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Background: Poliovirus importations and related outbreaks occurred in the Horn of Africa (HoA) following an initial outbreak, which started in Somalia, spread into Kenya within ten days and later into Ethiopia and gradually to other countries in the region. National preparedness plans for responding to poliovirus introduction were insufficient in many countries of the Region. We describe a series of polio outbreak simulation exercises that were implemented to formally test polio outbreak preparedness plans in the HoA countries, as a step to interrupting further transmission., Methods: The Polio Outbreak Simulation Exercises (POSEs) were designed and implemented. The results were evaluated and recommendations made. The roles of outbreak simulation exercises in maintaining regional polio-free status were assessed. In addition, we performed a comprehensive review of the national plans of all for seven countries in the HoA Region., Results: Seven simulation exercises, delivered between 2016 and 2017 revealed that participating countries were generally prepared for poliovirus introduction, but the level of preparedness needed improvement. The areas in particular need of strengthening were national preparedness plans, initial response, plans for securing vaccine supply, and communications., Conclusions: Polio outbreak simulation exercises can be valuable tools to help maintain polio-free status and should be extended to other high-risk countries and subnational areas in the HoA Region and elsewhere. There is also need to standardize the process and methods for conducting POSE for comparability.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: the August 2018 ebola outbreak in the Democratic Republic of Congo turns out to be second largest outbreak of ebola in public health history. The response to the outbreak which would have halted wider spread to neighboring countries failed. Hence, high risk districts in Uganda initiated preparedness activities in the wake of a possible inflow of cases. This study was therefore designed to identify, describe and assess surveillance activities and preparedness in the Kasese, Ntoroko and Bundibugyo districts of Uganda., Methods: the study employed the mixed method approach. The qualitative arm involved the use of participant observation to describe surveillance activities that were carried out as part of the ebola preparedness surveillance in the high-risk districts. The quantitative arm included assessment of 102 health facilities on ebola virus disease preparedness with a WHO standard checklist hosted on the Open Data Kit software. Descriptive statistics were performed using STATA (version 14)., Results: the study showed that high risk districts employed numerous interlocking public health emergency activities which included readiness assessment, risk mapping and temperature-based screening for ebola at points of entry. Most health workers (91.18%) could correctly state the case definition of ebola although only 56.86% of them were trained on ebola surveillance., Conclusion: health worker knowledge on ebola virus disease case definition was high but training and logistics were inadequate. Continuous efforts are required to sustain health workers knowledge on ebola surveillance through trainings and supportive supervision whiles addressing gaps in the operation of ebola screening posts., Competing Interests: The authors declare no competing interests., (Copyright: Emmanuel Angmorteh Mensah et al.)

Background: HIV-associated neurocognitive disorders remain prevalent despite effective antiretroviral therapy (ART), but there are limited longitudinal data on people living with HIV (PLWH) in sub-Saharan Africa. We examined neuropsychological (NP) performance in PLWH in a longitudinal study in Uganda., Methods: Participants enrolled through the Rakai Community Cohort Study (400 ART-naive PLWH and 400 matched HIV-negative persons) were administered NP assessments. In 2017, PLWH who had initiated ART underwent a 2-year follow-up assessment. Demographically adjusted Z-scores for each NP test were established using data from the HIV- controls. Multivariable linear and logistic regressions were conducted to examine group differences in NP performance. Mixed-effects regressions were conducted to examine ART-related changes in NP outcomes., Results: Of 333 PLWH who returned for their 2-year follow-up visit, 312 (94%) had initiated ART. Those on ART had a mean age of 35.6 years (SD ± 8.5 years) and mean education of 5.4 years (SD ± 3.3 years); 49% were women. ART-associated NP improvements occurred in verbal learning and memory (P's < 0.05), motor (P's < 0.01), and some measures of processing speed (P = 0.002), whereas there were declines in attention/working memory (P's < 0.001) and semantic fluency (P < 0.001). Pre-ART CD4 count and efavirenz use were associated with a more impaired change in NP performance., Conclusions: PLWH in this resource-limited setting showed improved neurocognitive performance on most NP tests after ART initiation. However, the declines in attention/working memory and fluency performance, as well as relationship to efavirenz, warrant further study.

Background: Control of Rubella and Congenital Rubella Syndrome using vaccination has shown great success in the America's. Uganda is due to introduce the Rubella vaccine however the magnitude of transmission is not well documented. Therefore this study was done to determine IgM sero-prevalance for Rubella in order to help monitor vaccine effectiveness post introduction of the vaccine in routine vaccination programme., Methods: A retrospective review of suspected measles cases data for the reporting period January 2007 to December 2016 in Uganda was Done. rubella IgM testing was done on 15,296 of the cases and the data was analyzed using STATA version 13., Results: In total 15,296 cases were tested and 4255 (27.8%) tested positive and among females aged 15-49 years 88 out of 322 (27%) tested positive. The age distribution range was 0-80 years, rubella IgM positivity was reported in all the 15 regions of Uganda and throughout the ten year period in every month. Age group 5-15 years had OR 2.5 p-value < 0.001 of being rubella IgM positive compared to age < 5 years and testing measles IgM negative OR 6.3 p-value < 0.001., Conclusion: Rubella is endemic in Uganda and although rubella IgM positivity is highest in the age 5-15 years even the younger, older and women of reprodutive age are affected. This means the risk of Congenital Rubella Syndrome is high hence the need to introduce the rubella vaccine for infants and pregnant mothers and continued surveillance to enhance its control.

Background: We assessed the utility of the International HIV Dementia Scale (IHDS) in detecting HIV-associated neurocognitive disorder (HAND) in Uganda in antiretroviral (ART)-naïve and ART-experienced adults., Setting: A longitudinal observational cohort study in Rakai, Uganda., Methods: Three hundred ninety-nine HIV+ ART-naïve adults underwent neurological, functional status, and neuropsychological assessments including the IHDS. Three hundred twelve participants who initiated ART were re-evaluated after 2 years. HAND stages [asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia (HAD)] were determined based on Frascati criteria using local normative data. Sensitivity, specificity, and area under the ROC curve were determined for various IHDS thresholds (≤9, ≤ 9.5, and ≤10)., Results: At baseline, the participants' mean age was 35 years (SD ± 8), 53% were men, and 84% had less than a high school education. At baseline, sensitivity for detecting any HAND stage, symptomatic HAND [mild neurocognitive disorder, HAD], and HAD alone were maximized at IHDS ≤10 (81%, 83%, 92%, respectively). Among 312 individuals who returned for the 2-year follow-up and had initiated ART, a score of ≤10 provided a lower or equal sensitivity for detecting different stages of HAND (all HAND: 70%; symptomatic HAND: 75%; HAD: 94%). The area under the ROC curve was higher for ART-experienced versus ART-naïve individuals., Conclusions: The IHDS is a potentially useful screening tool for neurocognitive impairment in rural Uganda for both ART-naïve and ART-experienced adults. A cutoff ≤10 demonstrates higher sensitivity for more severe HAND stages compared with less severe HAND. Future studies should focus on potential modifications to the IHDS to improve its specificity.

Background: High-quality vaccination data are critical to planning, implementation and evaluation of immunization programs. However, sub-optimal administrative vaccination data quality in low- and middle-income countries persist for heterogeneous reasons, though most relate to organizational factors and human behavior. The nationwide Data Improvement Team (DIT) strategy in Uganda aimed to strengthen human resource capacity to generate quality administrative vaccination data at the health facility., Methods: A financial cost analysis of the Uganda DIT strategy (2014-2016) was conducted from the program funder perspective. Activity-based micro-costing from funder financial and program monitoring records was used to estimate total and unit costs by program area (in 2016 US dollars). Hypothetical scenarios were developed to illustrate potential approaches to reducing costs., Results: Over 25 months the DIT strategy was implemented in all 116 operational districts and 3443 (89%) health facilities in Uganda at a total financial cost of US $575 275. Training and deployment of DITs accounted for the highest proportion of expenditure across program areas (69%). Transport, per diems, lodging, and honoraria for DIT members and national supervisors were the main cost drivers of the strategy. Deployment of 557 DIT members cost US $839 per DIT member, US $4 030 per district, and US $136 per health facility. The estimated opportunity cost of government staff time wasn't a major cost driver (2.5%) of total cost., Conclusion: The results provide the first estimates of the magnitude and drivers of cost to implement a national workforce capacity building strategy to improve administrative vaccination data quality in a low- or middle-income country. Financial costs are a critical input to combine with future outcome data to describe the cost of strategies relative to performance outcomes. The operational costs of the strategy were modest (0.5-1.6%) relative to the estimated operational costs of Uganda's national immunization program., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AEH has received grant support from GlaxoSmithKline for investigator-driven research unrelated to the work presented in this manuscript. All other authors have no competing interests to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Serum interleukin-6 (IL-6) and D-dimer have been associated with multiple adverse outcomes in HIV-infected (HIV+) individuals, but their association with neuropsychiatric outcomes, including HIV-associated neurocognitive disorder (HAND) and depression, headaches, and peripheral neuropathy have not been investigated. Three hundred ninety-nine HIV+ antiretroviral therapy (ART)-naïve adults in Rakai, Uganda, were enrolled in a longitudinal cohort study and completed a neurological evaluation, neurocognitive assessment, and venous blood draw. Half of the participants had advanced immunosuppression (CD4 count < 200 cells/μL), and half had moderate immunosuppression (CD4 count 350-500 cells/μL). All-cause mortality was determined by verbal autopsy within 2 years. HAND was determined using Frascati criteria, and depression was defined by the Center for Epidemiologic Studies-Depression (CES-D) scale. Neuropathy was defined as the presence of > 1 neuropathy symptom and > 1 neuropathy sign. Headaches were identified by self-report. Serum D-dimer levels were determined using ELISA and IL-6 levels using singleplex assays. Participants were 53% male, mean age 35 + 8 years, and mean education 5 + 3 years. Participants with advanced immunosuppression had significantly higher levels of IL-6 (p < 0.001) and a trend toward higher D-dimer levels (p = 0.06). IL-6 was higher among participants with HAND (p = 0.01), with depression (p = 0.03) and among those who died within 2 years (p = 0.001) but not those with neuropathy or headaches. D-dimer did not vary significantly by any outcome. Systemic inflammation as measured by serum IL-6 is associated with an increased risk of advanced immunosuppression, all-cause mortality, HAND, and depression but not neuropathy or headaches among ART-naïve HIV+ adults in rural Uganda.

Considerable heterogeneity exists in patterns of neurocognitive change in people with HIV (PWH). We examined heterogeneity in neurocognitive change trajectories from HIV diagnosis to 1-2 years post-antiretroviral therapy (ART). In an observational cohort study in Rakai, Uganda, 312 PWH completed a neuropsychological (NP) test battery at two-time points (ART-naïve, 1-2 years post-ART initiation). All NP outcomes were used in a latent profile analysis to identify subgroups of PWH with similar ART-related neurocognitive change profiles. In a subset, we examined subgroup differences pre-ART on cytokine and neurodegenerative biomarkers CSF levels. We identified four ART-related change subgroups: (1) decline-only (learning, memory, fluency, processing speed, and attention measures), (2) mixed (improvements in learning and memory but declines in attention and executive function measures), (3) no-change, or (4) improvement-only (learning, memory, and attention measures). ART-related NP outcomes that are most likely to change included learning, memory, and attention. Motor function measures were unchanged. Subgroups differed on eight of 34 pre-ART biomarker levels including interleukin (IL)-1β, IL-6, IL-13, interferon-γ, macrophage inflammatory protein-1β, matrix metalloproteinase (MMP)-3, MMP-10, and platelet-derived growth factor-AA. The improvement-only and mixed subgroups showed lower levels on these markers versus the no-change subgroup. These findings provide support for the need to disentangle heterogeneity in ART-related neurocognitive changes, to focus on higher-order cognitive processes (learning, memory, attention) as they were most malleable to change, and to better understand why motor function remained unchanged despite ART treatment. Group differences in pre-ART CSF levels provide preliminary evidence of biological plausibility of neurocognitive phenotyping.

Background: Combination antiretroviral therapy (ART) improves HIV-associated neurocognitive disorder (HAND) stage in the United States where subtype B predominates, but the effect of ART and subtype on HAND stage in individuals in Uganda with subtypes D and A is largely unknown., Setting: A community-based cohort of participants residing in Rakai, Uganda., Methods: Three hundred ninety-nine initially ART-naive HIV-seropositive (HIV+) individuals were followed up over 2 years. Neurological and neuropsychological tests and functional assessments were used to determine HAND stage. Frequency and predictors of HAND and HIV-associated dementia (HAD) were assessed at baseline and at follow-up after ART initiation in 312 HIV+ individuals. HIV subtype was determined from gag and env sequences., Results: At 2-year follow-up, HAD frequency among HIV+ individuals on ART (n = 312) decreased from 13% to 5% (P < 0.001), but the overall frequency of HAND remained unchanged (56%-51%). Subtype D was associated with higher rates of impaired cognition (global deficit score ≥ 0.5) compared with HIV+ individuals with subtype A (55% vs. 24%) (P = 0.008). Factors associated with HAD at baseline were older age, depression, and plasma HIV viral load >100,000 copies/mL. At follow-up, age and depression remained significantly associated with HAD., Conclusions: HIV+ individuals on ART in rural Uganda had a significant decrease in the frequency of HAD, but HAND persists after 2 years on ART. The current guideline of immediate ART initiation after HIV diagnosis is likely to greatly reduce HAD in sub-Saharan Africa. Further studies of the effect of HIV subtype and neurocognitive performance are warranted.

Ear infections in the United Kingdom were reported at a prevalence of 90% in children aged 0-6 years peaking at six years, the commonest age for Ugandan children to start primary school. This study was done to determine prevalence of ear infections in primary one children in Mbarara district, identify commonest ear infections, the causative pathogens isolated and their antibiograms and comparing the prevalence of ear infection in urban and rural schools. A cross sectional study was carried out among three urban day schools and three rural day schools randomly chosen in Mbarara district. History was taken using a data collection form and examinations were done using an otoscope. All pus swabs from infected ears were inoculated on Blood agar, Chocolate agar, MacConkey Agar plates before smears for Gram staining were made. Identification of the pathogen was through biochemical tests and API system. Sensitivity tests to antibiotics were set on Mueller Hinton Agar using the disc diffusion technique of Kirby-Bauer. Otoscopy was done on 600 children, 8.0 %( 48) showed signs of ear infections. The commonest ear infection was otitis externa. Staphylococcus aureus species showed the highest prevalence with 75% (6). Staphylococcus aureus species showed 100% sensitivity to gentamicin, 80% sensitivity to ciproflaxin. Serratia marcencens also showed 100% sensitivity to ciproflaxin, The prevalence of ear infection was 8.0% among children in primary one in Mbarara district in a cross sectional study.

A retrospective study to identify VAPP cases from the entire Uganda was conducted between January 2003 and December 2011. Eleven of the 106 AFP cases were VAPPs. The VAPP rate ranged from 0 to 3.39 cases per 1,000,000 birth cohorts and the peak was in 2009 when there was scaling up of OPV immunization activities following an importation of wild poliovirus in the country. All the subsequent polio suspect cases since then have been vaccine-associated polio cases. Our data support the strategy to withdraw OPV and introduce IPV progressively in order to mitigate against the paralysis arising from Sabin polioviruses., (© 2015 Wiley Periodicals, Inc.)

We determined impact and cost-effectiveness of pneumococcal and rotavirus vaccination programs among children<5 years of age in Uganda from the public health system perspective. Disease-specific models compared the disease burden and cost with and without a vaccination program. If introduced, pneumococcal and rotavirus vaccine programs will save 10,796 and 5265 lives, respectively, prevent 94,071 Streptococcus pneumoniae and 94,729 rotavirus cases in children<5 years, and save 3886 and 996 million Ugandan shillings ($2.3 and $0.6 million US dollars), respectively, in direct medical costs annually. At the GAVI price ($0.15/dose), pneumococcal vaccine will be cost-saving and rotavirus vaccine highly cost-effective., (Published by Elsevier Ltd.)

In a region with high rates of mortality among children aged <5 years, the underfunded health care systems of sub-Saharan Africa have few resources available to perform surveillance activities that can help determine the causes of morbidity and mortality in the region. At present, there are few examples of attempts to promote public health care surveillance that might inform current debates about how to expand and improve surveillance, particularly for bacterial diseases. Driven by this gap in knowledge, we attempted to explore the successes and failures of the Network for Surveillance of Pneumococcal Disease in the East African Region and to share the experiences of what are essentially nonresearch public-sector hospitals in East Africa, with the hopes that surveillance systems for other diseases, especially those that require complex diagnostic support, may be informed by these experiences. The state of services essential for surveillance and the measures taken to overcome any shortcomings are described, as is the progress made in improving clinical diagnosis, laboratory processing, and data management. For surveillance to play a role in public health care, ministries of health and associated institutions must own and push forward the surveillance agenda, with support from global partners, and take advantage of the developments that have been achieved within the institutions.

Affordable pneumococcal conjugate vaccines will soon become available to developing countries through the Global Alliance for Vaccines and Immunization. Data on Streptococcus pneumoniae meningitis epidemiology in Uganda will assist decision makers in determining the best national vaccine policy. We reviewed acute bacterial meningitis surveillance data for children aged <5 years from 3 sentinel surveillance sites in 3 Ugandan districts collected from 2001 through 2006. Serotype and antibiotic-resistance testing were performed on pneumococcal isolates collected from 2005 through 2006 from the Kampala district in the tropical central region of Uganda. Minimum pneumococcal meningitis incidence estimates were calculated for a portion of the Kampala district and all of the Gulu district, where case ascertainment was more complete. At the 3 sites, 14,388 probable acute bacterial meningitis cases were observed. The most common cause identified was S. pneumoniae (n = 331; 35% of all confirmed cases), which had an overall case fatality ratio of 19%. Yearly pneumococcal meningitis incidence was 3-20 cases per 100,000 population in Kampala versus 28-42 cases per 100,000 population in Gulu. The most commonly identified serotypes were 6A/6B (40%); 43% of isolates were serotypes that are in the available 7-valent pneumococcal conjugate vaccine and 70% are in the proposed 13-valent pneumococcal vaccine. Twenty-five isolates (83%) had intermediate resistance to penicillin but none were fully resistant. Pneumococcal meningitis is common and severe in Uganda, indicating a role for the pneumococcal conjugate vaccine.

Objective: To guide immunization policy, we determined the public health benefit of introducing Haemophilus influenzae type b (Hib) vaccine in Uganda and estimated the vaccine effectiveness., Methods: Surveillance data for acute bacterial meningitis among children aged 0-59 months were reviewed from three hospital sentinel sites, for July 2001 to June 2007, to determine the incidence of Hib meningitis, the effectiveness of Hib vaccine with a case-control design, and the number of vaccine-preventable cases and deaths of Hib disease in Uganda., Findings: Of the 13 978 children from 17 districts with suspected bacterial meningitis, 269 had confirmed Hib meningitis, declining from 69 patients in the prevaccine year (2001-2002) to three in 2006-2007. Hib meningitis incidence dropped from 88 cases per 100,000 children aged < 5 years in the year before vaccine introduction to 13 within 4 years, and to near zero in the fifth year. Vaccine effectiveness for 2 or more doses was 93% (95% confidence interval, CI: 69-99) against confirmed Hib meningitis and 53% (95% CI: 11-68) against purulent meningitis of unknown cause. In Uganda, Hib vaccine prevents an estimated 28 000 cases of pneumonia and meningitis, 5000 deaths and 1000 severe meningitis sequelae each year., Conclusion: Infant immunization with Hib vaccine has virtually eliminated Hib meningitis in Uganda within 5 years. Ensuring long-term benefits of Hib vaccine urgently requires sustainable vaccine financing, high-quality ongoing surveillance, and a health sector able to deliver a robust immunization programme.