RESUMEN
BACKGROUND: An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited. METHODS: We conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. Immunogenicity was assessed at day 28. The noninferiority of NmCV-5 to MenACWY-D was assessed on the basis of the difference in the percentage of participants with a seroresponse (defined as prespecified changes in titer; margin, lower limit of the 96% confidence interval [CI] above -10 percentage points) or geometric mean titer (GMT) ratios (margin, lower limit of the 98.98% CI >0.5). Serogroup X responses in the NmCV-5 group were compared with the lowest response among the MenACWY-D serogroups. Safety was also assessed. RESULTS: A total of 1800 participants received NmCV-5 or MenACWY-D. In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% (95% CI, 67.8 to 73.2) for serogroup A to 98.5% (95% CI, 97.6 to 99.2) for serogroup W; the percentage with a serogroup X response was 97.2% (95% CI, 96.0 to 98.1). The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points (96% CI, -0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI, 15.4 to 25.6) for serogroup A. The overall GMT ratios for the four shared serogroups ranged from 1.7 (98.98% CI, 1.5 to 1.9) for serogroup A to 2.8 (98.98% CI, 2.3 to 3.5) for serogroup C. The serogroup X component of the NmCV-5 vaccine generated seroresponses and GMTs that met the prespecified noninferiority criteria. The incidence of systemic adverse events was similar in the two groups (11.1% in the NmCV-5 group and 9.2% in the MenACWY-D group). CONCLUSIONS: For all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine elicited immune responses that were noninferior to those elicited by the MenACWY-D vaccine. NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident. (Funded by the U.K. Foreign, Commonwealth, and Development Office and others; ClinicalTrials.gov number, NCT03964012.).
Asunto(s)
Epidemias , Estado de Salud , Meningitis , Vacunas Meningococicas , Vacunas Conjugadas , Humanos , Gambia/epidemiología , Malí/epidemiología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/uso terapéutico , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/efectos adversos , Vacunas Meningococicas/uso terapéutico , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Inmunogenicidad Vacunal , Inyecciones Intramusculares , Meningitis/epidemiología , Meningitis/prevención & control , Epidemias/prevención & controlRESUMEN
BACKGROUND: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).
Asunto(s)
Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Adulto , Niño , Humanos , Anticuerpos Antivirales , República Democrática del Congo , Vacunas contra el Virus del Ébola/uso terapéutico , Fiebre Hemorrágica Ebola/prevención & controlRESUMEN
Hepatitis B virus (HBV) infection is the tenth leading cause of death worldwide. Mother-to-child transmission of HBV occurring mainly at delivery remains one of the most common routes of infection in developing countries. One of the main challenges concerning HBV in Africa is to implement a prevention policy aiming at interrupting the cycle of pseudo-vertical transmission of this infection. The aim of this study was to assess the implication of certain bacterial and viral factors in mother-to-child transmission of HBV. This prospective study was conducted on 165 pregnant women carriers of HBV surface antigen (HBsAg) and their 169 newborns who attended care at the Gynecology Department of the University Hospital of Cocody. Serological, molecular, and bacteriological analyses were performed on blood samples and vaginal secretions. Mean viral load (VL) was 4.5 ± 1.3 log10 IU/ml, while mean HBsAg titres were 3.5 ± 0.9 log10 IU/ml. HBV DNA was found in vaginal secretions in 13.3% of mothers and in the blood of 10.3% of the newborns. Six bacterial species were identified in the vaginal discharge of pregnant women during labour before delivery. Staphylococcus aureus and Enterococcus faecalis were the most frequent species found in 23.0% and 13.9% of cases. Mothers positive for vaginal HBV DNA displayed higher plasma HBV DNA loads than negative mothers (6.2 ± 1.6 log10 IU/ml vs. 4.3 ± 1.0 log10 IU/ml, p < .0001). In conclusion, our study showed that presence of HBV DNA in vaginal secretions and the presence of S. aureus could play a role in mother-to-child transmission of HBV. HBV DNA detection in vaginal discharge represents a promising biomarker to identify newborns at risk of perinatal persistent infection.
Asunto(s)
Hepatitis B , Complicaciones Infecciosas del Embarazo , ADN Viral , Femenino , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Estudios Prospectivos , Staphylococcus aureus , Carga ViralRESUMEN
BACKGROUND: Few studies describe the respiratory syncytial virus (RSV) burden in African populations, and most have utilized hospital-based surveillance. In Mali, no community-based studies exist of the incidence or epidemiology of RSV infection. This study provides the first estimates of RSV incidence in Mali. METHODS: In a cohort of infants enrolled in a clinical trial of maternal influenza vaccination, we estimate incidence of RSV-associated febrile illness in the first 6 months of life and identify risk factors for RSV infection and progression to severe disease. Infants (N = 1871) were followed from birth to 6 months of age and visited weekly to detect pneumonia and influenza-like illness. Baseline covariates were explored as risk factors for RSV febrile illness and RSV pneumonia or hospitalization. RESULTS: Incidence of RSV illness was estimated at 536.8 per 1000 person-years, and 86% (131/153) of RSV illness episodes were positive for RSV-B. RSV illness was most frequent in the fifth month of life and associated with having older mothers and with lower parity. The incidence of RSV-associated hospitalizations was 45.6 per 1000 person-years. Among infants with RSV illness, males were more likely to be hospitalized. The incidence of RSV pneumonia was 29 cases per 1000 person-years. CONCLUSIONS: In the first 6 months of life, Malian infants have a high incidence of RSV illness, primarily caused by RSV-B. Prevention of early RSV will require passive protection via maternal immunization in pregnancy. Mali is the first country where RSV-B has been identified as the dominant subtype, with potential implications for vaccine development.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Femenino , Hospitalización , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Malí/epidemiología , Embarazo , Infecciones por Virus Sincitial Respiratorio/epidemiología , Factores de RiesgoRESUMEN
Background: Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low-resource countries. Methods: We conducted an open-label, individual-randomized trial in Bamako, Mali. We assigned 600 infants aged 9-11 months to receive measles vaccine (MV), yellow fever vaccine (YFV), and meningococcal A conjugate vaccine (MenAV) with or without pentavalent rotavirus vaccine (PRV). We assessed the noninferiority (defined as a difference of ≤10%) of seroconversion and seroresponse rates to MV, YFV, and MenAV. We compared the seroresponse to PRV. Results: Seroconversion to MV occurred in 255 of 261 PRV recipients (97.7%) and 246 of 252 control infants (97.6%; difference, 0.1% [95% confidence interval {CI}, -4.0%-4.2%]). Seroresponse to YFV occurred in 48.1% of PRV recipients (141 of 293), compared with 52.2% of controls (153 of 293; difference, -4.1% [95% CI, -12.2%-4.0%]). A 4-fold rise in meningococcus A bactericidal titer was observed in 273 of 292 PRV recipients (93.5%) and 276 of 293 controls (94.2%; difference, -0.7% [95% CI, -5.2%-3.8%]). Rises in geometric mean concentrations of immunoglobulin A and immunoglobulin G antibodies to rotavirus were higher among PRV recipients (118 [95% CI, 91-154] and 364 [95% CI, 294-450], respectively), compared with controls (68 [95% CI, 50-92] and 153 [95% CI, 114-207], respectively). Conclusions: PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels. Clinical Trials Registration: NCT02286895.
Asunto(s)
Inmunización Secundaria , Vacuna Antisarampión/administración & dosificación , Vacunas Meningococicas/administración & dosificación , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacuna contra la Fiebre Amarilla/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/sangre , Interacciones Farmacológicas , Femenino , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/sangre , Lactante , Masculino , Malí , Vacuna Antisarampión/inmunología , Vacunas Meningococicas/inmunología , Vacunas contra Rotavirus/inmunología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología , Vacuna contra la Fiebre Amarilla/inmunologíaRESUMEN
BACKGROUND: rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. METHODS: We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS: In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9-100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3-100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae. INTERPRETATION: The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters. FUNDING: WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development).
Asunto(s)
Vacunas contra el Virus del Ébola , Fiebre Hemorrágica Ebola/prevención & control , Adolescente , Adulto , Niño , Análisis por Conglomerados , Trazado de Contacto , Ebolavirus , Femenino , Guinea , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/transmisión , Humanos , Masculino , Glicoproteínas de Membrana , Persona de Mediana Edad , Resultado del Tratamiento , Vesiculovirus , Adulto JovenRESUMEN
BACKGROUND: A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. METHODS: For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2â×â10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS: Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. INTERPRETATION: The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. FUNDING: WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.
Asunto(s)
Vacunas contra el Virus del Ébola , Fiebre Hemorrágica Ebola/prevención & control , Adulto , Ebolavirus/inmunología , Femenino , Vectores Genéticos , Guinea/epidemiología , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Vacunación/métodos , Vesiculovirus/metabolismo , Adulto JovenRESUMEN
BACKGROUND: A safe, affordable, and highly immunogenic meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed to control epidemic group A meningitis in Africa. Documentation of the safety specifications of the PsA-TT vaccine was warranted, with sufficient exposure to detect potential rare vaccine-related adverse reactions. METHODS: This phase 3, double-blind, randomized, active controlled clinical study was designed to evaluate the safety--primarily vaccine-related serious adverse events (SAEs)--up to 3 months after administration of a single dose of the PsA-TT vaccine to subjects aged 1-29 years in Mali. Safety outcomes were also compared to those following a single dose of a licensed meningococcal ACWY polysaccharide vaccine (PsACWY). RESULTS: No vaccine-related SAEs occurred during the 3 months of follow-up of 4004 subjects vaccinated with a single dose of PsA-TT. When compared to PsACWY (1996 subjects), tenderness at the injection site appeared to be more frequent in the PsA-TT group. However, rates of local induration, systemic reactions, adverse events (AEs), and SAEs were similar in both groups, and unsolicited AEs and SAEs were all unrelated to the study vaccines. CONCLUSIONS: The study confirmed on a large scale the excellent safety profile of a single dose of PsA-TT when administered to its entire target population of 1-29 years of age. CLINICAL TRIALS REGISTRATION: PACTR ATMR201003000191317.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/efectos adversos , Adolescente , Adulto , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Lactante , Masculino , Malí/epidemiología , Meningitis Meningocócica/epidemiología , Meningitis Meningocócica/microbiología , Meningitis Meningocócica/prevención & control , Neisseria meningitidis Serogrupo A/inmunología , Adulto JovenRESUMEN
BACKGROUND: Following mass vaccination campaigns in the African meningitis belt with group A meningococcal conjugate vaccine, MenAfriVac (PsA-TT), disease due to group A meningococci has nearly disappeared. Antibody persistence in healthy African toddlers was investigated. METHODS: African children vaccinated at 12-23 months of age with PsA-TT were followed for evaluation of antibody persistence up to 5 years after primary vaccination. Antibody persistence was evaluated by measuring group A serum bactericidal antibody (SBA) with rabbit complement and by a group A-specific IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Group A antibodies measured by SBA and ELISA were shown to decline in the year following vaccination and plateaued at levels significantly above baseline for up to 5 years following primary vaccination. CONCLUSIONS: A single dose of PsA-TT induces long-term sustained levels of group A meningococcal antibodies for up to 5 years after vaccination. CLINICAL TRIALS REGISTRATION: ISRTCN78147026.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Actividad Bactericida de la Sangre , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/inmunología , África , Animales , Proteínas del Sistema Complemento , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/sangre , Lactante , Masculino , Conejos , Factores de TiempoRESUMEN
INTRODUCTION: Few studies on SARS-CoV-2 seroprevalence in Ivory Coast have been conducted since the first case was reported on March 11, 2020. The main objective of this study was to observe and better understand the circulation of SARS-CoV-2 in Abidjan. METHODOLOGY: This prospective study collected data concerning age, sex, vaccination status, municipality of origin, monthly income, frequency of malaria, and frequency of diarrheal diseases in persons who gave their informed consent. Venous blood samples were taken to test for anti-SARS-COV-2 antibodies (IgM and IgG) using the VIDAS automated system. RESULTS: A total of 1504 patients were recruited and tested for antibodies directed against SARS-COV-2. Data analysis revealed the presence of anti-SARS-CoV-2 in 53.5% of participants, 17.3% of the participants had a previous symptomatic infection, 31.4% had an asymptomatic infection, and 44.8% were never in contact with the virus. Seroprevalence of SARS-CoV-2 was higher in Marcory (70.9%) and Cocody (61.1%) than in the remaining townships (48.4%). Township rates of serologically confirmed SARS-CoV-2 infection correlated with poverty index (p = 0.025), children < 5 years' proportion in the township (p = 0.026), and levels of malaria (p = 0.034). CONCLUSIONS: In the city of Abidjan, COVID-19 is strongly modulated by poverty, the proportion of babies and toddlers in the community, or exposure to malaria.
Asunto(s)
Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Humanos , Côte d'Ivoire/epidemiología , COVID-19/epidemiología , Estudios Prospectivos , Masculino , Femenino , Estudios Seroepidemiológicos , SARS-CoV-2/inmunología , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Anticuerpos Antivirales/sangre , Niño , Preescolar , Lactante , Anciano , Inmunoglobulina G/sangre , Inmunoglobulina M/sangreRESUMEN
It is currently unknown how quantitative diffusion and myelin MRI designs affect the results of a longitudinal study. We used two independent datasets containing 6 monthly MRI measurements from 20 healthy controls and 20 relapsing-remitting multiple sclerosis (RR-MS) patients. Six designs were tested, including 3 MRI acquisitions, either over 6 months or over a shorter study duration, with balanced (same interval) or unbalanced (different interval) time intervals between MRI acquisitions. First, we show that in RR-MS patients, the brain changes over time obtained with 3 MRI acquisitions were similar to those observed with 5 MRI acquisitions and that designs with an unbalanced time interval showed the highest similarity, regardless of study duration. No significant brain changes were found in the healthy controls over the same periods. Second, the study duration affects the sample size in the RR-MS dataset; a longer study requires more subjects and vice versa. Third, the number of follow-up acquisitions and study duration affect the sensitivity and specificity of the associations with clinical parameters, and these depend on the white matter bundle and MRI measure considered. Together, this suggests that the optimal design depends on the assumption of the dynamics of change in the target population and the accuracy required to capture these dynamics. Thus, this work provides a better understanding of key factors to consider in a longitudinal study and provides clues for better strategies in clinical trial design.
Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Estudios de Seguimiento , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Vaina de MielinaRESUMEN
Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in young children and is associated with subsequent recurrent wheezing illness and asthma (wheeze/asthma). RSV prevention may therefore reduce wheeze/asthma prevalence. Objectives: We estimated the contribution of RSV LRTI and the impact of RSV prevention on recurrent wheeze/asthma in Mali. Methods: We simulated 12 consecutive monthly birth cohorts in Mali and estimated RSV LRTI cases through 2 years and recurrent wheeze/asthma prevalence at 6 years under different RSV prevention scenarios: status quo, seasonal birth-dose extended half-life mAb, and seasonal birth-dose extended half-life mAb followed by 2 doses of pediatric vaccine (mAb + vaccine). We used World Health Organization (WHO) Preferred Product Characteristics for RSV prevention, demographic and RSV epidemiologic data from Mali, regional recurrent wheeze/asthma prevalence, and relative risk of recurrent wheeze/asthma given early childhood RSV LRTI. Results: Among the simulated cohort of 778,680 live births, 10.0% had RSV LRTI by 2 years and 89.6% survived to 6 years. We estimated that 13.4% of all recurrent wheeze/asthma at 6 years was attributable to RSV LRTI. Recurrent wheeze/asthma prevalence at 6 years was 145.0 per 10,000 persons (RSV LRTI attributable) and 1084.2 per 10,000 persons (total). In mAb and mAb + vaccine scenarios, RSV LRTI cases decreased by 11.8% and 44.4%, respectively, and recurrent wheeze/asthma prevalence decreased by 11.8% and 44.4% (RSV LRTI attributable) and 1.6% and 5.9% (total). Conclusion: In Mali, RSV prevention programs may have a meaningful impact on chronic respiratory disease, strengthening the case for investment in RSV prevention.
RESUMEN
Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.
RESUMEN
Although seroprevalence studies have demonstrated the wide circulation of SARS-COV-2 in African countries, the impact on population health in these settings is still poorly understood. Using representative samples of the general population, we evaluated retrospective mortality and seroprevalence of anti-SARS-CoV-2 antibodies in Lubumbashi and Abidjan. The studies included retrospective mortality surveys and nested anti-SARS-CoV-2 antibody prevalence surveys. In Lubumbashi the study took place during April-May 2021 and in Abidjan the survey was implemented in two phases: July-August 2021 and October-November 2021. Crude mortality rates were stratified between pre-pandemic and pandemic periods and further investigated by age group and COVID waves. Anti-SARS-CoV-2 seroprevalence was quantified by rapid diagnostic testing (RDT) and laboratory-based testing (ELISA in Lubumbashi and ECLIA in Abidjan). In Lubumbashi, the crude mortality rate (CMR) increased from 0.08 deaths per 10 000 persons per day (pre-pandemic) to 0.20 deaths per 10 000 persons per day (pandemic period). Increases were particularly pronounced among <5 years old. In Abidjan, no overall increase was observed during the pandemic period (pre-pandemic: 0.05 deaths per 10 000 persons per day; pandemic: 0.07 deaths per 10 000 persons per day). However, an increase was observed during the third wave (0.11 deaths per 10 000 persons per day). The estimated seroprevalence in Lubumbashi was 15.7% (RDT) and 43.2% (laboratory-based). In Abidjan, the estimated seroprevalence was 17.4% (RDT) and 72.9% (laboratory-based) during the first phase of the survey and 38.8% (RDT) and 82.2% (laboratory-based) during the second phase of the survey. Although circulation of SARS-CoV-2 seems to have been extensive in both settings, the public health impact varied. The increases, particularly among the youngest age group, suggest indirect impacts of COVID and the pandemic on population health. The seroprevalence results confirmed substantial underdetection of cases through the national surveillance systems.
RESUMEN
BACKGROUND: Although most births in Mali occur in health facilities, a substantial number of newborns still die during delivery and within the first 7 days of life, mainly because of existing training deficiencies and the challenges of maintaining intrapartum and postpartum care skills. OBJECTIVE: This trial aims to assess the effectiveness and cost-effectiveness of an intervention combining clinical audits and low-dose, high-frequency (LDHF) in-service training of health care providers and community health workers to reduce perinatal mortality. METHODS: The study is a three-arm cluster randomized controlled trial in the Koulikoro region in Mali. The units of randomization are each of 84 primary care facilities. Each trial arm will include 28 facilities. The facilities in the first intervention arm will receive support in implementing mortality and morbidity audits, followed by one-day LDHF training biweekly, for 6 months. The health workers in the second intervention arm (28 facilities) will receive a refresher course in maternal neonatal and child health (MNCH) for 10 days in a classroom setting, in addition to mortality and morbidity audits and LDHF hands-on training for 6 months. The control arm, also with 28 facilities, will consist solely of the standard MNCH refresher training delivered in a classroom setting. The main outcomes are perinatal deaths in the intervention arms compared with those in the control arm. A final sample of approximately 600 deliveries per cluster was expected for a total of 30,000 newborns over 14 months. Data sources included both routine health records and follow-up household surveys of all women who recently gave birth in the study facility 7 days postdelivery. Data collection tools will capture perinatal deaths, complications, and adverse events, as well as the status of the newborn during the perinatal period. A full economic evaluation will be conducted to determine the incremental cost-effectiveness of each of the case-based focused LDHF hands-on training strategies in comparison to MNCH refresher training in a classroom setting. RESULTS: The trial is complete. The recruitment began on July 15, 2019, and data collection began on July 23, 2019, and was completed in November 2020. Data cleaning or analyses began at the time of submission of the protocol. CONCLUSIONS: The results will provide policy makers and practitioners with crucial information on the impact of different health care provider training modalities on maternal and newborn health outcomes and how to successfully implement these strategies in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03656237; https://clinicaltrials.gov/ct2/show/NCT03656237. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28644.
RESUMEN
IMPORTANCE: Low- and middle-income countries have a high burden of respiratory syncytial virus lower respiratory tract infections. A monoclonal antibody administered monthly is licensed to prevent these infections, but it is cost-prohibitive for most low- and middle-income countries. Long-acting monoclonal antibodies and maternal vaccines against respiratory syncytial virus are under development. OBJECTIVE: We estimated the likelihood of respiratory syncytial virus preventive interventions (current monoclonal antibody, long-acting monoclonal antibody, and maternal vaccine) being cost-effective in Mali. DESIGN: We modeled age-specific and season-specific risks of respiratory syncytial virus lower respiratory tract infections within monthly cohorts of infants from birth to six months. We parameterized with respiratory syncytial virus data from Malian cohort studies, as well as product efficacy from clinical trials. Integrating parameter uncertainty, we simulated health and economic outcomes for status quo without prevention, intra-seasonal monthly administration of licensed monoclonal antibody, pre-seasonal birth dose administration of a long-acting monoclonal antibody, and maternal vaccination. We then calculated the incremental cost-effectiveness ratio of each intervention compared to status quo from the perspectives of the government, donor, and society. RESULTS: At a price of $3 per dose and from the societal perspective, current monoclonal antibody, long-acting monoclonal antibody, and maternal vaccine would have incremental cost-effectiveness ratios of $4280 (95% CI $1892 to $122,434), $1656 (95% CI $734 to $9091), and $8020 (95% CI $3501 to $47,047) per disability-adjusted life-year averted, respectively. CONCLUSIONS AND RELEVANCE: In Mali, long-acting monoclonal antibody is likely to be cost-effective from both the government and donor perspectives at $3 per dose. Maternal vaccine would need higher efficacy over that measured by a recent trial in order to be considered cost-effective.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Análisis Costo-Beneficio , Humanos , Lactante , Malí , Políticas , Infecciones por Virus Sincitial Respiratorio/prevención & controlRESUMEN
The 2014-2015 outbreak of Ebola Virus Disease (EVD) in West Africa was unprecedented in size and scope. The World Health Organization, government of Guinea and other partners undertook a field trial of efficacy of an Ebola vaccine in Guinea, with a parallel immunogenicity study in front-line workers. However, several obstacles had to be overcome. One was the need to teach Good Clinical Practices to a large group of field workers who had never participated in vaccine clinical trial research. Because the trial design was complex, performing this efficacy trial during an Ebola outbreak would have been challenging even for experienced investigators. For field workers who had never previously participated in a clinical trial, this constituted a daunting challenge. Another challenge was to provide independent monitoring to document the quality and validity of the field trial data to support future regulatory agency licensure. Here we discuss how these challenges were overcome, and what lessons can be drawn for the future. Intensive GCP was expeditiously arranged for 251 clinical study staff on-site in Guinea. The trials were initiated within days after completion of training. Monitoring (100% of participants in the efficacy trial and 50% in the immunogenicity trial) began at the onset of the trials. Early monitoring detected many minor errors but prompt feedback and guidance from the monitors, who explained the mistakes and proposed corrective actions, diminished error frequency as the trials progressed. Monitoring later in the trials showed what one would expect in a study conducted by experienced investigators. Should a vaccine field trial have to be hastily arranged during a future emerging disease outbreak in a developing country setting, our methods of training and monitoring could provide a model.
Asunto(s)
Ensayos Clínicos como Asunto/normas , Vacunas contra el Virus del Ébola/inmunología , Personal de Salud/educación , Fiebre Hemorrágica Ebola , Inmunogenicidad Vacunal , Brotes de Enfermedades/prevención & control , Guinea/epidemiología , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Salud Pública , Proyectos de Investigación , Investigadores , Organización Mundial de la SaludRESUMEN
Type-E hepatitis is responsible for more than three million symptomatic cases and more than 40,000 deaths worldwide. The situation of this hepatitis is overall poorly known in sub-Saharan Africa. Notably, the baseline circulation of HEV outside sporadic outbreaks has been barely characterized in this large region. More specifically, the impact of superinfection by this virus on the health status of the large reservoir of patients chronically infected with other hepatitis viruses remains to be evaluated. We searched for anti-HEV immunoglobulins in a series of 200 pregnant women and 92 patients with persistent liver infections with hepatitis B or C viruses and subsequently tried to assess serological co-variations with demographical and clinical features. We observed that only 1.5 % of expectant mothers were seropositive of anti-HEV IgG while it was the case for 18.4 % of patients with chronic liver diseases (P=4.5E-07). The presence of anti-HEV was not linked to any of the collected demographical features (age, sex, education, pork meat consumption, water supply, ). By contrast, the presence of anti-HEV was significantly associated with increased levels (1.6-1.8-fold, P<0.0001) of blood aminotransferases (AST, ALT) in patients with persistent hepatitis B or C. Our work indicates that, in Ivory Coast, the presence of IgG directed against HEV might contribute to a deterioration of liver health in patients with already installed persistent liver infections. The mechanisms explaining such phenomenon at distance of acute phase of infection are still unknown but might be linked either to a residual persistence of HEV in a context of general immune exhaustion or to an inappropriate auto-immune reaction as already observed in the aftermath of other viral infection types.
RESUMEN
Influenza transmission is increased among household contacts. Vaccination decreases transmission; however it is unclear how vaccinating a single individual alters disease risk among household contacts, particularly in regions with low vaccination coverage. Pregnant women were randomized to influenza or control vaccination. Households were visited weekly until infants born to enrolled women reached 6 months. Household contacts younger than 5 years were tested for laboratory-confirmed influenza (LCI). Incidence of LCI and rate ratios (RtR) comparing incidence between vaccine groups were calculated. The secondary infection rate (SIR) was calculated for households where LCI was detected. The H1N1 strain in the vaccine was a match for circulating H1N1 during the study, thus, all analyses were performed for H1N1-LCI and any LCI. A total of 5,345 household contacts younger than 5 years followed for a mean of 228 days (standard deviation [SD] = 45 days) experienced 2,957 influenza-like illness episodes. Incidence of any LCI and H1N1-LCI was 23 (N = 276) and 7.3 per 100,000 days (N = 89), respectively. Household contacts of women who received influenza vaccine had fewer LCI (RtR = 0.90; 95% CI: 0.71, 1.14) and fewer H1N1-LCI (RtR = 0.73; 95% CI: 0.48, 1.11) episodes than contacts in control households. Incidence of LCI and household SIR were low in households of women enrolled in an influenza vaccine trial in Mali. Although low incidence made statistical significance difficult to detect, there was a trend for decreased rates of H1N1-LCI in households where a pregnant mother received influenza vaccination.
Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Gripe Humana/diagnóstico , Gripe Humana/transmisión , Vacunación/estadística & datos numéricos , Adulto , Preescolar , Familia , Femenino , Humanos , Incidencia , Lactante , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/prevención & control , Masculino , Malí , Madres , Embarazo , Factores de RiesgoRESUMEN
Preterm birth is a primary outcome of interest in maternal vaccination trials but determination of gestational age is challenging in limited-resource settings. This study compares the New Ballard Score and fundal height measurements with the current standard of early ultrasound for sensitivity of predicting preterm birth. A trial of maternal influenza vaccination was conducted in Bamako, Mali. The New Ballard Score and fundal height were collected on 4038 infants born in the trial, ultrasound data were available for 1893 of those infants. New Ballard Score and fundal height were compared, consecutively, to all ultrasound results, early ultrasound results from the first trimester, and the date of last menstrual period for estimation of gestational age. Sensitivity of the New Ballard Score for identifying preterm infants was 0.33 compared with early ultrasound and 0.1 compared with the last menstrual period based estimates of gestational age. Sensitivity of low birth weight alone was 0.43 compared with early ultrasound. New Ballard Score estimated gestational age within 1 week of ultrasound more frequently than fundal height (53% compared with 7.6%, respectively) yet New Ballard Score identified few infants as preterm (1.8% vs 5.8% by early ultrasound), and was biased toward categorizing low birth weight infants and infants requiring hospitalization as preterm. New Ballard Score is not an ideal measure for identifying preterm births in low-resource settings. Despite the time and cost of training required for correct measurement of New Ballard Score, measurement of low birth weight alone performed better than New Ballard Score for identifying preterm infants.