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Cerebral malaria in children in the highlands of Kenya: Aspects of pathogenesis and clinical presentation
Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
2002 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Background: Malaria affects over 300 million persons in the world each year with a mortality of close to 2 million. In developing countries malaria has been endemic in the lowlands for centuries with no occurrence in the highlands above 2000 metres above sea level. This pattern has changed over the last decade whereby malaria is occurs in epidemics with a high morbidity and mortality among the inhabitants of the highlands especially children and pregnant women. Eldoret and its environs in Kenya is a highland area with an altitude of 2300 metres above sea level where malaria was rare up to the late 1980s. Since 1988 malaria occurs in epidemics in this region with a high prevalence of severe malaria especially cerebral malaria(CM). This led to the conduct of stndies that fonn the basis of this thesis with the aim of delineating aspects of pathogenesis and the clinical presentation of CM in the Western highlands of Kenya.

Materials and Methods: Cross sectional, retrospective and prospective studies were conducted to study the prevalence of malaria among inpatients at the Moi Teaching and Referral Hospital (MTRH); to describe the clinical presentation of CM in the highlands; to compare temperatures in CM and uncomplicated malaria(UM) cases and to assay the serum tumour necrosis factor alpha (TNFa) and transforming growth factor beta (TGF-13)1 levels in these patients.

A total of 4 720 children were retrospectively and prospectively studied over an 18 month period (1991-1993) to establish the top 20 diseases at the MTRH. This was followed by a prospective study of 23 CM and 12 UM cases in 1997. All the presenting features of the cases with CM were tabulated on admission and analysed so as to establish the clinical presentation of CM in this region and compare this to the standard as described by the World Health Organisation (WHO). A comparison was made between the brain, core and skin temperatures of the CM and UM cases with normal children acting as controls.

This was a follow up of a similar stndy in 1993 that compared core and skin temperatures between measles, CM and UM with normal children as controls. Serum TNF-a and TGF-131 levels were assayed and compared among the CM and UM patients in the 1997 study and included the assay of cerebrospinal (CSF) TNF-α and TGF-β1 in CM.

Results and conclusions: Malaria accounted for 3 3% of all admissions over the study period with a case fatality rate of 2.2% and a mortality rate of 10.7%. Most children with CM were aged 3-10 years and were of good nutritional status. They presented in coma, with fever, headache, convulsions and hyperparasitaemia and with a short duration of illness of less than 3 days. Severe anaemia and hypoglycaemia were not common features. Malaria is the leading cause of morbidity in the children stndied. CM in the highlands presents as that seen among non-immunes. There were no differences in brain, core and skin temperatures between the CM and UM patients. The brain temperature was however always lower than core temperature even in normal controls with brain temperature having a positive correlation with core temperature as the body temperature rises. Thus, the role of fever in the pathogenesis of CM is still unclear The serum TNF-α and TGF-β1 levels were the same in UM and CM cases with TNF-α and TGF-β1 having an inverse relationship to each other. Patients with deeper levels of coma had higher levels of TNF-α and lower levels of TGF-β1.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2002. , s. 110
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 729
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-26649Lokal ID: 11214ISBN: 91-7373-171-4 (tryckt)OAI: oai:DiVA.org:liu-26649DiVA, id: diva2:247198
Disputas
2002-05-08, Elsa Brändströmssalen, Universitetssjukhuset, Linköping, 10:00 (svensk)
Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2012-09-13bibliografisk kontrollert
Delarbeid
1. Paediatric morbidity and mortality at the Eldoret District Hospital, Kenya
Åpne denne publikasjonen i ny fane eller vindu >>Paediatric morbidity and mortality at the Eldoret District Hospital, Kenya
1995 (engelsk)Inngår i: East African Medical Journal, ISSN 0012-835X, Vol. 72, nr 3, s. 165-169Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Over an 18 month period, there were 4,720 paediatric admissions at the Eldoret District Hospital in Western Kenya. The most frequent 20 diseases were identified and their respective case fatality rates calculated. Malaria was the most common cause for admission (33.0%) but the fourth most common cause of death with a case fatality rate of 2.2%. The overall mortality rate on the paediatric wards was 8.2% with 64.9% of the deaths occurring within the first 24 hours of hospitalization. Three-fourth of all admissions were due to four diseases: malaria, pneumonia, gastroenteritis and measles. Targeted interventional programmes aimed at these 4 diseases, coupled with a comprehensive primary health care system, would most likely result in much less morbidity and mortality for the children in the district. The systems for routinely collecting and storing medical records were found to be substandard, making it very difficult to accurately monitor morbidity and mortality.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-81403 (URN)7796768 (PubMedID)
Tilgjengelig fra: 2012-09-13 Laget: 2012-09-13 Sist oppdatert: 2017-12-07bibliografisk kontrollert
2. Clinical presentation and diagnosis of cerebral malaria in children in the highlands of western Kenya
Åpne denne publikasjonen i ny fane eller vindu >>Clinical presentation and diagnosis of cerebral malaria in children in the highlands of western Kenya
Vise andre…
1999 (engelsk)Inngår i: East African Medical Journal, ISSN 0012-835X, Vol. 76, nr 2, s. 89-92Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND:

The clinical presentation of cerebral malaria in children in the highlands has not been documented.

OBJECTIVE:

To describe the presentation of cerebral malaria in the age group one to twelve years.

DESIGN:

Prospective study conducted from May to September 1997, the rainy season during which malaria occurs in epidemics in the highlands of Kenya.

SETTING:

Paediatric wards of the Moi Teaching and Referral Hospital, Eldoret which is the Teaching Hospital for Moi University and the referral centre for surrounding districts of Western Kenya, with an altitude of over 2000 metres above sea level.

PATIENTS:

Twenty three consecutive children aged one to twelve years with cerebral malaria as defined by the WHO were studied. All children were treated with the standard quinine regimen for cerebral malaria.

RESULTS:

Majority of the children were six to ten years of age with 95.7% having a normal weight for age. 91.3%, 89.5% and 72.2% had fever, headache and convulsions respectively. 68.1% had a short duration of illness (less than three days) with only 9.5% presenting with hypoglycaemia. Severe anaemia was not observed but 72% had mild to moderate anaemia. Hyperparasitaemia (parasite counts greater than 100,000 per microlitre) was found in majority of the cases.

CONCLUSION:

Cerebral malaria presentation in the highlands is similar to that among non-immune populations and is an acute fulminant illness presenting with coma, hyperparasitaemia, fever and convulsions in children with normal nutritional status.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-81404 (URN)10442129 (PubMedID)
Tilgjengelig fra: 2012-09-13 Laget: 2012-09-13 Sist oppdatert: 2017-12-07bibliografisk kontrollert
3. A comparison of core and skin temperature among normal and febrile children with cerebral malaria, uncomplicated malaria, and measles
Åpne denne publikasjonen i ny fane eller vindu >>A comparison of core and skin temperature among normal and febrile children with cerebral malaria, uncomplicated malaria, and measles
Vise andre…
1995 (engelsk)Inngår i: Pathophysiology, ISSN 0928-4680, Vol. 2, nr 1, s. 55-59Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Forty-four children were studied to compare the pathogenesis of fever in cerebral malaria, uncomplicated malaria and measles at the Eldoret District Hospital (EDH). A control group of normal children was used. The three patient groups were studied for three consecutive days measuring skin and core temperature three-times a day using the Liquid Crystal Device (LCD) thermometer. A statistical analysis of the results within and between the groups was carried out for core and skin temperature over the study period. No statistical differences were found between the groups for either the skin or the core temperature, but a significant statistical difference was demonstrated between the core and the skin temperature for all of the groups for each of the three days. No statistical difference was found when the differences between the core and skin temperature were compared between cerebral malaria and uncomplicated malaria. The possible roles of fever in morbidity and mortality are discussed, with special reference to cerebral malaria.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-81407 (URN)10.1016/0928-4680(94)00034-K (DOI)
Tilgjengelig fra: 2012-09-13 Laget: 2012-09-13 Sist oppdatert: 2012-09-13bibliografisk kontrollert
4. A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria
Åpne denne publikasjonen i ny fane eller vindu >>A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria
2001 (engelsk)Inngår i: Journal of Tropical Pediatrics, ISSN 0142-6338, E-ISSN 1465-3664, Vol. 47, nr 3, s. 170-175Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A prospective study was carried out in which brain, core and skin temperatures were studied in children with cerebral malaria (n = 23), uncomplicated malaria (n = 12) and normal children (n = 9) using the zero heat flow method. Patients with cerebral or uncomplicated malaria were admitted to the paediatric wards (mean age, 6 years 8 months ± 2 years 8 months). Normal children, children of the investigators, of the same age group, served as controls. Parasitaemia levels were similar in the cerebral and uncomplicated malaria cases. Higher brain than core temperatures would have been expected in cerebral malaria but not in uncomplicated malaria but this was not the case in this study. There was no statistical difference in brain, core and skin temperature between cerebral and uncomplicated malaria patients. However, there was a highly significant difference between normal children and cerebral and uncomplicated malaria patients. Brain temperature was 0.02–0.2°C below core temperature in all the groups with larger differences during the febrile period. Mean differences of brain minus core, brain minus skin and core minus skin between the two groups of patients were not statistically significant. There was no correlation between temperature and the level of coma or parasitaemia for cerebral and uncomplicated malaria patients. There was a positive correlation between brain and core temperature in both groups of patients during the febrile phase. Brain temperature remained lower than core temperature in cerebral and uncomplicated malaria as in normal children. Normal thermoregulation appears to be maintained in cerebral malaria.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-25899 (URN)10.1093/tropej/47.3.170 (DOI)10340 (Lokal ID)10340 (Arkivnummer)10340 (OAI)
Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2019-12-29bibliografisk kontrollert
5. Cerebral malaria in children: Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome
Åpne denne publikasjonen i ny fane eller vindu >>Cerebral malaria in children: Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome
Vise andre…
2003 (engelsk)Inngår i: Journal of Tropical Pediatrics, ISSN 0142-6338, E-ISSN 1465-3664, Vol. 49, nr 4, s. 216-223Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

This was a prospective study conducted at the Moi Teaching and Referral Hospital, Eldoret, Kenya. Twenty‐three children admitted to the hospital with cerebral (CM) and 10 children with noncerebral malaria (NCM) were studied. The aim of the study was to establish and compare levels of tumour necrosis factor (TNF‐α) and transforming growth factor (TGF‐β1) in these children. Serum and cerebrospinal fluid (CSF) cytokine levels were assayed using ELISA kits. In serum, TGF‐β1 and TNF‐α decreased over 5 days after admission to the hospital in both groups of patients with CM and NCM. In the CSF of cerebral cases the levels of TNF‐α and TGF‐β1 were low and inversely related. Children in deeper coma had lower levels in serum of TGF‐β and higher levels of TNF‐α than those in lighter levels of coma. The serum TNF‐α levels in CM children were the same irrespective of the duration of illness before admission, but children with NCM who had been sick for a shorter duration before admission tended to have higher serum levels of TNF‐α and higher levels of TGF‐β than those with a longer duration of illness before admission. In conclusion, this study shows that TNF‐α and TGF‐β1 may not be useful in predicting the outcome for CM. They may, however, be useful in detecting children at risk of developing deep coma. TNF‐α and TGF‐β levels were inversely related both in serum and CSF.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-46358 (URN)10.1093/tropej/49.4.216 (DOI)
Merknad

On the day of the defence day the status of this article was submitted.

Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2020-01-16bibliografisk kontrollert

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