A comparison of clinical and immunologic features in children and older patients hospitalized with severe cholera in Bangladesh

Abstract

Background: : Infection with Vibrio cholerae induces protection from subsequent severe disease, suggesting that an effective vaccine could be an important preventive strategy. Available vaccines provide less protection against cholera than natural infection, particularly in children.

Methods: : We examined a cohort of 121 children (2 years-12 years of age) and 276 older patients (>12 years of age) hospitalized with cholera in Dhaka, Bangladesh over a 4-year period, to compare clinical features in older patients and children and immune responses to key antigens.

Results: : Older patients had more severe disease. Children with cholera were more commonly retinol deficient, while zinc deficiency was equally prevalent in both groups. Children developed higher vibriocidal and serum immune responses to the B subunit of cholera toxin (CTB). In contrast, older patients mounted higher immune responses to 2 other key V. cholerae antigens, the lipopolysaccharide (LPS) and toxin coregulated pilus antigens (TcpA). We compared immune responses following infection with those occurring after receipt of a live, oral vaccine in both children and older patients in Bangladesh, during a similar time period. The response rates for vibriocidal and LPS antibodies were higher after infection than after vaccination. Both vaccinated older patients and children responded poorly to CTB and TcpA.

Conclusions: : Although children developed vigorous vibriocidal and CTB-specific responses following infection, they had lessened responses to LPS and TcpA compared with older patients, as well as lessened responses to vaccination. More studies need to be carried out to determine factors, including micronutrient interventions that can improve responses in children to both natural infection and vaccination.

FIGURE 1

Fold increases in serum vibriocidal antibodies (log₁₀ transformed) in children compared with those seen in older patients in the subset with infection with V. cholerae O1. (Bars) represent the mean (and 95% CI of the mean) increase in vibriocidal responses >16-fold in children and older patients measured as a ratio between convalescence at day 7 (black bars) or day 21 (shaded bars), compared with titers at the acute stage on day 2. *P = 0.01 and 0.0004 for the magnitude of differences between children and older patients at days 7 and 21, respectively.

FIGURE 2

Fold increases between days 2 and 7 in serum IgG (black bars) and IgA (shaded bars) to CTB in children compared to older patients with cholera. Error bars represent the 95% CI of the means. *P = 0.002 for the difference in the magnitude of rises in IgA between children and older patients.

FIGURE 3

Fold increases between days 2 and 7 in serum IgG (black bars) and IgA (shaded bars) to LPS in children compared to older patients with cholera. Error bars represent the 95% CI of the means. *P = 0.03 and **P = 0.0008 for the differences in the magnitude of rises between children and older patients, respectively.

FIGURE 4

Fold increases between days 2 and 7 in serum IgG (black bars) and IgA antibodies (shaded bars) to TcpA children compared to older patients with cholera. Error bars represent the 95% CI of the means. *P = 0.04 and **P = 0.03 for the differences in the magnitude of rises between children and older patients, respectively.