Scale-up of a novel vital signs alert device to improve maternity care in Sierra Leone: a mixed methods evaluation of adoption.

BACKGROUND: The CRADLE (Community blood pressure monitoring in Rural Africa: Detection of underLying pre-Eclampsia) Vital Signs Alert device-designed specifically to improve maternity care in low resource settings-had varying impact when trialled in different countries. To better understand the contextual factors that may contribute to this variation, this study retrospectively evaluated the adoption of CRADLE, during scale-up in Sierra Leone. METHODS: This was a mixed methods study. A quantitative indicator of adoption (the proportion of facilities trained per district) was calculated from existing training records, then focus groups were held with 'CRADLE Champions' in each district (n = 32), to explore adoption qualitatively. Template Analysis was used to deductively interpret qualitative data, guided by the NASSS (non-adoption, abandonment, scale-up, spread, sustainability) Framework. FINDINGS: Substantial but non-significant variation was found in the proportion of facilities trained in each district (range 59-90%) [X2 (7, N = 8) = 10.419, p = 0.166]. Qualitative data identified complexity in two NASSS domains that may have contributed to this variation: 'the technology' (for example, charging issues, difficulty interpreting device output and concerns about ongoing procurement) and 'the organisation' (for example, logistical barriers to implementing training, infighting and high staff turnover). Key strategies mentioned to mitigate against these issues included: transparent communication at all levels; encouraging localised adaptations during implementation (including the involvement of community leaders); and selecting Champions with strong soft skills (particularly conflict resolution and problem solving). CONCLUSIONS: Complexity related to the technology and the organisational context were found to influence the adoption of CRADLE in Sierra Leone, with substantial inter-district variation. These findings emphasise the importance of gaining an in-depth understanding of the specific system and context in which a new healthcare technology is being implemented. This study has implications for the ongoing scale-up of CRADLE, and for those implementing or evaluating other health technologies in similar contexts.

Many women die during pregnancy and childbirth from causes that could be prevented, and the vast majority of these deaths occur in low-resource settings. The 'CRADLE Vital Signs Alert' is a medical device that helps identify problems during pregnancy­designed specifically for healthcare professionals in low-resource settings. However, for unknown reasons, the device appears to have varying impact according to the country or setting in which it is used. This study aimed to explore in depth whether, and why, healthcare professionals in Sierra Leone adopted the device and engaged in training (or not). Between March 2020 and January 2021, the CRADLE device and training package was disseminated across 8 districts in Sierra Leone. This relied on a few healthcare workers (nominated 'CRADLE Champions') to voluntarily distribute the devices and training in their local areas. Group discussions were held with CRADLE Champions in each district after the rollout to gather their feedback. In addition, the proportion of facilities trained in each district was recorded. The study found differences in how well the device and training was adopted in each district. Common challenges reported across districts related to technological difficulties (such as issues charging the devices) and organisational barriers (such as high levels of staff turnover at facilities). These findings will help to inform future rollout of the CRADLE device and training in Sierra Leone and highlight factors that may need to be considered by those implementing other health technologies in similar settings.

Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.

BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation.

Improving the quality of COVID-19 care in Sierra Leone: A modified Delphi process and serial nationwide assessments of quality of COVID-19 care in Sierra Leone.

INTRODUCTION: Improving the quality of care that patients receive is paramount to improving patient outcomes and engendering trust during infectious disease outbreaks. Whilst Quality Improvement (QI) is well established to drive improvement in routine care and in health systems, there are fewer reports of its use during infectious disease outbreaks. METHODS: A modified Delphi process was undertaken to create a standardized assessment tool for the quality of COVID-19 care in Sierra Leone. Four rounds of assessment were undertaken between July 2020 and July 2021. To assess change across the four assessment periods compared to baseline we used a mixed effects model and report coefficients and p values. RESULTS: During the Delphi process, 12/14 participants selected the domains to be assessed within the tool. The final 50 questions included 13 outcome questions, 17 process questions and 20 input questions. A total of 94 assessments were undertaken over four assessment periods at 27 facilities. An increase of 8.75 (p = <0.01) in total score was seen in round 2, 10.67 (p = <0.01) in round 3 and 2.17 (p = 0.43) in round 4 compared to baseline. Mean cumulative scores for COVID-19 Treatment Centres were higher than Hospital Isolation Units (p<0.02) at all four timepoints. Significant improvements were reported in coordination, diagnostics, staffing, infection prevention and control (IPC), nutrition, and vulnerable populations domains, but not in the oxygen, care processes, infrastructure and drugs domains. CONCLUSION: We demonstrate the feasibility of creating a quality of care assessment tool and conducting sequential nationwide assessments during an infectious disease outbreak. We report significant improvements in quality-of-care scores in round 2 and round 3 compared to baseline, however, these improvements were not sustained. We recommend the use of QI and the creation of standardised assessment tools to improve quality of care during outbreak responses.

Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveillance (CHAMPS), December 2016 -December 2021.

Each year, 2.4 million children die within their first month of life. Child Health and Mortality Prevention Surveillance (CHAMPS) established in 7 countries aims to generate accurate data on why such deaths occur and inform prevention strategies. Neonatal deaths that occurred between December 2016 and December 2021 were investigated with MITS within 24-72 hours of death. Testing included blood, cerebrospinal fluid and lung cultures, multi-pathogen PCR on blood, CSF, nasopharyngeal swabs and lung tissue, and histopathology examination of lung, liver and brain. Data collection included clinical record review and family interview using standardized verbal autopsy. The full set of data was reviewed by local experts using a standardized process (Determination of Cause of Death) to identify all relevant conditions leading to death (causal chain), per WHO recommendations. For analysis we stratified neonatal death into 24-hours of birth, early (1-<7 days) and late (7-<28 days) neonatal deaths. We analyzed 1458 deaths, 41% occurring within 24-hours, 41% early and 18% late neonatal deaths. Leading underlying causes of death were complications of intrapartum events (31%), complications of prematurity (28%), infections (17%), respiratory disorders (11%), and congenital malformations (8%). In addition to the underlying cause, 62% of deaths had additional conditions and 14% had ≥3 other conditions in the causal chain. The most common causes considering the whole causal chain were infection (40%), prematurity (32%) and respiratory distress syndrome (28%). Common maternal conditions linked to neonatal death were maternal hypertension (10%), labour and delivery complications (8%), multiple gestation (7%), placental complications (6%) obstructed labour and chorioamnionitis (5%, each). CHAMPS' findings showing the full causal chain of events that lead to death, in addition to maternal factors, highlights the complexities involved in each death along with the multiple opportunities for prevention. Highlighting improvements to prenatal and obstetric care and infection prevention are urgently needed in high-mortality settings.

Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings.

During Plasmodium falciparum malaria infections, von Willebrand factor (VWF) levels are elevated, postmortem studies show platelets colocalized with sequestered infected erythrocytes (IEs) at brain microvascular sites, whereas in vitro studies have demonstrated platelet-mediated IE adhesion to tumor necrosis factor-activated brain endothelium via a bridging mechanism. This current study demonstrates how all these observations could be linked through a completely novel mechanism whereby IEs adhere via platelet decorated ultra-large VWF strings on activated endothelium. Using an in vitro laminar flow model, we have demonstrated tethering and firm adhesion of IEs to the endothelium specifically at sites of platelet accumulation. We also show that an IE pro-adhesive state, capable of supporting high levels of binding within minutes of induction, can be removed through the action of the VWF protease ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). We propose that this new mechanism contributes to sequestration both independently of and in concert with current adhesion mechanisms.

Infection Prevention and Control in Three Tertiary Healthcare Facilities in Freetown, Sierra Leone during the COVID-19 Pandemic: More Needs to Be Done!

Infection Prevention and Control (IPC) measures are critical to the reduction in healthcare-associated infections, especially during pandemics, such as that of COVID-19. We conducted a hospital-based cross-sectional study in August 2021 at Connaught Hospital, Princess Christian Maternity Hospital and Ola During Children's Hospital located in Freetown, Sierra Leone. We used the World Health Organization's Infection Prevention and Control Assessment Framework Tool to assess the level of IPC compliance at these healthcare facilities. The overall IPC compliance score at Connaught Hospital was 323.5 of 800 points, 313.5 of 800 at Ola During Children's Hospital, 281 of 800 at Princess Christian Maternity Hospital, implying a 'Basic' IPC compliance grade. These facilities had an IPC program, IPC committees and dedicated IPC focal persons. However, there were several challenges, including access to safe and clean water and insufficient quantities of face masks, examination gloves and aprons. Furthermore, there was no dedicated budget or no healthcare-associated infection (HAI) surveillance, and monitoring/audit of IPC practices were weak. These findings are of concern during the COVID-19 era, and there is an urgent need for both financial and technical support to address the gaps and challenges identified.

After action review of the response to an outbreak of Lassa fever in Sierra Leone, 2019: Best practices and lessons learnt.

BACKGROUND: In November 2019, an outbreak of Lassa Fever occurred among health workers in a non-endemic district in Sierra Leone. The outbreak resulted in five cases, including two that were exported to the Netherlands. The outbreak tested multiple technical capacities in the International Health Regulations (2005) in a real-life setting. As such, an after action review (AAR) was undertaken as recommended by World Health Organization. We report on the findings of the AAR including best practices and lessons learnt. METHODS: A two stage review process was employed. The first stage involved national pillar level reviews for each technical pillar and one review of the district level response. The second stage brought together all pillars, including participants from the national and sub-national level as well as health sector partners. National guidelines were used as references during the deliberations. A standardized template was used to report on the key findings on what happened, what was supposed to happen, what went well and lessons learnt. RESULTS: This was a hospital associated outbreak that likely occurred due to a breach in infection prevention and control (IPC) practices resulting in three health workers being infected during a surgical operation. There was a delay in detecting the outbreak on time due to low index of suspicion among clinicians. Once detected, the outbreak response contained the outbreak within one incubation period. Areas that worked well included coordination, contact tracing, active case search and ring IPC. Notable gaps included delays in accessing local emergency funding and late distribution of IPC and laboratory supplies. CONCLUSIONS: The incident management system worked optimally to contain this outbreak. The core technical gaps identified in surveillance, IPC and delay in deployment of resources should be addressed through systemic changes that can mitigate future outbreaks.

Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU/ml versus 1.9 IU/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

Emergency Triage Assessment and Treatment Plus (ETAT+): adapting training to strengthen quality improvement and task-sharing in emergency paediatric care in Sierra Leone.

BACKGROUND: Over the past 25 years Sierra Leone has made progress in reducing maternal and child mortality, but the burden of preventable paediatric deaths remains high. Further progress towards achieving the Sustainable Development Goals will require greater strengthening of the health care system, including hospital care for perinatal and paediatric conditions. Emergency Triage Assessment and Treatment Plus (ETAT+) may offer a useful tool. METHODS: The five-day ETAT+ course was adapted as a six-month programme of in-situ training and mentoring integrated with patient flow and service delivery improvements in 14 regional and district government hospitals across the country. Nurses were trained to carry out the initial resuscitation and assessment of the sick paediatric patient, and to administer the first dose of medication per protocol. The course was for all clinical staff; most participants were nurses. RESULTS: The intervention was associated with an improvement in the quality of paediatric care and a reduction in mortality. In 2017 mortality decreased by 33.1%, from 14.5% at baseline to 9.7% after six months of the intervention. Mortality at the start of the 2018 intervention was 8.5% and reduced over six months to 6.5%. Care quality indicators showed improvement across the two intervention periods, with some evidence of sustained effect. CONCLUSIONS: These results suggest that adapted ETAT+ training with in-situ mentoring alongside improved patient flow and service delivery supports improvements in the quality of paediatric care in Sierra Leonean hospitals. ETAT+ may provide an affordable framework for improving the quality of secondary paediatric care in Sierra Leone and a model of nurse-led resuscitation may allow for prompt and timely emergency paediatric care in Sierra Leonean hospitals where there are fewer physicians and other resources for care.

Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.

BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID).

Common mental disorder and associated factors amongst women with young infants in rural Malawi.

BACKGROUND: Common mental disorder (CMD) affecting women during the childbearing years is an important health problem in low and middle income countries. This study investigates CMD and associated factors amongst women with young infants in rural Malawi. METHODS: In this cross-sectional study, mothers of infants due for measles vaccination were recruited from a district hospital child health clinic. Maternal CMD was measured using a Chichewa version of the Self-Reporting Questionnaire (SRQ). DSM-IV diagnoses of major and minor depressive disorder were made using the structured clinical interview for DSM-IV (SCID). Socio-demographic, maternal and infant variables were measured and associations with CMD were determined. RESULTS: Of 519 eligible women, 501 were included in the analysis. Mean age was 24.4 years and median infant age was 9.9 months. The weighted prevalence of any current depressive episode (minor or major) was 30.4% (95% CI 22.8-38.1%). The weighted prevalence of current major depressive episode was 13.9% (95% CI 8.2-19.5%). Mean SRQ score for the total sample was 5.71 (SD 4.42). On multivariate analysis, SRQ score was significantly associated with lower socioeconomic status, lack of a confiding relationship with partner or relative, and recent infant illness. Amongst the women who knew their HIV status (n = 314), SRQ score was also associated with HIV infection. CONCLUSIONS: This study demonstrates that CMD is a significant health burden among women with infants in rural Malawi, and is associated with poverty, relationship difficulties, HIV infection and infant health problems.

A Public Health Response to a Mudslide in Freetown, Sierra Leone, 2017: Lessons Learnt.

On August 14, 2017, a 6-kilometer mudslide occurred in Regent Area, Western Area District of Sierra Leone following a torrential downpour that lasted 3 days. More than 300 houses along River Juba were submerged; 1141 people were reported dead or missing and 5905 displaced. In response to the mudslide, the World Health Organization (WHO) Country Office in Sierra Leone moved swiftly to verify the emergency and constitute an incident management team to coordinate the response. Early contact was made with the Ministry of Health and Sanitation and health sector partners. A Public Health Emergency Operations Center was set up to coordinate the response. Joint assessments, planning, and response among health sector partners ensured effectiveness and efficiency. Oral cholera vaccination was administered to high-risk populations to prevent a cholera outbreak. Surveillance for 4 waterborne diseases was enhanced through daily reporting from 9 health facilities serving the affected population. Performance standards from the WHO Emergency Response Framework were used to monitor the emergency response. An assessment of the country's performance showed that the country's response was well executed. To improve future response, we recommend enhanced district level preparedness, update of disaster response protocols, and pre-disaster mapping of health sector partners.

Validation of a Chichewa version of the self-reporting questionnaire (SRQ) as a brief screening measure for maternal depressive disorder in Malawi, Africa.

BACKGROUND: Depressive disorder affecting women during the perinatal period is common in low-income countries. The detection and study of maternal depression in a resource-poor setting requires a brief screening tool that is both accurate and practical to administer. METHOD: A Chichewa version of the Self Reporting Questionnaire (SRQ) was developed through a rigorous process of forward and back translation, focus-group discussion and piloting. Criterion validation was conducted as part of a larger study in a sample of women who had brought their infants to a child health clinic in rural Malawi, using DSM-IV major and minor depressive episode as the gold standard diagnoses. RESULTS: The criterion validation was conducted on 114 subjects who did not differ on health and sociodemographic characteristics from the total study sample (n=501). Test characteristics for each possible SRQ cut-off were calculated and Receiver Operator Characteristic (ROC) curves derived. Area under the ROC curve (AUROC) for detection of current major depressive disorder was 0.856 (95% CI 0.813 to 0.900), and for current major or minor depressive disorder was 0.826 (95% CI 0.783 to 0.869). Internal consistency of the SRQ was high (Cronbach's alpha 0.85). LIMITATION: Inter-rater reliability testing was not conducted. CONCLUSION: This Chichewa version of the SRQ shows utility as a brief screening measure for detection of probable maternal depression in rural Malawi.

Improved assessment of child nutritional status using target weights and a novel, low-cost, weight-for-height slide chart.

Correctly identifying malnourished or at-risk children is the critical first step towards appropriate nutritional interventions. To improve weight-for-height assessment and classification of nutritional status, we present a novel, low-cost, weight-for-height slide chart. We also describe a target weight system for monitoring children's progress towards nutritional recovery.

Maternal common mental disorder and infant growth--a cross-sectional study from Malawi.

The objective of the study was to investigate the association between maternal common mental disorder (CMD) and infant growth in rural Malawi. A cross-sectional study was conducted at a district hospital child health clinic. Participants were consecutive infants due for measles vaccination, and their mothers. Mean infant weight-for-age and length-for-age z-scores were compared between infants of mothers with and without CMD as measured using the self-reporting questionnaire (SRQ). Of 519 eligible infants/mothers, 501 were included in the analysis. Median infant age was 9.9 months. 29.9% of mothers scored 8 or above on the SRQ indicating CMD. Mean length-for-age z-score for infants of mothers with CMD (-1.50 SD 1.24) was significantly lower than for infants of mothers without CMD (-1.11 SD 1.12) Student's t-test: P = 0.001. This association was confirmed in multivariate analysis. Mean weight-for-age z-score for infants of mothers with CMD (-1.77 SD 1.16) was lower than for infants of mothers without CMD (-1.59 SD 1.09) but this difference was not significant on univariate (Student's t-test: P = 0.097) or multivariate analysis. The study demonstrates an association between maternal CMD and infant growth impairment in rural sub-Saharan Africa.

ABO blood group phenotypes and Plasmodium falciparum malaria: unlocking a pivotal mechanism.

Host susceptibility to Plasmodium falciparum infection is central for improved understanding of malaria in human populations. Red blood cell (RBC) polymorphisms have been proposed as factors associated with malaria infection or its severity, although no systematic appraisal of ABO phenotypes and malaria risk has been undertaken. This analysis summarises epidemiological, clinical and immunological evidence on the nature of ABO histo-blood antigens and their interaction with malaria in terms of population genetics, infection risk, severe malaria and placental malaria. In non-pregnant subjects, a meta-analysis showed no conclusive evidence associating ABO phenotypes with risk of uncomplicated malaria. There was stronger evidence that ABO phenotype modulates severity of P. falciparum malaria, with group A associated with severe disease and blood group O with milder disease. Among pregnant subjects, group O was associated with increased risk of placental malaria in primigravidae and reduced risk in multigravidae. The biological basis for ABO-related susceptibility to malaria is reviewed. Several mechanisms relate to these associations including affinity for Anopheles gambiae; shared ABO antigens with P. falciparum; impairment of merozoite penetration of RBCs; and cytoadherence, endothelial activation and rosetting. ABO phenotypic associations with malaria are related to its pathogenesis and improved understanding of these interactions is required for understanding the glycobiology of malaria infection.

Chronic disease outcomes after severe acute malnutrition in Malawian children (ChroSAM): a cohort study.

BACKGROUND: Tackling severe acute malnutrition (SAM) is a global health priority. Heightened risk of non-communicable diseases (NCD) in children exposed to SAM at around 2 years of age is plausible in view of previously described consequences of other early nutritional insults. By applying developmental origins of health and disease (DOHaD) theory to this group, we aimed to explore the long-term effects of SAM. METHODS: We followed up 352 Malawian children (median age 9·3 years) who were still alive following SAM inpatient treatment between July 12, 2006, and March 7, 2007, (median age 24 months) and compared them with 217 sibling controls and 184 age-and-sex matched community controls. Our outcomes of interest were anthropometry, body composition, lung function, physical capacity (hand grip, step test, and physical activity), and blood markers of NCD risk. For comparisons of all outcomes, we used multivariable linear regression, adjusted for age, sex, HIV status, and socioeconomic status. We also adjusted for puberty in the body composition regression model. FINDINGS: Compared with controls, children who had survived SAM had lower height-for-age Z scores (adjusted difference vs community controls 0·4, 95% CI 0·6 to 0·2, p=0·001; adjusted difference vs sibling controls 0·2, 0·0 to 0·4, p=0·04), although they showed evidence of catch-up growth. These children also had shorter leg length (adjusted difference vs community controls 2·0 cm, 1·0 to 3·0, p<0·0001; adjusted difference vs sibling controls 1·4 cm, 0·5 to 2·3, p=0·002), smaller mid-upper arm circumference (adjusted difference vs community controls 5·6 mm, 1·9 to 9·4, p=0·001; adjusted difference vs sibling controls 5·7 mm, 2·3 to 9·1, p=0·02), calf circumference (adjusted difference vs community controls 0·49 cm, 0·1 to 0·9, p=0·01; adjusted difference vs sibling controls 0·62 cm, 0·2 to 1·0, p=0·001), and hip circumference (adjusted difference vs community controls 1·56 cm, 0·5 to 2·7, p=0·01; adjusted difference vs sibling controls 1·83 cm, 0·8 to 2·8, p<0·0001), and less lean mass (adjusted difference vs community controls -24·5, -43 to -5·5, p=0·01; adjusted difference vs sibling controls -11·5, -29 to -6, p=0·19) than did either sibling or community controls. Survivors of SAM had functional deficits consisting of weaker hand grip (adjusted difference vs community controls -1·7 kg, 95% CI -2·4 to -0·9, p<0·0001; adjusted difference vs sibling controls 1·01 kg, 0·3 to 1·7, p=0·005,)) and fewer minutes completed of an exercise test (sibling odds ratio [OR] 1·59, 95% CI 1·0 to 2·5, p=0·04; community OR 1·59, 95% CI 1·0 to 2·5, p=0·05). We did not detect significant differences between cases and controls in terms of lung function, lipid profile, glucose tolerance, glycated haemoglobin A1c, salivary cortisol, sitting height, and head circumference. INTERPRETATION: Our results suggest that SAM has long-term adverse effects. Survivors show patterns of so-called thrifty growth, which is associated with future cardiovascular and metabolic disease. The evidence of catch-up growth and largely preserved cardiometabolic and pulmonary functions suggest the potential for near-full rehabilitation. Future follow-up should try to establish the effects of puberty and later dietary or social transitions on these parameters, as well as explore how best to optimise recovery and quality of life for survivors. FUNDING: The Wellcome Trust.

Impact of maternal depression on infant nutritional status and illness: a cohort study.

BACKGROUND: The risk for emotional and behavioral problems is known to be high among children of depressed mothers, but little is known about the impact of prenatal and postnatal depression on the physical health of infants. OBJECTIVE: To determine whether maternal depression is a risk factor for malnutrition and illness in infants living in a low-income country. DESIGN: Prospective cohort study. SETTING: Rural community in Rawalpindi, Pakistan. PARTICIPANTS: Six hundred thirty-two physically healthy women were assessed in their third trimester of pregnancy to obtain at birth a cohort of 160 infants of depressed mothers and 160 infants of psychologically well mothers. MAIN OUTCOME MEASURES: All infants were weighed and measured at birth and at 2, 6, and 12 months of age, and they were monitored for episodes of diarrhea and acute respiratory infections. The mothers' mental states were reassessed at 2, 6, and 12 months. Data were collected on potential confounders of infant outcomes, such as birth weight and socioeconomic status. RESULTS: Infants of prenatally depressed mothers showed significantly more growth retardation than controls at all time points. The relative risks for being underweight (weight-for-age z score of less than -2) were 4.0 (95% confidence interval [CI], 2.1 to 7.7) at 6 months of age and 2.6 (95% CI, 1.7 to 4.1) at 12 months of age, and the relative risks for stunting (length-for-age z score of less than -2) were 4.4 (95% CI, 1.7 to 11.4) at 6 months of age and 2.5 (95% CI, 1.6 to 4.0) at 12 months of age. The relative risk for 5 or more diarrheal episodes per year was 2.4 (95% CI, 1.7 to 3.3). Chronic depression carried a greater risk for poor outcome than episodic depression. The associations remained significant after adjustment for confounders by multivariate analyses. CONCLUSIONS: Maternal depression in the prenatal and postnatal periods predicts poorer growth and higher risk of diarrhea in a community sample of infants. As depression can be identified relatively easily, it could be an important marker for a high-risk infant group. Early treatment of prenatal and postnatal depression could benefit not only the mother's mental health but also the infant's physical health and development.

Specific immunoglobulin A antibodies in maternal milk and delayed Helicobacter pylori colonization in Gambian infants.

BACKGROUND: Immunoglobulin A (IgA) in maternal milk may protect Gambian infants from early Helicobacter pylori colonization. This study sought evidence that this protection could be due to specific IgA antibodies. METHODS: Sixty-five infants were screened from 12 weeks of age with [13C]-urea breath tests. Antibodies in maternal milk were measured to determine total IgA content and to detect specific IgA antibodies against crude whole-cell and recombinant H. pylori urease antigen preparations. RESULTS: Ten children (15%) had no evidence of early H. pylori colonization, 10 (15%) had early H. pylori colonization, and 43 (66%) had mixed results. Levels of maternal circulating specific immunoglobulin G, total milk IgA, and IgA directed against crude whole-cell H. pylori antigen preparation were not significantly associated with the rate of infant H. pylori colonization. However, mothers of infants with no evidence of early colonization produced significantly higher levels of anti-recombinant urease IgA antibodies in milk than did control mothers, particularly at 8, 16, and 20 weeks postpartum (P<.01). CONCLUSIONS: These observations support the hypothesis that antibodies in mother's milk directed against H. pylori urease can protect against colonization in human infancy.