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  • A mixture model to assess the the immunogenicity of an oral rotavirus vaccine among healthy infants in Niger

    Hitchings, MDT; Cummings, DAT; Grais, RF; Isanaka, S (Elsevier, 2020-11-05)
    Analysis of immunogenicity data is a critical component of vaccine development, providing a biological basis to support any observed protection from vaccination. Conventional methods for analyzing immunogenicity data use either post-vaccination titer or change in titer, often defined as a binary variable using a threshold. These methods are simple to implement but can be limited especially in populations experiencing natural exposure to the pathogen. A mixture model can overcome the limitations of the conventional approaches by jointly modeling the probability of an immune response and the level of the immune marker among those who respond. We apply a mixture model to analyze the immunogenicity of an oral, pentavalent rotavirus vaccine in a cohort of children enrolled into a placebo-controlled vaccine efficacy trial in Niger. Among children with undetectable immunoglobulin A (IgA) at baseline, vaccinated children had 5.2-fold (95% credible interval (CrI) 3.7, 8.3) higher odds of having an IgA response than placebo children, but the mean log IgA among vaccinated responders was 0.9-log lower (95% CrI 0.6, 1.3) than among placebo responders. This result implies that the IgA response generated by vaccination is weaker than that generated by natural infection. Multivariate logistic regression of seroconversion defined by ≥ 3-fold rise in IgA similarly found increased seroconversion among vaccinated children, but could not demonstrate lower IgA among those who seroresponded. In addition, we found that the vaccine was less immunogenic among children with detectable IgA pre-vaccination, and that pre-vaccination infant serum IgG and mother’s breast milk IgA modified the vaccine immunogenicity. Increased maternal antibodies were associated with weaker IgA response in placebo and vaccinated children, with the association being stronger among vaccinated children. The mixture model is a powerful and flexible method for analyzing immunogenicity data and identifying modifiers of vaccine response and independent predictors of immune response.
  • Learning from a massive epidemic: measles in DRC.

    Ducomble, T; Gignoux, E (Elsevier, 2020-03-31)
  • Field challenges to measles elimination in the Democratic Republic of the Congo

    Coulborn, RM; Nackers, F; Bachy, C; Porten, K; Vochten, H; Ndele, E; Van Herp, M; Bibala-Faray, E; Cohuet, S; Panunzi, I (Elsevier, 2020-03-17)
    BACKGROUND: During a measles epidemic, the Ministry of Public Health (MOH) of the Democratic Republic of the Congo conducted supplementary immunization activities (2016-SIA) from August 28-September 3, 2016 throughout Maniema Province. From October 29-November 4, 2016, Médecins Sans Frontières and the MOH conducted a reactive measles vaccination campaign (2016-RVC) targeting children six months to 14 years old in seven health areas with heavy ongoing transmission despite inclusion in the 2016-SIA, and a post-vaccination survey. We report the measles vaccine coverage (VC) and effectiveness (VE) of the 2016-SIA and VC of the 2016-RVC. METHODS: A cross-sectional VC cluster survey stratified by semi-urban/rural health area and age was conducted. A retrospective cohort analysis of measles reported by the parent/guardian allowed calculation of the cumulative measles incidence according to vaccination status after the 2016-SIA for an estimation of crude and adjusted VE. RESULTS: In November 2016, 1145 children (6-59 months old) in the semi-urban and 1158 in the rural areas were surveyed. Post-2016-SIA VC (documentation/declaration) was 81.6% (95%CI: 76.5-85.7) in the semi-urban and 91.0% (95%CI: 84.9-94.7) in the rural areas. The reported measles incidence in October among children less than 5 years old was 5.0% for 2016-SIA-vaccinated and 11.2% for 2016-SIA-non-vaccinated in the semi-urban area, and 0.7% for 2016-SIA-vaccinated and 4.0% for 2016-SIA-non-vaccinated in the rural area. Post-2016-SIA VE (adjusted for age, sex) was 53.9% (95%CI: 2.9-78.8) in the semi-urban and 78.7% (95%CI: 0-97.1) in the rural areas. Post 2016-RVC VC (documentation/declaration) was 99.1% (95%CI: 98.2-99.6) in the semi-urban and 98.8% (95%CI: 96.5-99.6) in the rural areas. CONCLUSIONS: Although our VE estimates could be underestimated due to misclassification of measles status, the VC and VE point estimates of the 2016-SIA in the semi-urban area appear suboptimal, and in combination, could not limit the epidemic. Further research is needed on vaccination strategies adapted to urban contexts.
  • 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.
  • 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.
  • High cholera vaccination coverage following emergency campaign in Haiti: Results from a cluster survey in three rural Communes in the South Department, 2017

    Sharp, A; Blake, A; Backx, J; Panunzi, I; Barrais, R; Nackers, F; Luquero, F; Deslouches, YG; Cohuet, S (Public Library of Science, 2020-01-31)
    Oral cholera vaccine (OCV) has increasingly been used as an outbreak control measure, but vaccine shortages limit its application. A two-dose OCV campaign targeting residents aged over 1 year was launched in three rural Communes of Southern Haiti during an outbreak following Hurricane Matthew in October 2016. Door-to-door and fixed-site strategies were employed and mobile teams delivered vaccines to hard-to-reach communities. This was the first campaign to use the recently pre-qualified OCV, Euvichol. The study objective was to estimate post-campaign vaccination coverage in order to evaluate the campaign and guide future outbreak control strategies. We conducted a cluster survey with sampling based on random GPS points. We identified clusters of five households and included all members eligible for vaccination. Local residents collected data through face-to-face interviews. Coverage was estimated, accounting for the clustered sampling, and 95% confidence intervals calculated. 435 clusters, 2,100 households and 9,086 people were included (99% response rate). Across the three communes respectively, coverage by recall was: 80.7% (95% CI:76.8-84.1), 82.6% (78.1-86.4), and 82.3% (79.0-85.2) for two doses and 94.2% (90.8-96.4), 91.8% (87-94.9), and 93.8% (90.8-95.9) for at least one dose. Coverage varied by less than 9% across age groups and was similar among males and females. Participants obtained vaccines from door-to-door vaccinators (53%) and fixed sites (47%). Most participants heard about the campaign through community 'criers' (58%). Despite hard-to-reach communities, high coverage was achieved in all areas through combining different vaccine delivery strategies and extensive community mobilisation. Emergency OCV campaigns are a viable option for outbreak control and where possible multiple strategies should be used in combination. Euvichol will help alleviate the OCV shortage but effectiveness studies in outbreaks should be done.
  • Impact of mass vaccination campaigns on measles transmission during an outbreak in Guinea, 2017

    Linton, NM; Keita, M; De Almeida, MM; Cuesta, JG; Guha-Sapir, D; Nishiura, H; van Loenhout, JA (Elsevier, 2020-01-17)
    OBJECTIVE: To estimate the time-dependent measles effective reproduction number (Rt) as an indicator of the impact of three outbreak response vaccination (ORV) campaigns on measles transmission during a nationwide outbreak in Guinea. METHODS: Rt represents the average number of secondary cases generated by a single primary case in a partially immune population during a given time period. Measles Rt was estimated using daily incidence data for 3,952 outbreak-associated measles cases in Guinea in 2017 for the time periods prior to, between, and following each of three ORV campaigns using a simple and extensible mathematical model. RESULTS: Rt was estimated to be above the threshold value of 1 during the initial growth period of the outbreak until the first ORV campaign began on March 13 (Rt =1.60, 95% CI: 1.55-1.67). It subsequently dropped below 1 and remained < 1 through the end of the year (range: 0.71-0.91), although low levels of transmission persisted. CONCLUSIONS: Reduction in Rt coincided with implementation of the ORV campaigns, indicating success of the campaigns at maintaining measles transmission intensity below epidemic growth levels. However, persistent measles transmission remains an issue in Guinea due to insufficient levels of herd immunity. Estimation of Rt should be further leveraged to help decision makers and field staff understand outbreak progress and the timing and type of vaccination efforts needed to halt transmission.
  • 'When you welcome well, you vaccinate well': a qualitative study on improving vaccination coverage in urban settings in Conakry, Republic of Guinea.

    Gil Cuesta, J; Whitehouse, K; Kaba, S; Nanan-N'Zeth, K; Haba, B; Bachy, C; Panunzi, I; Venables, E (Oxford University Press, 2020-01-13)
    BACKGROUND: Recurrent measles outbreaks followed by mass vaccination campaigns (MVCs) occur in urban settings in sub-Saharan countries. An understanding of the reasons for this is needed to improve future vaccination strategies. The 2017 measles outbreak in Guinea provided an opportunity to qualitatively explore suboptimal vaccination coverage within an MVC among participants through their perceptions, experiences and challenges. METHODS: We conducted focus group discussions with caregivers (n=68) and key informant interviews (n=13) with health professionals and religious and community leaders in Conakry. Data were audio-recorded, transcribed verbatim from Susu and French, coded and thematically analysed. RESULTS: Vaccinations were widely regarded positively and their preventive benefits noted. Vaccine side effects and the subsequent cost of treatment were commonly reported concerns, with further knowledge requested. Community health workers (CHWs) play a pivotal role in MVCs. Caregivers suggested recruiting CHWs from local neighbourhoods and improving their attitude, knowledge and skills to provide information about vaccinations. Lack of trust in vaccines, CHWs and the healthcare system, particularly after the 2014-2016 Ebola epidemic, were also reported. CONCLUSIONS: Improving caregivers' knowledge of vaccines, potential side effects and their management are essential to increase MVC coverage in urban settings. Strengthening CHWs' capacities and appropriate recruitment are key to improving trust through a community involvement approach.
  • Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

    Grais, R; 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.
  • 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.
  • 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.
  • 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.
  • 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.

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