Elsevier

Vaccine

Volume 34, Issue 44, 17 October 2016, Pages 5384-5390
Vaccine

A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children

https://doi.org/10.1016/j.vaccine.2016.07.040Get rights and content

Abstract

Background

We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells.

Methods

In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12 weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day −28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique.

Results

Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant difference in antibody and B-cell response between children receiving albendazole compared to those receiving placebo.

Conclusion

A single-dose treatment with albendazole prior to immunization had no effect on meningococcal or cholera vaccine immunogenicity in our study population.

Introduction

Infection with geohelminths, mainly Ascaris (A.) lumbricoides, Trichuris (T.) trichiura and hookworm, is a major public health problem affecting 20% of the world‘s population, especially in Sub-Saharan Africa (SSA). It is one of the most neglected tropical diseases with serious health, nutritional and social outcomes for affected individuals [1], [2], [3]. According to the World Health Organization (WHO) in 2014 approximately 2 billion of the world’s population were infected with helminths [2], mainly children [3] and pregnant women [4]. Van den Biggelaar reported in 2004 that 46% of children, aged between 5–13 were infected with A. lumbricoides and 71% were infected with T. trichiura [5]. Three years later van Riet reported that 15% (living in a semi-urban area) and 55% (living in a rural area) of 7–12 year-olds were infected with A. lumbricoides and 12% (semi-urban area) and 64% (rural area) had a T. trichiura infection [6]. Chronic infection with geohelminths has an impact on health as well as on cognitive skills [7], [8], [9], [10], [11] and it has been shown that infection with helminths leads to altered immune responses [12].

Vaccination is one of the most effective tools to prevent infectious diseases. Nonetheless, seroconversion and therefore efficacy is variable in vaccinated individuals depending on age, environment and genetic host factors [13], [14], [15]. In addition, acute and chronic infections have an influence on vaccine outcome [16], [17]. We and others have recently shown that helminth infections impair immune response to vaccination [5], [6], [18], [19], [20], [21], [22]. The WHO promotes helminth control by periodic deworming once or twice a year, depending on prevalence, as a cost-effective intervention [2], [22]. Regular antihelminthic treatment through mass drug administration programs in high-risk groups like school children is considered effective for controlling the helminth infection burden, but it is not regularly applied in Gabon and other endemic countries [23]. Therefore we aimed to investigate the effect of a single-dose antihelminthic treatment on vaccine immunogenicity. Recently, we reported results of the first part of the present study, where primary school children were vaccinated with a seasonal influenza vaccine [18]. Here we report the second part of the study investigating the vaccine immunogenicity of a meningococcal and an oral cholera vaccine following a single-dose of antihelminthic treatment. The vaccines were chosen to assess whether different routes of administration (subcutaneous vs. oral) have different effects on vaccine immunogenicity in helminth infected children. Furthermore these vaccines are not part of the Expanded Program on Immunization (EPI) and we expected that no basic or low level antibody titer would be detectable if the individuals did not report recent infection with these pathogens.

Section snippets

Trial design and setting

The study design is reported in detail elsewhere [18]. In brief, participants received one dose of antihelminthic treatment (albendazole 400 mg) (Micro Lab ltd, India) or placebo (Laboratories Sterop, Belgium) four weeks (Day −28) prior to vaccination with either a seasonal influenza vaccine (VAXIGRIP®, Sanofi Pasteur, season 2011/2012) intra muscularly ((i.m.) (n = 98) (part I)), meningococcal vaccine containing polysaccharides of Neisseria (N.) meningitidis group A and C (Sanofi Pasteur)

Results

From December 2011 until September 2012, 280 primary school children in Lambaréné and surroundings were screened, from whom 209 were randomized to receive either a single-dose 400 mg albendazole (n = 104) or placebo (n = 105). 71 participants were excluded due to S. haematobium infection, which was an exclusion criterion. One group received a polysaccharide meningococcal A + C vaccine (n = 96) and the other group received the oral cholera vaccine (n = 89). The study was conducted during different time

Discussion

Recent studies suggest that infection with helminths influences the immunological outcome of vaccination [18], [19], [21]. In a study conducted in Ecuador Cooper et al. showed that children infected with A. lumbricoides had a reduced antibody response towards the oral cholera vaccine CVD 103-HgR [21]. During a Phase 1 trial in Gabon to assess immunogenicity of a malaria vaccine candidate we found that children infected with T. trichiura exhibited a lower antibody response compared to those who

Funding

The study was supported by the German Federal Ministry of Education and Research (01 KA 1009).

Conflict of interest

All other authors declare that they have no conflicts of interest.

Acknowledgement

The authors thank Angelika Tremmel of the University of Würzburg for performing the serum bactericidal assays, the staff of CERMEL and all participants, Sonja Killinger for logistics and data entry as well as the members of the Institute for Clinical Epidemiology and applied Biometry in Tübingen. Ulrich Vogel (University of Würzburg) is acknowledged for his contributions to the quality assurance and validation of the serum bactericidal assay.

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