Sustained S-IgG and S-IgA antibodies to Moderna's mRNA-1273 vaccine in a Sub-Saharan African cohort suggests need for booster timing reconsiderations.

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 spike-directed 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. Discussion: In conclusion, the mRNA-1273 vaccine elicited robust and persistent S-IgG and S-IgA antibody responses, particularly after the first dose, indicating potential for long-term immunity. Prior viral exposure enhances post-vaccination S-IgA responses compared to naive individuals, which aligned with the prior-naïve, post-boost. The stable antibody levels observed post-booster dose, remaining high over an extended period, with no significant secondary rise, and no difference by baseline exposure, suggest that initial vaccination may sufficiently prime the immune system for prolonged protection in this population, allowing for potential to delay booster schedules as antibody responses remained high at the time of boosting. This finding calls for a reassessment of the booster dose scheduling in this demographic.

Sustained spike-specific IgG antibodies following CoronaVac (Sinovac) vaccination in sub-Saharan Africa, but increased breakthrough infections in baseline spike-naive individuals.

Introduction: This study investigated the antibody responses to the inactivated COVID-19 vaccine, CoronaVac (Sinovac Biotech) in the African population to provide valuable insights into long-term immunity and breakthrough infections against SARS-CoV-2 in individuals with varying prior IgG seropositivity. Methods: Real-life cohorts were used to longitudinally track antibody levels against the SARS-CoV-2 spike and nucleoprotein in 60 participants over 12 months to examine the levels of multiple antibody isotypes (S-IgG, S-IgM, S-IgA, N-IgG, and N-IgM). Results: Throughout the 12 months, we observed consistently high and stable seropositivity rates for spike-IgG antibodies, spike-IgM antibodies showed a decline in frequencies over time, and spike-IgA levels remained moderate and stable. Vaccinated individuals previously positive for spike-IgG antibodies demonstrated strong and persistent seropositivity, while those initially negative experienced a gradual and delayed increase in seropositivity rates. The fold change analysis of S- and N- antibody responses demonstrated a consistently stable and comparable profile over time, indicating that vaccine-induced antibody responses remain constant and lack significant fluctuations beyond the initial boost. The study emphasized that individuals lacking previous IgG positivity showed reduced vaccine-induced spike-IgG antibodies and were more susceptible to breakthrough infections, highlighting their higher vulnerability. All cases of breakthrough infections were asymptomatic, indicating the conferred protection to the vaccinated individuals. Discussion: The findings corroborated earlier studies on the effectiveness of the CoronaVac vaccine and emphasized the significance of accounting for pre-existing seropositivity in vaccine assessments. This study effectively demonstrated durable antibody responses against SARS-CoV-2 in the African population following the CoronaVac vaccination, providing crucial insights for informing vaccination strategies and safeguarding vulnerable populations. Continuous surveillance is imperative for tracking breakthrough infections and monitoring waning immunity. The insights gained offer crucial direction for public health strategies and enhance comprehension of vaccine effectiveness in sub-Saharan Africa. Further research should explore functional outcomes, cellular immune responses, and the vaccine's effectiveness against different variants to enhance our understanding and optimize vaccine strategies.

Spike protein is a key target for stronger and more persistent T-cell responses-a study of mild and asymptomatic SARS-CoV-2 infection.

OBJECTIVES: Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines and immunotherapies, yet remains poorly characterized. This longitudinal study examined the evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides in 109 asymptomatic or mildly symptomatic Ugandan COVID-19 patients across 365 days and explored their association with antibody generation. METHODS: T-cell responses to spike-containing clusters of differentiation (CD4)-S and CD8 nCoV-A (CD8-A) megapools, and the non-spike CD4-R and CD8 nCoV-B (CD8-B) megapools, were assessed and correlated with demographic and temporal variables. RESULTS: SARS-CoV-2-specific IFN-γ responses were consistently detected in all peptide pools and time points, with the spike-targeted response exhibiting higher potency and durability than the non-spike responses. Throughout the entire 365-day infection timeline, a robust positive correlation was observed between CD4 T-cell responses to the spike-derived peptides and anti-spike immunoglobulin G antibody levels, underscoring their interdependent dynamics in the immune response against SARS-CoV-2; in contrast, CD8 T-cell responses exhibited no such correlation, highlighting their distinctive, autonomous role in defense. No meaningful variations in complete blood count parameters were observed between individuals with COVID-19 infection and those without, indicating clinical insignificance. CONCLUSIONS: This study highlights the dominant role of spike-directed T-cell responses in mild and asymptomatic disease and provides crucial longitudinal data from Sub-Saharan African settings. The findings provide valuable insights into the dynamics of T-cell responses and their potential significance in developing effective strategies for combating COVID-19.

COVID-19 second wave and clinical characteristics of cases in Uganda: A retrospective cross-sectional survey of confirmed SARS-CoV-2 cases, March-June 2021.

We conducted a retrospective cross-sectional population-based survey among recovered COVID-19 cases in Uganda to establish the case presentations of the second wave SARS-CoV-2 infections. We interviewed 1,120 recovered COVID-19 cases from 10 selected districts in Uganda. We further conducted 38 key informant interviews with members of the COVID-19 District Taskforce and 19 in-depth interviews among COVID-19 survivors from March to June 2021. Among them, 62% were aged 39 years and below and 51.5% were female with 90.9% under home-based care management. Cases were more prevalent among businesspeople (25.9%), students (16.2%), farmers (16.1%), and health workers (12.4%). 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 asymptomatic, or under home-based care management (HBCM), working/operating/studying at schools, and not being vaccinated were among the major drivers of the second wave of the resurgence of COVID19 in Uganda. Managing future COVID-19 waves calls for proactive efforts for improving homebased care services, ensuring strict observation of SOPs in schools, and increasing the uptake of COVID-19 vaccination.

Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy.

Introduction: The 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. Methods: We 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. Results: Within 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 possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination. Discussion: Our results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.

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.

Optimisation and Validation of a conventional ELISA and cut-offs for detecting and quantifying anti-SARS-CoV-2 Spike, RBD, and Nucleoprotein IgG, IgM, and IgA antibodies in Uganda.

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 and 94.15%, respectively, and nucleoprotein sensitivity and specificity of 82.69 and 79.71%, ROC was chosen as the best method for determining cutoffs. Accuracy measurements were within the expected CV range of 25%. Serum and plasma OD values were highly correlated (r = 0.93, p=0.0001). ROC-derived cut-offs for S-, RBD-, and N-directed IgG, IgM, and IgA were 0.432, 0.356, 0.201 (S), 0.214, 0.350, 0.303 (RBD), and 0.395, 0.229, 0.188 (N). The sensitivity and specificity of the S-IgG cut-off were equivalent to the WHO 20/B770-02 S-IgG reference standard at 100% level. Spike negative IgG, IgM, and IgA ODs corresponded to median antibody concentrations of 1.49, 3.16, and 0 BAU/mL, respectively, consistent with WHO low titre estimates. Anti-spike IgG, IgM, and IgA cut-offs were equivalent to 18.94, 20.06, and 55.08 BAU/mL. For the first time, we provide validated parameters and cut-off criteria for the in-house detection of subclinical SARS-CoV-2 infection and vaccine-elicited binding antibodies in the context of Sub-Saharan Africa and populations with comparable risk factors.

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections.

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 during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1ß, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.

Long term trends and spatial distribution of animal bite injuries and deaths due to human rabies infection in Uganda, 2001-2015.

BACKGROUND: 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. METHODS: 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. RESULTS: A total of 208,720 cases of animal bite injuries were reported. Of these, 27% were in Central, 22% in Eastern, 27% in Northern and 23% in Western regions. Out of 48,720 animal bites between 2013 and 2015, 59% were suffered by males and 81% were persons aged above 5 years. Between 2001 and 2015, the overall incidence (per 100,000 population) of animal bites was 58 in Uganda, 76 in Northern, 58 in Central, 53 in Western and 50 in Eastern region. From 2001 to 2015, the annual incidence (per 100,000 population) increased from 21 to 47 (P = 0.02) in Central, 27 to 34 (P = 0.04) in Eastern, 23 to 70 (P = 0.01) in Northern and 16 to 46 (P = 0.001) in Western region. A total of 486 suspected human rabies deaths were reported, of which 29% were reported from Eastern, 28% from Central, 27% from Northern and 17% from Western region. CONCLUSION: Animal bite injuries, a potential exposure to rabies infection, and mortality attributed to rabies infection are public health challenges affecting all regions of Uganda. Eliminating rabies requires strengthening of rabies prevention and control strategies at all levels of the health sector. These strategies should utilize the "One Health" approach with strategic focus on strengthening rabies surveillance, controlling rabies in dogs and ensuring availability of post exposure prophylaxis at lower health facilities.

Risk Factors for Podoconiosis: Kamwenge District, Western Uganda, September 2015.

AbstractPodoconiosis, a noninfectious elephantiasis, is a disabling neglected tropical disease. In August 2015, an elephantiasis case-cluster was reported in Kamwenge District, western Uganda. We investigated to identify the disease's nature and risk factors. We defined a suspected podoconiosis case as onset in a Kamwenge resident of bilateral asymmetrical lower limb swelling lasting ≥ 1 month, plus ≥ 1 of the following associated symptoms: skin itching, burning sensation, plantar edema, lymph ooze, prominent skin markings, rigid toes, or mossy papillomata. A probable case was a suspected case with negative microfilaria antigen immunochromatographic card test (ruling out filarial elephantiasis). We conducted active case-finding. In a case-control investigation, we tested the hypothesis that the disease was caused by prolonged foot skin exposure to irritant soils, using 40 probable case-persons and 80 asymptomatic village control-persons, individually matched by age and sex. We collected soil samples to characterize irritants. We identified 52 suspected (including 40 probable) cases with onset from 1980 to 2015. Prevalence rates increased with age; annual incidence (by reported onset of disease) was stable over time at 2.9/100,000. We found that 93% (37/40) of cases and 68% (54/80) of controls never wore shoes at work (Mantel-Haenszel odds ratio [ORMH] = 7.7; 95% [confidence interval] CI = 2.0-30); 80% (32/40) of cases and 49% (39/80) of controls never wore shoes at home (ORMH = 5.2; 95% CI = 1.8-15); and 70% (27/39) of cases and 44% (35/79) of controls washed feet at day end (versus immediately after work) (OR = 11; 95% CI = 2.1-56). Soil samples were characterized as rich black-red volcanic clays. In conclusion, this reported elephantiasis is podoconiosis associated with prolonged foot exposure to volcanic soil. We recommended foot hygiene and universal use of protective shoes.

A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended beverages: Kampala, Uganda, January - June 2015.

BACKGROUND: On 6 February 2015, Kampala city authorities alerted the Ugandan Ministry of Health of a "strange disease" that killed one person and sickened dozens. We conducted an epidemiologic investigation to identify the nature of the disease, mode of transmission, and risk factors to inform timely and effective control measures. METHODS: We defined a suspected case as onset of fever (≥37.5 °C) for more than 3 days with abdominal pain, headache, negative malaria test or failed anti-malaria treatment, and at least 2 of the following: diarrhea, nausea or vomiting, constipation, fatigue. A probable case was defined as a suspected case with a positive TUBEX® TF test. A confirmed case had blood culture yielding Salmonella Typhi. We conducted a case-control study to compare exposures of 33 suspected case-patients and 78 controls, and tested water and juice samples. RESULTS: From 17 February-12 June, we identified 10,230 suspected, 1038 probable, and 51 confirmed cases. Approximately 22.58% (7/31) of case-patients and 2.56% (2/78) of controls drank water sold in small plastic bags (ORM-H = 8.90; 95%CI = 1.60-49.00); 54.54% (18/33) of case-patients and 19.23% (15/78) of controls consumed locally-made drinks (ORM-H = 4.60; 95%CI: 1.90-11.00). All isolates were susceptible to ciprofloxacin and ceftriaxone. Water and juice samples exhibited evidence of fecal contamination. CONCLUSION: Contaminated water and street-vended beverages were likely vehicles of this outbreak. At our recommendation authorities closed unsafe water sources and supplied safe water to affected areas.

Risk factors for Podoconiosis: Kamwenge District, Western Uganda, 2015

Introduction: Podoconiosis, a form of non-infectious elephantiasis, is a disabling Neglected Tropical Disease. In August 2015, a non-government organization reported an increase in elephantiasis cases in Kamwenge District. We conducted an investigation to confirm the diagnosis, identify causes and risk factors, and guide control efforts. Methods: we defined a suspect case-person as a Kamwenge resident with bilateral asymmetrical swelling of lower limbs lasting ≥ 1month, plus ≥ 1 of the following: skin itching; burning sensation; plantar oedema; lymph-ooze; prominent skin markings; rigid toes; mossy papillomata. A probable case was a suspect case with negative microfilaria antigen immunological-card test results. We conducted active case-finding in affected communities. In a case-control study we compared shoe-use and feet-washing practices before disease onset among 40 probable case-persons and 75 asymptomatic village control-persons, matched by age (± 5y) and sex. We collected soil samples to characterize soil-irritant composition. Results: our active case-finding identified 52 suspect cases in two affected sub-counties during 1980-2015 (incidence = 2.9/100,000/year), including 40 probable cases (mean age = 47y; range: 13-80y). The annual case counts did not increase significantly over time. All case-persons had negative immunological-card test. In the case-control study, 93% (37/40) of probable case-persons and 31% (23/75) of controls-persons never wore shoes at work (ORM-H = 6.7; 95%CI = 1.7-26); 80% (32/40) of probable case-persons and 55% (39/75) of control-persons never wore shoes at home (ORM-H = 4.4, 95%CI = 1.5-13); 70% (27/39) of probable case-persons and 47% (34/72) of control-persons washed feet at day-end rather than immediately after work (OR = 11, 95%CI = 2.1-57). Soils samples were characterized as being rich black-red volcanic clay. Conclusion: the reported elephantiasis was podoconiosis, which was associated with prolonged foot exposure to volcanic soil. We recommended health education on foot protection and washing, and universal use of protective shoes

Prevalence of hepatitis B and C and relationship to liver damage in HIV infected patients attending Joint Clinical Research Centre Clinic (JCRC), Kampala, Uganda.

BACKGROUND: Hepatitis B and C viruses cause death due to liver disease worldwide among Human Immunodeficiency Virus (HIV) positive individuals. Hepatitis B (HBV) and HIV have similar routes of transmission primarily; sexual, intravenous injections and prenatal while hepatitis C (HCV) is transmitted mainly through blood transfusion. Human immunodeficiency virus increases the pathological effect of hepatitis viruses and potentiates re-activation of latent hepatitis infections as a result of reduced immunity. The increase in use of antiretroviral (ARVs) drugs has led to longer period for patient survival and apparent increase in liver disease among HIV positive individuals. OBJECTIVE: This study aimed at determining the prevalence of HBV, HCV, their co-infection with HIV and their effect on liver cell function. METHOD: This was a cross sectional study conducted at the Joint Clinical Research Centre (JCRC) among HIV positive individuals attending the clinic. Patients were enrolled after obtaining a signed informed consent or assent for children below 17 years. Serum samples were collected for detection of Hepatitis B surface antigen (HBsAg), HCV specific antibodies and alanine aminotransferase (ALT) liver enzyme. RESULTS: Of the 89 patients enrolled, 20 (22.5%) had at least one hepatitis virus, 15 tested positive for HBsAg (16.9%) and 5 for HCV (5.6%), one had both viruses. Hepatitis B was more prevalent among women (13 out of 57, 22.8%) than men, (2 out of 32, 6.2%), while HCV was higher among men (4 out of 32, 12.5%) than women (1 out of 57, 1.8%). Seven of 89 patients (7.9%) had elevated ALT, indicative of liver cell injury. Of these with liver cell injury, one individual tested positive for HBsAg and another one individual tested positive for HCV specific antibodies. CONCLUSION: The prevalence of HBV is high in HIV positive individuals with more women commonly infected. The Prevalence of HCV is lower than that of HBV with more men commonly infected. Co-infection of Hepatitis B and C viruses was uncommon. This study reveals a high prevalence of liver cell injury among HIV positive individuals although the injury due to HBV or HCV infection was lower than that which has been documented. From this study, the high prevalence of HBV and HCV among HIV positive individuals point to a need for screening of HIV positive individuals for the hepatitis viruses.

The implementation of Integrated Disease Surveillance and Response in Uganda: a review of progress and challenges between 2001 and 2007.

BACKGROUND: In 2000 Uganda adopted the Integrated Disease Surveillance and Response (IDSR) strategy, which aims to create a co-ordinated approach to the collection, analysis, interpretation, use and dissemination of surveillance data for guiding decision making on public health actions. METHODS: We used a monitoring framework recommended by World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC)-Atlanta to evaluate performance of the IDSR core indicators at the national level from 2001 to 2007. To determine the performance of IDSR at district and health facility levels over a 5-year period, we compared the evaluation results of a 2004 surveillance survey with findings from a baseline assessment in 2000. We also examined national-level funding for IDSR implementation during 2000-07. RESULTS: Our findings show improvements in the performance of IDSR, including: (1) improved reporting at the district level (49% in 2001; 85% in 2007); (2) an increase and then decrease in timeliness of reporting from districts to central level; and (3) an increase in analysed data at the local level (from 10% to 47% analysing at least one target disease, P < 0.01). The case fatality rate (CFR) for two target priority diseases (cholera and meningococcal meningitis) decreased during IDSR implementation (cholera: from 7% to 2%; meningitis: from 16% to 4%), most likely due to improved outbreak response. A comparison before and after implementation showed increased funding for IDSR from government and development partners. However, funding support decreased ten-fold from the government budget of 2000/01 through to 2007/08. Per capita input for disease surveillance activities increased from US$0.0046 in 1996-99 to US$0.0215 in 2000-07. CONCLUSION: Implementation of IDSR was associated with improved surveillance and response efforts. However, decreased budgetary support from the government may be eroding these gains. Renewed efforts from government and other stakeholders are necessary to sustain and expand progress achieved through implementation of IDSR.

Prevalence and risk factors for zoonotic helminth infection among humans and animals - Jos, Nigeria, 2005-2009.

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, peri-urban dwellers and farmers. This calls for the formulation of workable collaboration between human and veterinary medical disciplines for better control of zoonotic helminth infections.

Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010-January 2011.

BACKGROUND: In November 2010, following reports of an outbreak of a fatal, febrile, hemorrhagic illness in northern Uganda, the Uganda Ministry of Health established multisector teams to respond to the outbreak. METHODS: This was a case-series investigation in which the response teams conducted epidemiological and laboratory investigations on suspect cases. The cases identified were line-listed and a data analysis was undertaken regularly to guide the outbreak response. RESULTS: Overall, 181 cases met the yellow fever (YF) suspected case definition; there were 45 deaths (case fatality rate 24.9%). Only 13 (7.5%) of the suspected YF cases were laboratory confirmed, and molecular sequencing revealed 92% homology to the YF virus strain Couma (Ethiopia), East African genotype. Suspected YF cases had fever (100%) and unexplained bleeding (97.8%), but jaundice was rare (11.6%). The overall attack rate was 13 cases/100000 population, and the attack rate was higher for males than females and increased with age. The index clusters were linked to economic activities undertaken by males around forests. CONCLUSIONS: This was the largest YF outbreak ever reported in Uganda. The wide geographical case dispersion as well as the male and older age preponderance suggests transmission during the outbreak was largely sylvatic and related to occupational activities around forests.

Land slide disaster in eastern Uganda: rapid assessment of water, sanitation and hygiene situation in Bulucheke camp, Bududa district.

BACKGROUND: On 1st March 2010, a major landslide occurred on Mt. Elgon in Eastern Uganda. This was triggered by heavy rains that lasted over three months. The landslide buried three villages in Bududa district, killing over 400 and displacing an estimate of 5,000 people. A comprehensive assessment of water, sanitation and hygiene was urgently needed to inform interventions by the Ministries of Health, and Relief, Disaster Preparedness and Refugees, Uganda. METHODS: This was a cross-sectional study where both qualitative and quantitative data were collected two weeks after the disaster. Quantitative interviews involved 397 heads of households and qualitative methods comprised of 27 Key Informant interviews, four focus group discussions and observations. The survey quantified water safety (collection, treatment, storage) and hygiene practices. This was supplemented and triangulated with qualitative data that focused on community perceptions and beliefs regarding water and sanitation needs and practices. Quantitative data was entered in Epi-Info Version 3.2.2 software and then exported to SPSS Version 12 for analysis. Summary statistics and proportions were generated and bi-variable analysis performed for selected variables. Associations were assessed using odds ratios at 95% confidence intervals. Qualitative data was analyzed using content analysis. RESULTS: Qualitative results showed that there were strong traditional beliefs governing water use and human excreta disposal. The use of river Manafwa water for household consumption was observed to potentially lead to disease outbreaks. Water from this river was reported tastier and the community culturally saw no need to boil drinking water. Latrines were few (23 for 5000 people), shallow, dirty (70% reported flies, 60% fecal littering), not separated by sex and had limited privacy and no light at night. This affected their use. Males were 3 times more likely to wash hands with soap after latrine use than females (OR = 3.584, 95%CI: 1.658-7.748). Of the 90% respondents who indicated that they always washed hands after latrine use, 76% said they used water and soap. Observations showed that water and soap were inconsistently available at the hand washing facilities. This situation influenced people's sanitation and hygiene behaviours. Nearly half (48%) indicated that at least a member of their household had fallen sick at least once since arrival at the camp. CONCLUSION: There was inadequate access to safe water in the camp. Pit-latrines were inadequate, poorly maintained and not user-friendly for most people. Responsible authorities should design means of increasing and sustaining access to safe water, increase sanitation facilities and continuously educate the public on the need to observe good hygiene practices.

The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening public health systems and building human resource capacity.

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 conducted more than 42 outbreaks investigations, 27analyses of surveillance data, evaluations of 11 surveillance systems, had28oral and poster presentation abstracts accepted at 10 scientific conferences and submitted 8 manuscripts of which 2are already published. The EFELTP has provided valuable opportunities to improve epidemiology and laboratory capacity building in Ethiopia. While the program is relatively young, positive and significant impacts are assisting the country better detect and respond to epidemics and address diseases of major public health significance.

Paradigm shift: contribution of field epidemiology training in advancing the "One Health" approach to strengthen disease surveillance and outbreak investigations in Africa.

The occurrence of major zoonotic disease outbreaks in Sub-Saharan Africa has had a significant impact on the already constrained public health systems. This has, as a result, justified the need to identify creative strategies to address threats from emerging and re-emerging infectious diseases at the human-animal-environmental interface, and implement robust multi-disease public health surveillance systems that will enhance early detection and response. Additionally, enhanced reporting and timely investigation of all suspected notifiable infectious disease threats within the health system is vital. Field epidemiology and laboratory training programs (FELTPs) have made significant contributions to public health systems for more than 10 years by producing highly skilled field epidemiologists. These epidemiologists have not only improved disease surveillance and response to outbreaks, but also improved management of health systems. Furthermore, the FETPs/FELTPs have laid an excellent foundation that brings clinicians, veterinarians, and environmental health professionals drawn from different governmental sectors, to work with a common purpose of disease control and prevention. The emergence of the One Health approach in the last decade has coincided with the present, paradigm, shift that calls for multi-sectoral and cross-sectoral collaboration towards disease surveillance, detection, reporting and timely response. The positive impact from the integration of FETP/FELTP and the One Health approach by selected programs in Africa has demonstrated the importance of multi-sectoral collaboration in addressing threats from infectious and non- infectious causes to man, animals and the environment.