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.

BACKGROUND: 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. CONCLUSIONS: 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.

Exploring the equity impact of a maternal and newborn health intervention: a qualitative study of participatory women's groups in rural South Asia and Africa.

BACKGROUND: A consensus is developing on interventions to improve newborn survival, but little is known about how to reduce socioeconomic inequalities in newborn mortality in low- and middle-income countries. Participatory learning and action (PLA) through women's groups can improve newborn survival and home care practices equitably across socioeconomic strata, as shown in cluster randomised controlled trials. We conducted a qualitative study to understand the mechanisms that led to the equitable impact of the PLA approach across socioeconomic strata in four trial sites in India, Nepal, Bangladesh, and Malawi. METHODS: We conducted 42 focus group discussions (FGDs) with women who had attended groups and women who had not attended, in poor and better-off communities. We also interviewed six better-off women and nine poor women who had delivered babies during the trials and had demonstrated recommended behaviours. We conducted 12 key informant interviews and five FGDs with women's group facilitators and fieldworkers. RESULTS: Women's groups addressed a knowledge deficit in poor and better-off women. Women were engaged through visual learning and participatory tools, and learned from the facilitator and each other. Facilitators enabled inclusion of all socioeconomic strata, ensuring that strategies were low-cost and that discussions and advice were relevant. Groups provided a social support network that addressed some financial barriers to care and gave women the confidence to promote behaviour change. Information was disseminated through home visits and other strategies. The social process of learning and action, which led to increased knowledge, confidence to act, and acceptability of recommended practices, was key to ensuring behaviour change across social strata. These equitable effects were enabled by the accessibility, relevance, and engaging format of the intervention. CONCLUSIONS: Participatory learning and action led to increased knowledge, confidence to act, and acceptability of recommended practices. The equitable behavioural effects were facilitated by the accessibility, relevance, and engaging format of the intervention across socioeconomic groups, and by reaching-out to parts of the population usually not accessed. A PLA approach improved health behaviours across socioeconomic strata in rural communities, around issues for which there was a knowledge deficit and where simple changes could be made at home.

Effects of women's groups practising participatory learning and action on preventive and care-seeking behaviours to reduce neonatal mortality: A meta-analysis of cluster-randomised trials.

BACKGROUND: The World Health Organization recommends participatory learning and action (PLA) in women's groups to improve maternal and newborn health, particularly in rural settings with low access to health services. There have been calls to understand the pathways through which this community intervention may affect neonatal mortality. We examined the effect of women's groups on key antenatal, delivery, and postnatal behaviours in order to understand pathways to mortality reduction. METHODS AND FINDINGS: We conducted a meta-analysis using data from 7 cluster-randomised controlled trials that took place between 2001 and 2012 in rural India (2 trials), urban India (1 trial), rural Bangladesh (2 trials), rural Nepal (1 trial), and rural Malawi (1 trial), with the number of participants ranging between 6,125 and 29,901 live births. Behavioural outcomes included appropriate antenatal care, facility delivery, use of a safe delivery kit, hand washing by the birth attendant prior to delivery, use of a sterilised instrument to cut the umbilical cord, immediate wrapping of the newborn after delivery, delayed bathing of the newborn, early initiation of breastfeeding, and exclusive breastfeeding. We used 2-stage meta-analysis techniques to estimate the effect of the women's group intervention on behavioural outcomes. In the first stage, we used random effects models with individual patient data to assess the effect of groups on outcomes separately for the different trials. In the second stage of the meta-analysis, random effects models were applied using summary-level estimates calculated in the first stage of the analysis. To determine whether behaviour change was related to group attendance, we used random effects models to assess associations between outcomes and the following categories of group attendance and allocation: women attending a group and allocated to the intervention arm; women not attending a group but allocated to the intervention arm; and women allocated to the control arm. Overall, women's groups practising PLA improved behaviours during and after home deliveries, including the use of safe delivery kits (odds ratio [OR] 2.92, 95% CI 2.02-4.22; I2 = 63.7%, 95% CI 4.4%-86.2%), use of a sterile blade to cut the umbilical cord (1.88, 1.25-2.82; 67.6%, 16.1%-87.5%), birth attendant washing hands prior to delivery (1.87, 1.19-2.95; 79%, 53.8%-90.4%), delayed bathing of the newborn for at least 24 hours (1.47, 1.09-1.99; 68.0%, 29.2%-85.6%), and wrapping the newborn within 10 minutes of delivery (1.27, 1.02-1.60; 0.0%, 0%-79.2%). Effects were partly dependent on the proportion of pregnant women attending groups. We did not find evidence of effects on uptake of antenatal care (OR 1.03, 95% CI 0.77-1.38; I2 = 86.3%, 95% CI 73.8%-92.8%), facility delivery (1.02, 0.93-1.12; 21.4%, 0%-65.8%), initiating breastfeeding within 1 hour (1.08, 0.85-1.39; 76.6%, 50.9%-88.8%), or exclusive breastfeeding for 6 weeks after delivery (1.18, 0.93-1.48; 72.9%, 37.8%-88.2%). The main limitation of our analysis is the high degree of heterogeneity for effects on most behaviours, possibly due to the limited number of trials involving women's groups and context-specific effects. CONCLUSIONS: This meta-analysis suggests that women's groups practising PLA improve key behaviours on the pathway to neonatal mortality, with the strongest evidence for home care behaviours and practices during home deliveries. A lack of consistency in improved behaviours across all trials may reflect differences in local priorities, capabilities, and the responsiveness of health services. Future research could address the mechanisms behind how PLA improves survival, in order to adapt this method to improve maternal and newborn health in different contexts, as well as improve other outcomes across the continuum of care for women, children, and adolescents.

Effect of women's groups and volunteer peer counselling on rates of mortality, morbidity, and health behaviours in mothers and children in rural Malawi (MaiMwana): a factorial, cluster-randomised controlled trial.

BACKGROUND: Women's groups and health education by peer counsellors can improve the health of mothers and children. We assessed their effects on mortality and breastfeeding rates in rural Malawi. METHODS: We did a 2×2 factorial, cluster-randomised trial in 185,888 people in Mchinji district. 48 equal-sized clusters were randomly allocated to four groups with a computer-generated number sequence. 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems. 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care. Primary outcomes for the women's group intervention were maternal, perinatal, neonatal, and infant mortality rates (MMR, PMR, NMR, and IMR, respectively); and for the peer counselling were IMR and exclusive breastfeeding (EBF) rates. Analysis was by intention to treat. The trial is registered as ISRCTN06477126. FINDINGS: We monitored outcomes of 26,262 births between 2005 and 2009. In a factorial model adjusted only for clustering and the volunteer peer counselling intervention, in women's group areas, for years 2 and 3, we noted non-significant decreases in NMR (odds ratio 0.93, 0.64-1.35) and MMR (0.54, 0.28-1.04). After adjustment for parity, socioeconomic quintile, and baseline measures, effects were larger for NMR (0.85, 0.59-1.22) and MMR (0.48, 0.26-0.91). Because of the interaction between the two interventions, a stratified analysis was done. For women's groups, in adjusted analyses, MMR fell by 74% (0.26, 0.10-0.70), and NMR by 41% (0.59, 0.40-0.86) in areas with no peer counsellors, but there was no effect in areas with counsellors (1.09, 0.40-2.98, and 1.38, 0.75-2.54). Factorial analysis for the peer counselling intervention for years 1-3 showed a fall in IMR of 18% (0.82, 0.67-1.00) and an improvement in EBF rates (2.42, 1.48-3.96). The results of the stratified, adjusted analysis showed a 36% reduction in IMR (0.64, 0.48-0.85) but no effect on EBF (1.18, 0.63-2.25) in areas without women's groups, and in areas with women's groups there was no effect on IMR (1.05, 0.82-1.36) and an increase in EBF (5.02, 2.67-9.44). The cost of women's groups was US$114 per year of life lost (YLL) averted and that of peer counsellors was $33 per YLL averted, using stratified data from single intervention comparisons. INTERPRETATION: Community mobilisation through women's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural populations in Africa. FUNDING: Saving Newborn Lives, UK Department for International Development, and Wellcome Trust.

Women's groups practising participatory learning and action to improve maternal and newborn health in low-resource settings: a systematic review and meta-analysis.

BACKGROUND: Maternal and neonatal mortality rates remain high in many low-income and middle-income countries. Different approaches for the improvement of birth outcomes have been used in community-based interventions, with heterogeneous effects on survival. We assessed the effects of women's groups practising participatory learning and action, compared with usual care, on birth outcomes in low-resource settings. METHODS: We did a systematic review and meta-analysis of randomised controlled trials undertaken in Bangladesh, India, Malawi, and Nepal in which the effects of women's groups practising participatory learning and action were assessed to identify population-level predictors of effect on maternal mortality, neonatal mortality, and stillbirths. We also reviewed the cost-effectiveness of the women's group intervention and estimated its potential effect at scale in Countdown countries. FINDINGS: Seven trials (119,428 births) met the inclusion criteria. Meta-analyses of all trials showed that exposure to women's groups was associated with a 37% reduction in maternal mortality (odds ratio 0.63, 95% CI 0.32-0.94), a 23% reduction in neonatal mortality (0.77, 0.65-0.90), and a 9% non-significant reduction in stillbirths (0.91, 0.79-1.03), with high heterogeneity for maternal (I(2)=58.8%, p=0.024) and neonatal results (I(2)=64.7%, p=0.009). In the meta-regression analyses, the proportion of pregnant women in groups was linearly associated with reduction in both maternal and neonatal mortality (p=0.026 and p=0.011, respectively). A subgroup analysis of the four studies in which at least 30% of pregnant women participated in groups showed a 55% reduction in maternal mortality (0.45, 0.17-0.73) and a 33% reduction in neonatal mortality (0.67, 0.59-0.74). The intervention was cost effective by WHO standards and could save an estimated 283,000 newborn infants and 41,100 mothers per year if implemented in rural areas of 74 Countdown countries. INTERPRETATION: With the participation of at least a third of pregnant women and adequate population coverage, women's groups practising participatory learning and action are a cost-effective strategy to improve maternal and neonatal survival in low-resource settings. FUNDING: Wellcome Trust, Ammalife, and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Birmingham and the Black Country programme.

Added value of an open narrative in verbal autopsies: a mixed-methods evaluation from Malawi.

Background: The WHO standardised verbal autopsy (VA) instrument includes closed questions, ascertaining signs and symptoms of illness preceding death, and an optional open narrative. As VA analyses increasingly use automated algorithms, inclusion of narratives should be justified. We evaluated the role of open narratives on VA processes, data quality and respondent's emotional stress. Methods: A mixed-methods analysis was conducted using VA data for child deaths (0-59 months), between April 2013 and November 2016 in Mchinji district, Malawi. Deaths were prospectively randomised to receive closed questions only or open narrative followed by closed questions. On concluding the VA, interviewers self-completed questions on respondents' emotional stress. Logistic regression was used to determine associations with visible emotional distress during VAs. A group discussion with interviewers was conducted at the project end, to understand field experiences and explore future recommendations; data were coded using deductive themes. Results: 2509 VAs were included, with 49.8% (n=1341) randomised to open narratives. Narratives lasted a median of 7 minuntes (range: 1-113). Interviewers described improved rapport and felt narratives improved data quality, although there was no difference in the proportion of deaths with an indeterminate cause using an automated algorithm (5.3% vs 6.1%). The majority of respondents did not display visible emotional stress (81%). Those with a narrative had higher, but not statistically significant, odds of emotional distress (adjusted OR: 1.20; 95% CI: 0.98 to 1.47). Factors associated with emotional stress were: infant deaths versus neonates; deaths at a health centre or en-route to hospital versus home; and higher socioeconomic status. Non-parental respondents and increased time between death and interview were associated with lower odds of emotional distress. Conclusion: Conducting an open narrative may help build rapport, something valued by the interviewers. However, additional time and emotional burdens should be further justified, with quality and utility of narratives promoted through standardised recommendations.

Population impact and effectiveness of sequential 13-valent pneumococcal conjugate and monovalent rotavirus vaccine introduction on infant mortality: prospective birth cohort studies from Malawi.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RV) are key tools for reducing common causes of infant mortality. However, measurement of population-level mortality impact is lacking from sub-Saharan Africa. We evaluated mortality impact and vaccine effectiveness (VE) of PCV13 introduced in November 2011, with subsequent RV1 roll-out in October 2012, in Malawi. METHODS: We conducted two independent community-based birth cohort studies. Study 1, in northern Malawi (40000population), evaluated population impact using change-point analysis and negative-binomial regression of non-traumatic 14-51-week infant mortality preintroduction (1 January 2004 to 31 September 2011) and postintroduction (1 October 2011 to 1 July 2019), and against three-dose coverage. Study 2, in central Malawi (465 000 population), was recruited from 24 November 2011 to 1 June 2015. In the absence of preintroduction data, individual three-dose versus zero-dose VE was estimated using individual-level Cox survival models. In both cohorts, infants were followed with household visits to ascertain vaccination, socioeconomic and survival status. Verbal autopsies were conducted for deaths. RESULTS: Study 1 included 20 291 live births and 216 infant deaths. Mortality decreased by 28.6% (95% CI: 15.3 to 39.8) post-PCV13 introduction. A change point was identified in November 2012. Study 2 registered 50 731 live births, with 454 deaths. Infant mortality decreased from 17 to 10/1000 live births during the study period. Adjusted VE was 44.6% overall (95% CI: 23.0 to 59.1) and 48.3% (95% CI: -5.9 to 74.1) against combined acute respiratory infection, meningitis and sepsis-associated mortality. CONCLUSION: These data provide population-level evidence of infant mortality reduction following sequential PCV13 and RV1 introduction into an established immunisation programme in Malawi. These data support increasing coverage of vaccine programmes in high-burden settings.

Care-seeking patterns amongst suspected paediatric pneumonia deaths in rural Malawi.

Background: Pneumonia remains a leading cause of paediatric deaths. To understand contextual challenges in care pathways, we explored patterns in care-seeking amongst children who died of pneumonia in Malawi. Methods: We conducted a mixed-methods analysis of verbal autopsies (VA) amongst deaths in children aged 1-59 months from 10/2011 to 06/2016 in Mchinji district, Malawi. Suspected pneumonia deaths were defined as: 1. caregiver reported cough and fast breathing in the 2-weeks prior to death; or, 2. the caregiver specifically stated the child died of pneumonia; or 3. cause of death assigned as 'acute respiratory infection' using InterVA-4. Data were extracted from free-text narratives based on domains in the 'Pathways to Survival' framework, and described using proportions. Qualitative analysis used a framework approach, with pre-specified themes. Results: We analysed 171 suspected pneumonia deaths. In total, 86% of children were taken to a healthcare facility during their final illness episode, and 44% sought care more than once.  Of children who went to hospital (n=119), 70% were admitted, and 25% received oxygen. Half of the children died within a healthcare setting (43% hospital, 5% health centre and 2% private clinics), 64 (37%) at home, and 22 (13%) in transit. Challenges in delayed care, transport and quality of care (including oxygen), were reported. Conclusions: Healthcare was frequently sought for children who died of suspected pneumonia, however several missed opportunities for care were seen. Sustained investment in timely appropriate care seeking, quick transportation to hospital and improved case management at all levels of the system is needed.

Performance of a novel reusable pediatric pulse oximeter probe.

OBJECTIVE: To assess the performance of reusable pulse oximeter probe and microprocessor box combinations, of varying price-points, in the context of a low-income pediatric setting. METHODS: A prospective, randomized cross-over study comparing time to biologically plausible oxygen saturation (SpO2 ) between: (1) Lifebox LB-01 probe with Masimo Rad-87 box (L + M) and (2) a weight-appropriate reusable Masimo probe with Masimo Rad-87 box (M + M). A post hoc secondary analysis comparison with historical usability testing data with the Lifebox LB-01 probe and Lifebox V1.5 box (L + L) was also conducted. Participants, children aged 0 to 35 months, were recruited from pediatric wards and outpatient clinics in the central region of Malawi. The primary outcome was time taken to achieve a biologically plausible SpO 2 measurement, compared using t tests for equivalence. RESULTS: We recruited 572 children. Plausible SpO2 measurements were obtained in less than 1 minute, 71%, 70%, and 63% for the M + M, L + M, and L + L combinations, respectively. A similar pattern was seen for less than 2 minutes, however, this effect disappeared at less than 5 minutes with 96%, 96%, and 95% plausible measurements. Using a ±10 second threshold for equivalence, we found L + M and M + M to be equivalent, but were under-powered to assess equivalence for L + L. CONCLUSIONS: The novel reusable pediatric Lifebox probe can achieve a quality SpO2 measurement within a pragmatic time range of weight-appropriate Masimo equivalent probes. Further research, which considers the cost of the devices, is needed to assess the added value of sophisticated motion tolerance software.

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

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.

Reassessing pregnancy intention and its relation to maternal, perinatal and neonatal outcomes in a low-income setting: A cohort study.

BACKGROUND: It is unclear whether unintended pregnancies are associated with adverse outcomes. Data are predominantly from high-income countries and have methodological limitations, calling the findings into question. This research was designed to overcome these limitations and assess the relationships between pregnancy intention and miscarriage, stillbirth, low birthweight, neonatal death and postnatal depression in a low-income country. METHODS: The pregnancy intention of 4,244 pregnant women in Mchinji District, Malawi, was measured using the validated Chichewa version of the London Measure of Unplanned Pregnancy (LMUP). Women were re-interviewed postnatally to assess pregnancy outcome. Postnatal depression was assessed using the WHO's Self-Reporting Questionnaire. Multivariable regressions were conducted, with the choice of confounders informed by a pre-existing conceptual epidemiological hierarchy. RESULTS: Planned pregnancies are associated with a reduced risk of any (adjusted RR 0.90 [95%CI 0.86, 0.95]) or high symptoms of depression (adjusted RR 0.76 [95%CI 0.63, 0.91]) compared to unplanned pregnancies in rural Malawi. There was no relationship between pregnancy intention and the composite measure of miscarriage, stillbirth, low birthweight and neonatal death. There was some evidence that greater pregnancy intention was associated with reduced adjusted risk of stillbirth (0·93 [95%CI 0·87, 1·00]). CONCLUSION: Our study is the first to use a psychometrically valid measure of pregnancy intention, and to do so antenatally. As pregnancy intention increases, the risk of postnatal depression and, possibly, stillbirth decreases. This suggests a new, clinical use for the LMUP; identifying women antenatally who are at risk of these adverse pregnancy outcomes.

Non-adherence to oral antibiotics for community paediatric pneumonia treatment in Malawi - A qualitative investigation.

BACKGROUND: Pneumonia remains the leading cause of paediatric infectious mortality globally. Treatment failure, which can result from non-adherence to oral antibiotics, can lead to poor outcomes and therefore improving adherence could be a strategy to reduce pneumonia related morbidity and mortality. However, there is little published evidence from low-resource settings for the drivers of non-adherence to oral antibiotics in children. OBJECTIVE: We aimed to investigate reasons for adherence and non-adherence in children diagnosed and treated in the community with fast-breathing pneumonia in rural Malawi. METHODS: We conducted focus group discussions (FGDs) with caregivers of children known to have been diagnosed and treated with oral antibiotics for fast-breathing pneumonia in the community and key informant interviews with community healthcare workers (CHW). FGDs and interviews were conducted within communities in Chichewa, the local language. We used a framework approach to analyze the transcripts. RESULTS: We conducted 4 FGDs with caregivers and 10 interviews with CHWs. We identified four themes, which were common across caregivers and CHWs: knowledge and understanding, effort, medication perceptions and community influences. Caregivers and CHWs demonstrated good knowledge of pneumonia and types of treatment, but caregivers showed confusion around dosing and treatment durations. Effort was needed to seek care, prepare medication and understand regimens, acting as a barrier to adherence. Perceptions of how well the treatment was working influenced adherence, with both quick recovery and slow recovery leading to non-adherence. Community influences were both supportive, with transport assistance for referrals and home visits to improve adherence, and detrimental, with pressure to share treatments. CONCLUSION: Adherence to oral antibiotic treatment for fast-breathing pneumonia was understood to be important, however considerable barriers we described within this rural low-resource setting, such as the effort preparing and administering medication, community pressures to share drugs and potential complexity of regimens.

Family networks and infant health promotion: a mixed-methods evaluation from a cluster randomised controlled trial in rural Malawi.

OBJECTIVE: Parents may rely on information provided by extended family members when making decisions concerning the health of their children. We evaluate whether extended family members affected the success of an information intervention promoting infant health. METHODS: This is a secondary, sequential mixed-methods study based on a cluster randomised controlled trial of a peer-led home-education intervention conducted in Mchinji District, Malawi. We used linear multivariate regression to test whether the intervention impact on child height-for-age z-scores (HAZ) was influenced by extended family members. 12 of 24 clusters were assigned to the intervention, in which all pregnant women and new mothers were eligible to receive 5 home visits from a trained peer counsellor to discuss infant care and nutrition. We conducted focus group discussions with mothers, grandmothers and peer counsellors, and key-informant interviews with husbands, chiefs and community health workers to better understand the roles of extended family members in infant feeding. RESULTS: Exposure to the intervention increased child HAZ scores by 0.296 SD (95% CI 0.116 to 0.484). However, this effect is smaller in the presence of paternal grandmothers. Compared with an effect size of 0.441 to 0.467 SD (95% CI -0.344 to 1.050) if neither grandmother is alive, the effect size was 0.235 (95% CI -0.493 to 0.039) to 0.253 (95% CI -0.529 to 0.029) SD lower if the paternal grandmother was alive. There was no evidence of an effect of parents' siblings. Maternal grandmothers did not affect intervention impact, but were associated with a lower HAZ score in the control group. Qualitative analysis suggested that grandmothers, who act as secondary caregivers and provide resources for infants, were slower to dismiss traditionally held practices and adopt intervention messages. CONCLUSION: The results indicate that the intervention impacts are diminished by paternal grandmothers. Intervention success could be increased by integrating senior women.

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

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.

Women's groups' perceptions of maternal health issues in rural Malawi.

BACKGROUND: Improvements in preventive and care-seeking behaviours to reduce maternal mortality in rural Africa depend on the knowledge and attitudes of women and communities. Surveys have indicated a poor awareness of maternal health problems by individual women. We report the perceptions of women's groups to such issues in the rural Mchinji district of Malawi. METHODS: Participatory women's groups in the Mchinji district identified maternal health problems (172 groups, 3171 women) and prioritised problems they considered most important (171 groups, 2833 women). In-depth qualitative data was obtained through six focus-group discussions with the women's groups, three with women's group facilitators, and four interviews with facilitator supervisors. FINDINGS: The maternal health problems most commonly identified by more than half the groups were anaemia (87%), malaria (80%), retained placenta (77%), obstructed labour (76%), malpresentation (71%), antepartum and postpartum haemorrhage (70% each), and pre-eclampsia (56%). The five problems prioritised as most important were anaemia (sum of rank score 304), malpresentation (295), retained placenta (277), obstructed labour (276). and postpartum haemorrhage (275). HIV/AIDS and sepsis were identified or prioritised much less because complexity and contextual factors hindered their consideration. INTERPRETATION: Rural Malawian women meeting in participatory groups showed a developed awareness of maternal health problems and the concern and motivation to address them. Community mobilisation strategies, such as women's groups, might be effective at reducing maternal mortality because they can draw on the collective capacity in communities to solve problems and make women's voices heard by decision-makers.

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.

Prevalence and Determinants of Unintended Pregnancy in Mchinji District, Malawi; Using a Conceptual Hierarchy to Inform Analysis.

BACKGROUND: In 2012 there were around 85 million unintended pregnancies globally. Unintended pregnancies unnecessarily expose women to the risks associated with pregnancy, unsafe abortion and childbirth, thereby contributing to maternal mortality and morbidity. Studies have identified a range of potential determinants of unplanned pregnancy but have used varying methodologies, measures of pregnancy intention and analysis techniques. Consequently there are many contradictions in their findings. Identifying women at risk of unplanned pregnancy is important as this information can be used to help with designing and targeting interventions and developing preventative policies. METHODS: 4,244 pregnant women from Mchinji District, Malawi were interviewed at home between March and December 2013. They were asked about their pregnancy intention using the validated Chichewa version of the London Measure of Unplanned Pregnancy, as well as their socio-demographics and obstetric and psychiatric history. A conceptual hierarchical model of the determinants of pregnancy intention was developed and used to inform the analysis. Multiple random effects linear regression was used to explore the ways in which factors determine pregnancy intention leading to the identification of women at risk of unplanned pregnancies. RESULTS: 44.4% of pregnancies were planned. On univariate analyses pregnancy intention was associated with mother and father's age and education, marital status, number of live children, birth interval, socio-economic status, intimate partner violence and previous depression all at p<0.001. Multiple linear regression analysis found that increasing socio-economic status is associated with increasing pregnancy intention but its effect is mediated through other factors in the model. Socio-demographic factors of importance were marital status, which was the factor in the model that had the largest effect on pregnancy intention, partner's age and mother's education level. The effect of mother's education level was mediated by maternal reproductive characteristics. Previous depression, abuse in the last year or sexual abuse, younger age, increasing number of children and short birth intervals were all associated with lower pregnancy intention having controlled for all other factors in the model. This suggests that women in Mchinji District who are either young, unmarried women having their first pregnancy, or older, married women who have completed their desired family size or recently given birth, or women who have experienced depression, abuse in the last year or sexual abuse are at higher risk of unintended pregnancies. CONCLUSION: A simple measure of pregnancy intention with well-established psychometric properties was used to show the distribution of pregnancy planning among women from a poor rural population and to identify those women at higher risk of unintended pregnancy. An analysis informed by a conceptual hierarchical model shed light on the pathways that lead from socio-demographic determinants to pregnancy intention. This information can be used to target family planning services to those most at risk of unplanned pregnancies, particularly women with a history of depression or who are experiencing intimate partner violence.

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.

Methods and challenges in measuring the impact of national pneumococcal and rotavirus vaccine introduction on morbidity and mortality in Malawi.

BACKGROUND: Pneumonia and gastroenteritis are leading causes of vaccine-preventable childhood morbidity and mortality. Malawi introduced pneumococcal conjugate and rotavirus vaccines to the immunisation programme in 2011 and 2012, respectively. Evaluating their effectiveness is vital to ensure optimal implementation and justify sustained investment. METHODS/DESIGN: A national evaluation platform was established to determine vaccine effectiveness and impact in Malawi. Impact and effectiveness against vaccine-type invasive pneumococcal disease, radiological pneumonia and rotavirus gastroenteritis are investigated using before-after incidence comparisons and case-control designs, respectively. Mortality is assessed using a prospective population cohort. Cost-effectiveness evaluation is nested within the case-control studies. We describe platform characteristics including strengths and weaknesses for conducting vaccine evaluations. DISCUSSION: Integrating data from individual level and ecological methods across multiple sites provides comprehensive information for policymakers on programme impact and vaccine effectiveness including changes in serotype/genotype distribution over time. Challenges to robust vaccine evaluation in real-world conditions include: vaccination ascertainment; pre-existing rapid decline in mortality and pneumococcal disease in the context of non-vaccine interventions; and the maintenance of completeness and quality of reporting at scale and over time. In observational non-randomised designs ascertainment of vaccine status may be biased particularly in infants with fatal outcomes. In the context of multiple population level interventions targeting study endpoints attribution of reduced incidence to vaccine impact may be flawed. Providing evidence from several independent but complementary studies will provide the greatest confidence in assigning impact. Welcome declines in disease incidence and in child mortality make accrual of required sample sizes difficult, necessitating large studies to detect the relatively small but potentially significant contribution of vaccines to mortality prevention. Careful evaluation of vaccine effectiveness and impact in such settings is critical to sustaining support for vaccine programmes. Our evaluation platform covers a large population with a high prevalence of HIV and malnutrition and its findings will be relevant to other settings in sub-Saharan Africa.

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.