Accuracy of non-physician health workers in respiratory rate measurement to identify paediatric pneumonia in low- and middle-income countries: a systematic review and meta-analysis

BACKGROUND: Non-physician health workers play an important role in identifying and treating pneumonia in children in low- and middle-income countries (LMICs). In this systematic review, we summarized the evidence on whether health workers can accurately measure respiratory rate (RR) and identify fast breathing to diagnose pneumonia in children under five years of age. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Scopus from January 1990 to August 2020 without any language restrictions. Reference lists of included studies were also screened for additional records. Studies evaluating the performance of health workers in measuring RR and/or identifying fast breathing compared to a reference standard were included. The methodological quality of the included studies was assessed using the QUADAS-2 tool. A meta-analysis was conducted to report pooled estimates of sensitivity and specificity. Hierarchical summary receiver operating characteristic curve (HSROC) models were fitted, and subgroup and sensitivity analyses were performed to examine the effects of study variables. RESULTS: We included 16 studies, eight of which reported the agreement in RR count between health workers and a reference standard. The median agreements were 39%, 47%, and 67% within ±2, ±3, and ±5 breaths per minute, respectively. Among the 16 included studies, we identified 15 studies that reported the accuracy of a health worker classifying breathing into either fast or normal categories compared to a reference standard. The median sensitivity, specificity, accuracy, and kappa value were 77%, 86%, 81%, and 0.75, respectively. Seven studies reporting the accuracy of identifying fast breathing were included in the meta-analysis. The pooled estimates of sensitivity and specificity were 78% (95% CI = 72-82) and 86% (95% CI = 78-91), respectively. CONCLUSIONS: Despite the problematic nature of reference standards and their variability across studies, our review suggests that the health worker performance in accurately counting RR is relatively poor. However, their performance shows reasonable specificity and moderate sensitivity in identifying fast breathing. Improving the detection of fast breathing in children with suspected pneumonia among health workers is an important child health programme objective and should be given appropriate priority

Bioelectrical impedance vector analysis as an indicator of malnutrition in children under five years with and without pneumonia in Mchinji District, Malawi: An exploratory mixed-methods analysis [version 1; peer review: awaiting peer review]

Background: Bioelectrical impedance vector analysis (BIVA) is a non-invasive assessment of body composition and cellular health, which may improve the assessment of nutritional status in sick children. We explored the reliability, clinical utility, and acceptability of BIVA, as an indicator of nutritional status for children under five years with and without pneumonia, in Malawi. Methods: We conducted a parallel convergent mixed-methods exploratory study in Mchinji District Hospital, Malawi, in 2017. We planned to recruit a convenience sample of children aged 0-59 months with clinical pneumonia, and without an acute illness. Children had duplicate anthropometric and BIVA measurements taken. BIVA measurements of phase angle (PA) were taken of the whole body, and trunk and arm segments. Reliability was assessed by comparing the variability in the two measures, and clinical utility by estimating the association between anthropometry and PA using linear regression. Focus group discussions with healthcare workers who had not previously used BIVA instrumentation were conducted to explore acceptability. Results: A total of 52 children (24 with pneumonia and 28 healthy) were analysed. The reliability of sequential PA measurements was lower than anthropometric measurements, but trunk and arm segments performed better. The largest associations with PA were a negative relationship with weight-for-age z-score (WAZ) and PA in children with pneumonia in the trunk segment, and a positive association with WAZ in the full body measurement in healthy children. Healthcare workers in focus group discussions expressed trust in BIVA technology and that it would enable more accurate diagnosis of malnutrition; however, they raised concerns about the sustainability and necessary resources to implement BIVA. Conclusions: While healthcare workers were positive towards BIVA as a novel technology, implementation challenges should be expected. The differential direction of association between anthropometry and PA for children with pneumonia warrants further investigation

Bioelectrical impedance vector analysis as an indicator of malnutrition in children under five years with and without pneumonia in Mchinji District, Malawi: An exploratory mixed-methods analysis [version 3; peer review: 1 approved, 1 approved with reservations]

Background: Bioelectrical impedance vector analysis (BIVA) is a non-invasive approach to assessing body composition and cellular health, which may improve the assessment of nutritional status in sick children. We explored the reliability, clinical utility, and acceptability of BIVA, as an indicator of nutritional status for children under five years with and without pneumonia, in Malawi. Methods: We conducted a parallel convergent mixed-methods exploratory study in Mchinji District Hospital, Malawi, in 2017. We recruited a convenience sample of children aged 0–59 months with clinical pneumonia, and without an acute illness. Children had duplicate anthropometric and BIVA measurements taken. BIVA measurements of phase angle were taken of the whole body, and trunk and arm segments. Reliability was assessed by comparing the variability in the two measures, and clinical utility by estimating the association between anthropometry and phase angle using linear regression. Focus group discussions with healthcare workers who had not previously used BIVA instrumentation were conducted to explore acceptability. Results: A total of 52 children (24 with pneumonia and 28 healthy) were analysed. The reliability of sequential phase angle measurements was lower than anthropometric measurements, but trunk and arm segments performed better. The largest associations with phase angle were a negative relationship with weight-for-age z-score (WAZ) in children with pneumonia in the trunk segment, and a positive association with WAZ in the full body measurement in healthy children. Healthcare workers in focus group discussions expressed trust in BIVA technology and that it would enable more accurate diagnosis of malnutrition; however, they raised concerns about the sustainability and necessary resources to implement BIVA. Conclusions: While healthcare workers were positive towards BIVA as a novel technology, implementation challenges should be expected. The differential direction of association between anthropometry and phase angle for children with pneumonia warrants further investigation

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001–12: a retrospective observational study

Background Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Methods Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi’s Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children’s clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2–11 months of age, and 12–59 months of age using separate multivariable mixed eff ects logistic regression models. Findings Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92∧7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4–6·7). The case fatality rate signifi cantly decreased between 2001 (15·2% [13·4–17·1]) and 2012 (4·5% [4·1–4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors signifi cantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2–11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). Interpretation Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specifi c subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of suffi cient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of eff ective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study.

BACKGROUND: Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. METHODS: Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed effects logistic regression models. FINDINGS: Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92·7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4-6·7). The case fatality rate significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). INTERPRETATION: Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. FUNDING: Bill & Melinda Gates Foundation

Risk and accuracy of outpatient-identified hypoxaemia for death among suspected child pneumonia cases in rural Bangladesh: a multifacility prospective cohort study

BACKGROUND: Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh. METHODS: We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult breathing (defined as suspected pneumonia) were enrolled in the study; because lower respiratory tract infection mortality mainly occurs in children younger than 1 year, the primary study population comprised children aged 3-11 months. Study physicians recorded WHO IMCI pneumonia guideline clinical signs and peripheral arterial oxyhaemoglobin saturations (SpO2) in room air. They treated children with pneumonia with antibiotics (oral amoxicillin [40 mg/kg per dose twice per day for 5-7 days, as per local practice]), and recommended oxygen, parenteral antibiotics, and hospitalisation for those with an SpO2 of less than 90%, WHO IMCI danger signs, or severe malnutrition. Community health workers documented the children's vital status and the date of any vital status changes during routine household surveillance (one visit to each household every 2 months). The primary outcome was death at 2 weeks after enrolment in children aged 3-11 months (primary study population) and 12-35 months (secondary study population). Primary analyses included estimating the outpatient prevalence, mortality risk, and prognostic accuracy of hypoxaemia for death in children aged 3-11 months with suspected pneumonia. Risk ratios were produced by fitting a multivariable model that regressed predefined SpO2 ranges (<90%, 90-93%, and 94-100%) on the primary 2-week mortality outcome (binary outcome) using Poisson models with robust variance estimation. We established the prognostic accuracy of WHO IMCI guidelines for death with and without varying SpO2 thresholds. FINDINGS: Participants were recruited between Sept 1, 2015, to Aug 31, 2017. During the study period, a total of 7440 children aged 3-35 months with the first suspected pneumonia episode were enrolled, of whom 3848 (54·3%) with an attempted pulse oximeter measurement and 2-week outcome were included in our primary study population of children aged 3-11-months. Among children aged 3-11 months, an SpO2 of less than 90% occurred in 102 (2·7%) of 3848 children, an SpO2 of 90-93% occurred in 306 (8·0%) children, a failed SpO2 measurement occurred in 67 (1·7%) children, and 24 (0·6%) children with suspected pneumonia died. Compared with an SpO2 of 94-100% (3373 [87·7%] of 3848), the adjusted risk ratio for death was 10·3 (95% CI 3·2-32·3; p<0·001) for an SpO2 of less than 90%, 4·3 (1·5-11·8; p=0·005) for an SpO2 of 90-93%, and 11·4 (3·1-41·4; p<0·001) for a failed measurement. When not considering pulse oximetry, of the children who died, WHO IMCI guidelines identified only 25·0% (95% CI 9·7-46·7; six of 24 children) as eligible for referral to hospital. For identifying deaths, in children with an SpO2 of less than 90% WHO IMCI guidelines had a 41·7% sensitivity (95% CI 22·1-63·4) and 89·7% specificity (88·7-90·7); for children with an SpO2 of less than 90% or measurement failure the guidelines had a 54·2% sensitivity (32·8-74·4) and 88·3% specificity (87·2-89·3); and for children with an SpO2 of less than 94% or measurement failure the guidelines had a 62·5% sensitivity (40·6-81·2) and 81·3% specificity (80·0-82·5). INTERPRETATION: These findings support pulse oximeter use during the outpatient care of young children with suspected pneumonia in Bangladesh as well as the re-evaluation of the WHO IMCI currently recommended threshold of an SpO2 less than 90% for hospital referral. FUNDING: Fogarty International Center of the National Institutes of Health (K01TW009988), The Bill & Melinda Gates Foundation (OPP1084286 and OPP1117483), and GlaxoSmithKline (90063241)

Determining the quality of IMCI pneumonia care in Malawian children

Although pneumonia is the leading cause of child mortality worldwide, little is known about the quality of routine pneumonia care in high burden settings like Malawi that utilize World Health Organization’s Integrated Management of Childhood Illnesses (IMCI) guidelines. Due to severe human resource constraints, the majority of clinical care in Malawi is delivered by non-physician clinicians called Clinical Officers (COs)

Clinical hypoxemia score for outpatient child pneumonia care lacking pulse oximetry in Africa and South Asia

Background: Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia. / Methods: This was a retrospective pooled analysis of two outpatient datasets of 3–35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO2 < 93% and <90%: (1) Integrated Management of Childhood Illness guidelines, (2) WHO-composite guidelines, (3) Independent variable least absolute shrinkage and selection operator (LASSO); (4) Composite variable LASSO. / Results: 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO2 < 93% and ≥94%; model predictive capacities remained moderate after adjusting for potential overfitting (C-statistic 0.74 and 0.75). The IMCI and WHO-composite models had poorer discrimination (C-statistic 0.56 and 0.68) and identified 20.6% and 56.8% of SpO2 < 93% cases. The highest score stratum of the independent and composite LASSO models identified 46.7% and 49.0% of SpO2 < 93% cases. Both LASSO models had similar performance for a SpO2 < 90%. / Conclusions: In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases than the WHO guidelines. Score external validation and implementation are needed