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  • 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.
  • Pneumococcal conjugate vaccine use during humanitarian crises

    van Zandvoort, K; Checchi, F; Diggle, E; Eggo, RM; Gadroen, K; Mulholland, K; McGowan, CR; le Polain de Waroux, O; Rao, VB; Satzke, C; et al. (Elsevier, 2019-09-24)
    Streptococcus pneumoniae is a common human commensal that causes a sizeable part of the overall childhood mortality in low income settings. Populations affected by humanitarian crises are at especially high risk, because a multitude of risk factors that are enhanced during crises increase pneumococcal transmission and disease severity. Pneumococcal conjugate vaccines (PCVs) provide effective protection and have been introduced into the majority of routine childhood immunisation programmes globally, though several barriers have hitherto limited their uptake during humanitarian crises. When PCV coverage cannot be sustained during crises or when PCV has not been part of routine programmes, mass vaccination campaigns offer a quick acting and programmatically feasible bridging solution until services can be restored. However, we currently face a paucity of evidence on which to base the structure of such campaigns. We believe that, now that PCV can be procured at a substantially reduced price through the Humanitarian Mechanism, this lack of information is a remaining hurdle to PCV use in humanitarian crises. Considering the difficulties in conducting research in crises, we propose an evidence generation pathway consisting of primary data collection in combination with mathematical modelling followed by quasi-experimental evaluation of a PCV intervention, which can inform on optimal vaccination strategies that consider age targeting, dosing regimens and impact duration.
  • Global oral cholera vaccine use

    Pezzoli, L; Cavailler, P; Mengel, M; Matzger, H; Lorenson, T; Sur, D; Luquero, F; Grais, R; 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.
  • 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.
  • Measles seroprevalence after reactive vaccination campaigns during the 2015 measles outbreak in four health zones of the former Katanga Province, Democratic Republic of Congo.

    Keating, P; Carrion Martin, AI; Blake, A; Lechevalier, P; Uzzeni, F; Gignoux, E; Okonta, C; Langendorf, C; Smit, S; Ahuka, S; et al. (BioMed Central, 2019-08-22)
    BACKGROUND: Measles continues to circulate in the Democratic Republic of Congo, and the country suffered from several important outbreaks over the last 5 years. Despite a large outbreak starting in the former province of Katanga in 2010 and the resulting immunization activities, another outbreak occurred in 2015 in this same region. We conducted measles seroprevalence surveys in four health zones (HZ) in the former Katanga Province in order to assess the immunity against measles in children 6 months to 14 years after the 2015 outbreak. METHODS: We conducted multi-stage cluster surveys stratified by age group in four HZs, Kayamba, Malemba-Nkulu, Fungurume, and Manono. The age groups were 6-11 months, 12-59 months, and 5-14 years in Kayamba and Malemba-Nkulu, 6-59 months and 5-14 years in Manono and Fungurume. The serological status was measured on dried capillary blood spots collected systematically along with vaccination status (including routine Extended Program of Immunization (EPI), and supplementary immunization activities (SIAs)) and previous self-reported history of suspected measles. RESULTS: Overall seroprevalence against measles was 82.7% in Kayamba, 97.6% in Malemba-Nkulu, 83.2% in Manono, and 74.4% in Fungurume, and it increased with age in all HZs. It was 70.7 and 93.8% in children 12-59 months in Kayamba and Malemba-Nkulu, and 49.8 and 64.7% in children 6-59 months in Fungurume and Manono. The EPI coverage was low but varied across HZ. The accumulation of any type of vaccination against measles resulted in an overall vaccine coverage (VC) of at least 85% in children 12-59 months in Kayamba and Malemba-Nkulu, 86.1 and 74.8% in children 6-59 months in Fungurume and Manono. Previous measles infection in 2015-early 2016 was more frequently reported in children aged 12-59 months or 6-59 months (depending on the HZ). CONCLUSION: The measured seroprevalence was consistent with the events that occurred in these HZs over the past few years. Measles seroprevalence might prove a valuable source of information to help adjust the timing of future SIAs and prioritizing support to the EPI in this region as long as the VC does not reach a level high enough to efficiently prevent epidemic flare-ups.
  • The impact of reactive mass vaccination campaigns on measles outbreaks in the Katanga region, Democratic Republic of Congo

    Funk, S; Takahashi, S; Hellewell, J; Gadroen, K; Carrion-Martin, I; van Lenthe, M; Rivette, K; Dietrich, S; Edmunds, WJ; Siddiqui, MR; et al. (2019-08-17)
    The Katanga region in the Democratic Republic of Congo (DRC) has been struck by repeated epidemics of measles, with large outbreaks occurring in 2010–13 and 2015. In many of the affected health zones, reactive mass vaccination campaigns were conducted in response to the outbreaks. Here, we attempted to determine how effective the vaccination campaigns in 2015 were in curtailing the ongoing outbreak. We further sought to establish whether the risk of large measles outbreaks in different health zones could have been determined in advance to help prioritise areas for vaccination campaign and speed up the response. In doing so, we first attempted to identify factors that could have been used in 2015 to predict in which health zones the greatest outbreaks would occur. Administrative vaccination coverage was not a good predictor of the size of outbreaks in different health zones. Vaccination coverage derived from surveys, on the other hand, appeared to give more reliable estimates of health zones of low vaccination coverage and, consequently, large outbreaks. On a coarser geographical scale, the provinces most affected in 2015 could be predicted from the outbreak sizes in 2010–13. This, combined with the fact that the vast majority of reported cases were in under-5 year olds, would suggest that there are systematic issues of undervaccination. If this was to continue, outbreaks would be expected to continue to occur in the affected health zones at regular intervals, mostly concentrated in under-5 year olds. We further used a model of measles transmission to estimate the impact of the vaccination campaigns, by first fitting a model to the data including the campaigns and then re-running this without vaccination. We estimated the reactive campaigns to have reduced the size of the overall outbreak by approximately 21,000 (IQR: 16,000–27,000; 95% CI: 8300–38,000) cases. There was considerable heterogeneity in the impact of campaigns, with campaigns started earlier after the start of an outbreak being more impactful. Taken together, these findings suggest that while a strong routine vaccination regime remains the most effective means of measles control, it might be possible to improve the effectiveness of reactive campaigns by considering predictive factors to trigger a more targeted vaccination response.
  • Potential use of microarray patches for vaccine delivery in low- and middle-income countries

    Peyraud, N; Zehrung, D; Jarrahian, C; Frivold, C; Orubu, T; Giersing, B (Elsevier, 2019-06-28)
    Microarray patches (MAPs), also referred to as microneedle patches, are a novel methodology that have the potential to overcome barriers to vaccine delivery in low- and middle-income countries (LMICs), and transform the way that vaccines are delivered within immunization programs. The World Health Organization’s Initiative for Vaccine Research and its partners are working to understand how MAPs could ease vaccine delivery and increase equitable access to vaccines in LMICs. Global stakeholders have been engaged to evaluate technical, economic, and programmatic challenges; to validate assumptions where possible; and to propose areas of focus to facilitate future vaccine-MAP product development. This report summarizes those learnings.
  • Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi.

    Kundrick, A; Huang, Z; Carran, S; Kagoli, M; Grais, RF; Hurtado, N; Ferrari, M (BioMed Central, 2019-06-15)
    Background Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (RE) in the context of the 2010 measles epidemic in Malawi. Methods Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, RE, at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. Results The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated RE ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. Conclusions Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.
  • Oral cholera vaccination in hard-to-reach communities, Lake Chilwa, Malawi

    Grandesso, F; Rafael, F; Chipeta, S; Alley, I; Saussier, C; Nogareda, F; Burns, M; Lechevalier, P; Page, AL; Salumu, L; et al. (The World Health Organization, 2018-12-01)
    To evaluate vaccination coverage, identify reasons for non-vaccination and assess satisfaction with two innovative strategies for distributing second doses in an oral cholera vaccine campaign in 2016 in Lake Chilwa, Malawi, in response to a cholera outbreak.
  • Oral cholera vaccination in hard-to-reach communities, Lake Chilwa, Malawi

    Grandesso, F; Rafael, F; Chipeta, S; Alley, I; Saussier, C; Nogareda, F; Burns, M; Lechevalier, P; Page, AL; Salumu, L; et al. (World Health Organization, 2018-09-27)
  • Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: A modelling study

    Cooper, BS; White, LJ; Siddiqui, R (Public Library of Science, 2018-09-25)
    Hepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination.
  • Safety of the rVSV ZEBOV vaccine against Ebola Zaire among frontline workers in Guinea

    Juan-Giner, A; Tchaton, M; Jemmy, JP; Soumah, A; Boum, Y; Faga, EM; Cisse, M; Grais, RF (Elsevier, 2018-09-25)
    As part of the ring vaccination trial in Guinea, Front Line Workers were invited to participate in a sub-study to provide additional information on the immunogenicity and safety of rVSVΔG/ZEBOV-GP. Here we summarize the information on the safety follow-up.
  • Progress and Challenges in Using Oral Cholera Vaccines to Control Outbreaks: The Médecins Sans Frontières Experience

    Ciglenecki, I; Azman, AS; Jamet, C; Serafini, M; Luquero, FJ; Cabrol, JC (Oxford University Press, 2018-09-14)
    The use of oral cholera vaccine (OCV) has increased since 2011, when Shanchol, the first OCV suitable for large-scale use, became available. Médecins Sans Frontières considers OCVs an essential cholera outbreak control tool and has contributed to generating new evidence on OCV use in outbreaks. We showed that large-scale mass campaigns are feasible during outbreaks, documented high short-term effectiveness and showed that vaccines are likely safe in pregnancy. We found that a single-dose regimen has high short-term effectiveness, making rapid delivery of vaccine during outbreaks easier, especially given the on-going global vaccine shortage. Despite progress, OCV has still not been used widely in some of the largest recent outbreaks and thousands of cholera deaths are reported every year. While working towards improving our tools to protect those most at-risk of cholera, we must strive to use all available effective interventions in efficient ways, including OCV, to prevent avoidable deaths today.
  • Oral cholera vaccine in cholera prevention and control, Malawi

    M'bangombe, M; Pezzoli, L; Reeder, B; Kabuluzi, S; Msyamboza, K; Masuku, H; Ngwira, B; Cavailler, P; Grandesso, F; Palomares, A; et al. (World Health Organization, 2018-06-01)
    With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed.
  • Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial

    Coldiron, ME; Guindo, O; Makarimi, R; Soumana, I; Matar Seck, A; Garba, S; Macher, E; Isanaka, S; Grais, RF (Elsevier, 2018-05-08)
    Rotavirus remains a major cause of diarrhea among children under 5 years of age. The efficacy of RotaSIIL, a pentavalent rotavirus vaccine, was shown in an event-driven trial in Niger. We describe the two-year safety follow-up of this trial.
  • Highly targeted cholera vaccination campaigns in urban setting are feasible: The experience in Kalemie, Democratic Republic of Congo

    Massing, LA; Aboubakar, S; Blake, A; Page, AL; Cohuet, S; Ngandwe, A; Mukomena Sompwe, E; Ramazani, R; Allheimen, M; Levaillant, P; et al. (Public Library of Science, 2018-05-07)
    Oral cholera vaccines are primarily recommended by the World Health Organization for cholera control in endemic countries. However, the number of cholera vaccines currently produced is very limited and examples of OCV use in endemic countries, and especially in urban settings, are scarce. A vaccination campaign was organized by Médecins Sans Frontières and the Ministry of Health in a highly endemic area in the Democratic Republic of Congo. This study aims to describe the vaccine coverage achieved with this highly targeted vaccination campaign and the acceptability among the vaccinated communities.
  • The new WHO decision-making framework on vaccine use in acute humanitarian emergencies: MSF experience in Minkaman, South Sudan

    Rull, M; Masson, S; Peyraud, N; Simonelli, M; Ventura, A; Dorion, C; Luquero, FJ; Uzzeni, F; Cigleneki, I (BioMed Central, 2018-03-26)
    The main causes of death during population movements can be prevented by addressing the population's basic needs. In 2013, the World Health Organization (WHO) issued a framework for decision making to help prioritize vaccinations in acute humanitarian emergencies. This article describes MSF's experience of applying this framework in addition to addressing key population needs in a displacement setting in Minkaman, South Sudan.
  • Single-Dose Cholera Vaccine in Response to an Outbreak in Zambia

    Ferreras, E; Chizema-Kawesha, E; Blake, A; Chewe, O; Mwaba, J; Zulu, G; Poncin, M; Rakesh, A; Page, AL; Stoitsova, S; et al. (Massachusetts Medical Society, 2018-02-08)
  • Infectious Disease Risk and Vaccination in Northern Syria after 5 Years of Civil War: The MSF Experience

    de Lima Pereira, A; Southgate, R; Ahmed, H; O'Connor, P; Cramond, V; Lenglet, A (Public Library of Science, 2018-02-02)
    In 2015, following an influx of population into Kobanê in northern Syria, Médecins Sans Frontières (MSF) in collaboration with the Kobanê Health Administration (KHA) initiated primary healthcare activities. A vaccination coverage survey and vaccine-preventable disease (VPD) risk analysis were undertaken to clarify the VPD risk and vaccination needs. This was followed by a measles Supplementary Immunization Activity (SIA). We describe the methods and results used for this prioritisation activity around vaccination in Kobanê in 2015.
  • Immunogenicity and Protection from a Single Dose of Internationally available killed oral Cholera Vaccine: a systematic review and meta-analysis

    Lopez, AL; Deen, J; Azman, AS; Luquero, FJ; Kanungo, S; Dutta, S; von Seidlein, L; Sack, DA (Oxford University Press, 2017-11-21)
    In addition to improved water supply and sanitation, the two-dose killed oral cholera vaccine (OCV) is an important tool for the prevention and control of cholera. We aimed to document the immunogenicity and protection (efficacy and effectiveness) conferred by a single OCV dose against cholera. The meta-analysis showed an estimated 73% and 77% of individuals seroconverted to the Ogawa and Inaba serotypes, respectively, after an OCV first dose. The estimates of single-dose vaccine protection from available studies are 87% at 2 months decreasing to 33% at 2 years. Current immunologic and clinical data suggest that protection conferred by a single dose of killed OCV may be sufficient to reduce short-term risk in outbreaks or other high-risk settings, which may be especially useful when vaccine supply is limited. However, until more data suggests otherwise, a second dose should be given as soon as circumstances allow to ensure robust protection.

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