Predictors and outcome of tetanus in newborns in slum areas of Karachi city: A case control study

Background: Tetanus in newborns, is an under-reported public health problem and a major cause of mortality in developing countries. This study aimed to determine the predictors and outcome of tetanus in newborn infants in the slums of Bin-Qasim town, Karachi, Pakistan.Methods: We conducted a case-control study at primary health care centers of slums of Bin-Qasim town, area located adjacent to Bin Qasim seaport in Karachi, from January 2003 to December 2013. Cases were infants aged ≤30 days with tetanus, as defined by the World Health Organization. Controls were newborn infants aged ≤30 days without Tetanus, who were referred for a checkup or minor illnesses. The case to control ratio was 1:2.Results: We analyzed 26 cases and 52 controls. The case fatality was 70.8%. We identified four independent predictors of Tetanus in newborns: maternal education (only religious education with no formal education OR 51.95; 95% CI 3.69-731), maternal non-vaccination (OR 24.55; 95% CI 1.01-131.77), lack of a skilled birth attendant (OR 44.00; 95% CI 2.30-840.99), and delivery at home (OR 11.54; 95% CI 1.01-131.77).Conclusions: We identified several potentially modifiable socio-demographic risk factors for Tetanus in newborns, including maternal education and immunization status, birth site, and lack of a skilled birth attendant. Prioritization of these risk factors could be useful for planning preventive and cost-effective measures

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial

Background: Parenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection.Methods: We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov , numberNCT01027429 . Findings: Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference −1·9, 95% CI −5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, −2·3 to 4·5). Interpretation: Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital

Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial.

BACKGROUND: Infection in young infants is a major cause of morbidity and mortality in low-middle income countries, with high neonatal mortality rates. Timely case management is lifesaving, but the current standard of hospitalization for parenteral antibiotic therapy is not always feasible. Alternative, simpler antibiotic regimens that could be used in outpatient settings have the potential to save thousands of lives. METHODS: This trial aims to determine whether 2 simplified antibiotic regimens are equivalent to the reference therapy with 7 days of once-daily (OD) intramuscular (IM) procaine penicillin and gentamicin for outpatient management of young infants with clinically presumed systemic bacterial infection treated in primary health-care clinics in 5 communities in Karachi, Pakistan. The reference regimen is close to the current recommendation of the hospital-based intravenous ampicillin and gentamicin therapy for neonatal sepsis. The 2 comparison arms are (1) IM gentamicin OD and oral amoxicillin twice daily for 7 days; and (2) IM penicillin and gentamicin OD for 2 days, followed by oral amoxicillin twice daily for 5 days; 2250 "evaluable" infants will be enrolled. The primary outcome of this trial is treatment failure (death, deterioration or lack of improvement) within 7 days of enrollment. Results are expected by early 2014. DISCUSSION: This trial will determine whether simplified antibiotic regimens with fewer injections in combination with high-dose amoxicillin are equivalent to 7 days of IM procaine penicillin and gentamicin in young infants with clinical severe infection. Results will have program and policy implications in countries with limited access to hospital care and high burden of neonatal deaths

Performance of lung ultrasound in the diagnosis of pediatric pneumonia in Mozambique and Pakistan

Introduction: Improved pneumonia diagnostics are needed in low-resource settings (LRS); lung ultrasound (LUS) is a promising diagnostic technology for pneumonia. The objective was to compare LUS versus chest radiograph (CXR), and among LUS interpreters, to compare expert versus limited training with respect to interrater reliability.Methods: We conducted a prospective, observational study among children with World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) chest-indrawing pneumonia at two district hospitals in Mozambique and Pakistan, and assessed LUS and CXR examinations. The primary endpoint was interrater reliability between LUS and CXR interpreters for pneumonia diagnosis among children with WHO IMCI chest-indrawing pneumonia.Results: Interrater reliability was excellent for expert LUS interpreters, but poor to moderate for expert CXR interpreters and onsite LUS interpreters with limited training.Conclusions: Among children with WHO IMCI chest-indrawing pneumonia, expert interpreters may achieve substantially higher interrater reliability for LUS compared to CXR, and LUS showed potential as a preferred reference standard. For point-of-care LUS to be successfully implemented for the diagnosis and management of pneumonia in LRS, the clinical environment and amount of appropriate user training will need to be understood and addressed

Serial lung ultrasounds in pediatric pneumonia in Mozambique and Pakistan

Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing and managing pneumonia. We sought to explore serial LUS examinations in children with chest-indrawing pneumonia in resource-constrained settings and compare their clinical and LUS imaging courses longitudinally. We conducted a prospective, observational study among children aged 2 through 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at 2 district hospitals in Mozambique and Pakistan. We assessed serial LUS at enrollment, 2, 6, and 14 days, and performed a secondary analysis of enrolled children\u27s longitudinal clinical and imaging courses. By Day 14, the majority of children with chest-indrawing pneumonia and consolidation on enrollment LUS showed improvement on follow-up LUS (100% in Mozambique, 85.4% in Pakistan) and were clinically cured (100% in Mozambique, 78.0% in Pakistan). In our cohort of children with chest-indrawing pneumonia, LUS imaging often reflected the clinical course; however, it is unclear how serial LUS would inform the routine management of non-severe chest-indrawing pneumonia

Lung ultrasound patterns in paediatric pneumonia in Mozambique and Pakistan

Objective: Improved pneumonia diagnostics are needed, particularly in resource-constrained settings. Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing pneumonia. The objective was to explore LUS patterns associated with paediatric pneumonia.Methods: We conducted a prospective, observational study among children aged 2 to 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at two district hospitals in Mozambique and Pakistan. We assessed LUS and chest radiograph (CXR) examinations, and viral and bacterial nasopharyngeal carriage, and performed a secondary analysis of LUS patterns.Results: LUS demonstrated a range of distinctive patterns that differed between children with and without pneumonia and between children in Mozambique versus Pakistan. The presence of LUS consolidation or interstitial patterns was more common in children with chest-indrawing pneumonia than in those without pneumonia. Consolidations were also more common among those with only bacterial but no viral carriage detected (50.0%) than among those with both (13.0%) and those with only virus detected (8.3%; p=0.03). LUS showed high interrater reliability among expert LUS interpreters for overall determination of pneumonia (κ=0.915), consolidation (κ=0.915) and interstitial patterns (κ=0.901), but interrater reliability between LUS and CXR for detecting consolidations was poor (κ=0.159, Pakistan) to fair (κ=0.453, Mozambique).Discussion: Pattern recognition was discordant between LUS and CXR imaging modalities. Further research is needed to define and standardise LUS patterns associated with paediatric pneumonia and to evaluate the potential value of LUS as a reference standard

Community-based asthma assessment in young children: Adaptations for a multicentre longitudinal study in South Asia

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan.Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the \u27Aetiology of Neonatal Infection in South Asia (ANISA)\u27 study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a \u27Child Card\u27 to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels.Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges.Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children\u27s respiratory outcomes in future translational research studies

Feasibility, usability and acceptability of paediatric lung ultrasound among healthcare providers and caregivers for the diagnosis of childhood pneumonia in resource-constrained settings: A qualitative study

Objectives: Paediatric pneumonia burden and mortality are highest in low-income and middle-income countries (LMIC). Paediatric lung ultrasound (LUS) has emerged as a promising diagnostic tool for pneumonia in LMIC. Despite a growing evidence base for LUS use in paediatric pneumonia diagnosis, little is known about its potential for successful implementation in LMIC. Our objectives were to evaluate the feasibility, usability and acceptability of LUS in the diagnosis of paediatric pneumonia.Design: Prospective qualitative study using semistructured interviews SETTING: Two referral hospitals in Mozambique and Pakistan PARTICIPANTS: A total of 21 healthcare providers (HCPs) and 20 caregivers were enrolled.Results: HCPs highlighted themes of limited resource availability for the feasibility of LUS implementation, including perceived high cost of equipment, maintenance demands, time constraints and limited trained staff. HCPs emphasised the importance of policymaker support and caregiver acceptance for long-term success. HCP perspectives of usability highlighted ease of use and integration into existing workflow. HCPs and caregivers had positive attitudes towards LUS with few exceptions. Both HCPs and caregivers emphasised the potential for rapid, improved diagnosis of paediatric respiratory conditions using LUS.Conclusions: This was the first study to evaluate HCP and caregiver perspectives of paediatric LUS through qualitative analysis. Critical components impacting feasibility, usability and acceptability of LUS for paediatric pneumonia diagnosis in LMIC were identified for initial deployment. Future research should explore LUS sustainability, with a particular focus on quality control, device maintenance and functionality and adoption of the new technology within the health system. This study highlights the need to engage both users and recipients of new technology early in order to adapt future interventions to the local context for successful implementation.Trial registration number: NCT03187067

Community-based asthma assessment in young children:Adaptations for a multicentre longitudinal study in South Asia

BACKGROUND: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan. METHOD: We followed a group of children of age 6–8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the ‘Aetiology of Neonatal Infection in South Asia (ANISA)’ study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a ‘Child Card’ to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels. RESULTS: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges. CONCLUSION: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children’s respiratory outcomes in future translational research studies

Performance of lung ultrasound in the diagnosis of pediatric pneumonia in Mozambique and Pakistan.

INTRODUCTION: Improved pneumonia diagnostics are needed in low-resource settings (LRS); lung ultrasound (LUS) is a promising diagnostic technology for pneumonia. The objective was to compare LUS versus chest radiograph (CXR), and among LUS interpreters, to compare expert versus limited training with respect to interrater reliability. METHODS: We conducted a prospective, observational study among children with World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) chest-indrawing pneumonia at two district hospitals in Mozambique and Pakistan, and assessed LUS and CXR examinations. The primary endpoint was interrater reliability between LUS and CXR interpreters for pneumonia diagnosis among children with WHO IMCI chest-indrawing pneumonia. RESULTS: Interrater reliability was excellent for expert LUS interpreters, but poor to moderate for expert CXR interpreters and onsite LUS interpreters with limited training. CONCLUSIONS: Among children with WHO IMCI chest-indrawing pneumonia, expert interpreters may achieve substantially higher interrater reliability for LUS compared to CXR, and LUS showed potential as a preferred reference standard. For point-of-care LUS to be successfully implemented for the diagnosis and management of pneumonia in LRS, the clinical environment and amount of appropriate user training will need to be understood and addressed