Implication of the 2014 World Health Organization Integrated Management of Childhood Illness Pneumonia Guidelines with and without pulse oximetry use in Malawi: A retrospective cohort study [version 2; peer review: 2 approved]

Background: Under-5 pneumonia mortality remains high in low-income countries. In 2014 the World Health Organization (WHO) advised that children with chest indrawing pneumonia, but without danger signs or peripheral oxygen saturation (SpO 2) < 90% be treated in the community, rather than hospitalized. In Malawi there is limited pulse oximetry availability. Methods: Secondary analysis of 13,413 under-5 pneumonia cases in Malawi. Pneumonia associated case fatality ratios (CFR) were calculated by disease severity under the assumptions of the 2005 and 2014 WHO Integrated Management of Childhood Illness (IMCI) guidelines, with and without pulse oximetry. We investigated if pulse oximetry readings were missing not at random (MNAR). Results: The CFR of patients classified as having non-severe pneumonia per the 2014 IMCI guidelines doubled under the assumption that pulse oximetry was not available (1.5% without pulse oximetry vs 0.7% with pulse oximetry, P<0.001). When 2014 IMCI guidelines were applied with pulse oximetry and a SpO 2 < 90% as the threshold for referral and/or admission, the number of cases meeting hospitalization criteria decreased by 70.3%. Unrecorded pulse oximetry readings were MNAR with an adjusted odds for mortality of 4.9 (3.8, 6.3), similar to that of a SpO 2 < 90%. Although fewer girls were hospitalized, female sex was an independent mortality risk factor. Conclusions: In Malawi, implementation of the 2014 WHO IMCI pneumonia guidelines, without pulse oximetry, will miss high risk cases. Alternatively, implementation of pulse oximetry may result in a large reduction in hospitalization rates without significantly increasing non-severe pneumonia associated CFR if the inability to obtain a pulse oximetry reading is considered a WHO danger sign

Non-adherence to community oral-antibiotic treatment in children with fast-breathing pneumonia in Malawi– secondary analysis of a prospective cohort study

Background Despite significant progress, pneumonia is still the leading cause of infectious deaths in children under five years of age. Poor adherence to antibiotics has been associated with treatment failure in World Health Organisation (WHO) defined clinical pneumonia; therefore, improving adherence could improve outcomes in children with fast-breathing pneumonia. We examined clinical factors that may affect adherence to oral antibiotics in children in the community setting in Malawi. Methods We conducted a sub-analysis of a prospective cohort of children aged 2–59 months diagnosed by community health workers (CHW) in rural Malawi with WHO fast-breathing pneumonia. Clinical factors identified during CHW diagnosis were investigated using multivariate logistic regression for association with non-adherence, including concurrent diagnoses and treatments. Adherence was measured at both 80% and 100% completion of prescribed oral antibiotics. Results Eight hundred thirty-four children were included in our analysis, of which 9.5% and 20.0% were non-adherent at 80% and 100% of treatment completion, respectively. A concurrent infectious diagnosis (OR: 1.76, 95% CI: 0.84–2.96/OR: 1.81, 95% CI: 1.21–2.71) and an illness duration of >24 h prior to diagnosis (OR: 2.14, 95% CI: 1.27–3.60/OR: 1.88, 95% CI: 1.29–2.73) had higher odds of non-adherence when measured at both 80% and 100%. Older age was associated with lower odds of non-adherence when measured at 80% (OR: 0.41, 95% CI: 0.21–0.78). Conclusion Non-adherence to oral antibiotics was not uncommon in this rural sub-Saharan African setting. As multiple diagnoses by the CHW and longer illness were important factors, this provides an opportunity for further investigation into targeted interventions and refinement of referral guidelines at the community level. Further research into the behavioural drivers of non-adherence within this setting is needed

The Epidemiology of Hypoxemic Pneumonia among Young Infants in Malawi

We describe hypoxemic pneumonia prevalence in outpatient and inpatient settings, in-hospital mortality, and clinical guideline performance for identifying hypoxemia in young infants in Malawi. In this retrospective analysis of a prospective cohort study, we investigate infants younger than 2 months participating in pneumonia surveillance at seven hospitals and 18 outpatient health centers in Malawi between 2011 and 2014. Logistic regression, multiple imputations with chained equations, and pattern mixture modeling were used to determine the association between peripheral oxyhemoglobin saturation (SpO2) levels and hospital mortality. We describe referral recommendations based on clinical characteristics and SpO2 distributions. Among 1,879 analyzed cases, SpO2 < 90% was more prevalent among outpatient health center cases than that among hospitalized cases (22.6% versus 13.5%, 95% CI: 17.6–28.4% and 12.0–15.3%, respectively). A larger proportion of hospitalized infants had signs of respiratory distress than infants at health centers (67.7% versus 56.6%, P < 0.001) and the signs were higher in male versus female infants (56.7% versus 40.6%, P < 0.001). An SpO2 of 90–92% and < 90% was associated with similarly increased odds of in-hospital mortality (adjusted odds ratio [aOR]: 4.3 and 4.4, 95% CI: 1.7–11.1 and 1.8–10.5, respectively). Unrecorded, or unobtainable, SpO2 was highly associated with mortality (n = 127, aOR: 18.1; 95% CI: 7.6–42.8). Four of 22 (18%) infants at health centers who did not meet clinical referral criteria had an SpO2 ≤ 92%. Clinicians should consider hospital referral in young infants with SpO2 ≤ 92%. Infants with unobtainable SpO2 readings should be considered a high-risk group, and hospital referral of these cases may be appropriate

Multicenter study of hypoxemia prevalence and quality of oxygen treatment for hospitalized Malawian children

Although hypoxemic children have high mortality, little is known about hypoxemia prevalence and oxygen administration in African hospitals. We aimed to determine the hypoxemia prevalence and quality of oxygen treatment by local clinicians for hospitalized Malawian children

Pulse oximetry for children with pneumonia treated as outpatients in rural Malawi

OBJECTIVE: To investigate implementation of outpatient pulse oximetry among children with pneumonia, in Malawi. METHODS: In 2011, 72 health-care providers at 18 rural health centres and 38 community health workers received training in the use of pulse oximetry to measure haemoglobin oxygen saturations. Data collected, between 1 January 2012 and 30 June 2014 by the trained individuals, on children aged 2-59 months with clinically diagnosed pneumonia were analysed. FINDINGS: Of the 14 092 children included in the analysis, 13 266 (94.1%) were successfully checked by oximetry. Among the children with chest indrawing and/or danger signs, those with a measured oxygen saturation below  90% were more than twice as likely to have been referred as those with higher saturations (84.3% [385/457] vs 41.5% [871/2099]; P < 0.001). The availability of oximetry appeared to have increased the referral rate for severely hypoxaemic children without chest indrawing or danger signs from 0% to 27.2% (P < 0.001). In the absence of oximetry, if the relevant World Health Organization (WHO) guidelines published in 2014 had been applied, 390/568 (68.7%) severely hypoxaemic children at study health centres and 52/84 (61.9%) severely hypoxaemic children seen by community health workers would have been considered ineligible for referral. CONCLUSION: Implementation of pulse oximetry by our trainees substantially increased the referrals of Malawian children with severe hypoxaemic pneumonia. When data from oximetry were excluded, retrospective application of the guidelines published by WHO in 2014 failed to identify a considerable proportion of severely hypoxaemic children eligible only via oximetry

The NeoTree application: developing an integrated mHealth solution to improve quality of newborn care and survival in a district hospital in Malawi

More than two-thirds of newborn lives could be saved worldwide if evidence-based interventions were successfully implemented. We developed the NeoTree application to improve quality of newborn care in resource-poor countries. The NeoTree is a fully integrated digital health intervention that combines immediate data capture, entered by healthcare workers (HCW) on admission, while simultaneously providing them with evidence-based clinical decision support and newborn care education. We conducted a mixed-methods intervention development study, codeveloping and testing the NeoTree prototype with HCWs in a district hospital in Malawi. Focus groups explored the acceptability and feasibility of digital health solutions before and after implementation of the NeoTree in the clinical setting. One-to-one theoretical usability workshops and a 1-month clinical usability study informed iterative changes, gathered process and clinical data, System Usability Scale (SUS) and perceived improvements in quality of care. HCWs perceived the NeoTree to be acceptable and feasible. Mean SUS before and after the clinical usability study were high at 80.4 and 86.1, respectively (above average is >68). HCWs reported high-perceived improvements in quality of newborn care after using the NeoTree on the ward. They described improved confidence in clinical decision-making, clinical skills, critical thinking and standardisation of care. Identified factors for successful implementation included a technical support worker. Coproduction, mixed-methods approaches and user-focused iterative development were key to the development of the NeoTree prototype, which was shown to be an agile, acceptable, feasible and highly usable tool with the potential to improve the quality of newborn care in resource-poor settings

Non-treatment of children with community health worker-diagnosed fast-breathing pneumonia in rural Malawi: exploratory subanalysis of a prospective cohort study

BACKGROUND: Despite recent progress, pneumonia remains the largest infectious killer of children globally. This paper describes outcomes of not treating community-diagnosed fast-breathing pneumonia on patient recovery. METHODS: We conducted an exploratory subanalysis of an observational prospective cohort study in Malawi. We recruited children (2-59 months) diagnosed by community health workers with fast-breathing pneumonia using WHO integrated community case management (iCCM) guidelines. Children were followed at days 5 and 14 with a clinical assessment of recovery. We conducted bivariate and multivariable logistic regression for the association between treatment of fast-breathing pneumonia and recovery, adjusting for potential confounders. RESULTS: We followed up 847 children, of whom 78 (9%) had not been given antibiotics (non-treatment). Non-treatment cases had higher baseline rates of diarrhoea, non-severe hypoxaemia and fever. Non-recovery (persistence or worsening of symptoms) was 13% and 23% at day 5 in those who did receive and those who did not receive co-trimoxazole. Non-recovery, when defined as worsening of symptoms only, at day 5 was 7% in treatment and 10% in non-treatment cases. For both definitions, combined co-trimoxazole and lumefantrine-artemether (LA) treatment trended towards protection (adjusted OR (aOR) 0.28; 95% CI 0.12 to 0.68/aOR 0.29; 95% CI 0.08 to 1.01). CONCLUSION: We found that children who did not receive co-trimoxazole treatment had worse clinical outcomes; malaria co-diagnosis and treatment also play a significant role in non-recovery. Further research into non-treatment of fast-breathing pneumonia, using a pragmatic approach with consideration for malaria co-diagnosis and HIV status is needed to guide refinement of community treatment algorithms in this region

An assessment of PCV13 vaccine coverage using a repeated cross-sectional household survey in Malawi

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Malawi from November 2011 using a three dose primary series at 6, 10, and 14 weeks of age to reduce Streptococcus pneumoniae -related diseases. To date, PCV13 paediatric coverage in Malawi has not been rigorously assessed.  We used household surveys to longitudinally track paediatric PCV13 coverage in rural Malawi. METHODS: Samples of 60 randomly selected children (30 infants aged 6 weeks to 4 months and 30 aged 4-16 months) were sought in each of 20 village clinic catchment ‘basins’ of Kabudula health area, Lilongwe, Malawi between March 2012 and June 2014. Child health information was reviewed and mothers interviewed to determine each child’s PCV13 dose status and vaccine timing. The survey was completed six times in 4-8 month intervals. Survey inference was used to assess PCV13 dose coverage in each basin for each age group. All 20 basins were pooled to assess area-wide vaccination coverage over time, by age in months, and adherence to the vaccination schedule. RESULTS: We surveyed a total of 8,562 children in six surveys; 82% were in the older age group. Overall, in age-eligible children, two-dose and three-dose coverage increased from 30% to 85% and 10% to 86%, respectively, between March 2012 and June 2014.  PCV13 coverage was higher in the older age group in all surveys. Although it varied by basin, PCV13 coverage was consistently delayed: median ages at first, second and third doses were 9, 15 and 21 weeks, respectively. CONCLUSION: In our rural study area, PCV13 introduction did not meet the Malawi Ministry of Health one-year three-dose 90% coverage target, but after 2 years reached levels likely to reduce the prevalence of both invasive and non-invasive paediatric pneumococcal diseases. Better adherence to the PCV13 schedule may reduce pneumococcal disease in younger Malawian children

Antibiotic treatment failure in children aged 1 to 59 months with World Health Organization-defined severe pneumonia in Malawi: A CPAP IMPACT trial secondary analysis

Background Pneumonia is a leading cause of mortality in children <5 years globally. Early identification of hospitalized children with pneumonia who may fail antibiotics could improve outcomes. We conducted a secondary analysis from the Malawi CPAP IMPACT trial evaluating risk factors for antibiotic failure among children hospitalized with pneumonia. Methods Participants were 1–59 months old with World Health Organization-defined severe pneumonia and hypoxemia, severe malnutrition, and/or HIV exposure/infection. All participants received intravenous antibiotics per standard care. First-line antibiotics were benzylpenicillin and gentamicin for five days. Study staff assessed patients for first-line antibiotic failure daily between days 3–6. When identified, patients failing antibiotics were switched to second-line ceftriaxone. Analyses excluded children receiving ceftriaxone and/or deceased by hospital day two. We compared characteristics between patients with and without treatment failure and fit multivariable logistic regression models to evaluate associations between treatment failure and admission characteristics. Results From June 2015–March 2018, 644 children were enrolled and 538 analyzed. Antibiotic failure was identified in 251 (46.7%) participants, and 19/251 (7.6%) died. Treatment failure occurred more frequently with severe malnutrition (50.2% (126/251) vs 28.2% (81/287), p<0.001) and amongst those dwelling 10km from a health facility (22.3% (56/251) vs 15.3% (44/287), p = 0.026). Severe malnutrition occurred more frequently among children living 10km from a health facility than those living <10km (49.0% (49/100) vs 35.7% (275/ 428), p = 0.014). Children with severe malnutrition (adjusted odds ratio (aOR) 2.2 (95% CI 1.52, 3.24), p<0.001) and pre-hospital antibiotics ((aOR 1.47, 95% CI 1.01, 2.14), p = 0.043) had an elevated aOR for antibiotic treatment failure. Conclusion Severe malnutrition and pre-hospital antibiotic use predicted antibiotic treatment failure in this high-risk severe pneumonia pediatric population in Malawi. Our findings suggest addressing complex sociomedical conditions like severe malnutrition and improving pneumonia etiology diagnostics will be key for better targeting interventions to improve childhood pneumonia outcomes

Implementation of World Health Organization Integrated Management of Childhood Illnesses (IMCI) Guidelines for the Assessment of Pneumonia in the Under 5s in Rural Malawi

The Cooking and Pneumonia Study (CAPS) is a pragmatic cluster-level randomized controlled trial of the effect of an advanced cookstove intervention on pneumonia in children under the age of 5 years (under 5s) in Malawi (www.capstudy.org). The primary outcome of the trial is the incidence of pneumonia during a two-year follow-up period, as diagnosed by healthcare providers who are using the World Health Organization (WHO) integrated management of childhood illnesses (IMCI) pneumonia assessment protocol and who are blinded to the trial arms. We evaluated the quality of pneumonia assessment in under 5s in this setting via a cross-sectional study of provider-patient encounters at nine outpatient clinics located within the catchment area of 150 village-level clusters enrolled in the trial across the two study locations of Chikhwawa and Karonga, Malawi, between May and June 2015 using the IMCI guidelines as a benchmark. Data were collected using a key equipment checklist, an IMCI pneumonia knowledge test, and a clinical evaluation checklist. The median number of key equipment items available was 6 (range 4 to 7) out of a possible 7. The median score on the IMCI pneumonia knowledge test among 23 clinicians was 75% (range 60% to 89%). Among a total of 176 consultations performed by 15 clinicians, a median of 9 (range 3 to 13) out of 13 clinical evaluation tasks were performed. Overall, the clinicians were adequately equipped for the assessment of sick children, had good knowledge of the IMCI guidelines, and conducted largely thorough clinical evaluations. We recommend the simple pragmatic approach to quality assurance described herein for similar studies conducted in challenging research settings