Papers by Monica Musenero
Frontiers in immunology, Jan 31, 2024
Introduction: This study sought to elucidate the long-term antibody responses to the Moderna mRNA... more Introduction: This study sought to elucidate the long-term antibody responses to the Moderna mRNA-1273 COVID-19 vaccine within a Ugandan cohort, aiming to contribute to the sparse data on m-RNA vaccine immunogenicity in Sub-Saharan Africa. Methods: We tracked the development and persistence of the elicited antibodies in 19 participants aged 18 to 67, who received two doses of the mRNA-1273 vaccine. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibodies against the spike (S) and nucleoproteins (N). The study's temporal scope extended from the baseline to one year, capturing immediate and long-term immune responses. Statistical analyses were performed using the Wilcoxon test to evaluate changes in antibody levels across predetermined intervals with the Hochberg correction for multiple comparisons. Results: Our results showed a significant initial rise in spike-directed IgG (S-IgG) and spike-directed IgA (S-IgA) levels, which remained elevated for the duration of the study. The S-IgG concentrations peaked 14 days afterboosting, while spikedirected IgM (S-IgM) levels were transient, aligning with their early response role. Notably, post-booster antibody concentrations did not significantly change. Prior S-IgG status influenced the post-priming S-IgA dynamics, with baseline S-IgG positive individuals maintaining higher S-IgA responses, a difference that did not reach statistical difference post-boost. Three instances of breakthrough infections: two among participants who exhibited baseline seropositivity for S-IgG, and one in a participant initially seronegative for S-IgG.
Background This study examined the early response of individuals with mild and asymptomatic SARS-... more Background This study examined the early response of individuals with mild and asymptomatic SARS-CoV-2 infection by analysing cytokine, chemokine, and growth factor responses to CD4 and CD8 cell stimulation, aiming to understand early immune expressions that might inform potential targets for immunotherapy and interventions.Methods Between July and November 2020, we assessed 15 individuals, predominantly males with a median age of 25. Of these, eight displayed mild symptoms, while seven were asymptomatic. We evaluated their response to CD4 and CD8 T-cell stimulation by measuring 48 unique cytokines, chemokines, and growth factors. Random forest and principal component analysis (PCA) methods were utilized to identify pivotal cytokines and classify them according to their functional roles.Results Consistently low levels of specific cytokines suggested their minimal impact on immune activation processes, moderate concentrations of others after CD4 or CD8 T-cell stimulation, implied vit...
International Journal of Infectious Diseases
Frontiers in Immunology, Mar 16, 2023
Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBDdirected antibody response... more Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBDdirected 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 Sand 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 Frontiers in Immunology frontiersin.org 01
Epidemiology and Infection
We conducted a retrospective cross-sectional population-based survey among recovered COVID-19 cas... more We conducted a retrospective cross-sectional population-based survey among recovered COVID-19 cases to establish the case presentations of the 2 nd wave SARS-CoV-2 infections. We retrospectively interviewed 1120 recovered COVID-19 cases from 10 selected districts in Uganda. We further conducted 38 Key Informant Interviews of members of the COVID-19 District Taskforce and 19 indepth interviews among COVID-19 survivors from March to June 2021. Out of the 1,120 recovered COVID-19 cases interviewed, 62% were aged 39 years and below and 51.5% female with 90.9% under home based care management. Cases were more prevalent in business (25.9%), students (16.2%), farmers (16.1%) and health workers (12.4%) and 69.9% developed COVID-19 symptoms mainly cough, flu, and fever. Being asymptomatic was found to be associated with not seeking healthcare (APR 2, P <0.001). The mortality rate was 3.6% mostly among the elderly (6.3%) and 31.3% aged 40 years and above had comorbidities of high blood pressure, diabetes, and asthma. Being young, asymptomatic, under Home-Based Care Management (HBCM), working/operating/studying at schools, not being vaccinated were among the major drivers of the second wave of the resurgence of COVID-19 in Uganda. Managing future COVID-19 waves calls for proactive efforts for improving homebased care services, ensuring strict observation of SOPs in schools but increasing the uptake of COVID-19 vaccination. To continue protecting populations from emerging variants/strains of SARS-COV2, all stakeholders (Policy makers, health workers, non-government organizations, public and researchers) need to work together in ensuring vigilant surveillance services at community/home level and uptake of COVID-19 vaccinations.
Frontiers in Immunology
IntroductionThe duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan ... more IntroductionThe duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans.MethodsWe recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections.ResultsWithin two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p < 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals poss...
Frontiers in Immunology
There is an urgent need for better immunoassays to measure antibody responses as part of immune-s... more There is an urgent need for better immunoassays to measure antibody responses as part of immune-surveillance activities and to profile immunological responses to emerging SARS-CoV-2 variants. We optimised and validated an in-house conventional ELISA to identify and quantify SARS-CoV-2 spike- (S-), receptor binding domain- (RBD-), and nucleoprotein- (N-) directed IgG, IgM, and IgA binding antibodies in the Ugandan population and similar settings. Pre- and post-pandemic specimens were used to compare the utility of mean ± 2SD, mean ± 3SD, 4-fold above blanks, bootstrapping, and receiver operating characteristic (ROC) analyses in determining optimal cut-off optical densities at 450 nm (OD) for discriminating between antibody positives and negatives. “Limits of detection” (LOD) and “limits of quantitation” (LOQ) were validated alongside the assay’s uniformity, accuracy, inter-assay and inter-operator precision, and parallelism. With spike-directed sensitivity and specificity of 95.33 an...
The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-... more The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-year competency-based training and service program designed to build sustainable public health expertise and capacity. Established in 2009, the program is a partnership between the Ethiopian Federal Ministry of Health, the Ethiopian Health and Nutrition Research Institute, Addis Ababa University School of Public Health, the Ethiopian Public Health Association and the US Centers of Disease Control and Prevention. Residents of the program spend about 25% of their time undergoing didactic training and the 75% in the field working at program field bases established with the MOH and Regional Health Bureaus investigating disease outbreaks, improving disease surveillance, responding to public health emergencies, using health data to make recommendations and undertaking other field Epidemiology related activities on setting health policy. Residents from the first 2 cohorts of the program have co...
The Pan African medical journal, Dec 5, 2012
Background: Zoonotic infections are among the most common on earth and are responsible for over 6... more Background: Zoonotic infections are among the most common on earth and are responsible for over 60% of human infectious diseases, some of which are caused by helminth parasites. Infection may result from ingestion of infective stage of worms with food, contaminated soil; skin penetration or direct animal contact. This study estimates the prevalence of zoonotic helminth infections (ZHI) among animals and humans in Jos and identifies associated risk factors. Methods: We reviewed laboratory records from five hospitals, one veterinary clinic and meat inspection record at abattoir in Jos from 2005-2009. Prevalence was defined as the observed frequency of cases of zoonotic helminth in the sampled population within the study period. Odd ratio analysis was used to identify factors associated with ZHI. Results: Of 6689 humans tested, 524 (7.8%) were positive. Observed ZHI are: Ascaris species (4.5%), Taeniasis-Cysticercosis (1.5%), Schistosoma species (1.1%), Strongyloidosis (0.09%). Among animals, 3520 (18.1%) of 19508 tested/observed were positive; including Fasciola species (12.7%), Taeniasis-Cysticercosis (5.0%), Strongyloidosis (0.4%), Ascaris species (0.04%). The risk of infection was higher among humans aged 6-19 (OR: 3.2; 95% CI: 2.0-5.2) and 20-60 (OR: 2.3; 95% CI: 1.7-3.9). Peri-urban dwellers are at higher risk (OR: 1.5; 95% CI: 1.3-1.9); and so are farmers. Conclusion: The prevalence of zoonotic helminth infection is high among humans and animals in Jos. Risk of infection are higher among human age 6-60, periurban dwellers and farmers. This calls for the formulation of workable collaboration between human and veterinary medical disciplines for better control of zoonotic helminth infections.
The questionnaire that was used in the collection of information from cases and controls is avail... more The questionnaire that was used in the collection of information from cases and controls is available as a supplementary file called Typhoid questionnaire. It provides details on which questions were asked about food and water exposures. (DOC 87 kb)
BackgroundThe COVID-19 continued to pose several public health, social, economic challenges and t... more BackgroundThe COVID-19 continued to pose several public health, social, economic challenges and the drivers for the occurrence of different COVID-19 waves remains undocumented in Uganda. We conducted a cross-sectional population-based survey among recovered COVID-19 cases to establish the drivers of SAR-CoV-2 infections. We performed a retrospective study and interviewed 1120 recovered COVID-19 cases from 10 selected districts in Uganda. We further conducted 38 Key Informant Interviews of members of the COVID-19 District Taskforce and 19 in-depth interviews among COVID-19 survivors from March to June, 2021. Results Out of the 1120 recovered COVID-19 cases interviewed, 62% were aged 39 years and below and 51.5% females with 90.9% under home based care management. Cases were more prevalent in business (25.9%), students (17.2%), farmers (17.1%) and health workers (12.4%) and 79.9% developed COVID-19 symptoms mainly cough, flu, and fever. Being asymptomatic was found to be associated wi...
Background: Zoonotic infections are among the most common on earth and are responsible for over 6... more Background: Zoonotic infections are among the most common on earth and are responsible for over 60 % of human infectious diseases, some of which are caused by helminth parasites. Infection may result from ingestion of infective stage of worms with food, contaminated soil; skin penetration or direct animal contact. This study estimates the prevalence of zoonotic helminth infections (ZHI) among animals and humans in Jos and identifies associated risk factors. Methods: We reviewed laboratory records from five hospitals, one veterinary clinic and meat inspection record at abattoir in Jos from 2005- 2009. Prevalence was defined as the observed frequency of cases of zoonotic helminth in the sampled population within the study period. Odd ratio analysis was used to identify factors associated with ZHI. Results: Of 6689 humans tested, 524
Paradigm shift: contribution of field epidemiology training in advancing the “One
This article is published as part of the supplement "Field Epidemiology in Africa". Sup... more This article is published as part of the supplement "Field Epidemiology in Africa". Supplement sponsored by PAMJ and The African Field
Life, 2021
Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic... more Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed d...
Pan African Medical Journal Conference Proceedings, 2018
Introduction : bacterial infections cause 20% of hospital deaths and 25% of under-five mortality ... more Introduction : bacterial infections cause 20% of hospital deaths and 25% of under-five mortality in Uganda. We analyzed laboratory data on antibiotic resistance (ABR) patterns in Kampala, Uganda, to inform interventions to reduce ABR. Methods : we abstracted culture and sensitivity data from 10 laboratory registers for all blood specimens cultured from 2010-2015 using a standardized data abstraction form. We defined high ABR as ≥50% of species resistant to a drug in a year; moderate ABR as 10-49% resistant; low as Results : among gram-positive species, Staphylococcus accounted for 86% (1541/1794) of the infections; under-five (incidence = 218/100,000) and elderly (incidence = 125/100,000) age-groups were most affected. Of gram-negative species, Salmonella accounted for 21% (251/1193) of the infections; the age-specific incidence (/100,000) ranged from 7 (young adults age-group) to 17(under-fives). Non-specified coliforms were identified in 28% of the isolates. 11% of the Staphylococcal species had moderate ABR and 89% had high ABR to commonly used antibiotics (CAF, CTX, Erythromycin, Tetracycline). Over the six-year study period, MRSA increased from 44% to 81% (p=0.03, Chi-square for trends); among Salmonella species, ABR to first-line antibiotics reduced from high to moderate levels; MDR Salmonella ranged from 0-20%; intermediate resistance levels to Ciprofloxacin increased from 2% to 39% (p Conclusion : salmonella and staphylococcus were the most common causes of septicaemia. MRSA was at a high level, with rapidly increasing ABR to Ciprofloxacin and Ceftriaxone. Susceptibility to first-line antibiotics among Salmonella species gradually returned. We recommend adherence to ABR testing standards and rational use of antibiotics guided by ABR patterns to prevent ABR.
PloS one, 2018
In the absence of accurate data on trends and the burden of human rabies infection in developing ... more In the absence of accurate data on trends and the burden of human rabies infection in developing countries, animal bite injuries provide useful information to bridge that gap. Rabies is one of the most deadly infectious diseases, with a case fatality rate approaching 100%. Despite availability of effective prevention and control strategies, rabies still kills 50,000 to 60,000 people worldwide annually, the majority of whom are in the developing world. We describe trends and geographical distribution of animal bite injuries (a proxy of potential exposure to rabies) and deaths due to suspected human rabies in Uganda from 2001 to 2015. We used 2001-2015 surveillance data on suspected animal bite injuries, collected from health facilities in Uganda. To describe annual trends, line graphs were used and linear regression tested significance of observed trends at P<0.05. We used maps to describe geographical distribution of animal bites by district. A total of 208,720 cases of animal bi...
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Papers by Monica Musenero