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1.
BMC Infect Dis ; 22(1): 103, 2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35093029

RESUMEN

BACKGROUND: Group A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis. Asymptomatic bacterial colonization is considered a necessary step towards sepsis. Intra-partum azithromycin may reduce GAS carriage. METHODS: A posthoc analysis of a double-blind, placebo-controlled randomized-trial was performed to determine the impact of 2 g oral dose of intra-partum azithromycin on maternal and neonatal GAS carriage and antibiotic resistance. Following screening, 829 mothers were randomized who delivered 843 babies. GAS was determined by obtaining samples from the maternal and newborn nasopharynx, maternal vaginal tract and breastmilk. Whole Genome Sequencing (WGS) of GAS isolates was performed using the Illumina Miseq platform. RESULTS: GAS carriage was lower in the nasopharynx of both mothers and babies and breast milk among participants in the azithromycin arm. No differences in GAS carriage were found between groups in the vaginal tract. The occurrence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm. WGS revealed all macrolide-resistant vaginal tract isolates from the azithromycin arm were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)) harbouring macrolide resistant genes msr(D) and mef(A). Ten of the 45 GAS isolates (22.2%) were SDSE(A). CONCLUSIONS: Oral intra-partum azithromycin reduced GAS carriage among Gambian mothers and neonates however carriage in the maternal vaginal tract was not affected by the intervention due to azithromycin resistant SDSE(A). SDSE(A) resistance must be closely monitored to fully assess the public health impact of intrapartum azithromycin on GAS. Trial registration ClinicalTrials.gov Identifier NCT01800942.


Asunto(s)
Azitromicina , Portador Sano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Portador Sano/tratamiento farmacológico , Portador Sano/epidemiología , Femenino , Gambia/epidemiología , Humanos , Lactante , Recién Nacido , Streptococcus pyogenes
2.
Clin Infect Dis ; 69(Suppl 2): S140-S147, 2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31505630

RESUMEN

BACKGROUND: Pediatric bacterial meningitis (PBM) remains an important cause of disease in children in Africa. We describe findings from sentinel site bacterial meningitis surveillance in children <5 years of age in the Republic of Benin, 2011-2016. METHODS: Cerebrospinal fluid (CSF) was collected from children admitted to Parakou, Natitingou, and Tanguieta sentinel hospitals with suspected meningitis. Identification of Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (meningococcus) was performed by rapid diagnostic tests, microbiological culture, and/or polymerase chain reaction; where possible, serotyping/grouping was performed. RESULTS: A total of 10 919 suspected cases of meningitis were admitted to the sentinel hospitals. Most patients were 0-11 months old (4863 [44.5%]) and there were 542 (5.0%) in-hospital deaths. Overall, 4168 CSF samples were screened for pathogens and a total of 194 (4.7%) PBM cases were confirmed, predominantly caused by pneumococcus (98 [50.5%]). Following pneumococcal conjugate vaccine (PCV) introduction in 2011, annual suspected meningitis cases and deaths (case fatality rate) progressively declined from 2534 to 1359 and from 164 (6.5%) to 14 (1.0%) in 2012 and 2016, respectively (P < .001). Additionally, there was a gradual decline in the proportion of meningitis cases caused by pneumococcus, from 77.3% (17/22) in 2011 to 32.4% (11/34) in 2016 (odds ratio, 7.11 [95% confidence interval, 2.08-24.30]). Haemophilus influenzae meningitis fluctuated over the surveillance period and was the predominant pathogen (16/34 [47.1%]) by 2016. CONCLUSIONS: The observed decrease in pneumococcal meningitis after PCV introduction may be indicative of changing patterns of PBM etiology in Benin. Maintaining vigilant and effective surveillance is critical for understanding these changes and their wider public health implications.


Asunto(s)
Meningitis Bacterianas/epidemiología , Vacunas Neumococicas/administración & dosificación , Vigilancia de Guardia , Benin/epidemiología , Preescolar , Femenino , Haemophilus influenzae/clasificación , Humanos , Lactante , Recién Nacido , Masculino , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/microbiología , Neisseria meningitidis/clasificación , Serotipificación , Streptococcus pneumoniae/clasificación , Vacunas Conjugadas/administración & dosificación
3.
Clin Infect Dis ; 67(8): 1191-1197, 2018 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-29608659

RESUMEN

Background: Oral azithromycin given to women in labor decreases maternal and neonatal bacterial carriage but increases azithromycin-resistant bacteria during at least 4 weeks following the intervention. We assessed the prevalence of bacterial carriage and azithromycin resistance 12 months after treatment among study infants. Methods: Nasopharyngeal swabs (NPSs) were collected between November 2014 and May 2015 from children aged 11-13 months whose mothers had received azithromycin or placebo during labor. Streptococcus pneumoniae and Staphylococcus aureus were isolated using conventional microbiological methods. Antibiotic susceptibility was determined by disk diffusion and confirmed by Etest or VITEK-2. Results: NPSs were collected from 461 children. The prevalence of S. pneumoniae and S. aureus was similar between children from the azithromycin and placebo arms (85.0% vs 82.1%; odds ratio [OR], 1.23 [95% confidence interval {CI}, .73-2.08] for S. pneumoniae and 21.7% vs 21.3%; OR, 1.02 [95% CI, .64-1.64] for S. aureus). Prevalence of azithromycin-resistant S. pneumoniae was similar in both arms (1.8% vs 0.9% in children from the azithromycin and placebo arms, respectively; OR, 2.10 [95% CI, .30-23.38]); resistance to other antibiotics was also similar between arms. For S. aureus, there was no difference in azithromycin resistance between children in the azithromycin (3.1%) and placebo (2.6%) arms (OR, 1.22 [95% CI, .35-4.47]) or resistance to any other antibiotics. Conclusions: The higher prevalence of S. aureus azithromycin resistance observed among women treated during labor and their babies 4 weeks after treatment had waned 12 months after delivery. Azithromycin intervention did not induce other antibiotic resistance to S. pneumoniae or S. aureus. Clinical Trials Registration: NCT01800942.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Administración Oral , Adulto , Portador Sano/tratamiento farmacológico , Portador Sano/microbiología , Femenino , Estudios de Seguimiento , Gambia , Humanos , Lactante , Trabajo de Parto , Efectos Adversos a Largo Plazo , Masculino , Exposición Materna , Pruebas de Sensibilidad Microbiana , Nasofaringe/microbiología , Embarazo , Prevalencia , Adulto Joven
4.
Clin Infect Dis ; 64(suppl_3): S253-S261, 2017 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-28575359

RESUMEN

BACKGROUND.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1-59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. RESULTS.: A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (κ = 0.50) and between arbitrators was 84% (κ = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (κ = 0.25) and 48.5% (κ = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). CONCLUSIONS.: Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process.


Asunto(s)
Neumonía/diagnóstico por imagen , Neumonía/etiología , Radiografía Torácica/normas , Preescolar , Femenino , Hospitalización , Humanos , Lactante , Masculino , Neumonía/diagnóstico , Neumonía/epidemiología , Estándares de Referencia , Organización Mundial de la Salud
5.
BMC Infect Dis ; 17(1): 799, 2017 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-29282015

RESUMEN

BACKGROUND: Vertical transmission can result in neonatal infection and disease. Reducing the transmission of bacterial pathogens from mother to infant may be an effective means of preventing neonatal infection, including bacterial conjunctivitis. METHODS: In a double-blind, randomized trial, we assessed the effect of administering a single dose of oral azithromycin to women in labour on bacterial colonization of the neonate. A reduction in purulent neonatal conjunctivitis was a secondary objective of the trial. Ocular samples were collected from the lower fornix of infants presenting with clinical signs of purulent conjunctivitis during the first eight weeks of life. Incidence of purulent conjunctivitis was compared between trial arms. Bacterial infection was assessed using PCR and incidence of purulent conjunctivitis due to bacteria was also compared between arms. RESULTS: Forty of 843 infants (4.7%) presented clinical signs of purulent conjunctivitis. No significant difference in incidence of purulent conjunctivitis was seen between azithromycin and placebo arms [4.3% (18/419) versus 5.2% (22/424), OR = 0.82, 95% CI (0.44,1.54), p = 0.628]. S. aureus was the most commonly identified pathogen, detected in 38% of cases. Incidence of purulent-conjunctivitis due to bacterial infection was lower in the azithromycin arm [1.2% (5/419) versus 3.8% (16/424), OR = 0.31, 95% CI (0.12-0.82), p = 0.025)]. The incidence of gram-positive bacteria was also lower in the azithromycin arm [1.0% (4/419) versus 3.3% (14/424), OR = 0.28, 95%CI (0.10-0.82), p = 0.029]. CONCLUSIONS: Oral azithromycin given to women during labour may have the potential to reduce the incidence of bacterial neonatal conjunctivitis. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01800942 , registration date 26 Feb 2013.


Asunto(s)
Azitromicina/uso terapéutico , Conjuntivitis Bacteriana/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Administración Oral , Adulto , Bacterias/genética , Bacterias/aislamiento & purificación , Conjuntivitis Bacteriana/epidemiología , Conjuntivitis Bacteriana/microbiología , ADN Bacteriano/aislamiento & purificación , ADN Bacteriano/metabolismo , Método Doble Ciego , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Oportunidad Relativa , Parto , Efecto Placebo , Factores de Riesgo , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Resultado del Tratamiento , Adulto Joven
6.
Antimicrob Agents Chemother ; 60(3): 1592-9, 2015 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-26711756

RESUMEN

Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.).


Asunto(s)
Antimaláricos/farmacocinética , Azitromicina/farmacocinética , Leche Humana/química , Adulto , Antimaláricos/efectos adversos , Azitromicina/efectos adversos , Cromatografía Liquida , Método Doble Ciego , Femenino , Gambia/epidemiología , Humanos , Espectrometría de Masas , Exposición Materna , Leche Humana/metabolismo , Placebos , Embarazo , Atención Prenatal , Estenosis Hipertrófica del Piloro/inducido químicamente , Estenosis Hipertrófica del Piloro/epidemiología , Adulto Joven
7.
BMC Pregnancy Childbirth ; 15: 302, 2015 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-26585192

RESUMEN

BACKGROUND: Neonatal deaths, estimated at approximately 4 million annually, now account for almost 40% of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn's bacterial carriage in the nasopharynx. Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life. METHODS/DESIGN: This is a Phase III, double -blind, placebo controlled randomized clinical trial in which 830 women in labour were randomized to either a single dose of 2 g oral azithromycin or placebo (ratio 1:1). The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia. A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8-10 days after delivery. Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery. Vaginal swabs and breast milk samples were collected from the mothers, and the pathogens Streptococcus pneumoniae, Group B Streptococcus (GBS) and Staphylococcus aureus were isolated from the study samples. For bacterial isolates, susceptibility pattern to azithromycin was determined using disk diffusion and E-test. Eye swabs were collected from newborns with eye discharge during the follow up period, and Chlamydial infection was assessed using molecular methods. DISCUSSION: This is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn. If the trial confirms this hypothesis, the next step will be to assess the impact of this intervention on neonatal sepsis. The proposed intervention should be easily implementable in developing countries. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT01800942--First received: February 26, 2013.


Asunto(s)
Antibacterianos/administración & dosificación , Azitromicina/administración & dosificación , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Adolescente , Adulto , Parto Obstétrico , Método Doble Ciego , Femenino , Gambia , Humanos , Lactante , Recién Nacido , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Leche Humana/microbiología , Nariz/microbiología , Embarazo , Staphylococcus aureus/aislamiento & purificación , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Vagina/microbiología , Adulto Joven
8.
Clin Infect Dis ; 58(12): 1707-15, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24696240

RESUMEN

BACKGROUND: Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management. METHODS: We conducted a mass spectrometry-based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC). RESULTS: Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval, .64-.79]) and highly predictive of bacteremia (78% [64%-92%]), pneumococcal bacteremia (84% [71%-98%]), and "probable bacterial etiology" (91% [84%-98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%-100%]) and Kenyan children (82% [74%-91%]). CONCLUSIONS: Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies.


Asunto(s)
Lipocalinas/sangre , Neumonía Bacteriana/sangre , Proteínas Proto-Oncogénicas/sangre , Insuficiencia Respiratoria/sangre , Índice de Severidad de la Enfermedad , Proteínas de Fase Aguda , Área Bajo la Curva , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Preescolar , Femenino , Gambia , Haptoglobinas/metabolismo , Humanos , Lactante , Kenia , Lipocalina 2 , Malaria Falciparum/complicaciones , Masculino , Espectrometría de Masas , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/terapia , Valor Predictivo de las Pruebas , Proteómica , Curva ROC , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/parasitología , Factor de von Willebrand/metabolismo
9.
Clin Infect Dis ; 59(5): 682-5, 2014 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-24867789
10.
Clin Infect Dis ; 57(11): 1527-34, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24046305

RESUMEN

BACKGROUND: The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. METHODS: Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to <2 years, Hib antibody levels in children aged <5 years, and Hib vaccine coverage and timing in children aged 1 to <2 years. RESULTS: The incidence of Hib meningitis remained low (averaging 1.3 per 100 000 children aged <5 years annually), as did the Hib oropharyngeal carriage rate (0.9%). Hib antibody levels were protective in >99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. CONCLUSIONS: Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries.


Asunto(s)
Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae tipo b/inmunología , Vacunas Conjugadas/inmunología , Portador Sano/epidemiología , Preescolar , Estudios Transversales , Gambia/epidemiología , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/inmunología , Vacunas contra Haemophilus/inmunología , Humanos , Lactante , Vacunación Masiva , Vigilancia en Salud Pública , Vacunas Conjugadas/administración & dosificación
11.
J Pediatr ; 163(1 Suppl): S4-7, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23773593

RESUMEN

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine. STUDY DESIGN: This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002. RESULTS: The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100,000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months. CONCLUSION: Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose.


Asunto(s)
Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae tipo b/inmunología , Meningitis por Haemophilus/epidemiología , Cápsulas Bacterianas/inmunología , Femenino , Gambia/epidemiología , Vacunas contra Haemophilus/inmunología , Humanos , Incidencia , Lactante , Masculino , Meningitis por Haemophilus/prevención & control , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología
12.
PLoS Med ; 8(10): e1001107, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22028630

RESUMEN

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia. METHODS AND FINDINGS: A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively). A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small. CONCLUSIONS: Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a "herd effect" in non-vaccinated older children and adults. No significant serotype replacement was detected. Please see later in the article for the Editors' Summary.


Asunto(s)
Nasofaringe/microbiología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Femenino , Gambia/epidemiología , Humanos , Masculino , Vacunas Meningococicas/uso terapéutico , Serotipificación , Adulto Joven
13.
Front Pediatr ; 9: 579922, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33659227

RESUMEN

Background: The Gambia Demographic and Health Survey 2013 data showed that up to 63% of deliveries in the country occur in health facilities. Despite such a high rate, there are few facility-based studies on delivery outcomes in the country. This analysis ancillary to a randomized control trial describes occurrence of poor pregnancy outcomes in a cohort of women and their infants delivering in a government health facility in urban Gambia. Methods: Using clinical information obtained during the trial, we calculated rates of poor pregnancy outcomes including stillbirths, hospitalization and neonatal deaths. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) in the risk factors analysis. Results: Between April 2013 and 2014, 829 mothers delivered 843 babies, including 13 stillbirths [15.4 (7.1-23.8)] per 1,000 births. Among 830 live born infants, 7.6% (n = 63) required hospitalization during the 8-week follow-up period. Most of these hospitalizations (74.6%) occurred during the early neonatal period (<7 days of life). Severe clinical infections (i.e., sepsis, meningitis and pneumonia) (n = 27) were the most common diagnoses, followed by birth asphyxia (n = 13), major congenital malformations (n = 10), jaundice (n = 6) and low birth weight (n = 5). There were sixteen neonatal deaths, most of which also occurred during the early neonatal period. Overall, neonatal mortality rate (NMR) and perinatal mortality rate (PMR) were 19.3 (CI: 9.9-28.7) per 1,000 live births and 26.1 (CI: 15.3-36.9) per 1,000 total births, respectively. Severe clinical infections and birth asphyxia accounted for 37 and 31% of neonatal deaths, respectively. The risk of hospitalization was higher among neonates with severe congenital malformations, low birth weight, twin deliveries, and those born by cesarean section. Risk of mortality was higher among neonates with severe congenital malformations and twin deliveries. Conclusion: Neonatal hospitalization and deaths in our cohort were high. Although vertical interventions may reduce specific causes of morbidity and mortality, data indicate the need for a holistic approach to significantly improve the rates of poor pregnancy outcomes. Critically, a focus on decreasing the high rate of stillbirths is warranted. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01800942.

14.
Ann Clin Microbiol Antimicrob ; 8: 3, 2009 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-19154571

RESUMEN

We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively.


Asunto(s)
Meningitis Neumocócica/microbiología , Análisis de Secuencia de ADN , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Femenino , Gambia , Humanos , Lactante , Meningitis Neumocócica/prevención & control , Recurrencia , Serotipificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidad
15.
BMC Infect Dis ; 8: 81, 2008 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-18547404

RESUMEN

BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. CONCLUSION: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas , Streptococcus pneumoniae/genética , Alelos , Preescolar , Ensayos Clínicos como Asunto , Gambia/epidemiología , Genotipo , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Serotipificación , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación
16.
PLoS One ; 13(10): e0206348, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30359447

RESUMEN

OBJECTIVE: To assess the effect of administering an oral dose of 2g of azithromycin in Gambian women during labour on infant growth. METHODS: Children whose mothers had been randomized to receive either an oral dose of 2g of azithromycin or placebo during labour were visited at home at the end of infancy by trained study nurses blind to the treatment allocation. The follow-up visit of these cohorts (exposed and non-exposed to azithromycin), which was not part of the original trial design, was conducted between November 2014 and May 2015 when the infants were 11 to 13 months of age. During visits, nurses recorded anthropometrical measurements and transcribed information from the infants' welfare cards. RESULTS: Four-hundred and sixty-five (79.6%) of the 584 infants aged 11-13 months at the time of the survey were recruited. The proportion of children with an age-adjusted Z-score <-2SD for mid-upper-arm circumference (MUAC) was lower among those exposed to azithromycin [1.3% versus 6.3%, OR = 0.21 95%CI (0.06,0.72), p = 0.006] and there was weak evidence of a difference in the proportion of infants with weight-for-age (WAZ) Z-score <-2SD [7.1% versus 12.1%, OR = 0.58 95%CI (0.33,1.04), p = 0.065]. For all other malnutrition indicators the proportions were similar in the exposed and un-exposed cohort. CONCLUSIONS: Our results show that azithromycin in labour may have a beneficial effect in MUAC among children who are below the curve. Larger studies with closer follow-up are warranted. TRIAL REGISTRATION (MAIN TRIAL): ClinicalTrials.gov Identifier NCT01800942.


Asunto(s)
Azitromicina/farmacología , Desarrollo Infantil/efectos de los fármacos , Estudios de Seguimiento , Fenómenos Fisiológicos Nutricionales del Lactante/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Administración Oral , Azitromicina/administración & dosificación , Peso Corporal , Femenino , Gambia , Humanos , Lactante , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
J Glob Health ; 8(1): 010418, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29713463

RESUMEN

BACKGROUND: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient. METHODS: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each arm for six months post-enrolment, and height-gain, nutritional status, plasma zinc concentrations, and immune competence were compared. RESULTS: Percentage of treatment failure were similar in placebo and zinc arms both on day 5 (14.0% vs 14.1%) and day 10 (5.2% vs 5.9%). The time to recovery from lower chest wall indrawing and sternal retraction was longer in the placebo compared to zinc arm (24.4 vs 23.0 hours; P = 0.011 and 18.7 vs 11.0 hours; P = 0.006 respectively). The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms (42.3 vs 30.9 hours respectively; P = 0.242). In the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment. CONCLUSIONS: In this population, zinc given as an adjunct treatment for severe pneumonia showed no benefit in treatment failure rates, or clinically important benefit in time to recovery from respiratory symptoms and showed marginal benefit in rapidity of resolution of some signs of severity. This finding does not support routine use of zinc as an adjunct treatment in severe pneumonia in generally zinc replete children. TRIAL REGISTRATION: ISRCTN33548493.


Asunto(s)
Adyuvantes Farmacéuticos/uso terapéutico , Neumonía/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Zinc/uso terapéutico , Niño , Preescolar , Método Doble Ciego , Femenino , Gambia , Humanos , Lactante , Masculino , Resultado del Tratamiento , Zinc/deficiencia
18.
Trop Med Int Health ; 12(11): 1377-85, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18045264

RESUMEN

OBJECTIVE: To assess the effect of vaccines against pneumonia in Gambian children. METHODS: Data from a randomized, controlled trial of a 9-valent pneumococcal conjugate vaccine (PCV) were used. Radiographic findings, interpreted using WHO definitions, were classified as primary end point pneumonia, 'other infiltrates/abnormalities' pneumonia and pneumonia with no abnormality. We calculated the incidence of the different types of radiological pneumonia, and compared clinical and laboratory features between these groups. RESULTS: Among children who did not receive PCV, the incidence of pneumonia with no radiographic abnormality was about twice that of 'other infiltrates' pneumonia and three times that of primary endpoint pneumonia. Most respiratory symptoms, reduced feeding and vomiting occurred most frequently in children with primary endpoint pneumonia. These children were more likely to be malnourished, to have bronchial breath sounds or invasive bacterial diseases, and to die within 28 days of consultation than children in the other groups. Conversely, a history of convulsion, diarrhoea or fast breathing, malaria parasitaemia and isolation of salmonellae were commoner in children with pneumonia with no radiographic abnormality. Lower chest wall indrawing and rhonchi on auscultation were seen most frequently in children with 'other infiltrates/abnormalities' pneumonia. CONCLUSION: Primary endpoint pneumonia is strongly associated with bacterial aetiology and severe pneumonia. Since this category of pneumonia is significantly reduced after vaccination with Hib and pneumococcal vaccines, the risk-benefit of antimicrobial prescription for clinical pneumonia for children with increased respiratory rate may warrant re-examination once these vaccines are in widespread use.


Asunto(s)
Infecciones Neumocócicas/clasificación , Vacunas Neumococicas/uso terapéutico , Neumonía/epidemiología , Preescolar , Gambia/epidemiología , Humanos , Incidencia , Lactante , Infecciones Neumocócicas/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Neumonía/tratamiento farmacológico , Radiografía , Vacunas Conjugadas/uso terapéutico
19.
J Med Microbiol ; 56(Pt 11): 1479-1484, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17965348

RESUMEN

Sixty-two invasive non-typhoidal Salmonella (NTS) isolates from children aged 2-29 months in rural Gambia were examined for serovar prevalence and antimicrobial susceptibility, and characterized using multilocus sequence typing (MLST) of seven genes, aroC, dnaN, hemD, hisD, purE, sucA and thrA. Salmonella enterica serovar Enteritidis was the most common serovar (80.6 %), followed by S. enterica serovar Typhimurium (8.0 %). Thirty-three per cent of the isolates were resistant to all eight antimicrobials tested, including ampicillin (74.2 %), cotrimoxazole (64.5 %) and tetracycline (63 %). A total of 40.3 % of the NTS cases had an initial clinical diagnosis of malaria, whilst 27.3 % had a diagnosis of clinical pneumonia and 18 % had a diagnosis of septicaemia. MLST of NTS resulted in ten different sequence types (STs), of which five were novel, representing five different NTS serovars. In general, STs were restricted to the same serovar. One type (ST11) encompassed 80.6 % of the NTSs. A new NTS serovar named S. enterica serovar Dingiri was discovered. S. Dingiri was isolated from a 6-month-old male with an initial clinical diagnosis of malaria but a final clinical diagnosis of anaemia and septicaemia. S. Dingiri, which possesses an antigenic formula of 17:z:1,6, was sensitive to ampicillin, cefotaxime, chloramphenicol, ciprofloxacin, cotrimoxazole and tetracycline but resistant to gentamicin, and was ST338.


Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones por Salmonella/epidemiología , Infecciones por Salmonella/microbiología , Salmonella enterica/clasificación , Salmonella enterica/aislamiento & purificación , Antibacterianos/farmacología , Técnicas de Tipificación Bacteriana , Preescolar , ADN Bacteriano/química , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple , Gambia/epidemiología , Genotipo , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Población Rural , Salmonella enterica/efectos de los fármacos , Análisis de Secuencia de ADN , Serotipificación
20.
Pediatrics ; 139(2)2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28130432

RESUMEN

BACKGROUND AND OBJECTIVES: We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor. Here, we aim to assess the effect of the intervention on maternal and neonatal clinical infections. METHODS: This was a double-blind, placebo-controlled randomized trial. Gambian women in labor were given either an oral dose of azithromycin (2 g) or placebo. Follow-up was conducted for 8 weeks after delivery. RESULTS: From April 2013 to April 2014, we recruited 829 mothers and their 830 newborns. Sixteen infants died during the follow-up period (8 per arm). No maternal deaths or serious adverse events related to the intervention were reported. Maternal infections were lower in the azithromycin group (3.6% vs 9.2%; relative risk [RR], 0.40; 95% confidence interval [CI], 0.22-0.71; P = .002), as was the prevalence of mastitis (1.4% vs 5.1%; RR, 0.29; 95% CI, 0.12-0.70; P = .005) and fever (1.9% vs 5.8%; RR, 0.33; 95% CI, 0.15-0.74; P = .006). Among newborns, the overall prevalence of infections was also lower in the azithromycin group (18.1% vs 23.8%; RR, 0.76; 95% CI, 0.58-0.99; P = .052) and there was a marked difference in prevalence of skin infections (3.1% vs 6.4%; RR, 0.49; 95% CI, 0.25-0.93; P = .034). CONCLUSIONS: Azithromycin given to women in labor decreases infections in both women and newborns during the puerperal period. Larger studies designed to evaluate the effect of the intervention on severe morbidity and mortality are warranted.


Asunto(s)
Azitromicina/administración & dosificación , Infecciones Bacterianas/prevención & control , Países en Desarrollo , Enfermedades del Recién Nacido/prevención & control , Infección Puerperal/prevención & control , Administración Oral , Portador Sano/prevención & control , Método Doble Ciego , Femenino , Fiebre de Origen Desconocido/prevención & control , Gambia , Humanos , Recién Nacido , Mastitis/prevención & control , Infecciones Neumocócicas/prevención & control , Embarazo , Enfermedades Cutáneas Bacterianas/prevención & control , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae
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