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1.
Science ; 384(6693): eadj3166, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38669570

RESUMO

Despite an increasingly detailed picture of the molecular mechanisms of bacteriophage (phage)-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. In this work, we report a year-long, nationwide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative polymerase chain reaction while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of antiphage defenses, predation was "effective," with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of antiphage defenses, predation was "ineffective," with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.


Assuntos
Bacteriófagos , Cólera , Variação Genética , Vibrio cholerae , Cólera/microbiologia , Vibrio cholerae/genética , Vibrio cholerae/virologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Humanos , Bangladesh , Antibacterianos/uso terapêutico , Índice de Gravidade de Doença , Adulto , Metagenômica
2.
BMJ Paediatr Open ; 8(1)2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191203

RESUMO

OBJECTIVE: To develop and evaluate a guideline for a paediatric telemedicine and medication delivery service (TMDS). METHODS: A clinical guideline for paediatric telemedicine was derived from the World Health (WHO) Organization Integrated Management of Childhood Illness (IMCI) Handbook. The guideline was deployed at a TMDS in Haiti and evaluated through a prospective cohort study; children ≤10 years were enrolled. For non-severe cases, paired virtual and in-person examinations were conducted at the call centre and household; severe cases were referred to the hospital. The performance of virtual examination components were evaluated by comparison with the paired in-person examination findings (reference). RESULTS: A total of 391 cases were enrolled. Among the 320 cases with paired examinations, no general WHO danger signs were identified during in-person examinations; 5 cases (2%) required hospital referral due to problem-specific danger signs or other reasons for escalation. Cohen's kappa for the virtual designation of mild cases was 0.78 (95% CI: 0.69 to 0.87). The sensitivity and specificity of a virtually reported fever were 91% (95% CI: 87% to 96%) and 69% (95% CI: 62% to 76%), respectively; the sensitivity and specificity of virtually reported 'fast breathing' were 47% (95% CI: 21% to 72%) and 89% (95% CI: 85% to 94%), respectively. Kappa for 'no' and 'some' dehydration indicated moderate congruence between virtual and in-person examinations (0.69; 95% CI: 0.41 to 0.98). At 10 days, 273 (95%) of the 287 cases reached by phone were better/recovered. CONCLUSION: Critical components of the virtual examination (triage, danger signs and dehydration assessment) performed well despite varied performance among the problem-specific components. The study and associated resources represents formative steps towards an evidence-based paediatric telemedicine guideline built on WHO clinical principles. In-person examinations for select cases were important to address limitations with virtual examinations and identify cases for escalation. TRIAL REGISTRATION NUMBER: NCT03943654.


Assuntos
Call Centers , Telemedicina , Humanos , Criança , Desidratação/diagnóstico , Desidratação/terapia , Estudos Prospectivos , Região de Recursos Limitados
4.
Am J Trop Med Hyg ; 110(1): 159-164, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38081051

RESUMO

Diarrheal diseases are a major cause of morbidity and mortality in children worldwide and a significant contributor to antimicrobial resistance. In the absence of laboratory diagnostics to establish diarrhea etiology, electronic clinical decision support tools can help physicians make informed treatment decisions for children with diarrhea. In Bangladesh, we assessed the feasibility and acceptability of an electronic Diarrhea Etiology Prediction algorithm (DEP tool) embedded into a rehydration calculator, which was designed to help physicians manage children with diarrhea, including decisions on antibiotic use. A team of Bangladeshi anthropologists conducted in-depth interviews with physicians (N = 13) in three public hospitals in Bangladesh about their experience using the tool in the context of a pilot trial. Physicians expressed positive opinions of the DEP tool. Participants perceived the tool to be simple and easy to use, with structured guidance on collecting and entering clinical data from patients. Significant strengths of the tool were as follows: standardization of protocol, efficiency of clinical decision-making, and improved clinical practice. Participants also noted barriers that might restrict the widespread impact of the tool, including physicians' reluctance to use an electronic tool for clinical decision-making, increasing work in overburdened healthcare settings, unavailability of a smartphone, and patients' preferences for antibiotics. We conclude that an electronic clinical decision support tool is a promising method for improving diarrheal management and antibiotic stewardship. Future directions include developing and implementing such a tool for informal healthcare physicians in low-resource settings, where families may first seek care for pediatric diarrhea.


Assuntos
Smartphone , Telemedicina , Humanos , Criança , Bangladesh , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Antibacterianos/uso terapêutico
5.
bioRxiv ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37398242

RESUMO

Despite an increasingly detailed picture of the molecular mechanisms of phage-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. Here we report a year-long, nation-wide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative PCR, while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of anti-phage defenses, predation was 'effective,' with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of anti-phage defenses, predation was 'ineffective,' with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.

6.
Lancet Glob Health ; 11(11): e1725-e1733, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37776870

RESUMO

BACKGROUND: Despite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in older children and adults with acute diarrhoea (both developed during the NIRUDAK study) and compare their accuracy and reliability with current WHO guidelines. METHODS: A random sample of patients aged 5 years or older presenting with diarrhoea to the icddr,b Dhaka Hospital in Bangladesh between Jan 30 and Dec 13, 2022 were included in this prospective cohort study. Patients with fewer than three loose stools per day, more than 7 days of symptoms, previous enrolment in the study, or a diagnosis other than acute gastroenteritis were excluded. Patients were weighed on arrival and assessed separately by two nurses using both our novel clinical tools and WHO guidelines. Patients were weighed every 4 h to determine their percent weight change with rehydration, our criterion standard for dehydration. Accuracy for the diagnosis of dehydration category (none, some, or severe) was assessed using the ordinal c-index (ORC). Reliability was assessed by comparing the prediction of severe dehydration from each nurse's independent assessment using the intraclass correlation coefficient (ICC). FINDINGS: 1580 patients were included in our primary analysis, of whom 921 (58·3%) were female and 659 (41·7%) male. The ORC was 0·74 (95% CI 0·71-0·77) for the CDST, 0·75 (0·71-0·78) for the simplified score, and 0·64 (0·61-0·67) for the WHO guidelines. The ICC was 0·98 (95% CI 0·97-0·98) for the CDST, 0·94 (0·93-0·95) for the simplified score, and 0·56 (0·52-0·60) for the WHO guidelines. INTERPRETATION: Use of our CDST or simplified score by clinicians could reduce undertreatment and overtreatment of older children and adults with acute diarrhoea, potentially reducing morbidity and mortality for this common disease. FUNDING: US National Institutes of Health. TRANSLATION: For the Bangla translation of the abstract see Supplementary Materials section.


Assuntos
Desidratação , Diarreia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Algoritmos , Bangladesh , Desidratação/diagnóstico , Diarreia/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Organização Mundial da Saúde , Pré-Escolar
7.
Emerg Infect Dis ; 29(10): 2072-2082, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37735743

RESUMO

The 2010 cholera epidemic in Haiti was thought to have ended in 2019, and the Prime Minister of Haiti declared the country cholera-free in February 2022. On September 25, 2022, cholera cases were again identified in Port-au-Prince. We compared genomic data from 42 clinical Vibrio cholerae strains from 2022 with data from 327 other strains from Haiti and 1,824 strains collected worldwide. The 2022 isolates were homogeneous and closely related to clinical and environmental strains circulating in Haiti during 2012-2019. Bayesian hypothesis testing indicated that the 2022 clinical isolates shared their most recent common ancestor with an environmental lineage circulating in Haiti in July 2018. Our findings strongly suggest that toxigenic V. cholerae O1 can persist for years in aquatic environmental reservoirs and ignite new outbreaks. These results highlight the urgent need for improved public health infrastructure and possible periodic vaccination campaigns to maintain population immunity against V. cholerae.


Assuntos
Cólera , Vibrio cholerae , Humanos , Vibrio cholerae/genética , Haiti/epidemiologia , Teorema de Bayes , Cólera/epidemiologia , Surtos de Doenças
8.
Trop Med Int Health ; 28(9): 763-770, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536706

RESUMO

OBJECTIVE: We sought to evaluate the prerequisites (demand, interest, feasibility) for adapting a paediatric nighttime telemedicine and medication delivery service (TMDS) to Ghana. METHODS: A cross-sectional survey of households and associated healthcare providers was conducted in urban and rural Ghana. Households were identified through randomised geospatial sampling; households with at least one child <10 years were enrolled. Household surveys collected information relating to demographics, household resources, standardised case scenarios, recent paediatric health events, satisfaction with healthcare access, and interest in TMDS intervention models. Providers were identified by households and enrolled. Provider surveys collected provider type, hours of operation, services, and opinions of a TMDS model. RESULTS: A total of 511 (263 urban, 248 rural) households and 18 providers (10 urban, 8 rural) were surveyed. A total of 262 health events involving children <10 years were reported, of which 47% occurred at night. Care was sought for >70% of health events presenting at night; however, care-seeking was delayed until morning or later for >75% of these events; 54% of households expressed dissatisfaction with their current access to paediatric care at night; 99% of households expressed that a nighttime TMDS service for children would be directly useful to their families. Correspondingly, 17 of 18 providers stated that a TMDS was needed in their community; >99% of households had access to a cellular phone. All households expressed willingness to use their phones to call a TMDS and allow a TMDS provider into their homes at night. Willingness to pay and provider-recommended price points varied by setting. CONCLUSIONS: Prerequisites for adapting a TMDS to Ghana were met. A nighttime paediatric TMDS service was found to be needed, appealing, and feasible in Ghana. These data motivate the adaptation of a TMDS to urban and rural Ghana.


Assuntos
Acessibilidade aos Serviços de Saúde , Telemedicina , Humanos , Criança , Estudos Transversais , Aceitação pelo Paciente de Cuidados de Saúde , Características da Família , Gana
9.
Emerg Infect Dis ; 29(9): 1864-1867, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37487168

RESUMO

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children.


Assuntos
Cólera , Vibrio cholerae O1 , Criança , Humanos , Pré-Escolar , Cólera/epidemiologia , Haiti/epidemiologia , Anticorpos Antibacterianos , Vibrio cholerae O1/genética , Surtos de Doenças
10.
PLOS Glob Public Health ; 3(6): e0001937, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37368867

RESUMO

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build clinical prognostic models (CPMs) to predict death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived CPM. Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieved an area under the ROC curve (AUC) of 0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC = 0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.

11.
Front Public Health ; 11: 1003923, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969651

RESUMO

Objectives: To identify risk factors associated with symptoms of anxiety, depression, and obsessive-compulsive disorder (OCD) among children during the 1st year of the COVID-19 pandemic. Methods: A longitudinal study with three cross-sectional timepoints [April 2020 (n = 273), October 2020 (n = 180), and April 2021 (n = 116)] was conducted at a K-12 public school in Florida. Infection and sero-positivity for SARS-CoV-2 was determined by molecular and serologic approaches. Adjusted odds ratios using mixed effect logistic regression models for symptom-derived indicators of anxiety, depression, and OCD in children in April 2021 are presented; past infection and seropositivity were included in the models. Results: The prevalence of anxiety, depression, or OCD moved from 47.1, to 57.2, to 42.2% across the three timepoints during the study. By endline of the study, in April 2021, non-white children were at higher risk for depression and OCD. Risk for anxiety, depression, and OCD was associated with students who lost a family member due to COVID-19 and who were identified as at-risk in previous timepoints. Rates of SARS-CoV-2 infection and seropositivity were low and not statistically associated with assessed outcomes. Conclusions: In situations like the COVID-19 pandemic, targeted mental health interventions and screenings are needed in children and adolescents, especially among minority children.


Assuntos
COVID-19 , Criança , Adolescente , Humanos , COVID-19/epidemiologia , Estudos Longitudinais , Pandemias , Estudos Transversais , Florida/epidemiologia , SARS-CoV-2
12.
medRxiv ; 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36798150

RESUMO

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models for death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived clinical prognostic model (CPM). Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieve an AUC=0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC=0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.

13.
medRxiv ; 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36798289

RESUMO

After three years with no confirmed cholera cases in Haiti, an outbreak of Vibrio cholerae O1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti. We found lower levels of circulating IgG and IgA antibodies against V. cholerae lipopolysaccharide (LPS, IgG and IgA p<0.0001) in those below 5 years of age compared to those five years and older. Among a subset of patients with higher titers of antibodies, we were unable to detect any functional (vibriocidal) antibodies. In conclusion, the lack of detectable functional antibodies, and age-discordant levels of V. cholerae LPS IgG, suggest that populations in Haiti may be highly susceptible to cholera disease, especially among young children.

14.
Elife ; 122023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607225

RESUMO

Background: Nearly 150 million children under-5 years of age were stunted in 2020. We aimed to develop a clinical prediction rule (CPR) to identify children likely to experience additional stunting following acute diarrhea, to enable targeted approaches to prevent this irreversible outcome. Methods: We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models of linear growth faltering (decrease of ≥0.5 or ≥1.0 in height-for-age z-score [HAZ] at 60-day follow-up) in children ≤59 months presenting with moderate-to-severe diarrhea, and community controls, in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using fivefold cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to (1) re-derive, and (2) externally validate our GEMS-derived CPR. Results: Of 7639 children in GEMS, 1744 (22.8%) experienced severe growth faltering (≥0.5 decrease in HAZ). In MAL-ED, we analyzed 5683 diarrhea episodes from 1322 children, of which 961 (16.9%) episodes experienced severe growth faltering. Top predictors of growth faltering in GEMS were: age, HAZ at enrollment, respiratory rate, temperature, and number of people living in the household. The maximum area under the curve (AUC) was 0.75 (95% confidence interval [CI]: 0.75, 0.75) with 20 predictors, while 2 predictors yielded an AUC of 0.71 (95% CI: 0.71, 0.72). Results were similar in the MAL-ED re-derivation. A 2-variable CPR derived from children 0-23 months in GEMS had an AUC = 0.63 (95% CI: 0.62, 0.65), and AUC = 0.68 (95% CI: 0.63, 0.74) when externally validated in MAL-ED. Conclusions: Our findings indicate that use of prediction rules could help identify children at risk of poor outcomes after an episode of diarrheal illness. They may also be generalizable to all children, regardless of diarrhea status. Funding: This work was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award NIH T32AI055434 and by the National Institute of Allergy and Infectious Diseases (R01AI135114).


Assuntos
Regras de Decisão Clínica , Diarreia , Humanos , Criança , Lactente , Recém-Nascido , Diarreia/diagnóstico , Diarreia/epidemiologia , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Ásia , África
15.
J Pediatr ; 257: 113304, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36528053

RESUMO

OBJECTIVE: Determine the clinical safety and feasibility of implementing a telemedicine and medication delivery service (TMDS) to address gaps in nighttime access to health care for children in low-resource settings. STUDY DESIGN: We implemented a TMDS called 'MotoMeds' in Haiti as a prospective cohort study. A parent/guardian of a sick child ≤ 10 years contacted the call center (6 PM-5 AM). A nurse provider used decision support tools to triage cases (mild, moderate, or severe). Severe cases were referred to emergency care. For nonsevere cases, providers gathered clinical findings to generate an assessment and plan. For cases within the delivery zone, a provider and driver were dispatched and the provider performed a paired in-person exam as a reference standard for the virtual call center exam. Families received a follow-up call at 10 days. Data were analyzed for clinical safety and feasibility. RESULTS: A total of 391 cases were enrolled from September 9, 2019, to January 19, 2021. Most cases were nonsevere (92%; 361); household visits were completed for 89% (347) of these cases. Among the 30 severe cases, 67% (20) sought referred care. Among all cases, respiratory problems were the most common complaint (63%; 246). At 10 days, 95% (329) of parents reported their child had "improved" or "recovered". Overall, 99% (344) rated the TMDS as "good" or "great". The median phone consultation time was 20 minutes, time to household arrival was 73 minutes, and total case time was 114 minutes. CONCLUSION: The TMDS was a feasible health care delivery model. Although many cases were likely self-limiting, the TMDS was associated with high rates of reported improvement in clinical status at 10 days. TRIAL REGISTRATION: clinicaltrials.gov: NCT03943654.


Assuntos
Telemedicina , Criança , Humanos , Estudos de Viabilidade , Projetos Piloto , Estudos Prospectivos , Encaminhamento e Consulta
16.
Clin Infect Dis ; 76(3): e491-e494, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36029095

RESUMO

We screened 65 longitudinally collected nasal swab samples from 31 children aged 0-16 years who were positive for severe acute respiratory syndrome coronavirus 2 Omicron BA.1. By day 7 after onset of symptoms, 48% of children remained positive by rapid antigen test. In a sample subset, we found 100% correlation between antigen test results and virus culture.


Assuntos
COVID-19 , Humanos , Criança , COVID-19/diagnóstico , SARS-CoV-2 , Testes Imunológicos
18.
JAMA Pediatr ; 176(10): 973-979, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36036920

RESUMO

Importance: Inappropriate use of antibiotics for diarrheal illness can result in adverse effects and increase in antimicrobial resistance. Objective: To determine whether the diarrheal etiology prediction (DEP) algorithm, which uses patient-specific and location-specific features to estimate the probability that diarrhea etiology is exclusively viral, impacts antibiotic prescriptions in patients with acute diarrhea. Design, Setting, and Participants: A randomized crossover study was conducted to evaluate the DEP incorporated into a smartphone-based electronic clinical decision-support (eCDS) tool. The DEP calculated the probability of viral etiology of diarrhea, based on dynamic patient-specific and location-specific features. Physicians were randomized in the first 4-week study period to the intervention arm (eCDS with the DEP) or control arm (eCDS without the DEP), followed by a 1-week washout period before a subsequent 4-week crossover period. The study was conducted at 3 sites in Bangladesh from November 17, 2021, to January 21, 2021, and at 4 sites in Mali from January 6, 2021, to March 5, 2021. Eligible physicians were those who treated children with diarrhea. Eligible patients were children between ages 2 and 59 months with acute diarrhea and household access to a cell phone for follow-up. Interventions: Use of the eCDS with the DEP (intervention arm) vs use of the eCDS without the DEP (control arm). Main Outcomes and Measures: The primary outcome was the proportion of children prescribed an antibiotic. Results: A total of 30 physician participants and 941 patient participants (57.1% male; median [IQR] age, 12 [8-18] months) were enrolled. There was no evidence of a difference in the proportion of children prescribed antibiotics by physicians using the DEP (risk difference [RD], -4.2%; 95% CI, -10.7% to 1.0%). In a post hoc analysis that accounted for the predicted probability of a viral-only etiology, there was a statistically significant difference in risk of antibiotic prescription between the DEP and control arms (RD, -0.056; 95% CI, -0.128 to -0.01). No known adverse effects of the DEP were detected at 10-day postdischarge. Conclusions and Relevance: Use of a tool that provides an estimate of etiological likelihood did not result in a significant change in overall antibiotic prescriptions. Post hoc analysis suggests that a higher predicted probability of viral etiology was linked to reductions in antibiotic use. Trial Registration: Clinicaltrials.gov Identifier: NCT04602676.


Assuntos
Gestão de Antimicrobianos , Assistência ao Convalescente , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Estudos Cross-Over , Diarreia/tratamento farmacológico , Eletrônica , Feminino , Humanos , Lactente , Masculino , Alta do Paciente , Probabilidade
19.
Infect Immun ; 90(8): e0016122, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35862704

RESUMO

Cholera is an acute watery, diarrheal disease that causes high rates of morbidity and mortality without treatment. Early detection of the etiologic agent of toxigenic Vibrio cholerae is important to mobilize treatment and mitigate outbreaks. Monoclonal antibody (mAb) based rapid diagnostic tests (RDTs) enable early detection in settings without laboratory capacity. However, the odds of an RDT testing positive are reduced by nearly 90% when the common virulent bacteriophage ICP1 is present. We hypothesize that adding a mAb for the common, and specific, virulent bacteriophage ICP1 as a proxy for V. cholerae to an RDT will increase diagnostic sensitivity when virulent ICP1 phage is present. In this study, we used an in-silico approach to identify immunogenic ICP1 protein targets that were conserved across disparate time periods and locations. Specificity of targets to cholera patients with known ICP1 was determined, and specific targets were used to produce mAbs in a murine model. Candidate mAbs to the head protein demonstrated specificity to ICP1 by Enzyme linked immunosorbent assay (ELISA) and an ICP1 phage neutralization assay. The limit of detection of the final mAb candidate for ICP1 phage particles spiked into cholera stool matrix was 8 × 105 PFU by Western blotting analysis. This mAb will be incorporated into a RDT prototype for evaluation in a future diagnostic study to test the guiding hypothesis behind this study.


Assuntos
Bacteriófagos , Cólera , Vibrio cholerae , Doença Aguda , Animais , Anticorpos Monoclonais/metabolismo , Cólera/diagnóstico , Cólera/epidemiologia , Diarreia , Fezes , Humanos , Camundongos
20.
Am J Trop Med Hyg ; 107(1): 32-34, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35895365

RESUMO

Nonindicated antibiotics for childhood diarrhea is a major contributor to global antimicrobial resistance. Electronic clinical decision support tools (eCDSTs) may reduce unnecessary antibiotics. This study examined how providers' expectations of an eCDST to predict diarrhea etiology compared with their experiences using the tool. Providers were enrolled from public hospitals in Bangladesh (n = 15) and Mali (n = 15), and surveys were completed at baseline and after using the eCDST. Baseline surveys assessed expectations (utility, ease of use, and threat to autonomy), and post surveys assessed experiences in the same domains. Providers' experiences with ease of use exceeded their baseline expectations, and providers reported less experienced threat to autonomy after use, compared with baseline expectations. Providers' expectations of threat to autonomy significantly predicted their experienced threat to autonomy. Findings suggest that an eCDST to inform antimicrobial prescribing for diarrhea is feasible and acceptable, but training should promote local ownership for sustainability.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Antibacterianos/uso terapêutico , Bangladesh , Criança , Diarreia/tratamento farmacológico , Eletrônica , Humanos , Mali , Motivação
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