• A Survey on Vaccine Efficacy in the City of Bongor (Chad) and its Operational Consequences for the Vaccination Program

      Luthi, J; Kessler, W; Boelaert, M; Médecins sans Frontières, Bruxelles, Belgique. (Published by WHO, 1997)
      A measles epidemic occurred in the city of Bongor, Chad, from 22 September 1993 to 26 June 1994. A total of 792 patients were hospitalized, with a case fatality rate of 5.2%. After the epidemic, the district management team evaluated the expanded programme on immunization (EPI). Through a cluster survey the attack rate was estimated to be 29.1% (95% confidence interval (CI) = 20.4-37.8%) for the age group 12-59 months (n = 206). For this same age group, the measles immunization coverage was estimated to be 44.2% (95% CI = 34.6-53.8%) and the vaccine efficacy 9.5% (95% CI = 0-41.5%). Several flaws in the logistic handling of the vaccines and especially in the cold chain were identified. These results indicated a serious management problem in the EPI, which the district team then immediately started to rectify. The method used to estimate the immunization coverage and efficacy in the study is rapid and low cost. Also, it is feasible at the district level and permits identification of management problems in the EPI.
    • Adapting to the Global Shortage of Cholera Vaccines: Targeted Single Dose Cholera Vaccine in Response to an Outbreak in South Sudan

      Parker, LA; Rumunu, J; Jamet, C; Kenyi, Y; Lino, RL; Wamala, JF; Mpairwe, AM; Ciglenecki, I; Luquero, FJ; Azman, AS; et al. (Elsevier, 2017-01-18)
      Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies.
    • Alternative observational designs to estimate the effectiveness of one dose of oral cholera vaccine in Lusaka, Zambia

      Ferreras, E; Blake, A; Chewe, O; Mwaba, J; Zulu, G; Poncin, M; Rakesh, A; Page, AL; Quilici, ML; Azman, AS; et al. (Cambridge University Press, 2020-03-13)
      We conducted a matched case-control (MCC), test-negative case-control (TNCC) and case-cohort study in 2016 in Lusaka, Zambia, following a mass vaccination campaign. Confirmed cholera cases served as cases in all three study designs. In the TNCC, control-subjects were cases with negative cholera culture and polymerase chain reaction results. Matched controls by age and sex were selected among neighbours of the confirmed cases in the MCC study. For the case-cohort study, we recruited a cohort of randomly selected individuals living in areas considered at-risk of cholera. We recruited 211 suspected cases (66 confirmed cholera cases and 145 non-cholera diarrhoea cases), 1055 matched controls and a cohort of 921. Adjusted vaccine effectiveness of one dose of oral cholera vaccine (OCV) was 88.9% (95% confidence interval (CI) 42.7-97.8) in the MCC study, 80.2% (95% CI: 16.9-95.3) in the TNCC design and 89.4% (95% CI: 64.6-96.9) in the case-cohort study. Three study designs confirmed the short-term effectiveness of single dose OCV. Major healthcare-seeking behaviour bias did not appear to affect our estimates. Most of the protection among vaccinated individuals could be attributed to the direct effect of the vaccine.
    • 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.
    • 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, R; 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, R (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.
    • Continuing effectiveness of serogroup a meningococcal conjugate vaccine, Chad, 2013

      Gamougam, K; Daugla, D M; Toralta, J; Ngadoua, C; Fermon, F; Page, A-L; Djingarey, M H; Caugant, D A; Manigart, O; Trotter, C L; et al. (Center for Disease Control, 2015-01-01)
      In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted.
    • Delayed second dose of oral cholera vaccine administered before high-risk period for cholera transmission: Cholera control strategy in Lusaka, 2016.

      Ferreras, E; Matapo, B; Chizema-Kawesha, E; Chewe, O; Mzyece, H; Blake, A; Moonde, L; Zulu, G; Poncin, M; Sinyange, N; et al. (The Public Library of Science, 2019-08-30)
      BACKGROUND: In April 2016, an emergency vaccination campaign using one dose of Oral Cholera Vaccine (OCV) was organized in response to a cholera outbreak that started in Lusaka in February 2016. In December 2016, a second round of vaccination was conducted, with the objective of increasing the duration of protection, before the high-risk period for cholera transmission. We assessed vaccination coverage for the first and second rounds of the OCV campaign. METHODS: Vaccination coverage was estimated after each round from a sample selected from targeted-areas for vaccination using a cross-sectional survey in to establish the vaccination status of the individuals recruited. The study population included all individuals older than 12 months residing in the areas targeted for vaccination. We interviewed 505 randomly selected individuals after the first round and 442 after the second round. Vaccination status was ascertained either by vaccination card or verbal reporting. Households were selected using spatial random sampling. RESULTS: The vaccination coverage with two doses was 58.1% (25/43; 95%CI: 42.1-72.9) in children 1-5 years old, 59.5% (69/116; 95%CI: 49.9-68.5) in children 5-15 years old and 19.9% (56/281; 95%CI: 15.4-25.1) in adults above 15 years old. The overall dropout rate was 10.9% (95%CI: 8.1-14.1). Overall, 69.9% (n = 309/442; 95%CI: 65.4-74.1) reported to have received at least one OCV dose. CONCLUSIONS: The areas at highest risk of suffering cholera outbreaks were targeted for vaccination obtaining relatively high vaccine coverage after each round. However, the long delay between doses in areas subject to considerable population movement resulted in many individuals receiving only one OCV dose. Additional vaccination campaigns may be required to sustain protection over time in case of persistence of risk. Further evidence is needed to establish a maximum optimal interval time of a delayed second dose and variations in different settings.
    • Did the Ebola Outbreak Disrupt Immunisation Services? A Case Study from Liberia

      Wesseh, C; Najjemba, R; Edwards, J; Owiti, P; Tweya, H; Bhat, P (International Union Against Tuberculosis and Lung Disease, 2017-06-21)
      Setting: All health facilities providing routine immunisation services in Liberia. Objective: To compare the number of routine facility-based and outreach immunisations and measles cases before, during and after the Ebola outbreak. Design: A descriptive cross-sectional study. Results: Immunisation coverage for fully immunised children before the Ebola outbreak was 73%. Immunisation coverage for all antigens declined by half compared to baseline during the outbreak. These findings were similar in facility-based and outreach immunisations. During the outbreak, the proportion of fully immunised children dropped by respectively 58%, 33% and 39% in the most, moderately and least Ebola-affected counties. Immunisation rate of recovery in the post-Ebola period was respectively 82%, 21% and 9% in the most, moderately and least affected counties compared to the Ebola-outbreak period. Outreach immunisation recovered slowly compared to facility-based immunisation. The mean number of measles cases reported per month was 12 pre-Ebola, 16 Ebola and 60 post-Ebola. Conclusion: This study provides insights into the possible impact of an Ebola outbreak on countrywide immunisation. The outbreak weakened a struggling national immunisation programme, and post-outbreak recovery took significant time, which likely contributed to the measles epidemic. Recommendations for the improvement of immunisation services that could limit further preventable epidemics in Liberia and similar contexts at risk for Ebola are provided.
    • Economic Impact of Thermostable Vaccines

      Lee, BY; Wedlock, PT; Haidari, LA; Elder, K; Potet, J; Manring, R; Connor, DL; Spiker, ML; Bonner, K; Rangarajan, A; et al. (Elsevier, 2017-04-25)
      While our previous work has shown that replacing existing vaccines with thermostable vaccines can relieve bottlenecks in vaccine supply chains and thus increase vaccine availability, the question remains whether this benefit would outweigh the additional cost of thermostable formulations.
    • Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community trial

      Daugla, D M; Gami, J P; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, M E; et al. (Elsevier, 2013-09-11)
      A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic.
    • Effectiveness of oral cholera vaccine in Haiti

      Luquero, F J; Sack, D A (Elsevier, 2015-03)
    • Effectiveness of oral cholera vaccine in preventing cholera among fishermen in Lake Chilwa, Malawi: A case-control study

      Grandesso, F; Kasambara, W; Page, AL; Debes, AK; M'bang'ombe, M; Palomares, A; Lechevalier, P; Pezzoli, L; Alley, I; Salumu, L; et al. (Elsevier, 2019-06-19)
      Background: In response to a cholera outbreak among mobile, difficult-to-reach fishermen on Lake Chilwa, Malawi in 2016, a novel vaccine distribution strategy exploited the proven vaccine thermostability. Fishermen, while taking the first vaccine dose under supervision, received the second dose in a sealed bag, and were told to drink it two weeks later. This study assessed short-term vaccine protection of this strategy. Methods: Patients with diarrhoea admitted to health facilities around lake were interviewed and a stool sample collected for PCR testing. Vaccine effectiveness was assessed in a case-control test-negative design by comparing cases (PCR-positive for V. cholerae O1) and controls (patients with diarrhoea but PCR-negative) and with the screening method that compared the proportions of vaccinated among cholera cases versus the general fishermen population. Results: Of 145 study participants, 120 were fishermen living on the lake. Vaccine effectiveness at three-months was 90.0% [95%CI:38.8;98.4] among fishermen and 83.3% [95%CI: 20.8; 96.5] among all participants in the case-control test-negative design, and 97.5% [95%CI: 90.9;99.3] with the screening method. Conclusion: This strategy was effective in providing short-term protection in fishermen against cholera. Further research is needed to determine the adding value of the second dose and to identify the optimal vaccination strategies for different contexts.
    • 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.
    • Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger

      Isanaka, S; Guindo, O; Langendorf, C; Matar Seck, A; Plikaytis, BD; Sayinzoga-Makombe, N; McNeal, MM; Meyer, N; Adehossi, E; Djibo, A; et al. (Massachusetts Medical Society, 2017-03-23)
      Background Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. Methods We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. Results Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. Conclusions Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).
    • Ensuring access to affordable, timely vaccines in emergencies

      Elder, K; Saitta, B; Tanja, D; Elder, G; Close, R; Scourse, R; Kahn, P; Scheele, S; Miriam, A; Erickson, E; et al. (WHO Press, 2019-10-28)
      Vaccination is an effective intervention to reduce disease, disability, death and health inequities worldwide. Over the last two decades, vaccines have become more accessible in low-income countries; however, significant gaps remain, particularly in humanitarian emergencies, where populations face increased risks of many diseases. In 2013, the World Health Organization (WHO) published Vaccination in acute humanitarian emergencies: a framework for decision-making, to provide guidance on which vaccines to prioritize during emergencies.1 However, substantial obstacles, especially high prices for new vaccines, hinder implementation of this framework and of critical vaccination activities in emergency settings. In response to these challenges, global health stakeholders held a series of consultations in 2016 and proposed a WHO-based mechanism, the Humanitarian Mechanism, for the rapid procurement of affordable vaccines during emergencies, to be used by nongovernmental organizations (NGOs), civil society organizations, United Nations (UN) agencies and governments. Here we present the background of the creation of the mechanism from the perspective of Médecins Sans Frontières (MSF), including a description of our past challenges in accessing affordable pneumococcal conjugate vaccine (PCV; Box 1), a critical vaccine during many emergencies. We then describe how the mechanism has so far facilitated access to more affordable PCV and outline steps that could increase its potential for saving lives.
    • Estimating transmission intensity for a measles epidemic in Niamey, Niger: lessons for intervention.

      Grais, R; 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.
    • Evaluation of the stability of measles vaccine out of the cold chain under extended controlled temperature conditions.

      Juan-Giner, A; Alsalhani, A; Panunzi, I; Lambert, V; Van Herp, M; Gairola, S (Elsevier, 2020-02-08)
      Measles outbreaks occur periodically in remote and difficult to reach areas in countries such as the Democratic Republic of Congo. The possibility to keep measles vaccines at temperatures outside the cold chain for a limited period prior to administration would be an advantage for organizations such as Médecins Sans Frontières, which repeatedly respond to measles outbreaks in difficult contexts. Using stability data at 37 °C and 40 °C provided by Serum Institute of India Private Limited we applied the product release model for Extended Controlled Temperature Conditions (ECTC) to evaluate the possibility of an out of the cold chain excursion. Measles vaccine in the lyophilized form remains above the minimum required potency at the end of the shelf-life for up to 6 days at 37 °C or for 2 days at 40 °C. This evaluation supports the use of a monodose presentation of measles vaccine in ECTC. This could be an advantage for outbreak response in isolated and difficult to reach areas. However the operational advantages of this approach need to be established.
    • Factors influencing participation in an Ebola vaccine trial among front-line workers in Guinea

      Grantz, KH; Claudot, C; Kambala, M; Kouyate, M; Soumah, A; Boum, Y; Juan-Giner, A; Jemmy, JP; Cummings, DAT; Grais, RF (Elsevier, 2019-10-14)
      Background Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals’ decisions to participate – or not to participate – in the study. Methods In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis. Results Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization. Conclusions Despite the unique nature of the 2014–2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials.