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.

Novel Oral Poliovirus Vaccine 2 Safety Evaluation during Nationwide Supplemental Immunization Activity, Uganda, 2022.

Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.

Rubella virus genotype 2B endemicity and related utility of serum-based molecular characterization in Uganda.

There are 13 globally recognized rubella virus genotypes of which only 2 (1E and 2B) have been detected recently. The largest percentage of all reported rubella virus sequences come from China and Japan with Africa reporting limited data. In a bid to address the lack of rubella genotype data in Uganda and the World Health Organization Africa region, we sought to characterize rubella viruses retrospectively using sera collected from suspected measles patients that turned out rubella IgM positive.Seven sequences belonging to genotype 2B sub-lineage 2B-L2c were obtained. These sequences clustered with other genotype 2B sequences previously reported from Uganda. None of the other genotypes (1E and 1G) reported from Uganda in the earlier years were detected. In addition, none of the sequences were obtained after the introduction of the measles-rubella containing vaccine. The above highlight the need for continuous rubella virological surveillance to confirm interruption of endemic rubella genotype circulation.

Cholera and COVID-19 pandemic prevention in multiple hotspot districts of Uganda: vaccine coverage, adverse events following immunization and WASH conditions survey.

BACKGROUND: Between March, 2020 and December, 2021 due to cholera and coronavirus disease 2019 (COVID-19) pandemics, there were 1,534 cholera cases with 14 deaths and 136,065 COVID-19 cases with 3,285 deaths reported respectively in Uganda. This study investigated mass vaccination campaigns for the prevention of the two pandemics namely: oral cholera vaccine (OCV) and COVID-19 vaccine coverage; adverse events following immunization (AEFI); barriers and enablers for the vaccine uptake and assessed water, sanitation and hygiene (WASH) conditions in the six cholera and COVID-19 hotspot districts of Uganda. METHODS: A household survey was conducted between January and February, 2022 in the six cholera hotspot districts of Uganda which had recently conducted OCV mass vaccination campaigns and had ongoing COVID-19 mass vaccination campaigns. The survey randomly enrolled 900 households with 4,315 persons of whom 2,085 were above 18 years. Data were collected using a data entry application designed in KoBoToolbox and analysed using STATA version 14. Frequencies, percentages, odds ratios, means, confidence intervals and maps were generated and interpreted. RESULTS: The OCV coverage for dose one and two were 85% (95% CI: 84.2-86.4) and 67% (95% CI: 65.6-68.4) respectively. Among the 4,315 OCV recipients, 2% reported mild AEFI, 0.16% reported moderate AEFI and none reported severe AEFI. The COVID-19 vaccination coverage for dose one and two were 69.8% (95% CI: 67.8-71.8) and 18.8% (95% CI: 17.1-20.5) respectively. Approximately, 23% (478/2,085) of COVID-19 vaccine recipient reported AEFI; most 94% were mild, 0.6% were moderate and 2 cases were severe. The commonest reason for missing COVID-19 vaccine was fear of the side effects. For most districts (5/6), sanitation (latrine/toilet) coverage were low at 7.4%-37.4%. CONCLUSION: There is high OCV coverage but low COVID-19 vaccine and sanitation coverage with high number of moderate cases of AEFI recorded due to COVID-19 vaccines. The low COVID-19 vaccine coverage could indicate vaccine hesitancy for COVID-19 vaccines. Furthermore, incorporation of WASH conditions assessment in the OCV coverage surveys is recommended for similar settings to generate data for better planning. However, more studies are required on COVID-19 vaccine hesitancy.

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.

Development of a Scorecard to Monitor Progress toward National Cholera Elimination: Its Application in Uganda.

In 2017, the Global Task Force for Cholera Control (GTFCC) set a goal to eliminate cholera from ≥ 20 countries and to reduce cholera deaths by 90% by 2030. Many countries have included oral cholera vaccine (OCV) in their cholera control plans. We felt that a simple, user-friendly monitoring tool would be useful to guide national progress toward cholera elimination. We reviewed cholera surveillance data of Uganda from 2015 to 2021 by date and district. We defined a district as having eliminated cholera if cholera was not reported in that district for at least 4 years. We prepared maps to show districts with cholera, districts that had eliminated it, and districts that had eliminated it but then "relapsed." These maps were compared with districts where OCV was used and the hotspot map recommended by the GTFCC. Between 2018 and 2021, OCV was administered in 16 districts previously identified as hotspots. In 2018, cholera was reported during at least one of the four previous years from 36 of the 146 districts of Uganda. This number decreased to 18 districts by 2021. Cholera was deemed "eliminated" from four of these 18 districts but then "relapsed." The cholera elimination scorecard effectively demonstrated national progress toward cholera elimination and identified districts where additional resources are needed to achieve elimination by 2030. Identification of the districts that have eliminated cholera and those that have relapsed will assist the national programs to focus on addressing the factors that result in elimination or relapse of cholera.

Field investigation of high reported non-neonatal tetanus burden in Uganda, 2016-2017.

BACKGROUND: Despite providing tetanus-toxoid-containing vaccine (TTCV) to infants and reproductive-age women, Uganda reports one of the highest incidences of non-neonatal tetanus (non-NT). Prompted by unusual epidemiologic trends among reported non-NT cases, we conducted a retrospective record review to see whether these data reflected true disease burden. METHODS: We analysed nationally reported non-NT cases during 2012-2017. We visited 26 facilities (14 hospitals, 12 health centres) reporting high numbers of non-NT cases (n = 20) or zero cases (n = 6). We identified non-NT cases in facility registers during 1 January 2016-30 June 2017; the identified case records were abstracted. RESULTS: During 2012-2017, a total of 24 518 non-NT cases were reported and 74% were ≥5 years old. The average annual incidence was 3.43 per 100 000 population based on inpatient admissions. Among 482 non-NT inpatient cases reported during 1 January 2016-30 June 2017 from hospitals visited, 342 (71%) were identified in facility registers, despite missing register data (21%). Males comprised 283 (83%) of identified cases and 60% were ≥15 years old. Of 145 cases with detailed records, 134 (92%) were clinically confirmed tetanus; among these, the case-fatality ratio (CFR) was 54%. Fourteen cases were identified at two hospitals reporting zero cases. Among >4000 outpatient cases reported from health centres visited, only 3 cases were identified; the remainder were data errors. CONCLUSIONS: A substantial number of non-NT cases and deaths occur in Uganda. The high CFR and high non-NT burden among men and older children indicate the need for TTCV booster doses across the life course to all individuals as well as improved coverage with the TTCV primary series. The observed data errors indicate the need for data quality improvement activities.

Trends of key surveillance performance indicators of acute flaccid paralysis: a descriptive analysis, Uganda, 2015-2020.

BACKGROUND: Polio is disease caused by poliovirus which can in turn cause irreversible paralytic disease, presenting as Acute Flaccid Paralysis (AFP). A sensitive AFP surveillance system, in which all reported AFP cases are evaluated, first to determine if they are true AFP cases or not, is key for tracking polio eradication. True AFP cases are then later categorized as polio AFP or non-polio AFP (NPAFP) cases. Sensitivity is defined by meeting an annual NPAFP rate/100,000 population < 15 years of ≥ 4/100,000, and an annual stool adequacy (SA) rate of ≥ 80%. We describe Uganda's AFP surveillance performance between 2015-2020, based on the WHO-recommended indicators, including; NPAFP and stool adequacy rate. METHODS: We performed a descriptive analysis of national AFP surveillance data, 2015-2020 obtained from ministry of health. We evaluated proportion of reported AFP cases that were true AFP, and changes in NPAFP and stool adequacy (SA) rate over the study period. We evaluated the trends in achieving the targeted NPAFP and SA rates from 2015-2020. We used QGIS to illustrate patterns in NPAFP and SA rates across districts and subregions. RESULTS: Among 3,605 AFP cases reported and investigated countrywide from 2015-2020, 3,475 (96%) were true AFP cases. All the true AFP cases were non-polio related. District reporting was near-complete (97-100% each year). Overall, the mean NPAFP rate declined from 3.1/100,000 in 2015 to 2.1/100,000 in 2020. Less than 40% of districts met the NPAFP target rate in all years. The proportion of districts achieving the NPAFP target rate of ≥ 4/100,000 significantly declined from 35% in 2015 to 20% in 2020. The mean annual SA rate nationally was 88% from 2015-2020. Only 66% of districts achieved the SA target rate of ≥ 80% in the study period. The proportion of districts with SA rate ≥ 80% significantly increased from 68 to 80% between 2015 and 2020. CONCLUSION: Most districts reported AFP cases. However, there was a decline in the NPAFP rate from 2015-2020 and few districts achieved the target rate. The suboptimal AFP surveillance system performance leaves the country at risk of missing ongoing poliovirus transmission. We recommend health worker training on active AFP searches, intensified supportive supervision, increase the number of environmental surveillance sentinel sites to boost AFP surveillance in the country, and periodic review meetings with districts to assess AFP surveillance performance.

Simulation Exercises To Strengthen Polio Outbreak Preparedness in The Horn of Africa: Experiences and Lessons Learnt.

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.

Descriptive epidemiology of rubella disease and associated virus strains in Uganda.

Rubella virus causes a mild disease; however, infection during the first trimester of pregnancy may lead to congenital rubella syndrome (CRS) in over 80% of affected pregnancies. Vaccination is recommended and has been shown to effectively reduce CRS incidence. Uganda plans to introduce routine rubella vaccination in 2019. The World Health Organization recommends assessing the disease burden and obtaining the baseline molecular virological data before vaccine introduction. Sera collected during case-based measles surveillance from January 2005 to July 2018 were tested for rubella immunoglobulin M (IgM) antibodies. Sera from confirmed rubella outbreaks from January 2012 to August 2017 were screened using real-time reverse-transcription polymerase chain reaction (RT-PCR); for positive samples, a region within the E1 glycoprotein coding region was amplified and sequenced. Of the 23 196 suspected measles cases serologically tested in parallel for measles and rubella, 5334 (23%) were rubella IgM-positive of which 2710 (50.8%) cases were females with 2609 (96.3%) below 15 years of age. Rubella IgM-positive cases were distributed throughout the country and the highest number was detected in April, August, and November. Eighteen (18%) of the 100 sera screened were real-time RT-PCR-positive of which eight (44.4%) were successfully sequenced and genotypes 1G and 2B were identified. This study reports on the seroprevalence and molecular epidemiology of rubella. Increased knowledge of former and current rubella viruses circulating in Uganda will enhance efforts to monitor the impact of vaccination as Uganda moves toward control and elimination of rubella and CRS.

Financial cost analysis of a strategy to improve the quality of administrative vaccination data in Uganda.

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.

Ebola virus disease surveillance in the absence of a confirmed case; the case of the Rwenzori region of Uganda.

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.

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.

Enhancing Workforce Capacity to Improve Vaccination Data Quality, Uganda.

In Uganda, vaccine dose administration data are often not available or are of insufficient quality to optimally plan, monitor, and evaluate program performance. A collaboration of partners aimed to address these key issues by deploying data improvement teams (DITs) to improve data collection, management, analysis, and use in district health offices and health facilities. During November 2014-September 2016, DITs visited all districts and 89% of health facilities in Uganda. DITs identified gaps in awareness and processes, assessed accuracy of data, and provided on-the-job training to strengthen systems and improve healthcare workers' knowledge and skills in data quality. Inaccurate data were observed primarily at the health facility level. Improvements in data management and collection practices were observed, although routine follow-up and accountability will be needed to sustain change. The DIT strategy offers a useful approach to enhancing the quality of health data.

Positive predictive value and effectiveness of measles case-based surveillance in Uganda, 2012-2015.

INTRODUCTION: Disease surveillance is a critical component in the control and elimination of vaccine preventable diseases. The Uganda National Expanded Program on Immunization strives to have a sensitive surveillance system within the Integrated Disease Surveillance and Response (IDSR) framework. We analyzed measles surveillance data to determine the effectiveness of the measles case-based surveillance system and estimate its positive predictive value in order to inform policy and practice. METHODS: An IDSR alert was defined as ≥1 suspected measles case reported by a district in a week, through the electronic Health Management Information System. We defined an alert in the measles case-based surveillance system (CBS) as ≥1 suspected measles case with a blood sample collected for confirmation during the corresponding week in a particular district. Effectiveness of CBS was defined as having ≥80% of IDSR alerts with a blood sample collected for laboratory confirmation. Positive predictive value was defined as the proportion of measles case-patients who also had a positive measles serological result (IgM +). We reviewed case-based surveillance data with laboratory confirmation and measles surveillance data from the electronic Health Management Information System from 2012-2015. RESULTS: A total of 6,974 suspected measles case-persons were investigated by the measles case-based surveillance between 2012 and 2015. Of these, 943 (14%) were measles specific IgM positive. The median age of measles case-persons between 2013 and 2015 was 4.0 years. Between 2013 and 2015, 72% of the IDSR alerts reported in the electronic Health Management Information System, had blood samples collected for laboratory confirmation. This was however less than the WHO recommended standard of ≥80%. The PPV of CBS between 2013 and 2015 was 8.6%. CONCLUSION: In conclusion, the effectiveness of measles case-based surveillance was sub-optimal, while the PPV showed that true measles cases have significantly reduced in Uganda. We recommended strengthening of case-based surveillance to ensure that all suspected measles cases have blood samples collected for laboratory confirmation to improve detection and ensure elimination by 2020.

Vaccine associated paralytic poliomyelitis cases from children presenting with acute flaccid paralysis in Uganda.

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.

The National Stop Transmission of Polio (STOP) Programme in Uganda 2012-2014

In 2012 Uganda established a pool of national STOP (Stop Transmission of Polio) volunteers who assist subnational staff in strengthening surveillance - detection and reporting. In addition to surveillance activities; the volunteers have built capacity of operational health workers in basic skills for routine immunization. This article gives a brief overview of the initiative and the impressive achievements it is making

Rotavirus prevalence and genotypes among children younger than 5 years with acute diarrhea at Mulago National Referral Hospital, Kampala, Uganda.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea among children <5 years of age worldwide. To determine the prevalence of severe rotavirus infection in children admitted with acute diarrhea attending Mulago National Referral Hospital in Uganda, active sentinel surveillance was conducted from July 2006 to December 2012. METHODS: A total of 6387 children with acute diarrhea were enrolled into the public health surveillance system and of these, 5627 had stool samples collected and tested for rotavirus antigens by enzyme immunoassay ProSpecT Rotavirus kit. RESULTS: Rotavirus was detected in 1844 (32.8%) of 5627 children with acute diarrhea that had stool specimens collected, and 93% of positive cases of rotavirus gastroenteritis were between 3 and 23 months of age, with highest prevalence in children 6-11 months of age. Rotavirus infections occurred throughout the year. During the surveillance period (2006-2012), a total of 354 positive stool samples were subjected to reverse transcription polymerase chain reaction and genotyping assays. The most common genotypes detected were G1P[8] (16.1%) and G9P[8] (15.3%), followed by G2P[4] (7.6%), G9P[6] (7.1%), G8P[4] (6.5%) and G12P[6](5.6%). Mixed G or P types (17.9%) and partially typed either G or P types (10.7%) were common. CONCLUSION: Uganda would benefit by introducing rotavirus vaccine and hence reduce the hospitalization burden of managing acute diarrhea cases.

Projected health benefits and costs of pneumococcal and rotavirus vaccination in Uganda.

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.

Possible interruption of measles virus transmission, Uganda, 2006-2009.

To determine what measles virus genotype(s) circulated in Uganda after strategic interventions aimed at controlling/eliminating measles, we examined samples obtained during 2006-2009 and found only genotype B3.1, which had not been previously detected. Kenya was the likely source, but other countries cannot be excluded.