Effect of Antihelminthic Treatment on Vaccine Immunogenicity to a Seasonal Influenza Vaccine in Primary School Children in Gabon: A Randomized Placebo-Controlled Trial

Abstract

BackgroundHelminth infections are a major public health problem, especially in the tropics. Infected individuals have an altered immune response with evidence that antibody response to vaccination is impaired. Hence, treatment of helminth infections before vaccination may be a simple intervention to improve vaccine immunogenicity. In the present study we investigated whether a single-dose antihelminthic treatment influences antibody responses to a seasonal influenza vaccine in primary school children living in Gabon, Central Africa.MethodsIn this placebo-controlled double-blind trial conducted in Gabon the effect of a single-dose antihelminthic treatment with 400 mg albendazole versus a placebo one month prior to immunization with a seasonal influenza vaccine was investigated. Antiviral antibody titers against all three vaccine strains were assessed by haemagglutination inhibition (HI) test at baseline (Day 0; vaccination) and four weeks (Day 28) as well as 12 weeks (Day 84) following vaccination. Vaccine-specific memory B-cell response was measured at Day 0 and Day 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The trial is registered with the Pan African Clinical Trials Registry (PACTR) (PACTR201303000434188).Results98 school children aged 6–10 years were randomly allocated to receive either antihelminthic treatment or placebo and were vaccinated one month after the treatment. The prevalence of helminths at baseline was 21%. Vaccine-specific HI titers against at least one of the three vaccine strains increased at Day 28 and Day 84 in all participants. HI titers against both influenza A strains as well as memory B-cell response were modestly higher in the antihelminthic treated group compared to the placebo group but the difference was not statistically significant. Total but not specific IgA was elevated in the antihelminthic treated group compared to the control group at Day 28.ConclusionIn our setting antihelminthic treatment had no significant effect on influenza vaccine immunogenicity. A trend towards better antiviral and vaccine immunogenicity in the antihelminthic treated group encourages studies to be conducted with alternative treatment schedules or in populations with a higher helminth burden.

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

“…The HPV specific IgG level titers were slightly higher in the group that underwent anti-helminth treatment compared to the group with the chronic S. mansoni infection. This finding is in accordance with a study that investigated the effect anti-helmithic treatment has on the efficacy of the influenza and Tetanus toxoid vaccine [21,40].…”

“…The study provided an indication that the study subjects with chronic schistosomiasis were capable of responding to the vaccines and produced HPV specific IgG antibodies, however, after the 6 th week a decrease in IgG levels was observed. This reduced humoral response has also been observed in helminth infected subjects administered with a number of vaccines [22,[40][41][42].…”

The efficacy, effectiveness, and immunogenicity of influenza vaccines in Africa: a systematic review

“…The presence of helminths was associated with poorer immunogenicity. A follow up study 22 failed to show a significant effect of albendazole on HAI response to IIV3, although the study was powered for a much higher helminth burden than observed.…”

“…Studies varied by study design, vaccine type (inactivated influenza vaccine, IIV3; live attenuated influenza vaccine, LAIV) and study population (Table 1). 16 were from South Africa, [11][12][13][14][16][17][18][19]23,25,[27][28][29][30][31][32] two each from Gabon 21,22 and Kenya, 20,26 and one study each from Mali 15,33 Senegal 24 and The Gambia. 33 The following study populations were identified: pregnant women (6 studies), children (6), elderly (3), HIV-Positive adults (1), healthcare workers (1) and all age groups (6).…”

“…Twelve studies were identified that evaluated influenza vaccine immunogenicity, [11][12][13][15][16][17]19,21,22,25,32,33 the majority of which focused on haemagglutination inhibition (HAI) titres, considered at present to be the gold standard immune correlate of protection following immunisation. 35 This is, however, primarily true following IIV3 and not LAIV (which does not induce potent serum HAI responses), and where a clear correlate of protection is not yet established.…”