Machine learning from fetal flow waveforms to predict adverse perinatal outcomes: A study protocol

Background: In Pakistan, stillbirth rates and early neonatal mortality rates are amongst the highest in the world. The aim of this study is to provide proof of concept for using a computational model of fetal haemodynamics, combined with machine learning. This model will be based on Doppler patterns of the fetal cardiovascular, cerebral and placental flows with the goal to identify those fetuses at increased risk of adverse perinatal outcomes such as stillbirth, perinatal mortality and other neonatal morbidities.Methods: This will be prospective one group cohort study which will be conducted in Ibrahim Hyderi, a peri-urban settlement in south east of Karachi. The eligibility criteria include pregnant women between 22-34 weeks who reside in the study area. Once enrolled, in addition to the performing fetal ultrasound to obtain Dopplers, data on socio-demographic, maternal anthropometry, haemoglobin and cardiotocography will be obtained on the pregnant women.Discussion: The machine learning approach for predicting adverse perinatal outcomes obtained from the current study will be validated in a larger population at the next stage. The data will allow for early interventions to improve perinatal outcomes

Intussusception in an infant as a manifestation of COVID-19

Gastrointestinal manifestations of COVID-19 are rare and have primarily been limited to diarrhea or vomiting. Intussusception is the most common cause of bowel obstruction in infants, with up to 30% of pediatric intussusception cases having a preceding viral illness. We present the rare case of intussusception in a SARS-CoV-2 positive infant. This is the first documented case of survival in a SARS-CoV-2 positive patient presenting with intussusception as the primary manifestation. As our knowledge of this disease evolves, surgeons need to remain suspicious for possible gastrointestinal manifestations of COVID-19

Use of miltefosine in the treatment of visceral leishmaniasis in children at a tertiary care hospital of Karachi

Existing standard treatment options for visceral leishmaniasis are less than optimal. We report here the use of oral miltefosine in the treatment of two paediatric cases of visceral leishmaniasis at a tertiary care hospital in Karachi, Pakistan. One patient came from Balochistan while the second patient was from Northern Pakistan. Both presented with a prolonged history of fever, massive hepatosplenomegaly, anaemia and thrombocytopenia. Visceral leishmaniasis was diagnosed with bone marrow studies. Amphotericin B was first started in the first patient; however severe hypokalaemia and allergic reaction occurred. Oral miltefosine was then administered. The child showed clinical improvement with regards to signs of leishmania infection but succumbed to a nosocomial infection during the hospital stay. In the second patient, miltefosine was started in the first instance. He showed remarkable clinical improvement. At 2 months follow-up, the child showed adequate weight gain along with successful resolution of hepatosplenomegaly and fever. Miltefosine has the potential to be considered a first line therapy for visceral leishmaniasis in developing countries; however larger studies are warranted to validate the trends observed in this small case series

Multicentre pilot study evaluation of lung ultrasound for the management of paediatric pneumonia in low-resource settings: a study protocol

Introduction: Pneumonia is the leading infectious cause of death among children under 5 years of age worldwide. However, pneumonia is challenging to diagnose. Lung ultrasound (LUS) is a promising diagnostic technology. Further evidence is needed to better understand the role of LUS as a tool for the diagnosis of childhood pneumonia in low-resource settings. Methods and analysis: This study aims to pilot LUS in Mozambique and Pakistan and to generate evidence regarding the use of LUS as a diagnostic tool for childhood pneumonia. Children with cough \u3c14 days with chest indrawing (n=230) and without chest indrawing (n=40) are enrolled. World Health Organization Integrated Management of Childhood Illness assessment is performed at enrolment, along with a chest radiograph and LUS examination. Respiratory and blood specimens are collected for viral and bacterial testing and biomarker assessment. Enrolled children are followed for 14 days (in person) and 30 days (phone call) post-enrolment with LUS examinations performed on Days 2, 6 and 14. Qualitative and quantitative data are also collected to assess feasibility, usability and acceptability of LUS among healthcare providers and caregivers. The primary outcome is LUS findings at enrolment with secondary outcomes including patient outcomes, repeat LUS findings, viral and bacterial test results, and patient status after 14 and 30 days of follow-up. Ethics and dissemination: This trial was approved by the Western Institutional Review Board as well as local ethics review committees at each site. We plan to disseminate study results in peer-reviewed journals and international conferences. Trial registration number: NCT03187067

Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries

OBJECTIVE: To assess the rates, timing and causes of neonatal deaths and the burden of stillbirths in rural Uttar Pradesh, India. We discuss the implications of our findings for neonatal interventions. METHODS: We used verbal autopsy interviews to investigate 1048 neonatal deaths and stillbirths. FINDINGS: There were 430 stillbirths reported, comprising 41% of all deaths in the sample. Of the 618 live births, 32% deaths were on the day of birth, 50% occurred during the first 3 days of life and 71% were during the first week. The primary causes of death on the first day of life (i.e. day 0) were birth asphyxia or injury (31%) and preterm birth (26%). During days 1–6, the most frequent causes of death were preterm birth (30%) and sepsis or pneumonia (25%). Half of all deaths caused by sepsis or pneumonia occurred during the first week of life. The proportion of deaths attributed to sepsis or pneumonia increased to 45% and 36% during days 7–13 and 14–27, respectively. CONCLUSION: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care. Health interventions to improve essential neonatal care and care-seeking behavior are also needed, particularly for preterm neonates in the early postnatal period

Clinical signs predictive of severe illness in young Pakistani infants

Objective: Early detection of specific signs and symptoms to predict severe illness is essential to prevent infant mortality. As a continuation of the results from the multicenter Young Infants Clinical Signs and Symptoms (YICSS) study, we present here the performance of the seven-sign algorithm in 3 age categories (0-6 days, 7-27 days and 28-59 days) in Pakistani infants aged 0-59 days.Results: From September 2003 to November 2004, 2950 infants were enrolled (age group 0-6 days = 1633, 7-27 days = 817, 28-59 days = 500). The common reason for seeking care was umbilical redness or discharge (29.2%) in the 0-6 days group. Older age groups presented with cough (16.9%) in the 7-27 age group and (26.9%) infants in the 28-59 days group. Severe infection/sepsis was the most common primary diagnoses in infants requiring hospitalization across all age groups. The algorithm performed well in every age group, with a sensitivity of 85.9% and specificity of 71.6% in the 0-6 days age group and a sensitivity of 80.5% and specificity of 80.2% in the 28-59 days group; the sensitivity was slightly lower in the 7-27 age group (72.4%) but the specificity remained high (83.1%)

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

Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005-2013

While pneumococcal conjugate vaccines have been implemented in most countries worldwide, use in Asia has lagged in part because of a lack of data on the amount of disease that is vaccine preventable in the region. We describe pneumococcal serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD) from 2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n = 81) of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years and n = 5 among adults). Serotypes were determined by target amplification of DNA extracted from pneumococcal isolates (n = 52) or CSF specimens (n = 59). Serogroup 18 was the most common serogroup causing meningitis in children \u3c5 \u3eyears, accounting for 21% of cases (n = 13). The 10-valent pneumococcal conjugate vaccine (PCV 10) or PCV10- related serotypes were found in 61% (n = 47) of childhood (age 0-15 years) meningitis episodes. PCV-13 increased this coverage to 63% (one additional serotype 19A; n = 48). Our data indicate that use of PCVs would prevent a large proportion of serious pneumococcal disease