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1.
J Antimicrob Chemother ; 77(2): 448-456, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35107141

RESUMO

OBJECTIVES: This study aimed to simultaneously investigate the pharmacokinetics of ampicillin and gentamicin, currently the WHO standard of care for treating neonatal sepsis. METHODS: Pharmacokinetic data were collected in 59 neonates receiving ampicillin and gentamicin for suspected or proven sepsis in the NeoFosfo trial (NCT03453177). A panel of 23 clinical Escherichia coli isolates from neonates with sepsis, resistant to either ampicillin, gentamicin or both, were tested for susceptibility using chequerboards. Pharmacokinetic/pharmacodynamic (PKPD) modelling and simulations were used to compare single-agent (EUCAST MIC) and combination (chequerboard MIC) target attainment with standard dosing regimens. RESULTS: A model was established that simultaneously estimated parameters of a one-compartment ampicillin model and a two-compartment gentamicin model. A common clearance for both drugs was used (6.89 L/h/70 kg) relating to glomerular filtration (CLGFR), with an additional clearance term added for ampicillin (5.3 L/h/70 kg). Covariate modelling included a priori allometric weight and post-menstrual age scaling of clearance. Further covariate relationships on renal clearance were postnatal age and serum creatinine.Simulation-based PKPD assessments suggest good Gram-positive (MIC ≤ 0.25 mg/L) cover. However, less than one-quarter of neonates were predicted to receive efficacious coverage against Enterobacterales (MIC ≤ 2 mg/L). The benefit of the ampicillin/gentamicin combination was limited, with only 2/23 E. coli clinical strains showing FIC index < 0.5 (synergy) and most in the range 0.5-1 (suggesting additivity). Simulations showed that feasible dosing strategies would be insufficient to cover resistant strains. CONCLUSIONS: PKPD simulations showed ampicillin and gentamicin combination therapy was insufficient to cover Enterobacterales, suggesting the need for alternative empirical treatment options for neonatal sepsis.


Assuntos
Sepse Neonatal , Sepse , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Humanos , Recém-Nascido , Sepse Neonatal/tratamento farmacológico , Sepse/tratamento farmacológico
2.
BMC Med ; 19(1): 122, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34082778

RESUMO

BACKGROUND: Diagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days. METHODS: We conducted a retrospective cohort study to validate seven clinical features identified in 2002 (KCH-2002): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/µL, or CSF to blood glucose ratio <0.1. RESULTS: Among 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77-92) and specificity of 38% (95% CI 37-38). Exclusion of 'fever without malaria parasitaemia' reduced sensitivity to 58% (95% CI 48-68) and increased specificity to 80% (95% CI 79-80). IMCI signs had a sensitivity of 80% (95% CI 70-87) and specificity of 62% (95% CI 61-63). CONCLUSIONS: A lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs.


Assuntos
Criança Hospitalizada , Meningites Bacterianas , Criança , Humanos , Lactente , Quênia/epidemiologia , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/epidemiologia , Estudos Retrospectivos , Punção Espinal
3.
J Antimicrob Chemother ; 76(7): 1855-1864, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33855449

RESUMO

BACKGROUND: Fosfomycin has the potential to be re-purposed as part of a combination therapy to treat neonatal sepsis where resistance to current standard of care (SOC) is common. Limited data exist on neonatal fosfomycin pharmacokinetics and estimates of bioavailability and CSF/plasma ratio in this vulnerable population are lacking. OBJECTIVES: To generate data informing the appropriate dosing of IV and oral fosfomycin in neonates using a population pharmacokinetic analysis of plasma and CSF data. METHODS: The NeoFosfo study (NCT03453177) was a randomized trial that examined the safety and pharmacokinetics of fosfomycin comparing SOC versus SOC plus fosfomycin. Sixty-one neonates received fosfomycin (100 mg/kg IV q12h for 48 h) and then they converted to oral therapy at the same dose. Two plasma pharmacokinetic samples were taken following the first IV and oral doses, sample times were randomized to cover the whole pharmacokinetic profile and opportunistic CSF pharmacokinetic samples were collected. A population pharmacokinetic model was developed in NONMEM and simulations were performed. RESULTS: In total, 238 plasma and 15 CSF concentrations were collected. A two-compartment disposition model, with an additional CSF compartment and first-order absorption, best described the data. Bioavailability was estimated as 0.48 (95% CI = 0.347-0.775) and the CSF/plasma ratio as 0.32 (95% CI = 0.272-0.409). Allometric weight and postmenstrual age (PMA) scaling was applied; additional covariates included postnatal age (PNA) on clearance and CSF protein on CSF/plasma ratio. CONCLUSIONS: Through this analysis a population pharmacokinetic model has been developed that can be used alongside currently available pharmacodynamic targets to select a neonatal fosfomycin dose based on an infant's PMA, PNA and weight.


Assuntos
Doenças Transmissíveis , Fosfomicina , Sepse Neonatal , Antibacterianos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/tratamento farmacológico
4.
Curr Opin Infect Dis ; 28(3): 225-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25887615

RESUMO

PURPOSE OF REVIEW: This review discusses the rational development of guidelines for the management of neonatal sepsis in developing countries. RECENT FINDINGS: Diagnosis of neonatal sepsis with high specificity remains challenging in developing countries. Aetiology data, particularly from rural, community-based studies, are very limited, but molecular tests to improve diagnostics are being tested in a community-based study in South Asia. Antibiotic susceptibility data are limited, but suggest reducing susceptibility to first-and second-line antibiotics in both hospital and community-acquired neonatal sepsis. Results of clinical trials in South Asia and sub-Saharan Africa assessing feasibility of simplified antibiotic regimens are awaited. SUMMARY: Effective management of neonatal sepsis in developing countries is essential to reduce neonatal mortality and morbidity. Simplified antibiotic regimens are currently being examined in clinical trials, but reduced antimicrobial susceptibility threatens current empiric treatment strategies. Improved clinical and microbiological surveillance is essential, to inform current practice, treatment guidelines, and monitor implementation of policy changes.


Assuntos
Antibacterianos/administração & dosagem , Sepse/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Países em Desenvolvimento/estatística & dados numéricos , Estudos de Viabilidade , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Guias de Prática Clínica como Assunto , Vigilância de Evento Sentinela , Sepse/mortalidade , Resultado do Tratamento
5.
BMJ Glob Health ; 9(10)2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39433400

RESUMO

BACKGROUND: Anaemia and malaria are leading causes of paediatric hospitalisation and inpatient mortality in sub-Saharan Africa. However, there is limited empirical data on survival following hospital discharge. We aimed to estimate independent effects of anaemia and malaria parasitaemia on inpatient and 1 year postdischarge mortality among Kenyan children. METHODS: A retrospective cohort study among children admitted to Kilifi County Hospital (KCH) from 2010 to 2019 and followed-up for 1 year postdischarge in Kilifi Health and Demographic Surveillance System (KHDSS). The main exposures were anaemia and malaria parasitaemia at the time of hospital admission while inpatient and 1 year postdischarge mortality were the outcomes. RESULTS: We included 9431 admissions among 7578 children (43% girls), median (IQR) age 19 (9.9‒23) months. 2069 (22%), 3893 (41%) and 1140 (12%) admissions had mild, moderate and severe anaemia, whereas 366 (3.9%), 779 (8.3%) and 224 (2.4%) had low, medium and high malaria parasitaemia, respectively. Overall, there were 381 (4.0%) inpatient deaths: 317/381 (83%) and 47/381 (12%) among children with any level of anaemia and malaria parasitaemia, respectively. Moderate and severe, but not mild anaemia, were positively associated with inpatient death. Low and high level parasitaemia were positively associated with inpatient mortality, while medium level parasitaemia was negatively associated. There were 228 (3.1%) postdischarge deaths: 32.8 (95% CI 28.8‒37.3) deaths/1000 child-years. 180/228 (79%) deaths occurred within 6 months after index discharge and 99/228 (43%) occurred in the community. Overall, 180/228 (79%) and 10/228 (4.4%) postdischarge deaths occurred among children with any level of anaemia and malaria parasitaemia, respectively. Severe anaemia was positively associated with postdischarge mortality (adjusted HR 1.94 (95% CI 1.11‒3.40)), while medium level parasitaemia was negatively associated. CONCLUSION: Interventions to create awareness of postdischarge risks, improve uptake of existing interventions and improved discharge processes targeting high-risk groups such as children admitted with severe anaemia, need to be prioritised.


Assuntos
Anemia , Malária , Humanos , Quênia/epidemiologia , Anemia/mortalidade , Anemia/epidemiologia , Feminino , Masculino , Malária/mortalidade , Lactente , Estudos Retrospectivos , Pré-Escolar , Alta do Paciente/estatística & dados numéricos , Parasitemia/mortalidade , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Estudos de Coortes , Criança , Mortalidade da Criança
6.
BMJ Open ; 13(1): e067482, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631234

RESUMO

OBJECTIVES: To describe admission trends and estimate inpatient and post-discharge mortality and its associated exposures, among young infants (YI) admitted to a county hospital in Kenya. DESIGN: Retrospective cohort study. SETTING: Secondary level hospital. PARTICIPANTS: YI aged less than 60 days admitted to hospital from January 2009 to December 2019: 12 271 admissions in 11 877 individuals. YI who were resident within a Kilifi Health and Demographic Surveillance System (KHDSS): n=3625 with 4421 admissions were followed-up for 1 year after discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient and 1-year post-discharge mortality, the latter in KHDSS residents. RESULTS: Of 12 271 YI admissions, 4421 (36%) were KHDSS-resident. Neonatal sepsis, preterm complications and birth asphyxia accounted for 83% of the admissions. The proportion of YI among under-5s admissions increased from 19% in 2009 to 34% in 2019 (Ptrend=0.02). Inpatient case fatality was 16%, with 66% of the deaths occurring within 48 hours of admission. The introduction of free maternity care in 2013 was not associated with a change in admissions or inpatient mortality among YI. During 1-year post-discharge, 208/3625 (5.7%) YI died, 64.3 (95% CI 56.2 to 73.7) per 1000 infant-years. 49% of the post-discharge deaths occurred within 1 month of discharge, and 49% of post-discharge deaths occurred at home. Both inpatient and post-discharge deaths were associated with low admission weight. Inpatient mortality was associated with clinical signs of disease severity, while post-discharge mortality was associated with the length of hospitalisation, leaving against advice and referral to a specialised hospital. CONCLUSIONS: YIs accounted for an increasing proportion of paediatric admissions and their overall mortality remains high. Post-discharge mortality accounts for a lower proportion of deaths but mortality rate is higher than among children aged 2-59 months. Services to address post-discharge mortality are needed and should focus on infants at higher risk.


Assuntos
Serviços de Saúde Materna , Alta do Paciente , Recém-Nascido , Lactente , Criança , Humanos , Feminino , Gravidez , Pré-Escolar , Estudos Retrospectivos , Quênia/epidemiologia , Pacientes Internados , Assistência ao Convalescente , Hospitais de Condado , Hospitalização , Mortalidade Hospitalar
7.
J Virus Erad ; 9(4): 100355, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38213904

RESUMO

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6-4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4-6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity.

8.
Antibiotics (Basel) ; 12(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37237826

RESUMO

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

9.
Wellcome Open Res ; 7: 3, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600002

RESUMO

Background: Early onset neonatal sepsis (EONS) typically begins prior to, during or soon after birth and may be rapidly fatal. There is paucity of data on the aetiology of EONS in sub-Saharan Africa due to limited diagnostic capacity in this region, despite the associated significant mortality and long-term neurological impairment. Methods: We compared pathogens detected in cord blood samples between neonates admitted to hospital with possible serious bacterial infection (pSBI) in the first 48 hours of life (cases) and neonates remaining well (controls). Cord blood was systematically collected at Kilifi County Hospital (KCH) from 2011-2016, and later tested for 21 bacterial, viral and protozoal targets using multiplex PCR via TaqMan Array Cards (TAC). Results: Among 603 cases (101 [17%] of whom died), 179 (30%) tested positive for ≥1 target and 37 (6.1%) tested positive for multiple targets. Klebsiella oxytoca, Escherichia coli/Shigella spp., Pseudomonas aeruginosa, and Streptococcus pyogenes were commonest. Among 300 controls, 79 (26%) tested positive for ≥1 target, 11 (3.7%) were positive for multiple targets, and K. oxytoca and P. aeruginosa were most common. Cumulative odds ratios across controls: cases (survived): cases (died) were E. coli/Shigella spp. 2.6 (95%CI 1.6-4.4); E. faecalis 4.0 (95%CI 1.1-15); S. agalactiae 4.5 (95%CI 1.6-13); Ureaplasma spp. 2.9 (95%CI 1.3-6.4); Enterovirus 9.1 (95%CI 2.3-37); and Plasmodium spp. 2.9 (95%CI 1.4-6.2). Excluding K. oxytoca and P. aeruginosa as likely contaminants, aetiology was attributed in 9.4% (95%CI 5.1-13) cases using TAC. Leading pathogen attributions by TAC were E. coli/Shigella spp. (3.5% (95%CI 1.7-5.3)) and Ureaplasma spp. (1.7% (95%CI 0.5-3.0)). Conclusions: Cord blood sample may be useful in describing EONS pathogens at birth, but more specific tests are needed for individual diagnosis. Careful sampling of cord blood using aseptic techniques is crucial to minimize contamination. In addition to culturable bacteria, Ureaplasma and Enterovirus were causes of EONS.

10.
Arch Dis Child ; 107(9): 802-810, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35078765

RESUMO

OBJECTIVE: To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. DESIGN: A single-centre open-label randomised controlled trial. SETTING: Kilifi County Hospital, Kenya. PATIENTS: 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019. INTERVENTION: We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. MAIN OUTCOMES AND MEASURES: Serum sodium, AEs and fosfomycin pharmacokinetics. RESULTS: 61 and 59 infants aged 0-23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference -0.95 events/100 infant-days (95% CI -2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged <7 days or weighing <1500 g. CONCLUSION AND RELEVANCE: Fosfomycin offers potential as an affordable regimen with a simple dosing schedule for neonatal sepsis. Further research on its safety is needed in larger cohorts of hospitalised neonates, including very preterm neonates or those critically ill. Resistance suppression would only be achieved for the most sensitive of organisms so fosfomycin is recommended to be used in combination with another antimicrobial. TRIAL REGISTRATION NUMBER: NCT03453177.


Assuntos
Fosfomicina , Sepse Neonatal , Sepse , Antibacterianos/efeitos adversos , Criança , Fosfomicina/efeitos adversos , Gentamicinas , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/tratamento farmacológico , Sepse/tratamento farmacológico , Sódio/uso terapêutico
11.
Front Immunol ; 13: 971866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203568

RESUMO

Shigella is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against Shigella species are currently under clinical development. The investigational 1790GAHB vaccine against Shigella sonnei is based on GMMA (Generalized Modules for Membrane Antigens) technology. The vaccine was well tolerated and induced high antibody levels in early-phase clinical trials in both Shigella-endemic and non-endemic settings. The present analysis assessed the bactericidal activity of antibodies induced by 1790GAHB in healthy Kenyan adults during a phase 2a, controlled, randomized study (NCT02676895). Participants received two doses of 1790GAHB 4 weeks apart containing either 1.5/25 µg or 6/100 µg O antigen/protein, or active comparator vaccines (Control). Serum bactericidal activity (SBA) against S. sonnei was assessed at pre-vaccination (D1), 28 days post-first dose (D29) and 28 days post-second dose (D57), using a luminescence-based assay. Most participants had SBA titers above the lower limit of quantification of the assay at D1. SBA geometric mean titers increased 3.4-fold in the 1.5/25 µg group and 6.3-fold in the 6/100 µg group by D29 and were maintained at D57. There was no increase in SBA geometric mean titers in the Control group. A strong correlation was observed between SBA titers and anti-S. sonnei lipopolysaccharide serum immunoglobulin G antibody concentrations (Pearson correlation coefficient = 0.918), indicating that SBA can effectively complement enzyme-linked immunosorbent assay data by indicating the functionality of 1790GAHB-induced antibodies.


Assuntos
Disenteria Bacilar , Shigella , Vacinas , Adulto , Anticorpos Antibacterianos , Criança , Pré-Escolar , Disenteria Bacilar/prevenção & controle , Humanos , Imunoglobulina G , Quênia , Lipopolissacarídeos , Metilmetacrilatos , Antígenos O , Shigella sonnei
12.
Arch Dis Child ; 106(2): 130-136, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32819909

RESUMO

BACKGROUND: Detection of meningitis is essential to optimise the duration and choice of antimicrobial agents to limit mortality and sequelae. In low and middle-income countries most health facilities lack laboratory capacity and rely on clinical features to empirically treat meningitis. OBJECTIVE: We conducted a diagnostic validation study to investigate the performance of clinical features (fever, convulsions, irritability, bulging fontanel and temperature ≥39°C) and WHO-recommended signs (drowsiness, lethargy, unconsciousness, convulsions, bulging fontanel, irritability or a high-pitched cry) in discriminating meningitis in young infants. DESIGN: Retrospective cohort study. SETTING: Kilifi County Hospital. PATIENTS: Infants aged <60 days hospitalised between 2012 and 2016. MAIN OUTCOME MEASURE: Definite meningitis defined as positive cerebrospinal fluid (CSF) culture, microscopy or antigen test, or leucocytes ≥0.05 x 10∧9/L. RESULTS: Of 4809 infants aged <60 days included, 81 (1.7%) had definite meningitis. WHO-recommended signs had sensitivity of 58% (95% CI 47% to 69%) and specificity of 57% (95% CI 56% to 59%) for definite meningitis. Addition of history of fever improved sensitivity to 89% (95% CI 80% to 95%) but reduced specificity to 26% (95% CI 25% to 27%). Presence of ≥1 of 5 previously identified signs had sensitivity of 79% (95% CI 69% to 87%) and specificity of 51% (95% CI 50% to 53%). CONCLUSIONS: Despite a lower prevalence of definite meningitis, the performance of previously identified signs at admission in predicting meningitis was unchanged. Presence of history of fever improves the sensitivity of WHO-recommended signs but loses specificity. Careful evaluation, repeated assessment and capacity for lumbar puncture and CSF microscopy to exclude meningitis in most young infants with potential signs are essential to management in this age group.


Assuntos
Testes Diagnósticos de Rotina/normas , Meningites Bacterianas/diagnóstico , Serviços de Saúde da Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Prevalência , Estudos Retrospectivos , Serviços de Saúde Rural , Sensibilidade e Especificidade
13.
Wellcome Open Res ; 5: 234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195820

RESUMO

Background: Far less is known about the reasons for hospitalization or mortality during and after hospitalization among school-aged children than among under-fives in low- and middle-income countries. This study aimed to describe common types of illness causing hospitalisation; inpatient mortality and post-discharge mortality among school-age children at Kilifi County Hospital (KCH), Kenya. Methods: A retrospective cohort study of children 5-12 years old admitted at KCH, 2007 to 2016, and resident within the Kilifi Health Demographic Surveillance System (KHDSS). Children discharged alive were followed up for one year by quarterly census. Outcomes were inpatient and one-year post-discharge mortality. Results: We included 3,907 admissions among 3,196 children with a median age of 7 years 8 months (IQR 74-116 months). Severe anaemia (792, 20%), malaria (749, 19%), sickle cell disease (408, 10%), trauma (408, 10%), and severe pneumonia (340, 8.7%) were the commonest reasons for admission. Comorbidities included 623 (16%) with severe wasting, 386 (10%) with severe stunting, 90 (2.3%) with oedematous malnutrition and 194 (5.0%) with HIV infection. 132 (3.4%) children died during hospitalisation. Inpatient death was associated with signs of disease severity, age, bacteraemia, HIV infection and severe stunting. After discharge, 89/2,997 (3.0%) children died within one year during 2,853 child-years observed (31.2 deaths [95%CI, 25.3-38.4] per 1,000 child-years). 63/89 (71%) of post-discharge deaths occurred within three months and 45% of deaths occurred outside hospital. Post-discharge mortality was positively associated with weak pulse, tachypnoea, severe anaemia, HIV infection and severe wasting and negatively associated with malaria.  Conclusions: Reasons for admissions are markedly different from those reported in under-fives. There was significant post-discharge mortality, suggesting hospitalisation is a marker of risk in this population. Our findings inform guideline development to include risk stratification, targeted post-discharge care and facilitate access to healthcare to improve survival in the early months post-discharge in school-aged children.

14.
PLoS One ; 12(8): e0182354, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28787002

RESUMO

BACKGROUND: Bloodstream infection is a common cause of morbidity in children aged <5 years in developing countries. In studies reporting bacteremia in Africa, coagulase-negative Staphylococci (CoNS) are commonly isolated. However, it is currently unclear whether children who are highly susceptible to infection because of severe acute malnutrition (SAM) or HIV should be treated with antimicrobials specifically to cover CoNS. We aimed to determine the clinical significance of CoNS amongst children admitted to a rural hospital in Kenya in relation to nutritional and HIV status. METHODS: Systematically collected clinical and microbiological surveillance data from children aged 6-59 months admitted to Kilifi County Hospital (2007-2013) were analysed. Multivariable regression was used to test associations between CoNS isolation from blood cultures and SAM (MUAC <11.5cm or nutritional oedema (kwashiorkor)), and HIV serostatus; and among children with SAM or HIV, associations between CoNS isolation and mortality, duration of hospitalization and clinical features. RESULTS: CoNS were isolated from blood culture in 906/13,315 (6.8%) children, of whom 135/906 (14.9%) had SAM and 54/906 (6.0%) were HIV antibody positive. CoNS isolation was not associated with SAM (MUAC<11.5cm (aOR 1.11, 95% CI 0.88-1.40) or kwashiorkor (aOR 0.84, 95% CI 0.48-1.49)), or a positive HIV antibody test (aOR 1.25, 95% CI 0.92-1.71). Among children with SAM or a positive HIV antibody test, CoNS isolation was not associated with mortality or prolonged hospitalization. CONCLUSION: In a large, systematic study, there was no evidence that antimicrobial therapy should specifically target CoNS amongst children with SAM or HIV-infection or exposure.


Assuntos
Antibacterianos/farmacologia , Infecções por HIV/complicações , Kwashiorkor/complicações , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/enzimologia , Staphylococcus/fisiologia , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Pré-Escolar , Coagulase/metabolismo , Feminino , Humanos , Lactente , Quênia , Masculino , Staphylococcus/efeitos dos fármacos
15.
Pediatr Infect Dis J ; 36(11): 1073-1078, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28731901

RESUMO

BACKGROUND: Neonatal mortality remains high in sub-Saharan Africa, and a third of deaths are estimated to result from infection. While coagulase-negative staphylococci (CoNS) are leading neonatal pathogens in resource-rich settings, their role, and the need for early anti-Staphylococcal treatment in empiric antibiotic guidelines, is unknown in sub-Saharan Africa. METHODS: We examined systematic clinical and microbiologic surveillance data from all neonatal admissions to Kilifi County Hospital (1998-2013) to determine associated case fatality and/or prolonged duration of admission associated with CoNS in neonates treated according to standard World Health Organization guidelines. RESULTS: CoNS was isolated from blood culture in 995 of 9552 (10%) neonates. Case fatality among neonates with CoNS isolated from blood did not differ from other neonatal admissions (P = 0.2), and duration of admission was not prolonged [odds ratio (OR) = 0.9 (0.7-1.0), P = 0.040]. Neonates with CoNS were more likely to have convulsions [OR = 1.4 (1.0-1.8), P = 0.031] but less likely to have impaired consciousness or severe indrawing [OR = 0.8 (0.7-0.9), P = 0.025; OR = 0.9 (0.7-1.0), P = 0.065]. CONCLUSIONS: CoNS isolation in blood cultures at admission was not associated with adverse clinical outcomes in neonates treated according to standard World Health Organization guidelines for hospital care in this setting. There is no evidence that first-line antimicrobial treatment guidelines should be altered to increase cover for CoNS infections in neonates in this setting.


Assuntos
Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Adolescente , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Hemocultura/estatística & dados numéricos , Criança , Pré-Escolar , Coagulase , Pesquisa Empírica , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/mortalidade , Quênia , Masculino , Estudos Retrospectivos , Infecções Estafilocócicas/epidemiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/enzimologia , Adulto Jovem
17.
Front Immunol ; 8: 1884, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29375556

RESUMO

Shigellosis is a mild-to-severe diarrheal infection, caused by the genus Shigella, and is responsible for significant morbidity and mortality worldwide. We evaluated the safety and immunogenicity of an investigational Shigella sonnei vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in Kenya, a Shigella-endemic country. This phase 2a, observer-blind, controlled randomized study (NCT02676895) enrolled 74 healthy adults aged 18-45 years, of whom 72 were vaccinated. Participants received, in a 1:1:1 ratio, two vaccinations with the 1790GAHB vaccine at doses of either 1.5/25 µg of O antigen (OAg)/protein (group 1.5/25 µg) or 5.9/100 µg (group 5.9/100 µg) at day (D) 1 and D29, or vaccination with a quadrivalent meningococcal vaccine at D1 and tetanus, diphtheria, and acellular pertussis vaccine at D29 (control group). Solicited and unsolicited adverse events (AEs), serious AEs (SAEs), and AEs of special interest (neutropenia and reactive arthritis) were collected. Anti-S. sonnei lipopolysaccharide (LPS) serum immunoglobulin G (IgG) geometric mean concentrations (GMC) were evaluated at D1, D29, and D57 and compared to anti-S. sonnei LPS antibody levels in convalescent patients naturally exposed to S. sonnei. The percentages of participants with seroresponse were also calculated. The most frequently reported solicited local and systemic AEs across all groups were pain and headache, respectively. Only one case of severe systemic reaction was reported (severe headache after first vaccination in group 5.9/100 µg). Seven and three episodes of neutropenia, assessed as probably or possibly related to vaccination respectively, were reported in the investigational and control groups, respectively. No other SAEs were reported. Despite very high baseline anti-S. sonnei LPS serum IgG levels, the 1790GAHB vaccine induced robust antibody responses. At D29, GMC increased 2.10- and 4.43-fold from baseline in groups 1.5/25 and 5.9/100 µg, respectively, whereas no increase was observed in the control group. Antibody titers at D57 were not statistically different from those at D29. Seroresponse was 68% at D29 and 90% at D57 in group 1.5/25 µg, and 96% after each vaccination in group 5.9/100 µg. The 1790GAHB vaccine was well tolerated and highly immunogenic in a population of African adults, regardless of the GMMA OAg/protein content used.

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