Seroprevalence of Diphtheria in Antananarivo, Madagascar, and Cambodia

Abstract

Background: Amidst a global resurgence of diphtheria cases with numerous outbreaks recorded worldwide since 2000, a better understanding of this vaccine-preventable disease's circulation is needed.

Methods: We retrospectively analyzed sera from 2 sero-epidemiological cross-sectional studies in Madagascar and Cambodia on fully primo-vaccinated 3- to 15-year-olds. Using enzyme-linked immunosorbent assay (ELISA) and seroneutralization (Vero Cell TNT) for the 3- to 8-year-olds with low ELISA titration values (<0.01 IU/mL), we assessed (i) the duration of protection by primary vaccination for 3- to 8-year-olds and (ii) the level of diphtheria in children and adolescents. Seropositivity was defined as a titration value (by ELISA or TNT) of at least 0.1 IU/mL and was used as a proxy for diphtheria infection among individuals >6 years postvaccination.

Results: Seven hundred forty-five children in Cambodia and 949 children in Madagascar were included. Our results show significantly more unprotected children among the 5- to 6-year-olds than among the 3- to 4-year-olds, with 41.1% (39/95) vs 26.7% (27/101; P = .03) in Cambodia and 21.4% (27/126) vs 8.0% (9/113; P < .01) in Madagascar. In Cambodia and Madagascar, respectively, 27.8% and 20.7% of the participants whose primary vaccination was performed >6 years earlier were seropositive, suggesting diphtheria infection. In both countries, we observed a higher rate of infected children when the last vaccine injection had been received 7-8 years or 11-12 years earlier vs 5-6 years earlier.

Conclusions: Our data show that the disease is present at high levels in Cambodia and Madagascar and that the national recommendation-primary vaccination-is not sufficient: Booster doses appear necessary at around 6 years of age and for adolescents, as recommended by the World Health Organization.

Keywords: Cambodia; Madagascar; diphtheria; serology; vaccination.

Figure 1.

Flowcharts, for Cambodia (top) and Madagascar (bottom). Abbreviation: ELISA, enzyme-linked immunosorbent assay.

Figure 2.

In Cambodia, age-stratified analysis. Rate, per age category based on ELISA and TNT results, of unprotected children (IgG < 0.01 IU/mL), of partially protected children (IgG between 0.01 and 0.1 IU/mL), and of protected children (IgG ≥ 0.1 IU/mL). Differences between the rates of unprotected children between age categories are reported. Abbreviations: ELISA, enzyme-linked immunosorbent assay; TNT, toxin neutralization.

Figure 3.

In Cambodia, analysis per time since last vaccine injection. Rate of protected/infected children (IgG ≥ 0.1 IU/mL) and of not/partially protected children (IgG < 0.1 IU/mL) based on ELISA results. Stars indicate time span categories for which the rate of protected (red)/not or partially protected (blue) individuals is significantly different when compared with the 5–6-year time span category. Of note, due to the titration values for protected/infected and not/partially protected, the blue curve is a “mirror version” of the red curve. Abbreviations: ELISA, enzyme-linked immunosorbent assay; IgG, immunoglobulin G.

Figure 4.

In Madagascar, age-stratified analysis. Rate, per age category based on ELISA and TNT results, of unprotected children (IgG < 0.01 IU/mL), of partially protected children (IgG between 0.01 and 0.1 IU/mL), and of protected children (IgG≥0.1 IU/mL). Differences between the rates of unprotected children between age categories are reported. Abbreviations: ELISA, enzyme-linked immunosorbent assay; TNT, toxin neutralization.

Figure 5.

In Madagascar, analysis per time since last vaccine injection. Rate of protected/infected children (IgG ≥ 0.1 IU/mL) and of not/partially protected children (IgG < 0.1 IU/mL) based on ELISA results. Stars indicate time span categories for which the rate of protected (red)/not or partially protected (blue) individuals is significantly different when compared with the 5–6-year time span category. Of note, due to the titration values for protected/infected and not/partially protected, the blue curve is a “mirror version” of the red curve. Abbreviations: ELISA, enzyme-linked immunosorbent assay; IgG, immunoglobulin G.