Socio-economic determinants are not major risk factors for severe malaria in Gambian children

151

TRANSACTIONS OFTHEROYALSOCIETY OFTROPICAL MEDICINEANDHYGIENE(1995) 89,15 1-154

Socio-economic determinants Gambian children

are not major risk factors for severe malaria

in

‘Medical Research Council Laboratories, and B. M. Greenwood’ K. A. Koraml*, S. Bennett*, J. H. Adiamah”* Fajara, P.O. Box 273, Banjul, The Gambia; *Tropical Health Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London, WClE 7HT, UK Abstract

Only a small proportion of subjects infected with Plasmodium falciparum develop severe disease. Why this should be is not fully understood. To investigate the possible importance of socio-economic variables on the severity of malaria in Gambian children we undertook a case-control study of 384 children with severe or mild malaria. Few differences were found between the 2 groups. Children with severemalaria had a longer duration of symptoms when recruited than mild casesbut this difference was largely accounted for by the fact that most children with severe diseasewere recruited at a referral hospital, whilst mild caseswere recruited at a primary health care facility nearer their home. There was no difference between groups in the time before mothers sought some form of health care. Mothers of children with severe diseasewere less ready to take their child to hospital than mothers of mild cases,suggesting that education on the importance of taking a child with features of malaria to a health centre as soon as possible might have some effect on the development of severedisease.However, overall, the results of this study suggestedthat socio-economicand behavioural factors are not the major determinants for severemalaria in African children. Keywords: malaria, Plasmodiumfalciparum, risk factors, The Gambia Introduction

Infection with Plasmodium falciparum can result in an illness characterized by little more than mild fever or in a fulminating infection which kills within a day of the first onset of symptoms. In The Gambia, we have estimated that about 1%2% of P. falciparum infections are characterized by severediseaseand that, in rural communities, about one-half of these severe infections are fatal (GREENWOOD et al., 1991).

The reasons why some infections with P. falciparum are much more severe than others has recently attracted considerable interest. Most attention has concentrated on the characteristics of the parasite and on the genetic characteristics of the host. Thus, it has been shown that parasites obtained from children with severemalaria form rosettes with uninfected red blood cells more readily than do parasites obtained from children with mild disease (CARLSON et al., 1990) and that they induce higher levels of tumour necrosis factor production by human mononuclear cells in vitro (S. J. Allen et al., unpublished observations). Host genetic factors shown to influence diseaseseverity include the haemoglobin genotype and the possession of certain human leucocyte antigens (HLA) classI and classII (HILL et al., 1991). Socio-economic and environmental factors, such as poor housing, crowding, lack of knowledge of the causes of malaria, and educational level have been shown to predispose to malaria in parts of Asia and Latin America (BANGUERO, 1984; BUTTRAPORN et al., 1986; FUNGLADDA et al., 1987) and we have demonstrated that some socio-economic factors are risk factors for overall malaria illness in The Gambia (ADIAMAH et al., 1993; KORAM et al., in press). Could such factors also be important in modulating the severity of malaria illness, for example by increasing human/vector contact or by predisposing to late or inappropriate treatment? We have undertaken a study in Gambian children, using a casecontrol technique (HAYES et al., 1992), to investigate whether this is the case. Materials

and Methods

The study area, study design and case recruitment methods have been described elsewhere (KORAM et al., 1995). Briefly, the study was carried out in the periurban areas around Banjul, the capital of The Gambia. Children with severe malaria (mainly cerebral malaria or *Current address: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. **Current address: Health Research Station, P.O. Box 114, Navrongo, UER, Ghana.

severe anaemia) were recruited from the Royal Victoria Hospital (RVH), Banjul and the Medical ResearchCouncil Laboratories (MRC) hospital in Fajara. These children met the World Health Organization criteria for severe malaria. Mild cases were recruited from Serrekunda, Fajikunda or Brikama Health Centres and were matched for agewith severecases.Healthy children, also matched for age, were recruited randomly from the immediate neighbourhoods of severe and mild cases. A structured questionnaire was administered shortly after recruitment by trained interviewers to parents or guardians of the casesand controls to collect information on a wide range of socio-economic indicators (Table l), and Table 1. Potential malaria investigated

socio-economic

risk factors

for

Family background Migration, residence and travel patterns in and out of the study area Caretaker of index child Mother’s marital status and marriage arrangement Domicile of the father Ethnic origin of both parents Occupation of both arents Educational level of TJ0th parents Total number of children of mother Total number of children of father Total number of persons sleeping with index child Presenceof other relatives in the compound Parents’ understanding of malaria, its causation, treatment and prevention Mos uito avoidance behaviour of the family s y ownershipof selectedconsumeritems Fame Compound characteristics Family owners or tenants in compound General state of the compound Sourceof water supply and water storage in the compound Structure of the house-wall, roof, mosquito proofing on doors and/or windows Presenceof animals in the compound

households of casesand controls were visited. During the dry season of the year following the malaria illness in their child, mothers were visited at home, told a story about a hypothetical child with a malaria-like illness, and askedwhat they would do if this was their own child. A matched case-control analysis, using the statistical packageEGRET, was performed to produce estimates of the odds ratio (OR) associated with each factor. Multivariate analysis of factors significant in the t&variate analysis was performed by conditional logistic regression to construct a parsimonious model that included only those factors that remained statistically significant in the presenceof other factors.

152 The study was approved by the Gambia Government/MRC Ethical Committee. Results

A total of 384 children with malaria was recruited, 192 with severedisease(116 cerebral malaria. 76 severemalarial anaemia) and 192 with mild disease,together with an equal number of control children. Children with severe malaria and those with mild malaria were well matched with regard to age (mean ages43 and 45 months respectively), sex and ethnic group. Children with cerebral malaria (mean age 52 months) were much older than those with severe malaria anaemia (mean age 30 months). All infections were caused by P. falciparum, apart from 3 P. malariae infections among the mild cases.The geometric mean parasite density was higher among the severecases (mean 49 24O/yL, 95% confidence interval [CI] 2980442 41O/uL) than among the mild cases(mean 22 66OiuL 95% CI 250&242 SOO/uL)(t = 6.01; P
Potential risk factor

odds ratios for socio-economic

Severemalaria No.

all cases had sought treatment on the same day that symptoms started, but 20% had not sought treatment for the first time until more than 3 d after the onset of symptoms. Treatments included giving antipyretics and tepid sponging for fever (81% of responses), and using charms and amulets (2%). There was no difference between the time taken to seek first treatment, of whatever type, between the groups. When, during the dry seasonfollowing the illness of their child, mothers were told a story about a hypothetical child with malaria. mothers of children with mild malaria indicated that they would be more likely to take their children to the hospital or clinic (health centre) as the first course of action than did mothers of severecases of malaria (OR = 2.53, 95% CI 1.04-6.13; P = 0.04). Other courses of action reported, including tepid sponging and use of antipyretics (69% of responses), visits to the local medicine man (9%), and use of amulets and charms against the disease (3%), did not differ between the groups. A significantly higher proportion of severecases(32%) than mild cases(19%) was found in houses built on plots of land owned bv the familv (OR = 3.12. 95% CI 1.397.14; P = 0.006). This was among a series of items investigated as surrogate measures for the wealth of the family, the distribution of which did not differ between the groups in any other way. Compounds or houses of children with severe malaria were generally similar in construction to those of children with mild malaria. However, a higher proportion of children with severe malaria (38%) than of children with mild malaria (26%) lived in mud-walled houses. This difference, though significant in the univariate analysis, was not statistically significant in the multivariate analysis. Methods used to

factors associated with severe malaria (severe cases vs. mild

MildNylaria

Crude odds ratiob

P

Adjusted odds ratiob+

P

Dut;tii of symptoms 88 (46%) ;3d 102 (54%) Mother’s referred treatment of malaria I-k-k~$ Pacihty 1;; ;;;$ i I

138 (72%) 53 (28%)

1.00 2.81 (1.7w.54)

0.001

I.00 3.08 (1.68-5.67)


135 86% 22 t 14%!

1.00 3.33 (1.54-7.98)

0.02 1

1.00 2.53 (1.04-6.13)

0.040

Far+-iiiyowns plot on which6:o;ls$s built 131 t 684 1

37 19% 155 t 81%j

1.00 0.49 (0.28-0.83)

0.007

it!

0.006

Fan&y N? burns mosquito No Material used for wall Cement/brick Mud Ill;nesfhe previous year

121 (63%) 71 (37%)

1.00 1.51 (0.98-2.36)

0.007 0.060

1.00 1.76 (0.98-3.15)

0.06

1.00 1.81 (1.10-3.04)

0.019

:::

(0.84-3.27)

NSd

1.00 1.60 (0.95-2.75)

0.082

1.00 1.25 (0.89-3.09)

NSd

No

42 (23%) 144 (77%)

60 (32%) 130 (68%)

(0. U-0.72)

aAll variables for which the uncorrected odds ratio had a value of P
prevent mosquito bites in homes included burning mosquito coils (56% of all families), spraying insecticides (25%), buring of churai, the bark of a local tree (Danida &err) (51%), and sleeping under bed nets (32%). No significant difference between the utilization of any of these anti-mosquito measures was found between children with severeor mild disease. Only 10% of mothers had obtained formal education beyond primary level and the majority (85%) could neither read nor write. No significant difference was found between the level of education of mothers of child-

153 ren who had experienced severe or mild malaria. More than three-quarters of mothers described themselves as ‘housewives’ and were not in any gainful employment outside the home. There was no association between the occupation of either parent and the occurrence of severe or mild malaria. Discussion

We have found little evidence that socio-economicfactors are important determinants of severe malaria in Gambian children. We found only 6 positive associations among more than 50 potential factors investigated using univariate analysis and only 3 of these remained positive in a multivariate analysis. These factors were the duration of illness (at thi time of presentation to hospital/health facilitv). the mother’s oreferred treatment of malaria, and fanuly ownership of the land upon which their house was built. The detection of an association between duration of symptoms before entry into the study and disease severity is potentially important asit suggeststhat reducing the time before presentation might reduce disease severity. However, this interpretation may be incorrect. Children with severe malaria were nearly all recruited in a central hospital after referral from a peripheral health centre, whilst mild caseswere seen when they presented at a health centre. Becausetransport between peripheral health centres and the central hospital is not always easy to obtain, especially at night, the difference in mean duration of symptoms between the groups, of approximately 24 h, is likely to have been accounted for mainly by delay in getting to the central referral hospital rather than by a difference in the duration of symptoms between the 2 groups. There was no difference between groups in the time between the first onset of symptoms and the first contact with a source of treatment. When visited some months after the illness of their own child and presented with the story of a child with malaria, more mothers whose children had previously had mild malaria reoorted that their first choice of treatment for such a child would be a health facility than did the mothers of children who had severe disease. This finding suggeststhat it might be possible to prevent some casesof malaria progressing to severediseaseif mothers were educated about the importance of taking children with the symptoms of malaria, including fits which are frequently not a feature of malaria, to a health centre as the first line of treatment. Becauseof the delav that frequently occurs between referral from a periphkral clinic to the specialist hospital in the capital, it is essential that health centres should have available parenteral drugs suitable for the treatment of severe casesunable to take medication and that treatment should be started immediately. Meningococcal infection provides an example of another infectious diseaseof widely varying severity for which treatment on first contact appears to modify severity (CARTWRIGHTet al., 1992; STRANG& PUGH, 1992). The detection of an association between ownership of land and severe malaria was surprising, for the opposite might have been expected. This association may have arisen by chance, as a large number of different risk factors were assessed.However, a possible explanation is that compound owner-occupiers are more likely to live in newly settled areason the periphery of communities, in areas with stagnant water, poor drainage and near to swamps. Important negative findings were the absence of any association between severediseaseand maternal or paternal education, occupation, household wealth, crowding, or the use of personal protection measuresagainst malaria such as mosquito coils and bed nets. An association with the use of coils was found in the univariate analysis but disappeared on multiple logistic regression. An interesting finding was that relatively few urban children slept under bed nets, in contrast to the situation in rural areas

of The Gambia where bed nets are widely used and have been shown to provide powerful protection against malaria when treated with insecticide (ALONSOet al., 1991). The probable reason for this is that in rural areas mosquitoes are more numerous and more of a nuisance than in the urban and peri-urban areasnear the capital. Our conclusions differ from those of a recent study in Brazzaville (CARMEet al., 1994), in which children with severe malaria were reported to come from households with a lower socio-economic standard than those of the control group. However, the design of this study may have led to differences in family size between the 2 groups and in any risk factors which are related to family size. In The Gambia it seems likelv that the characteristics of the parasite and genetic &aracteristics of the host are much more important determinants of whether an individual infection will result in mild or severe disease. This conclusion has important practical implications for it suggeststhat, although improving knowledge of the recognition and management of malaria and improving treatment facilities may have an important role to play in reducing malaria morbidity, these measures may not be particularly effective in reducing the incidence of severedisease.To achieve the latter it may be necessaryto reduce the level of infection by vector control, reduction of human/vector contact, or other measuressuch asvaccination. Acknowledgements

We are grateful to Messrs Lamin Manneh, Lang Bayo, SambaBahandJosephBassour field workers; Drs Ayo Palmer,

D. Brewster and T. McKay of the RVH; the staff of Serrekunda, Fajikunda and Brikama Health Centres for help with the study; and the parents of our children for welcoming us to their homes and giving much of their valuable time. This study received financial report from the Joint UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseasesand the Rockefeller Foundation through their joint funding venture. References Adiamah, J. H., Koram, K. A., Thomson, M. C., Lindsay? S. W., Todd, J. & Greenwood, B. M. (1993). Entomologxal risk factors for severe malaria in a peri-urban area of The ~;~G~, Annals of Tropical Medicine and Parasitology, 87,

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Banguero,H. (1984). Socio-economicfactors associatedwith

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Buttraporn, P., Sornmani, S. & Hungsapruek, T. (1986). Social, behavioural, housing factors and their interactive effects associatedwith malaria occurrence in East Thailand. Southeast AsianJournal of Tropical Medicine and Public Health, 17, 3X6-392.

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Hayes, R. J., Marsh, K. & Snow, R. W. (1992). Case control studies of severemalaria. Journal of Tropical Medicine and Hygiene,95,157-166. Hill, A. V. S., Allsop, C. E. M., Kwiatkowski, D., Anstey, N. M., Twumasi, P., Rowe, P. A., Bennett, S., Brewster, D.,

154 McMichael, A. J. & Greenwood, B. M. (1991). Common West African HLA antigens are associated with protection from severemalaria. Nature, 352,595-600. Koram, K. A., Bennett, S., Adiamah, J. H. & Greenwood, B. M. (1995). Socio-economic risk factors for malaria in a periurban area of The Gambia. Transactions of the Royal Society of Tropical Medicine and Hygiene, 89, 146150.

Strang, J. R. & Pugh, E. J. (1992). Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. Brirish MedicalJournal, 305, 141-143. Received I1 July 1994; revised 20 October 1994; accepted for publication 20 October 1994

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