Virological failure on first-line antiretroviral therapy; associated factors and a pragmatic approach for switching to second line therapy-evidence from a prospective cohort study in rural South-Western Uganda, 2004-2011.

INTRODUCTION: We investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART. METHODS: Between 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models. RESULTS: The 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06). CONCLUSION: A pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended

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

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies

Marburg virus disease outbreak in Kween District Uganda, 2017: Epidemiological and laboratory findings.

INTRODUCTION: In October 2017, a blood sample from a resident of Kween District, Eastern Uganda, tested positive for Marburg virus. Within 24 hour of confirmation, a rapid outbreak response was initiated. Here, we present results of epidemiological and laboratory investigations. METHODS: A district task force was activated consisting of specialised teams to conduct case finding, case management and isolation, contact listing and follow up, sample collection and testing, and community engagement. An ecological investigation was also carried out to identify the potential source of infection. Virus isolation and Next Generation sequencing were performed to identify the strain of Marburg virus. RESULTS: Seventy individuals (34 MVD suspected cases and 36 close contacts of confirmed cases) were epidemiologically investigated, with blood samples tested for MVD. Only four cases met the MVD case definition; one was categorized as a probable case while the other three were confirmed cases. A total of 299 contacts were identified; during follow- up, two were confirmed as MVD. Of the four confirmed and probable MVD cases, three died, yielding a case fatality rate of 75%. All four cases belonged to a single family and 50% (2/4) of the MVD cases were female. All confirmed cases had clinical symptoms of fever, vomiting, abdominal pain and bleeding from body orifices. Viral sequences indicated that the Marburg virus strain responsible for this outbreak was closely related to virus strains previously shown to be circulating in Uganda. CONCLUSION: This outbreak of MVD occurred as a family cluster with no additional transmission outside of the four related cases. Rapid case detection, prompt laboratory testing at the Uganda National VHF Reference Laboratory and presence of pre-trained, well-prepared national and district rapid response teams facilitated the containment and control of this outbreak within one month, preventing nationwide and global transmission of the disease

The contribution of the polio eradication initiative on the operations and outcomes of non-polio public health programs: a survey of programs in the African region

Introduction: the effect of the Global polio eradication initiative (PEI) on public health programs beyond polio is widely debated. PEI contribution to other health programs has been assessed from the perspective of polio-funded personnel, which may introduce bias as PEI staff are probably more likely to show that they have benefited of other programs. We set out to identify and document how public health programs have benefited from the public health capacity that was provided at the country level as part of the PEI program in a systematic and standardized manner. Methods: between July and November 2017, we conducted a mixed-methods cross-sectional study, which combined two methods: a multi-country quantitative survey and a qualitative study. We created a self-administered electronic multi-lingual questionnaire in English, French and Portuguese. The qualitative study, which followed an interim analysis of the quantitative survey, comprised interviews with national and subnational level staff in a few countries. Results: a total of 127 public health workers from 43 of the 47 countries in the African WHO Region responded online. Most of the respondents 56/127 (42.7%) belonged to the immunization sector and 51/127 (38.9%) belonged to the emergencies and outbreaks sector. Respondents who identified themselves with the immunization (50/64 (78%)) and maternal health program (64/82 (78%)) reported the highest level of greatly benefiting from PEI resources. A total of 78/103 (76%) respondents rated PEI’s contribution data management system to their program very high and high. Of the 127 respondents, the majority 91 (71.6%) reported that the withdrawal of PEI resources would result in a weakening of surveillance for other diseases; 88 (62.9%) reported that there would be inadequate resources to carry out planned activities and 80 (62.9%) reported that there would be poor logistics and transport for implementation of activities. Cameroon, DRC, Nigeria and Uganda participated in the qualitative study. Each country had between 7-8 key informants from the national and sub-national level for a total of 31 key informants. Polio funds and other PEI resources have supported various activities in the ministries of health of the four countries especially IDSR, data management, laboratories and development of the public health workforce. Respondents believed that the infrastructure and processes that PEI has created need to be maintained, along with the workforce and they believed that this was an essential role of their governments with support from the partners. Conclusion: there is a high awareness of the PEI program in all the countries and at all levels which should be leveraged into improving other child survival activities for example routine immunizations. Future large-scale programs of this nature should be designed to benefit other public health programs beyond the specific program. The public health workforce, surveillance development, data management and laboratory strengthening that have been developed by PEI need to be maintained

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

The study is about human rabies infection in developing countries.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 ªOne Healthº approach with strategic focus on strengthening rabies surveillance, controlling rabies in dogs and ensuring availability of post exposure prophylaxis at lower health facilities

Spatio-temporal distribution of under-five malaria morbidity and mortality hotspots in Ghana, 2012 – 2017: a case for evidence-based targeting of malaria interventions

Introduction: The spatiotemporal variation in malaria burden underpins the need for targeted malaria interventions. Despite the scale-up of malaria control interventions in Ghana, malaria remains the leading cause of hospital admissions and deaths among children below 5 years (U5). We described spatiotemporal distribution of U5 malaria morbidity and mortality from 2012 to 2017 to provide evidence for deployment of specific malaria interventions to regions of hotspots in Ghana. Methods: We conducted a retrospective review of district-level malaria surveillance data from 2012 to 2017. We obtained confirmed U5 malaria case and population data for all districts in Ghana, and computed yearly smoothed malaria incidence and mortality rates. Hotspot analysis was performed using GeoDa’s Global and Local Moran I tests of spatial autocorrelation. Results: Overall, 8,132,769 U5 malaria cases and 5,932 deaths were reported, with case fatality rate of 0.1%. Under-five malaria incidence increased from 16.4% in 2012 to 31.3% in 2017, and the mortality rate per 100,000 decreased from 30.2 in 2012 to 6.1 in 2017. We found variation in morbidity hotspots from 8 to 23 in the western, south-western and north-eastern areas of the country each year, and six persistent mortality hotspots in the north-eastern areas. Conclusion: Over the review period, U5 malaria morbidity increased while mortality decreased. Variability in morbidity hotspots occurred across the western and northern regions unlike persistence of mortality hotspots in the north-eastern region. We recommend that the National Malaria Control Program systematically deploys preventive and case management interventions to areas of hotspots and also conduct a further evaluation to identify the causes of high mortality in the northeastern areas

Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm(3) compared to the general population: data from a population-based prospective HIV cohort in Uganda.

BACKGROUND: Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm(3). OBJECTIVE: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm(3) with mortality in the general Ugandan population and to investigate risk factors for death. DESIGN: Population-based prospective HIV cohort. METHODS: The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). RESULTS: A total of 374 participants with CD4 ≥350 cells/mm(3) were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95-29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15-49 years. Mortality was higher in periods during which participants had CD4 350-499 cells/mm(3) than during periods of CD4 ≥500 cells/mm(3) although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm(3) (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3) (246%, 117%-516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m(2) and ≥18.5 Kg/m(2): 6.11, 2.30-16.20). CONCLUSION: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm(3) had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI