BackgroundKaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. MethodsChildren with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. FindingsFifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event=death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. ConclusionOverall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.

Keywords : adapted treatment regimensAfricacost efficiency analysislow income countriesnephroblastomatwinnigwilms tumor

We describe five children who died of clinical rabies in a three month period (September to November 2011) in the Queen Elizabeth Central Hospital. From previous experience and hospital records, this number of cases is higher than expected. We are concerned that difficulty in accessing post-exposure prophylaxis (PEP) rabies vaccine may be partly responsible for this rise. We advocate: (a) prompt course of active immunisation for all patients with significant exposure to proven or suspected rabid animals. (b) the use of an intradermal immunisation regime that requires a smaller quantity of the vaccine than the intramuscular regime and gives a better antibody response. (c) improved dog rabies control measures

BACKGROUND AND PURPOSE: There have been few neuroimaging studies of pediatric CM, a common often fatal tropical condition. We undertook a prospective study of pediatric CM to better characterize the MRI features of this syndrome, comparing findings in children meeting a stringent definition of CM with those in a control group who were infected with malaria but who were likely to have a nonmalarial cause of coma.MATERIALS AND METHODS: Consecutive children admitted with traditionally defined CM (parasitemia, coma, and no other coma etiology evident) were eligible for this study. The presence or absence of malaria retinopathy was determined. MRI findings in children with ret+ CM (patients) were compared with those with ret- CM (controls). Two radiologists blinded to retinopathy status jointly developed a scoring procedure for image interpretation and provided independent reviews. MRI findings were compared between patients with and without retinopathy, to assess the specificity of changes for patients with very strictly defined CM.RESULTS: Of 152 children with clinically defined CM, 120 were ret+, and 32 were ret-. Abnormalities much more common in the patients with ret+ CM were markedly increased brain volume; abnormal T2 signal intensity; and DWI abnormalities in the cortical, deep gray, and white matter structures. Focal abnormalities rarely respected arterial vascular distributions. Most of the findings in the more clinically heterogeneous ret- group were normal, and none of the abnormalities noted were more prevalent in controls.CONCLUSIONS: Distinctive MRI findings present in patients meeting a stringent definition of CM may offer insights into disease pathogenesis and treatment.

Severe anaemia is major cause of childhood morbidity and mortality in Africa and accounts for up to 54% of malaria-related deaths (Slutsker et al, 1994). Most severe anaemia-related deaths occur in children with signs of respiratory distress and/or cardiac failure, often within the first 24 h of admission to hospital (Marsh et al, 1995). The World Health Organization (WHO) advises that severely anaemic children should be transfused with 10 ml/kg of packed red cells (PRC), or 20 ml/kg of whole blood (WB) if PRC are not available (WHO 2000). This study assessed the clinical and early haematological responses of severely anaemic children transfused according to WHO guidelines. In addition, we attempted to identify clinical and laboratory markers that would predict a transfusion failure. A prospective cohort study was conducted at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi in March–April 2007. Children <5 years of age presenting with signs and symptoms suggestive of severe anaemia [defined as haemoglobin (Hb) of <40 g/l or Hb <60 g/l with evidence of hypoxia or hyperparasitaemia] were screened, and eligible children enrolled after obtaining informed consent. A physical examination was performed and a blood sample collected for Hb check (Hemocue Hb 301; HemoCue AB, Angelholm, Sweden), thick film for malaria parasites, glucose, blood group and cross-match. When a diagnosis other than malaria was suspected, children were managed according to hospital protocol. Blood for transfusion was obtained from the Malawi Blood Transfusion Service (MBTS) and screened according to MBTS standard operating procedures. Severely anaemic children were transfused over 3 h with either 10 ml/kg of PRC or 20 ml/kg of WB, depending on hospital availability. Clinical assessments were done every 15 min for the first two hours and half-hourly for the last hour. Post-transfusion Hb was measured after 24 h. Ethical approvals were obtained from the College of Medicine Research Ethics Committee and the Liverpool School of Tropical Medicine (LSTM) Ethics Committee. Statistical analysis was done using stata version 10 (StataCorp, College Station, TX, USA). Continuous data were analysed by independent samples Student t-tests; categorical data were analysed using the chi-squared or Fisher’s exact test. The change in Hb (delta Hb) was defined as the difference between the post- and pre-transfusion Hb. Delta respiratory rate (RR) and delta heart rate (HR) were defined as the difference in RR/HR between the start of transfusion and the RR/HR at 60, 120 and 180 min after transfusion was commenced. Transfusion failure was defined by a post-transfusion Hb ≤ 60 g/l (WHO cut-off for symptomatic severe anaemia). Univariate and multivariate logistic regression analyses, using transfusion failure as the outcome, were performed and important clinical and baseline parameters were analysed after patients were categorized into groups based on presence or absence of malaria parasitaemia. One hundred and twenty-eight children were recruited with a mean (SD) age of 22·6 (13·8) months (Table I). Malaria parasites were found in 73·4% of children, suspected septicaemia in 14·1% and suspected pneumonia in 7%. The in-patient mortality rate was 4·7% (6/128). Thirty children (23·4%) were classified as transfusion failures (post-transfusion Hb ≤ 60 g/l). Multivariate analysis identified a high pre-transfusion Hb (Adjusted Odds Ratio [adj. OR] 0·4; 95% confidence interval [CI] 0·25–0·68; P = 0·001) and a reduction in respiratory rate (delta RR) (Adj. OR 0·93; 95% CI 0·88–0·98; P = 0·008) to be significantly associated with a reduced risk of transfusion failure (Table II). Children without malaria had better Hb responses to blood transfusion compared with malaria-infected children (mean (SD) Hb increase 31 (12) g/l vs. 26 (11) g/l; P = 0·02) (Table III), but transfusion failures were not predicted by malaria infection (Table II). The high transfusion failure rate (23·4%) observed in this study, comparable with the 24% transfusion failure rate (defined as post-transfusion Hb ≤ 50 g/l) observed in Kenya (English et al, 2002), raises concern as to whether the current WHO guidelines are adequate for the treatment severe anaemia in resource-limited settings. In many clinics across sub-Saharan Africa, access to laboratory investigations is limited and post-transfusion Hb checks are not routine. Children inadequately transfused, but clinically improved, are discharged home without a follow-up appointment, putting them at risk of rebound severe anaemia. When this occurs, parents may chose not to return to hospital but instead keep the child at home or seek advice from a traditional healer (Mota et al, 2009). In this way transfusion failures may contribute significantly to the high post-discharge mortality observed in Malawi, Kenya and Gambia following hospital admission for severe anaemia (Bojang et al, 1997; Lackritz et al, 1992, 1997; Phiri et al, 2008; Zucker et al, 1996). Our results suggest that early identification of children at high risk of transfusion failure may be possible. A low pre-transfusion Hb level and the absence of a significant reduction in respiratory rate (delta RR) during transfusion were reliable predictors of transfusion failure. Malaria infection was associated with poor early Hb response to blood transfusion. Adequate emphasis should be placed on parasitological clearance and close clinical monitoring during hospitalization in areas endemic for Falciparum malaria. A limitation of the study was that the type of transfusion (either PRC or WB) given was based on availability and not random allocation. All clinical assessments were done manually, so were subject to observer bias. Human immunodeficiency virus testing was not part of routine practice at the paediatric department during our study and thus was a missed opportunity. Blood transfusion in resource-limited settings using the current WHO guidelines results in a high transfusion failure rate. A low pre-transfusion Hb level and little reduction in respiratory rate during transfusion may help to detect early those at high risk of failing. Introducing post-transfusion Hb checks in resource-limited settings and reviewing the ‘one-size-fits-all’ approach on transfusion policy may need to be considered. There is a need to evaluate the safety and efficacy of alternative transfusion strategies. MOE developed the study protocol and wrote the manuscript; BC- logistics; MM- statistical advice and editorial input was provided by KSP, BC, EMM and MBvH. Special thanks to Professors Bernard Brabin, Feiko ter Kuile and Dr Imelda Bates of LSTM, Dr Bridon M’baya of MBTS. The study was funded by the LSTM Master of Tropical Paediatrics programme.

In addition to parasite resistance, inadequate levels of exposure to antimalarial drugs may contribute to treatment failure. We developed population pharmacokinetic (PK) models to describe the distribution of sulfadoxine (SDX) and pyrimethamine (PYM) in children with uncomplicated malaria in Malawi. The concentration levels of antimalarial drugs in whole blood were determined using high-performance liquid chromatography. We found no evidence of underdosing in children as compared with adults; the children had drug exposure levels similar to those described in adults. Treatment failure was more likely in children with lower PYM concentrations on day 14 (P = 0.024), and there was a trend for lower SDX concentrations on day 14 (P = 0.061). SDX and PYM concentrations at levels predictive of treatment failure have been identified at day 14. Less than one-third of the children displayed drug concentration levels above these thresholds after receiving the recommended SDX-pyrimethamine (SP) dose. Our findings suggest that PK factors contributed to the observed high rate of treatment failure, and we therefore recommend a higher SP dose for children under the age of 5 years.

Objective To assess the impact of HIV infection and exposure on survival in critically ill children requiring resuscitation.Methods A 6-month descriptive prospective cohort study of all live admissions to the resuscitation room of an urban paediatric emergency department in Blantyre, Malawi.Results 583 children were resuscitated, of whom 401 (69%) survived to hospital discharge. 26% of all children tested positive for HIV infection (152/576), and this was highest in patients presenting with shock (66%; 162/247), clinically diagnosed septicaemia (57%; 125/218) and malnutrition (40%; 24/60). Of 152 HIV-seropositive children, 30 (20%) died within 24 h, while among 424 seronegative children 36 (8.4%) died within 24 h (p<0.001). Later deaths (>24 h) were also more common in HIV-seropositive children compared with HIV-uninfected patients (24.3% vs 12.3%; p<0.001). Survival to 24 h was 80% (122/152) and to discharge 56% (85/152) in HIV-seropositive children. In HIV-uninfected children survival to 24 h was 92% (388/424) and to discharge 79% (336/424).Conclusion Early and late case death rates are greater in HIV-seropositive than in HIV-uninfected children. 80% of HIV-infected children survived the period most influenced by the process of resuscitation, that is, the first 24 h. HIV status alone should not influence the limitation of intervention decisions in the resuscitation room when faced with a critically ill child.

Severe anaemia is a common childhood emergency in developing countries. Practical evidence‐based guidance on when to transfuse, volume of transfusion and ideal duration of transfusion is lacking. The aim of this study is to develop a paediatric transfusion protocol for use in under‐resourced environments and evaluate its usability in a busy African hospital setting. A paediatric transfusion protocol based on the WHO Guidelines was developed for the Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. On the basis of simple bedside clinical features of respiratory, cardiovascular and neurological compromise, the protocol allocates children with severe anaemia (haemoglobin ≤ 6 g dL−1) to one of the three groups: complicated anaemia, uncomplicated anaemia and anaemia with severe malnutrition. Data were collected to monitor protocol adherence, delays to transfusion, post‐transfusion haemoglobin and need for repeat transfusion. Two‐hundred and fifteen severely anaemic children were enrolled: 180 complicated, 25 uncomplicated and 10 severely malnourished. With respect to protocol adherence, all children were allocated to the correct transfusion group; correct volume (±10%) was given in 89·3%; correct duration (±30 min) in 86·2% and correct overall rate (±10%) in 78·6%. Comparing old and new transfusion guidelines, a potential avoidable transfusion rate of 29% was found. This study demonstrates that clear and detailed transfusion guidelines based on simple bedside clinical features can be used in a very busy children's hospital in sub‐Saharan Africa. With minimal additional equipment, volume and duration of transfusion can be well controlled. Furthermore, having a protocol in place results in a significant reduction of avoidable transfusions.

Introduction: The clinical course and outcome of non-typhoidal salmonella (NTS) meningitis in Malawian children over a 10-year period (1997-2006) is described.Methods: Demographic, clinical and laboratory data were collected for all children over 2 months of age admitted with salmonella meningitis to Queen Elizabeth Central Hospital from 1997 to 2006. In the 1st year, salmonellae were susceptible to chloramphenicol, and children received 2 weeks of chloramphenicol treatment. When NTS resistance to chloramphenicol started to appear in 1998, treatment was changed to ceftriaxone. From 2002, the duration of antibiotic therapy was extended to 4 weeks which included 2 weeks of intravenous ceftriaxone and a further 2 weeks of oral ciprofloxacin.Results: The in-hospital case fatality rate (CFR) was 52.3% (48.2% until 2002 and 53.9% after prolonged antibiotic therapy was introduced). Of the survivors, one in 12 (8.3%) became completely well (sequelae-free) in the period 1997-2001 while 18 of 31 survivors (58.1%) made a complete recovery during 2002-2006 (p<0.01). After the 4-week course of antimicrobial therapy was introduced, the number of relapses or recurrences fell from nine in 15 (60%) survivors treated with chloramphenicol or ceftriaxone to three in 35 (8.7%) survivors who received 4 weeks of antibiotics (p<0.0001).Conclusion: In Malawi, salmonella meningitis has a CFR of similar to 50%, which has remained constant over many years. Residual morbidity, however, has decreased over 10 years, despite rising numbers of multi-drug-resistant cases of NTS. This improvement might be owing to better treatment and management and/or reduced pathogenicity of the multi-drug-resistant bacteria.

SETTING:Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis (TB) control. Methods to augment sputum collection are available, but their additional benefit is uncertain in resource-limited settings. OBJECTIVE:To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. DESIGN:Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients provided physiotherapy-assisted sputum and induced sputum, followed the next morning by gastric washing and bronchoalveolar lavage (BAL) samples. RESULTS:A total of 150 patients diagnosed with smear-negative PTB by the hospital service were screened; 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled in the study; 89% were human immunodeficiency virus positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. Of the 46 smear-positive cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy-assisted samples. CONCLUSIONS:For countries such as Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using BAL after induced sputum is limited.

Objectives:Bronchoalveolar lavage obtained at bronchoscopy is useful for research on pulmonary defence mechanisms. Bronchoscopy involves some discomfort and risk to subjects. We audited the process of consent, experienced adverse effects and reasons for participation among research bronchoscopy volunteers.Design:100 consecutive volunteer research subjects attending for bronchoscopy, repeat bronchoscopy or routine recruitment clinic were interviewed. Information was gathered about volunteer motivation, perception of the consent process and adverse effects of bronchoscopy. Suggestions for improvement were requested. Responses were themed by a second investigator prior to data analysis.Results:81 bronchoscopy-experienced subjects (total of 263 procedures) and 19 new volunteers were interviewed. 19 subjects (21%) reported adverse symptoms during or after bronchoscopy, but no symptoms were of sufficient severity that they would not repeat the procedure. The frequency of symptoms was not related to gender, the quality of the lavage or the HIV status of the subject. 76 subjects (94%) reported that the information given pre-procedure was useful and adequate but 43 (56%) had further questions mostly relating to their own results. The reasons given for research participation were access to health assessment (75 subjects), access to treatment when ill (61 subjects), desire to participate in research (15 subjects) and remuneration (6 subjects). 7 subjects complained that the remuneration was inadequate.Conclusions:The main incentive to participation in research bronchoscopy was access to healthcare. Informed consent and procedure technique were adequate but subjects would value more feedback about individual and project results.

Evidence from autopsy and in vitro binding studies suggests that adhesion of erythrocytes infected with Plasmodium falciparum to the human host intercellular adhesion molecule (ICAM)-1 receptor is important in the pathogenesis of severe malaria. Previous association studies between polymorphisms in the ICAM1 gene and susceptibility to severe malarial phenotypes have been inconclusive and often contradictory. We performed genetic association studies with 15 single nucleotide polymorphisms (SNPs) around the ICAM1 locus. All SNPs were screened in a family study of 1071 trios from The Gambia, Malawi and Kenya. Two key non-synonymous SNPs with previously reported associations, rs5491 (K56M or ‘ICAM-1Kilifi’) and rs5498 (K469E), were tested in an additional 708 Gambian trios and a case-control study of 4058 individuals. None of the polymorphisms were associated with severe malaria phenotypes. Pooled results across our studies for ICAM-1Kilifi were, in severe malaria, odds ratio (OR) 1.02, 95% confidence interval (CI) 0.96–1.09, P=0.54, and cerebral malaria OR 1.07, CI 0.97–1.17, P=0.17. We assess the available epidemiological, population genetic and functional evidence that links ICAM-1Kilifi to severe malaria susceptibility.

Objectives To document surgical activities at all district hospitals in Malawi in relation to human and material resources available. Materials And Methods Twenty-one district hospitals were visited by two surgical registrars (trainees). Using a structured questionnaire data were collected regarding surgical facilities at the district hospital after interviewing key officers (district health officer, medical officer, matron or clinical officer). The operating theatre logbooks were reviewed and all recorded surgical activities for the calendar year 2003 were analyzed. Results All district hospitals had functioning operating theatres. None of the hospitals had a resident trained surgeon. Most district hospitals are manned by a single general doctor (medical officer) and two or more paramedical officers (clinical officer / medical assistant). In 2003 a total of 28594 surgical procedures were performed in the district hospitals. 12506 (44%) were obstetric or gynaecological procedures. Only 821 (3%) were general surgical cases. Conclusions And Recommendations It appears district clinicians are happy to manage emergency obstetric and gynaecological cases but tend to refer emergency general surgical cases. Delay in operating on abdominal emergencies increases morbidity and mortality, thus there is a strong case for improving surgical manpower and skills at the district hospital so that these cases can be performed at the district hospital. To have a surgeon at every district hospital is a distant goal, however training of existing medical 1.

This article describes high-performance liquid chromatographic assays for the quantification of sulfadoxine (SDX), pyrimethamine (PYM), chloroquine (CQ), amodiaquine (AQ) and desethylamodiaquine (AQM) from whole blood. All four assays were set up and validated in Malawi using a common high-performance liquid chromatography platform and column and involved the use of simple mobile phase and extraction reagents. Calibration curves were linear (r2>0.95) in the ranges 5–100μg/ml, 50–1000, 150–1500, 100–1000 and 100–1000ng/ml for SDX, PYM, CQ, AQ and AQM, respectively. Intra-assay and inter-assay coefficients of variation were <15% at 3 points spanning the concentration range and <20% at the lower limit of quantification. The assays were specific with no interference from the other antimalarials described in this report. All four assays use liquid–liquid extraction, reversed-phase chromatography and UV detection and require between 50 and 200μl of blood. Because the assays share common instruments and reagents, they are cost-efficient and could be used to optimise antimalarial drug therapies in other resource poor settings.

Background Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children. Procedure. A retrospective audit of the spectrum and clinical presentation of cancers among children (< 16 years) seen at Queen Elizabeth's Central Hospital (QECH), between 1998 and 2003. Results. Seven hundred seven children with cancer were seen, the number of cases per year increased over the time period; 50% (351) had Burkitt lymphoma, 13% (89) had retinoblastoma, and 9% (61) had Kaposi sarcoma, with a variety of other tumors comprising the remainder. Kaposi sarcoma markedly increased in frequency over time. Histological verification of diagnosis was available for 49% (348). The proportion of children with cancer who were tested for HIV increased over time, but varied by cancer type. Amongst those tested, the seroprevalence was 93% (52/56) for children with Kaposi sarcoma, 4% (11/289) for those with Burkitt lymphoma, 31% (8/26) for those with other nonHodgkin lymphomas, 7% (1/15) for those with Hodgkin disease, and 5% (5/103) for those with other cancers. Conclusions. The number of cases seen per year has increased over the study period for almost all cancers, hut in particular for Kaposi sarcoma. Burkitt lymphoma remains the commonest pediatric tumor in Malawi. In the case of Burkitt lymphoma, non-Hodgkin lymphoma, and Kaposi sarcoma there is a significant difference in the presentation of HIV-seropositive and -seronegative children.

Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, and human immunodeficiency virus (HIV) infection. We conducted a pharmacokinetic study of children treated for tuberculosis with thrice-weekly pyrazinamide (n = 27; mean age, 5.7 years) and of a separate group of children treated with thrice-weekly ethambutol (n = 18; mean age, 5.5 years) as portions of tablets according to national guidelines. Malnutrition and HIV infection were common in both groups. Blood samples were taken just prior to oral administration of the first dose, and subsequent samples were taken at intervals of 2, 3, 4, 7, 24, and 48 h after drug administration. Serum drug levels were low in all children for both drugs; in almost all cases, the maximum concentration of the drug in serum (Cmax) failed to reach the MIC for Mycobacterium tuberculosis. The Cmax of pyrazinamide was significantly lower in younger children (<5 years) than in older children. The Cmax of pyrazinamide was also lower for HIV-infected children and children with severe malnutrition, but these differences did not reach statistical significance. No differences were found for ethambutol in relation to age, HIV infection, or malnutrition, but the Cmax was <2 mg/liter in all cases. Studies of pharmacokinetic parameters and clinical outcomes obtained by using higher dosages of drugs for treatment of childhood tuberculosis are needed, and recommended dosages may need to be increased.

Neonatal sepsis is common and often fatal in Malawi. The aim of this retrospective study was to report causes, antibiotic resistance and outcome of sepsis in Malawian neonates. We reviewed all blood and cerebrospinal fluid isolates collected between January, 1996, and December, 2001, from inpatients aged 0-30 days with suspected sepsis at the Queen Elizabeth Central Hospital, Blantyre. In vitro resistance to antibiotics commonly used in Malawi was assessed. Case-fatality rate was analysed with respect to age, bacterial pathogen and infection site. A total of 801 bacteria were isolated from 784 neonates over six years – 599 isolates from blood and 202 from cerebrospinal fluid. Overall, 54% of bacteria were Gram positive and 46% were Gram negative. The commonest causes of neonatal sepsis were Group B Streptococcus (17%) and non-typhoidal Salmonella (14%). In vitro antibiotic susceptibility to the first-line antibiotic combination of penicillin and gentamicin was 78% for all isolates, but in vitro sensitivity to gentamicin for Klebsiella spp. and non-typhoidal Salmonella was 33% and 53% respectively. In-hospital case-fatality rate was known for only 301 cases and was high at 48%. Group B Streptococcus was associated with the best outcome. Mortality was significantly higher if presentation was in the first week of life or if sepsis was due to Gram-negative bacteria. Malawi Medical Journal Vol. 17(3) 2005: 92-96

Objective: To investigate capillary blood flow in the optic nerve head ( ONH) of children with cerebral malaria.Methods: Malawian children with cerebral malaria admitted to a paediatric research ward were examined by direct and indirect ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF) in suitable patients. Mean blood volume and velocity were obtained from 30 to 60 s recordings from the temporal ONH and used to calculate blood flow. These were compared with admission variables, funduscopic findings and disease outcomes.Results: 45 children with cerebral malaria had LDF recordings; 6 subsequently died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The mean microvascular blood volume was higher in patients with papilloedema (3.28 v 2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = 20.49, p = 0.001).Conclusion: The increase in ONH microvascular blood volume in papilloedema measured by LDF is consistent with current theories of pathogenesis of papilloedema. LDF has potential as a tool to distinguish papilloedema from pseudopapilloedematous disc swellings. The relationship between blood velocity and haematocrit may relate to levels of sequestration in cerebral malaria.

Falciparum malaria is characterized by cytoadherence of host erythrocytes containing mature asexual-stage parasites and the consequent sequestration of these forms in tissue microvasculature. A postmortem study of pediatric malaria provided us with the opportunity to compare the genetic complexity of circulating and sequestered Plasmodium falciparum populations, in patients with fatal cerebral malaria ( CM) versus control subjects with incidental P. falciparum parasitemia who died of causes other than malaria. Parasite genotypes identified in peripheral blood collected at the time of admission to the hospital constituted a subset of those detected in the tissues at death. Despite a higher tissue burden of parasitized erythrocytes in patients with CM than in parasitemic control subjects, parasite populations in tissues from patients with CM were less genetically complex, and the genotypes were more homogeneously distributed throughout the body, than in patients with incidental infection. Our findings support the notion that CM is associated with the emergence of a small number of dominant genotypes in an infected individual.