Addressing Reemergence of Diphtheria among Adolescents through Program Integration in India

We report a diphtheria outbreak mostly among children (median 12 years; range 4–26 years) of a religious minority in urban India. Case-fatality rate (15%, 19/124) was higher among unimmunized patients (relative risk 4.1, 95% CI 1.5–11.7). We recommend mandating and integrating immunization into school health programs to prevent reemergence.

We report a diphtheria outbreak mostly among children (median 12 years; range 4-26 years) of a religious minority in urban India. Case-fatality rate (15%, 19/124) was higher among unimmunized patients (relative risk 4.1, 95% CI 1.5-11.7). We recommend mandating and integrating immunization into school health programs to prevent reemergence.
This investigation was a public health response to an outbreak. Requisite approvals were obtained from national and state health authorities.
We conducted a retrospective cohort study to assess factors associated with death among casepatients. We defined the cohort as all patients with laboratory-confirmed diphtheria in Telangana during January 1-December 31, 2017. Among 124 case-patients identified, 25 (20%) were not located or declined to provide immunization information; 99 (80%) patients participated in the cohort study. Among the 99 patients, immunization coverage for DTP3 was 53% and for DTP second booster was 36%, based on vaccination card or parental recall when the card was not available (Table 1). Casepatients without all 3 doses of the primary immunization series were more likely than those having had the full DPT3 to die from diphtheria (relative risk [RR] 4.1; 95% CI 1.5-11.7) with 60% attributable risk. Symptoms significantly associated with death were hoarseness (100%), dyspnea (100%), bull neck appearance (89%), and stridor (42%) (p <0.001 for all). Delayed hospital admission (i.e., >72 hours elapsed after sore throat onset) was also significantly associated with death (RR 2.8, 95% CI 1.2-6.8) ( Table 2).
We reviewed DTP immunization coverage trends in Telangana during 1998-2016 by assessing National We assessed the available records during 2014-2017 from 12 healthcare facilities in urban Hyderabad. None had periods when vaccines were out of stock, all had cold chain temperature logs maintained within the appropriate range, and all conducted >80% of the immunization sessions across all quarters; administrative immunization reported >90% DTP3 coverage. Interviews of health facility staff revealed that all 12 facilities had an immunization-tracking system in place for children <2 years of age. However, for children ≥2 years of age, there was no tracking mechanism, and they were not included in the routine coverage surveys and administrative coverage reports. Mission Indradhanush, a nationwide immunization drive by the government of India, has made major gains in improving immunization coverage; however, it did not target children ≥2 years of age (7).
Our study is limited because probable cases of diphtheria not confirmed by laboratory testing and asymptomatic cases were excluded, so the outbreak was likely underestimated. In addition, we did not conduct population immunization coverage surveys in the affected community and relied on published government estimates instead.

Conclusions
The age shift of diphtheria cases is of global concern. suggested that areas with greater immunization coverage have experienced an age-shift with a higher incidence among older children (8,9). In this diphtheria outbreak, cases were primarily among adolescents and school-age children; no cases were reported in children <4 years of age, probably because of high (>90%) vaccine coverage in birth cohorts since 2014. Gaps in booster-dose coverage probably resulted in waning immunity provided by the primary series (10,11). This outbreak had a much higher CFR (15%) compared with the national CFR of 3% for diphtheria in 2017 (12). CFR was higher among underimmunized children and those with delayed hospital admission, similar to previously reported outbreaks (13)(14)(15). Hyderabad reported incidence 5 times higher than the average in the state. The Muslim community makes up only for 12% of Telangana's population but accounted for 60% of cases and 74% of deaths due to diphtheria reported in the state.
To address the factors leading to this outbreak and to prevent diphtheria outbreaks in the future, we recommended 2 main strategies. First, we recommend adding 2 adolescent booster doses at 10 and 16 years of age to the routine immunization schedule, which would address possible waning of immunity from the primary series. To help accomplish this, we recommend integrating the immunization program with school health programs. Schools annually identify and track eligible schoolchildren for administration of age-appropriate vaccine doses. The government could mandate that schools require a second DTP booster before students enter primary school (ages 5-6 years) and a tetanus-diphtheria booster as they leave primary school (ages 10-11 years) and secondary school (ages 15-16 years). Second, we recommend implementing focused immunization services in urban Muslim communities by engaging religious leaders and community stakeholders. Addressing gaps in routine delivery of immunization service in marginalized and underserved populations is essential for averting future vaccine-preventable disease outbreaks.