High Measles Complication Rates and Vaccine Breakthroughs Among Pediatric Cases in Iraq: A Cross-Sectional Study

Study design

A retrospective cross-sectional study examined laboratory-confirmed measles cases to analyze epidemiological and clinical characteristics across age groups and demographics.

Study setting

Data were collected from surveillance systems and clinical facilities at Ramadi Teaching Hospital for Maternity and Children in Al-Anbar Province, Iraq, covering urban and rural populations.

Case ascertainment and surveillance system

The hospital’s passive surveillance system, serving approximately 500,000 individuals, identified suspected measles cases through primary care and emergency referrals. Of 247 suspected cases tested, 200 (81%) were laboratory-confirmed and analyzed.

Study duration

Data on measles cases reported between January 2023 and March 2024 were compiled through retrospective record review to capture seasonal variation and outbreak dynamics.

Sample size and statistical power

Sample size calculation assumed 30% complication rates with 80% power and α = 0.05, yielding a minimum of 196 patients. All 200 laboratory-confirmed measles cases at Ramadi Teaching Hospital during the study period were included. Post-hoc analysis showed >90% power to detect 20% differences in complication rates between age groups.

Inclusion and exclusion criteria

Inclusion criteria: children aged 0-15 years with measles-consistent clinical features (fever >38°C, maculopapular rash, plus cough, coryza, or conjunctivitis), laboratory confirmation (IgM-positive or RT-PCR), and Al-Anbar Province residency. Exclusion criteria: unconfirmed diagnosis, immunodeficiency, incomplete records, and post-exposure prophylaxis within 72 hours.

Ethical approval

This study received retrospective ethical approval from the Ethics Committee of the College of Medicine, University of Anbar (Protocol No. 299, dated 26/10/2024-AMC). Retrospective approval was necessitated due to the emergent nature of the measles outbreak investigation, which required immediate public health response and data collection during the outbreak period (January 2023 to March 2024). The study utilized de-identified retrospective clinical and laboratory data collected as part of routine measles surveillance and patient care activities. Written informed consent was obtained from parents/guardians at the time of hospital admission for clinical care and routine surveillance purposes. The Ethics Committee determined that retrospective approval was appropriate given: (1) the public health emergency context requiring immediate outbreak investigation; (2) utilization of data collected during routine clinical care and mandatory disease surveillance; (3) complete anonymization of patient identifiers prior to analysis; and (4) minimal risk to participants. All data management procedures adhered to the principles of the Declaration of Helsinki and National Data Protection Laws.

Case definition

Measles was defined per WHO criteria as fever with maculopapular rash and cough. Confirmed cases were identified through measles-specific IgM antibodies (ELISA; Euroimmun, Germany) and/or RT-PCR from throat swabs.

Vaccination status verification

Vaccination status was verified using official Iraqi Ministry of Health immunization cards. Verbal reports without documentation were excluded from vaccine effectiveness analyses. Data included doses administered, vaccination dates, and batch numbers. Patients were classified as unvaccinated (zero doses), partially vaccinated (one dose), or fully vaccinated (two doses).

Data collection

Data were collected using standardized case report forms including demographic characteristics, clinical features, laboratory findings (measles-specific IgM, RT-PCR, complete blood count, C-reactive protein), vaccination history, nutritional status, household size, comorbidities, and outcomes. Complications (pneumonia, encephalitis, otitis media) were defined per WHO criteria.

Cold chain assessment

Cold chain integrity was assessed across 15 primary health centers. Cold chain breaches (temperatures >8°C) were documented in 40% of facilities, primarily due to power failures. Breakthrough infection analysis by vaccine batch showed no clustering pattern, suggesting systemic factors rather than batch-specific failures.

Statistical analysis

Statistical analyses used IBM SPSS Statistics version 26. Descriptive statistics are presented as frequencies with percentages (95% CI) for categorical variables and means ± standard deviations for continuous variables. Chi-square tests evaluated associations between categorical variables. Multivariable logistic regression identified independent predictors of complications (p < 0.05) after adjusting for vaccination status, age, sex, residence, nutritional status, household density, comorbidities, and C-reactive protein levels.

Demographic characteristics

Among 200 laboratory-confirmed measles cases (serological or molecular confirmation), 64 were infants aged <12 months (32%, 95% CI: 25.6-38.9%) and 136 were children aged 1-9 years (68%, 95% CI: 61.1-74.4%). No adolescent cases were documented. The cohort comprised 120 males (60%) and 80 females (40%). Rural residents accounted for 58% (n = 116) of total cases ( Table 1).

Vaccination status and breakthrough infections

Of 200 confirmed cases, 142 (71%, 95% CI: 64.2-77.1%) were breakthrough infections in vaccinated individuals: 82 (58%) had one dose and 60 (42%) had two doses. Despite 94% population vaccination coverage among children aged 1-9 years, breakthrough infections represented 71% of cases. Most cases were rural residents (58%), with 93% developing complications versus 81% in urban patients, suggesting geographic disease burden variation ( Table 1).

Clinical manifestations

All patients presented with fever (100%; mean 38.9°C, range 38.0-40.2°C) and maculopapular rash (100%). The complete measles triad (cough, coryza, conjunctivitis) occurred in 56.0% of cases. Koplik’s spots were documented in 22.0%. Systemic manifestations included anorexia (76.0%), malaise (70.0%), headache (60.0%; more frequent in older children, p = 0.049), and fatigue (56.0%). Rash was generalized (44.0%) or trunk-predominant (56.0%), with pruritus in 62.0%. Symptom frequencies were similar across age groups except headache ( Table 2).

Complications

The most frequent complications were pneumonia (154 cases, 77%, 95% CI: 70.6-82.5%), diarrhea (146 cases, 73%, 95% CI: 66.3-78.9%), otitis media (90 cases, 45%, 95% CI: 38.1-52.1%), and encephalitis (46 cases, 23%, 95% CI: 17.5-29.4%). Unvaccinated children had significantly higher odds of pneumonia (OR: 3.2, 95% CI: 1.8-5.6, p < 0.001) and encephalitis (OR: 2.8, 95% CI: 1.2-6.4, p = 0.015) versus vaccinated children ( Table 3).

Laboratory findings

Mean C-reactive protein was 56.8 mg/dL (SD ± 23.4). Laboratory confirmation showed positive measles-specific IgM in 180 cases (90%) and positive RT-PCR in 138 cases (69%), with 118 positive by both methods. A limitation was potential serological cross-reactivity with other paramyxoviruses, though ELISA specificity was 98.7%. Universal C-reactive protein elevation (mean 56.8 ± 24.6 mg/dL; range 12-98) correlated with pneumonia and encephalitis severity. Mild-to-moderate ALT elevation (68.0%; mean 52.1 ± 5.2 U/L) and AST elevation (72.0%; mean 61.3 ± 6.1 U/L) were observed. Mean WBC count was 10.8 ± 4.1 × 10³/μL (range 2.3-17.8), with lymphopenia (<1.5 × 10³/μL) in 42.0%, consistent with measles-associated immunosuppression ( Table 4).

Dose-specific clinical outcomes

Among 142 vaccinated cases, 57.7% had one dose and 42.3% had two doses. Two-dose recipients had lower complication rates: pneumonia 68.3% versus 79.3% (p = 0.131), otitis media 25.0% versus 43.9% (p = 0.020), diarrhea 66.7% versus 75.6% (p = 0.240), and encephalitis 18.3% versus 25.6% (p = 0.300). Only otitis media reduction reached statistical significance, suggesting partial protective effect ( Table 5).

Vaccination status and breakthrough infections

Unvaccinated individuals comprised 28.0% of cases, while 71.0% were breakthrough infections in vaccinated individuals. Age-stratified analysis showed 25.0% vaccination coverage in infants (<12 months). Among children aged 1-9 years, 94% (126/134) had breakthrough infections, suggesting vaccine failure potentially from cold chain breaches or waning immunity ( Table 6). Children under 12 months are ineligible for routine measles vaccination per national immunization schedules. Population-level vaccination coverage data are needed to calculate accurate vaccine effectiveness estimates.

Risk factor analysis

Multivariable logistic regression identified significant independent predictors of complications (Nagelkerke R² = 0.34, Hosmer-Lemeshow p = 0.42). Rural residence predicted pneumonia and diarrhea. Children aged <12 months had 3.8-fold elevated encephalitis risk. Approximately one-quarter developed otitis media, with nearly four-fold increased risk among unvaccinated children. Male sex was not significantly associated with complications (OR 1.3, 95% CI 0.8-2.0, p = 0.298) ( Table 7).

The vaccination paradox: Interpretation framework

The finding that 94% of children aged 1-9 years with confirmed measles had been vaccinated, with 42% completing two doses, warrants urgent investigation. While population-level coverage denominators are needed to establish vaccine failure definitively, multiple indicators suggest genuine program deficiencies. Breakthrough disease among two-dose recipients (42%) substantially exceeded the expected 1-3% failure rate.²⁰ Vaccinated cases manifested severe disease (74.6% pneumonia prevalence), indicating primary vaccine failure or waning immunity. Cold chain breaches during conflict provide mechanistic explanations for potency loss.^21,22 Importantly, dose-response relationships (otitis media: 43.9% single dose vs. 25.0% two doses, p = 0.020) suggest partial rather than complete vaccine failure.

Alternative explanations and contributing factors

Several mechanisms may explain breakthrough infections. Maternal antibodies may reduce vaccine immunogenicity in approximately one-quarter of infants under one year.²³ Administration errors are anticipated in resource-constrained settings. Peripheral storage failures with inadequate temperature monitoring may compromise vaccine potency despite intact central cold chain infrastructure. Waning immunity, particularly in children vaccinated during infancy with maternal antibodies present, may contribute to susceptibility.²³ Nutritional factors, including vitamin A deficiency documented among Iraqi children, affect vaccine immunogenicity and enhance disease severity.²⁴ Circulation of vaccine-resistant strains warrants molecular epidemiological investigation, though measles vaccine demonstrates remarkable antigenic stability.

Comparison with regional and global data

Iraq’s measles epidemiological pattern resembles other conflict-affected Eastern Mediterranean countries (Syria, Yemen, Afghanistan), with elevated complication rates and vaccine breakthrough infections.^25,26 Iraq’s documented vaccination coverage among cases (71%) exceeds regional averages, suggesting implementation deficiencies beyond inadequate coverage.²⁶ Recent literature indicates 95-99% two-dose vaccine effectiveness, contrasting with our findings. Post-conflict sub-Saharan Africa showed vaccine effectiveness declining to 70-85% due to cold chain issues, paralleling our observations.^27,28 This 200-case analysis provides greater statistical power than typical regional reports (50-100 cases) and revealed strong associations between rural residence and complications (pneumonia OR 2.4; diarrhea OR 1.9). Global disease resurgence during 2019-2025 demonstrates how conflict-related health disruptions can reverse elimination progress despite approaching 95% two-dose coverage targets.^29,30

Exceptional complication burden

Complications demonstrate multifactorial etiology, including healthcare access barriers, malnutrition, and post-conflict vitamin A deficiency. Additional investigation is needed for potential strain virulence factors. Encephalitis prevalence (23%) substantially exceeds high-income settings (0.1-0.3%), potentially reflecting tertiary facility ascertainment bias or genuine biological phenomena. Permanent neurological sequelae developed in 8.7% of encephalitis cases.²¹ Diarrhea (73%) and pneumonia (77%) rates exceed middle-income countries, primarily due to delayed presentation, malnutrition, and overwhelmed healthcare infrastructure.¹⁸ Low Koplik’s spot detection (22% versus expected 60-70%) likely reflects observation timing constraints, as these pathognomonic lesions appear 2-3 days before rash and fade rapidly.¹⁷ Healthcare provider training for early measles recognition is needed.

Urgent research priorities

Critical research priorities include: (a) population-based serosurveys for immunity assessment; (b) vaccine potency testing of field samples; (c) comprehensive cold chain audits; (d) case-control effectiveness studies; (e) molecular epidemiology with viral genotyping; and (f ) operational research on implementation barriers. In the absence of definitive data, conservative assumptions regarding program performance are warranted.

Clinical implications

Clinicians should maintain high clinical suspicion for measles in vaccinated children with fever and rash. The 77% pneumonia prevalence warrants early chest radiography and oxygen saturation monitoring. With 23% encephalitis incidence and 8.7% permanent neurological sequelae, patients with altered mental status require immediate intensive care consultation. Vitamin A supplementation is imperative, as deficiency increases mortality 2- to 4-fold.³¹ Patients require intensive fluid therapy for dehydration. Integration of WHO treatment guidelines with local protocols can improve outcomes.^32–34 When breakthrough infections occur, investigation should focus on vaccine handling and administration rather than discouraging vaccination. Outbreak investigations must include vaccinated individuals to assess transmission dynamics comprehensively.

Implications for measles elimination strategy

Achieving measles elimination in Iraq requires multi-level interventions addressing identified programmatic gaps.

Cold Chain and Delivery System Improvements: Establishing solar-powered cold chain infrastructure at over 500 primary health facilities to ensure vaccine potency during electrical power outages; implementing quarterly vaccine potency testing and continuous temperature monitoring with automated alert systems.²⁷

Immunization Strategy: Conducting supplementary immunization campaigns targeting 1.2 million children aged 1-9 years to address immunity gaps. Future integrated measles-vitamin A campaigns will enhance vaccine immunogenicity and reduce complication rates.³¹

Health System Strengthening: Training over 3,000 healthcare workers in proper vaccine administration and cold chain management; deploying mobile vaccination teams to rural populations given elevated complication rates (pneumonia OR 2.4, p = 0.002); improving case detection through community-based surveillance.

Surveillance Enhancement: Establishing real-time reporting from health facilities; strengthening laboratory capacity; implementing sentinel site monitoring. Supplementary immunization activities can achieve high coverage even in challenging security contexts.²⁹

Study limitations

The single-center retrospective design limits generalizability and may introduce selection bias toward severe cases, though RT-PCR confirmation in 69% supports diagnostic reliability. Additional limitations include reliance on parental recall for 29% of vaccination status (potential misclassification bias), absence of population-level vaccine coverage data preventing accurate vaccine effectiveness calculation, conflict-related healthcare disruptions, lack of viral genotyping, and no long-term outcome assessment. Hospital-based ascertainment likely overrepresents severe disease versus community surveillance.

Recommendations

Priorities include cold chain integrity assessment, field vaccine potency testing, post-vaccination seroconversion evaluation, supplementary immunization campaigns, surveillance strengthening, and waning immunity investigation. Future studies should assess seroconversion rates and conduct molecular genotyping to identify potential vaccine-escape variants. Measles elimination requires sustained political commitment, adequate resources, and enhanced regional cooperation.