Mefloquine treatment in infants and children with Plasmodium falciparum malaria: an efficient and well tolerated treatment

OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerance of mefloquine treatment in children, especially in infants of less than 15 kg, in an endemic area of malaria (French Guiana). METHOD: This 5-years (1996-2000) retrospective study included 61 children aged 6 months to 16 years who had been treated with mefloquine for acute Plasmodium falciparum malaria. Twenty-six of these children weighted less than 15 kg. The efficiency of the treatment was evaluated using clinical and parasitic data that had been validated according to the criteria of the World Health Organization (WHO). Tolerance was compared with the data in the medical literature. RESULTS: None of the 59 patients who were given the treatment correctly presented signs of early therapeutic failure as defined by the WHO. Apyrexia was obtained in 48 h on average (CI 95%: 39-57; median: 36 h). The mean time required to obtain negative parasitism was 91 h (CI 95%: 80-101; median: 96 h) among the 51 patients in whom this was measured. Mild side effects were observed in 27.8% of the cases affecting mainly the digestive system. No differences were observed regarding efficacy or tolerance for children who weighed less than 15 kg. CONCLUSION: Mefloquine represents an efficient treatment for acute uncomplicated P. falciparum malaria in children and is well-tolerated even in infants.     

Severe forms of malaria in children in a general hospital pediatric department in Yaounde, Cameroon]

Severe forms of malaria in children are responsible for 1 million deaths yearly in young children in hyperendemic areas. The main objective of this study was to identify and compare common manifestations of different forms of severe malaria and to evaluate the prognosis for hospital treatment in an endemic area. 271 files of children admitted into hospital between March 1991 and September 1996 were analysed. These children were confirmed to have Plasmodium falciparum in their peripheral blood. 78 patients (29%) had the severe form of malaria. 43 patients (53%) were under 5 years of age. The 5 severe types identified were characterized by very high temperatures 28 cases (36%), cerebral malaria 20 cases (26%), prostration and weakness 15 cases (19%), severe anaemia 14 cases (18%) and haemoglobinuria 1 case (1.3%). Cerebral malaria and severe anaemia were more common in children under 5 years old. The average parasitemia was 16,366 +/- 1390 parasites per microlitre. Clearance of parasitemia was obtained on day 3 in almost all cases; 6 patients with very high temperatures presented neither sign of visceral complications nor convulsions. The average period in coma for cases of cerebral malaria was 1.7 days; 12 anaemic patients were transfused. There were no deaths. No abnormality was found on physical examination after an average hospitalisation of 5.3 days. An early diagnosis and adequate treatment of severe forms of malaria in children by qualified personnel will usually result in a favourable prognosis in our area.     

Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion

During the past decade the incidence of Plasmodium falciparum malaria in the United States has increased 10-fold. Treatment may be delayed because the therapy recommended for severe or complicated disease, intravenous quinine dihydrochloride, is available only from the Centers for Disease Control. We studied 17 patients who were treated for severe or complicated P. falciparum malaria in the United States between 1985 and 1987. Five patients were treated with a continuous infusion of quinidine gluconate, 10 with an exchange transfusion in addition to the continuous infusion of quinidine gluconate, and 2 with intermittently administered intravenous quinine dihydrochloride and an exchange transfusion. All 16 patients with P. falciparum malaria (1 patient had P. vivax malaria) had hyperparasitemia at the time of diagnosis (6 to 54 percent of the erythrocytes infected; median, 13 percent). Three patients with marked hyperparasitemia (54, 38, and 30 percent) and multiple other indicators of a poor prognosis, including advanced age, died. The 13 patients who completed their courses of quinidine with or without exchange transfusion had a parasitemia level of 1.1 percent or less 28 to 72 hours (mean, 44.4 hours) after the start of therapy. Side effects of quinidine treatment were observed in only two patients, one of whom had a serum quinidine concentration above the toxic level. We conclude that the continuous infusion of quinidine gluconate is well tolerated alone and with exchange transfusion and is effective in the treatment of severe and complicated malaria.     

Hypoxemia predicts death from severe falciparum malaria among children under 5 years of age in Nigeria: the need for pulse oximetry in case management

Background

Oxygen saturation is a good marker for disease severity in emergency care. However, studies have not considered its use in identifying individuals infected with Plasmodium falciparum at risk of deaths.

Objective

To investigate the prevalence and predictive value of hypoxaemia for deaths in under-5s with severe falciparum malaria infection.

Methods

Oxygen saturation was prospectively measured alongside other indicators of disease severity in 369 under-5s admitted to a tertiary hospital in Nigeria. Participants were children in whom falciparum malaria parasitaemia was confirmed with blood film microscopy in the presence of any of the World Health Organization-defined life-threatening features for malaria.

Results

Overall mortality rate was 8.1%. Of the 16 indicators of the disease severity assessed, hypoxaemia (OR=7.54; 95% CI=2.80, 20.29), co-morbidity with pneumonia (OR=19.27; 95% CI=2.87, 29.59), metabolic acidosis (OR=6.21; 95% CI=2.21, 17.47) and hypoglycaemia (OR=19.71; 95% CI=2.61, 25.47) were independent predictors of death. Cerebral malaria, male gender, wasting, hypokalaemia, hyponatriaemia, azotaemia and renal impairment were significantly associated with death in univariate analysis but not logistic regression model.

Conclusions

Hypoxaemia predicts deaths in Nigerian children with severe malaria, irrespective of other features. Efforts should always be made to measure oxygen saturation as part of the treatments for severe malaria in children.     

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.     

Health care related factors associated with severe malaria in children in Kampala,Uganda

Background

Severe malaria is responsible for the high load of malaria mortality. It is not clearly understood why some malaria episodes progress to severe malaria.

Objective

To determine factors associated with severe malaria in children aged 6 months to 5 years living in Kampala.

Methods

Over a 6-month period, 100 children with severe malaria were matched by age and place of residence with 100 children with non-severe malaria. We collected health care information from care takers.

Results

Mean duration of illness before getting antimalarial treatment was shorter for controls than cases (8hours vs. 20hours, p 0.015). Children with severe malaria were less likely to have been treated with sulphadoxine-pyrimethamine in the preceding 2 weeks (OR 0.2, 95% CI 0.04–0.85, p 0.016). Odds of severe malaria were higher in those who reported lack of protective measures (mosquito coils (OR = 20.63, 95% CI 1.5–283.3, p=0.02 and insecticide sprays OR 10.93, 95% CI 1.13–105.64, p=0.03), although few reported their use.

Conclusions

Early anti-malarial treatment and use of barriers against mosquitoes prevent severe malaria in children. There is need to increase the use of barriers against mosquito bites and to scale up prompt treatment and community-based interventions to reduce the incidence of severe malaria in children.     

Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria

There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across three African populations. Using population- and family-based tests, we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: case-control allelic odds ratio (OR), 1.2; 95% confidence interval (CI), 1.09-1.32; P = 0.0003; family-studies allelic OR, 1.19; 95% CI, 1.08-1.32; P = 0.001; pooled across all studies allelic OR, 1.18; 95% CI, 1.11-1.26; P = 2 x 10(-7). We found suggestive evidence of a parent-of-origin effect at the ABO locus by analyzing the family trios. Non-O haplotypes inherited from mothers, but not fathers, are significantly associated with severe malaria (likelihood ratio test of Weinberg, P = 0.046). Finally, we used HapMap data to demonstrate a region of low F(ST) (-0.001) between the three main HapMap population groups across the ABO locus, an outlier in the empirical distribution of F(ST) across chromosome 9 (approximately 99.5-99.9th centile). This low F(ST) region may be a signal of long-standing balancing selection at the ABO locus, caused by multiple infectious pathogens including P. falciparum.     

Risk factors for peripartum blood transfusion in women with placenta previa: a retrospective analysis

BACKGROUND: The incidence of placenta previa has been increasing. It is of a great importance to determine the clinical risk factors for peripartum blood transfusion in women with placenta previa in an effort to anticipate cases of severe hemorrhage. METHODS: A total of 129 consecutive cases of placenta previa (64 cases of complete placenta previa and 65 cases of marginal placenta previa), including 43 cases requiring blood transfusion, were retrospectively analyzed. Maternal and neonatal clinical data were examined with univariate and multivariate logistic regression analyses for potential risk factors for peripartum blood transfusion. RESULTS: The independent risk factors for blood transfusion were maternal age greater than 34 years (adjusted odds ratio [OR]=3.7; 95% confidence interval [CI]=1.5-7.5, p<0.05), history of having undergone dilatation and curettage more than once (adjusted OR=4.8; 95% CI=1.1-26.2, p<0.05), and complete placenta previa (adjusted OR=2.6, 95% CI=1.2-5.9, p<0.05). Body mass index, gravidity, parity, previous cesarean section, antepartum hemorrhage, use of tocolytic agents, gestational age at delivery, preoperative anemia, emergent surgery, birth weight, and Apgar score were not associated with the incidence of blood transfusion. CONCLUSION: Risk factors for blood transfusion in women with placenta previa are advanced maternal age, repeat dilatation and curettage, and complete placenta previa. Women with placenta previa who are at risk for blood transfusion should be carefully managed with sufficient preparation for blood transfusion.     

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.     

The role of serum immunoglobulin E in the pathogenesis of Plasmodium falciparum malaria in Ivorian children

The aim of the study was to determine the role of immunoglobulin E (IgE) in the pathogenesis of Plasmodium falciparum malaria in Ivorian children. The study comprised of 90 Ivorian children of both sexes, aged 6-72 months: 30 children suffering from severe malaria, 30 suffering from mild malaria and 30 in good heath (serving as the control population). The children underwent a total serum IgE test for the determination of haemoglobin and platelet level and parasite density. We noted a significant rise in IgE level in the children affected with malaria. The level was higher when the malaria was more severe, increasing from 84.61 kUI/l in the control children to 339.9 kUI/l in the children with mild malaria and 659.9 kUI/l in children with severe malaria. Among the comatose patients with severe malaria, the increase in IgE level was related to the level of deterioration of the consciousness. Moreover, we noted a negative correlation between IgE level and the level of haemoglobin and between the IgE level and platelet level. These results are in accordance with the results found in literature and confirm the use of IgE level as an indicator of P. falciparum malaria.     

Evaluation of the Sensitivity of a pLDH-Based and an Aldolase-Based Rapid Diagnostic Test for Diagnosis of Uncomplicated and Severe Malaria Caused by PCR-Confirmed Plasmodium knowlesi,Plasmodium falciparum,and Plasmodium vivax

Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDH-PfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity.     

Immunoglobulin G antibody reactivity to a group A Plasmodium falciparum erythrocyte membrane protein 1 and protection from P. falciparum malaria

Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP1. PF11_0008 has previously been found to be highly transcribed in a nonimmune Dutch volunteer experimentally infected with NF54 parasites. A high proportion of the Tanzanian donors had antibodies against recombinant PF11_0008 domains, and in children who were 4 to 9 years old the presence of antibodies to the PF11_0008 CIDR2beta domain was associated with reduced numbers of malaria episodes. These results indicate that homologues of PF11_0008 are present in P. falciparum field isolates and suggest that PF11_0008 CIDR2beta-reactive antibodies might be involved in protection against malaria episodes.     

Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

ABSTRACT: BACKGROUND: Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. METHODS: A case-control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases) and healthy pregnant women (controls). RESULTS: The median (interquartile) platelet counts were significantly lower in patients with malaria (N=60) than in the controls (N=60), 61, 000 (43,000-85,000) vs. 249,000 (204,000-300,000)/uL, respectively, p < 0.001. However, there was no significant difference in the platelet counts in patients with severe P. falciparum malaria (N=12) compared with those patients with uncomplicated P. falciparum malaria (N=48), 68, 000 (33,000-88,000)/uL vs. 61, 000 (45,000-85,000)/uL, respectively, p=0.8. While none of the control group had thrombocytopenia (platelet count <75, 000/ uL), it was found that 6/12 (50%) and 27/48 (56.2%) (p <0.001) of the patients with severe malaria and uncomplicated malaria had thrombocytopenia, respectively. Pregnant women with P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR=10.1, 95% CI=4.1-25.18; p<0.001) of thrombocytopenia. Two patients experienced bleeding, and there was one maternal death due to cerebral malaria where the patient's platelet count was only 28,000/uL. CONCLUSION: P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.     

Plasmodium Falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children

BACKGROUND. It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease. METHODS. We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1-seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine. RESULTS. A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those with the acquired immunodeficiency syndrome (AIDS), those who were HIV-1-seropositive throughout the study, those who were born to HIV-1-seropositive mothers but reverted to seronegative, and those who were seronegative throughout the study. During the 13-month period the incidence of malaria in the 36 children with HIV infection in whom AIDS developed was lower, although not significantly so, than in the 37 in whom AIDS did not. CONCLUSIONS. In this study malaria was not more frequent or more severe in children with progressive HIV-1 infection and malaria did not appear to accelerate the rate of progression of HIV-1 disease.     

Blood glucose levels in Malawian children before and during the administration of intravenous quinine for severe falciparum malaria

Hypoglycemia may develop in patients with severe untreated malaria and can complicate the course of treatment with parenteral quinine as a result of quinine-induced hyperinsulinemia. Intravenous quinine is used increasingly as the therapy of choice in patients with severe malaria, most of whom are children. To assess the importance of both pretreatment and quinine-related hypoglycemia in children in an area in which the disease is endemic, we prospectively studied 95 Malawian children with falciparum malaria and altered consciousness who were treated with intravenous quinine. Nineteen patients had hypoglycemia before treatment. Seven (37 percent) died, and five of the survivors (26 percent) had neurologic sequelae. The corresponding values for patients who were initially normoglycemic were 4 percent and 4 percent, respectively (P less than 0.0001). Hypoglycemia was associated with low plasma insulin concentrations and with elevated plasma concentrations of lactate, alanine, and 5'-nucleotidase--a finding that suggests that impaired hepatic gluconeogenesis but not hyperinsulinemia contributes to the pathogenesis of pretreatment hypoglycemia. All patients were given quinine dihydrochloride in a 5 percent dextrose infusion, and those with hypoglycemia received 50 percent dextrose. Hypoglycemia recurred in seven of the patients with pretreatment hypoglycemia, but these episodes were also not associated with hyperinsulinemia. Of the 76 children who were initially normoglycemic, none became hypoglycemic during the course of treatment with intravenous quinine. We conclude that hypoglycemia is a frequent complication of falciparum malaria in children and that it reflects severe disease and is associated with a poor prognosis. We did not find it to be a complication of quinine treatment.     

Double-Unit Cord Blood Transplantation after Myeloablative Conditioning for Patients with Hematologic Malignancies: A Multicenter Phase II Study in Japan

We analyzed the outcomes of 61 patients with hematologic malignancies who underwent double-unit cord blood transplantation (dCBT) after myeloablative conditioning performed as part of a prospective multicenter phase II study. The conditioning regimen for dCBT included total body irradiation, cyclophosphamide, and granulocyte colony-stimulating factor combined with cytosine arabinoside for myeloid malignancies and with total body irradiation and cyclophosphamide for lymphoid malignancies. The cumulative incidence of neutrophil engraftment after dCBT was 85% (95% confidence interval [CI], 73%-92%). All 51 of the patients who engrafted had complete chimerism derived from a single donor by day +60. Only the degree of HLA disparity in the host-versus-graft direction had an impact on unit dominance. The cumulative incidence of grade II-IV acute graft-versus-host disease was 25% (95% CI, 15%-37%), and that of chronic graft-versus-host disease was 32% (95% CI, 20%-44%). The 1-year cumulative incidence of relapse was 23% (95% CI, 13%-34%), and that of transplantation-related mortality was 28% (95% CI, 17%-39%). With a median follow-up of 41 months, event-free survival was 48% (90% CI, 37%-58%) at 1 year and 46% (90% CI, 35%-56%) at 3 years. Event-free survival at 3 years was 67% (95% CI, 46%-81%) for patients with standard risk and 29% (95% CI, 15%-45%) for those with advanced risk. This study suggests that dCBT after myeloablative conditioning is a promising alternative for adults and large children with hematologic malignancies who need stem cell transplantation but lack a suitable adult donor or an adequate single-unit cord blood graft.     

Malaria and Nutritional Status in Children Living on the Coast of Kenya

The relationship between malnutrition and malaria is controversial. On one hand, malaria may cause malnutrition, while on the other, malnutrition itself may modulate susceptibility to the disease. We investigated the association between Plasmodium falciparum malaria and malnutrition in a cohort of children living on the coast of Kenya. The study involved longitudinal follow-up for clinical malaria episodes and anthropometric measurements at four cross-sectional surveys. We used Poisson regression analysis to investigate the association between malaria and nutritional status. Compared to baseline (children with a WAZ or HAZ score of ≥−2), the crude incidence rate ratios (IRRs) for malaria in children with low HAZ or WAZ scores (<−2) during the period prior to assessment were 1.17 (95% CI 0.91–1.50; 0 = 0.21) and 0.94 (0.71–1.25; 0.67), respectively, suggesting no association between malaria and the subsequent development of PEM. However, we found that age was acting as an effect modifier in the association between malaria and malnutrition. The IRR for malaria in children 0–2 years old who were subsequently characterized as wasted was 1.65 (1.10–2.20; P  = 0.01), and a significant overall relationship between malaria and low-HAZ was found on regression analysis when adjusting for the interaction with age (IRR 1.89; 1.01–3.53; P  < 0.05). Although children living on the coast of Kenya continue to suffer clinical episodes of uncomplicated malaria throughout their first decade, the association between malaria and malnutrition appears to be limited to the first 2 years of life.     

Control of malaria: the rapid fever surveillance programme

Eighty-five villages out of nearly 300 villages of Tiptur taluka covering a population of 47,271 where the incidence of Plasmodium falciparum (PF) malaria was very high, were selected for a programme during Aug 93 which lasted for 29 months until the end of Dec 95. Ten days of fever radical treatment (FRT) and 54 weekly and 29 fortnightly rapid fever surveillance (RFS) programmes were conducted. 64,142 blood smears were examined out of which 21,542 were positive for malaria and 14,291 were of PF type. There were 9858 PF cases during the last 5 months of 1993, which came down to 349 by the end of 1995. Fever morbidity which was nearly 1000 new cases per day during FRT came down to 120, 78, and 30 new cases per day during 1993, 1994 and 1995, respectively. Parasite index (PI) for PF Malaria was 140-321 during 1993, came down to 0.6-15 at the end of the study. Four rounds of DDT, two rounds of Ikon and one round of Delta-methrin were sprayed in four and two PHC areas, respectively during this period. Asymptomatic carriers for PF malaria were detected in the children under 14 years of age (3.1%). This programme did prove very effective in bringing down morbidity and mortality due to PF Malaria in the community.     

Severe malaria in Gambian children is not due to lack of previous exposure to malaria.

The reasons why only a small proportion of African children infected with Plasmodium falciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but, with only one exception, there were no significant differences in antibody titres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure to the infection.