Congenital rubella syndrome in Ethiopia: a retrospective review of records in four tertiary hospitals

¹WHO Ethiopia Country Office, Addis Ababa, Ethiopia, ²National Immunisation Program, Federal Ministry of Health, Ethiopia, ³Maternal, Child and Adolescent Health Service, Federal Ministry of Health, Ethiopia, ⁴WHO Regional Office for Africa, Brazzaville, Congo

^&Corresponding author
Habtamu Alemay Anteneh, WHO Ethiopia Country Office, Addis Ababa, Ethiopia

Introduction    

Rubella virus infection manifests as a mild and self-limiting febrile rash illness. However, rubella infection occurring in the first 12 weeks of pregnancy can lead to abortions, intrauterine fetal deaths or serious birth defects known as congenital rubella syndrome (CRS), and this constitutes the most concerning public health problem of rubella infections [1]. Newborns and infants with CRS frequently exhibit signs of intrauterine damage to developing organs, including cardiac defects, ocular manifestations like cataracts, hearing defects, and mental disability [1,2]. The World Health Organization (WHO) African Region has adopted a goal to eliminate measles and rubella in at least 80% of the countries by 2030, and countries have been implementing proven strategies including routine immunisation with two doses of measles-rubella vaccine, periodic preventive supplemental immunisation activities, and intensive disease surveillance supported by laboratory confirmation [3].

Globally, as of 2022, 175 out of 194 countries have introduced rubella vaccines and global vaccination coverage with rubella-containing vaccine (RCV) was estimated at 68% [4]. Rubella vaccine has been highly effective at reducing the burden of CRS. Reported rubella cases declined by 81%, from 93,816 cases in 2012 to 17,407 cases in 2022 globally. The elimination of rubella and CRS has already been achieved and verified in 98 countries across the world by 2022 [4]. In 2019, global estimates indicate that 32,000 cases of CRS occur annually. Of these, an estimated 25000 cases were in the WHO African Region, with an estimated CRS incidence of 64 per 100,000 live births. The global incidence of CRS fell by 66% during 2010-2019, and this declining trend reflects the introduction of rubella-containing vaccines [5]. By the end of 2024, only 35 of the 47 countries in the African Region have introduced rubella-containing vaccines [6]. The remaining 12 countries include populous countries like Nigeria, Ethiopia, DR Congo, which are estimated to account for most of the new CRS cases in the Region [5].

The national immunisation program in Ethiopia provides two doses of measles monovalent vaccine at 9 and 15 months of age [7]. According to the 2023 WHO-UNICEF vaccination coverage estimates, the first and second dose measles vaccination coverage in Ethiopia were 61% and 53% in 2023 [8]. The country has not yet introduced rubella containing vaccine into the national vaccination schedule. WHO has recently revised the policy recommendations for rubella vaccines allowing for universal introduction [9].

In the 10 years between 2014 and 2023, Ethiopia officially reported to WHO a total of 4,836 confirmed rubella cases [10]. Various studies have analysed the age patterns of rubella in the country, with the majority of cases occurring among children under 15 years of age. Cases have been documented from all parts of the country and tend to peak between March and June [11,12]. However, there are limited published studies documenting CRS in Ethiopia. One study conducted from December 2015 to August 2017 in 3 referral hospitals in Amhara Region described 50 suspected CRS cases (of which 9 were laboratory confirmed) [13]. Our study attempts to describe the occurrence of and the clinical characteristics of CRS cases in Ethiopia, through a retrospective review of clinical records in selected tertiary hospitals.

Methods     

Assessment site and period: the assessment was conducted in four selected tertiary referral hospitals in Ethiopia, with the relevant specialties and serving large populations. These are Felege-Hiwot Comprehensive Specialized Hospital (in the North-West part of the country in Amhara region), Jimma University Teaching Hospital (in the South-Western part of the country in Oromia region), St. Paulos Millennium Medical College Hospital (in the central part of the country in Addis Ababa), and Ayder Comprehensive Specialized Hospital (in the Northern part of the country in Tigray Region). The data collection was conducted from 1 November to 15 December 2024. The records review covered 10 years of data from January 2015 to December 2024.

Target population: the assessment included children under one year of age who visited the health facilities during the time of study. The Cardiology clinic, Pediatrics Outpatient Departments (OPD), Neonatal Intensive Care Units (NICU), Pediatric emergency units, Ophthalmology clinics, Ear-Nose-Throat/ audiology clinics, and Developmental clinics were assessed using the logbooks, HMIS register, and patient card.

Design: the retrospective record review involved reviewing patient logbooks, Health management information system (HMIS) registers, morning session logbooks, and patient records. The data collectors first checked the logbooks and registers in each service unit to identify the possible CRS cases and proceeded to retrieve and review the clinical records based on the medical record numbers.

Data collection and analysis: clinicians (pediatricians) and documentation personnel working in the respective hospitals were identified and assigned to collect data. The data collectors were trained on CRS burden, clinical signs and symptoms, and the WHO surveillance definition for CRS. They were provided with an online listing tool to identify and document CRS cases accurately from the records in the health facilities. A team from the National level conducted on-site supervision to ensure the data quality. Anonymised information from the identified suspected CRS cases was documented using the data collection tool, including clinical and demographic information extracted from individual medical records. Based on the available information, the cases were initially captured as suspected CRS cases and then classified as Clinically Compatible, Laboratory-confirmed CRS cases, or discarded (non-CRS) cases according to the WHO surveillance definition [14]. The descriptive analysis was conducted using Excel and SPSS version 24.

The following WHO standard case definition was used to classify cases:

Suspected CRS case: An infant less than one year of age with heart disease and/or, suspicion of deafness and/or, one or more of the following eye signs such as white pupil (cataract), diminished vision, pendular movement of the eyes (nystagmus), squint, smaller eyeball (microphthalmus), or larger eyeball (congenital glaucoma).

Clinically Compatible CRS case: if a child < 1 year with two complications in group (a) OR one from (a) and one from (b). a) Cataract and/or, congenital glaucoma, congenital heart disease, loss of hearing, pigmentary retinopathy b) Purpura, splenomegaly, microcephaly, mental retardation, meningoencephalitis, radiolucent bone disease, jaundice with onset within 24 hours after birth

Discarded case: a suspected CRS case without an adequate laboratory specimen and not meeting the clinically compatible case definition.

Results     

The hospital-based retrospective record review identified 1213 suspected cases of congenital rubella syndrome, of which 631 (52%) were male. The majority (57%) were born in a health facility, while 28 (2.3%) were born at home and 490 (40.4%) had no record of the place of birth. A total of 356 (29.35%) of the suspected CRS cases were aged <1 month, while 379 (31.24%) were 1 to 6 months of age, and 478 (39.41%) were >6 months old. Most of the suspected CRS cases 490(40%) were detected from records in the cardiology clinics of the respective hospitals (Table 1).

In this assessment, the most common clinical findings among the suspected CRS cases were congenital heart disease (83%), followed by various types of ocular manifestations (19%) and hepatomegaly (17%). Following a thorough review of the clinical signs according to the WHO case definition, 823 (69%) were discarded as not being CRS, while 378 (31%) were clinically compatible, and 3 (0.25%) were laboratory-confirmed CRS cases. Most of the clinically compatible cases 126 (33.3%), were detected from Jimma University Hospital followed by 100 (26.5%) compatible cases from Felgehiwot Comprehensive Specialised Hospital (Table 2).

The age distribution of the 381 laboratory-confirmed and clinically compatible CRS cases shows that 138 (36%) were 6-to-11 months of age, 127 (33%) were between 1 and 5 months old at the time of presentation to the hospitals (Table 3). Clinically compatible cases were detected in all the years covered by the study, with an increasing number of cases detected in the years 2021 - 2024 as compared to previous years (Figure 1).

The common clinical signs among the compatible and laboratory confirmed CRS cases were congenital heart disease, which accounted for 364 (96%). Hepatomegaly and hepatosplenomegaly were noted in 201 (53%) and 76 (20%) cases respectively. There were 62 (16%) cases with different ocular manifestations, while 31 (8%) had developmental delay and 32 (8.4%) had microcephaly. Cataracts were the most common ocular manifestation (Table 4). There were different types and combinations of congenital heart disease detected through the review, with some patients having multiple types of defects. Patent Ductus Arteriosus (PDA) was the defect detected in most of the cases (48% of confirmed CRS cases), followed by Ventricular Septal Defect (43%) (Table 5).

Discussion     

From 2014 to 2023, the 47 countries in the WHO African Region officially reported to WHO a total of 86,099 rubella cases and 414 CRS cases. During these 10 years, Ethiopia reported 4,836 rubella cases, while there were only 7 cases of CRS reported in 2016 [15]. Ideally, countries should keep a national register of congenital defects or implement sentinel surveillance for CRS where feasible. However, very few countries in the African Region currently have functioning sentinel surveillance sites. Retrospective reviews provide an alternative way of documenting the occurrence of CRS, especially to demonstrate trends over time. One limitation, as we saw in this study, is that the opportunity for laboratory confirmation is often lost during retrospective reviews [16]. In this series, the rubella IgM testing laboratory service is not well utilized for rubella/ CRS testing within clinical services, but mostly for epidemiological testing of suspected measles/ rubella cases as part of the measles-rubella case-based surveillance system. As a result, only 3 cases from Addis Ababa had rubella IgM testing done by laboratories abroad. In our study, the clinical manifestations of the CRS cases are somewhat influenced by the type of specialty clinic records that were consulted, and the availability of detailed clinical information. However, we note that the pattern is similar to that reported through sentinel CRS surveillance in 5 countries in AFR, where congenital heart defects, cataracts, microcephaly and splenomegaly were the commonest clinical findings among 119 CRS cases [17]. Comparable findings were reported from the Amhara Region in Ethiopia, as well as from studies in Vietnam, India and South Africa [13,18-20].

Our review detected that patent ductus arteriosus (PDA) and ventricular septal defects (VSD) were the most common types of cardiac defects. Similar clinical patterns of cardiac defects were reported in other studies [21,22]. Sentinel surveillance in 31 health facilities in India detected complex defects in one third of confirmed CRS cases with congenital heart defects, while isolated VSD, PDA and atrial septal defects (ASD) were the commonest findings among the simple defects [21]. In general, it is expected that CRS cases increase a few months after rubella outbreaks [18]. Therefore, during rubella outbreaks, CRS surveillance should be strengthened in maternity hospitals and pediatric specialty clinics to maximize the likelihood of identifying mothers at risk of fetal rubella infections, and newborns with CRS. The Ethiopian measles-rubella case-based surveillance system reported a spike in laboratory confirmed rubella cases in 2018 (683 laboratory confirmed rubella cases), in 2022 (620 cases) and in 2023 (933 cases), with the majority of cases reported from Addis Ababa, Amhara and Oromia Regions [23]. The higher number of compatible CRS cases detected in 2022 - 2024 in this retrospective review mirrors the rise in rubella cases in 2022 and 2023. However, at this point, we do not have adequate data to correlate the rubella and CRS epidemiology. This observation could also be a reflection of increased clinician awareness or due to the ease of availability of clinical records from recent years during the record review process. Infants with CRS and those with congenital rubella infection (infants who have none of the clinical signs of CRS from group A, but who meet the laboratory criteria for CRS) are known to shed rubella virus for the first few months of life, and so appropriate infection control measures should be implemented to avoid infecting health workers and other patients. WHO advises that specimens from CRS cases should be processed for molecular testing, since the viral genotype information helps to understand the source of infection, especially in near-elimination and post-elimination settings [14].

Conclusion     

In conclusion, based on the measles and rubella surveillance data and the CRS retrospective assessment, it is evident that there is widespread rubella virus circulation, and that CRS cases indeed occur in Ethiopia. We recommend that the facilities of the national measles-rubella serology laboratory should be utilized for the laboratory testing and confirmation of suspected CRS cases. As Ethiopia prepares to introduce rubella containing vaccine in the next few years, it will be important to strengthen measles-rubella surveillance, and establish sentinel surveillance sites, mainly targeting cardiac and ophthalmology units, to help monitor the CRS trends and help measure the impact of vaccine introduction in the long term. This study has the following limitations. The study population in this retrospective study from 4 hospitals may not be representative of the general population. The selected tertiary hospitals are likely to see only severe cases and referred patients from within the respective region and neighboring regions. During the retrospective record review, suspected CRS cases may be missed if medical records are not readily accessible, complete, detailed or accurate enough in describing clinical signs and diagnoses. Retrospectively identified cases usually lack laboratory confirmation, and therefore lack a definitive diagnosis. Even though data collectors were trained and supervised, there may be some variability in the quality of data collected. With all clinical registration books not being available at the time of the study, there is a possibility that suspected CRS cases are missed in the review process.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Habtamu Alemay Anteneh and Wondimu Bekele did the preliminary data analysis. Habtamu Alemay Anteneh developed the draft manuscript. Balcha Girma Masresha provided detailed inputs into the draft and further developed the manuscript. All authors have been involved in the editing of the manuscript. All authors have read and agreed to the final manuscript.

Acknowledgments     

We would like to thank the National immunization program of the Federal Ministry of Health of Ethiopia, and the management of the four tertiary hospitals for their approval to do this retrospective review. Our appreciation also goes to all the data collectors who participated in this study.

Tables and figure     

Table 1: distribution of suspected CRS cases according to the site of detection-CRS retrospective review, Ethiopia

Table 2: distribution and classification of CRS cases by hospital-CRS retrospective review, Ethiopia

Table 3: age of confirmed CRS cases by Region of residence

Table 4: frequency of clinical signs among confirmed CRS cases

Table 5: types of congenital heart defect: confirmed CRS cases, Ethiopia

Figure 1: distribution of clinically compatible and laboratory confirmed CRS cases detected by year - CRS retrospective review, Ethiopia

References