• Carriage Prevalence and Serotype Distribution of Streptococcus Pneumoniae Prior to 10-Valent Pneumococcal Vaccine Introduction: A Population-Based Cross-Sectional Study in South Western Uganda, 2014

      Nackers, F; Cohuet, S; le Polain de Waroux, O; Langendorf, C; Nyehangane, D; Ndazima, D; Nanjebe, D; Karani, A; Tumwesigye, E; Mwanga-Amumpaire, J; et al. (Elsevier, 2017-08-04)
      Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda.
    • The case for reactive mass oral cholera vaccinations

      Reyburn, R; Deen, J L; Grais, RF; Bhattacharya, S K; Sur, D; Lopez, A L; Jiddawi, M S; Clemens, J D; von Seidlein, L; International Vaccine Institute (IVI), Seoul, Korea; Epicentre, Paris, France; NICED, Kolkata, India; Ministry of Health and Social Welfare, Zanzibar, Tanzania; Menzies School of Health Research, Casuarina, Australia (2011-01-25)
      The outbreak of cholera in Zimbabwe intensified interest in the control and prevention of cholera. While there is agreement that safe water, sanitation, and personal hygiene are ideal for the long term control of cholera, there is controversy about the role of newer approaches such as oral cholera vaccines (OCVs). In October 2009 the Strategic Advisory Group of Experts advised the World Health Organization to consider reactive vaccination campaigns in response to large cholera outbreaks. To evaluate the potential benefit of this pivotal change in WHO policy, we used existing data from cholera outbreaks to simulate the number of cholera cases preventable by reactive mass vaccination.
    • A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain

      Juan-Giner, A; Domicent, C; Langendorf, C; Roper, M H; Baoundoh, P; Fermon, F; Gakima, P; Zipursky, S; Tamadji, M; Grais, RF (2014-09-23)
      In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in "Controlled Temperature Chain" (CTC; up to 40°C for <30 days before administration), compared to standard cold chain (SCC; 2-8°C). Prior to the study, stability parameters of TT-CTC were shown to meet international requirements.
    • Efficacy and Effectiveness of an rVSV-Vectored Vaccine Expressing Ebola Surface Glycoprotein: Interim Results from the Guinea Ring Vaccination Cluster-Randomised Trial

      Henao-Restrepo, A M; Longini, I M; Egger, M; Dean, N E; Edmunds, W J; Camacho, A; Carroll, M W; Doumbia, M; Draguez, B; Duraffour, S; et al. (Elsevier, 2015-08-03)
      A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa.
    • 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 Mass Vaccination Campaign with Oral Cholera Vaccines in Response to an Outbreak in Guinea

      Ciglenecki, I; Sakoba, K; Luquero, F J; Heile, M; Itama, C; Mengel, M; Grais, RF; Verhoustraeten, F; Legros, D (2013-09-10)
    • Global oral cholera vaccine use

      Pezzoli, L; Cavailler, P; Mengel, M; Matzger, H; Lorenson, T; Sur, D; Luquero, F; Grais, RF; Ko, M; Soble, A; et al. (Elsevier, 2019-09-10)
      Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs. In 2013–2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD. The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings.
    • Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial

      Juan-Giner, A; Kimathi, D; Grantz, KH; Hamaluba, M; Kazooba, P; Njugana, P; Fall, G; Dia, M; Bob, NS; Monath, TP; et al. (Elsevier, 2021-01-09)
      Background Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. Methods We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18–59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT02991495. Findings Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI −2·60 to 5·28) for Bio-Manguinhos-Fiocruz, −0·90% (–4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (–2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (–3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. Interpretation Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage.
    • 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.
    • Local discrepancies in measles vaccination opportunities: results of population-based surveys in Sub-Saharan Africa

      Grout, L; Conan, N; Juan Giner, A; Hurtado, N; Fermon, F; N'goran, A; Grellety, E; Minetti, A; Porten, K; Grais, RF (BioMed Central Ltd, 2014)
      The World Health Organization recommends African children receive two doses of measles containing vaccine (MCV) through routine programs or supplemental immunization activities (SIA). Moreover, children have an additional opportunity to receive MCV through outbreak response immunization (ORI) mass campaigns in certain contexts. Here, we present the results of MCV coverage by dose estimated through surveys conducted after outbreak response in diverse settings in Sub-Saharan Africa.
    • Measles in Democratic Republic of Congo: an outbreak description from Katanga, 2010--2011

      Grout, L; Minetti, A; Hurtado, N; François, G; Fermon, F; Chatelain, A; Harczi, G; Ngoie, J; N Goran, A; Luquero, F J; et al. (BioMed Central (Springer Science), 2013-05-22)
      BACKGROUND: The Democratic Republic of Congo experiences regular measles outbreaks. From September 2010, the number of suspected measles cases increased, especially in Katanga province, where Medecins sans Frontieres supported the Ministry of Health in responding to the outbreak by providing free treatment, reinforcing surveillance and implementing non-selective mass vaccination campaigns. Here, we describe the measles outbreak in Katanga province in 2010--2011 and the results of vaccine coverage surveys conducted after the mass campaigns. METHODS: The surveillance system was strengthened in 28 of the 67 health zones of the province and we conducted seven vaccination coverage surveys in 2011. RESULTS: The overall cumulative attack rate was 0.71% and the case fatality ratio was 1.40%.The attack rate was higher in children under 4 and decreased with age. This pattern was consistent across districts and time. The number of cases aged 10 years and older barely increased during the outbreak. CONCLUSIONS: Early investigation of the age distribution of cases is a key to understanding the epidemic, and should guide the vaccination of priority age groups.
    • Measles outbreak response immunization is context-specific: insight from the recent experience of médecins sans frontières.

      Minetti, A; Bopp, C; Fermon, F; François, G; Grais, RF; Grout, L; Hurtado, N; Luquero, F J; Porten, K; Sury, L; et al. (PLoS, 2013-11)
      Andrea Minetti and colleagues compare measles outbreak responses from the Democratic Republic of the Congo and Malawi and argue that outbreak response strategies should be tailored to local measles epidemiology. Please see later in the article for the Editors' Summary.
    • Measles Seroprevalence in Chiradzulu District, Malawi: Implications for Evaluating Vaccine Coverage

      Polonsky, J A; Juan-Giner, A; Hurtado, N; Masiku, C; Kagoli, M; Grais, RF (Elsevier, 2015-07-26)
      Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies.
    • Outbreak response immunisation: the experience of Chad during recurrent measles epidemics in 2005 and 2010

      Guerrier, G; Guerra, J; Fermon, F; Talkibing, W B; Sekkenes, J; Grais, RF; Epicentre, Paris, France; Medecins Sans Frontieres-Paris, France; Ministry of Health, N'Djamena, Chad (Elsevier, 2011-12)
    • Performance of Small Cluster Surveys and the Clustered LQAS Design to estimate Local-level Vaccination Coverage in Mali

      Minetti, A; Riera-Montes, M; Nackers, F; Roederer, T; Koudika, M H; Sekkenes, J; Taconet, A; Fermon, F; Touré, A; Grais, RF; et al. (2012-08-12)
    • Post-licensure deployment of oral cholera vaccines: a systematic review

      Martin, S; Lopez, A L; Bellos, A; Deen, J; Ali, M; Alberti, K; Anh, D D; Costa, A; Grais, RF; Legros, D; et al. (World Health Organization, 2014-12-01)
      To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs.
    • Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

      Grais, RF; Warimwe, G; Kimathi, D; Juan, A; Bejon, P; epicentre (F1000 Research Ltd, 2019-11-20)
      Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops.
    • Reaching Hard-to-Reach Individuals: Nonselective Versus Targeted Outbreak Response Vaccination for Measles

      Minetti, A; Hurtado, N; Grais, RF; Ferrari, M (Oxford University Press, 2013-10-16)
      Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals.
    • Reactive vaccination as an effective tool for measles outbreak control in measles mortality reduction settings, Democratic Republic of Congo, 2005–2006

      Alberti, K P; King, L A; Burny, M-E; Ilunga, B K; Grais, RF; Epicentre, Paris, France; Institut de Veille Sanitaire, Saint-Maurice, France; European Programme for Intervention Epidemiology Training; Médecins Sans Frontières, Brussels, Belgium; Ministère de la Santé Publique, Gombe, Democratic Republic of Congo (2010-01-03)