Cerebral malaria in adults at the Infectious Diseases Clinic in the Fann Hospital in Dakar, Senegal

This study aimed at describing cerebral malaria cases findings in the Fann Hospital in Dakar. Data were collected from patients files recorded from 2001 to 2005. One hundred and twenty nine cases of cerebral malaria were admitted to the clinic, accounting for 21.4% of all malaria cases. The sex-ratio M/F was 2.48 and the mean age of patients 28.24 years old +/- 13.7 [12-85 years old]. Patients presented with either coma (91.4%) or mental confusion (10.07%) along with fever (80.6%), convulsions (33.3%). Other severe malaria conditions were observed: jaundice (7 cases), severe anaemia (5 cases), acute renal failure (3 cases), and circulatory collapse (3 cases). Acute pulmonary infection (4 cases) and Salmonella bacteraemia (2 cases) occurred as complications during patient's hospitalisation. The case fatality rate was 20.2% (26 deaths). No neurological sequelae were found among survivors. Cerebral malaria lethality is still high enough to urge for the improvement of working conditions in our clinic. Together with promotion of preventive measures in the community better health care services will help to reduce malaria related morbidity and mortality.     

Severe anaemia in childhood cerebral malaria is associated with profound coma

Background

Severe anaemia in children with cerebral malaria has been associated with respiratory distress secondary to lactic acidosis and/or hypoxia. The ensuing metabolic derangement may further depress the level of consciousness culminating in presentation with profound coma. This association has poorly been studied.

Objective

To determine the relationship between profound coma at presentation and the presence of severe anaemia in children with cerebral malaria.

Methods

This cross-sectional study involved 100 children with cerebral malaria who were consecutively recruited at admission in the Paediatric emergency unit of Mulago hospital in Uganda from July to December 2000. Clinical and laboratory evaluation was done using the hospital''s guidelines for the management of severe malaria. The exposure factor of interest was severe anaemia (Hb < 5.0 g/dl) and occurrence of profound coma (Blantyre coma Scale 0) was the outcome measure.

Results

Severe anaemia and profound coma were seen in 20% and 9% of the children respectively. Severe anaemia was independently associated with profound coma, adjusted OR 1.34 (CI 1.17–1.95), p = 0. 002 and age < 3 years, adjusted OR 1.42 (CI 1.13–1.54), p = 0.001). Thirty percent of those with severe anaemia had deep sighing (acidotic) breathing compared to only 15% of those with haemoglobin (Hb) > 5 g/dl, OR 1.21 (CI 0.90–1.64), p = 0.118. There was no association between the malaria parasite density and severe anaemia. A similar proportion of those with severe anaemia regained consciousness within 24 hours compared to those with Hb > 5 g/dl (30 vs 42.5 %), OR 1.56 (0.65–3.71), p = 0.307.

Conclusions

The findings suggest that profound coma in cerebral malaria may not only result from primary malaria encephalitis but possibly also from a metabolic dysfunction due to severe anaemia.     

Clinical and parasitological aspects of severe malaria in adults in an urban area of Bobo-Dioulasso (Burkina Faso)

From March to December 2000, we carried out a prospective study in the emergency and the internal medicine wards of Bobo-Dioulasso central hospital (Burkina Faso). Among 280 adults with clinical diagnosis of severe malaria, only 60 were confirmed to have severe forms of malaria after the laboratory investigations. Most of these patients (49 cases) were living in the city. The average age was 29.2 years +/- 13.1. At hospital admission, the average temperature was 39.1 degrees C +/- 1 and signs of severe malaria were dominated by impaired consciousness (43 cases), multiple convulsions (6 cases) and severe anaemia (6 cases). Two of these signs were associated in the third of patients. The average parasite density at admission was 11,660 parasites per microliter. 85% of patients hospitalized recovered, 8% died and 7% escaped. The control thick smear at day 3 showed that 23% of patients were still positive. At day 7 none of them was positive. Malaria in adults in urban area is a phenomenon which needs to be assessed and followed in African big towns.     

Genetic diversity of P. falciparum and pathogenesis of the severe malarial anaemia in children under 5 years old in the province of Boulgou, Burkina Faso

The clinical presentation of malaria mainly the severe form may be related to Plasmodium falciparum msp-2 (merozoite surface protein 2) specific family To verify this hypothesis, during the high malaria transmission season in 2001; we analyzed the allelic polymorphism of the msp-2 gene of P. falciparum in children under 5 years old with different presentation of malaria in the regional Hospital and at community level in the Boulgou Province (Burkina Faso). A total of 405 children (107 severe malarial anaemia cases, 102 severe malaria cases without severe anaemia and 196 non severe malaria cases) were enrolled in the study. The frequencies of the FC27 were 89.2% in severe malarial anaemia children group, then 89.7% and 86.9% respectively in severe malaria non anaemic children cases and non severe malaria cases (P = 0.4). The frequencies of the 3D7 were 72.5%; 84.1% and 77% respectively severe malaria non anaemic children, severe malarial anaemia cases and non severe malaria cases (P = 0.7). The complexity of the FC27 genotypes was significantly higher in children with severe malaria (with and without severe anaemia) compared to the non severe malarial children (P < 0.001). No significant difference was pointed up in the complexity of the 3D7 genotypes.     

Severe imported malaria. The experience of the military hospital of Marrakech

Incidence of severe imported malaria increases with the multiplication of humanitarian and military missions in malarial endemic areas. The purpose of this study was to describe the demographic, clinical, therapeutic and outcome aspects of 9 cases which have been hospitalized in the intensive care unit and medecine service of the military hospital of Marrakech, between january 2001 and december 2004. Out of 68 patients admitted with symptomatic malaria during this period, 9 cases were considered as severe. All of them were male soldiers (mean age: 33,3 years), 7 of them have stayed in Democratic Republic of Congo, and 2 in Ivory Coast. Chemoprophylaxis consisted in chloroquine plus proguanil in 5 cases and mefloquine in 4 cases. The mean duration of stay in endemic area was 9,3 months. The clinical presentation was dominated by troubles of consciousness, which justified initial admission in the intensive care unit. The mean duration of hospitalization was 3,3 days in intensive care unit and 5,6 days in the medical department. Thick smear always revealed high parasitemia (5-15%) with Plasmodium falciparum, associated with Plasmodium ovale in two cases. Antimalarial treatment consisted in quinine salts administration. Evolution was favourable without recurrence in 7 cases, but 2 deaths were recorded. Severe imported malaria remains associated with bad outcome and requires early diagnosis and close monitoring of such cases.     

Liver pathology in Malawian children with fatal encephalopathy

A common clinical presentation of Plasmodium falciparum is parasitemia, complicated by an encephalopathy for which other explanations cannot be found, termed cerebral malaria-an important cause of death in young children in endemic areas. Our objective was to study hepatic histopathology in Malawian children with fatal encephalopathy, with and without P falciparum parasitemia, to assess the contributions of severe malaria. We report autopsy results from a series of 87 Malawian children who died between 1996 and 2008. Among 75 cases with P falciparum parasitemia, 51 had intracerebral sequestered parasites, whereas 24 without sequestered parasites had other causes of death revealed by autopsy including 4 patients with clinicopathologic findings which may represent Reye syndrome. Hepatic histology in parasitemic cases revealed very limited sequestration of parasites in hepatic sinusoids, even in cases with extensive sequestration elsewhere, but increased numbers of hemozoin-laden Kupffer cells were invariably present with a strong association with histologic evidence of cerebral malaria by quantitative analysis. Of 12 patients who were consistently aparasitemic during their fatal illness, 5 had clinicopathologic findings which may represent Reye syndrome. Hepatic sequestration of parasitized erythrocytes is not a feature of fatal malaria in Malawian children, and there is no structural damage in the liver. Reye syndrome may be an important cause of fatal encephalopathy in children in Malawi with and without peripheral parasitemia and warrants close scrutiny of aspirin use in malaria-endemic areas.     

Severe malaria in native adults in Abidjan (Côte d'Ivoire)

Our retrospective study carried out from 1985 to 1998 in the Unit of Infectious Diseases in Abidjan aimed at describing the epidemiological, clinical and prognosis features of severe malaria among native adults. Within 14 years, we have listed 274 cases of severe malaria for 54 098 hospitalizations (0.5%). 164 men and 110 women were recorded (sex-ratio = 1.5), aged of 33 years (16-86), among them 48% were HIV positive. 23% of the patients had already received an antimalarial treatment. The main clinical presentation was cerebral malaria (78%). The other manifestations were respiratory symptoms (13%), kidney failure (11%), anaemia (11%), macroscopic haemoglobinuria (6%), hypoglycaemia (9%), cardiovascular shock (4%). The average parasite load in blood was 27 222 plasmodium/microl (25 000 - 180200). The treatment used was quinine IV (172 patients), and arthemeter (102 patients). The outcome was favourable in 232 cases (84%) and 42 patients died. Prognosis factors identified were age > 65 years, Glasgow coma score < 7, convulsions, cardio-vascular shock, macroscopic haemoglobinuria. HIV infection has not been identified as a pejorative factor Our results confirm that severe malaria in native adult is a reality in tropical area. This study shows how difficult it is to have an adequate care management regarding this pathology in our context.     

Severe imported malaria in adults: a retrospective study of 32 cases admitted to intensive care units

INTRODUCTION: Few studies have focused on severe imported malaria in patients admitted to intensive care units. We, therefore, undertook a retrospective study in the University Hospital of Montpellier. MATERIAL AND METHODS: All patients, more than 15 years-old with falciparum malaria who were admitted to intensive care units between October 1997 and April 2004 were included. Main epidemiological features, criteria of admission, treatment and outcome were investigated. RESULTS: Thirty-two patients were included, representing 9% of falciparum malaria cases diagnosed in the same period. The mean age was 44 years. All patients acquired falciparum malaria in sub-Sahara Africa and 25 patients were nonimmune. Chemoprophylaxis was absent or inadequate in 94%. The mean time from symptom onset and treatment initiation was 6 days. Mean parasitemia on admission was 15%. Criteria of admission were impaired consciousness in 69%, acute renal failure in 19% and isolated high parasitemia in 19% of the cases. All, but one received quinine therapy and a loading dose was performed in 34%. Seven patients (22%) had community-acquired coinfections and six (19%) had nosocomial infections. Mortality was 16%. Causes of death were refractory shock, cerebral edema, and acute respiratory distress syndrome. CONCLUSION: Severe imported malaria remains associated with a bad outcome. Improving chemoprophylaxis and an earlier diagnosis may reduce significantly this mortality.     

Manifestations, quality of emergency care and outcome of severe malaria in Mulago Hospital, Uganda

Background

About 100,000 children die annually from severe malaria in Uganda and more than 75% of health unit based deaths occur within 24 hours of admission. Most of these deaths are associated with poor resuscitation systems, delays within the units by health workers and lack of essential drugs and supplies.

Objective

To describe the manifestations and quality of care children with severe malaria receive in Mulago Hospital Paediatric emergency unit and evaluate its impact on outcome.

Methods

A cohort of 784 children with severe malaria was recruited at admission and followed up. Selected measures of quality were the exposure factor and death, the outcome measure.

Results

Only 22.5% of the children were brought at night. The commonest defining manifestations were severe anaemia (39.4%), respiratory distress (17.1%), multiple generalized convulsions (13.3%), hypoglycaemia (11.4%) and cerebral malaria (7.2%). Over 50% lacked an essential drug or supply needed for resuscitation and 23.4% were seen within 1 hour of arrival. Commonly lacking items were intravenous cannulae (53.1%) syringes (23.3%) and blood transfusion sets (15.0%). Children brought at night took a shorter time before being seen by a doctor (1.9 SD 2.4 vs 2.5 SD 2.0 hours, p=0.002), received the first dose of quinine earlier (4.1 SD 3.2 vs 5.2 SD 3.2 hours, p<0.0001), fewer lacked essential drugs and supplies (45% vs 57.9%, p=0.003) and fewer died (0.6% vs 3.8%, p=0.028). Children who lacked an item for resuscitation took 30 minutes longer to receive the first dose of quinine. Caretaker satisfaction was predictive of mortality in the unit.

Conclusions

Quality of care for severe malaria in Mulago paediatric emergency unit is still poor although nighttime services are comparatively better. Caretakers buy at least one resuscitation item in over 50% of cases and their level of satisfaction is predictive of mortality.

Recommendations

The unit should set targets for quality improvement to include increased staffing and supplies, a time limit within which children should be seen and measures of decongestion. Determination of blood sugar in patients with severe malaria should be made a basic requirement.     

Malaria morbidity in Barkedji, village of Ferlo, in Senegal Sahelian area

A study of malaria morbidity was carried out from November 1994 to October 1995, in a Ferlo village (Barkedji) characterized by a long persistence of the temporary ponds. The objective was to evaluate the repercussions of the strong and long anopheles transmission in humans. A clinical follow-up of a group of residents was conducted at home every 10 days by an investigator trained for taking axillary temperature and making thick smears, when suspecting malaria. Were included in the group, 123 voluntary subjects among whom 50% were children under 10 years old. Any feverish subject (T degree >37 degrees 5) or subject presenting other malaria symptoms (headaches, hot body shivers, sweats, aches...) was regarded as having a malaria attack as well as a parasitemia >2500 P/mm3 in children aged of 0 to 14 years old and 1000 P/mm3 in the oldest. During the study subjects with at least one feverish access, plasmodium infection and malaria attack were 58%, 33% and 22%, respectively. On 172 hyperthermias observed, 49% were accompanied by a circulating parasitemia and 30% corresponded to malaria attack. The feverish subjects (74% vs. 42%), the subjects with parasitemia (51% vs. 16%) and the cases of malaria (34% vs. 10%) were more frequently encountered in children under10 than in the oldest. The cases of malaria attacks were more frequent from November to January (70%). The strong intensity of malaria transmission in Barkedji and the persistence of its temporary ponds until January were sufficient to influence the level of malaria morbidity and consequently the development of an anti-malaria immunity by the indigenous population.     

The clinical spectrum of severe malaria in children in the east provincial hospital of Bertoua, Cameroon

Severe malaria claims 1.5 to 2.7 million lives annually most of which are young children in rural areas in sub-Saharan Africa. We retrospectively reviewed the files of 387 patients, admitted and treated for severe malaria according to WHO guidelines, in the Bertoua provincial hospital, a peripheral health center in East Cameroon from 1st October 1998 to 30h October 2000. Our main objective was to study the epidemiological aspects, clinical presentation and outcome. The mean age was 2.7 years (range 2 months - 15 years) among them 214 males and 173 females giving a sex ratio of 1.2. Transmission was observed all year round at variable frequencies with peaks in the rainy seasons. Major symptoms were fever in 202 patients (52.2%), convulsions in 150 (38.8%), prostration in 79 (20.4%) and persistent vomiting in 78 patients (20.2%). Major clinical findings were severe pallor in 196 patients (50.6%) and splenomegaly in 75 patients (19.4%). The average time between onset of symptoms and consultation was 4.4 days (range 1 - 21 days). Blood smears were positive for Plasmodium falciparum in 288 patients (74.4%) and negative in 99 (25.6%). Concerning outcome, recovery was observed in 317 patients (81.9%), interruption of treatment (because of financial constraints) in 58 (15%) and 12 deaths (3.8%). Among the 317 patients who recovered, neurological sequelae were observed in six patients, blindness in four patients and deafness in three patients were the most frequent. We conclude that severe malaria constitutes a major challenge of early diagnosis together with implementation of appropriate treatment especially in rural areas. The use of WHO guidelines in the management of this disease and the recommended preventive measures of vector control have yielded good results in patients managed and followed up in our hospital.     

Falciparum malaria in French residents in Yaounde]

In South Cameroon, malaria is a disquieting problem. It represented 2.6% of consultants and concerned each year 10% among French residents. We have included 310 cases of Falciparum malaria between January 1, 1990 and December 31, 1990. There were 207 adults and 103 children with a mean age of 26 years. The duration of the stay was over one year in 137 cases and lower than 1 year in 183 patients. The chemoprophylaxis was correct in 194 patients according to the dose and duration. Forty-nine patients followed a combination of chloroquine and proguanil. Malaria attack was observed in 272 patients. Among them, there were 95 children. A severe malaria occurred in 38 cases. Mean parasitemia was of 0.24% (range: 0.002-7.5%). Therapy regimen was quinine: 36 cases, halofantrine: 266 cases, amodiaquine: 7 cases and association MFP (Fansimef) in 12 patients. The study shows the importance of malaria in an endemic area among expatriates despite the observance of chemoprophylactics regimens including proguanil.     

Polymorphisms in interleukin-1beta and interleukin-1 receptor antagonist genes and malaria in Ghanaian children

We have investigated the possible associations between polymorphisms in two interleukin-1 (IL-1) genes and severity of Plasmodium falciparum malaria in Ghanaian children with cerebral malaria, severe anaemia or uncomplicated malaria and controls. There was no significant difference in genotype and allele frequencies in IL-1beta exon 5 or interleukin-1 receptor antagonist (IL-1ra) polymorphisms between the studied groups, suggesting that the two polymorphisms may not be involved in the pathogenesis of severe malaria. When parasitaemias in uncomplicated malaria patients were evaluated, a significantly higher level of parasitaemia was observed among carriers of IL-1beta A2 allele as compared with noncarriers of this allele (P = 0.01). The mean parasitaemia in an age-matched asymptomatic group did not reveal such associations. These data suggest that IL-1beta exon 5 allele 2 may play a possible role in the clinical outcome of uncomplicated malaria.     

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. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69⁺ NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4⁺ lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.     

Diagnostic et prise en charge du paludisme grave chez l’adulte : observance des directives nationales au Burkina Faso

The purpose of this study was to assess the application of national guidelines on the diagnosis and treatment of severe malaria in adults in Burkina Faso. We conducted a retrospective study of medical records of the patients admitted for severe malaria in the emergency service of the regional hospital of Fada N'Gourma in the east of Burkina Faso in the year 2008; 165 records were chosen by simple random sampling. We reported all the severe clinical and biological signs of malaria and its treatment. We compared them with the criteria of severe malaria diagnosis and its treatment according to the national guidelines. The mean age of patients was 38 ± 16.2 and male to female ratio was 0.96. The most frequent period of admissions was between July and October. Fever or recent past of fever was reported in 142 cases (86.1%). According to the two criteria for severe malaria (means existing of at least one of the severe signs associated and positive parasitemia with Falciparum plasmodium), we noted that only 74 cases had at least one of the severe signs (44.8%) which were: anemia (51.3%), cardiovascular collapse (7.9%), jaundice (7.3%), dyspnea (6.7%), impairment of consciousness (5.5%), prostration (5.5%), renal failure (4.8%), hypoglycemia (2.4%), hemorrhage (1.8%) and seizures (1.2%). The biological signs were not systematically searched. Parasitological exam was conducted in 91 cases (55.1%). Only 18 were positive (19.8%). In total, only 18 cases (10.9%) met the guidelines' criteria of severe malaria. The other cases were over-diagnosed; note that the investigation was not complete for 74 of these cases (50.3%). Among the 165 cases, the treatment was appropriate in 146 (88.5%) and 19 cases (11.5%) didn't receive treatment for malaria. CONCLUSION: So much we observed an over diagnosis of severe malaria in adults that we can suggest an under diagnosis of the disease due to the lack of biological investigations.     

Increased eosinophil activity in acute Plasmodium falciparum infection—association with cerebral malaria

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8–10.7 ng/ml)) than in SA (4.7 ng/ml (3.0–7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6–5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.     

Pertinence of the 2000 WHO criteria in non-immune children with severe malaria in Dakar, Senegal

The relevance of World Health Organization (WHO) criteria for severe malaria has not been assessed in non-immune children. The objectives of this study were (i) to evaluate the significance of 1990 WHO definition reconsidered in 2000 on distribution and lethality of severe cases in children admitted with falciparum malaria, and (ii) to contribute to the study of relevance of the WHO severe criteria in Dakar, an hypoendemic area in Senegal. PATIENTS AND METHODS: The 1990 WHO criteria, respiratory distress and platelet counts were prospectively collected in 1997-99 from children admitted to H?pital Principal de Dakar, Senegal, with falciparum malaria diagnosed on a thick blood film. This method allowed also the definition of severe cases according to 2000 WHO criteria. RESULTS: Among 311 patients (median age: 8 years old), according to the 2000 WHO criteria, the frequency of severe malaria cases was increased by 23% (75% versus 52%) and case-fatality rates thereof were decreased by 5% (17% versus 12%) compared with 1990 WHO definition. One death occurred among cases defined as severe on admission only according to criteria modified by WHO in 2000. A multivariate logistic regression model identified several independent prognostic factors: cerebral malaria, hypoglycaemia, respiratory distress, renal failure, collapse, abnormal bleedings, pupillary abnormalities and thrombocytopaenia defined as a platelet count below 100,000/mm3. A significant association (p < 0.001) was observed between platelet count increase and consciousness level improvement, evaluated on day of first platelet count control (time from admission: 1-7 d). Among survivors, a lesser improvement in coma score was associated with a decrease in platelet counts (p < 0.04). CONCLUSIONS: The 1990 WHO criteria, which predicted death among malaria cases in children living under stable falciparum transmission, are relevant in this series of non-immune children living in a low and seasonal transmission. Nevertheless new WHO criteria showed poor prognostic significance. However, the 2000 WHO definition was highly sensitive to detect severe malaria cases. These findings should be considered for managing severe malaria in migrant children.     

Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications

Cerebral malaria is associated with decreased production of nitric oxide and decreased levels of its precursor, l-arginine. Abnormal amino acid metabolism may thus be an important factor in malaria pathogenesis. We sought to determine if other amino acid abnormalities are associated with disease severity in falciparum malaria. Subjects were enrolled in Dar es Salaam, Tanzania (children) (n = 126), and Papua, Indonesia (adults) (n = 156), in two separate studies. Plasma samples were collected from subjects with WHO-defined cerebral malaria (children), all forms of severe malaria (adults), and uncomplicated malaria (children and adults). Healthy children and adults without fever or illness served as controls. Plasma amino acids were measured using reverse-phase high-performance liquid chromatography with fluorescence detection. Several plasma amino acids were significantly lower in the clinical malaria groups than in healthy controls. Despite the differences, phenylalanine was the only amino acid with mean levels outside the normal range (40 to 84 microM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] microM; P < 0.0001) and adults with all forms of severe malaria (median [95% confidence interval], 129 [111 to 155] microM; P < 0.0001). In adults who survived severe malaria, phenylalanine levels returned to normal, with clinical improvement (P = 0.0002). Maintenance of plasma phenylalanine homeostasis is disrupted in severe malaria, leading to significant hyperphenylalaninemia. This is likely a result of an acquired abnormality in the function of the liver enzyme phenylalanine hydroxylase. Determination of the mechanism of this abnormality may contribute to the understanding of neurological complications in malaria.     

Therapeutic efficiency of chloroquine in the savannah region in the north of Côte d'Ivoire (1997)

We evaluated from August to December 1997 the therapeutic effect of chloroquine (CQ) in treatment of mild malaria. Five villages of the savannah area of C?te d'Ivoire were selected for this study In this area and season, the transmission of malaria is of hyper-endemic type. The 14-day protocol of WHO was used and all the patients were treated with CQ 25 mg/kg over three days. 360 febrile children between 6 and 83 months old out of 545 were selected, and 286 were fully followed. At the beginning of the study axillary temperatures and parasitemia showed no difference in the 5 villages. The average therapy failure rate was 11.5% (IC to 95%; 7.8-15.2) with a maximum of 18.5%. The failure rates estimated in the various villages showed a hardly significant difference (p = 0.05). In the North of C?te d'Ivoire, the good efficiency of CQ can be explained by the low drugs pressure related to the behaviour of populations who use traditional phytotherapy in first resort to treat the fevers.     

Management of severe falciparum malaria

Plasmodium falciparum is the most common cause of severe and life-threatening malaria. Falciparum malaria causes over one million deaths every year. In Africa, a vast majority of these deaths occur in children under five years of age. The presentation of severe malaria varies with age and geographical distribution. The mortality rate is higher in adults than in children but African children develop neuro-cognitive sequelae following severe malaria more frequently. The management of severe malaria includes prompt administration of appropriate parenteral anti-malarial agents and early recognition and treatment of the complications. In children, the complications include metabolic acidosis (often caused by hypovolaemia), hypoglycaemia, hyperlacticacidaemia, severe anaemia, seizures and raised intracranial pressure. In adults, renal failure and pulmonary oedema are more common causes of death. In contrast, concomitant bacterial infections occur more frequently in children and are associated with mortality in children. Admission to critical or intensive care units may help reduce the mortality, and the frequency and severity of sequelae related to severe malaria.