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.

Molecular characterization of non-polio enteroviruses isolated from acute flaccid paralysis patients in Uganda.

Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non-polio enteroviruses (NPEVs). Specific NPEVs have been described in polio-like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% were Enterovirus B and 9% were Enterovirus A species. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children less than 5 years (77/89; 86.5%) and male patients were more common (54/89; 60.7%). Echovirus 11 (11/89; 12.4%) was frequently observed and phylogenetic analysis of these sequences revealed high diversity. Coxsackievirus B5 (CV-B5), CV-B6, E21, and EV-B69 were only seen in patients with residual paralysis. Analyses of the EV-A71 sequence indicated a unique genogroup.

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.

Serum anti-tetanus and measles antibody titres in Ugandan children aged 4 months to 6 years: implications for vaccine programme.

To study the antibody response to tetanus toxoid and measles by age following vaccination in children aged 4 months to 6 years in Entebbe, Uganda. Serum samples were obtained from 113 children aged 4-15 months, at the Mother-Child Health Clinic (MCHC), Entebbe Hospital and from 203 of the 206 children aged between 12 and 75 months recruited through the Outpatients Department (OPD). Antibodies to measles were quantified by plaque reduction neutralisation test (PRNT) and with Siemens IgG EIA. VaccZyme IgG EIA was used to quantify anti-tetanus antibodies. Sera from 96 of 113 (85.0%) children attending the MCHC contained Measles PRNT titres below the protective level (120 mIU/ml). Sera from 24 of 203 (11.8%) children attending the OPD contained PRNT titres 0.15 IU/ml by EIA, a level considered protective. The overall concentration of anti-tetanus antibody was sixfold higher in children under 12 months compared with the older children, with geometric mean concentrations of 3.15 IU/ml and 0.49 IU/ml, respectively. For each doubling in age between 4 and 64 months, the anti-tetanus antibody concentration declined by 50%. As time since the administration of the third DTP vaccination doubled, anti-tetanus antibody concentration declined by 39%. The low measles antibody prevalence in the children presenting at the MCHC is consistent with the current measles epidemiology in Uganda, where a significant number of measles cases occur in children under 1 year of age and earlier vaccination may be indicated. The consistent fall in anti-tetanus antibody titre over time following vaccination supports the need for further vaccine boosters at age 4-5 years as recommended by the WHO.

Phylogenetic analysis of rubella viruses identified in Uganda, 2003-2012.

Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes.

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.