Carina King

Cause-specific neonatal mortality: analysis of 3772 neonatal deaths in Nepal, Bangladesh, Malawi and India

Objective Understanding the causes of death is key to tackling the burden of three million annual neonatal deaths. Resource-poor settings lack effective vital registration systems for births, deaths and causes of death. We set out to describe cause-specific neonatal mortality in rural areas of Malawi, Bangladesh, Nepal and rural and urban India using verbal autopsy (VA) data. Design We prospectively recorded births, neonatal deaths and stillbirths in seven population surveillance sites. VAs were carried out to ascertain cause of death. We applied descriptive epidemiological techniques and the InterVA method to characterise the burden, timing and causes of neonatal mortality at each site. Results Analysis included 3772 neonatal deaths and 3256 stillbirths. Between 63% and 82% of neonatal deaths occurred in the first week of life, and males were more likely to die than females. Prematurity, birth asphyxia and infections accounted for most neonatal deaths, but important subnational and regional differences were observed. More than one-third of deaths in urban India were attributed to asphyxia, making it the leading cause of death in this setting. Conclusions Population-based VA methods can fill information gaps on the burden and causes of neonatal mortality in resource-poor and data-poor settings. Local data should be used to inform and monitor the implementation of interventions to improve newborn health. High rates of home births demand a particular focus on community interventions to improve hygienic delivery and essential newborn care.

Community-linked maternal death review (CLMDR) to measure and prevent maternal mortality: a pilot study in rural Malawi.

Background In Malawi, maternal mortality remains high. Existing maternal death reviews fail to adequately review most deaths, or capture those that occur outside the health system. We assessed the value of community involvement to improve capture and response to community maternal deaths. Methods We designed and piloted a community-linked maternal death review (CLMDR) process in Mchinji District, Malawi, which partnered community and health facility stakeholders to identify and review maternal deaths and generate actions to prevent future deaths. The CLMDR process involved five stages: community verbal autopsy, community and facility review meetings, a public meeting and bimonthly reviews involving both community and facility representatives. Results The CLMDR process was found to be comparable to a previous research-driven surveillance system at identifying deaths in Mchinji District (population 456 500 in 2008). 52 maternal deaths were identified between July 2011 and June 2012, 27 (52%) of which would not have been identified without community involvement. Based on district estimates of population (500 000) and crude birth rate (35 births per 1000 population), the maternal mortality ratio was around 300 maternal deaths per 100 000 live births. Of the 41 cases that started the CLMDR process, 28 (68%) completed all five stages. We found the CLMDR process to increase the quantity of information available and to involve a wider range of stakeholders in maternal death review (MDR). The process resulted in high rates of completion of community-planned actions (82%), and district hospital (67%) and health centre (65%) actions to prevent maternal deaths. Conclusions CLMDR is an important addition to the established forms of MDR. It shows potential as a maternal death surveillance system, and may be applicable to similar contexts with high maternal mortality.

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

Abstract 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.

Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi) from Malawi

Background Pneumonia is the leading infectious cause of under-5 mortality in sub-Saharan Africa. Clinical prediction tools may aide case classification, triage, and allocation of hospital resources. We performed an external validation of two published prediction tools and compared this to a locally developed tool to identify children admitted with pneumonia at increased risk for in-hospital mortality in Malawi. Methods We retrospectively analyzed the performance of the Respiratory Index of Severity in Children (RISC) and modified RISC (mRISC) scores in a child pneumonia dataset prospectively collected during routine care at seven hospitals in Malawi between 2011–2014. RISC has both an HIV-infected and HIV-uninfected tool. A local score (RISC-Malawi) was developed using multivariable logistic regression with missing data multiply imputed using chained equations. Score performances were assessed using c-statistics, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood statistics. Results 16,475 in-patient pneumonia episodes were recorded (case-fatality rate (CFR): 3.2%), 9,533 with complete data (CFR: 2.0%). The c-statistic for the RISC (HIV-uninfected) score, used to assess its ability to differentiate between children who survived to discharge and those that died, was 0.72. The RISC-Malawi score, using mid-upper arm circumference as an indicator of malnutrition severity, had a c-statistic of 0.79. We were unable to perform a comprehensive external validation of RISC (HIV-infected) and mRISC as both scores include parameters that were not routinely documented variables in our dataset. Conclusion In our population of Malawian children with WHO-defined pneumonia, the RISC (HIV-uninfected) score identified those at high risk for in-hospital mortality. However the refinement of parameters and resultant creation of RISC-Malawi improved performance. Next steps include prospectively studying both scores to determine if incorporation into routine care delivery can have a meaningful impact on in-hospital CFRs of children with WHO-defined pneumonia.

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.

Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort study

Summary Background Rotavirus is a major contributor to child mortality. The effect of rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but not low-income settings, where mortality is high and vaccine effectiveness in reducing admissions to hospital is lower. Empirical population-based mortality studies have not been done in any setting. Malawi introduced monovalent rotavirus vaccine (RV1) in October, 2012. We aimed to investigate the impact and effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in infants aged 10–51 weeks. Methods In this population-based cohort study, we included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central Malawi and analysed data on those surviving 10 weeks. Individual vaccination status was extracted from caregiver-held records or report at home visits at 4 months and 1 year of age. Survival to 1 year was confirmed at home visit, or cause of death ascertained by verbal autopsy. We assessed impact (1 minus mortality rate ratio following vs before vaccine introduction) using Poisson regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed effectiveness (1 minus hazard ratio) using Cox regression. Findings Between Jan 1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom 38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus zero-dose effectiveness analysis included 28 141 infants, of whom 101 had diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality declined by 31% (95% CI 1–52; p=0·04) after RV1 introduction. Effectiveness against diarrhoea-mortality was 34% (95% CI –28 to 66; p=0·22). Interpretation RV1 was associated with substantial reduction in diarrhoea-associated deaths among infants in this rural sub-Saharan African setting. These data add considerable weight to evidence showing the impact of rotavirus vaccine programmes. Funding Wellcome Trust and GlaxoSmithKline Biologicals.

The equity impact of community women’s groups to reduce neonatal mortality: a meta-analysis of four cluster randomized trials

Abstract Background Socioeconomic inequalities in neonatal mortality are substantial in many developing countries. Little is known about how to address this problem. Trials in Asia and Africa have shown strong impacts on neonatal mortality of a participatory learning and action intervention with women’s groups. Whether this intervention also reduces mortality inequalities remains unknown. We describe the equity impact of this women’s groups intervention on the neonatal mortality rate (NMR) across socioeconomic strata. Methods We conducted a meta-analysis of all four participatory women’s group interventions that were shown to be highly effective in cluster randomized trials in India, Nepal, Bangladesh and Malawi. We estimated intervention effects on NMR and health behaviours for lower and higher socioeconomic strata using random effects logistic regression analysis. Differences in effect between strata were tested. Results Analysis of 69120 live births and 2505 neonatal deaths shows that the intervention strongly reduced the NMR in lower (50–63% reduction depending on the measure of socioeconomic position used) and higher (35–44%) socioeconomic strata. The intervention did not show evidence of ‘elite-capture’: among the most marginalized populations, the NMR in intervention areas was 63% lower [95% confidence interval (CI) 48–74%] than in control areas, compared with 35% (95% CI: 15–50%) lower among the less marginalized in the last trial year (P-value for difference between most/less marginalized: 0.009). The intervention strongly improved home care practices, with no systematic socioeconomic differences in effect. Conclusions Participatory women’s groups with high population coverage benefit the survival chances of newborns from all socioeconomic strata, and perhaps especially those born into the most deprived households.

Incidence and degree of hypoxaemia in Malawian infants under 2 months of age presenting to district hospitals and its correlation with mortality: a retrospective analysis

Abstract Background Pneumonia is a leading cause of death in Malawian infants under 2 months of age. Consensus defines hypoxaemia in infants as a peripheral capillary oxygen saturation (SpO 2 ) of less than 90%. We aimed to estimate the incidence and degree of hypoxaemia and its correlation with mortality in infants younger than 2 months presenting to district hospitals in Malawi. Methods We retrospectively analysed a child pneumonia surveillance dataset prospectively collected during routine care at seven hospitals in Malawi between 2011 and 2014. Infants aged 0–2 months with pneumonia according to 2012 WHO case management guidelines were included. We used logistic regression to determine correlation between degree of hypoxaemia and in-hospital death. Findings 1810 infant pneumonia admissions were analysed. The case fatality rate was 3·6% (n=65). SpO 2 could not be measured in 8·5% (n=154) of patients. Median SpO 2 was 96% (IQR 91–98). Infants for whom SpO2 measurement was successful versus unsuccessful had a similar prevalence of chest indrawing (85·6% vs 79·2%) and WHO danger signs (68·4% vs 61·0%; p=0·064), and the distribution of girls (40·9% vs 39·6%) was also comparable. Compared with infants with an SpO 2 of 93–100% (n=1160), infants with an SpO 2 of 90–92% (n=187) or 2 was not measurable (n=154) had a greatly increased adjusted odds of death compared with infants with a SpO2 of 93–100% (aOR 17·5, 95% CI 7·5–40·8). Interpretation The case definition of hypoxaemia in infants less than 2 months of age warrants re-evaluation. Infants with an SpO 2 of 90–92% have a higher odds of death than those with a SpO 2 of 93–100%. Infants for whom SpO 2 could not be measured, despite having similar demographic and physical examination findings, had a higher odds ratio for death than any other observed group. Interestingly, these infants had a lower rate of WHO danger signs, but probably had severe disease such as shock with diminished peripheral perfusion resulting in inability to measure SpO 2 . WHO danger signs may not adequately capture such physiological derangements. The inability to measure pulse oximetry is clinically meaningful in our setting. Implementation of compulsory SpO 2 measurement could result in improved referral rates and recognition of severe disease in infants younger than 2 months of age with pneumonia. Funding None.

Designing a brief behaviour change intervention to reduce sexually transmitted infections: a discrete choice experiment.

To understand whether people attending sexual health (SH) clinics are willing to participate in a brief behavioural change intervention (BBCI) to reduce the likelihood of future sexually transmitted infections (STIs) and to understand their preferences for different service designs, we conducted a discrete choice experiment (DCE) with young heterosexual adults (aged 16–25 years), and men who have sex with men (MSM) aged 16 or above, attending SH clinics in England. Data from 368 participants showed that people particularly valued BBCIs that involved talking (OR 1.45; 95%CI 1.35, 1.57 compared with an ‘email or text’-based BBCIs), preferably with a health care professional rather than a peer. Findings also showed that 26% of respondents preferred ‘email/texts’ to all other options; the remaining 14% preferred not to participate in any of the offered BBCIs. These results suggest that most people attending SH clinics in England are likely to participate in a BBCI if offered, but the type/format of the BBCI is likely to be the single important determinant of uptake rather than characteristics such as the length and the number of sessions. Moreover, participants generally favoured ‘talking’-based options rather than digital alternatives, which are likely to require the most resources to implement.