Improving adherence to antiretroviral treatment in Uganda with a low-resource facility-based intervention

Objective: To assess the effects of facility-based interventions using existing resources to improve overall patient attendance and adherence to antiretroviral therapy (ART) at ART-providing facilities in Uganda. Methods: This was an interventional study which tracked attendance and treatment adherence of two distinct cohorts: experienced patients who had been on treatment for at least 12 months prior to the intervention and patients newly initiated on ART before or during the intervention. The interventions included instituting appointment system, fast-tracking, and giving longer prescriptions to experienced stable patients. Mixed-effects models were used to examine intervention effects on the experienced patients, while Cox proportional hazards models were used to determine the intervention effects on time until newly treated patients experienced gaps in medication availability. Results: In all, 1481 patients’ files were selected for follow-up from six facilities – 720 into the experienced cohort, and 761 into the newly treated cohort. Among patients in the experienced cohort, the interventions were associated with a significant reduction from 24.4 to 20.3% of missed appointments (adjusted odds ratio (AOR): 0.67; 95% confidence interval (CI): 0.59–0.77); a significant decrease from 20.2 to 18.4% in the medication gaps of three or more days (AOR: 0.69; 95% CI: 0.60–0.79); and a significant increase from 4.3 to 9.3% in the proportion of patients receiving more than 30 days of dispensed medication (AOR: 2.35; 95% CI: 1.91–2.89). Among newly treated patients, the interventions were associated with significant reductions of 44% (adjusted hazard rate (AHR): 0.56, 95% CI: 0.42–0.74) and 38% (AHR: 0.62; 95% CI: 0.45–0.85) in the hazards of experiencing a medication gap of 7 and 14 days or more, respectively. Conclusions: Patients’ adherence was improved with low-cost and easily implemented interventions using existing health facilities’ resources. We recommend that such interventions be considered for scale-up at national levels as measures to improve clinic attendance and ART adherence among patients in Uganda and other low-resource settings in sub-Saharan Africa

Fermented Food for Life: Stories of Inspiration, Struggle & Success

The Fermented Food for Life” project aims to improve food and nutrition security by increasing local production, distribution and consumption of health-promoting probiotic fermented yoghurt in Kenya, Tanzania, and Uganda, targeting to reach 250,000 consumers in the three countries by its end in June 2018. A pro-poor value chain-based business model was identified as a common approach to achieve project’s main objective. In Uganda, over 100 production units of probiotic yoghurt are up and running across the whole country reaching at least 60,000 regular consumers. The project supported also the establishment of 58 production units in Tanzania and 37 in Kenya, producing in total around 14,000 litres of probiotic yoghurt per week. In Tanzania and Uganda, 56% of production units are owned by women, and 68% of all people involved in probiotic yoghurt production and sales are female. The project has also provided a unique opportunity for employment of rural youth involved in the distribution of yoghurt. Partners in project’s implementation include Heifer International, Jomo Kenyatta University of Agriculture and Technology, University of Western Ontario and Yoba for Life Foundation. The project is undertaken with the financial support of Canada’s International Development Research Centre (IDRC), www.idrc.ca and the Government of Canada, provided through Global Affairs Canada (GAC), www.international.gc.ca Collected here are stories about the Fermented Food for Life project

Arbovirus circulation, epidemiology and spatiotemporal distribution in Uganda

BackgroundArboviruses are endemic in Uganda; however, little is known about their epidemiology, seasonality, and spatiotemporal distribution. This study sought to provide information on arbovirus outbreaks from acute clinical presentations.MethodsA retrospective analysis of IgM and confirmatory Plaque Reduction Neutralization Test (PRNT)and results for arbovirus diagnosis of samples collected from 2016 to 2019 was carried out. Demographic data were used to determine the epidemiology and spatiotemporal distribution of arboviruses using the SaTScan and SPSS software.ResultsArbovirus activity peaked consistently during March-May rainy seasons. The overall arbovirus seroprevalence was 9·5% (137/1441). Of the 137 IgM positives, 72 (52·6%) were confirmed by PRNT, of which the central region (53/72; 73·6%) and YFV (20/72; 27·8%) had the highest prevalence. The 5-14 age group were four times more likely to be infected with an arbovirus p=0·003, 4·1 (1·3- 12·3 CI). Significant arboviral activity was observed among indoor (p=0·003) and outdoor (p=0·05) patients. Spatiotemporal analysis indicated arboviral activity in 23 districts with five distinct clusters in 6 districts. Masaka, in the Central region, was the most affected among the districts, with a significant YFV cluster (p˂0·001) from March to May 2016.InterpretationThis study shows that arbovirus activity peak during the March-May rainy season and highlights the need for YFV mass vaccination to reduce the clinical burden of arboviruses transmitted within the region

Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda

In this report we describe a newly discovered ebolavirus species which caused a large hemorrhagic fever outbreak in western Uganda. The virus is genetically distinct, differing by more than 30% at the genome level from all other known ebolavirus species. The unique nature of this virus created challenges for traditional filovirus molecular based diagnostic assays and genome sequencing approaches. Instead, we quickly determined over 70% of the virus genome using a recently developed random-primed pyrosequencing approach that allowed the rapid development of a molecular detection assay that was deployed in the disease outbreak response. This draft sequence allowed easy completion of the whole genome sequence using a traditional primer walking approach and prompt confirmation that this virus represented a new ebolavirus species. Current efforts to design effective diagnostics, antivirals and vaccines will need to take into account the distinct nature of this important new member of the filovirus family

Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains

Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23–99.65%, 95.31–99.79%, and 95.46–100% amino acid similarity to the 2010–2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017–2019. Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control

Main Routes of Entry and Genomic Diversity of SARS-CoV-2, Uganda.

We established rapid local viral sequencing to document the genomic diversity of severe acute respiratory syndrome coronavirus 2 entering Uganda. Virus lineages closely followed the travel origins of infected persons. Our sequence data provide an important baseline for tracking any further transmission of the virus throughout the country and region

Evaluation of the performance of 25 SARS-CoV-2 serological rapid diagnostic tests using a reference panel of plasma specimens at the Uganda Virus Research Institute.

INTRODUCTION: Serological testing is needed to better understand the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Rapid diagnostic tests (RDTs) have been developed to detect specific antibodies, IgM and IgG, to the virus. The performance of 25 of these RDTs was evaluated. METHODS: A serological reference panel of 50 positive and 100 negative plasma specimens was developed from SARS-CoV-2 PCR and antibody positive patients and pre-pandemic SARS-CoV-2-negative specimens collected in 2016. Test performance of the 25 RDTs was evaluated against this panel. RESULTS: A total of 10 RDTs had a sensitivity ≥98%, while 13 RDTs had a specificity ≥98% to anti-SARS-CoV-2 IgG antibodies. Four RDTs (Boson, MultiG, Standard Q, and VivaDiag) had both sensitivity and specificity ≥98% to anti-SARS-CoV-2 IgG antibodies. Only three RDTs had a sensitivity ≥98%, while 10 RDTs had a specificity ≥98% to anti-SARS-CoV-2 IgM antibodies. Three RDTs (Autobio, MultiG, and Standard Q) had sensitivity and specificity ≥98% to combined IgG/IgM. The RDTs that performed well also had perfect or almost perfect inter-reader agreement. CONCLUSIONS: This evaluation identified three RDTs with a sensitivity and specificity to IgM/IgG antibodies of ≥98% with the potential for widespread antibody testing in Uganda

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months.

INTRODUCTION: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. METHODS: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. RESULTS: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. DISCUSSION: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings

Field evaluation of the performance of a SARS-CoV-2 antigen rapid diagnostic test in Uganda using nasopharyngeal samples.

OBJECTIVES: There is a high demand for SARS-CoV-2 testing to identify COVID-19 cases. Real-time quantitative PCR (qRT-PCR) is the recommended diagnostic test but a number of constraints prevent its widespread implementation, including cost. The aim of this study was to evaluate a low cost and easy to use rapid antigen test for diagnosing COVID-19 at the point of care. METHODS: Nasopharyngeal swabs from suspected COVID-19 cases and low-risk volunteers were tested with the STANDARD Q COVID-19 Ag Test and the results were compared with the qRT-PCR results. RESULTS: In total, 262 samples were collected, including 90 qRT-PCR positives. The majority of samples were from males (89%) with a mean age of 34 years and only 13 (14%) of the positives were mildly symptomatic. The sensitivity and specificity of the antigen test were 70.0% (95% confidence interval (CI): 60-79) and 92% (95% CI: 87-96), respectively, and the diagnostic accuracy was 84% (95% CI: 79-88). The antigen test was more likely to be positive for samples with qRT-PCR Ct values ≤29, with a sensitivity of 92%. CONCLUSIONS: The STANDARD Q COVID-19 Ag Test performed less than optimally in this evaluation. However, the test may still have an important role to play early in infection when timely access to molecular testing is not available but the results should be confirmed by qRT-PCR

The effect of intermittent preventive treatment for malaria with dihydroartemisinin-piperaquine on vaccine-specific responses among schoolchildren in rural Uganda (POPVAC B): a double-blind, randomised controlled trial.

BACKGROUND: Several important vaccines differ in immunogenicity and efficacy between populations. We hypothesised that malaria suppresses responses to unrelated vaccines and that this effect can be reversed-at least partially-by monthly malaria intermittent preventive treatment (IPT) in high-transmission settings. METHODS: We conducted an individually randomised, double-blind, placebo-controlled trial of the effect of malaria IPT with dihydroartemisinin-piperaquine on vaccine responses among schoolchildren aged 9-17 years in Jinja district, Uganda. Participants were recruited from two schools and did not have exposure to vaccines of interest after the age of 5 years, with the exception of human papillomavirus (HPV). Computer-generated 1:1 randomisation was implemented in REDCap. 3-day courses of dihydroartemisinin-piperaquine (dosage by weight) or placebo were administered monthly, including twice before the first vaccination. Trial participants were vaccinated with the live parenteral BCG vaccine (Serum Institute of India, Pune, India) at week 0; yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France); live oral typhoid vaccine (Ty21a; PaxVax, London, UK), and quadrivalent virus-like particle HPV vaccine (Merck, Rahway, NJ, USA) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated, and a tetanus-diphtheria booster was given after completion of the trial at week 52. Primary outcomes were vaccine responses at week 8 and, for tetanus-diphtheria, at week 52, and analysis was done in the intention-to-treat population. Malaria parasite prevalence at enrolment and during follow-up was determined retrospectively by PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN62041885) and is complete. FINDINGS: Between May 25 and July 14, 2021, we assessed 388 potential participants for eligibility. We enrolled and randomly allocated 341 participants to the two groups (170 [50%] to dihydroartemisinin-piperaquine and 171 [50%] to placebo); 192 (56%) were female and 149 (44%) participants were male. 145 (85%) participants in the dihydroartemisinin-piperaquine group and 140 participants (82%) in the placebo group were followed up until the week 52 endpoint. At enrolment, 109 (64%) of all participants in the dihydroartemisinin-piperaquine group and 99 (58%) of 170 participants in the placebo group had malaria; this reduced to 6% or lower at all follow-up visits in the dihydroartemisinin-piperaquine group. There was no effect of dihydroartemisinin-piperaquine versus placebo on primary outcomes: BCG-specific IFNγ ELISpot response had a geometric mean ratio (GMR) of 1·09 (95% CI 0·93-1·29), p=0·28; yellow fever neutralising antibody was 1·19 (0·91-1·54), p=0·20 for plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) and 1·24 (0·97-1·58), p=0·09 for PRNT90 titres (reciprocal of the last plasma dilution that reduced by 90%); and IgG to Salmonella enterica serovar Typhi O-lipopolysaccharide was 1·09 (0·81-1·46), p=0·58, HPV-16 was 0·72 (0·44-1·77), p=0·19, HPV-18 was 0·71 (0·47-1·09), p=0·11; tetanus toxoid was 1·22 (0·91-1·62), p=0·18, and diphtheria toxoid was 0·97 (0·83-1·13), p=0·72. There was some evidence that dihydroartemisinin-piperaquine reduced waning of the yellow fever response. INTERPRETATION: IPT for malaria with dihydroartemisinin-piperaquine did not improve peak vaccine responses, despite reducing malaria prevalence. Possible longer-term effects on response waning should be further explored. FUNDING: UK Medical Research Council. TRANSLATION: For the Luganda translation of the abstract see Supplementary Materials section