Elimination of Measles disease and mortality became one of the most important global health targets during the past decades. [1] According to Dixon et al [2] and Perin et al [3], there was a substantial decline in both annual measles incidence and mortality rate (mainly among under-

five-years old children) during the years 2000–2016. Nevertheless, during the years 2017–2019, this decline was followed by resurgence of measles and multiple outbreaks in many countries [4].

During 2018–2019 a nation-wide measles outbreak emerged in Israel (national population 9.3 million), with 4158 measles cases notified in the country [3]. The Jerusalem district (district population 1.3 million) was profoundly affected (2254 notified measles cases), with 7.4% of the measles cases necessitating hospitalization [3], [4]. Most of the measles cases reported in the 2018–2019 outbreak in the Jerusalem district, were unvaccinated children residing in several overcrowded Jewish ultra-orthodox communities [3]. The majority of the measles-related hospitalizations (53.4%) in Jerusalem were observed among children younger than 5 years of age, 9.9% of the hospitalized measles patients were aged between five and 20 years and 36.6% were 20 years of age and older [4].

The current study aims were to evaluate the measles clinical characteristics, measles- related hospitalizations, the vaccination status (number of vaccine doses received prior to infection) and measles vaccine effectiveness, among children, under 18 years of age, during the 2018–2019 measles outbreak in the Jerusalem district. [5]

Measles is a highly contagious viral disease. Before the introduction of measles-containing vaccines (MCV) in the 1960s, more than 2 million deaths occurred globally each year, and more than 95% of individuals had been infected with measles virus by the age of 15 years [6]. As routine immunization coverage rises – from 2000 to 2017, global coverage with the first dose of MCV for children 1 year of age had increased from 72% to 85% [7] - measles incidence decreased significantly. During 2000–2017, annual reported measles cases decreased from 145 to 25 cases per million population, and annual estimated measles deaths decreased by 80% [6]. Nevertheless, estimated global coverage with a second MCV had reached only 67% in 2017 [5], and measles is still circulating in parts of Africa and Asia, especially in countries with lower vaccine coverage rates. Achieving and maintaining a high (≥95%) 2-dose measles vaccination coverage with both doses equitably to all children in every district is the key to eliminating measles [7].

The study spanned for 1 year from 01/6/2022 to 31/05/2023 in immunization OPD of Brajarambha UPHC in Cuttack district. Parents of the children were enquired through structured questionnaire regarding occurrence of measles or travel history to a high-risk measles areas, and the treatment received for measles cases i.e. Vit A Prophylaxis.

We extracted the publicly available Health Management Information System (HMIS) data for monthly aggregated measles cases, deaths, and child immunization (0–15 year) with the first dose of measles vaccine (or measles containing vaccine like MR/MMR). The HMIS is a web-based monitoring system established by the Indian Ministry of Health & Family Welfare. It monitors the key indicators of various national health programs, offering crucial insights for policy development and program interventions. It collects monthly data on service delivery like maternal and child health related, immunization family planning, quarterly training information, and annual infrastructure data from health facilities, enabling gap analysis and evidence-based corrections. The HMIS portal facilitates data fow and generates periodic reports on health service and resource status.

To ensure that vaccine coverage is realistically represented among the target population in this analysis, we verified the vaccination coverage from other data sources including immunization data under the National Health Mission (NHM), and universal immunization coverage data, to rule out any major variations in the coverage

In this study, our primary focus was on measuring measles incidence, which represents the number of measles cases per million population of children under five years of age. Measles incidence was calculated by taking the monthly aggregated data on measles cases obtained from HMIS and dividing it by the estimated children under five years population in each state for each year. Case Fatality Rate (CFR) was determined by dividing the monthly aggregated data on measles-related deaths by the monthly measles cases in each state for each year.

The final variable of interest was the coverage of the first dose of measles containing vaccine (MCV1), recommended for children aged 9 to 11 months. To calculate this coverage, we used the same HMIS data to observe the number of vaccinated children and paired it with population estimate data. This coverage was computed by dividing the total number of vaccinated children by the total infant population in each state for each year.

By incorporating the lagged variable of vaccination coverage and its estimation, we were able to determine the impact of vaccination coverage on

measles incidence rates. Furthermore, we included dummy variables in our analysis to account for any additional unobservable time-invariant characteristics within each state that could influence measles incidence.

A total of 260 blood samples were randomly collected (not collected specifically for measles study) from children aged 0–15 years. The children were categorized into two age groups: 0–5 years and >5 years. Of the 260 children, 145 (59.8%) had received the Measles Mumps Rubella (MMR) vaccine, while 115 (40.2%) were unvaccinated, as reported by their parents.

Out of the 260 samples, 148 (56.9%) tested positive for measles IgM antibodies. Among the positive cases, 89 (60.1%) were male, and 59 (39.9%) were female, resulting in a male-to-female (M/F) ratio of 1.51:1. However, there was no significant difference in the prevalence of measles virus infection between male and female children (P > 0.25, as shown in Table 1).

Children aged 0–5 years showed the highest positive rate for measles antibodies, with 93 (62.8%) cases, compared to 55 (37.2%) cases among children aged >5 years. This difference was not statistically significant (P > 0.46). Additionally, it was concerning that some vaccinated children also tested positive for measles virus infection, raising questions about the effectiveness of vaccination or other underlying factors.

Below is a structured table presenting the demographic characteristics of fever-rash ill children with and without measles virus infection:

TABLE: 1 n=260 Measles Virus Infection

Table 2: Age Group Distribution of Measles Cases

Table: 3 Clinical Manifestations in Pre-Immunized Children

Table 4: Outcomes in Pre-Immunized Children

The data show that measles can occur in pre-immunized children, though cases are generally milder compared to unvaccinated children. The highest prevalence of pre-immunized cases was observed in the 6–10 age group, suggesting potential waning immunity or incomplete vaccine coverage.^[7]

Clinical symptoms in pre-immunized children were consistent with typical measles presentations, but complications and mortality rates were relatively low, underscoring the protective effects of vaccination. ^[8]

We presented results of a measles outbreak investigation in a hospital that included 8 HCWs with measles, of whom 6 were twice vaccinated with measles vaccine. Quantitative virological and serological results of the twice-vaccinated cases were available at multiple time points before and subsequent to measles virus infection, allowing detailed characterization of vaccine failure. [9] The occurrence of measles in twice-vaccinated individuals is nevertheless an important concern for measles elimination efforts, which rely on a 2-dose measles vaccination schedule [10].

Outbreaks of measles among twice-vaccinated individuals have been reported previously, albeit infrequently [11]. Rosen et al described an outbreak of 5 measles cases in persons with prior immunity, whereby the index case was twice vaccinated [17]. The authors state that the index case had evidence of SVF. This conclusion was only based on the high-

avidity antibodies detected in the serum samples after onset of rash. However, this case showed very low antibody concentrations (81 mIU/mL) and rather poor development of virus neutralizing antibodies (402 mIU/mL), which contrasts with the high levels in other cases of SVF and even with levels found in unvaccinated individuals with acute measles. [12-17]

A high intensity of exposure coupled with possibly a more pathogenic strain, as discussed above, could have contributed to this outbreak of measles among twice-vaccinated HCWs. Another explanation may be the relatively long period since individuals in our cohort received their most recent MMR dose, allowing for increased waning of immunity. If waning was the only explanatory factor, however, we would have expected a relatively higher attack rate in older HCWs. ^[18] Yet, there were relatively few cases among the first birth cohorts having been offered monovalent measles and MMR vaccine, compared with the later birth cohort, which is offered 2 doses of MMR. We did not find a difference in effectiveness between these schedules, but this comparison lacked power owing to the low number of cases.

Measles in pre-immunized children underscores the importance of ensuring complete immunization schedules, timely booster doses, and maintaining high herd immunity. Further studies are needed to investigate vaccine efficacy and immunity durability in different populations. This article highlights the need for robust vaccination programs and surveillance to mitigate the burden of measles, even in partially immunized populations. The results of this study indicate that the burden of measles infection is still high among vaccinated and unvaccinated children in Indian population. This study familiar with age, gender and vaccination history of children shows the demographic risk factors for Measles Virus (MeV) infection in children.

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