Prevalence and correlates of paediatric guideline non-adherence for initial empirical care in six low and middle-income settings: a hospital-based cross-sectional study.

OBJECTIVES: This study evaluated the prevalence and correlates of guideline non-adherence for common childhood illnesses in low-resource settings. DESIGN AND SETTING: We used secondary cross-sectional data from eight healthcare facilities in six Asian and African countries. PARTICIPANTS: A total of 2796 children aged 2-23 months hospitalised between November 2016 and January 2019 with pneumonia, diarrhoea or severe malnutrition (SM) and without HIV infection were included in this study. PRIMARY OUTCOME MEASURES: We identified children treated with full, partial or non-adherent initial inpatient care according to site-specific standard-of-care guidelines for pneumonia, diarrhoea and SM within the first 24 hours of admission. Correlates of guideline non-adherence were identified using generalised estimating equations. RESULTS: Fully adherent care was delivered to 32% of children admitted with diarrhoea, 34% of children with pneumonia and 28% of children with SM when a strict definition of adherence was applied. Non-adherence to recommendations was most common for oxygen and antibiotics for pneumonia; fluid, zinc and antibiotics for diarrhoea; and vitamin A and zinc for SM. Non-adherence varied by site. Pneumonia guideline non-adherence was more likely among patients with severe disease (OR 1.82; 95% CI 1.38, 2.34) compared with non-severe disease. Diarrhoea guideline non-adherence was more likely among lower asset quintile groups (OR 1.16; 95% CI 1.01, 1.35), older children (OR 1.10; 95% CI 1.06, 1.13) and children presenting with wasting (OR 6.44; 95% CI 4.33, 9.57) compared with those with higher assets, younger age and not wasted. CONCLUSIONS: Non-adherence to paediatric guidelines was common and associated with older age, disease severity, and comorbidities, and lower household economic status. These findings highlight opportunities to improve guidelines by adding clarity to specific recommendations.

Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.

Ultrasound assessment of malnutrition in infancy: a pilot case-control study.

This study aimed at determining the intra- and inter-rater reliability in ultrasound body composition measurements and investigating the differences between malnourished and non-malnourished infants. Sonographic images for measurements of fat and muscle thickness were compared between 9 malnourished and 9 non-malnourished hospitalized infants. The mean of fat and muscle thickness sums were 12.44 ± 7.58 mm and 28.98 ± 7.18 mm, respectively. The intra- and inter-rater intraclass correlation coefficient were above 0.9 for both measurements, indicating high intra- and inter-rater reliability. Compared to non-malnourished infants, malnourished infants have 45% of fat thickness sum and 71% of muscle thickness sum. Ultrasound measurements of body composition in infants were different between hospitalized malnourished and non-malnourished infants. This approach has the potential to be utilized more broadly, from assessing the nutritional status of critically ill infants in intensive care units to screening for malnutrition in high-risk infant populations.

Evaluating blood culture collection practice in children hospitalized with acute illness at a tertiary hospital in Malawi.

BACKGROUND: Blood culture collection practice in low-resource settings where routine blood culture collection is available has not been previously described. METHODOLOGY: We conducted a secondary descriptive analysis of children aged 2-23 months enrolled in the Malawi Childhood Acute Illness and Nutrition (CHAIN) study, stratified by whether an admission blood culture had been undertaken and by nutritional status. Chi-square test was used to compare the differences between groups. RESULTS: A total of 347 children were included, of whom 161 (46%) had a blood culture collected. Children who had a blood culture collected, compared to those who did not, were more likely to present with sepsis (43% vs. 20%, p < 0.001), gastroenteritis (43% vs. 26%, p < 0.001), fever (86% vs. 73%, p = 0.004), and with poor feeding/weight loss (30% vs. 18%, p = 0.008). In addition, hospital stay in those who had a blood culture was, on average, 2 days longer (p = 0.019). No difference in mortality was observed between those who did and did not have a blood culture obtained. CONCLUSION: Blood culture collection was more frequent in children with sepsis and gastroenteritis, but was not associated with mortality. In low-resource settings, developing criteria for blood culture based on risk factors rather than clinician judgement may better utilize the existing resources.

Blood culture is key to investigating bloodstream infections, but in-hospital decisions to perform blood culture in a low-resource setting have not been previously described. We linked blood culture data to the Childhood Acute Illness and Nutrition (CHAIN) cohort at a Malawi tertiary hospital and compared clinical characteristics and outcomes of children between those who did and did not have a blood culture done on admission. Of those hospitalized, 46% of the children had a blood culture collected at admission. Only 3% of blood cultures had significant growth of pathogenic bacteria. There were significant differences in nutritional status, presenting symptoms, clinical diagnoses and hospital length of stay between those who received blood culture collection on admission and those who did not, but there was no difference in mortality. Clinical judgement used to determine blood culture collection may not best identify children most at risk.

Predicting Acute and Post-Recovery Outcomes in Cerebral Malaria and Other Comas by Optical Coherence Tomography (OCT in CM) - A protocol for an observational cohort study of Malawian children.

Cerebral malaria (CM) remains a significant global health challenge with high morbidity and mortality. Malarial retinopathy has been shown to be diagnostically and prognostically significant in the assessment of CM. The major mechanism of death in paediatric CM is brain swelling. Long term morbidity is typically characterised by neurological and neurodevelopmental sequelae. Optical coherence tomography can be used to quantify papilloedema and macular ischaemia, identified as hyperreflectivity. Here we describe a protocol to test the hypotheses that quantification of optic nerve head swelling using optical coherence tomography can identify severe brain swelling in CM, and that quantification of hyperreflectivity in the macula predicts neurodevelopmental outcomes post-recovery. Additionally, our protocol includes the development of a novel, low-cost, handheld optical coherence tomography machine and artificial intelligence tools to assist in image analysis.

A protocol for a proof-of-concept randomized control trial testing increased protein quantity and quality in ready-to-use therapeutic food in improving linear growth among 6-23-month-old children with severe wasting in Malawi.

INTRODUCTION: Ready-to-use therapeutic foods (RUTFs) have successfully promoted recovery from severe wasting and increased treatment coverage. However, RUTFs do not sufficiently improve linear growth, leaving many survivors of severe wasting at risk of persistent stunting, which is associated with high mortality risk, poor child development and non-communicable diseases in adulthood. High protein quantity and quality can stimulate linear growth. AIM: The trial aims to assess whether higher-protein-RUTF leads to higher concentrations of markers of linear growth compared to standard RUTF among 6-23 months old children with severe wasting. METHODS: We designed a higher protein quantity and quality RUTF for a proof-of-concept (PoC) double-blind randomized controlled trial. OUTCOMES: The primary outcome is a change in insulin-like growth factor-1 (IGF-1), a hormone positively associated with linear growth after four weeks of treatment. Secondary outcomes include changes in ponderal and linear growth and in body composition from baseline to eight weeks later; plasma amino acid profile at four weeks; acceptability and safety. IMPLICATIONS: These findings will help in informing the potential impact of increased protein in RUTF on linear growth when treating severe wasting towards conducting a larger clinical trial. TRIAL REGISTRATION: The trial has been registered on clinicaltrial.gov (NCT05737472).

Neurodevelopment and Recovery From Wasting.

BACKGROUND AND OBJECTIVES: Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness. METHODS: Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid-upper arm circumference for age z-score. Neurodevelopment was assessed with the Malawi Developmental Assessment Tool (MDAT development-for-age z-score [DAZ]) at hospital discharge and after 6 months. RESULTS: We included 645 children at hospital discharge (mean age 12.3 months ± 5.5; 55% male); 262 (41%) with severe wasting, 134 (21%) with moderate wasting, and 249 (39%) without wasting. Four recovery trajectories were identified: high-stable, n = 112; wasted-improved, n = 404; severely wasted-greatly improved, n = 48; and severely wasted-not improved, n = 28. The children in the severely wasted-greatly improved group demonstrated a steep positive MDAT-DAZ recovery slope. This effect was most evident in children with both wasting and stunting (interaction wasted-improved × time × stunting: P < .001). After 6 months, the MDAT DAZ in children with wasting recovery did not differ from community children. In children who never recovered from wasting, there remained a significant delay in MDAT DAZ scores. CONCLUSIONS: Neurodevelopment recovery occurred in parallel with wasting recovery in children convalescing from acute illness and was influenced by stunting.

The Role of Food Insecurity and Dietary Diversity on Recovery from Wasting among Hospitalized Children Aged 6-23 Months in Sub-Saharan Africa and South Asia.

Background: Current guidelines for the management of childhood wasting primarily focus on the provision of therapeutic foods and the treatment of medical complications. However, many children with wasting live in food-secure households, and multiple studies have demonstrated that the etiology of wasting is complex, including social, nutritional, and biological causes. We evaluated the contribution of household food insecurity, dietary diversity, and the consumption of specific food groups to the time to recovery from wasting after hospital discharge. Methods: We conducted a secondary analysis of the Childhood Acute Illness Network (CHAIN) cohort, a multicenter prospective study conducted in six low- or lower-middle-income countries. We included children aged 6−23 months with wasting (mid-upper arm circumference [MUAC] ≤ 12.5 cm) or kwashiorkor (bipedal edema) at the time of hospital discharge. The primary outcome was time to nutritional recovery, defined as a MUAC > 12.5 cm without edema. Using Cox proportional hazards models adjusted for age, sex, study site, HIV status, duration of hospitalization, enrollment MUAC, referral to a nutritional program, caregiver education, caregiver depression, the season of enrollment, residence, and household wealth status, we evaluated the role of reported food insecurity, dietary diversity, and specific food groups prior to hospitalization on time to recovery from wasting during the 6 months of posthospital discharge. Findings: Of 1286 included children, most participants (806, 63%) came from food-insecure households, including 170 (13%) with severe food insecurity, and 664 (52%) participants had insufficient dietary diversity. The median time to recovery was 96 days (18/100 child-months (95% CI: 17.0, 19.0)). Moderate (aHR 1.17 [0.96, 1.43]) and severe food insecurity (aHR 1.14 [0.88, 1.48]), and insufficient dietary diversity (aHR 1.07 [0.91, 1.25]) were not significantly associated with time to recovery. Children who had consumed legumes and nuts prior to diagnosis had a quicker recovery than those who did not (adjusted hazard ratio (aHR): 1.21 [1.01,1.44]). Consumption of dairy products (aHR 1.13 [0.96, 1.34], p = 0.14) and meat (aHR 1.11 [0.93, 1.33]), p = 0.23) were not statistically significantly associated with time to recovery. Consumption of fruits and vegetables (aHR 0.78 [0.65,0.94]) and breastfeeding (aHR 0.84 [0.71, 0.99]) before diagnosis were associated with longer time to recovery. Conclusion: Among wasted children discharged from hospital and managed in compliance with wasting guidelines, food insecurity and dietary diversity were not major determinants of recovery.

A Mixed-Methods Cluster-Randomized Controlled Trial of a Hospital-Based Psychosocial Stimulation and Counseling Program for Caregivers and Children with Severe Acute Malnutrition.

BACKGROUND: Children with severe acute malnutrition (SAM) who require nutritional rehabilitation unit (NRU) treatment often have poor developmental and nutritional outcomes following discharge. The Kusamala Program is a 4-d hospital-based counseling program for caregivers of children with SAM that integrates nutrition, water, sanitation, and hygiene and psychosocial stimulation, aimed at improving these outcomes. OBJECTIVES: The aim was to evaluate the effects of the Kusamala Program on child development and nutritional status in children with SAM 6 mo after NRU discharge. The other aim was to qualitatively understand perceptions and experiences of caregivers who participated in the intervention. METHODS: A cluster-randomized controlled trial was conducted with caregivers and their children 6-59 mo of age with SAM admitted to the Moyo NRU in Blantyre, Malawi. The primary outcome of the trial was child development according to Malawi Developmental Assessment Tool (MDAT) composite z-scores of gross motor, fine motor, language, and social domains. A qualitative component with focus group discussions and in-depth interviews was also completed with a subset of caregivers who participated in the trial. RESULTS: Sixty-eight caregivers and children were enrolled to clusters by week and randomly assigned to the comparison arm and 104 to the intervention arm. There were no differences in child development, with mean MDAT composite z-scores in the comparison arm of -1.2 (95% CI: -2.1, -0.22) and in the intervention arm of -1.1 (95% CI: -1.9, -0.40) (P = 0.93). The qualitative evaluation with 20 caregivers indicated that the 3 modules of the Kusamala Program were appropriate and that they applied many of the lessons learned at home as much as possible. CONCLUSIONS: The Kusamala Program did not result in improved developmental or nutritional outcomes, yet it was viewed positively by caregivers according to qualitative results. Future research should evaluate more intensive interventions for caregivers and children with SAM. This trial was registered at www.clinicaltrials.gov as NCT03072433.

Pathways between caregiver body mass index, the home environment, child nutritional status, and development in children with severe acute malnutrition in Malawi.

Children with severe acute malnutrition (SAM) remain vulnerable after treatment at nutritional rehabilitation units (NRUs). The objective was to assess the concurrent pathways in a hypothesized model between caregiver body mass index (BMI), the home environment, and child nutritional status, and development (gross motor, fine motor, language, and social domains) in children with SAM following discharge from inpatient treatment. Structural equation modelling (SEM) was performed with data from a cluster-randomized controlled trial at the Moyo Nutritional Rehabilitation and Research Unit in Blantyre, Malawi. This approach was undertaken to explore simultaneous relationships between caregiver BMI, the home environment (Home Observation for Measurement of the Environment Inventory scores), child nutritional status (anthropometric indicators including weight-for-age z-scores [WAZ]), and child development (Malawi Developmental Assessment Tool (MDAT) z-scores as a latent variable) in children with SAM. These data were collected at participants' homes six months after discharge from NRU treatment. This analysis included 85 children aged 6-59 months with SAM and their caregivers recruited to the trial at the NRU and followed up successfully six months after discharge. The model with WAZ as the nutritional indicator fit the data according to model fit indices (χ2 = 28.92, p = 0.42). Caregiver BMI was predictive of better home environment scores (ß = 0.23, p = 0.03) and child WAZ (ß = 0.30, p = 0.005). The home environment scores were positively correlated with MDAT z-scores (ß = 0.32, p = 0.001). Child nutritional status based on WAZ was also correlated with MDAT z-scores (ß = 0.37, p<0.001). This study demonstrates that caregiver BMI could ultimately relate to child development in children with SAM, through its links to the home environment and child nutritional status.

The introduction of a paediatric nutrition support program led by a clinical dietitian at a low-resource hospital setting in Malawi.

In low- and middle-income countries, nutrition support strategies are often suboptimal or non-existent in hospital settings. This is further compounded by high rates of malnutrition in these countries. The first four dietitians graduated in Malawi in 2017 providing a new opportunity to build capacity to introduce nutrition support in an acute care setting. A paediatric nutrition support program was implemented at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi including the hiring of a local dietitian. This capacity building paper explains the development and introduction of the nutrition support program including a description of perceptions of health professionals at QECH working alongside the dietitian. In the first four months of the program at QECH, the dietitian provided nutrition support to 183 different patients across paediatric wards. Nutritional interventions predominantly included infant formula and breastmilk fortification, provision of therapeutic feeds orally or via nasogastric tubes, increased dietary protein intake for children identified to be at high risk, and nutritional counselling to caregivers. More complex nutritional interventions were also given such as the insertion of gastrostomy tubes to deliver nutrition directly to the stomach. Following the introduction of the program, qualitative interviews were done with health professionals at QECH including nurses (n = 5) and physicians (n = 11). All participants emphasized the importance and impact of the nutrition support program in enhancing the care of hospitalized children, therefore improving outcomes such as tolerability of clinical interventions, decreased duration of stay, and reduced risk of hospital readmission. In conclusion, there is a need for nutrition support provided by a dietitian for different paediatric patients which was corroborated by positive feedback from health professionals at QECH. Integration of dietitians into the healthcare system by respective Ministries of Health will require advocacy around the potential for nutrition support to strengthen the quality of care of vulnerable children. A Chichewa abstract for this paper is available in a supplementary file.

A quantitative cross-sectional survey of psychosocial stimulation and counselling interventions at nutritional rehabilitation units in Southern Malawi.

Background: Inpatient treatment at nutritional rehabilitation units (NRUs) is needed for children who have severe acute malnutrition (SAM) and acute illness, loss of appetite, or severe oedema. World Health Organization guidelines state that nutritional counselling should be done with primary caregivers at NRUs. These recommendations also include psychosocial stimulation interventions to improve developmental outcomes in children with SAM. However, there is limited information about the delivery of these types of interventions for caregivers and children in NRU settings. The primary objective of this research was therefore to obtain data about NRU resources, activities, and protocols relevant to psychosocial stimulation and counselling interventions during inpatient treatment of children with SAM. Methods: A cross-sectional survey was administered by interview at all 16 NRUs in seven districts in Southern Malawi. Participants were health workers, nurses, and nutritionists employed at the respective NRUs. Results: The response rate was 100% across NRUs. Half of participants said that psychosocial stimulation interventions are conducted at their respective NRUs, yet none of the NRUs have protocols for delivery of these interventions. Furthermore, 7/16 (44%) NRUs have no resources for psychosocial stimulation including play materials. Thirteen of 16 (81%) participants said that they feel this type of intervention is very important and 3/16 (19%) participants said that this somewhat important for children with SAM. All NRUs provide counselling to caregivers about breastfeeding and nutrition; 15/16 (94%) also give counselling about water, sanitation and hygiene. Conclusions: Ultimately, results from this survey highlighted that there is a need to invest in comprehensive interventions to improve developmental and nutritional outcomes in these vulnerable children requiring admission to NRUs.

Exploring neurodevelopmental outcome measures used in children with cerebral malaria: the perspectives of caregivers and health workers in Malawi.

BACKGROUND: Progress has been made in tackling malaria however there are still over 207 million cases worldwide, the majority in children. As survival rates improve, numbers of children with long-term neurodisabling sequelae are likely to increase. Most outcome studies in cerebral malaria (CM) have focused only on body function and structure and less on outcomes within the broader framework of the International Classification of Functioning and Disability (ICF). The aim of this study was to utilise qualitative methods to identify relevant clinical outcomes in CM to support formulation of a core outcome set relevant to CM and other acquired brain injuries for use in future clinical trials. METHODS: In depth interviews with parent/caregivers (CGs) of children with/without previous CM (N = 19), and in depth interviews with health professionals (N = 18) involved in their care were conducted in community and clinical settings in and around Blantyre, Malawi. Interviews were audio taped, transcribed, translated and a thematic content analysis was conducted. Themes were categorised and placed firstly in an iterative framework derived from the data but then within the ICF framework. RESULTS: Outcomes perceived as important to carers and professionals fulfilled each level of the ICF. These included impairment in body function and structure (contractures, impaired mobility, visual problems, seizures, cognitive function and feeding); activity and participation outcomes (learning, self-care, relationships in school, play and activities of daily living). Other issues emerging included the social and emotional implications of CM on the family, and balancing care of children with neurodisability with demands of daily life, financial pressures, and child protection. Themes of stigma and discrimination were described; these were perceived to negatively influence care, participation and integration of carer and child into the community. CONCLUSIONS: Outcomes considered important for parents/caregivers and professionals working with children post CM cross all aspects of the ICF framework (impairment, functioning and participation). Outcomes emphasised by families and carers in cross-cultural settings must be given adequate attention when conducting clinical studies in these settings.

HIV coinfection influences the inflammatory response but not the outcome of cerebral malaria in Malawian children.

OBJECTIVES: Study of the effect of HIV on disease progression in heterogeneous severe malaria syndromes with imprecise diagnostic criteria has led to varying results. Characteristic retinopathy refines cerebral malaria (CM) diagnosis, enabling more precise exploration of the hypothesis that HIV decreases the cytokine response in CM, leading to higher parasite density and a poor outcome. METHODS: We retrospectively reviewed data on clinical progression and laboratory parameters in 877 retinopathy-positive CM cases admitted 1996-2011 (14.4% HIV-infected) to a large hospital in Malawi. Admission plasma levels of TNF, interleukin-10, and soluble intercellular adhesion molecule (sICAM-1) were measured by ELISA in 135 retinopathy-positive CM cases. RESULTS: HIV-infected CM cases had lower median plasma levels of TNF (p = 0.008), interleukin-10 (p = 0.045) and sICAM-1 (p = 0.04) than HIV-uninfected cases. Although HIV-infected children were older and more likely to have co-morbidities, HIV-status did not significantly affect parasite density (p = 0.90) or outcome (24.8% infected, vs. 18.5% uninfected; p = 0.13). CONCLUSION: In this well-characterised CM cohort, HIV-coinfection was associated with marked blunting of the inflammatory response but did not affect parasite density or outcome. These data highlight the complex influence of HIV on severe malaria and bring into question systemic inflammation as a primary driver of pathogenesis in human CM.

Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection.

Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV(+)) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV(+) and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV(+) children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV(+) children exacerbates the pathological features associated with CM. IMPORTANCE : There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing coma and death are uncertain. Sub-Saharan Africa has a high HIV prevalence, with 3 million HIV-infected (HIV(+)) children, but the effects of HIV on CM pathogenesis and mortality are unknown. In a study of pediatric CM in Malawi, HIV prevalence was high and CM-attributed mortality was higher in HIV(+) than in HIV-uninfected children. Brain pathology in children with fatal CM was notable not only for sequestered malaria parasites but also for intravascular accumulations of monocytes and platelets that were more severe in HIV(+) children. Our findings raise the possibility that HIV(+) children at risk for malaria may benefit from targeted malaria prophylaxis and that adjunctive treatments targeting inflammation and/or coagulation may improve CM outcomes.