Publications by authors named "Patricia Pavlinac"

With increasing antibiotic resistance in gram-negative bacteria, including those causing Shigellosis, evidence of safety and pharmacokinetics data on new oral antibiotics is crucial. We aimed to investigate the safety and pharmacokinetic properties of an oral carbapenem, tebipenem pivoxil, along with it's ability to produce desired results in childhood shigellosis. This randomized pilot clinical trial was conducted at Dhaka Hospital, icddr,b in 2022 between May and September.

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  • * A machine learning approach was applied using data from the VIDA and EFGH-Shigella studies in rural Kenya to create predictive models for LGF among children aged 6-35 months, encompassing 65 potential predictors including demographic and health-related factors.
  • * The models showed a prevalence of LGF at 16.9% and 22.4% in different cohorts, with the gradient boosting model providing the best prediction accuracy, demonstrating its usefulness in identifying at-risk children for targeted healthcare interventions
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Background: Among diarrheal children, injudicious use of antibiotics is a major public health concern particularly in low- and middle-income countries. There are evidence-based guidelines by the World Health Organization (WHO) to prescribe antibiotics for bloody diarrhea in children. There is a scarcity of published data regarding the judicious use of antibiotics for bloody diarrhea in children.

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Introduction: We used machine learning to identify novel strategies to target azithromycin to the children with watery diarrhea who are most likely to benefit.

Methods: Using data from a randomized trial of azithromycin for watery diarrhea, we developed personalized treatment rules given sets of diagnostic, child, and clinical characteristics, employing a robust ensemble machine learning-based procedure. For each rule, we estimated the proportion treated under the rule and the average benefits of treatment.

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Introduction: Children with moderate or severe wasting are at particularly high risk of recurrent or persistent diarrhoea, nutritional deterioration and death following a diarrhoeal episode. Lactoferrin and lysozyme are nutritional supplements that may reduce the risk of recurrent diarrhoeal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function.

Methods And Analysis: In this factorial, blinded, placebo-controlled randomised trial, we aim to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhoea incidence and improving nutritional recovery in Kenyan children convalescing from comorbid diarrhoea and wasting.

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Background: Antimicrobial resistance (AMR) is a global threat to infectious disease control, particularly among recently hospitalized children. We sought to determine the prevalence and mitigating factors of resistance in enteric among children discharged from health facilities in western Kenya.

Methods: Between June 2016 and November 2019, children aged 1 to 59 months were enrolled at the point of discharge from the hospital.

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Background: The emergence and spread of β-lactamase-producing Klebsiella spp. has been associated with a substantial healthcare burden resulting in therapeutic failures. We sought to describe the proportion of phenotypic resistance to commonly used antibiotics, characterize β-lactamase genes among isolates with antimicrobial resistance (AMR), and assess the correlates of phenotypic AMR in Klebsiella spp.

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Objective: The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD).

Design: A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114).

Patients: Children with MSD (defined as 3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample.

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Background: is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date diarrhea incidence data.

Methods: The Enterics for Global Health (EFGH) surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru).

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  • qPCR is a more efficient method for detecting pathogens in clinical samples than traditional culture methods, which often miss cases, leading to underestimation of disease burden by 2- to 3-fold.
  • The Enterics for Global Health (EFGH) study will use a TaqMan Array Card (TAC) to detect and differentiate various pathogens and antimicrobial resistance genes, analyzing samples from rectal swabs or stool.
  • The high sensitivity of TAC allows for better estimation of disease burden caused by specific pathogens, which is important for influencing health policy and designing future clinical trials.
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  • Molecular diagnostics have revealed a higher prevalence of shigellosis from human fecal samples than traditional culture methods, highlighting the need for improved identification of its causes.* -
  • The study involves testing dried blood spots for specific antibodies to determine immune responses in individuals with shigellosis and comparing these responses among various case types to identify patterns.* -
  • The findings aim to enhance our understanding of shigellosis, establish baseline immunity, and ultimately aid in the development of effective vaccines against diarrhea.*
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  • The study aims to improve the detection of bacterial diarrhea episodes by using fecal inflammatory biomarkers, which could help in deciding when antibiotics are needed.
  • A systematic review was conducted to analyze previous research on the effectiveness of these biomarkers, focusing on their sensitivity and specificity in identifying different bacteria associated with diarrhea.
  • The Enterics for Global Health (EFGH) study plans to test specific biomarkers in stool samples from various countries and develop prediction scores to better categorize diarrhea types using advanced detection methods like qPCR.
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  • The EFGH surveillance study aims to accurately estimate diarrhea incidence in children aged 6-35 months by considering both the population at risk and those who don't seek medical care.
  • It will utilize a combination of facility-based surveillance and population-based surveys to determine the size of the target population and healthcare-seeking behaviors.
  • The study design addresses challenges like discrepancies in coverage, seasonal changes, and variations in health-seeking behavior to improve the accuracy of its findings over a 24-month period.
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Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of -associated diarrhea in children 6 to 35 months old.

Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making.

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Background: is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis.

Methods: The Enterics for Global Health (EFGH) surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings.

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  • * Risk factors for stunting include being older (12-59 months), having HIV or being HIV-exposed, and not being exclusively breastfed, while lower caregiver education and poor sanitation conditions also contribute significantly.
  • * Hospital discharge provides a critical chance to identify stunted children and implement targeted nutritional interventions to improve their long-term health outcomes.
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The global public health nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, from November 29 to December 1, 2022. This international gathering focused on cutting-edge research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and non-typhoidal Salmonella. In addition to the conference's plenary content, the agenda featured ten breakout workshops on topics of importance to the enteric vaccine field.

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Dehydration is a major cause of death among children with wasting and diarrhea. We reviewed the evidence for the identification and management of dehydration among these children. Two systematic reviews were conducted to assess 1) the diagnostic performance of clinical signs or algorithms intended to measure dehydration, and 2) the efficacy and safety of low-osmolarity ORS versus ReSoMal on mortality, treatment failure, time to full rehydration, and electrolyte disturbances (management review).

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Shigellosis causes considerable public health burden, leading to excess deaths as well as acute and chronic consequences, particularly among children living in low-income and middle-income countries (LMICs). Several Shigella vaccine candidates are advancing in clinical trials and offer promise. Although multiple target populations might benefit from a Shigella vaccine, the primary strategic goal of WHO is to accelerate the development and accessibility of safe, effective, and affordable Shigella vaccines that reduce mortality and morbidity in children younger than 5 years living in LMICs.

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  • Bacterial germs can cause serious diarrhea in kids, but doctors usually only give medicine for certain types like dysentery or cholera.
  • A study in seven countries tested a medicine called azithromycin on young children with watery diarrhea and found it helped reduce diarrhea and hospital visits for those likely infected with bacteria.
  • The results suggest that treating watery diarrhea suspected to be caused by bacteria with azithromycin can be beneficial for children.
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  • Diarrhea remains a major cause of death in children under five, particularly after acute treatment, highlighting the need for effective risk identification to improve interventions.
  • Researchers developed clinical prognostic models using data from the Global Enteric Multicenter Study (GEMS) and validated them with data from Kenya, revealing key predictive factors for mortality in children experiencing moderate-to-severe diarrhea.
  • The study demonstrated that a simple two-variable prediction model could effectively identify high-risk children, suggesting a potential cost-effective strategy for resource targeting to prevent childhood mortality related to diarrhea.
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  • The study found a high prevalence of ciprofloxacin non-susceptible E. coli and Klebsiella spp in children under five after hospital discharge, with around 68% of the isolates exhibiting resistance.
  • About 80% of resistant isolates carried plasmid-mediated quinolone resistance genes, with aac(6')lb-cr being the most common.
  • Factors such as ceftriaxone use during hospitalization and ESBL production were significantly linked to the presence of these resistant bacteria.
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Background: Diarrheal diseases are a leading cause of death for children aged <5 years. Identification of etiology helps guide pathogen-specific therapy, but availability of diagnostic testing is often limited in low-resource settings. Our goal is to develop a clinical prediction rule (CPR) to guide clinicians in identifying when to use a point-of-care (POC) diagnostic for in children presenting with acute diarrhea.

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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.

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Objectives: We conducted a systematic review of the longitudinal consequences of Shigella infection in children to inform the value proposition for an effective vaccine.

Methods: We searched PubMed and Embase for studies published from January 01, 1980 to December 12, 2022 and conducted in low- and middle-income countries that included longitudinal follow-up after Shigella detection among children aged <5 years, irrespective of language. We collected data on all outcomes subsequent to Shigella detection, except mortality.

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