Typhoid is a persistent contributor to childhood morbidity in certain countries. Although the typhoid conjugate vaccine (TCV) has proven to be effective in reducing disease risk in patients, it is unclear what the duration of protection is. In a study published in International Journal of Infectious Diseases, investigators assessed the serologic response in children from outbreak areas in Hyderabad, Pakistan following immunization with the TCV.
For this prospective cohort study, 958 children aged 6 months to 10 years from Hyderabad, Pakistan were enrolled. Each participant received a single intramuscular TCV immunization, and of this cohort, 81 children received a second dose of TCV in November 2019. Participants must be “healthy” to be eligible for enrollment, and any child with an acute illness or underlying chronic diseases were excluded.
Blood samples were collected for anti-Vi immunoglobulin G (IgG) antibodies prior to immunization (baseline), and then again at 4 to 6 weeks, 6 months, and years 1, 2, 3, and 4 after vaccination. Additionally, data on socio-demographic characteristics, date of vaccination, and parent’s education were all collected using a questionnaire at the time of enrollment.
Participants’ caregivers were provided with a vaccination care that contained the number of a 24-hour hotline to use if they had any questions related to the vaccine. Surveillance was also conducted through monthly phone calls to identify any cases of fever, and during these calls, research staff asked the primary caregiver whether their child had a history of fever for 3 or more days during the past month, if the child was taken to a health care facility for treatment, or if any blood tests were performed. Children who had a persistent fever for 3 or more days without a clear sign of infection within the last 7 days of the phone call were offered blood cultures.
The study’s outcomes were the seroconversion rate, or the 4-fold rise in anti-Vi IgG titer, at each time point (4-6 weeks, 6 months, and years 1, 2, 3, and 4) compared with baseline. Additionally, the number of breakthrough infections during the study’s follow-up period were also assessed.
After vaccination, 837 children had provided a sample at 4 to 6 weeks, 602 at 6 months, 762 at 1 year, 722 at 2 years, 287 at 3 years, and 639 at 4 years. The median age of study participants at the time of enrollment was 3.5 years (IQR: 1.9-5.3 years), with approximately 59.3% of children enrolled from the Qasimabad area (n = 568). Additionally, the investigators considered approximately 81.1% (n = 693) of children “well-nourished.”
At 4 to 6 weeks after a single dose of TCV, the investigators observed seroconversion in nearly all participants (n = 802; 95.8%). Most continued to remain above the seroconversion threshold during follow-up, with about 75.6% (n = 438) of children remaining seroconverted at 4 years following vaccination. Further, the frequency of seroconversion at 4 to 6 weeks was higher in children aged 2 years or younger (99.5%) than in children aged >2 to 5 years (95.8%) and >5 to 10 years (92.5%); however, during follow-up, antibody decay was faster in younger children, with only 63.1% of children aged 2 years or younger remaining somewhat seroconverted at the 4-year time point compared with older children (>2-5 years: 78.2%; >5-10 years: 82.7%).
Key Takeaways
- High Seroconversion, Varying Longevity of Protection: Nearly all children (95.8%) demonstrated seroconversion at 4 to 6 weeks after receiving a single dose of the typhoid conjugate vaccine (TCV), but younger children experienced faster antibody decay, with only 63.1% of those aged 2 years or younger remaining seroconverted at 4 years, compared to older age groups.
- Sustained Immunity With an Additional Dose: Among children who received a second dose of TCV (n = 81), 96.3% seroconverted at 4 to 6 weeks and 91.5% remained seroconverted at 2 years, showing improved and sustained immune responses in this small subpopulation.
- Ongoing Surveillance Needed: The study highlights the importance of continued surveillance to monitor long-term vaccine efficacy, assess population impact, and determine if booster doses or adjusted vaccination protocols may be necessary to optimize protection, especially in younger children.
In addition, the anti-Vi IgG geometric mean antibody titers peaked at 4 to 6 weeks in all children, then declined over the 4-year follow-up period; however, levels remained elevated compared to baseline in all age groups. Children aged 2 years or younger had lower anti-Vi titers at each time point than in children above the age of 2. Participants who did not seroconvert at 4 to 6 weeks already had high antibody titers at baseline and similar titers at the later post-immunization time points compared with those who did seroconvert.
Further, of the 81 children who received a second dose of TCV, approximately 26% (n = 21) had received it between 6 months to 1 year following the first dose (median time: 9.4 months [IQR: 9.6-9.6]), and 60 children (74%) received it between 1 to 2 years (median: 14.4 months [IQR: 12.0-16.4]). In addition, 80 children (99%) provided at blood sample for anti-Vi IgG ELISA at the 4- to 6-week time period and 71 (88%) at the 2-year time period. Seroconversion was observed in 77 (96.3%) of the children at 4 to 6 weeks and 65 (91.5%) at 2 years. Only 3 children failed to seroconvert even after receiving a second dose before the 2-year time point, but generally, higher sustained responses at 2 years and beyond were observed in this subpopulation.
The investigators note that despite the number of follow-ups, not all participants were able to be contacted because of refusals, migration, and COVID-19 pandemic lockdowns. Additionally, another limitation could be missed or unreported episodes of fever. The investigators urge that continued surveillance and monitoring of patients are essential to better assess the population impact of routine TCV vaccination and explore the potential need to reevaluate vaccination protocol.
REFERENCE
Qamar FN, Qureshi S, Haq Z, et al. Longevity of immune response after a single dose of typhoid conjugate vaccine against Salmonella Typhi among children in Hyderabad, Pakistan. IJID. 2024;147:107187. doi:10.1016/j.ijid.2024.107187
