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1.
BMJ Open Respir Res ; 6(1): e000415, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31548894

RESUMO

Introduction: Pneumonia is the leading infectious killer of children. We conducted a double-blind, randomised controlled non-inferiority trial comparing placebo to amoxicillin treatment for fast breathing pneumonia in HIV-negative children aged 2-59 months in Malawi. Occurrence of serious adverse events (SAEs) during the trial were examined to assess disease progression, co-morbidities, recurrence of pneumonia and side effects of amoxicillin. Methods: Enrolled children with fast breathing for age and a history of cough <14 days or difficult breathing were randomised to either placebo or amoxicillin for 3 days, and followed for 14 days to track clinical characteristics and outcomes. Medical history, physical exam, laboratory results and any chest radiographs collected at screening, enrolment and during hospitalisation were evaluated. All SAE reports were reviewed for additional information regarding hospitalisation, course of treatment and outcome. Results: In total, 102/1126 (9.0%) enrolled children with fast breathing pneumonia were reported to have a SAE. Seventy-five per cent (n=77) of SAEs were pneumonia-related (p<0.01). Children<2 years of age represented the greatest proportion (61/77, 79.2%) of those with a pneumonia-related SAE. In the amoxicillin group, there were 46 SAEs and 5 (10.9%) cases were identified as possibly related to study drug (4 gastroenteritis and 1 fever). There were no life-threatening pneumonia SAEs or deaths in either group, and by the time of exit from the study, all children recovered without sequelae. Discussion: In this fast breathing pneumonia clinical trial, SAEs occurred infrequently in both the amoxicillin and placebo groups, and amoxicillin was well tolerated. Trial registration number: NCT02760420. https://clinicaltrials.gov/ct2/show/NCT02760420?term=ginsburg&rank=9.

2.
Lancet Respir Med ; 7(11): 964-974, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31562059

RESUMO

BACKGROUND: Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings. METHODS: This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1-59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed. FINDINGS: We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02-2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (<1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares. INTERPRETATION: bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care. FUNDING: Bill & Melinda Gates Foundation, International AIDS Society, Health Empowering Humanity.

3.
Pediatr Blood Cancer ; 66(11): e27954, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397075

RESUMO

INTRODUCTION: Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub-Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to limited region-specific evidence for safety and efficacy. METHODS: We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi. From January 2015 to November 2017, hydroxyurea at doses of 10-20 mg/kg/day was administered to children with clinically severe disease (targeted use policy). From December 2017 to July 2018, hydroxyurea was prescribed to all patients (universal use policy). RESULTS: Of 187 patients with SCD, seven (3.7%) died and 23 (12.3%) were lost to follow-up. The majority (135, 72.2%) were prescribed hydroxyurea, 59 (43.7%) under the targeted use policy and 76 (56.3%) under the universal use policy. There were no documented severe toxicities. Under the targeted use policy, children with SCD demonstrated absolute decreases in the rates of hospitalization (-4.1 per 1000 person-days; -7.2, -1.0; P = .004), fevers (-4.2 per 1000 person-days; -7.2, -1.1; P = .002), transfusions (-2.3 per 1000 person-days; 95% confidence interval: -4.9, 0.3; P = .06), and annual school absenteeism (-51.2 per person-year; -60.1, -42.3; P < .0001) within 6 months of hydroxyurea commencement. CONCLUSION: We successfully implemented universal administration of hydroxyurea to children with SCD at a tertiary hospital in Malawi. Similar to recently reported trials, hydroxyurea was safe and effective during routine programmatic experience, with clinical benefits particularly among high-risk children. This highlights the importance of continued widespread scale-up of hydroxyurea within SCD programs across SSA.


Assuntos
Anemia Falciforme/tratamento farmacológico , Países em Desenvolvimento , Hidroxiureia/uso terapêutico , Absenteísmo , Adolescente , Anemia Falciforme/epidemiologia , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Terapia Combinada , Feminino , Febre/epidemiologia , Febre/etiologia , Hemoglobinas/análise , Hospitalização/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Humanos , Hidroxiureia/efeitos adversos , Hidroxiureia/provisão & distribução , Lactente , Cooperação Internacional , Malaui/epidemiologia , Masculino , North Carolina , Pacientes Desistentes do Tratamento , Utilização de Procedimentos e Técnicas , Estudos Prospectivos , Centros de Atenção Terciária/estatística & dados numéricos
4.
BMC Health Serv Res ; 19(1): 533, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366394

RESUMO

BACKGROUND: In some low-resource settings bubble continuous positive airway pressure (bCPAP) is increasingly used to treat children with pneumonia. However, the time required for healthcare workers (HCWs) to administer bCPAP is unknown and may have implementation implications. This study aims to compare HCW time spent administering bCPAP and low-flow nasal oxygen care at a district hospital in Malawi during CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial). METHODS: Eligible participants were 1-59 months old with WHO-defined severe pneumonia and HIV-infection, HIV-exposure, severe malnutrition, or hypoxemia and were randomized to either bCPAP or oxygen. We used time motion techniques to observe hospital care in four hour blocks during treatment initiation or follow up (maintenance). HCW mean time per patient at the bedside over the observation period was calculated by study arm. RESULTS: Overall, bCPAP required an average of 34.71 min per patient more than low-flow nasal oxygen to initiate (bCPAP, 118.18 min (standard deviation (SD) 42.73 min); oxygen, 83.47 min (SD, 20.18 min), p < 0.01). During initiation, HCWs spent, on average, 12.45 min longer per patient setting up bCPAP equipment (p < 0.01) and 11.13 min longer per patient setting up the bCPAP nasal interface (p < 0.01), compared to oxygen equipment and nasal cannula set-up. During maintenance care, HCWs spent longer on average per patient adjusting bCPAP, compared to oxygen equipment (bCPAP 4.57 min (SD, 4.78 min); oxygen, 1.52 min (SD, 2.50 min), p = 0.03). CONCLUSION: Effective bCPAP implementation in low-resource settings will likely create additional HCW burden relative to usual pneumonia care with oxygen. TRIAL REGISTRATION: Clinicaltrials.gov NCT02484183 , June 29, 2015.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Corpo Clínico Hospitalar , Oxigenoterapia/métodos , Pneumonia/terapia , Carga de Trabalho/estatística & dados numéricos , Pré-Escolar , Feminino , Pesquisa sobre Serviços de Saúde , Hospitais de Distrito , Humanos , Lactente , Malaui/epidemiologia , Masculino , Pneumonia/mortalidade , Fatores de Tempo , Estudos de Tempo e Movimento
6.
JMIR Res Protoc ; 8(7): e13377, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359870

RESUMO

BACKGROUND: Pneumonia is the leading infectious cause of death worldwide among children below 5 years of age. Clinical trials are conducted to determine optimal treatment; however, these trials often exclude children with comorbidities and severe illness. CONCLUSIONS: Given the paucity of data from Africa, African-based research is necessary to establish optimal management of childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base that includes children with pneumonia and other comorbidities, who are at high risk for mortality or have other complications and are therefore typically excluded from childhood pneumonia clinical trials, can contribute to future iterations of the World Health Organization Integrated Management of Childhood Illness guidelines. METHODS: The study enrolled 1000 children with pneumonia presenting to the outpatient departments of Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi, who were excluded from concurrent randomized controlled clinical trials investigating fast breathing and chest indrawing pneumonia and who met the inclusion criteria for this prospective observational study. Each child received standard care for their illnesses per Malawian guidelines and hospital protocol and was prospectively followed up with scheduled study visits on days 1, 2 (if hospitalized), 6, 14 (in person), and 30 (by phone). Our primary objectives are to describe the clinical outcomes of children who meet the inclusion criteria for this study and to investigate whether the percentages of children cured at day 14 among those with either fast breathing or chest indrawing pneumonia and comorbidities such as severe malaria, anemia, severe acute malnutrition, or HIV are lower than those in children without these comorbidities in the standard care groups in concurrent clinical trials. This study was approved by the Western Institutional Review Board, Malawi College of Medicine Research and Ethics Committee, and the Malawi Pharmacy, Medicines and Poisons Board. OBJECTIVE: This prospective observational study aimed to assess the clinical outcomes of children aged 2-59 months with both pneumonia and other comorbidities in a malaria-endemic region of Malawi. RESULTS: The Innovative Treatments in Pneumonia project was funded by the Bill and Melinda Gates Foundation (OPP1105080) in April 2014. Enrollment in this study began in 2016, and the primary results are expected in 2019. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13377.

7.
PLoS One ; 14(6): e0214583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220085

RESUMO

BACKGROUND: Due to increasing antimicrobial resistance in low-resource settings, strategies to rationalize antibiotic treatment of children unlikely to have a bacterial infection are needed. This study's objective was to utilize a database of placebo treated Malawian children with World Health Organization (WHO) fast breathing pneumonia to develop a prognostic risk score that could aid antibiotic decision making. METHODS: We conducted a secondary analysis of children randomized to the placebo group of the Innovative Treatments in Pneumonia (ITIP) fast breathing randomized, controlled, noninferiority trial. Participants were low-risk HIV-uninfected children 2-59 months old with WHO fast breathing pneumonia in Lilongwe, Malawi. Study endpoints were treatment failure, defined as either disease progression at any time on or before Day 4 of treatment or disease persistence on Day 4, or relapse, considered as the recurrence of pneumonia or severe disease among previously cured children between Days 5 and 14. We utilized multivariable linear regression and stepwise model selection to develop a model to predict the probability of treatment failure or relapse. RESULTS: Treatment failure or relapse occurred in 11.5% (61/526) of children included in this analysis. The final model incorporated the following predictors: heart rate terms, mid-upper arm circumference, malaria status, water source, family income, and whether or not a sibling or other child in the household received childcare outside the home. The model's area under the receiver operating characteristic score was 0.712 (95% confidence interval 0.66, 0.78) and it explained 6.1% of the variability in predicting treatment failure or relapse (R2, 0.061). For the model to categorize all children with treatment failure or relapse correctly, 77% of children without treatment failure or relapse would require antibiotics. CONCLUSION: The model had inadequate discrimination to be appropriate for clinical application. Different strategies will likely be required for models to perform accurately among similar pediatric populations.


Assuntos
Antibacterianos/uso terapêutico , Modelos Teóricos , Pneumonia/tratamento farmacológico , Pré-Escolar , Tomada de Decisão Clínica , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Lactente , Modelos Lineares , Malaui , Masculino , Análise Multivariada , Estudos Prospectivos , Medição de Risco , Falha de Tratamento , Organização Mundial da Saúde
8.
BMJ Open Respir Res ; 6(1): e000414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179007

RESUMO

Background: Pneumonia is the leading infectious killer of children less than 5 years of age worldwide. In addition to vaccines that help prevent pneumonia, understanding the environmental and socioeconomic risk factors for child pneumonia is critical to further prevention. Methods: Data from children with fast breathing pneumonia enrolled in a non-inferiority clinical trial assessing the effectiveness of 3-day placebo versus antibiotic treatment in Lilongwe, Malawi were used to examine environmental and socioeconomic characteristics within the study population. Location of residence was collected for enrolled children, and spatial enrolment rates were compared across Lilongwe using a spatial scan statistic. Results: Data from 1101 children were analysed. Three urban subdistricts (locally known as 'Areas') (Areas 24, 36 and 38) out of 51 were identified with higher than expected enrolment. These three areas were associated with higher rates of poverty (37.8% vs 23.9%) as well as informal settlements and poorer sanitation (42.4% vs 7.4%) than other areas. Parents of enrolled children from these areas also had lower rates of secondary education compared with parents of children enrolled from other areas (55% vs 67% (p<0.01) among fathers; 47% vs 54% (p<0.01) among mothers). Conclusion: In Lilongwe, areas with higher rates of poverty, informal settlements and poor sanitation contributed higher than expected enrolment of children to our fast breathing child pneumonia clinical trial when compared with other areas. Additional research is needed to evaluate the impact of environmental and socioeconomic risk factors, along with vaccination status, on the incidence of fast breathing pneumonia in children living in this region.

9.
Pediatr Pulmonol ; 54(7): 1052-1059, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30912314

RESUMO

OBJECTIVE: To assess the performance of reusable pulse oximeter probe and microprocessor box combinations, of varying price-points, in the context of a low-income pediatric setting. METHODS: A prospective, randomized cross-over study comparing time to biologically plausible oxygen saturation (SpO2 ) between: (1) Lifebox LB-01 probe with Masimo Rad-87 box (L + M) and (2) a weight-appropriate reusable Masimo probe with Masimo Rad-87 box (M + M). A post hoc secondary analysis comparison with historical usability testing data with the Lifebox LB-01 probe and Lifebox V1.5 box (L + L) was also conducted. Participants, children aged 0 to 35 months, were recruited from pediatric wards and outpatient clinics in the central region of Malawi. The primary outcome was time taken to achieve a biologically plausible SpO 2 measurement, compared using t tests for equivalence. RESULTS: We recruited 572 children. Plausible SpO2 measurements were obtained in less than 1 minute, 71%, 70%, and 63% for the M + M, L + M, and L + L combinations, respectively. A similar pattern was seen for less than 2 minutes, however, this effect disappeared at less than 5 minutes with 96%, 96%, and 95% plausible measurements. Using a ±10 second threshold for equivalence, we found L + M and M + M to be equivalent, but were under-powered to assess equivalence for L + L. CONCLUSIONS: The novel reusable pediatric Lifebox probe can achieve a quality SpO2 measurement within a pragmatic time range of weight-appropriate Masimo equivalent probes. Further research, which considers the cost of the devices, is needed to assess the added value of sophisticated motion tolerance software.

10.
JAMA Pediatr ; 173(1): 21-28, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30419120

RESUMO

Importance: Pneumonia is the leading infectious killer of children. Rigorous evidence supporting antibiotic treatment of children with nonsevere fast-breathing pneumonia in low-resource African settings is lacking. Objective: To assess whether treatment with placebo for nonsevere fast-breathing pneumonia is substantively less effective than 3 days of treatment with amoxicillin. Design, Setting, and Participants: This double-blind, 2-arm, randomized clinical noninferiority trial with follow-up of 14 days screened 1343 HIV-uninfected children aged 2 to 59 months with nonsevere fast-breathing pneumonia at outpatient departments of hospitals in Lilongwe, Malawi, Africa, between June 2016 and June 2017. Interventions: Placebo or amoxicillin dispersible tablets administered twice daily for 3 days. Main Outcomes and Measures: The primary end point was the proportion of children failing treatment by day 4 with a relative noninferiority margin of 1.5 times the failure rate in the amoxicillin group. Primary analyses were performed based on the intention-to-treat principle. Planned secondary analyses included treatment failure or relapse by day 14. Results: In total, 1126 children were randomized to 3 days of amoxicillin (n = 564) or placebo (n = 562) therapy. Baseline demographic and clinical characteristics were similar between the groups. For the entire study population, the mean (SD) age was 21.3 (15.1) months, and 601 (53.4%) were female. After an interim analysis, the data safety monitoring board stopped the study because children receiving amoxicillin had a 4.0% (22 of 552 with outcome data) treatment failure rate by day 4, whereas children receiving placebo had a 7.0% (38 of 543) treatment failure rate (adjusted relative risk, 1.78; 95% CI, 1.07%-2.97%; adjusted absolute difference, 3.0%; 95% CI, 0.4%-5.7%). Among children with known day 14 outcomes, 56 of 552 (10.1%) receiving amoxicillin and 64 of 543 (11.8%) receiving placebo had either treatment failure by day 4 or relapse by day 14 (relative risk, 1.16; 95% CI, 0.83%-1.63%; absolute difference, 1.6%; 95% CI, -2.1% to 5.4%). There were no deaths. Conclusions and Relevance: In HIV-uninfected children aged 2 to 59 months in a malaria-endemic region of Malawi, placebo treatment of nonsevere fast-breathing pneumonia was significantly inferior to treatment with amoxicillin. However, by day 4, approximately 93% of children receiving placebo were without treatment failure, and there was no significant difference between groups in treatment failure or relapse by day 14. The number of children with nonsevere fast-breathing pneumonia that needed amoxicillin treatment for 1 child to benefit was 33. Trial Registration: ClinicalTrials.gov Identifier: NCT02760420.


Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológico , Pré-Escolar , Países em Desenvolvimento , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Análise de Intenção de Tratamento , Modelos Lineares , Malaui , Masculino , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Int J Infect Dis ; 77: 40-47, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30244075

RESUMO

OBJECTIVES: This study was performed to investigate the epidemiology of bloodstream infection (BSI) in oncology patients at Red Cross War Memorial Children's Hospital (RCWMCH), Cape Town, with focus placed on the most common causes, complications, and antimicrobial susceptibilities in BSI. METHODS: A retrospective cross-sectional study was conducted in the Haematology-Oncology Unit of RCWMCH. All positive blood cultures from RCWMCH oncology patients obtained in 2012 to 2014 were retrieved to identify cases of BSI. RESULTS: Three hundred and forty-three positive cultures were identified, for 150 BSI episodes among 89 patients; 49.1% of the culture isolates were Gram-positive bacteria, 41.6% were Gram-negative bacteria, and 9.3% were fungal. Coagulase-negative Staphylococcus and viridans group Streptococcus were the most common Gram-positive isolates. Escherichia coli and Klebsiella species were the most common Gram-negative isolates. The majority of BSI episodes occurred in patients with haematological malignancies (74%), in the presence of severe neutropenia (76.4%), and were associated with chemotherapy (88%). Complications occurred in 14% of BSI. Fungal infections had the highest prevalence of complications (21.4%). Three children died during BSI, giving a case-fatality rate of 2%. CONCLUSIONS: BSI in these patients was caused mainly by Gram-positive bacteria and was associated with a low case-fatality rate. These results are consistent with worldwide experience of BSI in paediatric oncology.


Assuntos
Bacteriemia/epidemiologia , Neoplasias/microbiologia , Neutropenia/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Fungos/isolamento & purificação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Hospitais Pediátricos , Humanos , Masculino , Neoplasias/complicações , Neutropenia/microbiologia , Prevalência , Cruz Vermelha , Estudos Retrospectivos , África do Sul , Resultado do Tratamento
14.
BMC Infect Dis ; 18(1): 476, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241517

RESUMO

BACKGROUND: Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia. METHODS: This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study will enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the study will be hospitalized for 48 h after enrollment and will have scheduled study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary outcome. We hypothesize that the rates of treatment failure will be similar in both arms and that 3 days of treatment will be non-inferior to 5 days of amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority margin of 1.5. This trial was approved by the Western Institutional Review Board and Malawi College of Medicine Research and Ethics Committee. DISCUSSION: Given the paucity of data from Africa, African-based research is necessary to establish appropriate duration of treatment with amoxicillin DT for chest indrawing childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base will contribute to future iterations of World Health Organization Integrated Management of Childhood Illness guidelines. TRIAL REGISTRATION: NCT02678195 : Pre-results. Date registered February 9, 2016.


Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológico , Administração Oral , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lactente , Malaui , Masculino , Efeito Placebo , Comprimidos/química , Resultado do Tratamento
16.
BMJ Open Respir Res ; 4(1): e000195, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28883928

RESUMO

INTRODUCTION: Pneumonia is a leading cause of mortality among children in low-resource settings. Mortality is greatest among children with high-risk conditions including HIV infection or exposure, severe malnutrition and/or severe hypoxaemia. WHO treatment recommendations include low-flow oxygen for children with severe pneumonia. Bubble continuous positive airway pressure (bCPAP) is a non-invasive support modality that provides positive end-expiratory pressure and oxygen. bCPAP is effective in the treatment of neonates in low-resource settings; its efficacy is unknown for high-risk children with severe pneumonia in low-resource settings. METHODS AND ANALYSIS: CPAP IMPACT is a randomised clinical trial comparing bCPAP to low-flow oxygen in the treatment of severe pneumonia among high-risk children 1-59 months of age. High-risk children are stratified into two subgroups: (1) HIV infection or exposure and/or severe malnutrition; (2) severe hypoxaemia. The trial is being conducted in a Malawi district hospital and will enrol 900 participants. The primary outcome is in-hospital mortality rate of children treated with standard care as compared with bCPAP. ETHICS AND DISSEMINATION: CPAP IMPACT has approval from the Institutional Review Boards of all investigators. An urgent need exists to determine whether bCPAP decreases mortality among high-risk children with severe pneumonia to inform resource utilisation in low-resource settings. TRIAL REGISTRATION NUMBER: NCT02484183; Pre-results.

17.
Front Public Health ; 5: 183, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28798907

RESUMO

INTRODUCTION: To achieve sustained reductions in child mortality in low- and middle-income countries, increased local capacity is necessary. One approach to capacity building is support offered via partnerships with institutions in high-income countries. However, lack of cooperation between institutions can create barriers to successful implementation of programs and may inadvertently weaken the health system they are striving to improve. A coordinated approach is necessary. BACKGROUND: Three U.S.-based institutions have separately supported various aspects of pediatric care at Kamuzu Central Hospital (KCH), the main government referral hospital in the central region of Malawi, for several years. Within each institution's experience, common themes were recognized, which required attention in order to sustain improvements in care. Each recognized that support of clinical care is a necessary cornerstone before initiating educational or training efforts. In particular, the support of emergency and acute care is paramount in order to decrease in-hospital mortality. Through the combined efforts of Malawian partners and the US-based institutions, the pediatric mortality rate has decreased from >10 to <4% since 2011, yet critical gaps remain. To achieve further improvements, representatives with expertise in pediatric emergency medicine (PEM) from each US-based institution hypothesized that coordinated efforts would be most effective, decrease duplication, improve communication, and ensure that investments in education and training are aligned with local priorities. CALL TO ACTION: Together with local stakeholders, the three US-based partners created a multi-institutional partnership, Pediatric Alliance for Child Health Improvement in Malawi at Kamuzu Central Hospital and Environs (PACHIMAKE). Representatives from each institution gathered in Malawi late 2016 and sought input and support from local partners at all levels to prioritize interventions, which could be collectively undertaken by this consortium. Long- and short-term goals were identified and approved by local partners and will be implemented through a phased approach. CONCLUSION: The development of a novel partnership between relevant stakeholders in Malawi and US-based partners with expertise in PEM should help to further decrease pediatric mortality through the coordinated provision of acute care expertise and training as well as investment in the development of educational, research, and clinical efforts in PEM at KCH.

18.
Sci Rep ; 3: 1990, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23771124

RESUMO

Humoral immunity to Plasmodium falciparum circumsporozoite protein is partly mediated by a polymorphic NANP tetra-amino acid repeat. Antibody response to these repeats is the best correlate of protective immunity to the RTS,S malaria vaccine, but few descriptions of the natural variation of these repeats exist. Using capillary electrophoresis to determine the distribution of NANP repeat size polymorphisms among 98 isolates from Lilongwe, Malawi, we characterised the diversity of P. falciparum infection by several ecological indices. Infection by multiple distinct variants was common, and 20 distinct repeat sizes were identified. Diversity of P. falciparum appeared greater in children (18 variants) than adults (12 variants). There was evidence of genetic distance between different geographic regions by Nei's Standard Genetic Distance, suggesting parasite populations vary locally. We show that P. falciparum is very diverse with respect to NANP repeat length even on a local level and that diversity appears higher in children.


Assuntos
Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Adulto , Animais , Criança , Pré-Escolar , Eletroforese Capilar , Feminino , Humanos , Malaui , Masculino , Proteínas de Protozoários/química
19.
J Infect Dis ; 206(4): 580-7, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22551816

RESUMO

The development of an effective malaria vaccine has been hampered by the genetic diversity of commonly used target antigens. This diversity has led to concerns about allele-specific immunity limiting the effectiveness of vaccines. Despite extensive genetic diversity of circumsporozoite protein (CS), the most successful malaria vaccine is RTS/S, a monovalent CS vaccine. By use of massively parallel pyrosequencing, we evaluated the diversity of CS haplotypes across the T-cell epitopes in parasites from Lilongwe, Malawi. We identified 57 unique parasite haplotypes from 100 participants. By use of ecological and molecular indexes of diversity, we saw no difference in the diversity of CS haplotypes between adults and children. We saw evidence of weak variant-specific selection within this region of CS, suggesting naturally acquired immunity does induce variant-specific selection on CS. Therefore, the impact of CS vaccines on variant frequencies with widespread implementation of vaccination requires further study.


Assuntos
Epitopos de Linfócito T/imunologia , Variação Genética , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Adulto , Pré-Escolar , DNA de Protozoário/química , DNA de Protozoário/genética , Epitopos de Linfócito T/genética , Feminino , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Malaui , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/genética
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