Journal Article > CommentaryFull Text
NPJ Vaccines. 2022 November 2; Volume 7; 137.; DOI:10.1038/s41541-022-00552-3
Lindsey NP, Horton J, Barrett ADT, Demanou M, Monath TP, et al.
NPJ Vaccines. 2022 November 2; Volume 7; 137.; DOI:10.1038/s41541-022-00552-3
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 December 7; Volume 12 (Issue 12); e0007029.; DOI:10.1371/journal.pntd.0007029
Ingelbeen B, Weregemere NA, Noel H, Tshapenda G, Mossoko M, et al.
PLoS Negl Trop Dis. 2018 December 7; Volume 12 (Issue 12); e0007029.; DOI:10.1371/journal.pntd.0007029
BACKGROUND
Between December 2015 and July 2016, a yellow fever (YF) outbreak affected urban areas of Angola and the Democratic Republic of the Congo (DRC). We described the outbreak in DRC and assessed the accuracy of the YF case definition, to facilitate early diagnosis of cases in future urban outbreaks.
METHODOLOGY/PRINCIPAL FINDINGS
In DRC, suspected YF infection was defined as jaundice within 2 weeks after acute fever onset and was confirmed by either IgM serology or PCR for YF viral RNA. We used case investigation and hospital admission forms. Comparing clinical signs between confirmed and discarded suspected YF cases, we calculated the predictive values of each sign for confirmed YF and the diagnostic accuracy of several suspected YF case definitions. Fifty seven of 78 (73%) confirmed cases had travelled from Angola: 88% (50/57) men; median age 31 years (IQR 25–37). 15 (19%) confirmed cases were infected locally in urban settings in DRC. Median time from symptom onset to healthcare consultation was 7 days (IQR 6–9), to appearance of jaundice 8 days (IQR 7–11), to sample collection 9 days (IQR 7–14), and to hospitalization 17 days (IQR 11–26). A case definition including fever or jaundice, combined with myalgia or a negative malaria test, yielded an improved sensitivity (100%) and specificity (57%).
CONCLUSIONS/SIGNIFICANCE
As jaundice appeared late, the majority of cases were diagnosed too late for supportive care and prompt vector control. In areas with known local YF transmission, a suspected case definition without jaundice as essential criterion could facilitate earlier YF diagnosis, care and control.
Journal Article > ResearchSubscription Only
Vaccine. 2006 February 6; Volume 24 (Issue 6); 730-737.; DOI:10.1016/j.vaccine.2005.08.077
Huhn GD, Brown J, Perea W, Berthe A, Otero H, et al.
Vaccine. 2006 February 6; Volume 24 (Issue 6); 730-737.; DOI:10.1016/j.vaccine.2005.08.077
Yellow fever (YF) is a mosquito-borne vaccine-preventable disease with high mortality. In West Africa, low population immunity increases the risk of epidemic transmission. A cluster survey was conducted to determine the effectiveness of a mass immunization campaign using 17D YF vaccine in internally displaced person (IDP) camps following a reported outbreak of YF in Liberia in February 2004. Administrative data of vaccination coverage were reviewed. A cluster sample size was determined among 17,384 shelters using an 80% vaccination coverage threshold. A questionnaire eliciting demographic information, household size, and vaccination status was distributed to randomly selected IDPs. Data were analyzed to compare vaccination coverage rates of administrative versus survey data. Among 87,000 persons estimated living in IDP camps, administrative data recorded 49,395 (57%) YF vaccinated persons. A total of 237 IDPs were surveyed. Of survey respondents, 215 (91.9%, 95% CI 88.4-95.4) reported being vaccinated during the campaign and 196 (83.5%, 95% CI 78.6-88.5) possessed a valid campaign vaccination card. The median number of IDPs living in a shelter was 4 (range, 1-8) and 69,536 persons overall were estimated to be living in IDP camps. Coverage rates from a rapid survey exceeded 90% by self-report and 80% by evidence of a vaccination card, indicating that the YF immunization campaign was effective. Survey results suggested that administrative data overestimated the camp population by at least 20%. An emergency, mop-up vaccination campaign was avoided. Coverage surveys can be vital in the evaluation of emergency vaccination campaigns by influencing both imminent and future immunization strategies.
Conference Material > Video
Namulwana ML
Epicentre Scientific Day Paris 2022. 2022 June 21
Journal Article > LetterFull Text
Lancet. 2001 December 1; Volume 358 (Issue 9299); 2129-2130.; DOI:10.1016/S0140-6736(01)07185-9
Nathan N, Barry M, Van Herp M, Zeller H
Lancet. 2001 December 1; Volume 358 (Issue 9299); 2129-2130.; DOI:10.1016/S0140-6736(01)07185-9
A yellow fever epidemic erupted in Guinea in September, 2000. From Sept 4, 2000, to Jan 7, 2001, 688 instances of the disease and 225 deaths were reported. The diagnosis was laboratory confirmed by IgM detection in more than 40 patients. A mass vaccination campaign was limited by insufficient international stocks. After the epidemic in Guinea, the International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control decided that 2 million doses of 17D yellow fever vaccine, being stored as part of a UNICEF stockpile, should be used only in response to outbreaks.
Journal Article > ResearchFull Text
Lancet. 2021 January 9; Volume 397; DOI:10.1016/S0140-6736(20)32520-4
Juan-Giner A, Kimathi D, Grantz KH, Hamaluba M, Kazooba P, et al.
Lancet. 2021 January 9; Volume 397; DOI:10.1016/S0140-6736(20)32520-4
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.
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.
Conference Material > Abstract
Juan A
Epicentre Scientific Day Paris 2021. 2021 June 10
This presentation provides and overview of fractional dosing and discusses opportunities and barriers for other vaccines.
Fractional dosing of vaccines is considered a dose sparing solution for situations of vaccine shortages. Lower doses of vaccines, typically as 1/5th of the standard dose, are at present used for vaccines such as rabies, inactivated polio and yellow fever vaccines. However, the immunogenicity and safety of fractional doses compared to full dose need to be established before this strategy can be used. Since 2016, Epicentre has been working on assessing fractional doses of yellow fever vaccines. The aim of these studies is to provide the needed evidence to recommend fractional dosing of YF vaccines for outbreak response, when there are insufficient standard doses to protect the population at risk.
A non-inferiority trial assessing the non-inferiority of fractional doses of the four WHO-prequalified yellow fever vaccines in a general adult population, children and HIV+ adults has been recently completed in Uganda and Kenya. To complement these, a study looking at the non-inferiority of lower doses of the yellow fever vaccine manufactured by Institut Pasteur Dakar is currently ongoing. Several factors have been considered in the design of these studies to ensure that the results are sufficient for policy and practice change. These include the fraction to be studied, the study design and goal, evaluation of vaccine protection and practical aspects related to the administration of the vaccine.
This abstract is not to be quoted for publication.
Fractional dosing of vaccines is considered a dose sparing solution for situations of vaccine shortages. Lower doses of vaccines, typically as 1/5th of the standard dose, are at present used for vaccines such as rabies, inactivated polio and yellow fever vaccines. However, the immunogenicity and safety of fractional doses compared to full dose need to be established before this strategy can be used. Since 2016, Epicentre has been working on assessing fractional doses of yellow fever vaccines. The aim of these studies is to provide the needed evidence to recommend fractional dosing of YF vaccines for outbreak response, when there are insufficient standard doses to protect the population at risk.
A non-inferiority trial assessing the non-inferiority of fractional doses of the four WHO-prequalified yellow fever vaccines in a general adult population, children and HIV+ adults has been recently completed in Uganda and Kenya. To complement these, a study looking at the non-inferiority of lower doses of the yellow fever vaccine manufactured by Institut Pasteur Dakar is currently ongoing. Several factors have been considered in the design of these studies to ensure that the results are sufficient for policy and practice change. These include the fraction to be studied, the study design and goal, evaluation of vaccine protection and practical aspects related to the administration of the vaccine.
This abstract is not to be quoted for publication.
Journal Article > CommentaryFull Text
Lancet Global Health. 2024 March 1; Volume 12 (Issue 3); e352-e353.; DOI:10.1016/S2214-109X(23)00594-6
Juan-Giner A, Hombach J
Lancet Global Health. 2024 March 1; Volume 12 (Issue 3); e352-e353.; DOI:10.1016/S2214-109X(23)00594-6
Other > Pre-Print
medRxiv. 2022 February 21; DOI:10.1101/2022.02.17.22271108
Yakum MN, Funwie AD, Ajong AB, Tsafack M, Ebaze LE, et al.
medRxiv. 2022 February 21; DOI:10.1101/2022.02.17.22271108
Immunization is the most cost-effective health intervention in the world yet, vaccination uptake is still low with less than 50% of children aged 12-23 months fully vaccinated Cameroon. The objective of this study was to estimate the burden of vaccine hesitancy associated with routine EPI vaccines in Yaounde-Cameroon. A two-stage cross-sectional cluster survey was conducted in Yaoundé in May-June 2022, targeting parents/guardians of children 0-59 months. Clusters were selected with probability proportionate to size (PPS) and household’s selection done using a restricted sampling method. Data collection was done using an interviewer-administered questionnaire. Data were cleaned using MS-Excel 2019, and analyzed with R version 4.1.0 (2021-05-18). A total of 529 participants were enrolled out of 708 visited, giving a non-response rate of 25%. In total, vaccine hesitancy was reported in 137(25.90[22.35-29.80] %), and vaccine hesitancy prevalence did not vary significantly across different households’ wealth levels (p-value= 0.3786). However, in wealthy households’ refusal of vaccines (14%) was less than in poorer households (20%). Lack of trust, confidence, and perceived complacency are the leading causes of vaccine hesitancy related to routine immunization in Yaounde-Cameroon. We, therefore, recommend that the burden of vaccine hesitancy should be assessed at national scale and identify sources of misinformation that are at the origin of vaccine hesitancy. Having a clear notion of the effect of social media(Facebook, Instagram, WhatsApp, etc,), radio, TV, and other information sources might guide interventions to combat vaccine hesitancy.
Conference Material > Video
Juan A
Epicentre Scientific Day Paris 2021. 2021 June 10