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 imputation with chained equations, and pattern mixture modeling were used to determine the association between peripheral capillary oxyhemoglobin saturation (SpO2) levels and hospital mortality. We describe outpatient clinician hospital referral recommendations based on clinical characteristics and SpO2 distributions. Among 1,879 analyzed cases, SpO2 < 90% was more prevalent among outpatient health center cases compared with 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 compared with infants at health centers (67.7% versus 56.6%, P < 0.001) and most hospitalized infants were boys (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 a SpO2 ≤ 92%. Infants with unobtainable SpO2 readings should be considered a high-risk group, and hospital referral of these cases may be appropriate.

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.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An Observational Study.

BACKGROUND: The pneumococcal conjugate vaccine's (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia. METHODS AND FINDINGS: Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children <5 years at seven hospitals, 18 health centres, and with 38 community health workers in two districts, central Malawi. Eligible children had clinical pneumonia per Malawi guidelines, defined as fast breathing only, chest indrawing +/- fast breathing, or, ≥1 clinical danger sign. Since pulse oximetry was not in the Malawi guidelines, oxygenation <90% defined hypoxemic pneumonia, a distinct category from clinical pneumonia. We quantified the pneumonia case burden and rates in two ways. We compared the period immediately following vaccine introduction (early) to the period with >75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children <5 years. We observed a shift towards disease without danger signs, as the proportion of cases with danger signs decreased by 65% (-46%, -77%, p<0.0001). These results were generally robust to plausible alternative model specifications. CONCLUSIONS: Thirty months after PCV13 introduction in Malawi, the health system burden and rates of the severest forms of childhood pneumonia, including hypoxemia and death, have markedly decreased.

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.

Measurement and valuation of health providers' time for the management of childhood pneumonia in rural Malawi: an empirical study.

BACKGROUND: Human resources are a major cost driver in childhood pneumonia case management. Introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in Malawi can lead to savings on staff time and salaries due to reductions in pneumonia cases requiring admission. Reliable estimates of human resource costs are vital for use in economic evaluations of PCV-13 introduction. METHODS: Twenty-eight severe and twenty-four very severe pneumonia inpatients under the age of five were tracked from admission to discharge by paediatric ward staff using self-administered timesheets at Mchinji District Hospital between June and August 2012. All activities performed and the time spent on each activity were recorded. A monetary value was assigned to the time by allocating a corresponding percentage of the health workers' salary. All costs are reported in 2012 US$. RESULTS: A total of 1,017 entries, grouped according to 22 different activity labels, were recorded during the observation period. On average, 99 min (standard deviation, SD = 46) were spent on each admission: 93 (SD = 38) for severe and 106 (SD = 55) for very severe cases. Approximately 40 % of activities involved monitoring and stabilization, including administering non-drug therapies such as oxygen. A further 35 % of the time was spent on injecting antibiotics. Nurses provided 60 % of the total time spent on pneumonia admissions, clinicians 25 % and support staff 15 %. Human resource costs were approximately US$ 2 per bed-day and, on average, US$ 29.5 per severe pneumonia admission and US$ 37.7 per very severe admission. CONCLUSIONS: Self-reporting was successfully used in this context to generate reliable estimates of human resource time and costs of childhood pneumonia treatment. Assuming vaccine efficacy of 41 % and 90 % coverage, PCV-13 introduction in Malawi can save over US$ 2 million per year in staff costs alone.

Spatial modelling of perinatal mortality in Mchinji, Malawi.

BACKGROUND: Annual global estimates of perinatal mortality show Malawi among sub-Saharan Africa with the highest rates. Targeted interventions are required to reduce this mortality. This study aimed to quantify small-scale geographical variations in perinatal mortality, and estimate risk factors associated with perinatal mortality in Mchinji district. METHODS: As part of the 2005-2010 randomised controlled trial conducted in Mchinji district, prospective data from the control arm of the trial was collected on perinatal mortality. A Structured Additive Regression model was applied to account for influence of both individual and contextual factors, and jointly accounting for nonlinear effects of continuous covariates, spatially structured variation, unstructured heterogeneity and fixed effects. Modelling and inference used a fully Bayesian approach. RESULTS: Factors associated with reduced perinatal mortality were: previous pregnancy; early and consistent use of antenatal care; syphilis test; abdominal examination; pregnancy danger signs advice; skilled birth attendant; normal labour duration; gestation period of at least 9 months; and normal delivery. Perinatals whose mothers had blood test were associated with high probability of dying. Perinatals from mothers between 16 and 40 years had reduced prevalence of dying while those aged less than 16 years and greater than 40 years were associated with higher prevalence of dying. After accounting for all significant covariates, high perinatal mortality was observed in eastern part of the district whereas low perinatal mortality was observed in the western part. CONCLUSION: Targeting health interventions to higher risk areas and ensuring universal coverage are promising approaches for promoting equity and reducing perinatal mortality.

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.

Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

BACKGROUND: Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa. METHOD: We prospectively followed a cohort of children (2-59 months), diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO) integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping. RESULTS: We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted). The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26) were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56). CONCLUSION: This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.

The role of the parents' perception of the postpartum period and knowledge of maternal mortality in uptake of postnatal care: a qualitative exploration in Malawi.

BACKGROUND: Postpartum is the most risky period for both mothers and newborn babies. However, existing evidence suggests that utilization of postnatal care is relatively lower when compared to uptake of other similar health care services. Therefore, the aim of this study was to examine the perceptions of parents toward the postpartum period and postnatal care in order to deepen our understanding of the maternal care-seeking practices after childbirth. METHODS: A descriptive qualitative study, comprising four focus group discussions with 50 parents aged between 18 and 35 years, was conducted in Malawi between January and March 2014. Only young men and women who had either given birth or fathered a baby within 12 months prior to the study were eligible to participate in this study. This was to ensure that only participants who had recent first-hand postpartum experience were included. Local leaders purposively identified all parents who met the inclusion criteria and then simple random sampling was used to select participants from this pool of parents. Data analysis followed the six steps of thematic approach developed by Braun and Clarke, and NVivo software aided the process. FINDINGS: The parents interviewed described the various factors relating to pregnancy, childbirth, and postpartum periods that may possibly influence uptake of postnatal care. These factors were categorized into the following three themes: beliefs about the causes of maternal morbidity and mortality; risks associated with the pregnancy, childbirth and postpartum periods; and the importance of and barriers to postnatal care. Most participants perceived pregnancy and childbirth as the most risky periods to women, and their understanding of the causes of maternal death differed considerably from the existing evidence. In addition, segregation of mother and baby care in the clinics was identified as one of the potential barriers to postnatal care. CONCLUSION: The study findings suggest that parents' perception of the postpartum period and postnatal care as well as their knowledge of maternal morbidity and mortality play a vital role in the uptake of postnatal care. The study has also established that lack of knowledge of postnatal care, long waiting time for treatment, and separation of the mother and baby care in clinics are some of the key barriers to postnatal care. We recommend massive maternal health education programs as well as the integration of all postdelivery health care services provided in clinics, so that mothers and neonates receive health care together.

Opportunities to improve postpartum care for mothers and infants: design of context-specific packages of postpartum interventions in rural districts in four sub-Saharan African countries.

BACKGROUND: Postpartum maternal and infant mortality is high in sub-Saharan Africa and improving postpartum care as a strategy to enhance maternal and infant health has been neglected. We describe the design and selection of suitable, context-specific interventions that have the potential to improve postpartum care. METHODS: The study is implemented in rural districts in Burkina Faso, Kenya, Malawi and Mozambique. We used the four steps 'systems thinking' approach to design and select interventions: 1) we conducted a stakeholder analysis to identify and convene stakeholders; 2) we organised stakeholders causal analysis workshops in which the local postpartum situation and challenges and possible interventions were discussed; 3) based on comprehensive needs assessment findings, inputs from the stakeholders and existing knowledge regarding good postpartum care, a list of potential interventions was designed, and; 4) the stakeholders selected and agreed upon final context-specific intervention packages to be implemented to improve postpartum care. RESULTS: Needs assessment findings showed that in all study countries maternal, newborn and child health is a national priority but specific policies for postpartum care are weak and there is very little evidence of effective postpartum care implementation. In the study districts few women received postpartum care during the first week after childbirth (25 % in Burkina Faso, 33 % in Kenya, 41 % in Malawi, 40 % in Mozambique). Based on these findings the interventions selected by stakeholders mainly focused on increasing the availability and provision of postpartum services and improving the quality of postpartum care through strengthening postpartum services and care at facility and community level. This includes the introduction of postpartum home visits, strengthening postpartum outreach services, integration of postpartum services for the mother in child immunisation clinics, distribution of postpartum care guidelines among health workers and upgrading postpartum care knowledge and skills through training. CONCLUSION: There are extensive gaps in availability and provision of postpartum care for mothers and infants. Acknowledging these gaps and involving relevant stakeholders are important to design and select sustainable, context-specific packages of interventions to improve postpartum care.

Development, reliability and validity of the Chichewa WHOQOL-BREF in adults in Lilongwe, Malawi.

BACKGROUND: Quality of life measurement is a useful addition to measurement of health outcomes in evaluation of the benefits of many health and welfare interventions. The WHOQOL-BREF measures quality of life from a broad multi-dimensional perspective but was not used in Malawi. The objective of this study was to translate the WHOQOL-BREF questionnaire into the main local language of Malawi: Chichewa; and to validate it quantitatively with respect to internal consistency, domain structure, and discriminant validity for this context. METHODS: WHO-mandated guidelines were followed for translation, adaptation, pre-testing (focus groups), piloting (patient interviews) and data coding. Analyses using descriptive statistics, correlation and regression were undertaken to investigate the validity of the WHOQOL-BREF in the ways described above. Additional regression analyses examined the impact of socio-demographic variables on the domain scores. RESULTS: 309 respondents completed the questionnaire (with >98% response rates for all questions except Q21 (sex life)). 259 were sick with a variety of health problems, and 50 were considered healthy. All domains showed adequate internal consistency (Cronbach's alpha > =0.7) with all item scores also most highly correlated with the scores of their assigned domain. All domain scores varied by health problem, and more depressed respondents had significantly lower scores in all domains than those less depressed. Domain scores and their associations with socio-demographic variables are presented and discussed. CONCLUSION: This study demonstrates that the new Chichewa WHOQOL-BREF questionnaire is acceptable and comprehensible to respondents in Malawi. The questionnaire also passed a number of tests of the validity of its psychometric properties. In the pilot population we found that older age was associated with lower Physical domain scores. Conversely, higher levels of educational attainment were found to be associated with higher quality of life in all domains except for Social Relationships. Respondents living as married or single were found to have higher quality of life in the Physical, Psychological and Social domains, and those who were widowed lower Physical quality of life.