• Avidity of serogroup A meningococcal IgG antibodies after immunization with different doses of a tetravalent A/C/Y/W135 polysaccharide vaccine

      Bårnes, G K; Naess, L M; Rosenqvist, E; Guerin, P J; Caugant, D A; Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Infectious Disease Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Epicentre, Paris, France; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, CCVTM, Oxford, UK; Department of International Health, University of Oslo, Oslo, Norway (Blackwell, 2011-06-08)
      In the absence of an affordable conjugate meningococcal vaccine, mass vaccination campaigns with polysaccharide vaccines are the means to control meningitis epidemics in sub-Saharan Africa. Facing global vaccine shortage, the use of reduced doses, which have been shown to be protective by serum bactericidal activity, can save many lives. In this study, we investigated the antibody responses and avidity of IgG antibodies evoked against the serogroup A capsule of Neisseria meningitidis by different doses of an A/C/Y/W135 polysaccharide vaccine. Volunteers in Uganda were vaccinated with 1/10, 1/5 or a full dose (50 μg) and revaccinated with a full dose after 1 year. Specific IgG geometric mean concentrations and geometric mean avidity indices (GMAI) were determined by a modified enzyme-linked immunosorbent assay (ELISA) using thiocyanate as a chaotropic agent. After vaccination with 1/10 or 1/5 doses, the GMAI increased from 1 month to 1 year. One year following the initial dose, the GMAI levels were higher in the arm receiving reduced doses than for the arm receiving a full dose. Following the second full dose, avidity indices equalized at approximately the same level in the three arms. Although there are practical challenges to the use of reduced doses in the field, our findings suggest that reduced doses of polysaccharide vaccine are able to elicit antibodies of as good avidity against serogroup A polysaccharide as a full dose.
    • Estimating transmission intensity for a measles epidemic in Niamey, Niger: lessons for intervention.

      Grais, RF; Ferrari, M J; Dubray, C; Bjørnstad, O N; Grenfell, B T; Djibo, A; Fermon, F; Guerin, P J; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. rebecca.grais@epicentre.msf.org (Elsevier, 2006-09)
      The objective of this study is to estimate the effective reproductive ratio for the 2003-2004 measles epidemic in Niamey, Niger. Using the results of a retrospective and prospective study of reported cases within Niamey during the 2003-2004 epidemic, we estimate the basic reproductive ratio, effective reproductive ratio (RE) and minimal vaccination coverage necessary to avert future epidemics using a recent method allowing for estimation based on the epidemic case series. We provide these estimates for geographic areas within Niamey, thereby identifying neighbourhoods at high risk. The estimated citywide RE was 2.8, considerably lower than previous estimates, which may help explain the long duration of the epidemic. Transmission intensity varied during the course of the epidemic and within different neighbourhoods (RE range: 1.4-4.7). Our results indicate that vaccination coverage in currently susceptible children should be increased by at least 67% (vaccine efficacy 90%) to produce a citywide vaccine coverage of 90%. This research highlights the importance of local differences in vaccination coverage on the potential impact of epidemic control measures. The spatial-temporal spread of the epidemic from district to district in Niamey over 30 weeks suggests that targeted interventions within the city could have an impact.
    • Feasibility of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban cholera-endemic setting in Mozambique.

      Cavailler, P; Lucas, M; Perroud, V; McChesney, M; Ampuero, S; Guerin, P J; Legros, D; Nierle, T; Mahoudeau, C; Lab, B; et al. (2006-05-29)
      We conducted a study to assess the feasibility and the potential vaccine coverage of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban endemic neighbourhood of Beira, Mozambique. The campaign was conducted from December 2003 to January 2004. Overall 98,152 doses were administered, and vaccine coverage of the target population was 58.6% and 53.6% for the first and second rounds, respectively. The direct cost of the campaign, which excludes the price of the vaccine, amounted to slightly over 90,000 dollars, resulting in the cost per fully vaccinated person of 2.09 dollars, which is relatively high. However, in endemic settings where outbreaks are likely to occur, integrating cholera vaccination into the routine activities of the public health system could reduce such costs.
    • Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: Results from a randomized non-inferiority controlled trial in Uganda

      Guerin, P J; Næss, L M; Fogg, C; Rosenqvist, E; Pinoges, L; Bajunirwe, F; Nabasumba, C; Borrow, R; Frøholm, L O; Ghabri, S; et al. (Public Library of Science (PLoS), 2008-12-02)
      BACKGROUND: Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine. METHODS AND FINDINGS: We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a >/=4-fold increase in SBA against a target strain from each serogroup and SBA titer >/=128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies. CONCLUSIONS: While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa, the use of 1/5 fractional doses should be considered as an alternative in mass vaccination campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT00271479.
    • Late vaccination reinforcement during a measles epidemic in Niamey, Niger (2003-2004).

      Dubray, C; Gervelmeyer, A; Djibo, A; Jeanne, I; Fermon, F; Soulier, M; Grais, RF; Guerin, P J; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. Christine.Dubray@epicentre.msf.org (2006-05-01)
      Low measles vaccination coverage (VC) leads to recurrent epidemics in many African countries. We describe VC before and after late reinforcement of vaccination activities during a measles epidemic in Niamey, Niger (2003-2004) assessed by Lot Quality Assurance Sampling (LQAS). Neighborhoods of Niamey were grouped into 46 lots based on geographic proximity and population homogeneity. Before reinforcement activities, 96% of lots had a VC below 70%. After reinforcement, this proportion fell to 78%. During the intervention 50% of children who had no previous record of measles vaccination received their first dose (vaccination card or parental recall). Our results highlight the benefits and limitations of vaccine reinforcement activities performed late in the epidemic.