alternatives to bodyweight for estimating the dose of praziquantel needed to treat schistosomiasis

6
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE (1999) 93,653-658 Alternatives to bodyweight for estimating the dose of praziquantel needed to treat schistosomiasis Andrew Hall’, Catherine Nokes’, Su-Tung Wen’, Sam Adjei2, Charles Kihamia3, Lillian Mwanri3, Emily Bobrod, Joseph de Graft-Johnson4 and Don Bundy’ ‘Partnership for Child Development, Wellcome Trust Centre for the Epidemiology of Infectious Disease, Oxford University, South Parks Road, Oxford OX1 3FY, UK; ‘Ghana Partnership for Child Development, Health Research Unit, I? 0. Box 184, Ministry of Health, Adabraka, Accra, Ghana; ‘Tanzania Partnership for Child Development, Ocean Road Hospital, I? 0. Box 9383, Dar es Salaam, Tanzania; 4Save the Children Federation, I? 0. Box 30374, NGO Onions Village, Lilongwe, Malawi Abstract Data on age, height and mid upper-arm circumference (MUAC) from nearly 6000 schoolchildren in Ghana, Tanzania and Malawi (not MUAC) were used to examine their power to predict bodyweight and thus the dosage of praziquantel required to treat schistosomiasis. Height was found to provide a simple and reasonably accurate estimate of weight, and about 75% of children would have been given a dosage of praziquantel within the range normally given using bodyweight at a dosage of 40 mg/kg bodyweight. The upper and lower ranges in dosage did not exceed dosages of praziquantel which have been used before or are currently recommended to treat schistosomiasis. A pole marked with the number of tablets could thus be used as a simple way to determine the dose of praziquantel to treat children in school-based health programmes. Keywords: schistosomiasis, Schistosoma mansoni, Schistosomahaematobium, chemotherapy, praziquantel, dosage determination, school health programmes, Ghana, Tanzania, Malawi Introduction The Partnership for Child Development (PCD) has been working since 1992 to strengthen or establish school-based health services, including periodic de- worming (PCD, 1997). Because most anthelmintics are safe. effective and simule to give, the WHO recom- mends ‘mass treatment bf all schoolchildren if the prevalence of worms is greater than 50% (WHO, 1995a). The drug most widely used to treat schistoso- miasis is praziquantel given as a single dose of 40 mg per kg bodyweight (mg/kg), although in some areas this may be increased to 60 mg/kg (WHO, 1995b). Praziquantel was previously recommended at this higher dosage to treat Schistosoma japonicum or S. mansoni infections or mixed infections with S. mansoni and S. haematobium (WHO, 1990). The drughas also beenused at a dosage of 20 mg/kg and achieved egg reduction rates no different from a dosage of 40 mg/kg (TAYLOR et al., 1988; KING et al., 1989). mended dosage is 40 mg/kg bodyweight (WHO, 1995b), praziquantel cannot always be given at precisely the recommended dosage. If African schoolchildren are weighed to a precision of 0.1 kg then in practice a dosage of praziquantel ranging between 36 and 44 mg/kg is administered. Similarly when the target dosage is 60 mg/kg the actual dosage ranges from 56 to 64 mg/kg, and when the target dosage is 20 mg/kg the actual dosage ranges from 16 to 24 mg/kg. The fact that the dose of praziquantel needs to be adjusted for bodyweight adds a significant complication to school-based treatment programmes because the cost and fragility of weighing scales mean that it is usually not possible to supply and maintain a scale in every school. If teachers are to administer praziquantel to their pupils as a part of school-based programmes then a simple and inexpensive alternative is needed to determine the dose of praziquantel. One such alternative to weight is height, a measurement which has been used to estimate the dose of ivermectin for treating onchocerciasis (ALEXANDER et aZ., 1993). The analysis described here had 3 aims. First, to examine the power of a number of simple alternative measures to predict the bodyweight of children in 3 African countries in order to administer praziquantel. Second, to investigate whether separate predictions of weight were required for boys and girls. And third, to examine whether predictions for children in one African country could be applied in another. Methods and Results Praziquantel is supplied by the proprietary and some generic manufacturers as scored tablets weighing 600 mg each that can be broken into quarters. Because the smallest unit of delivery is thus 150 mg, and the recom- Address for correspondence: Andrew Hall, Wellcome Trust Centre for the Epidemiology of Infectious Disease, Oxford University, South Parks Road, Oxford OX1 3FY, UK; phone +44 (0)1865 281231,fax+44 (0)1865 281245, e-mail [email protected] Alternatives to weight Any alternative to weight used to calculate the dose of praziquantel for treating schoolchildren must be highly correlated with bodyweight and easy for teachers to determine with reasonable accuracy using simple, robust and inexpensive equipment. We explore here the use of age. mid uuuer-arm circumference (MUAC), height and some combinations of these variables to’ pre&ct the bodvweight of schoolchildren and then, from predicted weight, the dosage of praziquantel. Data on schoolchildren in Ghana, Tanzania and Malawi were used for these analyses: The data sets comprised age, recorded to a precision of 1 year; height measured to-a precision of 0.1 cm; weight measured to a precision of 0.1 kg (except in Malawi where it was measured to 0.5 kg); and MUAC measured to a preci- sion of 2 mm (except in Malawi where it was not meas- ured). The anthropbmetric measurements were made by trained nutritionists. Table 1 shows the distribution bv sex and age of the samples of children in each country: Data analysis There were 4 steps. First, scatter plots were done to examine the nature of the relationship between weight and each alternative variable, with weight on the y-axis. Linear or quadratic functions were used to tit lines by minimizing residuals using least squares, and the good- ness of fit was assessed by maximizing r’. Second, the equation for the line of best fit was then used to predict the bodyweight of each subject from the alternative measure. Third, the predicted weight was used to work out the dose of praziquantel that would have been given to each child, to the nearest quarter tablet, at a target dosage of 40 mg/kg. Finally, the dosage of praziquantel that would have been given was calculated in mg/kg. The predictive power of iach alternative measure’ was as- sessed in terms of the percentage of children who would have been given praziquantel within the normal target range of 36-44 mg/kg. The relationships between height and weight were

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TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE (1999) 93,653-658

Alternatives to bodyweight for estimating the dose of praziquantel needed to treat schistosomiasis

Andrew Hall’, Catherine Nokes’, Su-Tung Wen’, Sam Adjei2, Charles Kihamia3, Lillian Mwanri3, Emily Bobrod, Joseph de Graft-Johnson4 and Don Bundy’ ‘Partnership for Child Development, Wellcome Trust Centre for the Epidemiology of Infectious Disease, Oxford University, South Parks Road, Oxford OX1 3FY, UK; ‘Ghana Partnership for Child Development, Health Research Unit, I? 0. Box 184, Ministry of Health, Adabraka, Accra, Ghana; ‘Tanzania Partnership for Child Development, Ocean Road Hospital, I? 0. Box 9383, Dar es Salaam, Tanzania; 4Save the Children Federation, I? 0. Box 30374, NGO Onions Village, Lilongwe, Malawi

Abstract Data on age, height and mid upper-arm circumference (MUAC) from nearly 6000 schoolchildren in Ghana, Tanzania and Malawi (not MUAC) were used to examine their power to predict bodyweight and thus the dosage of praziquantel required to treat schistosomiasis. Height was found to provide a simple and reasonably accurate estimate of weight, and about 75% of children would have been given a dosage of praziquantel within the range normally given using bodyweight at a dosage of 40 mg/kg bodyweight. The upper and lower ranges in dosage did not exceed dosages of praziquantel which have been used before or are currently recommended to treat schistosomiasis. A pole marked with the number of tablets could thus be used as a simple way to determine the dose of praziquantel to treat children in school-based health programmes.

Keywords: schistosomiasis, Schistosoma mansoni, Schistosoma haematobium, chemotherapy, praziquantel, dosage determination, school health programmes, Ghana, Tanzania, Malawi

Introduction The Partnership for Child Development (PCD) has

been working since 1992 to strengthen or establish school-based health services, including periodic de- worming (PCD, 1997). Because most anthelmintics are safe. effective and simule to give, the WHO recom- mends ‘mass treatment bf all schoolchildren if the prevalence of worms is greater than 50% (WHO, 1995a). The drug most widely used to treat schistoso- miasis is praziquantel given as a single dose of 40 mg per kg bodyweight (mg/kg), although in some areas this may be increased to 60 mg/kg (WHO, 1995b). Praziquantel was previously recommended at this higher dosage to treat Schistosoma japonicum or S. mansoni infections or mixed infections with S. mansoni and S. haematobium (WHO, 1990). The drughas also beenused at a dosage of 20 mg/kg and achieved egg reduction rates no different from a dosage of 40 mg/kg (TAYLOR et al., 1988; KING et al., 1989).

mended dosage is 40 mg/kg bodyweight (WHO, 1995b), praziquantel cannot always be given at precisely the recommended dosage. If African schoolchildren are weighed to a precision of 0.1 kg then in practice a dosage of praziquantel ranging between 36 and 44 mg/kg is administered. Similarly when the target dosage is 60 mg/kg the actual dosage ranges from 56 to 64 mg/kg, and when the target dosage is 20 mg/kg the actual dosage ranges from 16 to 24 mg/kg.

The fact that the dose of praziquantel needs to be adjusted for bodyweight adds a significant complication to school-based treatment programmes because the cost and fragility of weighing scales mean that it is usually not possible to supply and maintain a scale in every school. If teachers are to administer praziquantel to their pupils as a part of school-based programmes then a simple and inexpensive alternative is needed to determine the dose of praziquantel. One such alternative to weight is height, a measurement which has been used to estimate the dose of ivermectin for treating onchocerciasis (ALEXANDER et aZ., 1993). The analysis described here had 3 aims. First, to examine the power of a number of simple alternative measures to predict the bodyweight of children in 3 African countries in order to administer praziquantel. Second, to investigate whether separate predictions of weight were required for boys and girls. And third, to examine whether predictions for children in one African country could be applied in another.

Methods and Results Praziquantel is supplied by the proprietary and some

generic manufacturers as scored tablets weighing 600 mg each that can be broken into quarters. Because the smallest unit of delivery is thus 150 mg, and the recom-

Address for correspondence: Andrew Hall, Wellcome Trust Centre for the Epidemiology of Infectious Disease, Oxford University, South Parks Road, Oxford OX1 3FY, UK; phone +44 (0)1865 281231,fax+44 (0)1865 281245, e-mail [email protected]

Alternatives to weight Any alternative to weight used to calculate the dose of

praziquantel for treating schoolchildren must be highly correlated with bodyweight and easy for teachers to determine with reasonable accuracy using simple, robust and inexpensive equipment. We explore here the use of age. mid uuuer-arm circumference (MUAC), height and some combinations of these variables to’ pre&ct the bodvweight of schoolchildren and then, from predicted weight, the dosage of praziquantel.

Data on schoolchildren in Ghana, Tanzania and Malawi were used for these analyses: The data sets comprised age, recorded to a precision of 1 year; height measured to-a precision of 0.1 cm; weight measured to a precision of 0.1 kg (except in Malawi where it was measured to 0.5 kg); and MUAC measured to a preci- sion of 2 mm (except in Malawi where it was not meas- ured). The anthropbmetric measurements were made by trained nutritionists. Table 1 shows the distribution bv sex and age of the samples of children in each country:

Data analysis There were 4 steps. First, scatter plots were done to

examine the nature of the relationship between weight and each alternative variable, with weight on the y-axis. Linear or quadratic functions were used to tit lines by minimizing residuals using least squares, and the good- ness of fit was assessed by maximizing r’. Second, the equation for the line of best fit was then used to predict the bodyweight of each subject from the alternative measure. Third, the predicted weight was used to work out the dose of praziquantel that would have been given to each child, to the nearest quarter tablet, at a target dosage of 40 mg/kg. Finally, the dosage of praziquantel that would have been given was calculated in mg/kg. The predictive power of iach alternative measure’ was as- sessed in terms of the percentage of children who would have been given praziquantel within the normal target range of 36-44 mg/kg.

The relationships between height and weight were

654 ANDREW HALL ETAL.

Table 1. The number of subjects in each data set, by age and sex, in each country used for the analysis of alternatives to bodyweight for estimating praziquantel dose

Age (years) Boys

Ghana

Girls Total Boys

Tanzania Malawi

Girls Total Boys Girls Total

6

8 9

10 11 12

ii 15 16 17

Total

132 72 137 90 31 71 42 51

:: 59

69 I”oi 84 103 84 145

116 86 78 53 48 26

901 902

204 227 102 93

103 74

177 187 229 202 131 74

1803

22 ;8 89 111

142 166 199 172 81 81

214 220 220 244

44 24 13 4 4 1

-

1028

-

1041

- 89 91 180 40 94 95 189

200 95 92 187 308 96 94 190 371 96 96 192 162 95 96 191 434 96 96 192 464 95 96 191

68 95 2 190 17 96 191 5 92 93 185

- - - -

2069 1039 1039 2078

examined separately by sex in each country; several combinations of variables were tested empirically for their power to predict weight including height’, height X MUAC, and height2 X MUAC; and the equa- tion used to predict weight from height from a standard age-group in 1 country was applied to data from children of the same age-groups in the other 2 countries.

Figure 1 shows representative plots for Tanzanian children of bodyweight with age, height, MUAC, and height’ X MUAC, the last of which was judged by the correlation coefficient to be the best of the empirical tits. The plots were similar for the other countries (not shown). The plots revealed that the best predictor of weight was height’ X MUAC, with height alone as second best. The scatter of weight against height was tighter among the smallest and youngest children, and the variance increased with body size and therefore age.

Plots of the relationship between weight and height done separately for each sex in each country (not shown) revealed that the lines of best fit diverged among the taller, and thus older boys and girls. This indicated the

5o r v = 1,744.x + 6.8038 5o r Y= 0,2428x- 16.141

45 i=O.664 40 -

^M 35 -

c30 -

325 -

'3 B 20 -

15 -

10

5 1 Age

01 I 4 6 a 10 12 14 16 18

Age (years)

5” r _. 45 - y= 0~0035r2-0~4249x +21.915

40 _ r=0.906

8 35 -

c 30 -

8 25 -

'E B 20 -

15 -

10 Height 5

110 120 130 140 150 160 Height (cm)

need to evaluate differences between the sexes in terms of the dosage of praziquantel that would be given on the basis of any alternative measure.

Plots of the relationship for all 3 countries between weight and height for both sexes combined (not shown) also revealed that the lines of best fit were different for each country and that adolescent Tanzanian children were lighter than children in Ghana and Malawi of the same height. This again indicated the need to evaluate the differences between countries in terms of the dosage of praziquantel that would be given on the basis of any alternative measure.

Predicting the dosage ofpraziquantelfrom alternative variables

The upper part of Table 2 shows for each of the alternative measures used to predict bodyweight the percentage of children in each country who would have been given a dosage of praziquantel above, below or within the target range of 36-44 mg/kg. In Ghana, for example, 72.4% of children would have been given a

45 - I= 0.840

40 -

10 - 5 - MUAC

0 , 100 125 150 175 200 225 250

MUAC (mm)

50 - = 45 Y 7 x 10-6 n + 4.4731 .

4. I = _ 0.963

35 -

2 30 .

" -a 25 -

'a 20 .

B 15 . Height’ x MUAC

1000000 2000000 3000000 4000000 5000000 6000000 Height’ x MUAC

Fig. 1. The relationships between bodyweight of schoolchildren in Tanzania and age, mid upper-arm circumference (MUAC), height, and height’ X MUAC. The equations for the lines of best fit are shown and r, the correlation coefficient.

Tabl

e 2.

Th

e pe

rcen

tage

s of

sch

oolc

hild

ren

in t

hree

co

untri

es

who

w

ould

ha

ve

rece

ived

a

dosa

ge

of p

razi

quan

tel

with

in,

belo

w,

or

abov

e th

e ta

rget

ra

nge

whe

n F

wei

ght

and

the

dose

of

dru

g w

ere

calc

ulat

ed

from

w

eigh

t an

d va

rious

al

tern

ativ

e va

riabl

es

B G

hana

Ta

nzan

ia

Mal

awi

Aaes

Va

riabl

e (y

ears

) Se

xes”

<T

arge

t Ta

rget

>T

arge

t <T

arge

t Ta

rget

>T

arge

t <T

arge

t Ta

rget

>T

arge

t

Wei

ght

Age

M

UAC

All

B&G

0.

0

Hei

ght’

X M

UAC

Hei

ght

Hei

ght

Hei

ght

Hei

ght

All

All

All

B&G

27

.4

B&G

16

.9

B&G

18

.4

All

B&G

11

.6

All

Boys

10

-3

All

Girl

s 13

.3

All

B+G

11

.8

100.

0

42.3

59

.6

78.4

72.4

74

.8

70.4

72

.6

Gha

na

(n

= 73

6)

0.0

30.3

23

.5

3.2

16.0

14

.9

16.3

15

.6

0.0

100.

0

20.6

57

.0

14.2

69

.8

11.7

86

.9

8.8

79.7

1E

81.9

76

.9

9.4

79.4

Tanz

ania

(n

=

0.0

22.3

15

.9

1.4

11.6

9.

6 12

.8

11.2

1939

)

0.0

100.

0 0.

0

23.6

49

.7

26.7

-

-

11.8

72

.2

16.0

9.

5 78

.3

12.1

15

.7

68.7

15

.6

12.6

73

.5

13.9

Mal

awi

(n

= 11

43)

Hei

ght

(Gha

na)

8-13

B&

G

9.9

72.3

17

-S

7.1

77.9

15

.0

5.0

70.5

24

.5

Hei

ght

(Tan

zani

a)

8-13

B&

G

19.4

71

.2

9.4

8.7

79.4

11

.9

6.6

74.6

18

.8

Hei

ght

(Mal

awi)

8-13

B&

G

14.8

72

.1

13.0

12

.5

77.9

9.

5 7.

7 75

.2

17.1

The

targ

et r

ange

was

def

ined

as

36-

44

mg/

kg

(the

norm

al

rang

e gi

ven

if ta

rget

do

sage

is

40 m

g/kg

). So

me

perc

enta

ges

may

not

add

up

to 1

00 b

ecau

se

of r

ound

ing.

Sa

mpl

e si

zes

are

give

n in

Tab

le

1.

“Sex

es:

B&G

=

boys

and

girl

s to

geth

er;

B +

G =

boy

s an

d gi

rls a

naly

sed

sepa

rate

ly

and

then

res

ults

co

mbi

ned.

-,

no d

ata.

Th

e lo

wer

hal

f of

the

Tabl

e sh

ows

the

perc

enta

ge

in e

ach

dosa

ge c

ateg

ory

whe

n tlx

do

se w

as e

stim

ated

fro

m

the

equa

tions

fo

r he

ight

fo

r ea

ch c

ount

ry

sepa

rate

ly

and

appl

ied

to c

hild

ren

aged

8-

13 y

ears

in

rhe

sam

e co

untry

(s

how

n in

bol

d)

and

the

othe

r 2

coun

tries

.

656

dosage of praziquantel in the range 36-44 mg/kg based on their height, while 11.6% would have been given less than this target range and 16.0% would have been given more. These calculations were done for each country using the best-fit lines derived from data for boys and girls combined (B&G), from data for boys alone (Boys), from data for girls alone (Girls), and if the calculations had been done separately for each sex and the results combined (B+G).

The lower part of Table 2 shows the same percentages using data from 1 country to predict the weight of children in each of the 2 other countries and then calculate the dosage of praziquantel. For example, 71.2% of children in Ghana would have been treated within the target range of 36-44 mg/kg if the equation for the line of height against weight for Tanzanian boys and girls (B&G) had been used to predict the weight of Ghanaian boys and girls and thus tile dose of praziiuan- tel. Of the remainder 19.4% would have received less than, and 9.4% more than, the target range.

Table 2 reveals 4 main points. First, that neither age nor MUAC was as good as height at estimating body- weight and delivering a dosage of praziquantel in the range of 36-44 mg/kg. Using height alone to predict weight, between 72.2% and 79.7% of children would have been given a dosage ofpraziquantel within the target range.

Second, that height’ X MUAC was better than height alone at predicting weight in that 78.4% of children in Ghana and 86.9% of children in Tanzania would have been given a dosage of praziquantel within the target range. However, the distribution of dosages was skewed, with the result that a larger proportion of children would have received a dosage lower than the target range than above it: 18.4% lower vs 3.2% higher in Ghana and 11.7% vs 1.4%, respectively in Tanzania.

Third, that when calculations from height alone are done separately for boys and girls in each country, a

18

16

12 16 20 2428 32 36 40 44 48 52 56 60 64 68

Dosage in mgikg

18 -

16 -

14 -

2 12 -

g 10 -

2 8. % :: 6 -

4 -

2 -

o-

mg/h :9

- -Tanzania -Ghana - - I Malawi

Height

121620242832364044485256606468 12 16 20 24 28 32 36 40 44 46 52 56 60 64 68

Dosage in mgikg Dosage in mgikg

- -Tanzania

-Ghana - - -Malawi

ANDREW HALL ETAL.

greater percentage of boys than girls would have received praziquantel within the target range: 4.4% more boys than girls in Ghana (P = 0.25), 5.0% more in Tanzania (P = O.OOS), and 9.6% more in Malawi (P<O.OOl). However, the separate sex calculations (B + G in Table 2) were (at best, in Malawi) only around 1% better than using data for boys and girls combined to predict the dosage (B&G in Table 2), so there seems to be little advantage in separate predictions for boys and girls.

Fourth, using the equation for the relationship be- tween weight and height of children in one country to predict the weight of children in another country does not greatly affect the percentage of children who would have received praziquantel within the target range. For ex- ample, the lower part of Table 2 shows that 79.4% of Tanzanian children would have been given a dosage within the target range using the equation derived from Tanzanian data compared with 77.9% ifweight had been predicted from height using equations derived from data from Ghana or Malawi.

Table 2 fails, however, to capture both the range in dosages and the degree of skewness. Figure 2 shows the distribution of dosages of praziquantel that would have been given to children in Ghana, Tanzania and Malawi when age, MUAC, height, and height’ X MUAC were used to predict bodyweight. Even when MUAC was used to predict weight only 3 children in Ghana (0.2%) would have received a dosage of praziquantel>64 mg/kg and 2 (0.1%) would have received < 16 mg/kg. When height2 X MUAC was used to predict weight, although the variance and range in the dosage of praziquantel deliv- ered are considerably narrower than for height or MUAC alone, the distribution was skewed to the left so that there would be a tendency to under-dose. Using height alone to predict weight and the dosage of praziquantel (Fig. 2) gives a larger variance and range in dosage than if height’ X MUAC was used, but the distribution of dosages is normal around the target dosage of 40 mg/lg. Using

MUAC

12 16 20 24 28 32 36 40 44 48 52 56 60 64 68

Dosage in mgikg

ia mg,k< 40 mg/kg 60 mgikg : : ; ; Height’

x MUAC

i

Fig. 2. The distributions of the dosage of praziquantel that would have been given to schoolchildren in Ghana, Tanzania and Malawi if weight had been predicted from age, MUAC, height, or height2 X MUAC. The vertical dotted lines mark the upper and lower ranges of dosage given in practice if the target dosage is 20,40 or 60 mg/kg.

ESTIMATING THE DOSE OF PRAZIQUANTEL 657

height only 1 child (0.02%) in any country would have received a dosage (72 mg/kg) beyond the maximum range.

Factors affecting the range in dosage In order to examine the relationship between the

dosage of praziquantel given on the basis of height and whether children were fat or thin for their height, the body mass index (BMI = weight in kg divided by height in metres’) of each subject was calculated and plotted against dosage. Figure 3 shows that Malawian children with a low BMI (thin) would have been eiven dosages higher than the &rge;range of 36-44 mgykg, althouugh none would have received >64 mg/kg. The children with the highest BMIs, who tended to be adolescent girls, would have been given dosages lower than the target range, although none was lower than 24 mg/kg. The relationships were similar for children in Ghana and Tanzania.

Discussion This analysis indicates that if height had been used to

determine the number of tablets of praziquantel required to treat schistosomiasis, about 75% of children in 3 African countries would have received a dosage within the normally given range of 36-44 mg/kg. T&s could have been improved by about another 5% if height’ X MUAC had been used, urobablv for 2 reasons: because height squared is a ro;gh estimate of surface area, an accepted basis for administering drugs (HATHAWAY et al., 1991); and because MUAC helps to distinguish between thin and fat children of the same height. Height’ X MUAC has 2 disadvantages, however. First, it is complex: it requires 2 measurements, the calculations are best done using a calculator, and then the number of tablets has to be determined from a Table. Second, the distribution of dosages was skewed towards giving less than the target rang& of 36-44 mg/kg. - -

IfMUAC alone had been used then 60% of children in Ghana and 70% in Tanzania would have been given a dosage within the range 36-44 mg/kg, although the range in dosages was much larger than for height alone (Fin. 2). Although MUAC taues are inexnensive and

_I I

could be marked-with the number of tablets, it is a less commonplace measurement than height.

There was no great advantage in -estimating weight from height separately for each sex. Although using sex- specific data more boys than girls would have been treated within the target range of 36-44 mg/kg (Table

35

30

-

"E 25

2 - 20 G

a .; 15

z -? 10

w 5

0 ~ i

20 mglkg

i

2), when the proportions treated within this range were added together they were little different from the propor- tions calculated using combined data from both sexes.

The differences observed in the relationships between weight and height of children in different countries did not lead to big differences in the dosages of praziquantel given. When the equations predicting weight from height in 1 country were applied to the 2 others (see lower part of Table 2), very similar proportions of children would have been dosed within the target range when compared with the country-specific calculations. Generally though, the country-specific data were the most accurate, and it is possible that the relationships may be dissimilar in other countries, so using national data may be the wisest course.

If height or any alternative variable is to be used to determine the number of tablets of praziquantel to treat schoolchildren then it should result in a dosage within the range normally delivered based on bodyweight. In prac- tice the dosage given is largely dependent on the accuracy of the weighing scales and on the smallest unit of administration. For example if the 600-mg tablets could have been cut only in half then the range in dosage of praziquantel around a target of 40 mgrkg would have been 32-48 m&kg. The fact that maziauantel has been administered e&c&iously at dosages raiging from 20 to 60 mg/kg bodyweight (TAYLOR et al., 1988; KING et al., 1989; WHO, 1990) also provides considerable leeway around the currently recommended target dosage of 40 mg/kg (WHO, 1995b). Above a dosage of 64 mg/kg, there are likely to be few worries about efficacy, although there may be concerns for toxicity. But praziquantel is exceptionally well tolerated and side-effects seem to be related more to the intensity of infection at treatment (WHO, 1995b). At dosages lower than the target range there may be concerns for the potential to select resistant strains.

The general conclusion of this analysis is that height can predict weight and determine the dose of praziquan- tel with sufficient accuracy to deliver a dosage within a safe and acceptable range. This accuracy seems to depend on the fact that most schoolchildren in the countries studied are lean and undernourished (PCD, 1998a). Because fatness due to adiuose tissue will lead to underestimation of weight from hkight and under-dos- ing, this relationship is thus likely to be less useful for adults.

Having established the relationship for children in 3 countries it is, in fact, unnecessary to measure height at

40 mglkg 60 mglkg

12 16 20 24 28 32 36 40 44 48 52 56 60 64 68

Dosage of praziquantel (mg/kg)

Fig. 3. The relationship between the body mass index (kg/n?) and the dosage of praziquantel that would have been given to 2078 children (both sexes) in Malawi on the basis of height. The vertical dotted lines mark the upper and lower ranges of dosage given in practice if the target dosage is 20, 40 or 60 mg/kg.

658 ANDREW HALL ETAL.

all: a child to be treated can simply be stood against a pole marked with the number of tablets of praziquantel. Such a system has been used successfully to determine the dose of ivermectin in the Onchocerciasis Control Programme (ALEXANDER et al., 1993). Ivermectin is actually admin- istered much less accurately than praziquantel as the ratio between the smallest unit of delivery and the target dosage (6000 pg/150 yg/kg = 40) is larger than for praziquantel(l50 mg/40 mg/kg = 3.75). This suggests that drugs with ratios higher than 3.75 could also be administered to children in Africa on the basis of height.

As a result of the analysis presented here the school health programmes in Ghana and Tanzania have trained teachers to use tablet poles to administer praziquantel to children in nearly 1000 schools. This simple develop- ment has helped to keep the annual costs of school-based drug delivery to around US$ 1 per child (PCD, 1998b).

Acknowledgements The Partnership for Child Development programmes in

Ghana and Tanzania are supported by the Edna McConnell Clark Foundation. The Partnership receives support from the UNDP, the Rockefeller Foundation, the James S. McDonnell Foundation, the WHO, the Wellcome Trust and the World Bank. The Save the Children Federation programme in Malawi is supported by a private donor.

References Alexander. N. D. E., Cousens, S. N., Yahava, H., Abiose, A. &

Jones, fi. R. (1993). Ive&ecti&dose assessment without weighing scales. Bulletin of the World Health Organization, 71, 361-366.

Hathaway, W. E., Groothuis, J. R., Hay, W. W. &Paisley, J. W.

(1991). Current Pediatvic Diagnosis and Treatment, 10th edi- tion. Norwalk, Connecticut: Appleton & Lange.

King, C. H., Wiper, D. W., de Stigter, K. V., Peters, I’. A. S., Koech, D., Ouma, J. H., Arap Siongok, T. K. & Mahmoud, A. A. F. (1989). Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya. Amer- ican Journal of Tropical Medicine and Hygiene, 40, 507- 5 13.

PCD [Partnership for Child Development] (1997). Better health, nutrition and education for the school-aged child. Transactions of the Royal Society of Tropical Medicine and Hygiene, 91, 1-2.

PCD [Partnership for Child Development] (1998a). The anthropometric-status of school children in five countries in the Partnership for Child Development. Proceedings of the Nutrition Society, 57, 149-158.

PCD [Partnership for Child Development] (1998b). Cost of school-based drug delivery in Tanzania. Health Policy and Planning, 13, 384-396.

Taylor, P., Murare, H. M. & Manomano, K. (1988). Efficacy of low doses of praziquantel for Schistosoma mansoni and S. haematobium. Journal of Tropical Medicine and Hygiene, 91, 13-17.

WHO (1990). WHO Model Prescribing Information. Drugs used in Parasitic Diseases, 1st edition. Geneva: World Health Organi- zation.

WHO (1995a). Health of school children. Treatment of intestinal helminths and schistosomiasis. Geneva: World Health Organi- zation. WHOISCHISTOI95.112 & WHOICDSI95.1.

WHO (1995b). WHO Model Prescribing Information. Drugs used in Parasitic Diseases, 2nd edition. Geneva: World Health Organization.

Received 8 June 1999; revised 2 August 1999; accepted for publication 4 August 1999

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