Viruses associated with measles-like illnesses in Uganda.

OBJECTIVES: In this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance program in order to inform diagnostic assay selection and vaccination strategies. METHODS: We used metagenomic next-generation sequencing (M-NGS) on the Illumina platform to identify viruses associated with MLI (defined as fever and rash in the presence of either cough, coryza or conjunctivitis) in patient samples that had tested IgM negative for measles between 2010 and 2019. RESULTS: Viral genomes were identified in 87/271 (32%) of samples, of which 44/271 (16%) contained 12 known viral pathogens. Expected viruses included rubella, human parvovirus B19, Epstein Barr virus, human herpesvirus 6B, human cytomegalovirus, varicella zoster virus and measles virus (detected within the seronegative window-period of infection) and the blood-borne hepatitis B virus. We also detected Saffold virus, human parvovirus type 4, the human adenovirus C2 and vaccine-associated poliovirus type 1. CONCLUSIONS: The study highlights the presence of undiagnosed viruses causing MLI in Uganda, including vaccine-preventable illnesses. NGS can be used to monitor common viral infections at a population level, especially in regions where such infections are prevalent, including low and middle income countries to guide vaccination policy and optimize diagnostic assays.

Environmental surveillance detects circulating vaccine-derived poliovirus type 2 that was undetected by acute flaccid paralysis surveillance in 2021 in Uganda.

The success of the global polio eradication initiative is threatened by the genetic instability of the oral polio vaccine, which can result in the emergence of pathogenic vaccine-derived polioviruses following prolonged replication in the guts of individuals with primary immune deficiencies or in communities with low vaccination coverage. Through environmental surveillance, circulating vaccine-derived poliovirus type 2 was detected in Uganda in the absence of detection by acute flaccid paralysis (AFP) surveillance. This underscores the sensitivity of environmental surveillance and emphasizes its usefulness in supplementing AFP surveillance for poliovirus infections in the race towards global polio eradication.

The road to a polio-free Uganda; contribution of the Expanded Program on Immunization Laboratory (EPI-LAB) at Uganda Virus Research Institute.

Background: The control of poliomyelitis in Uganda dates back as far as 1950 and acute flaccid paralysis (AFP) surveillance has since been used as a criterion for identifying wild polioviruses. Poliovirus isolation was initially pursued through collaborative research however, in 1993, the Expanded Program on Immunization Laboratory (EPI-LAB) was established as a member of the Global Poliovirus Laboratory Network (GPLN) and spearheaded this activity at Uganda Virus Research Institute. Objectives: The aim of this report is to document the progress and impact of the EPI-LAB on poliovirus eradication in Uganda. Methods: Poliovirus detection and identification were achieved fundamentally through tissue culture and intra-typic differentiation of the poliovirus based on the real-time reverse transcriptase polymerase chain reaction (rRT PCR). The data obtained was entered into the national AFP database and analysed using EpiInfoTM statistical software. Results: Quantitative and qualitative detection of wild and Sabin polioviruses corresponded with the polio campaigns. The WHO target indicators for AFP surveillance were achieved essentially throughout the study period. Conclusion: Virological tracking coupled with attaining standard AFP surveillance indicators has been pivotal in achieving and maintaining the national wild polio-free status. Laboratory surveillance remains key in informing the certification process of polio eradication.

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.

Healthcare workers' experiences regarding scaling up of training on integrated disease surveillance and response (IDSR) in Uganda, 2016: cross sectional qualitative study.

BACKGROUND: The Integrated Disease Surveillance and Response (IDSR) strategy was adopted as the framework for implementation of International Health Regulation (2005) in the African region of World Health Organisation (WHO AFRO). While earlier studies documented gains in performance of core IDSR functions, Uganda still faces challenges due to infectious diseases. IDSR revitalisation programme aimed to improve prevention, early detection, and prompt response to disease outbreaks. However, little is known about health worker's perception of the revitalised IDSR training. METHODS: We conducted focus group discussions of health workers who were trained between 2015 and 2016. Discussions on benefits, challenges and possible solutions for improvement of IDSR training were recorded, transcribed, translated and coded using grounded theory. RESULTS: In total, 22/26 FGDs were conducted. Participants cited improved completeness and timeliness of reporting, case detection and data analysis and better response to disease outbreaks as key achievements after the training. Programme challenges included an inadequate number of trained staff, funding, irregular supervision, high turnover of trained health workers, and lack of key logistics. Suggestions to improve IDSR included pre-service and community training, mentorship, regular supervision and improving funding at the district level. CONCLUSION: Health workers perceived that scaling up revitalized IDSR training in Uganda improved public health surveillance. However, they acknowledge encountering challenges that hinder their performance after the training. Ministry of Health should have a mentorship plan, integrate IDSR training in pre-service curricula and advocate for funding IDSR activities to address some of the gaps highlighted in this study.

Evaluation of integrated disease surveillance and response (IDSR) core and support functions after the revitalisation of IDSR in Uganda from 2012 to 2016.

BACKGROUND: Uganda is a low income country that continues to experience disease outbreaks caused by emerging and re-emerging diseases such as cholera, meningococcal meningitis, typhoid and viral haemorrhagic fevers. The Integrated Disease Surveillance and Response (IDSR) strategy was adopted by WHO-AFRO in 1998 as a comprehensive strategy to improve disease surveillance and response in WHO Member States in Africa and was adopted in Uganda in 2000. To address persistent inconsistencies and inadequacies in the core and support functions of IDSR, Uganda initiated an IDSR revitalisation programme in 2012. The objective of this evaluation was to assess IDSR core and support functions after implementation of the revitalised IDSR programme. METHODS: The evaluation was a cross-sectional survey that employed mixed quantitative and qualitative methods. We assessed IDSR performance indicators, knowledge acquisition, knowledge retention and level of confidence in performing IDSR tasks among health workers who underwent IDSR training. Qualitative data was collected to guide the interpretation of quantitative findings and to establish a range of views related to IDSR implementation. RESULTS: Between 2012 and 2016, there was an improvement in completeness of monthly reporting (69 to 100%) and weekly reporting (56 to 78%) and an improvement in timeliness of monthly reporting (59 to 93%) and weekly reporting (40 to 68%) at the national level. The annualised non-polio AFP rate increased from 2.8 in 2012 to 3.7 cases per 100,000 population < 15 years in 2016. The case fatality rate for cholera decreased from 3.2% in 2012 to 2.1% in 2016. All districts received IDSR feedback from the national level. Key IDSR programme challenges included inadequate numbers of trained staff, inadequate funding, irregular supervision and high turnover of trained staff. Recommendations to improve IDSR performance included: improving funding, incorporating IDSR training into pre-service curricula for health workers and strengthening support supervision. CONCLUSION: The revitalised IDSR programme in Uganda was associated with improvements in performance. However in 2016, the programme still faced significant challenges and some performance indicators were still below the target. It is important that the documented gains are consolidated and challenges are continuously identified and addressed as they emerge.

Outbreak of yellow fever in central and southwestern Uganda, February-may 2016.

BACKGROUND: On 28 March, 2016, the Ministry of Health received a report on three deaths from an unknown disease characterized by fever, jaundice, and hemorrhage which occurred within a one-month period in the same family in central Uganda. We started an investigation to determine its nature and scope, identify risk factors, and to recommend eventually control measures for future prevention. METHODS: We defined a probable case as onset of unexplained fever plus ≥1 of the following unexplained symptoms: jaundice, unexplained bleeding, or liver function abnormalities. A confirmed case was a probable case with IgM or PCR positivity for yellow fever. We reviewed medical records and conducted active community case-finding. In a case-control study, we compared risk factors between case-patients and asymptomatic control-persons, frequency-matched by age, sex, and village. We used multivariate conditional logistic regression to evaluate risk factors. We also conducted entomological studies and environmental assessments. RESULTS: From February to May, we identified 42 case-persons (35 probable and seven confirmed), of whom 14 (33%) died. The attack rate (AR) was 2.6/100,000 for all affected districts, and highest in Masaka District (AR = 6.0/100,000). Men (AR = 4.0/100,000) were more affected than women (AR = 1.1/100,000) (p = 0.00016). Persons aged 30-39 years (AR = 14/100,000) were the most affected. Only 32 case-patients and 128 controls were used in the case control study. Twenty three case-persons (72%) and 32 control-persons (25%) farmed in swampy areas (ORadj = 7.5; 95%CI = 2.3-24); 20 case-patients (63%) and 32 control-persons (25%) who farmed reported presence of monkeys in agriculture fields (ORadj = 3.1, 95%CI = 1.1-8.6); and 20 case-patients (63%) and 35 control-persons (27%) farmed in forest areas (ORadj = 3.2; 95%CI = 0.93-11). No study participants reported yellow fever vaccination. Sylvatic monkeys and Aedes mosquitoes were identified in the nearby forest areas. CONCLUSION: This yellow fever outbreak was likely sylvatic and transmitted to a susceptible population probably by mosquito bites during farming in forest and swampy areas. A reactive vaccination campaign was conducted in the affected districts after the outbreak. We recommended introduction of yellow fever vaccine into the routine Uganda National Expanded Program on Immunization and enhanced yellow fever surveillance.

The design and implementation of the re-vitalised integrated disease surveillance and response (IDSR) in Uganda, 2013-2016.

BACKGROUND: Uganda adopted and has been implementing the Integrated Disease Surveillance (IDSR) strategy since 2000. The goal was to build the country's capacity to detect, report promptly, and effectively respond to public health emergencies and priorities. The considerable investment into the program startup realised significant IDSR core performance. However, due to un-sustained funding from the mid-2000s onwards, these achievements were undermined. Following the adoption of the revised World Health Organization guidelines on IDSR, the Uganda Ministry of Health (MoH) in collaboration with key partners decided to revitalise IDSR and operationalise the updated IDSR guidelines in 2012. METHODS: Through the review of both published and unpublished national guidelines, reports and other IDSR program records in addition to an interview of key informants, we describe the design and process of IDSR revitalisation in Uganda, 2013-2016. The program aimed to enhance the districts' capacity to promptly detect, assess and effectively respond to public health emergencies. RESULTS: Through a cascaded, targeted skill-development training model, 7785 participants were trained in IDSR between 2015 and 2016. Of these, 5489(71%) were facility-based multi-disciplinary health workers, 1107 (14%) comprised the district rapid response teams and 1188 (15%) constituted the district task forces. This training was complemented by other courses for regional teams in addition to the provision of logistics to support IDSR activities. Centrally, IDSR implementation was coordinated and monitored by the MoH's national task force (NTF) on epidemics and emergencies. The NTF and in close collaboration with the WHO Country Office, mobilised resources from various partners and development initiatives. At regional and district levels, the technical and political leadership were mobilised and engaged in monitoring and overseeing program implementation. CONCLUSION: The IDSR re-vitalization in Uganda highlights unique features that can be considered by other countries that would wish to strengthen their IDSR programs. Through a coordinated partner response, the program harnessed resources which primarily were not earmarked for IDSR to strengthen the program nation-wide. Engagement of the local district leadership helped promote ownership, foster accountability and sustainability of the program.

The detection of 3 ambiguous type 2 vaccine-derived polioviruses (VDPV2s) in Uganda.

BACKGROUND: The Oral Polio Vaccine (OPV or Sabin) is genetically unstable and may mutate to form vaccine-derived polioviruses (VDPVs). METHODS: In 2014, two VDPVs type 2 were identified during routine surveillance of acute flaccid paralysis (AFP) cases. Consequently, a retrospective VDPV survey was conducted to ensure that there was no circulating VDPV in the country. All Sabin poliovirus isolates identified in Uganda 6 months before and 6 months after were re-screened; Sabin 1 and 3 polioviruses were re-screened for Sabin 2 and Sabin 2 polioviruses were re-screened for VDPVs type 2. The Poliovirus rRT-PCR ITD/VDPV 4.0 assay and sequencing were used respectively. RESULTS: The first two VDPVs type2 were identified in Eastern Uganda and the third was identified during the survey from South-western Uganda. These regions had low OPV coverage and poor AFP surveillance indicators. CONCLUSION: The retrospective VDPV survey was a useful strategy to screen for VDPVs more exhaustively. Supplementary surveillance methods need to be encouraged.