Journal Article > ResearchFull Text
BMC Infect Dis. 2018 April 11; Volume 18 (Issue 1); 172.; DOI:10.1186/s12879-018-3073-1
le Polain de Waroux O, Cohuet S, Ndazima D, Kucharski AJ, Juan-Giner A, et al.
BMC Infect Dis. 2018 April 11; Volume 18 (Issue 1); 172.; DOI:10.1186/s12879-018-3073-1
BACKGROUND
Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce.
METHODS
We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as 'contacts') during the previous day. An estimate of the number of 'casual contacts' (i.e. < 5 min) was also obtained.
RESULTS
In total, 566 individuals were included in the study. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly (≥65 years) the fewest (P < 0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more often and further than others, and males travelled more frequently than females.
CONCLUSION
Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas.
Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce.
METHODS
We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as 'contacts') during the previous day. An estimate of the number of 'casual contacts' (i.e. < 5 min) was also obtained.
RESULTS
In total, 566 individuals were included in the study. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly (≥65 years) the fewest (P < 0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more often and further than others, and males travelled more frequently than females.
CONCLUSION
Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas.
Journal Article > Meta-AnalysisFull Text
Vaccine. 2020 February 8; Volume 38 (Issue 11); DOI:10.1016/j.vaccine.2020.02.005
Juan-Giner A, Alsalhani A, Panunzi I, Lambert V, Van Herp M, et al.
Vaccine. 2020 February 8; Volume 38 (Issue 11); DOI:10.1016/j.vaccine.2020.02.005
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.
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.
Journal Article > ResearchFull Text
Vaccine. 2014 September 23; Volume 32 (Issue 47); DOI:10.1016/j.vaccine.2014.09.027
Juan-Giner A, Domicent C, Langendorf C, Roper M, Baoundoh P, et al.
Vaccine. 2014 September 23; Volume 32 (Issue 47); DOI:10.1016/j.vaccine.2014.09.027
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.
Journal Article > ResearchFull Text
Vaccine. 2020 June 1; Volume 38 (Issue 31); DOI:10.1016/j.vaccine.2020.04.066
Boum Y II, Juan-Giner A, Hitchings MD, Soumah A, Strecker T, et al.
Vaccine. 2020 June 1; Volume 38 (Issue 31); DOI:10.1016/j.vaccine.2020.04.066
Background
As part of a Phase III trial with the Ebola vaccine rVSVΔG-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine.
Methods
We conducted an open‐label, non‐randomized, single-arm immunogenicity evaluation of one dose of rVSVΔG-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein–specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response.
Results
A total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1–88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0–95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0–3.8) at 28 days and 5.4% (95% CI 2.1–13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ≥ 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180.
Conclusions
We found one dose of rVSVΔG-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.
As part of a Phase III trial with the Ebola vaccine rVSVΔG-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine.
Methods
We conducted an open‐label, non‐randomized, single-arm immunogenicity evaluation of one dose of rVSVΔG-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein–specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response.
Results
A total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1–88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0–95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0–3.8) at 28 days and 5.4% (95% CI 2.1–13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ≥ 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180.
Conclusions
We found one dose of rVSVΔG-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.
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.
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
Journal Article > ResearchFull Text
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
Grantz KH, Claudot P, Kambala M, Kouyate M, Soumah A, et al.
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
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.
CLINICAL TRIAL REGISTRY NUMBER
This trial is registered with the Pan African Clinical Trials Registry, number
PACTR201503001057193.
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.
CLINICAL TRIAL REGISTRY NUMBER
This trial is registered with the Pan African Clinical Trials Registry, number
PACTR201503001057193.
Journal Article > ResearchFull Text
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
Grantz KH, Claudot P, Kambala M, Kouyate M, Soumah A, et al.
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
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.
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.
Journal Article > ResearchFull Text
Lancet Infect Dis. 2023 April 28; Volume S1473-3099 (Issue 23); 00131-7.; DOI:10.1016/S1473-3099(23)00131-7
Juan-Giner A, Namulwana ML, Kimathi D, Grantz KH, Fall G, et al.
Lancet Infect Dis. 2023 April 28; Volume S1473-3099 (Issue 23); 00131-7.; DOI:10.1016/S1473-3099(23)00131-7
BACKGROUND
Current supply shortages constrain yellow fever vaccination activities, particularly outbreak response. Although fractional doses of all WHO-prequalified yellow fever vaccines have been shown to be safe and immunogenic in a randomised controlled trial in adults, they have not been evaluated in a randomised controlled trial in young children (9-59 months old). We aimed to assess the immunogenicity and safety of fractional doses compared with standard doses of the WHO-prequalified 17D-213 vaccine in young children.
METHODS
This substudy of the YEFE phase 4 study was conducted at the Epicentre Mbarara Research Centre (Mbarara, Uganda). Eligible children were aged 9-59 months without contraindications for vaccination, without history of previous yellow fever vaccination or infection and not requiring yellow fever vaccination for travelling. Participants were randomly assigned, using block randomisation, 1:1 to standard or fractional (one-fifth) dose of yellow fever vaccine. Investigators, participants, and laboratory personnel were blinded to group allocation. Participants were followed for immunogenicity and safety at 10 days, 28 days, and 1 year after vaccination. The primary outcome was non-inferiority in seroconversion (-10 percentage point margin) 28 days after vaccination measured by 50% plaque reduction neutralisation test (PRNT50) in the per-protocol population. Safety and seroconversion at 10 days and 12-16 months after vaccination (given COVID-19 resctrictions) were secondary outcomes. This study is registered with ClinicalTrials.gov, NCT02991495.
FINDINGS
Between Feb 20, 2019, and Sept 9, 2019, 433 children were assessed, and 420 were randomly assigned to fractional dose (n=210) and to standard dose (n=210) 17D-213 vaccination. 28 days after vaccination, 202 (97%, 95% CI 95-99) of 207 participants in the fractional dose group and 191 (100%, 98-100) of 191 in the standard dose group seroconverted. The absolute difference in seroconversion between the study groups in the per-protocol population was -2 percentage points (95% CI -5 to 1). 154 (73%) of 210 participants in the fractional dose group and 168 (80%) of 210 in the standard dose group reported at least one adverse event 28 days after vaccination. At 10 days follow-up, seroconversion was lower in the fractional dose group than in the standard dose group. The most common adverse events were upper respiratory tract infections (n=221 [53%]), diarrhoea (n=68 [16%]), rhinorrhoea (n=49 [12%]), and conjunctivitis (n=28 [7%]). No difference was observed in incidence of adverse events and serious adverse events between study groups.
CONCLUSIONS
Fractional doses of the 17D-213 vaccine were non-inferior to standard doses in inducing seroconversion 28 days after vaccination in children aged 9-59 months when assessed with PRNT50, but we found fewer children seroconverted at 10 days. The results support consideration of the use of fractional dose of yellow fever vaccines in WHO recommendations for outbreak response in the event of a yellow fever vaccine shortage to include children.
Current supply shortages constrain yellow fever vaccination activities, particularly outbreak response. Although fractional doses of all WHO-prequalified yellow fever vaccines have been shown to be safe and immunogenic in a randomised controlled trial in adults, they have not been evaluated in a randomised controlled trial in young children (9-59 months old). We aimed to assess the immunogenicity and safety of fractional doses compared with standard doses of the WHO-prequalified 17D-213 vaccine in young children.
METHODS
This substudy of the YEFE phase 4 study was conducted at the Epicentre Mbarara Research Centre (Mbarara, Uganda). Eligible children were aged 9-59 months without contraindications for vaccination, without history of previous yellow fever vaccination or infection and not requiring yellow fever vaccination for travelling. Participants were randomly assigned, using block randomisation, 1:1 to standard or fractional (one-fifth) dose of yellow fever vaccine. Investigators, participants, and laboratory personnel were blinded to group allocation. Participants were followed for immunogenicity and safety at 10 days, 28 days, and 1 year after vaccination. The primary outcome was non-inferiority in seroconversion (-10 percentage point margin) 28 days after vaccination measured by 50% plaque reduction neutralisation test (PRNT50) in the per-protocol population. Safety and seroconversion at 10 days and 12-16 months after vaccination (given COVID-19 resctrictions) were secondary outcomes. This study is registered with ClinicalTrials.gov, NCT02991495.
FINDINGS
Between Feb 20, 2019, and Sept 9, 2019, 433 children were assessed, and 420 were randomly assigned to fractional dose (n=210) and to standard dose (n=210) 17D-213 vaccination. 28 days after vaccination, 202 (97%, 95% CI 95-99) of 207 participants in the fractional dose group and 191 (100%, 98-100) of 191 in the standard dose group seroconverted. The absolute difference in seroconversion between the study groups in the per-protocol population was -2 percentage points (95% CI -5 to 1). 154 (73%) of 210 participants in the fractional dose group and 168 (80%) of 210 in the standard dose group reported at least one adverse event 28 days after vaccination. At 10 days follow-up, seroconversion was lower in the fractional dose group than in the standard dose group. The most common adverse events were upper respiratory tract infections (n=221 [53%]), diarrhoea (n=68 [16%]), rhinorrhoea (n=49 [12%]), and conjunctivitis (n=28 [7%]). No difference was observed in incidence of adverse events and serious adverse events between study groups.
CONCLUSIONS
Fractional doses of the 17D-213 vaccine were non-inferior to standard doses in inducing seroconversion 28 days after vaccination in children aged 9-59 months when assessed with PRNT50, but we found fewer children seroconverted at 10 days. The results support consideration of the use of fractional dose of yellow fever vaccines in WHO recommendations for outbreak response in the event of a yellow fever vaccine shortage to include children.
Journal Article > ResearchFull Text
Vaccine. 2015 July 26; Volume 33 (Issue 36); 4554-4558.; DOI:10.1016/j.vaccine.2015.07.007
Polonsky JA, Juan-Giner A, Hurtado N, Masiku C, Kagoli M, et al.
Vaccine. 2015 July 26; Volume 33 (Issue 36); 4554-4558.; DOI:10.1016/j.vaccine.2015.07.007
INTRODUCTION
Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies.
METHODS
As part of a study exploring HIV infection and measles susceptibility, we conveniently sampled consenting HIV-uninfected patients presenting at the HIV voluntary counselling and testing centre, and HIV-infected patients presenting for regular care, in Chiradzulu district hospital, Malawi, between January and September 2012.
RESULTS
A total of 2106 participants were recruited between January and September 2012, three quarters of whom were HIV positive. Vaccination cards were available for just 7 participants (0.36%). 91.9% of participants were measles seropositive.
Older age (OR = 1.11 per year increase in age; 95%CI: 1.09–1.14) and being female (OR = 1.90; 95%CI: 1.26–2.87) were both associated with significantly increased odds for seroprotection. Prior vaccination history was associated with lower odds (Odds Ratio (OR) = 0.44; 95% confidence interval (CI): 0.22–0.85) for confirmed seropositivity. Previous measles infection was not significantly associated with seroprotection (OR = 1.31; 95%CI: 0.49–3.51).
Protection by history and serological status were concordant for 64.3% of participants <35 years old. However, analysis by age group reveals important differences in concordance between the ages, with a greater degree of discordance among younger ages.
Vaccination and/or infection history as a predictor of seropositivity was 75.8% sensitive, but just 10.3% specific.
CONCLUSION
Reported vaccination and previous infection were poor predictors of seropositivity, suggesting these may be unreliable indicators of seroprotection status. Such serosurveys may be indicated in similar settings in which overestimation of the proportion of seroprotected individuals could have important ramifications if used to guide vaccination strategies.
Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies.
METHODS
As part of a study exploring HIV infection and measles susceptibility, we conveniently sampled consenting HIV-uninfected patients presenting at the HIV voluntary counselling and testing centre, and HIV-infected patients presenting for regular care, in Chiradzulu district hospital, Malawi, between January and September 2012.
RESULTS
A total of 2106 participants were recruited between January and September 2012, three quarters of whom were HIV positive. Vaccination cards were available for just 7 participants (0.36%). 91.9% of participants were measles seropositive.
Older age (OR = 1.11 per year increase in age; 95%CI: 1.09–1.14) and being female (OR = 1.90; 95%CI: 1.26–2.87) were both associated with significantly increased odds for seroprotection. Prior vaccination history was associated with lower odds (Odds Ratio (OR) = 0.44; 95% confidence interval (CI): 0.22–0.85) for confirmed seropositivity. Previous measles infection was not significantly associated with seroprotection (OR = 1.31; 95%CI: 0.49–3.51).
Protection by history and serological status were concordant for 64.3% of participants <35 years old. However, analysis by age group reveals important differences in concordance between the ages, with a greater degree of discordance among younger ages.
Vaccination and/or infection history as a predictor of seropositivity was 75.8% sensitive, but just 10.3% specific.
CONCLUSION
Reported vaccination and previous infection were poor predictors of seropositivity, suggesting these may be unreliable indicators of seroprotection status. Such serosurveys may be indicated in similar settings in which overestimation of the proportion of seroprotected individuals could have important ramifications if used to guide vaccination strategies.