Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria: A Randomized Clinical Trial.

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae.

Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.

Capacity Building in Pediatric Critical Care-Global Health Research and Education: The Blantyre Experience.

Pediatric critical care medicine (PCCM), as it is practiced in high-income countries, is focused on specialized medical care for the most vulnerable pediatric patient populations. However, best practices for provision of that care globally are lacking. Thus, PCCM research and education programming can potentially fill significant knowledge gaps by facilitating the development of evidence-based clinical guidelines that reduce child mortality on a global scale.

Delayed presentation to hospital care is associated with sequelae but not mortality in children with cerebral malaria in Malawi.

Background: Cerebral malaria is still a major cause of death in children in sub-Saharan Africa. Among survivors, debilitating neurological sequelae can leave children with permanent cognitive impairments and societal stigma, resulting in taxing repercussions for their families. This study investigated the effect of delay in presentation to medical care on outcome in children with cerebral malaria in Malawi.

Overdiagnosis of Malaria Illness in an Endemic Setting: A Facility-Based Surveillance Study in Malawi.

In endemic settings where asymptomatic malaria infections are common, malaria infection can complicate fever diagnosis. Factors influencing fever misdiagnosis, including accuracy of malaria rapid diagnostic tests (mRDTs) and the malaria-attributable fraction of fevers (MAF), require further investigation. We conducted facility-based surveillance in Malawi, from January 2012 through December 2013 in settings of high perennial (Chikhwawa), high seasonal (Thoylo), and moderate seasonal (Ndirande) malaria transmission.

Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years.

Presentation of life-threatening invasive nontyphoidal Salmonella disease in Malawian children: A prospective observational study.

Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available.

Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status.

The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi.

Background: Persistence of sulfadoxine-pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low. Higher malaria transmission is associated with greater genetic diversity and more frequent genetic recombination, which could lead to a more rapid re-emergence of SP-sensitive parasites, as well as more rapid degradation of selective sweeps. In this study, the impact of local variation in malaria transmission on the prevalence of SP-resistant haplotypes and selective sweep characteristics was investigated at an urban site with low parasite prevalence and two rural sites with moderate and high parasite prevalence.

Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study.

Background: Fever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an important cause of CNS infection in such patients, and examined the relative contribution of viral pathogens and malaria parasitaemia.

Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children.

We investigated the benefit of 2 candidate adjunctive therapies in bacterial meningitis: glycerol, which has shown promise in earlier studies, and acetaminophen, which is reportedly beneficial in adult septicemia. In a hospital in Blantyre, Malawi, we enrolled 360 children aged ≥ 2 months with proven bacterial meningitis (36% HIV infected) in a double-blind, randomized, placebo-controlled trial of glycerol and acetaminophen in a 2 × 2 factorial design. Of 4 groups, first group received oral glycerol, second received rectal acetaminophen, third received both therapies and the fourth received placebos only.

Histidine-rich protein 2 plasma levels predict progression to cerebral malaria in Malawian children with Plasmodium falciparum infection.

Some children with uncomplicated malaria progress to cerebral malaria despite appropriate treatment; identifying them in advance might improve their care. The objective of this study was to determine if plasma concentrations of a malaria protein, HRP2 (histidine-rich protein 2) would serve this purpose. Cases and controls were children presenting with uncomplicated malaria; the cases (n = 25) developed cerebral malaria, and the controls (n = 125) did not.

Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children.

Background: Brain histology and ophthalmoscopy suggest that approximately 25% of children with World Health Organization-defined cerebral malaria (CM) have a nonmalarial cause of death. Misclassification complicates clinical care, confounds studies of association, and may obfuscate successes in malaria control. Retinopathy predicts intracerebral parasite sequestration with >90% sensitivity and specificity, but detecting retinopathy requires well-trained personnel and expensive equipment.