Immunogenicity and safety of MF59-adjuvanted and full-dose unadjuvanted trivalent inactivated influenza vaccines among vaccine-naïve children in a randomized clinical trial in rural Senegal.

INTRODUCTION: Effective, programmatically suitable influenza vaccines are needed for low-resource countries. MATERIALS AND METHODS: This phase II, placebo-controlled, randomized safety and immunogenicity trial (NCT01819155) was conducted in Senegal using the 2012-2013 Northern Hemisphere trivalent influenza vaccine (TIV) formulation. Participants were allocated in a 2:2:1 ratio to receive TIV (full-dose for all age groups), adjuvanted TIV (aTIV), or placebo. Participants were stratified into age groups: 6-11, 12-35, and 36-71 months. All participants were vaccine-naïve and received two doses of study vaccine 4 weeks apart. The two independent primary objectives were to estimate the immunogenicity of TIV and of aTIV as the proportion of children with a hemagglutination inhibition (HI) antibody titer of ≥1:40 to each vaccine strain at 28 days post-dose two. Safety was evaluated by solicited local and systemic reactions, unsolicited adverse events, and serious adverse events. RESULTS: 296 children received TIV, aTIV, or placebo, and 235 were included in the final analysis. After two doses, children aged 6-11, 12-35, and 36-71 months receiving TIV had HI titers ≥1:40 against A/H1N1 (73.1%, 94.1%, and 97.0%), A/H3N2 (96.2%, 100.0%, and 100.0%), and B (80.8%, 97.1%, and 97.0%), respectively. After two doses, 100% children aged 6-11, 12-35, and 36-71 months receiving aTIV had ≥1:40 titers against A/H1N1, A/H3N2, and B. After a single dose, the aTIV response was comparable to or greater than the TIV response for all vaccine strains. TIV and aTIV reactogenicity were similar, except for mild elevation in temperature (37.5-38.4 °C) which occurred more frequently in aTIV than TIV after each vaccine dose. TIV and aTIV had similarly increased pain/tenderness at the injection site compared to placebo. CONCLUSIONS: Both aTIV and full-dose TIV were well-tolerated and immunogenic in children aged 6-71 months. These vaccines may play a role in programmatically suitable strategies to prevent influenza in low-resource settings.

An insight into immunogenic salivary proteins of Anopheles gambiae in African children.

BACKGROUND: During blood feeding, the mosquito injects saliva into the vertebrate host. This saliva contains bioactive components which may play a role in pathogen transmission and in host-vector relationships by inducing an immune response in the vertebrate host. The evaluation of human immune responses to arthropod bites might also represent a research direction for assessing individual exposure to the bite of a malaria vector. METHODS: The present study examined the antibody (Ab) IgG response during the season of exposure to Anopheles gambiae bites in young children living in a malaria endemic area. Immunoblots were performed with An. gambiae saliva to detect anti-saliva Ab bands and the evolution of immunogenic bands at the peak of, and following, the transmission period. RESULTS: The results showed that anti-Anopheles Ab was directed against a limited number of salivary proteins (175, 115, 72 and 30 kDa bands). Specific IgG responses to mosquito salivary proteins were variable among exposed individuals; nevertheless, two major bands (175 and 72 kDa) were observed in all immune-responder children. Analysis of the intensity of immunogenic bands revealed that IgG levels against the 175 kDa band were significantly higher during the peak period compared to the end period malaria transmission. CONCLUSION: This preliminary work supports the potential of using anti-saliva immune responses as a measure of exposure to Anopheles bites. The use of immunoblots coupled with evaluation of band intensity could be an adequate tool for distinguishing immunogenic salivary proteins as candidate markers of bite exposure. Furthermore, this study may open the way to design new epidemiological tools for evaluating the risk of malaria exposure.

Antischistosomal efficacy of artesunate combination therapies administered as curative treatments for malaria attacks.

Artesunate is a highly effective antimalarial and there is some evidence that it is also active against schistosome infections. We therefore investigated whether treatment with artesunate of acute malaria in Senegalese children had an impact on their level of infection with Schistosoma haematobium. Twenty-seven children who were entered into a clinical trial of antimalaria treatment were excreting S. haematobium eggs in their urine on the day of treatment. Fifteen children received a combination of a single dose of sulfadoxine/pyrimethamine together with three daily doses of artesunate (4 mg/kg); the remaining 12 children received three daily doses of amodiaquine and artesunate. The overall cure rate and reduction in the mean number of excreted eggs at 28 days post treatment were 92.6% and 94.5%, respectively. Our findings indicate that artesunate, in addition to being a very effective treatment for uncomplicated malaria, can also sharply reduce the S. haematobium loads harboured by pre-school African children.

Preschool stunting, adolescent migration, catch-up growth, and adult height in young senegalese men and women of rural origin.

Available data on the long-term consequences of preschool stunting are scarce and conflicting. The objective of this study was to assess the amount of catch-up growth from preschool stunting and the effect of migration (change in environment) during adolescence. A cohort study from preschool age (1-5 y) to adulthood (18-23 y) was conducted among 2874 subjects born in a rural area of Senegal. The subjects were divided into 3 groups of preschool stunting: none, mild, and marked, with height-for-age Z-scores of >-1, -2 to -1, and <-2, respectively. At follow-up, the history of migration was recalled. Mean height was 161.3 cm for girls and 174.0 cm for boys (>/=20 y). Stunted subjects remained smaller than the others: the age-adjusted height deficit between the 2 extreme categories was 6.6 and 9.0 cm in girls and boys, respectively. However, their height increment from early childhood to adulthood differed (69.3, 70.5, and 72.0 cm, P = 0.0001, and 78.9, 80.0, and 80.3 cm, P < 0.01, for nonstunted, mildly stunted, and markedly stunted girls and boys, respectively). The duration of labor migration to the city was associated with height increment in girls only in a nonlinear relation (adjusted means: 67.2, 69.3, 67.4, and 67.7 cm for 4 groups of increasing duration, P < 0.01). In conclusion, Senegalese children caught up in height prior to adulthood, with the adult means approximately 2 cm below the WHO/NCHS reference. However, this global catch up did not reduce height differences between formerly stunted and nonstunted children to any greater extent and it was not enhanced by labor migration.

Domestic animals as carriers of Bordetella species in Senegal.

Despite intense efforts to maintain a high level of vaccine coverage against human whooping cough, rural senegalese areas are still endemic for Bordetella pertussis. One explanation being the potential existence of animal reservoirs, the objective of this work was to precise the carriage by domestic animals of bacteria belonging to the genus Bordetella in Senegal. Bacteriological samples (swabs and aspirates) were obtained from various domestic animals living in different parts of the country. No B. pertussis nor B. parapertussis were isolated. However, for the first time to our knowledge, B. bronchiseptica was identified from small ruminants located in Africa. The positive animals were two goats and two sheep from Dakar slaughterhouse together with a goat living in a rural compound. The fact that it was identified in goats and sheep underlines the potential zoonotic of that bacterial species in countries where small ruminants are of economical and cultural relevance.