Severe malaria: still counting the costs
http://www.100md.com
神经科学杂志 2005年第4期
1 Departments of Neurology & Epidemiology, Michigan State University, MI, USA
2 College of Osteopathic Medicine’s Department of Internal Medicine, Michigan State University
The cost of severe malaria
Keywords: Cerebral malaria; severe malaria
The burden of malaria in the developing world has largely been measured in terms of childhood mortality. Annually, 300–500 million infections occur resulting in 1 million deaths; these account for 20% of childhood mortality in malaria endemic regions.1 An article by Carter et al (this issue, pp 476–81) provides evidence that the burden of malaria includes chronic neurological consequences among survivors.2
The possibility that survivors of severe malaria suffer from neurological sequelae such as cognitive deficits or epilepsy has been suggested.3 Certainly, gross deficits at hospital discharge among a small proportion of survivors have been reported, but until recently, little systematic data on long term outcomes of severe malaria were available. Previous studies have suffered from loss to follow-up, short duration of follow-up, the lack of a comparison population, and evaluations limited to a bedside assessment.
The study by Carter et al utilised the Kilifi District Hospital database to identify survivors of severe malaria in rural Kenya. Subjects had experienced either cerebral malaria (CM) (peripheral parasitemia plus 4 hours of coma) or malaria with complicated seizures (M/S) (peripheral parasitemia plus multiple, prolonged, or focal seizures). A comparison group comprised of age matched children was identified from a census of the catchment region. Follow-up occurred up to 9 years after the infection. All study subjects underwent neurologic assessments, including standardised cognitive testing validated in this population. The findings were striking. Impairments were identified in 24% of CM and M/S children compared with 10% of the comparison population. Among impaired children, multiple impairments were also more common among CM (42%) and M/S (30%) than the comparison group (22%). Furthermore, a subpopulation of impaired children with CM or M/S were particularly devastated with language and attention deficits too severe to allow testing.
In this observational study, pre-existing neurologic abnormalities that predisposed to M/S cannot be excluded. Children with underlying brain abnormalities would be more likely to present with complicated seizures in the setting of malaria and hyperthermia. Among the CM group, the possibility of subtle status epilepticus related to premorbid "bad brain" is difficult to eliminate. The only published work systematically studying EEG in CM reported 23% of cases exhibiting sub-clinical electrographic seizures.4 Regardless of these limitations, this work should increase awareness of the potential for childhood malaria to produce chronic neurologic disorders.
Neuropsychiatric disorders comprise >10% of the global burden of disease and the developing world is disproportionately affected.5 Severe malaria may be contributing to this burden. Could interventions aimed at neuroprotection reduce the incidence of neurologic sequelae in this population? Since severe malaria survivors almost certainly have received medical care, an intervention to diminish the damage could be broadly applied. Moreover, survivors with cognitive deficits would benefit from educational and rehabilitation services. Further work including prospective, observational studies are needed to delineate the full burden of severe malaria sequelae, increase our understanding of how malaria contributes to neurologic problems, and to begin to develop interventions that may alleviate the burden of central nervous system injuries resulting from this common infection.
REFERENCES
Snow RW, Craig M, Deichmann U, et al. Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population.[see comment]. Bulletin of the World Health Organization 1999;77 (8) :624–40.
Carter J, Mung’ala-Odera V, Neville B, et al. Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry 2004;75:476–81.
IOM. Neurological and Psychiatric Disorders: Meeting the Challenge in the Developing World. Washington DC: Institute of Medicine, 2001.
Crawley J, Smith S, Muthinji P, et al. Electroencephalographic and clinical features of cerebral malaria. Arch Dis Child 2001;84:247–53.
Menken M, Munsat TL, Toole JF. The global burden of disease study: implications for neurology. Archives of Neurology 2000;57:418–20.(G L Birbeck and T E Taylo)
2 College of Osteopathic Medicine’s Department of Internal Medicine, Michigan State University
The cost of severe malaria
Keywords: Cerebral malaria; severe malaria
The burden of malaria in the developing world has largely been measured in terms of childhood mortality. Annually, 300–500 million infections occur resulting in 1 million deaths; these account for 20% of childhood mortality in malaria endemic regions.1 An article by Carter et al (this issue, pp 476–81) provides evidence that the burden of malaria includes chronic neurological consequences among survivors.2
The possibility that survivors of severe malaria suffer from neurological sequelae such as cognitive deficits or epilepsy has been suggested.3 Certainly, gross deficits at hospital discharge among a small proportion of survivors have been reported, but until recently, little systematic data on long term outcomes of severe malaria were available. Previous studies have suffered from loss to follow-up, short duration of follow-up, the lack of a comparison population, and evaluations limited to a bedside assessment.
The study by Carter et al utilised the Kilifi District Hospital database to identify survivors of severe malaria in rural Kenya. Subjects had experienced either cerebral malaria (CM) (peripheral parasitemia plus 4 hours of coma) or malaria with complicated seizures (M/S) (peripheral parasitemia plus multiple, prolonged, or focal seizures). A comparison group comprised of age matched children was identified from a census of the catchment region. Follow-up occurred up to 9 years after the infection. All study subjects underwent neurologic assessments, including standardised cognitive testing validated in this population. The findings were striking. Impairments were identified in 24% of CM and M/S children compared with 10% of the comparison population. Among impaired children, multiple impairments were also more common among CM (42%) and M/S (30%) than the comparison group (22%). Furthermore, a subpopulation of impaired children with CM or M/S were particularly devastated with language and attention deficits too severe to allow testing.
In this observational study, pre-existing neurologic abnormalities that predisposed to M/S cannot be excluded. Children with underlying brain abnormalities would be more likely to present with complicated seizures in the setting of malaria and hyperthermia. Among the CM group, the possibility of subtle status epilepticus related to premorbid "bad brain" is difficult to eliminate. The only published work systematically studying EEG in CM reported 23% of cases exhibiting sub-clinical electrographic seizures.4 Regardless of these limitations, this work should increase awareness of the potential for childhood malaria to produce chronic neurologic disorders.
Neuropsychiatric disorders comprise >10% of the global burden of disease and the developing world is disproportionately affected.5 Severe malaria may be contributing to this burden. Could interventions aimed at neuroprotection reduce the incidence of neurologic sequelae in this population? Since severe malaria survivors almost certainly have received medical care, an intervention to diminish the damage could be broadly applied. Moreover, survivors with cognitive deficits would benefit from educational and rehabilitation services. Further work including prospective, observational studies are needed to delineate the full burden of severe malaria sequelae, increase our understanding of how malaria contributes to neurologic problems, and to begin to develop interventions that may alleviate the burden of central nervous system injuries resulting from this common infection.
REFERENCES
Snow RW, Craig M, Deichmann U, et al. Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population.[see comment]. Bulletin of the World Health Organization 1999;77 (8) :624–40.
Carter J, Mung’ala-Odera V, Neville B, et al. Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry 2004;75:476–81.
IOM. Neurological and Psychiatric Disorders: Meeting the Challenge in the Developing World. Washington DC: Institute of Medicine, 2001.
Crawley J, Smith S, Muthinji P, et al. Electroencephalographic and clinical features of cerebral malaria. Arch Dis Child 2001;84:247–53.
Menken M, Munsat TL, Toole JF. The global burden of disease study: implications for neurology. Archives of Neurology 2000;57:418–20.(G L Birbeck and T E Taylo)