COVID-19 vaccines and a perspective on Africa.

Vaccines have dramatically changed the COVID-19 pandemic. Over 30 vaccines that were developed on four main platforms are currently being used globally, but a deep dissection of the immunological mechanisms by which they operate is limited to only a few of them. Here, we review the evidence describing specific aspects of the modes of action of COVID-19 vaccines; these include innate immunity, trained innate immunity, and mucosal responses. We also discuss the use of COVID-19 vaccines in the African continent which is ridden with inequality in its access to vaccines and vaccine-related immunological research. We argue that strengthening immunology research in Africa should inform on fundamental aspects of vaccination, including the relevance of genetics, trained innate immunity, and microbiome diversity.

Impact of antimalarial resistance and COVID-19 pandemic on malaria care among pregnant women in Northern Uganda (ERASE): protocol of a prospective observational study.

BACKGROUND: Uganda accounts for 5% of all malaria cases and deaths reported globally and, in endemic countries, pregnancy is a risk factor for both acquisition of P. falciparum infection and development of severe malaria. In recent years, malaria control has been threatened by COVID-19 pandemic and by the emergence, in Northern Uganda, of both resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. METHODS: In this facility-based, prospective, observational study, pregnant women will be recruited at antenatal-care visits and followed-up until delivery. Collected data will explore the incidence of asymptomatic parasitemia and malaria-related outcomes, as well as the attitudes towards malaria prevention, administration of intermittent preventive treatment, healthcare seeking behavior and use of insecticide-treated nets. A subpopulation of women diagnosed with malaria will be recruited and their blood samples will be analyzed for detection of genetic markers of resistance to artemisinin derivatives and sulfadoxine-pyrimethamine. Also, to investigate the impact of COVID-19 on malaria care among pregnant women, a retrospective, interrupted-time series will be conducted on at the study sites for the period January 2018 to December 2021. DISCUSSION: The present study will explore the impact of COVID-19 pandemic on incidence of malaria and malaria-related adverse outcomes, along with the prevalence of resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. To our knowledge, this is the first study aiming to explore the combined effect of these factors on a cohort of pregnant women. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov public website on 26th April, 2022. CLINICALTRIALS: gov Identifier: NCT05348746.

The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study.

BACKGROUND: Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB. METHODS: We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews. RESULTS: The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552-110.135) and drug stock-outs aOR 0.027 (95%CI 0.002-0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB. CONCLUSION: Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.

Impact of socio-economic factors on Tuberculosis treatment outcomes in north-eastern Uganda: a mixed methods study.

BACKGROUND: Tuberculosis (TB) is a major public health problem and at 48%, Karamoja in North-Eastern Uganda has the lowest treatment success rate nationally. Addressing the social determinants of TB is crucial to ending TB. This study sought to understand the extent and ways in which socio-economic factors affect TB treatment outcomes in Karamoja. METHODS: We conducted a convergent parallel mixed methods study in 10 TB Diagnostic and Treatment Units. The study enrolled former TB patients diagnosed with drug-susceptible TB between April 2018 and March 2019. Unit TB and laboratory registers were reviewed to identify pre-treatment losses to follow-up. Four focus group discussions with former TB patients and 18 key informant interviews with healthcare workers were conducted. Principle component analysis was used to generate wealth quintiles that were compared to treatment outcomes using the proportion test. The association between sociodemographic characteristics and TB treatment outcomes was evaluated using the chi-square test and multiple logistic regression. RESULTS: A total of 313 participants were randomly selected from 1184 former TB patients recorded in the unit TB registers. Of these, 264 were contacted in the community and consented to join the study: 57% were male and 156 (59.1%) participants had unsuccessful treatment outcomes. The wealthiest quintile had a 58% reduction in the risk of having an unsuccessful treatment outcome (adj OR = 0.42, 95% CI 0.18-0.99, p = 0.047). People who were employed in the informal sector (adj OR = 4.71, 95% CI 1.18-18.89, p = 0.029) and children under the age of 15 years who were not in school or employed (adj OR = 2.71, 95% CI 1.11-6.62, p = 0.029) had significantly higher odds of unsuccessful treatment outcome. Analysis of the pre-treatment loss to follow-up showed that 17.2% of patients with pulmonary bacteriologically confirmed TB did not initiate treatment with a higher proportion among females (21.7%) than males (13.5%). Inadequate food, belonging to migratory communities, stigma, lack of social protection, drug stock-outs and transport challenges affected TB treatment outcomes. CONCLUSIONS: This study confirmed that low socio-economic status is associated with poor TB treatment outcomes emphasizing the need for multi- and cross-sectoral approaches and socio-economic enablers to optimise TB care.

Measurement error of mean sac diameter and crown-rump length among pregnant women at Mulago hospital, Uganda.

BACKGROUND: Ultrasonography is essential in the prenatal diagnosis and care for the pregnant mothers. However, the measurements obtained often contain a small percentage of unavoidable error that may have serious clinical implications if substantial. We therefore evaluated the level of intra and inter-observer error in measuring mean sac diameter (MSD) and crown-rump length (CRL) in women between 6 and 10 weeks' gestation at Mulago hospital. METHODS: This was a cross-sectional study conducted from January to March 2016. We enrolled 56 women with an intrauterine single viable embryo. The women were scanned using a transvaginal (TVS) technique by two observers who were blinded of each other's measurements. Each observer measured the CRL twice and the MSD once for each woman. Intra-class correlation coefficients (ICCs), 95% limits of agreement (LOA) and technical error of measurement (TEM) were used for analysis. RESULTS: Intra-observer ICCs for CRL measurements were 0.995 and 0.993 while inter-observer ICCs were 0.988 for CRL and 0.955 for MSD measurements. Intra-observer 95% LOA for CRL were ± 2.04 mm and ± 1.66 mm. Inter-observer LOA were ± 2.35 mm for CRL and ± 4.87 mm for MSD. The intra-observer relative TEM for CRL were 4.62% and 3.70% whereas inter-observer relative TEM were 5.88% and 5.93% for CRL and MSD respectively. CONCLUSIONS: Intra- and inter-observer error of CRL and MSD measurements among pregnant women at Mulago hospital were acceptable. This implies that at Mulago hospital, the error in pregnancy dating is within acceptable margins of ±3 days in first trimester, and the CRL and MSD cut offs of ≥7 mm and ≥ 25 mm respectively are fit for diagnosis of miscarriage on TVS. These findings should be extrapolated to the whole country with caution. Sonographers can achieve acceptable and comparable diagnostic accuracy levels of MSD and CLR measurements with proper training and adherence to practice guidelines.

Cardiac Tuberculosis: A Case Series from Ethiopia, Italy, and Uganda and a Literature Review.

Extrapulmonary tuberculosis (TB) is estimated to account for up to 20% of active cases of TB disease, but its prevalence is difficult to ascertain because of the difficulty of diagnosis. Involvement of the heart is uncommon, with constrictive pericarditis being the most common cardiac manifestation. Diagnostic research for cardiac disease is frequently lacking, resulting in a high mortality rate. In addition to direct cardiac involvement, instances of cardiac events during antitubercular therapy are described. This case series describes five cases of TB affecting the heart (cardiac TB) from Italy and high-burden, low-income countries (Ethiopia and Uganda), including a case of Loeffler syndrome manifesting as myocarditis in a patient receiving antitubercular therapy. Our study emphasizes how cardiac TB, rare but important in high-burden areas, is a leading cause of pericardial effusion or pericarditis. Timely diagnosis and a comprehensive approach, including imaging and microbiological tools, are crucial. Implementing high-sensitivity methods and investigating alternative samples, such as detection of tuberculosis lipoarabinomannan or use of the GeneXpert assay with stool, is recommended in TB control programs.

Incidence and burden of long COVID in Africa: a systematic review and meta-analysis.

Long COVID, also known as "post-acute sequelae of COVID-19," affects at least 65 million individuals worldwide with a wide spectrum of symptoms that may last weeks, months, or permanently. Its epidemiology and burden in Africa are unclear. This meta-analysis examines long-term COVID-19 effects in the WHO African Region. A systematic search in several databases was carried out up to 12 February 2023 including observational studies from African countries reporting the cumulative incidence of long COVID signs and symptoms. Only studies conducted in African countries were included. Several sensitivity and meta-regression analyses were performed. Among 1547 papers initially screened, 25 were included, consisting of 29,213 participants. The incidence of any long COVID symptomatology was 48.6% (95% CI 37.4-59.8) as psychiatric conditions were the most frequent, particularly post-traumatic stress disorder reaching a cumulative incidence of 25% (95% CI 21.1-30.4). Higher age (p = 0.027) and hospitalization (p = 0.05) were associated with a higher frequency of long COVID. Long COVID poses a significant burden in Africa, particularly concerning psychiatric conditions. The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients. High-quality studies addressing this condition in African setting are urgently needed.

COVID Perceptions among Pregnant Women Living in a Malaria Hyperendemic Rural Region in Uganda: A Cross-Sectional Study.

Both SARS-CoV2 and Plasmodium falciparum infection during pregnancy increases the risk for adverse maternal and fetal outcomes, including abortion, severe disease, and death. Indeed, although malaria and COVID-19 show an overlapping clinical presentation, they require a profoundly different approach. The aim of this study was to explore COVID-19 awareness among pregnant women living in a P. falciparum hyperendemic region in rural Uganda. This cross-sectional, prospective study was conducted in one Hospital and two Health Centers (HC) in Lango region, Uganda, from July 14, 2022, to March 14, 2023. Data about demographics, COVID-19 history, and COVID-19 and malaria perceptions were collected using RedCap mobile app platform. Study endpoint was a context-specific COVID-19 awareness score, accounting for the most common disease misconceptions. Association between study variables and good COVID-19 awareness was assessed by χ2 and t test, as appropriate, and variables found to be statistically significant were further explored in multivariate logistic regression analysis. A total of 888 pregnant women were recruited. Median age was 24 (interquartile range: 20-29) years, whereas 79% (n = 704) attained only primary education and 66.6% (n = 591) were used in agriculture. SARS-CoV2 vaccination rate was 92%. In multivariate analysis (Table 3), variables associated with high COVID knowledge were presenting at antenatal care visit in Atipe HC (adjusted odds ratio [aOR]: 8.1, 95% CI: 4.1-16.48) having a previous good knowledge about malaria (aOR: 1.76, 95% CI: 1.21-2.56). Among pregnant women living in rural Uganda, COVID-19 awareness relies on the overall educational level, malaria knowledge and reference HC. Among pregnant women living in P. falciparum endemic areas, community-level malaria awareness might guide educational interventions during future pandemics.

Impact of the COVID-19 pandemic on malaria in pregnancy indicators in Northern Uganda: a joinpoint regression analysis.

BACKGROUND: Pregnancy is both a risk factor for P. falciparum infection and development of severe malaria. In low- and middle-income countries, the COVID-19 pandemic severely impacted health systems, including utilization of maternal services. This study aimed to assess trends in delivering malaria in pregnancy-related health-care services before and during COVID-19 in Northern Uganda. METHODS: An interrupted time-series study comparing pre-COVID-19 (January 2018 to April 2020) and COVID-19 (May to December 2021) periods, based on the date the first COVID case was detected. The study involved 30 health facilities in Northern Uganda with 22,650 estimated pregnancies per year, 14% of which took place in hospital. Monthly data were sourced from District routinely collected indicators. Trends were analyzed by joinpoint regression models. RESULTS: From the onset of the COVID pandemic in Uganda (May 2020), we found a significant reduction in the number of women accessing a fourth antenatal care visit (from APC + 183.5 to + 4.98; p < 0.001) and taking at least three doses of intermittent preventive treatment in pregnancy (IPTp, from APC + 84.28 to -63.12; p < 0.001). However, we found no significant change in the trend of the total number of pregnant women managed as outpatients or hospitalized for malaria, as well as in the number of women attending their first antenatal visit and in the number of institutional deliveries. CONCLUSIONS: In our study, the COVID-19 pandemic significantly reduced access to ANC visits and IPTp uptake. However, the healthcare system maintained its capacity for managing malaria cases, first antenatal visits, and institutional deliveries.Trial registration: This study has been registered on the ClinicalTrials.gov public website on 26 April 2022. ClinicalTrials.gov Identifier: NCT05348746.

Neurocysticercosis in Low- and Middle-Income Countries, a Diagnostic Challenge from Oyam District, Uganda.

BACKGROUND: In countries where Taenia solium is endemic, neurocysticercosis (NCC) is the leading identified cause of seizures, accounting for nearly 30% of all epilepsy cases and up to 2.8 million of Disability Adjusted Life Years. Diagnosis of this condition, however, is strictly reliant on either MRI or CT scan, which are poorly available in low- and middle-income countries (LMICs), creating challenges for proper case management and the acquisition of precise neuroepidemiologic data that may guide program and policy development. METHODS: Here, we report the case of a 73-year-old woman admitted in a rural hospital in Northern Uganda, who presented with seizures and a progressive inability to walk. She was then diagnosed with NCC after a brain CT scan. CONCLUSIONS: This case study represents a rare example of the detection of NCC in a rural district hospital, thus suggesting the potential feasibility of a CT-scan guided diagnostic approach in low resource settings.

Subacute Cardiac Tamponade Due to Tuberculous Pericarditis Diagnosed by Urine Lipoarabinomannan Assay in a Immunocompetent Patient in Oyam District, Uganda: A Case Report.

BACKGROUND: Uganda ranks among the countries with the highest burden of TB the world and tuberculous pericarditis (TBP) affects up to 2% of people diagnosed with pulmonary tuberculosis worldwide. In Africa, it represents the most common cause of pericardial disease. Here, we present the case of a 21-year-old male patient who was diagnosed of cardiac tamponade due to tuberculous pericarditis with a positive urine LF-LAM. CASE REPORT: We report a case of a 21-year-old male living in Oyam district, Uganda, who presented to the emergency department with difficulty in breathing, easy fatigability, general body weakness, and abdominal pain. A chest X-ray showed the presence of right pleural effusion and massive cardiomegaly. Thus, percutaneous pericardiocentesis was performed immediately and pericardial fluid resulted negative both for gram staining and real-time PCR test Xpert MTB/RIF. The following day's urine LF-LAM test resulted positive, and antitubercular therapy started with gradual improvement. During the follow-up visits, the patient remained asymptomatic, reporting good compliance to the antitubercular therapy. CONCLUSION: Our case highlights the potential usefulness of a LF-LAM-based diagnostic approach, suggesting that, in low-resource settings, this test might be used as part of routine diagnostic workup in patients with pericardial disease or suspected extra-pulmonary tuberculosis.

Back rubs or foot flicks for neonatal stimulation at birth in a low-resource setting: A randomized controlled trial.

BACKGROUND: Approximately 15% of infants require stimulation in low-resource settings, but data on effectiveness of different stimulation approaches are limited. We aimed to compare two recommended approaches of stimulation (back rubs vs. foot flicks) in reducing the need for face-mask ventilation in newly born infants who were not crying immediately after birth in a low-resource setting. METHODS: A single center, open-label, randomized, superiority trial was conducted at St. Kizito Hospital in Matany (Uganda) between November 2019 and May 2020. Newly born infants with expected birthweight > 1500 grams who were not crying immediately after birth were randomly assigned to stimulation using back rubs or foot flicks. The primary outcome measure was the success rate of the stimulation, defined as the achievement of an effective crying preventing the need for face-mask ventilation. RESULTS: Success of stimulation was achieved in 76/93 neonates (82%) using back rubs and 68/93 neonates (73%) using foot flicks (risk ratio 1.12, 95% confidence interval 0.96-1.31). No procedure-associated complications arose during the study. Time to first cry was not statistically different between the two arms (mean difference -11 seconds, 95% confidence interval -39 to 18). CONCLUSIONS: In newly born infants who were not crying immediately after birth, this trial did not provide a conclusive message in favor of back rubs or foot flicks. Nonetheless, we could not exclude a possible benefit of back rubs in avoiding the need for positive pressure ventilation and, possibly, further advanced resuscitative maneuvers. CLINICAL TRIALS REGISTRATION: clinicalTrial.gov: NCT04056091.

Capacity assessment for provision of quality sexual reproductive health and HIV-integrated services in Karamoja, Uganda.

INTRODUCTION: Sexual and reproductive health (SRH) and Human Immunodeficiency Virus (HIV) are crucial global health issues. Uganda continues to sustain a huge burden of HIV and AIDS. METHODS: A cross-sectional health facility-based assessment was performed in November and December 2016 in Karamoja Region, northern Uganda. All the 126 health facilities (HFs) in Karamoja, including 5 hospitals and 121 Health Centers (HCs), covering 51 sub-counties of the 7 districts were assessed. We assessed the capacity of a) leadership and governance, b) human resource, c) service delivery, d) SRH and HIV service integration and e) users satisfaction and perceptions. RESULTS: 64% of the established health staffing positions were filled leaving an absolute gap of 704 units in terms of human resources. As for service delivery capacity, on 5 domains assessed, the best performing was basic hygiene and safety measures in which 33% HCs scored "excellent", followed by the presence of basic equipment. The level of integration of SRH/HIV services was 55.56%. CONCLUSION: HFs in Karamoja have capacity gaps in a number of health system building blocks. Many of these gaps can be addressed through improved planning. To invest in improvements for these services would have a great gain for Uganda.

Quality of healthcare for children with severe acute malnutrition in a refugee setting: cross-sectional study in West Nile Region, Uganda.

OBJECTIVES: 5.0 million annual deaths in low-income and middle-income countries are due to poor quality of care (QOC). We evaluated the QOC provided to malnourished children in West Nile Region in Uganda. DESIGN: Cross-sectional study. SETTING: West Nile Region, an area hosting over one million refugees. PARTICIPANTS: Among 148 facilities providing nutritional services, 30 randomly selected facilities (20%) and the records of 1467 children with severe acute malnutrition (100% of those attending the 30 facilities during last year) were assessed. OUTCOMES: The national Nutrition Service Delivery Assessment (NSDA) tool was used to assess capacity areas related to QOC. Case management, data quality and health outcomes were assessed from official health records. Multivariate analysis was performed to explore factors significantly associated with better cure rates. RESULTS: Of 305 NSDA scores allocated to 30 participating centres, 201 (65.9%) were 'good' or 'excellent'. However, 20 (66.7%) facilities had 'poor' 'quality improvement mechanisms' and 13 (43.3%) had 'poor' 'human resources'. Overall data quality in official records was poor, while recorded quality of case management was overall fair. Average cure rate was significantly lower than international Sphere standards (50.4% vs 75% p<0.001) with a higher default rate (23.2% vs 15% p<0.001). Large heterogeneity among facilities was detected for all indicators. Refugee-hosting and non-refugee-hosting facilities had a similar cure rate (47.1% vs 52.1%) though transfer rates were higher for those hosting refugees (21.5% vs 1.9%, p<0.001) despite better 'equipment and supplies'. 'Good/excellent' 'equipment' and 'store management' were significantly associated with better cure rates in outpatient therapeutic centres (+55.9, p<0.001; +65.4, p=0.041, respectively) in multivariate analysis. CONCLUSIONS: Though most NSDA capacity areas were rated good or excellent, health outcomes of malnourished children in West Nile Region, both in refugee-hosting and non-refugee-hosting facilities, are significantly below international standards. Effective and sustainable approaches to improve malnourished child health outcomes are needed.