treatment for diabetic retinopathy and macular edema in Malawi

Objective To investigate the economic impact of introducing targeted screening and laser photocoagulation treatment for sight-threatening diabetic retinopathy and macular edema in a setting with no previous screening or laser treatment for diabetic retinopathy in sub-Saharan Africa. Materials and methods A cohort Markov model was built to compare combined targeted screening and laser treatment for patients with sight-threatening diabetic retinopathy and macular edema against no intervention. Primary outcomes were incremental cost per quality-adjusted life year (QALY) gained and per disability-adjusted life year (DALY) averted. Primary data were collected on 357 participants from the Malawi Diabetic Retinopathy Study, a prospective, observational cohort study. Multiple scenarios were explored and a probabilistic sensitivity analysis was performed. Results In the base case (age: 50 years, service utilization rate: 80%), the cost of the intervention and the years of severe visual impairment averted per patient screened were $209 and 2.2 years respectively. Applying the World Health Organization threshold of cost-effectiveness for Malawi ($679), the base case was cost-effective when QALYs were used ($400 per QALY gained) but not when DALYs were used ($766 per DALY averted). The intervention was more cost-effective when it targeted younger patients (age: 30 years) and less cost-effective when the utilization rate was lowered to 50%. Conclusions Annual photographic screening of diabetic patients attending medical diabetes clinics in Malawi, with the provision of laser treatment for those with sight-threatening diabetic retinopathy and macular edema, appears to be cost-effective in terms of QALYs gained, in our base case scenario. Cost-effectiveness improves if services are utilized more intensively and extended to younger patients

Diversity of Mollusc Vectors of Schistosomiasis in Miti-Murhesa Health Zone, Eastern of DRC, Kabare Territory

The main objective is to inventory the vectors of bilharziasis in the aquatic ecosystems of KABARE locally in Miti-Murhesa Health zone as well as other species of aquatic molluscs in order to activate the fight against this endemic disease of this region. A total of 2762 samples were collected during our investigation period in the aquatic ecosystems in Miti-Murhesa Health Zone. We carried out field work based on shellfish sampling using appropriate methods. This sampling was carried out in 12 different sites. After collect of samples, we identified the mollusc species using the indicated identification keys, counted them and compiled them in Excel software for statistical analyses using Past software. Thus, five species of aquatic molluscs were identified. These species are Biomphalaria pfeifferi, Bulinus globosus, Pisidium casernatum, B. forskalii and Lymnaea natalensis. The species Biomphalaria pfeifferi and Bilinus globosus are intermediate hosts of intestinal schistosomiasis and urinary schistosomiasis respectively%253B while Lymnaea natalensis is the intermediate host of fasciolosis. Depending on the frequency of species, Biomphalaria pfeifferi and Lymnaea natalensis are constant species, Bulinus globosus and Psidium casernatum are accessory species and finally B. forskalii is an accidental species.Depending on the sites prospected, one species of aquatic mollusc was abundant in the aquatic ecosystems in this area%253A Biomphalaria pfeifferi%253B three species are moderately abundant%253A Lymnaea natalensis, Bulinus globosus and Pisidium casernatum, and only one is rare%253A Tomichia ventricosa. All the prospected sites are diversified in aquatic mollusc species except the Kashekesheke site, but the 2nd tarmaque site, Mulungu River and Kamulonge sites are thus the richest sites in aquatic mollusc species of Miti-Murhesa Health zone. The presence of these species clearly shows the risk of contamination of the population of Miti-Murhesa Health zone. These intermediate hosts of bilharzia are proliferating in the aquatic ecosystems of Miti-Murhesa Health zone%253B it is therefore important to recommend ways to reduce this proliferation. This study provides the basis for future ecological studies of the intermediate bilharzia host molluscs in this entity

Prevalence and Predictors of Urinary Tract Infection and Severe Malaria Among Febrile Children Attending Makongoro Health Centre in Mwanza City, North-Western Tanzania.

In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania. From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages. A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively. Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania

Genetic diversity and risk factors for the transmission of antimicrobial resistance across human, animals and environmental compartments in East Africa: a review.

BACKGROUND The emergence and spread of antimicrobial resistance (AMR) present a challenge to disease control in East Africa. Resistance to beta-lactams, which are by far the most used antibiotics worldwide and include the penicillins, cephalosporins, monobactams and carbapenems, is reducing options for effective control of both Gram-positive and Gram-negative bacteria. The World Health Organization, Food and Agricultural Organization and the World Organization for Animal Health have all advocated surveillance of AMR using an integrated One Health approach. Regional consortia also have strengthened collaboration to address the AMR problem through surveillance, training and research in a holistic and multisectoral approach. This review paper contains collective information on risk factors for transmission, clinical relevance and diversity of resistance genes relating to extended-spectrum beta-lactamase-producing (ESBL) and carbapenemase-producing Enterobacteriaceae, and Methicillin-resistant Staphylococcus aureus (MRSA) across the human, animal and environmental compartments in East Africa. MAIN BODY The review of the AMR literature (years 2001 to 2019) was performed using search engines such as PubMed, Scopus, Science Direct, Google and Web of Science. The search terms included 'antimicrobial resistance and human-animal-environment', 'antimicrobial resistance, risk factors, genetic diversity, and human-animal-environment' combined with respective countries of East Africa. In general, the risk factors identified were associated with the transmission of AMR. The marked genetic diversity due to multiple sequence types among drug-resistant bacteria and their replicon plasmid types sourced from the animal, human and environment were reported. The main ESBL, MRSA and carbapenem related genes/plasmids were the CTX-Ms (45.7%), SCCmec type III (27.3%) and IMP types (23.8%), respectively. CONCLUSION The high diversity of the AMR genes suggests there may be multiple sources of resistance bacteria, or the possible exchange of strains or a flow of genes amongst different strains due to transfer by mobile genetic elements. Therefore, there should be harmonized One Health guidelines for the use of antibiotics, as well as regulations governing their importation and sale. Moreover, the trend of ESBLs, MRSA and carbapenem resistant (CAR) carriage rates is dynamic and are on rise over time period, posing a public health concern in East Africa. Collaborative surveillance of AMR in partnership with regional and external institutions using an integrated One Health approach is required for expert knowledge and technology transfer to facilitate information sharing for informed decision-making

Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial

Background: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. Methods: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18–45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. Findings: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22–30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73–1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06–0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3–2·57]; hazard ratio 0·12 [0·05–0·31]; p<0·0001; risk difference –1·6% [–1·0% to –2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9–1·7); no congenital birth anomalies were reported. Interpretation: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. Funding: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022

Background Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda. Methods A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2–10 years (PfPR 2–10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood methods. District level prevalence estimates adjusted for population are calculated for the years 2000 to 2022. Results A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modeled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region. Conclusions The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data