Risk factors for severe malaria: importance of careful study design: a reply.
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Case-Control Studies↗
Biomedical subjects
C Rogier
Publications and source records attributed to C Rogier.
Severe falciparum malaria in children: a comparative study of 1990 and 2000 WHO criteria for clinical presentation, prognosis and intensive care in Dakar, Senegal.
The relevance of WHO criteria for severe and complicated malaria has been debated for a while, especially as regards children. Recent data led WHO experts to modify the definition of severe malaria. The objective of this study was to evaluate retrospectively the significance of the new definition on severity, lethality and intensive care distribution in children admitted with falciparum malaria (in 1997-99) to Hôpital Principal de Dakar, Senegal. We used the paediatric risk of mortality score (PRISM) to compare the 2 definitions, WHO 2000 and WHO 1990. Finally, we evaluated the impact of the new definition in terms of major therapeutic interventions (MTIs): mechanical ventilation, haemodynamic support, transfusion, haemodialysis, and the use of sedatives. Among 311 patients, the frequencies of severe malaria cases and case-fatality rates thereof were 52% (n = 161) and 17% (n = 28) respectively using the 1990 WHO criteria, and 75% (n = 233) and 12% (n = 28) using the 2000 WHO criteria. Mean PRISM score among severe cases decreased with the new definition (6.5 versus 8.6). Both definitions predicted neurological sequelae and deaths with 100% sensitivity. One or more MTIs were required in severe malaria cases in 86% (n = 139) under the 1990 criteria and 73% (n = 170) under the 2000 criteria. In this area of low and seasonal transmission, the 2000 WHO definition of severe malaria proved broader and less specific, but was easier to apply and retained the high sensitivity of the earlier definition in identifying life-threatening infections.
Adolescent↗
Reducing the oral quinine-quinidine-cinchonin (Quinimax) treatment of uncomplicated malaria to three days does not increase the recurrence of attacks among children living in a highly endemic area of Senegal.
A 3 d shortened course of the quinine-quinidine-cinchonin association Quinimax was compared to the usual 7 d regimen for routinely treating 462 acute uncomplicated Plasmodium falciparum malaria attacks in 72 children under the age of 10 years in Dielmo, a holoendemic village in Senegal. 25 mg/kg Quinimax salt daily, given in 3 equal doses, improved clinical status in 99.6% of the patients receiving the course and in all of those treated for 7 d. Even if the 3 d course did not systematically eliminate parasitaemia, reducing oral Quinimax treatment of uncomplicated malaria from 7 to 3 d did not increase the recurrence of attacks, even among the youngest children. Both the quinine sensitivity of the Senegalese strains of P. falciparum and the partial acquired immunity of the children were probably responsible for the absence of any difference between the courses. Oral Quinimax for 3 d is a possible alternative regimen to chloroquine and sulfadoxine-pyrimethamine for treating uncomplicated malaria in highly endemic areas of Africa where clinical resistance to these drugs exists.
Administration, Oral↗
Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, Senegal.
While some genetic host factors are known to protect against severe Plasmodium falciparum malaria, little is known about parasite virulence factors. We have compared the genetic characteristics of P. falciparum isolates collected from 56 severe malaria patients and from 30 mild malaria patients recruited in Hôpital Principal, Dakar, Senegal. All isolates were typed using polymerase chain reaction amplification of polymorphic genetic loci (MSP-1, MSP-2, HRP1, GLURP, CSP, RESA, and the multigene family Pf60). The complexity of infections was lower in severe than in mild malaria and the parasite genetic diversity in both groups was very large. No specific genetic make-up was associated with severity; there were, however, marked differences in allele frequencies in both groups, with a prevalence up to 60% of MSP-2 alleles specifically observed in the severe malaria isolates. In addition, the presence of MSP-1/RO33 alleles was significantly associated with a higher plasma level of tumour necrosis factor alpha receptor 1 (P < 0.05), a reported indicator of severity in human malaria. These results point to potential differences in the genetic characteristics of parasites inducing severe versus mild pathology.
Adolescent↗
Malaria: even more chronic in nature than previously thought; evidence for subpatent parasitaemia detectable by the polymerase chain reaction.
In high endemicity areas, malaria is a chronic disease: examination of blood films reveals that up to half of the population, particularly children, harbour parasites at any one given time. The parasitological status of the remainder was addressed using the polymerase chain reaction, a technique 100 to 1000 times more sensitive than microscopy, on a series of samples from Dielmo, a holoendemic area of Senegal. Two-thirds of the microscopically negative individuals were found to harbour subpatent levels of Plasmodium falciparum, suggesting that more than 90% of the exposed population at any one time, i.e. in a cross-sectional survey, are chronically infected. This also means that the range of parasite loads harboured by humans with various degrees of exposure is remarkably large, probably reflecting a large range of effectiveness of the defence mechanisms against malaria parasites, none of which is fully efficient.
Adolescent↗
Incidence of clinical malaria in pregnant women exposed to intense perennial transmission.
The interaction between pregnancy and malaria attacks was investigated from 1990 to 1994 among women in the village of Dielmo, a holoendemic area in Senegal where malaria transmission is intense and perennial. Clinical and parasitological data collected during the daily follow-up of 48 pregnancies among 31 women were compared with those collected from the same women using the same methods during the year which preceded or followed their pregnancy. The parasite prevalence, mean and maximum parasite density in Plasmodium falciparum infections were significantly higher during pregnancy. The incidence rate of malaria attacks was, on average, 4.2 times higher during pregnancy than during the control period. Although most pregnancies were not associated with a malaria attack and the incidence of malaria attacks decreased as the number of previous pregnancies increased, a significant increase in risk of malaria attacks among multigravidae was noted until the fifth pregnancy.
Adolescent↗
Severe malaria among children in a low seasonal transmission area, Dakar, Senegal: influence of age on clinical presentation.
The influence of age on the clinical presentation of severe malaria and especially on its 2 most commonly encountered manifestations, cerebral malaria and severe anaemia, has been retrospectively examined in 161 children (< 16 years old) admitted to the paediatric department of Hôpital Principal de Dakar from 1 January 1990 to 29 February 1996. They lived in Dakar and its suburbs, a region of Senegal where the malaria transmission rate is very low. Cases were defined by at least one of the World Health Organization criteria of severe malaria and the presence of Plasmodium falciparum in blood smears. Severe anaemia was present in 73.1%, 52.1% and 26.2% cases of severe malaria among children aged 0-3 years, 4-7 years and 8-15 years, respectively (P < 0.0001). The frequency of cerebral malaria was 11.3%, 28.2% and 60.6%, respectively, in the same age groups (P < 0.0001). Severe anaemia and cerebral malaria were associated in 8.7% of the cases of severe malaria. The fatality rate was significantly lower in cases of severe anaemia without cerebral malaria (3%) than in cases of cerebral malaria without severe anaemia (17.5%; P < 0.02). Among young children, severe anaemia was associated with brief hyperparasitaemia or with prolonged lower parasitaemia. Other things being equal, older children had a lower risk of severe anaemia. The results suggest that the high prevalence of severe anaemia in young children, even in an area of very low endemicity, depends more on age and parasitaemia than on the transmission level.
Adolescent↗
Four years' entomological study of the transmission of seasonal malaria in Senegal and the bionomics of Anopheles gambiae and A. arabiensis.
From 1993 to 1996, an entomological survey was conducted in the village of Ndiop, Senegal, as part of a research programme on malaria epidemiology and the mechanisms of protective immunity. Mosquitoes were captured on human bait and by indoor spraying. Species from the Anopheles gambiae complex were identified using the polymerase chain reaction, and Plasmodium falciparum infections were detected by enzyme-linked immunosorbent assay for circumsporozoite protein. The vector species identified were A. gambiae (33.9%), A. arabiensis (63.2%), A. melas (0.3%) and A. funestus (2.5%). Similar proportions of A. gambiae (74.2%) and A. arabiensis (73.8%) contained human blood; 27.0% of A. gambiae and 28.3% of A. arabiensis had fed on cattle. The sporozoite rates were similar for A. gambiae (3.2%) and A. arabiensis (3.7%). The annual entomological inoculation rates varied greatly depending on the year. There were 63, 17, 37 and 7 infected bites per person per year in 1993, 1994, 1995 and 1996 respectively. Transmission was highly seasonal, from July to October. A. arabiensis was responsible for 66% of malaria transmission, A. gambiae for 31%, and A. funestus for 3%.
Animals↗
Plasmodium ovale in a highly malaria endemic area of Senegal.
During 4 months, from June to September 1990, the population of Dielmo village, Senegal, an area of intense and perennial malaria transmission, was enrolled in a follow-up study including daily clinical surveillance and bi-weekly malaria parasitaemia monitoring. Thick blood film examinations indicated that 48.5% of children (49/101) and 32.4% of adults (34/105) were infected at least once by Plasmodium ovale during the study period; 148 distinct episodes of patent parasitaemia were observed, with estimated maximum durations of 3-115 d. The mean duration at first decreased significantly with age, from 11.4 d in children under 5 years old to 4.2 d in adults aged 40-59 years, but then increased in older adults to 7.0 d. In all age groups, most infections were asymptomatic. Only high parasitaemias were significantly associated with fever; 3 clinical malaria attacks due to P. ovale were seen during the study period.
Adolescent↗
A cohort study of Plasmodium falciparum diversity during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria.
Prolonged carriage of Plasmodium falciparum in humans during the dry season is critical for parasite survival, as the infected subjects constitute a major reservoir in the absence of transmission. Yet, very little is known about the host/parasite interactions contributing to parasite persistence. In order to study the characteristics of P. falciparum infections during the dry season, we have genotyped parasites collected from untreated, asymptomatic individuals during 3 cross-sectional surveys conducted during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria. Monthly entomological surveillance did not detect any transmission during that period. Parasite prevalence decreased markedly in the children aged < 7 years after 7 months of undetected transmission, but was stable in older children and adults throughout the dry season. In all chronically infected individuals, infection complexity remained stable, but there were substantial fluctuations of individual genotype(s), reflecting complex dynamics of multiple-clone infections during chronic asymptomatic parasite carriage. This fluctuation resulted in changes in the msp1 and msp2 allelic distribution within the cohort after 7 months of undetected transmission, contrasting with the stability observed during the preceding rainy season in that village.
Adolescent↗
Increased multiplicity of Plasmodium falciparum infections and skewed distribution of individual msp1 and msp2 alleles during pregnancy in Ndiop, a Senegalese village with seasonal, mesoendemic malaria.
Pregnancy is associated with a greater susceptibility to Plasmodium falciparum infections, which may result in serious complications affecting both the mother and the fetus. To compare allelic diversity and multiplicity of infection in the same women during and outside pregnancy, we conducted a retrospective analysis of the monthly fingerprick blood samples collected during a longitudinal survey conducted in Ndiop, a Senegalese village with mesoendemic malaria. Merozoite surface protein-1 (msp1) block 2 and merozoite surface protein-2 (msp2) genotypes were determined for 308 blood samples collected from 20 women. Pregnancy was associated with a significantly higher prevalence of P. falciparum infection, higher parasite densities, and a higher multiplicity of infection. The highest multiplicity of infection was observed in the youngest pregnant women. Because of co-linearity, it was not possible to dissociate the impact of age from that of parity on multiplicity of infection. Some individual msp1 and msp2 alleles showed a highly skewed pregnancy-associated distribution. These results indicate that pregnancy is associated with increased permissiveness to a large number of clones, as well as with infection by specific genotypes.
Adolescent↗