Predictive value of pulse oximetry for mortality in infants and children presenting to primary care with clinical pneumonia in rural Malawi: A data linkage study

Autoři: Tim Colbourn aff001;  Carina King aff001;  James Beard aff001;  Tambosi Phiri aff003;  Malizani Mdala aff003;  Beatiwel Zadutsa aff003;  Charles Makwenda aff003;  Anthony Costello aff001;  Norman Lufesi aff004;  Charles Mwansambo aff004;  Bejoy Nambiar aff005;  Shubhada Hooli aff006;  Neil French aff007;  Naor Bar Zeev aff007;  Shamim Ahmad Qazi aff010;  Yasir Bin Nisar aff011;  Eric D. McCollum aff009
Působiště autorů: Institute for Global Health, University College London, London, United Kingdom aff001;  Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden aff002;  Parent and Child Health Initiative, Lilongwe, Malawi aff003;  Ministry of Health, Lilongwe, Malawi aff004;  UNICEF, Lilongwe, Malawi aff005;  Department of Pediatrics, Section of Emergency Medicine, Baylor College of Medicine, Houston, Texas, United States of America aff006;  Institute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdom aff007;  Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi aff008;  Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America aff009;  Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland aff010;  Department of Maternal, Newborn, Child and Adolescent Health and Ageing, World Health Organization, Geneva, Switzerland aff011;  Global Program in Pediatric Respiratory Sciences, Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America aff012
Vyšlo v časopise: Predictive value of pulse oximetry for mortality in infants and children presenting to primary care with clinical pneumonia in rural Malawi: A data linkage study. PLoS Med 17(10): e32767. doi:10.1371/journal.pmed.1003300
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003300



The mortality impact of pulse oximetry use during infant and childhood pneumonia management at the primary healthcare level in low-income countries is unknown. We sought to determine mortality outcomes of infants and children diagnosed and referred using clinical guidelines with or without pulse oximetry in Malawi.

Methods and findings

We conducted a data linkage study of prospective health facility and community case and mortality data. We matched prospectively collected community health worker (CHW) and health centre (HC) outpatient data to prospectively collected hospital and community-based mortality surveillance outcome data, including episodes followed up to and deaths within 30 days of pneumonia diagnosis amongst children 0–59 months old. All data were collected in Lilongwe and Mchinji districts, Malawi, from January 2012 to June 2014. We determined differences in mortality rates using <90% and <93% oxygen saturation (SpO2) thresholds and World Health Organization (WHO) and Malawi clinical guidelines for referral. We used unadjusted and adjusted (for age, sex, respiratory rate, and, in analyses of HC data only, Weight for Age Z-score [WAZ]) regression to account for interaction between SpO2 threshold (pulse oximetry) and clinical guidelines, clustering by child, and CHW or HC catchment area. We matched CHW and HC outpatient data to hospital inpatient records to explore roles of pulse oximetry and clinical guidelines on hospital attendance after referral. From 7,358 CHW and 6,546 HC pneumonia episodes, we linked 417 CHW and 695 HC pneumonia episodes to 30-day mortality outcomes: 16 (3.8%) CHW and 13 (1.9%) HC patients died. SpO2 thresholds of <90% and <93% identified 1 (6%) of the 16 CHW deaths that were unidentified by integrated community case management (iCCM) WHO referral protocol and 3 (23%) and 4 (31%) of the 13 HC deaths, respectively, that were unidentified by the integrated management of childhood illness (IMCI) WHO protocol. Malawi IMCI referral protocol, which differs from WHO protocol at the HC level and includes chest indrawing, identified all but one of these deaths. SpO2 < 90% predicted death independently of WHO danger signs compared with SpO2 ≥ 90%: HC Risk Ratio (RR), 9.37 (95% CI: 2.17–40.4, p = 0.003); CHW RR, 6.85 (1.15–40.9, p = 0.035). SpO2 < 93% was also predictive versus SpO2 ≥ 93% at HC level: RR, 6.68 (1.52–29.4, p = 0.012). Hospital referrals and outpatient episodes with referral decision indications were associated with mortality. A substantial proportion of those referred were not found admitted in the inpatients within 7 days of referral advice. All 12 deaths in 73 hospitalised children occurred within 24 hours of arrival in the hospital, which highlights delay in appropriate care seeking. The main limitation of our study was our ability to only match 6% of CHW episodes and 11% of HC episodes to mortality outcome data.


Pulse oximetry identified fatal pneumonia episodes at HCs in Malawi that would otherwise have been missed by WHO referral guidelines alone. Our findings suggest that pulse oximetry could be beneficial in supplementing clinical signs to identify children with pneumonia at high risk of mortality in the outpatient setting in health centres for referral to a hospital for appropriate management.

Klíčová slova:

Death rates – Global health – Inpatients – Malawi – Medical risk factors – Outpatients – Oxygen – Pneumonia


1. GBD 2017 Lower Respiratory Infections Collaborators. Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017. The Lancet Infectious diseases. 2020;20(1): 60–79. Epub 2019 Oct 31. doi: 10.1016/S1473-3099(19)30410-4 31678026; PubMed Central PMCID: PMC7185492.

2. Reiner RC, Welgan CA, Casey DC, Troeger CE, Baumann MM, Nguyen QP, et al. Identifying residual hotspots and mapping lower respiratory infection morbidity and mortality in African children from 2000 to 2017. Nature Microbiology. 2019;4(12): 2310–2318. doi: 10.1038/s41564-019-0562-y 31570869

3. McAllister DA, Liu L, Shi T, Chu Y, Reed C, Burrows J, et al. Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: a systematic analysis. The Lancet Global health. 2019;7(1): e47–e57. Epub 2018 Nov 26. doi: 10.1016/S2214-109X(18)30408-X 30497986; PubMed Central PMCID: PMC6293057.

4. Kallander K, Hildenwall H, Waiswa P, Galiwango E, Peterson S, Pariyo G. Delayed care seeking for fatal pneumonia in children aged under five years in Uganda: a case-series study. Bull World Health Organ. 2008;86(5): 332–8. doi: 10.2471/blt.07.049353 18545734; PubMed Central PMCID: PMC2647445.

5. Ngwalangwa F, Phiri CHA, Dube Q, Langton J, Hildenwall H, Baker T. Risk Factors for Mortality in Severely Ill Children Admitted to a Tertiary Referral Hospital in Malawi. The American journal of tropical medicine and hygiene. 2019;101(3): 670–675. doi: 10.4269/ajtmh.19-0127 31287044.

6. McCollum ED, King C, Deula R, Zadutsa B, Mankhambo L, Nambiar B, et al. Outpatient pulse oximetry implementation with rural facility and community health workers during three years of child pneumonia care in two central Malawi districts. Bulletin of the World Health Organisation. 2016;94: 893–902.

7. Mulholland K. Problems with the WHO guidelines for management of childhood pneumonia. Lancet Glob Health. 2018;6(1): e8–e9. doi: 10.1016/S2214-109X(17)30468-0 29241619.

8. World Health Organization. Integrated management of childhood illness: chart booklet [Internet]. 2014 [cited 2019 Jun 28]. Available from:

9. Hooli S, Colbourn T, Lufesi N, Costello A, Nambiar B, Makwenda C, et al. Predicting hospitalised paediatric pneumonia mortality risk: an external validation of RISC and mRISC, and local tool development (RISC-Malawi) from Malawi. PLoS ONE. 2016;11(12): e0168126. doi: 10.1371/journal.pone.0168126 28030608

10. Lazzerini M, Sonego M, Pellegrin MC. Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis. PLoS ONE. 2015;10(9): e0136166. doi: 10.1371/journal.pone.0136166 26372640; PubMed Central PMCID: PMC4570717.

11. Enoch AJ, English M, Shepperd S. Does pulse oximeter use impact health outcomes? A systematic review. Arch Dis Child. 2016;101(8):694–700. Epub 2015 Dec 23. doi: 10.1136/archdischild-2015-309638 26699537; PubMed Central PMCID: PMC4975806.

12. World Health Organization. Exploratory meeting to review new evidence for Integrated Management of Childhood Illness danger signs, Geneva, Switzerland, 4–5 September 2018. Geneva: World Health Organization (WHO/MCA/19.02); 2019.

13. McCollum ED, Nambiar B, Deula R, Zadutsa B, Bondo A, King C, et al. Impact of the 13-valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An observational study. PLoS ONE. 2017;12(1): e0168209. doi: 10.1371/journal.pone.0168209 28052071

14. Bar-Zeev N, King C, Phiri T, Beard J, Mvula H, Crampin AC, et al. Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort study. The Lancet Global health. 2018;6(9): e1036–e44. doi: 10.1016/S2214-109X(18)30314-0 30103981; PubMed Central PMCID: PMC6088152.

15. Bar-Zeev N, Kapanda L, King C, Beard J, Phiri T, Mvula H, et al. Methods and challenges in measuring the impact of national pneumococcal and rotavirus vaccine introduction on morbidity and mortality in Malawi. Vaccine. 2015;33(23): 2637–45. doi: 10.1016/j.vaccine.2015.04.053 25917672; PubMed Central PMCID: PMC4441035.

16. King C, Beard J, Crampin AC, Costello A, Mwansambo C, Cunliffe NA, et al. Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings. Vaccine. 2015;33(38): 4748–55. doi: 10.1016/j.vaccine.2015.07.062 26235370; PubMed Central PMCID: PMC4570930.

17. Government of the Republic of Malawi Ministry of Health. Management of children with Pneumonia (National Guidelines). Lilongwe, Malawi: Government of the Republic of Malawi Ministry of Health; 2000.

18. Hooli S, King C, Zadutsa B, Nambiar B, Makwenda C, Masache G, et al. The epidemiology of hypoxaemic pneumonia among young infants in Malawi: A prospective observational study. American Journal of Tropical Medicine & Hygiene. 2020;102(3): 676–683. doi: 10.4269/ajtmh.19-0516 31971153

19. World Health Organization. Caring for the sick child in the community: participant manual [Internet]. 2011 [cited 2019 Sep 24]. Available from:

20. Knol MJ, Le Cessie S, Algra A, Vandenbroucke JP, Groenwold RH. Overestimation of risk ratios by odds ratios in trials and cohort studies: alternatives to logistic regression. CMAJ. 2012;184(8): 895–9. Epub 2011 Dec 12. doi: 10.1503/cmaj.101715 22158397; PubMed Central PMCID: PMC3348192

21. Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PMM. The diagnostic odds ratio: a single indicator of test performance. Journal of Clinical Epidemiology. 2003;56(11): 1129–35. doi: 10.1016/s0895-4356(03)00177-x 14615004

22. World Health Organization. Oxygen therapy for children: a manual for health workers [Internet]. 2016 [cited 2020 Jul 24]. Available from:

23. Duke T, English M, Carai S, Qazi S. Paediatric care in the time of COVID-19 in countries with under-resourced healthcare systems. Arch Dis Child. 2020;105(7): 616–7. doi: 10.1136/archdischild-2020-319333 32424004

24. World Health Organization. IMCI: the integrated approach [Internet]. 1997 [cited 2019 Sep 24]. Available from:

25. World Health Organization. Recommendations for management of common childhood conditions. Evidence for technical update of pocket book recommendations [Internet]. 2012 [cited 2020 Jan 22]. Available from:

26. Lodha R, Kabra SK, Pandey RM. Antibiotics for community-acquired pneumonia in children. Cochrane Database Syst Rev. 2013;(6): CD004874. doi: 10.1002/14651858.CD004874.pub4 23733365

27. Patel AB, Bang A, Singh M, Dhande L, Chelliah LR, Malik A, et al. A randomized controlled trial of hospital versus home based therapy with oral amoxicillin for severe pneumonia in children aged 3–59 months: The IndiaCLEN Severe Pneumonia Oral Therapy (ISPOT) Study. BMC Pediatr. 2015;15: 186. doi: 10.1186/s12887-015-0510-9 26577943; PubMed Central PMCID: PMC4650851

28. Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, et al. Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis. 2015;60(8): 1216–24. doi: 10.1093/cid/ciu1166 25550349; PubMed Central PMCID: PMC4370168.

29. Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Phiri M, Schmicker R, et al. Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. N Engl J Med. 2020;383(1): 13–23. doi: 10.1056/NEJMoa1912400 32609979; PubMed Central PMCID: PMC7233470.

30. Agweyu A, Lilford RJ, English M. Appropriateness of clinical severity classification of new WHO childhood pneumonia guidance: a multi-hospital, retrospective, cohort study. The Lancet Global health. 2018;6(1): e74–e83. doi: 10.1016/S2214-109X(17)30448-5 29241618; PubMed Central PMCID: PMC5732316.

31. Florin TA, Ambroggio L, Brokamp C, Rattan MS, Crotty EJ, Kachelmeyer A, et al. Reliability of Examination Findings in Suspected Community-Acquired Pneumonia. Pediatrics. 2017;140(3): e20170310. doi: 10.1542/peds.2017-0310 28835381; PubMed Central PMCID: PMC5574720 conflicts of interest to disclose.

32. Zalisk K, Guenther T, Prosnitz D, Nsona H, Chimbalanga E, Sadruddin S. Achievements and challenges of implementation in a mature iCCM programme: Malawi case study. Journal of global health. 2019;9(1):010807. doi: 10.7189/jogh.09.010807 31263552; PubMed Central PMCID: PMC6594665

33. Munthali AC, Mannan H, MacLachlan M, Swartz L, Makupe CM, Chilimampunga C. Non-use of Formal Health Services in Malawi: Perceptions from Non-users. Malawi Med J. 2014;26(4): 126–32. 26167263; PubMed Central PMCID: PMC4325348.

34. Kozuki N, Guenther T, Vaz L, Moran A, Soofi SB, Kayemba CN, et al. A systematic review of community-to-facility neonatal referral completion rates in Africa and Asia. BMC Public Health. 2015;15: 989. doi: 10.1186/s12889-015-2330-0 26419934; PubMed Central PMCID: PMC4589085.

35. Hildenwall H, Nantanda R, Tumwine JK, Petzold M, Pariyo G, Tomson G, et al. Care-seeking in the development of severe community acquired pneumonia in Ugandan children. Ann Trop Paediatr. 2009;29(4): 281–9. doi: 10.1179/027249309X12547917869005 19941751.

36. Floyd J, Wu L, Hay Burgess D, Izadnegahdar R, Mukanga D, Ghani AC. Evaluating the impact of pulse oximetry on childhood pneumonia mortality in resource-poor settings. Nature. 2015;528(7580): S53–9. doi: 10.1038/nature16043 26633766.

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