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OBJECTIVES: Many African countries have reported fewer COVID-19 cases than countries elsewhere. By the end of 2020, Guinea-Bissau, West Africa, had <2500 PCR-confirmed cases corresponding to 0.1% of the â¼1.8 million national population. We assessed the prevalence of SARS-CoV-2 antibodies in urban Guinea-Bissau to help guide the pandemic response in Guinea-Bissau. STUDY DESIGN: Cross-sectional assessment of SARS-CoV-2 antibody in a cohort of staff at the Bandim Health Project. METHODS: We measured IgG antibodies using point-of-care rapid tests among 140 staff and associates at a biometric research field station in Bissau, the capital of Guinea-Bissau, during November 2020. RESULTS: Of 140 participants, 25 (18%) were IgG-positive. Among IgG-positives, 12 (48%) reported an episode of illness since the onset of the pandemic. Twenty-five (18%) participants had been PCR-tested between May and September; 7 (28%) had been PCR-positive. Four of these seven tested IgG-negative in the present study. Five participants reported that somebody had died in their house, corresponding crudely to an annual death rate of 4.5/1000 people; no death was attributed to COVID-19. Outdoor workers had a lower prevalence of IgG-positivity. CONCLUSIONS: In spite of the low official number of COVID-19 cases, our serosurvey found a high prevalence of IgG-positivity. Most IgG-positives had not been ill. The official number of PCR-confirmed COVID-19 cases has thus grossly underestimated the prevalence of COVID-19 during the pandemic. The observed overall mortality rate in households of Bandim Health Project employees was not higher than the official Guinean mortality rate of 9.6/1000 people.
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COVID-19 , SARS-CoV-2 , Adulto , Estudios Transversales , Atención a la Salud , Guinea Bissau/epidemiología , HumanosRESUMEN
Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) is recommended at birth in TB-endemic areas. Currently, BCG vaccination programmes use "BCG vaccination coverage by 12 months of age" as the performance indicator. Previous studies suggest that BCG-vaccinated children, who develop a scar, have better overall survival compared with BCG-vaccinated children, who do not develop a scar. We summarized the available studies of BCG scarring and child survival. A structured literature search for studies with original data and analysis of BCG scarring and mortality were performed. Combined analyses on the effect of BCG scarring on overall mortality. We identified six studies covering seven cohorts, all from Guinea-Bissau, West Africa, with evaluation of BCG scarring amongst BCG-vaccinated children and follow-up for mortality. Determinants of BCG scarring were BCG strain, intradermal injection route, size of injection wheal, and co-administered vaccines and micronutrients. In a combined analysis, having a BCG scar vs. no BCG scar was associated with a mortality rate ratio (MRR) of 0.61 (95% CI: 0.51-0.74). The proportion with a BCG scar varied from 52 to 93%; the estimated effect of a BCG scar was not associated with the scar prevalence. The effect was strongest in the first (MRR = 0.48 (0.37-0.62)) and second (MRR = 0.63 (0.44-0.92)) year of life, and in children BCG-vaccinated in the neonatal period (MRR = 0.45 (0.36-0.55)). The effect was not explained by protection against TB. Confounding and genetic factors are unlikely to explain the strong association between BCG scarring and subsequent survival. Including "BCG scar prevalence" as a BCG vaccination programme performance indicator should be considered. The effect of revaccinating scar-negative children should be studied.
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Vacuna BCG/efectos adversos , Mortalidad del Niño , Cicatriz/etiología , Enfermedades Endémicas/prevención & control , Tuberculosis/prevención & control , Vacuna BCG/inmunología , Causas de Muerte , Niño , Preescolar , Factores de Confusión Epidemiológicos , Estudios de Seguimiento , Guinea Bissau/epidemiología , Humanos , Lactante , Recién Nacido , Vacunación Masiva/efectos adversos , Estado NutricionalRESUMEN
Background: This study was performed to examine the effects of early BCG vaccination on the risk, cause, and severity of infant hospitalizations. The analysis included 3 trials randomizing low-weight neonates to early BCG vaccination (intervention) versus no BCG vaccination (usual practice in low-weight neonates, control), with hospitalizations as secondary outcome. Methods: Hospitalization data were collected at the pediatric ward of the National Hospital. Effects of BCG vaccination on hospitalization risk were assessed in Cox models providing overall and major disease-group incidence rate ratios (IRRs). Severity was assessed by means of in-hospital case-fatality rates and compared by group as cohort study risk ratios (RRs). Results: Among 6583 infants (3297 in BCG group, 3286 controls), there were 908 infant hospitalizations (450 BCG, 458 controls) and 135 in-hospital deaths (56 BCG, 79 controls). The neonatal (28 days), 6-week, and infant (1-year) BCG versus control hospitalization IRRs were 0.97 (95% confidence interval [CI], .72-1.31), 0.95 (.73-1.24), and 0.96 (.84-1.10). Corresponding BCG versus control case-fatality rate RRs were 0.58 (95% CI, .35-.94), 0.56 (.35-.90), and 0.72 (.53-.99). BCG vaccination tended to reduce neonatal and infant sepsis hospitalization rates (IRR, 0.75 [95% CI, .50-1.13] and 0.78 [.55-1.11], respectively), and it reduced the neonatal in-hospital sepsis mortality rate (RR, 0.46; 95% CI, .22-.98). There were no confirmed hospitalizations for tuberculosis. Conclusions: BCG vaccination did not affect hospitalization rates but reduced in-hospital mortality rates significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on the in-hospital mortality rate were entirely nonspecific. Clinical Trials Registration: NCT00146302, NCT00168610, and NCT00625482.
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Vacuna BCG/administración & dosificación , Enfermedades Transmisibles/mortalidad , Hospitalización/estadística & datos numéricos , Esquemas de Inmunización , Enfermedades Transmisibles/epidemiología , Femenino , Guinea Bissau/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de SupervivenciaRESUMEN
BACKGROUND: Measles and oral polio vaccinations may reduce child mortality to an extent that cannot be explained by prevention of measles and polio infections; these vaccines seem to have beneficial non-specific effects. In the last decades, billions of children worldwide have received measles vaccine (MV) and oral polio vaccine (OPV) through campaigns. Meanwhile the under-five child mortality has declined. Past MV and OPV campaigns may have contributed to this decline, even in the absence of measles and polio infections. However, cessation of these campaigns, once their targeted infections are eradicated, may reverse the decline in the under-five child mortality. No randomized trial has assessed the real-life effect of either campaign on child mortality and morbidity. We present the research protocol of two concurrent trials: RECAMP-MV and RECAMP-OPV. METHODS: Both trials are cluster-randomized trials among children registered in Bandim Health Project's rural health and demographic surveillance system throughout Guinea-Bissau. RECAMP-MV is conducted among children aged 9-59 months and RECAMP-OPV is conducted among children aged 0-8 months. We randomized 222 geographical clusters to intervention or control clusters. In intervention clusters, children are offered MV or OPV (according to age at enrolment) and a health check-up. In control clusters, children are offered only a health check-up. Enrolments began in November 2016 (RECAMP-MV) and March 2017 (RECAMP-OPV). We plan 18,000 enrolments for RECAMP-MV with an average follow-up period of 18 months and 10,000 enrolments for RECAMP-OPV with an average follow-up period of 10 months. Data collection is ongoing. The primary outcome in both trials is non-accidental death or non-accidental first non-fatal hospitalization with overnight stay (composite outcome). Secondary outcomes are: non-accidental death, repeated non-fatal hospitalizations with overnight stay, cause-specific primary outcome, outpatient visit, and illness. We obtained ethical approval from Guinea-Bissau and consultative approval from Denmark. DISCUSSION: Cluster randomization and minimum risk of loss to follow-up are strengths, and no placebo a limitation. Our trials challenge the understanding that MV and OPV only prevent measles and polio, and that once both infections are eradicated, campaigns with MV and OPV can be phased out without negative implications on child health and survival. TRIAL REGISTRATION: NCT03460002.
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Programas de Inmunización/organización & administración , Vacuna Antisarampión/administración & dosificación , Sarampión/prevención & control , Poliomielitis/prevención & control , Vacuna Antipolio Oral/administración & dosificación , Niño , Mortalidad del Niño , Preescolar , Femenino , Guinea Bissau/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. METHODS: The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency or no Danish-speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. RESULTS: Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). CONCLUSION: Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76).
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Vacuna BCG/uso terapéutico , Dermatitis Atópica/prevención & control , Dermatitis Atópica/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Países Bajos/epidemiologíaRESUMEN
Several studies have shown increased in vitro cytokine responses to non-related pathogens after Bacillus Calmette-Guérin (BCG) vaccination. A total of 158 infants (80 BCG administered within 7 days of birth; 78 controls) were bled 4 days post-randomization, and at age 3 and 13 months. Geometric mean concentrations of IL-1ß, TNF-α, IL-6 (24 h stimulation) and IFN-γ, IL-10, IL-17, IL-22 (96 h stimulation) in response to in vitro stimulation with RPMI, LPS, PHA, Escherichia coli, Streptococcus pneumoniae, Candida albicans and BCG were compared among BCG vaccinated children and controls. BCG vaccination did not affect in vitro cytokine production, except IFN-γ and IL-22 response to BCG. Stratifying for 'age at randomization' we found a potentiating effect of BCG on cytokine production (TNF-α, IL-6, IL-10) in the 4 days post randomization stimulations, among children who were vaccinated at age 2-7 days versus age 0-1 days. BCG vaccination did not potentiate cytokine production to non-BCG antigens. At 4 days post randomization, BCG was associated with higher cytokine production in the later randomized children.
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Vacuna BCG/inmunología , Citocinas/sangre , Mycobacterium bovis/inmunología , Vacuna BCG/administración & dosificación , Candida albicans/inmunología , Escherichia coli/inmunología , Femenino , Humanos , Recién Nacido , Masculino , Streptococcus pneumoniae/inmunología , VacunaciónRESUMEN
OBJECTIVES: Children younger than 12 months of age are eligible for childhood vaccines through the public health system in Guinea-Bissau. To limit open vial wastage, a restrictive vial opening policy has been implemented; 10-dose measles vaccine vials are only opened if six or more children aged 9-11 months are present at the vaccination post. Consequently, mothers who bring their child for measles vaccination can be told to return another day. We aimed to describe the household experience and estimate household costs of seeking measles vaccination in rural Guinea-Bissau. METHODS: Within a national sample of village clusters under demographic surveillance, we interviewed mothers of children aged 9-21 months about their experience with seeking measles vaccination. From information about time and money spent, we calculated household costs of seeking measles vaccination. RESULTS: We interviewed mothers of 1308 children of whom 1043 (80%) had sought measles vaccination at least once. Measles vaccination coverage was 70% (910/1308). Coverage decreased with increasing distance to the health centre. On average, mothers who had taken their child for vaccination took their child 1.4 times. Mean costs of achieving 70% coverage were 2.04 USD (SD 3.86) per child taken for vaccination. Half of the mothers spent more than 2 h seeking vaccination and 11% spent money on transportation. CONCLUSIONS: We found several indications of missed opportunities for measles vaccination resulting in suboptimal coverage. The household costs comprised 3.3% of the average monthly income and should be taken into account when assessing the costs of delivering vaccinations.
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Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Programas de Inmunización/estadística & datos numéricos , Vacuna Antisarampión/administración & dosificación , Características de la Residencia/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Países en Desarrollo , Financiación Personal , Guinea Bissau/epidemiología , Accesibilidad a los Servicios de Salud/economía , Humanos , Programas de Inmunización/economía , Lactante , Entrevistas como Asunto , Madres , Factores de Tiempo , TransportesRESUMEN
BACKGROUND: Providing an early, additional measles vaccine (MV) at 4.5 months of age has been shown to reduce child mortality in low-income countries. We studied the effects on growth at 9 and 24 months of age. METHODS: A randomized controlled trial was conducted in Guinea-Bissau from 2003-2007 including 6,648 children. Children were randomized 1:1:1 to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months (group C) Data on anthropometrics were obtained at enrolment at 4.5 months of age and again at 9 and 24 months of age. Analyses were stratified by sex, season of enrolment, and neonatal vitamin A supplementation (NVAS) status, as all these factors have been shown to modify the effect of early MV on mortality. RESULTS: Overall there was no effect of early MV on anthropometry at 9 months. At 24 months children who had received early MV had a significantly larger mid-upper-arm-circumference (MUAC/in cm) (Difference = 0.08; 95% CI (0.02;0.14)) compared with children in the control group; this effect was most pronounced among girls (0.12 (0.03;0.20)). The effect of early MV on MUAC remained significant in the dry season and in girls who received placebo rather than NVAS. CONCLUSION: Early MV was associated with a larger MUAC particularly in girls. These results indicate that a two-dose measles vaccination schedule might not only reduce child mortality but also improve growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT00168558 . Registered September 9, 2005, retrospectively registered.
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Estatura , Desarrollo Infantil , Esquemas de Inmunización , Vacuna Antisarampión , Sarampión/prevención & control , Aumento de Peso , Femenino , Estudios de Seguimiento , Guinea Bissau , Humanos , Lactante , Masculino , Evaluación de Resultado en la Atención de Salud , Estaciones del Año , Factores SexualesRESUMEN
BACKGROUND: Neonatal vitamin A supplementation (NVAS) is currently being considered as policy in countries at risk of deficiency. A previous study suggested that NVAS may be associated with increased atopy. We examined the effect of NVAS on atopy by conducting long-term follow-up of a previous randomized controlled trial in Guinea-Bissau. METHODS: In 2002-2004, we randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate) or placebo together with their Bacillus Calmette-Guérin vaccination. In 2013, we visited the 1692 (39%) children now aged 8-10 years who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as skin prick test reaction of ≥3 mm) were analysed using binomial regression. RESULTS: Of the 1430 children with a valid skin prick test, 228 (16%) were positive (more boys (20%) than girls (12%), P-value < 0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87-1.40]). However, NVAS was associated with significantly increased risk among females (RR 1.78 [1.17-2.72]) but not among males (0.86 [0.64-1.15], P-value for interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated with increased risk of wheezing among females (RR 1.80 [1.03-3.17], but not among males, P-value for interaction = 0.05). CONCLUSION: The study corroborated previous observations; NVAS was associated with increased risk of atopy and wheezing, in this study only among females. Further studies on NVAS and atopy are warranted.
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Suplementos Dietéticos/efectos adversos , Hipersensibilidad Inmediata/epidemiología , Hipersensibilidad Inmediata/etiología , Vitamina A/administración & dosificación , Vitamina A/efectos adversos , Distribución por Edad , Vacuna BCG/administración & dosificación , Niño , Países en Desarrollo , Femenino , Estudios de Seguimiento , Guinea Bissau , Humanos , Incidencia , Recién Nacido , Masculino , Medición de Riesgo , Distribución por Sexo , Pruebas Cutáneas/métodos , Vacunación/métodosRESUMEN
OBJECTIVE: To calculate Tuberculosis (TB) incidence rates in Guinea-Bissau over an 8-year period. METHODS: Since 2003, a surveillance system has registered all TB cases in six suburban districts of Bissau. In this population-based prospective follow-up study, 1205 cases of pulmonary TB were identified between January 2004 and December 2011. Incidence rates were calculated using census data from the Bandim Health and Demographic Surveillance System (HDSS). RESULTS: The overall incidence of pulmonary TB was 279 per 100,000 person-years of observation; the male incidence being 385, and the female 191. TB incidence rates increased significantly with age in both sexes, regardless of smear or HIV status. Despite a peak with unknown cause of 352 per 100,000 in 2007, the overall incidence of pulmonary TB declined over the period. The incidence of HIV infected TB cases declined significantly from 108 to 39 per 100,000, while the incidence of smear-positive TB cases remained stable; the overall figure was 188 per 100,000. CONCLUSIONS: Overall incidence of pulmonary TB in Guinea-Bissau has declined from 2004 to 2011. The decline was also seen in the subgroups of smear-negative and HIV-positive TB cases, probably due to antiretroviral treatment. Smear-positive TB incidence remains stable over the period.
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Antituberculosos/uso terapéutico , Seropositividad para VIH/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Estudios de Seguimiento , Guinea Bissau/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Estudios Prospectivos , Distribución por Sexo , Tuberculosis Pulmonar/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: To examine mortality and hospitalisations among infant twins and singletons after the perinatal period in Guinea-Bissau. METHODS: The study was conducted from September 2009 to November 2012 by the Bandim Health Project (BHP). Newborn twins and unmatched singleton controls were included at the National Hospital Simão Mendes in the capital Bissau. Children were examined clinically at enrolment. Maternal, pregnancy and obstetric information was collected and HIV testing offered at birth. Follow-up occurred at home at 2, 6 and 12 months and through linkage with the paediatric admission register at the National Hospital. RESULTS: About 495 twins and 333 singletons were alive on day 7 after birth. In total, 36 twins and 12 singletons died during follow-up, the post-perinatal infant mortality rate being 91/1000 person-years for twins and 42/1000 for singletons (HR = 2.11, 95% CI: 1.09-4.07). In a multivariable analysis among twins only, birth weight <2000 g [3.32, (1.36-8.07)], death of the cotwin perinatally [2.54, (1.16-5.57)] and severe maternal illness during pregnancy [2.35, (1.00-5.51)] were significant risk factors for twin death. In the subgroup with available HIV status, maternal HIV infection was strongly associated with twin mortality [3.16, (1.24-8.05)]. Death occurred at home for 60% of twins and 67% of singletons. During follow-up, 90 first-time hospital admissions were registered, with similar rates observed for twins (139/1000) and singletons (143/1000) [0.97, (0.61-1.52)]. CONCLUSION: The post-perinatal infant mortality rate of twins was double that of singletons. No excess in twin hospitalisations was observed, possibly implying obstacles to hospital admission for twins in case of severe illness.
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Hospitalización , Mortalidad Infantil , Gemelos , Adulto , Peso al Nacer , Femenino , Guinea Bissau/epidemiología , Infecciones por VIH/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , Mortalidad Perinatal , Embarazo , Complicaciones del Embarazo , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. METHODS: In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. RESULTS: Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96). CONCLUSIONS: There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. STUDY REGISTRATION: Clinicaltrials.gov NCT 01420705.
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Vacuna BCG/inmunología , Suplementos Dietéticos , Hipersensibilidad Inmediata/etiología , Vitamina A/administración & dosificación , Vacuna BCG/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Femenino , Estudios de Seguimiento , Humanos , Hipersensibilidad Inmediata/epidemiología , Recién Nacido , Masculino , Vacuna Antisarampión/administración & dosificación , Vacuna Antisarampión/inmunología , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Live attenuated vaccines have been observed to have particularly beneficial effects for child survival when given in the presence of maternally transferred immunity (priming). We aimed to test this finding and furthermore explore the role of paternal priming. METHODS: In an exploratory, retrospective cohort study in 2017, parental Bacillus Calmette-Guérin (BCG) scars were assessed for infants from the Bandim Health Project (BHP) who had participated in a 2008-2013 trial of neonatal BCG vaccination. Parental scar effects on mortality were estimated from birth to 42 days, the age of the scheduled diphtheria-tetanus-pertussis (DTP) vaccination, in Cox proportional hazard models adjusted with Inverse Probability of Treatment Weighting. FINDINGS: For 66% (510/772) of main trial infants that were still registered in the BHP area, at least one parent was located. BCG scar prevalence was 77% (353/461) among mothers and 63% (137/219) among fathers. In the first six weeks of life, maternal scars were associated with a mortality reduction of 60% (95%CI, 4% to 83%) and paternal scars with 49% (-68% to 84%). The maternal scar association was most beneficial among infants that had received BCG vaccination at birth (73% (-1% to 93%)). Although priming was less evident for paternal scars, having two parents with scars reduced mortality by 89% (13% to 99%) compared with either one or none of the parents having a scar. INTERPRETATION: Parental BCG scars were associated with strongly increased early-life survival. These findings underline the importance of future studies into the subject of inherited non-specific immunity and parental priming. FUNDING: Danish National Research Foundation; European Research Council; Novo Nordisk Foundation; University of Southern Denmark.
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BACKGROUND: Epidemiological and immunological studies are increasingly reporting non-specific effects (NSEs) of vaccines; i.e. vaccines may affect the risk and severity of non-targeted infections. We reviewed how epidemiological studies developed the concept of beneficial NSEs of live vaccines. SOURCES: This is a personal narrative of how we came to pursue the concept of NSEs in studies of measles vaccine (MV) from the late 1970s. We also searched Pubmed for epidemiological studies of nonspecific/non-specific effects (NSEs) of the most common human vaccines. CONTENT: When smallpox vaccine was introduced around 1800, bacillus Calmette-Guérin (BCG) against tuberculosis in the 1920s and oral polio vaccine (OPV) in the 1960s, there were suggestions that these live attenuated vaccines reduced mortality more than expected. However, scientific follow-up was limited and the concept of beneficial NSEs did not become mainstream. We observed beneficial NSEs after MV was introduced in low-income countries in the 1970s. Subsequent observational studies and randomized trials confirmed beneficial NSEs of smallpox vaccine, BCG and OPV. Recently, beneficial NSEs have been claimed for the non-live diphtheria-tetanus-pertussis and rabies vaccines. However, no non-live vaccine has yet been documented to produce beneficial NSEs. IMPLICATIONS: Observational and experimental research has shown beneficial NSEs of four live attenuated vaccines: smallpox vaccine, BCG, OPV and MV. With immunological evidence now supporting the epidemiological observations, it is urgent to take both the specific and NSEs into account in the planning of vaccination programmes.
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Protección Cruzada/inmunología , Vacunas Atenuadas/inmunología , Estudios Clínicos como Asunto , Femenino , Humanos , Masculino , Mortalidad , Factores Sexuales , Vacunación , Vacunas Atenuadas/administración & dosificación , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
OBJECTIVE: To determine whether the combined intervention of 50 000 IU vitamin A administered together with Bacille Calmette-Guerin (BCG) vaccination at birth was associated with adverse events, in particular bulging fontanels and adverse reactions to BCG. SUBJECTS/METHODS: From an ongoing trial, 2145 infants randomized to 50 000 IU vitamin A or placebo with BCG vaccination were recruited. Adverse events were monitored in two different ways: (A) daily clinical examinations by a medical doctor during the first 3 days post supplementation; (B) weekly interviews by a trained assistant during the first month post supplementation. RESULTS: In part A, 1271 infants were enrolled, in part B 2078. Vitamin A supplementation (VAS) was associated with a relative risk (RR) of bulging fontanels of 1.16 (95% confidence interval (CI)=0.82-1.65). The rate of health care contacts and various symptoms during the first month were comparable between the groups. VAS was associated with larger peak local reactions to BCG vaccination in boys, but not in girls (P-value for test of interaction between VAS and sex=0.02). CONCLUSION: 50 000 IU vitamin A with BCG was not associated with adverse events. The observed sex-differential effect of VAS on local reaction to BCG is in line with other observations of sex-differential effects of VAS.
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Vacuna BCG/administración & dosificación , Vacuna BCG/efectos adversos , Fontanelas Craneales/patología , Medición de Riesgo , Vitamina A/administración & dosificación , Vitamina A/efectos adversos , Vacuna BCG/inmunología , Interacciones Farmacológicas , Femenino , Guinea Bissau , Humanos , Esquemas de Inmunización , Recién Nacido , Masculino , Factores Sexuales , Factores de Tiempo , Tuberculosis/prevención & control , Vacunación/métodosRESUMEN
BACKGROUND: Smallpox vaccinations were stopped globally in 1980. Recent studies have shown that in women, being smallpox vaccinated was associated with a reduced risk of HIV infection compared with not being smallpox vaccinated. At the initial infection, HIV-1 most often uses CCR5 as a co-receptor to infect the T-lymphocytes. We therefore investigated whether smallpox vaccination is associated with a down-regulation of CCR5 on the surface of peripheral T-lymphocytes in healthy women in Guinea-Bissau. METHODS: We included HIV seronegative women from Bissau, Guinea-Bissau, born before 1974, with and without a smallpox vaccination scar. Blood samples were stabilised in a TransFix buffer solution and stained for flow cytometry according to a T-cell maturation profile. RESULTS: Ninety-seven women were included in the study; 52 with a smallpox vaccination scar and 45 without a scar. No association between smallpox vaccination scar and CCR5 expression was found in any T-lymphocyte subtype. CONCLUSION: Among HIV seronegative women, being smallpox vaccinated more than 40 years ago was not associated with a down-regulation of CCR5 receptors on the surface of peripheral T-lymphocytes.
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Receptores CCR5/metabolismo , Viruela/inmunología , Viruela/prevención & control , Linfocitos T/inmunología , Vacunación , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1 , Humanos , Persona de Mediana EdadRESUMEN
We performed a randomized study of the immunological effects of an early measles vaccine given at 4.5 months of age and aimed to obtain venous samples from the infants at baseline and 6 weeks later. If this was not feasible, a capillary sample was obtained. We analysed baseline samples from the first 50 children enrolled in the study to investigate the potential differences in ex vivo cytokine production between venous blood and capillary blood. We also obtained paired venous and capillary blood samples from 11 adult volunteers. Whole blood was stimulated with lipopolysaccharide (LPS) [a Toll-like receptor (TLR)-4 ligand], (S)-(2, 3-bis (palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, trihydrochloride (PAM3Cys) (a TLR-2 ligand), phytohaemagglutinin (PHA) or purified protein derivative (PPD). Cytokine concentrations in the supernatants were assessed by a multiplexed assay and were compared between venous and capillary samples in both infants and adults. The production of both the pro- and the anti-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10, was higher in cultures of capillary blood compared with venous blood. This was found in non-stimulated control samples as well as in blood stimulated with PAM3Cys and PPD. Adults produced more IL-5 in venous blood than in capillary blood upon PHA stimulation. We found no other difference in the levels of IL-5 or IFN-gamma between venous and capillary blood. In capillary blood we found sex differences in response to PHA but this was not the case in venous blood. We found significant differences in the production of cytokines between venous and capillary blood. Such differences should be taken into account when setting up immuno-epidemiological studies.
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Recolección de Muestras de Sangre/métodos , Citocinas/biosíntesis , Vacuna Antisarampión/inmunología , Adulto , Envejecimiento/inmunología , Capilares , Femenino , Humanos , Lactante , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Factor de Necrosis Tumoral alfa/biosíntesis , VenasRESUMEN
BACKGROUND: Measles vaccination campaigns targeting children aged 9-59months are conducted every three years in Guinea-Bissau. Studies have demonstrated beneficial non-specific effects of measles vaccine. We compared mortality one year after the December 2012 measles vaccination campaign in Bissau city for children who received campaign measles vaccine with children who did not receive campaign measles vaccine. METHODS: Field workers from Bandim Health Project registered all children living in the Bandim Health Project's study area who received measles vaccination at the campaign posts. Children not seen during the campaign were visited at home and campaign participation status was assessed. We compared mortality rates of participants vs. non-participants in Cox regression models. RESULTS: 5633 children aged 9-59months (85%) received campaign measles vaccination and 1006 (15%) did not. During the subsequent year 16 children died. Adjusted for background factors, the hazard ratio (HR) comparing measles vaccinated versus unvaccinated was 0.28 (95% CI: 0.10-0.77). The benefit was larger for girls (HR: 0.17 (0.05-0.59)) and for children who had received routine measles vaccine before the campaign (HR: 0.15 (0.04-0.63)). CONCLUSIONS: We found indications of strong beneficial non-specific effects of receiving measles vaccine during the 2012 campaign, especially for girls and children with previous routine measles vaccination. Measles vaccination campaigns may be an effective way of improving child survival.
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Mortalidad del Niño , Programas de Inmunización , Vacuna Antisarampión/administración & dosificación , Sarampión/mortalidad , Sarampión/prevención & control , Preescolar , Femenino , Guinea Bissau , Humanos , Lactante , Masculino , Población UrbanaRESUMEN
SETTING: A suburban area of Bissau, the capital of Guinea-Bissau; the study was conducted among presumptive pulmonary tuberculosis (prePTB) patients seeking medical care for signs and symptoms suggestive of PTB. OBJECTIVE: To determine if a clinical TB score and a biomarker suPAR (soluble urokinase plasminogen activator receptor) have separate and composite ability to predict PTB diagnosis and mortality in prePTB patients. DESIGN: Observational prospective follow-up study conducted from August 2010 to August 2012. RESULTS: We included 1011 prePTB patients (mean age 34 years, 95%CI 33-35); 55% (n = 559) were female and 161 (16%) had human immunodeficiency virus (HIV) infection. Of all included patients, 10% (n = 101) were diagnosed with PTB. Mortality during follow-up was 5% (n = 48), with a mean survival time of 158 days (95%CI 27-289) in prePTB patients diagnosed with PTB vs. 144 days (95%CI 109-178) in those not diagnosed with PTB (P = 0.774). After adjusting for HIV status and age, the best separate predictor was suPAR î¶5 ng/ml, with a hazard ratio (HR) of 4.6 (95%CI 2.1-9.9) for mortality and 6.7 (95%CI 4.0-11.2) for TB diagnosis. All patients who died had a TBscore II + suPAR î¶7; the HR of the composite score for subsequent PTB diagnosis was 33.0 (95%CI 4.6-236.6). CONCLUSION: The proposed composite score of suPAR + TBscore II î¶7 can improve TB case finding and clinical monitoring.
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Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/mortalidad , Adolescente , Adulto , Antituberculosos/uso terapéutico , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Guinea Bissau/epidemiología , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
Three studies from Guinea-Bissau found conflicting effects of OPV-at-birth (OPV0) on child survival. One study from 2004 suggested excess male mortality among children receiving OPV0 compared with children receiving NoOPV0 during a period of shortage of OPV. However, two subsequent studies showed beneficial effects of OPV0. In 2004, two national OPV-campaigns had been conducted in Guinea-Bissau. In a reanalysis of the 2004-study, in a survival analysis the age-adjusted mortality rate of study participants was 67% (95% CI=42-81%) lower after the OPV-campaigns than before the campaigns. In the OPV0 group only 22% (655/3031 person-years (pyrs)) of follow-up time was "after" the OPV-campaigns whereas 55% (473/859 pyrs) of the time in the NoOPV0 group was post-campaign (p<0.0001, Chi2). Censoring for OPV-campaigns in the original study removed excess male mortality and made the three studies more homogeneous. Overall, there is now considerable evidence that OPV, like other live vaccines, has important beneficial non-specific effects.