Rubella is an infectious disease caused by the rubella virus. The virus is transmitted through contact with droplets or nasopharyngeal secretions from an infected individual. The incubation period for acquired rubella ranges from 12 to 23 days. The major clinical manifestation is a generalized maculopapular rash beginning on the face and neck and progressing downwards. Transient joint symptoms may occur in adult women. However, symptoms of acquired rubella are generally mild, and a considerable proportion of infected individuals are asymptomatic [1, 2].
In addition to infection through contact, maternal rubella infection during pregnancy may result in vertical transmission to the fetus. After fetal infection, especially in the early stages of pregnancy, fetal malformation called congenital rubella syndrome (CRS) may develop. CRS symptoms include fetal death and spontaneous abortion, hearing impairment, ophthalmic abnormalities, cardiac malformations, and neurological problems [1, 2, 3]. Therefore, the prevention of rubella is a significant public health challenge. The World Health Organization (WHO) in 2012 targeted at eliminating rubella in at least five WHO regions by 2020 .
Universal vaccination with a rubella-containing vaccine (RCV) for susceptible individuals is necessary for eliminating rubella and CRS. In 2018, 168 (87%) countries introduced RCV in their vaccine schedule. However, only 81 WHO member states (42%) have verified eliminating rubella, and 26006 rubella cases have been reported globally . In Japan, although the goal of eliminating rubella by the fiscal year 2020 was set, 2941 and 2306 rubella cases were reported in 2018 and 2019, respectively [6, 7]. Further, four cases of CRS were also reported in 2019 and 2020 .
Surveillance with a rapid and exact diagnosis of rubella patients is important for patient and community interventions. However, the clinical diagnosis of rubella is unreliable because clinical manifestations are generally subclinical or non-specific [9, 10]. Detection of the rubella virus by polymerase chain reaction (PCR), rubella-specific IgM antibody, or a significant rise in the IgG antibody from paired sera provide a reliable diagnosis of acute rubella infection [2, 11, 12]. Although the detection of rubella-specific IgM is the standard method for laboratory diagnosis, it may not detect rubella until 4 days after the onset of the rash [11, 13]. PCR has been extensively evaluated for its usefulness in detecting the rubella virus in clinical specimens. Real-time reverse transcriptase (RT)-PCR can be used to detect rubella virus [12, 14]. However, the specimens for rubella RNA should be collected as soon as possible after the onset of the rash as the sensitivity of RNA detection methods decline considerably 5–7 days after the rash onset .
While a surveillance system with laboratory confirmation of cases may be important for regional elimination, the investigation of cases becomes very complex and time-consuming in the near-elimination stage . Since many patients develop acute rashes due to other diseases, RT-PCR test at the early stage of the disease as a public health intervention may impose a heavy burden on the laboratories when rubella is endemic and the resources for testing are limited in the area. It is also difficult to determine the case to prioritize for the rubella test, especially when the case is sporadic without contact or exposure” to avoid ambiguity.
In a rubella patient, especially an adult, the prodromal stage precedes the rash by one to five days. The prodromal symptoms present as low-grade fever, malaise, lymphadenopathy, and upper respiratory symptoms. We believe that fever is the most common noticeable symptom in the patient [2, 3, 16]. Data on the period between the onset of fever and the onset of rash in rubella patients may be useful for screening cases that need to be tested for rubella in resource-limited settings. However, to the best of our knowledge, no studies have reported data on this period.
Therefore, in this study, we investigated the period between the onset of fever, a prodromal symptom, and the onset of rash among laboratory-confirmed rubella patients. The study aimed to provide useful evidence to help screen cases for RT-PCR examination for rubella in resource-limited settings.