Tabish Hazir

Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial

BACKGROUND WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as effective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children. METHODS This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3-59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80-90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80-90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrollment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329. FINDINGS In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8.6%) treatment failures in the hospitalised group and 77 (7.5%) in the ambulatory group (risk difference 1.1%; 95% CI -1.3 to 3.5) by day 6. Five (0.2%) children died within 14 days of enrollment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial. INTERPRETATION Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.

Chest radiography in children aged 2-59 months diagnosed with non-severe pneumonia as defined by World Health Organization: descriptive multicentre study in Pakistan

Abstract Objectives To evaluate the chest radiographs of children diagnosed with non-severe pneumonia on the basis of the current World Health Organization guidelines (fast breathing alone) for radiological evidence of pneumonia. Design Descriptive analysis. Setting Outpatient departments of six hospitals in four cities in Pakistan. Participants 2000 children with non-severe pneumonia were enrolled; 1932 children were selected for chest radiography. Interventions Two consultant radiologists used standardised WHO definitions to evaluate chest radiographs; no clinical information was made available to them. If they disagreed, the radiographs were read by a third radiologist; the final classification was based on agreement between two of the three radiologists. Main outcome measures Presence or absence of pneumonia on radiographs. Results Chest radiographs were reported normal in 1519 children (82%). Radiological evidence of pneumonia was reported in only 263 (14%) children, most of whom had interstitial pneumonitis. Lobar consolidation was present in only 26 children. The duration of illness did not correlate significantly with the presence of radiological changes (relative risk 1.17, 95% confidence interval 0.91 to 1.49). Conclusion Most children diagnosed with non-severe pneumonia on the basis of the current WHO definition had normal chest radiographs.

Comparisons of complementary feeding indicators and associated factors in children aged 6-23 months across five South Asian countries

Improving infant and young child feeding practices will help South Asian countries achieve the Millennium Development Goal of reducing child mortality. This paper aims to compare key indicators of complementary feeding and their determinants in children aged 6-23 months across five South Asian countries - Bangladesh, India, Nepal, Pakistan and Sri Lanka. The latest Demographic and Health Survey and National Family Health Survey India data were used. The analyses were confined to last-born children aged 6-23 months - 1728 in Bangladesh, 15,028 in India, 1428 in Nepal, 2106 in Sri Lanka and 443 infants aged 6-8 months in Pakistan. Introduction of solid, semi-solid or soft foods, minimum dietary diversity, minimum meal frequency and minimum acceptable diet, and their significant determinants were compared across the countries. Minimum dietary diversity among children aged 6-23 months ranged from 15% in India to 71% in Sri Lanka, with Nepal (34%) and Bangladesh (42%) in between. Minimum acceptable diet among breastfed children was 9% in India, 32% in Nepal, 40% in Bangladesh and 68% in Sri Lanka. The most consistent determinants of inappropriate complementary feeding practices across all countries were the lack of maternal education and lower household wealth. Limited exposure to media, inadequate antenatal care and lack of post-natal contacts by health workers were among predictors of inappropriate feeding. Overall, complementary feeding practices among children aged 6-23 months need improvement in all South Asian countries. More intensive interventions are necessary targeting the groups with sup-optimal practices, while programmes that cover entire populations are being continued.

Comparison of Oral Amoxicillin with Placebo for the Treatment of World Health Organization–Defined Nonsevere Pneumonia in Children Aged 2–59 Months: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial in Pakistan

BACKGROUND world Health Organization (WHO) acute respiratory illness case management guidelines classify children with fast breathing as having pneumonia and recommend treatment with an antibiotic. There is concern that many of these children may not have pneumonia and are receiving antibiotics unnecessarily. This could increase antibiotic resistance in the community. The aim was to compare the clinical outcome at 72 h in children with WHO-defined nonsevere pneumonia when treated with amoxicillin, compared with placebo. METHODS we performed a double-blind, randomized, equivalence trial in 4 tertiary hospitals in Pakistan. Nine hundred children aged 2-59 months with WHO defined nonsevere pneumonia were randomized to receive either 3 days of oral amoxicillin (45mg/kg/day) or placebo; 873 children completed the study. All children were followed up on days 3, 5, and 14. The primary outcome was therapy failure defined a priori at 72 h. RESULTS in per-protocol analysis at day 3, 31 (7.2%) of the 431 children in the amoxicillin arm and 37 (8.3%) of the 442 in placebo group had therapy failure. This difference was not statistically significant (odds ratio [OR], .85; 95%CI, .50-1.43; P = .60). The multivariate analysis identified history of difficult breathing (OR, 2.86; 95% CI, 1.29-7.23; P = .027) and temperature >37.5°C 100°F at presentation (OR, 1.99; 95% CI, 1.37-2.90; P = .0001) as risk factors for treatment failure by day 5. CONCLUSION clinical outcome in children aged 2-59 months with WHO-defined nonsevere pneumonia is not different when treated with an antibiotic or placebo. Similar trials are needed in countries with a high burden of pneumonia to rationalize the use of antibiotics in these communities.

Assessment and management of children aged 1–59 months presenting with wheeze, fast breathing, and/or lower chest indrawing; results of a multicentre descriptive study in Pakistan

Background and Aims: Using current WHO guidelines, children with wheezing are being over prescribed antibiotics and bronchodilators are underutilised. To improve the WHO case management guidelines, more data is needed about the clinical outcome in children with wheezing/pneumonia overlap. Methodology: In a multicentre prospective study, children aged 1–59 months with auscultatory/audible wheeze and fast breathing and/or lower chest indrawing were screened. Response to up to three cycles of inhaled salbutamol was recorded. The responders were enrolled and sent home on inhaled bronchodilators, and followed up on days 3 and 5. Results: A total of 1622 children with wheeze were screened from May 2001 to April 2002, of which 1004 (61.8%) had WHO defined non-severe and 618 (38.2%) severe pneumonia. Wheeze was audible in only 595 (36.7%) of children. Of 1004 non-severe pneumonia children, 621 (61.8%) responded to up to three cycles of bronchodilator. Of 618 severe pneumonia children, only 166 (26.8%) responded. Among responders, 93 (14.9%) in the non-severe and 63 (37.9%) children in the severe pneumonia group showed subsequent deterioration on follow ups. No family history of wheeze, temperature >100°F, and lower chest indrawing were identified as predictors of subsequent deterioration. Conclusions: Two third of children with wheeze are not identified by current WHO ARI (acute respiratory infections) guidelines. Antibiotics are over prescribed and bronchodilators under utilised in children with wheeze. Children with wheeze constitute a special ARI group requiring a separate management algorithm. In countries where wheeze is common it would be worthwhile to train health workers in use of the stethoscope to identify wheeze.

Measuring Coverage in MNCH: Challenges in Monitoring the Proportion of Young Children with Pneumonia Who Receive Antibiotic Treatment

Pneumonia remains a major cause of child death globally, and improving antibiotic treatment rates is a key control strategy. Progress in improving the global coverage of antibiotic treatment is monitored through large household surveys such as the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), which estimate antibiotic treatment rates of pneumonia based on two-week recall of pneumonia by caregivers. However, these survey tools identify children with reported symptoms of pneumonia, and because the prevalence of pneumonia over a two-week period in community settings is low, the majority of these children do not have true pneumonia and so do not provide an accurate denominator of pneumonia cases for monitoring antibiotic treatment rates. In this review, we show that the performance of survey tools could be improved by increasing the survey recall period or by improving either overall discriminative power or specificity. However, even at a test specificity of 95% (and a test sensitivity of 80%), the proportion of children with reported symptoms of pneumonia who truly have pneumonia is only 22% (the positive predictive value of the survey tool). Thus, although DHS and MICS survey data on rates of care seeking for children with reported symptoms of pneumonia and other childhood illnesses remain valid and important, DHS and MICS data are not able to give valid estimates of antibiotic treatment rates in children with pneumonia.

Comparison of standard versus double dose of amoxicillin in the treatment of non-severe pneumonia in children aged 2–59 months: a multi-centre, double blind, randomised controlled trial in Pakistan

Introduction: WHO pneumonia case management guidelines recommend oral amoxicillin as first line treatment for non-severe pneumonia. Increasing treatment failure rates have been reported over a period of time, which could possibly be due to increasing minimum inhibitory concentrations of Streptococcus pneumoniae and Haemophilus influenzae for amoxicillin. Microbiological data show that this resistance can be overcome by increasing amoxicillin dosage. Based on this data, we examined whether we can improve the clinical outcome in non-severe pneumonia by doubling the dose of amoxicillin. Methods: A double blind randomised controlled trial was conducted in the outpatient departments of four large hospitals in Pakistan. Children aged 2–59 months with non-severe pneumonia were randomised to receive either standard (45 mg/kg/day) or double dose (90 mg/kg/day) oral amoxicillin for 3 days and then followed up for 14 days. Final outcome was treatment failure by day 5. Results: From September 2003 to June 2004, 876 children completed the study. 437 were randomised to standard and 439 to double dose oral amoxicillin. 20 (4.5%) children in the standard and 25 (5.7%) in the double dose group had therapy failure by day 5. Including the relapses, by day 14 there were 26 (5.9%) cumulative therapy failures with standard and 35 (7.9%) with double dose amoxicillin. These differences were not statistically significant (p = 0.55 and p = 0.29, respectively). Conclusion: Clinical outcome in children aged 2–59 months with non-severe pneumonia is the same with standard and double dose oral amoxicillin. Non-severe pneumonia can be treated effectively and safely with a 3 day course of a standard dose.

Determinants of suboptimal breast-feeding practices in Pakistan

OBJECTIVE Exclusive breast-feeding is estimated to reduce infant mortality in low-income countries by up to 13 %. The aim of the present study was to determine the risk factors associated with suboptimal breast-feeding practices in Pakistan. DESIGN A cross-sectional study using data extracted from the multistage cluster sample survey of the Pakistan Demographic and Health Survey 2006-2007. SETTING A nationally representative sample of households. SUBJECTS Last-born alive children aged 0-23 months (total weighted sample size 3103). RESULTS The prevalences of timely initiation of breast-feeding, bottle-feeding in children aged 0-23 months, exclusive breast-feeding and predominant breast-feeding in infants aged 0-5 months were 27·3 %, 32·1 %, 37·1 % and 18·7 %, respectively. Multivariate analysis indicated that working mothers (OR = 1·48, 95 % CI 1·16, 1·87; P = 0·001) and mothers who delivered by Caesarean section (OR = 1·95, 95 % CI 1·30, 2·90; P = 0·001) had significantly higher odds for no timely initiation of breast-feeding. Mothers from North West Frontier Province were significantly less likely (OR = 0·37, 95 % CI 0·23, 0·59; P < 0·001) not to breast-feed their babies exclusively. Mothers delivered by traditional birth attendants had significantly higher odds to predominantly breast-feed their babies (OR = 1·96, 95 % CI 1·18, 3·24; P = 0·009). The odds of being bottle-fed was significantly higher in infants whose mothers had four or more antenatal clinic visits (OR = 1·93, 95 % CI 1·46, 2·55; P < 0·001) and belonged to the richest wealth quintile (OR = 2·41, 95 % CI 1·62, 3·58; P < 0·001). CONCLUSIONS The majority of Pakistani mothers have suboptimal breast-feeding practices. To gain the full benefits of breast-feeding for child health and nutrition, there is an urgent need to develop interventions to improve the rates of exclusive breast-feeding.

Carers’ perception of childhood asthma and its management in a selected Pakistani community

Aims: To gather information on the level of disease awareness among the carers of asthmatic children and to determine whether it can help us draw inferences about the possible impact of prevailing perceptions on the management of asthma? Methods: Subjects were children’s parents/guardians visiting the asthma clinic, Children’s Hospital, Islamabad. The questionnaire included items on general understanding of asthma, its triggers, and management. Results: Two hundred carers of asthmatic patients participated. Thirty six per cent thought that asthma is a communicable disease. Rice and oily foods were blamed for asthmatic exacerbations in up to 57% of cases; 82% felt that inhalation therapy is effective in controlling asthma symptoms. Conclusions: Asthma awareness is inadequate. The majority of the carers unnecessarily blamed and withheld many nutritious foods. Social stigmata can undermine the self esteem of growing asthmatics. Lack of awareness is not significantly related to the socioeconomic or educational background. Awareness raising strategies are needed in the community.

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013–2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.