A comparative clinical trial of artemether and quinine in children with severe malaria

OBJECTIVE: To compare the efficacy of artemether and quinine in the treatment of severe malaria in hospitalized children. STUDY DESIGN: Open randomized trial. SETTING: Pediatric ward of a tertiary care center. METHODS: All children admitted with clinical manifestations of severe malaria (as per WHO criteria) and asexual forms of Plasmodium falciparum demonstrated on peripheral smear were randomized to receive either artemether or quinine. Their clinical status and smears for parasite count were assessed every 12 hours until two successive blood films were negative. The primary end point of the study was death in the hospital and residual damage to the organ involved. The secondary end points were clearance of parasites and fever, length of time of recovery from coma and normal functions of the involved system. RESULTS: Forty-six cases completed the study protocol, 23 assigned to each drug group. Cerebral malaria was the commonest manifestation (76.1%). Mean age in artemether versus quinine group (6.6 +/- 3.5 and 5.8 +/- 2.4 years) as well as degree of parasitemia at admission (55,800 and 60,300 per microlitre) were comparable. The overall mortality rate was 23.9% with no significant difference between the two groups. Twenty six cases (56.5%) presented with more than one manifestations of severe malaria. The mortality rate was 100% with four coexisting manifestations of severe malaria. Fever clearance time in artemether and quinine group was 44.5 and 45.9 hours respectively (P >0.05). Parasite clearance time was significantly shorter in artemether group (40.9 vs. 51.9 hours; P<0.001). Recovery from coma was shorter in artemether group (34.8 vs. 38.1 hours; P<0.05). CONCLUSION: Cerebral malaria is the most common manifestation of severe malaria in children. Artemether is a good alternative drug to quinine for P. falciparum malaria. Mortality rate is directly proportional to the number of coexisting manifestations of severe malaria.     

Imported malaria in children in 1999. Study of the Armand-Trousseau Hospital in Paris]

METHODS: Eighty children were treated at the hospital Armand-Trousseau (Paris, France) for a malaria attack from 1999-01-01 to 2000-02-01. RESULTS: The parasites were: Plasmodium falciparum: 87.5%, Plasmodium malariae: 12.6%, Plasmodium ovale: 10%, Plasmodium vivax: 6.3%. Mean age was 8.1 years (range: three months to 15 y). The origin of patients was: West Africa for 60 children, Central Africa for ten children and Comores for seven. Sixty-six patients suffered from common malaria attack and seven children were admitted with a presentation of severe malaria. The severe attacks were cerebral malaria for six cases, associated with severe anemia in five cases; the 7th child had a respiratory distress (ARDS) and died. The other six cases were cured without sequelae. Relapses were observed for eight patients: one after a severe cerebral malaria, six after a common P. falciparum attack, one after a P. ovale attack. Parasitemia was higher than in preceding years (mean 2.9%) and more than 5% in 11 cases, but without clear link with severity. Treatment by halofantrine with a single cure was followed by five relapses. None of those children received an effective prophylaxis during and after travel (55/80 without any prophylaxis). CONCLUSION: These data emphasize the importance of a good appraisal of criteria of severe malaria and lead to advice hospitalization of children with malaria in temperate zone.     

Follow-up of the Antibody Response to Measles Vaccine in a Rural Area of Guinea-Bissau

ABSTRACT. One hundred and fourty-four children who either were already immune or had been successfully immunized against measles were reexamined after 16 months. All still had circulating Elisa antibodies at a clearly detectable level. Titres were higher in the group of children stated to have had measles prior to the immunization. None of the children had measles after immunization. Boostering by the wild virus may have occurred, whereas no evidence of a booster effect from the vaccine was found. About one third of the children were underweight. Plasmodium falciparum parasitaemia rate, and also its seasonality, varied with the location of the child's homestead. Even children exposed to mesoendemic P. falciparum malaria and moderate malnutrition can be successfully immunized with a conventional live attenuated measles vaccine from 8 months of age, which probably results in a lasting protection.     

Follow-up of the antibody response to measles vaccine in a rural area of Guinea-Bissau

One hundred and fourty-four children who either were already immune or had been successfully immunized against measles were reexamined after 16 months. All still had circulating Elisa antibodies at a clearly detectable level. Titres were higher in the group of children stated to have had measles prior to the immunization. None of the children had measles after immunization. Boostering by the wild virus may have occurred, whereas no evidence of a booster effect from the vaccine was found. About one third of the children were underweight. Plasmodium falciparum parasitaemia rate, and also its seasonality, varied with the location of the child's homestead. Even children exposed to mesoendemic P. falciparum malaria and moderate malnutrition can be successfully immunized with a conventional live attenuated measles vaccine from 8 months of age, which probably results in a lasting protection.     

儿童脑型疟128例的诊断和治疗

目的了解儿童脑型疟临床特征和降低其病死率。 方法对1996～1997年住院128例儿童脑型疟的临床特征、诊断治疗、病死原因进行分析。 结果1～5a儿童发生率66％,痊愈113例,后遗症4例,死亡11例,死亡率8．6％。临床特征有发热、咳嗽、吐泻、惊厥、意识障碍等。血片见疟原虫可确诊,首次阴性应反复多次检查。惊厥、意识障碍者应排除其他疾患。 结论及时正确诊断,尽早抗疟治疗,对抗药性及有并发症等治疗是降低儿童脑型疟病死率的关键。     

Red blood cell exchange transfusion as an adjunct treatment for severe pediatric falciparum malaria, using automated or manual procedures

Pediatric falciparum malaria is associated with high morbidity and mortality rates. Cerebral malaria and renal failure are common among children with a high percentage of malaria-infected red blood cells. We report 3 cases of imported pediatric falciparum malaria with central nervous system involvement and/or renal failure that were treated initially with intravenous antimalarial therapy, with no clinical improvement. Red blood cell exchange transfusion (RBCET) was started; this resulted in decreases in the percentages of parasitized red blood cells of 80% to 90%. The RBCET was performed with either an automated 1-blood volume or manual 1.5-blood volume exchange. Most cases of falciparum malaria can be treated with intravenously administered antimalarial agents alone. However, for children who have high percentages of parasitized red blood cells with central nervous system involvement and/or renal failure, the use of RBCET as an adjunct treatment should be considered.     

Pretreatment blood concentrations of chloroquine in patients with malaria infection: relation to response to treatment

Resistance of Plasmodium falciparum to chloroquine has been reported in many areas in Ghana. Most of these reports, which are from hospital-based studies, indicate RI and RII rather than RIII type of resistance. Since high pretreatment levels of chloroquine have also been measured in patients with malaria infection in Ghana, we hypothesized that the 'added effect' of the pretreatment ingested drug to the full dose given at the hospital may be responsible for the low proportion of RIII type of resistance observed. To ascertain this, pretreatment blood levels of chloroquine were correlated with treatment outcomes in 231 paediatric malaria patients, referred to a major hospital in Ghana. The rate of parasite clearance and prevalence of recrudescence, 14 days post-treatment, were determined for each patient. Results from this study showed no correlation between pretreatment chloroquine levels and day 0 parasitaemia. Two hundred and seven patients (89.6 per cent) had parasites that were sensitive to chloroquine whilst 24 (10.4 per cent) had resistant parasites. Of the latter group 17, six, and one patients had P. falciparum parasites, which were resistant at RI, RII and RIII levels, respectively. Seventy-five per cent of the patients without any detectable pretreatment blood chloroquine had parasites that were sensitive to chloroquine whilst 89.8 per cent, 98 per cent, and 100 per cent with pretreatment blood chloroquine concentration ranges of 0.5--100.5 ng/ml, 100.5--200 ng/ml, and >200 ng/ml, respectively, had chloroquine-sensitive parasites. An inverse relationship was thus observed between pretreatment blood chloroquine concentration and the degree of resistance in this study. We conclude that pre-hospital treatment ingested chloroquine contributes significantly to the resolution of malaria in children in Ghana, in the presence of chloroquine resistance.     

Increasing burden of childhood severe malaria in a Nigerian tertiary hospital: implication for control

Malaria remains an important public heath concern in Nigeria because of its impact on child and maternal health, but the contribution of severe malaria to morbidity among Nigerian children was scantly reported. This study was undertaking to document the hospital-burden of severe malaria among children in Ibadan in order to reflect on the impacts and health implications of the current malaria control strategies. A review of 6-year case records of all children admitted to the emergency ward of the University College Hospital Ibadan was carried out. Cases of severe malaria were defined as those children in whom parasitaemia were confirmed with blood film microscopy and any of the WHO case definitions for severe malaria was documented. Severe malaria cases constituted 11.3% of 16 031 admissions (2000-05) with 89.1% being children <5 years old. Cerebral malaria accounted for about one-fifth (19.7%) of all severe malaria cases. The yearly proportional morbidity rate from severe malaria ranged from 8.7% to 13.2% with significant increase from 2000 to 2004 (X2 = 48.49; df = 5; P < 0.001). Severe malaria accounted for 12.4% of all paediatric deaths with an estimated overall case fatality rate of 9.6%. Deaths from malaria were significantly associated with wasting (Z-score for weight-for-height 相似文献   

Efficacy, safety and acceptability of halofantrine in the treatment of acute Plasmodium falciparum malaria in African children (Gabon).

Halofantrine chlorhydrate 2 per cent suspension was given to 50 children (mean age 6.2 years in a dose of 8 mg/kg three times a day as a single day treatment. The children were born and lived in Gabon, where malaria transmission is continuous. They all had acute Plasmodium falciparum malaria. The children were kept in hospital for 5 days, and regularly followed over a 15-day period. The 50 children were cured and efficacy was evaluated as good in 44 cases, and excellent in six cases, as judged by improvement in their clinical signs and parasitaemia. Two criterias were considered in the evaluation of efficacy: clearance of parasitaemia (mean day 4), fever clearance (mean hour 24). There were two cases of persistences of parasites at day 15 with a very low parasitaemia rate. Tolerance to halofantrine was good from a clinical and biological point of view. Acceptability was excellent in all cases. Halofantrine 2 per cent suspension is a good alternative in the treatment of acute Plasmodium falciparum malaria in children, especially with the present situation of multidrug-resistant strains in Central Africa.     

A bedside dipstick method to detect Plasmodium falciparum

We conducted this study to determine efficacy of Parasight-F (an HRP-II antigen dipstick method to detect P. Falciparum) in children. A total of 30 children were enrolled in the age group of 2 months to 12 years whose peripheral smear showed asexual forms of Plasmodium falciparum. All patients were tested for presence of HRP-II antigen of Plasmodium falciparum in their blood by the Parasight-F dipstick test by either an EDTA sample or a finger prick blood sample. The sensitivity of Parasight-F was 83.3 % However, the sensitivity of Parasight-F to detect Plasmodium Falciparum in case of mixed Plasmodium (Vivax + Falciparum) infection was only 25 %. Also, all patients less than 6 months of age had a negative Parasight-F test. Parasitic index, prior treatment with antimalarials or severity of Falciparum malaria have no effect on the sensitivity of Parasight-F test. We conclude that Parasight-F is an effective tool for diagnosis of Plasmoduim falciparum malaria in children.     

Inpatient mortality in children with clinically diagnosed malaria as compared with microscopically confirmed malaria

BACKGROUND: Inpatient treatment for malaria without microscopic confirmation of the diagnosis occurs commonly in sub-Saharan Africa. Differences in mortality in children who are tested by microscopy for Plasmodium falciparum infection as compared with those not tested are not well characterized. METHODS: A retrospective chart review was conducted of all children up to 15 years of age admitted to Mulago Hospital, Kampala, Uganda from January 2002 to July 2005, with a diagnosis of malaria and analyzed according to microscopy testing for P. falciparum. RESULTS: A total of 23,342 children were treated for malaria during the study period, 991 (4.2%) of whom died. Severe malarial anemia in 7827 (33.5%) and cerebral malaria in 1912 (8.2%) were the 2 common causes of malaria-related admissions. Children who did not receive microscopy testing had a higher case fatality rate than those with a positive blood smear (7.5% versus 3.2%, P < 0.001). After adjustment for age, malaria complications, and comorbid conditions, children who did not have microscopy performed or had a negative blood smear had a higher risk of death than those with a positive blood smear [odds ratio (OR): 3.49, 95% confidence interval (CI): 2.88-4.22, P < 0.001; and OR: 1.59, 95% CI: 1.29-1.96, P < 0.001, respectively]. CONCLUSIONS: Diagnosis of malaria in the absence of microscopic confirmation is associated with significantly increased mortality in hospitalized Ugandan children. Inpatient diagnosis of malaria should be supported by microscopic or rapid diagnostic test confirmation.     

Tolerance and efficacy of atovaquone-proguanil for the treatment of paediatric imported Plasmodium falciparum malaria in France: clinical practice in a university hospital in Paris]

Only few drugs for uncomplicated Plasmodium falciparum malaria are available in children. Atovaquone-proguanil is a recent antimalarial drug licensed in France for the uncomplicated P. falciparum malaria in adults. Few paediatric studies have evaluated atovaquone-proguanil in children for uncomplicated malaria in endemic area, but no study have evaluated this treatment for imported malaria. OBJECTIVE: To evaluate treatment by atovaquone-proguanil for uncomplicated and imported P. falciparum malaria in children. METHODS: We retrospectively evaluated the tolerance and the efficacy of atovaquone-proguanil in the children admitted in Robert-Debré Hospital (Paris) for a P. falciparum malaria. From January 2004 to December 2005, 48 children with a median age of 7,5 years (IQR 4-11) were treated with atovaquone-proguanil for a uncomplicated P. falciparum malaria, except for 5 children who had an isolated hyperparasitemia greater or equal to 5%. RESULTS: Atovaquone-proguanil was stopped for 3/48 children because of vomiting. Fever resolved in all the children between Day 3 and 7, following the beginning of the treatment. One child, with a favourable outcome, had a positive parasitemia at Day 4 equal to the initial parasitemia (0,1%). No late therapeutic failure was observed among the 24 children evaluated up to one month after starting treatment. CONCLUSION: Atovaquone-proguanil is an efficient and well-tolerated antimalarial treatment for uncomplicated P. falciparum malaria in children. The risk of vomiting should lead to a systematic initial hospitalisation of children treated with atovaquone-proguanil.     

儿童重症疟疾156例临床分析

目的探讨儿童重症疟疾的临床特征,提高早期诊断和治疗水平。方法对2005年6月—2006年5月在尼日尔马拉迪省中心医院儿科住院的156例<5岁重症疟疾患儿的临床表现、实验室检查及临床转归进行回顾性分析。结果重度贫血(45.51%)、高乳酸血症(23.72%)、脑型疟疾(23.08%)、血小板减少(21.15%)、低血糖(21.15%)、高原虫血症(12.18%)、呼吸窘迫(11.54%)是本组患儿的特征性临床表现。2岁以下患儿重度贫血的发生率显著高于2～5岁患儿,差异有统计学意义(P<0.05);而脑型疟疾的发生率2～5岁患儿显著高于2岁以下患儿,差异有统计学意义(P<0.05)。156例患儿中恶性疟的发病人数占显著优势,为113例(72.44%),三日疟25例(16.02%),卵形疟16例(10.26%),间日疟2例(1.28%)。死亡28例(17.95%)。脑型疟疾、惊厥、低血糖、高乳酸血症是患儿死亡的独立高危因素(P<0.05)。结论尼日尔地区儿童重症疟疾主要为恶性疟,重度贫血和脑型疟疾常见,并与患儿年龄相关。脑型疟疾、惊厥、低血糖、高乳酸血症是患儿死亡的独立高危因素。     

Thrombocytopenia and Plasmodium falciparum malaria in children with different exposures.

We studied thrombocytopenia during acute Plasmodium falciparum malaria in 64 traveller children from Paris (France), 85 children from Dakar (Senegal) with an intermittent exposure (69 with severe attack or cerebral malaria), and 81 children from Libreville (Gabon) with a perennial exposure (43 with severe attack or cerebral malaria). Initial thrombocytopenia was present in 43-58% of children with P falciparum malaria but was not more frequent in severe outcome or cerebral malaria. Low parasitaemia may lead to the misdiagnosis of malaria and delayed treatment when there is associated thrombocytopenia     

Thrombocytopenia and Plasmodium falciparum malaria in children with different exposures

We studied thrombocytopenia during acute Plasmodium falciparum malaria in 64 traveller children from Paris (France), 85 children from Dakar (Senegal) with an intermittent exposure (69 with severe attack or cerebral malaria), and 81 children from Libreville (Gabon) with a perennial exposure (43 with severe attack or cerebral malaria). Initial thrombocytopenia was present in 43-58% of children with P falciparum malaria but was not more frequent in severe outcome or cerebral malaria. Low parasitaemia may lead to the misdiagnosis of malaria and delayed treatment when there is associated thrombocytopenia     

Comparative efficacy study of combination fansidar-sulphate quinine and fansidar-HCl tetracycline in falciparum malaria in children above 7 years old

The objective of this study is to compare the results of treatment of children with falciparum malaria with the combinations of fansidar-sulphate quinine and fansidar-chlortetracycline as an alternative treatment of chloroquine resistant falciparum malaria. This study was carried out prospectively on 45 cases with the age equal or above 7 years, who had been admitted in the Pediatric Department, Gunung Wenang Hospital Manado during the period of January 1989-December 1989. Twenty three cases had been treated with fansidar-sulphate quinine and 22 cases with fansidar-chlortetracycline, all of them underwent blood examinations for malaria for 7 consecutive days (day 0-8). Asexual parasitemia and fever in the fansidar-sulphate quinine group significantly disappeared more rapidly than in the fansidar-chlortetracycline group (p less than 0.03 and less than 0.005). There occurred neither drug resistance nor serious side effect in both groups.     

Trends in imported childhood malaria in the UK: 1999-2003.

OBJECTIVE: To describe the epidemiology of imported malaria in children in the UK. METHODS: Surveillance data on children with imported malaria, collected through an enhanced surveillance network set up by the Malaria Reference Laboratory (London, UK), diagnosed between January 1999 and December 2003 were analysed. RESULTS: Over the 5-year study period, 9238 cases were reported to the Malaria Reference Laboratory, and children accounted for 1456 (14.8%) cases. The number of imported paediatric malaria cases fell from 326 in 1999 to 241 in 2003. Malarial infection occurred in children of all ages and the number of patients increased gradually with age. Visiting family and relatives was the most common reason for travel (59.5%), with only 7.2% travelling to an area endemic to malaria on holiday. Most infections (88.4%) were acquired in Africa, and mainly in Nigeria (49.7%). Plasmodium falciparum was responsible for 81.7% of all cases, followed by P. vivax (11.1%). The number of both P. falciparum and P. vivax cases fell gradually from 262 and 45 cases in 1999 to 196 and 20 cases in 2003, respectively. Malaria prophylaxis was taken by 39% of 500 children with malaria who had travelled to a country endemic to malaria. The proportion of children with malaria who had taken malaria prophylaxis decreased steadily from 53% in 1999 to 29% in 2003. Two (0.14%) children died compared with 62 (0.76%) adults over the 5-year study period (p = 0.007). CONCLUSIONS: Although the incidence of malaria has started to decline, a considerable number of children are still diagnosed with malaria in the UK. In addition, the proportion of children with malaria who had taken malaria prophylaxis is falling. Although it is reassuring to note the low mortality, there is an urgent need to improve preventive measures among families travelling to high-risk countries.     

Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence

BACKGROUND: Malaria and HIV are important pediatric problems in sub-Saharan Africa. It is uncertain how HIV-related immunosuppression and malaria interact in children. We aimed to describe associations among HIV status, presentation and outcome from malaria in children from Hlabisa district, KwaZulu-Natal, South Africa, a region of high HIV prevalence and unstable Plasmodium falciparum transmission. METHODS: Consecutive febrile children were screened for malaria with a rapid antigen test. After consent was given, clinical data were recorded, and blood spots were obtained for HIV antibody testing. Cases were managed according to national guidelines. RESULTS: Malaria was diagnosed in 663 children, of whom 10.1% were HIV antibody-positive. Semiquantitative asexual and sexual stage parasitemia densities were unrelated to HIV status. Overall 161 children were hospitalized; 19 (12%) were <1 year old; and 41 (25%) had severe/complicated malaria. Severe disease presented more frequently in HIV antibody-positive than in HIV-uninfected children (P = 0.05), particularly in those >1 year old with coma (P = 0.02) and hypoglycemia (P = 0.05). Receiving parenteral antibiotics was associated with severe disease (odds ratio, 3.0; 95% confidence interval, 1.3 to 6.7) whereas a low white blood cell count (<4 x 10(6)/l) was associated with nonsevere disease (odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Seven children (4.3%) died. Coma, age <1 year and low white blood cell count were the clearest predictors of poor outcome. CONCLUSION: HIV infection was associated with severe/complicated malaria, although the magnitude of the effect may be relatively small. Given that both malaria and HIV are widespread in Africa, even small effects may generate significant morbidity and mortality and major public health consequences.     

Increasing Plasmodium falciparum malaria in southwest London: a 25 year observational study.

AIMS: To identify changes in the presenting number and species of imported malaria in children in southwest London. METHODS: A prospective single observer study over 25 years (1975-99) of all cases of paediatric malaria seen at St George's Hospital. RESULTS: A confirmed diagnosis was made in 249 children (56% boys; 44% girls; median age 8.0 years). Of these, 53% were UK residents and 44% were children travelling to the UK. A significant increase was noted in the number of cases over the 25 years (1975-79: mean 4.8 cases/year; 1990-99: mean 13.7 cases/year). Over the 25 years Plasmodium falciparum was seen in 77%, P vivax in 14%, P ovale in 6%, and P malariae in 3% of cases. P falciparum had increased in frequency (1975-79: P falciparum 50%, P vivax 50%; 1990-99: P falciparum 82%, P vivax 6%), associated with an increase in the proportion of children acquiring their infection in sub-Saharan Africa. Median time between arrival in the UK to the onset of fever was: P falciparum, 5 days; P ovale, 25 days; P malariae, 37 days; and P vivax, 62 days. Median time interval between the onset of fever to commencement of treatment was 4 days. This had not improved over the 25 year period. Only 41% of UK resident children presenting to hospital had taken prophylaxis and the overall number of symptomatic children taking no prophylaxis was increasing. CONCLUSION: Imported childhood P falciparum malaria is increasing in southwest London associated with increasing travel from sub-Saharan Africa. Over the 25 year period there has been no improvement in chemoprophylaxis rates or time to diagnosis.     

Congenital malaria among inborn babies at a tertiary centre in Lagos, Nigeria

Congenital malaria is increasingly reported among babies born to mothers continually residing in endemic areas. Given the high morbidity and mortality associated with malaria it is pertinent to determine its current status among newborns in Lagos, Nigeria. The aim was to determine the incidence of congenital malaria in newborn babies delivered at the Lagos University Teaching Hospital and also to determine the frequency of parasitaemia in their mothers and placentae. A cross-sectional study of mothers attending the antenatal clinic of the Lagos University Teaching Hospital was done. The Sociodemographic and clinical characteristics of mothers were documented. Samples of maternal, placental, cord and neonatal blood were taken and stained with Giemsa and examined for malaria parasites. Neonatal samples were examined at birth, on days 3, 7, 14 and 28. One hundred mothers and their placentae, as well as 104 babies and their cord blood were studied. The incidence of congenital malaria was 16/104 (15.3%) and parasite counts ranged from 47 to 1019/mul. Plasmodium falciparum was the predominant species. There was a strong association between placental, maternal, cord and neonatal parasitaemia. All the babies with congenital malaria had infected mothers, placentae and cords (p < 0.0001). In conclusion congenital malaria is not uncommon in Lagos nowadays, and there are relatively high rates of maternal, placental and cord blood parasitaemia. It is, therefore, recommended that babies born to mothers with malaria should be screened for congenital malaria.