Efficacy of Atovaquone/Proguanil for Malaria Prophylaxis in Children and Its Effect on the Immunogenicity of Live Oral Typhoid and Cholera Vaccines

Abstract

A double-blind, placebo-controlled study was conducted to measure the impact of malaria prophylaxis with atovaquone/proguanil (A-P) on the immunogenicity of vaccines against typhoid fever and cholera, Salmonella serotype Typhi Ty21a and Vibrio cholerae CVD103-HgR, respectively. A total of 330 Gabonese schoolchildren were assigned to receive either A-P or placebo for 12 weeks. Vaccination occurred 3 weeks after the start of prophylaxis, and immunogenicity was assessed 4 weeks after vaccination. The protective efficacy of A-P against Plasmodium falciparum malaria was of 97% (95% confidence interval, 79%–100%). The 2 treatment groups did not differ significantly with regard to changes in antibody titers after vaccination (P = .96 for anti-S. Typhi IgG antibodies, P = .07 for anti-S. Typhi IgA antibodies, and P = .64 for vibriocidal antibodies). The A-P combination was highly effective for malaria prophylaxis, without interfering with the in vivo immunogenicity of CVD103-HgR and Ty21a vaccines, and it could therefore be simultaneously administered with these vaccines.