the distribution of ascaris lumbricoides in human hosts: a study of 1765 people in bangladesh
TRANSCRIPT
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE (1999) 93,503-5 10
The distribution of Ascaris lumbricoides in human hosts: a study of 1765 people in Bangladesh
Andrew Hall*, Kazi Selim Anwar**, Andrew Tomkim*** and Lutfar Rahman International Centre for Diarrhoeal Disease Research, Bangladesh, l? 0. Box 128, Dhaka 1000, Bangladesh
Abstract The Ascarzs Zutnbricoides expelled by 1765 people in a poor urban community in Bangladesh were recovered and counted after the subjects had been treated with pyrantel pamoate. The subjects were divided into 22 classes by age and sex (mean n = 80) to examine how prevalence, mean worm burdens and measures of aggregation of worms varied with age and between the sexes, and to see how a measure of aggregation, k, calculated in 3 ways (by maximum likelihood, from moments, or from the percentage uninfected) compared with an empirical aggregation index (the percentage of subjects who expelled an arbitrary 80% of all worms) and with the proportion who were moderately to heavily infected (defined as 3 15 worms). The prevalence of infection ranged from 64% to 95%, mean worm burdens ranged from 7 to 23 worms, and k ranged from 0.3 to 1.2. There were significant differences between adult males and females in the prevalence of infection, mean worm burdens and measures ofaggregation, differences which are probably driven more by behaviour than immunity. The parameter k was better described in terms of the proportion who were moderately to heavily infected (linear; range 0,15-0.58) than by the empirical aggregation index (non-linear; range 0.30- 0.49).
Keywords: Ascaris Zumbricoides, expulsion, aggregation, prevalence, worm burden, Bangladesh
Introduction The intestinal nematode Ascaris Zumbricoides is esti-
mated to infect about 24% of the world’s population (CHAN, 1997). Most infected people live in developing countries where warm and humid conditions combined with inadequate sanitation favour the transmission of infections (CROMPTON & PAWLOWSKI, 1985). Worms are not normally or evenly distributed between hosts and it is typical to find that a large proportion of all worms occur ‘In only a small proportion of all hosts (THEIN- HLAING et al, 1984; ELIUNS et aZ.. 1986: HOLLAND et al., 1989). Studies have shown that the distribution of worms is often empirically described by the negative binomial probability distribution. This distribution is defined by the prevalence of infection (p), the mean worm burden (M> and the parameter k, which varies inversely with the degree of aggregation (ELLIOTT, 1983). Values of k for intestinal worms typically range between 0.1 and 1 .O (ANDERSON & MAY, 199 1) and k is often explained in terms of the proportion of worms in hosts: for example, it is said to be not unusual to find 80% of all worms in as few as 20% of all hosts (ANDERSON & MAY, 1991).
The aggregation ofworms in a few hosts has important consequences: heavily infected hosts are of concern not only because they are most likely to experience disease, particularly if they are young or malnourished, but also because they may make a major contribution to the transmission of infections within their communities. The degree of aggregation of worms therefore has important implications for our understanding of the epidemiology of infections and how to control disease.
As a part of a study of the intensity of infection and reinfection with A. lumbricoides. neonle of all sees livine in a very poor urban area in Bangladesh were treited witg an anthelmintic on 3 occasions over a period of a year and all the worms they expelled were collected (HALL et al., 1992). The present paper examines 3 things. First, it examines the distribution of worms in the community to see how the prevalence of infection and worm burdens
*Present address for correspondence: Partnership for Child Development, Wellcome Trust Centre for the Epidemiology of Infectious Disease, South Parks Road, Oxford OX1 3FY. UK; phone f44 (0)1865 281231, fax +44x0)1865 281245, . . e-mail [email protected] Present addresses: l *Instimte of Public Health, Mohakhali, Dhaka 1212, Bangladesh; l **Centre for International Child Health, Institute of Child Health, 30 Guilford Street, London WClE IEH, UK.
vary with age, and between the sexes. Second, using the data on worm burdens for age and sex classes the relationship between several different ways of estimating the degree of aggregation of worms is examined. And finally, to return to the epidemiological context from which the data were derived, it examines how the degree of aggregation of worms within this community varies with age and between the sexes.
Subjects and Methods Households were visited in a crowded and very poor
area of Mirour. a suburb of Dhaka. Baneladesh. and all their occupants were invited to takepart & the study with the aim of recruiting and treating as many people as possible in 6 months. The age and sex of all potential subjects was recorded. Participation was on the basis of the informed consent of the head of each household and the study had been approved by the Ethical Review Committee of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B).
Stool examinations and worm recove y All people who agreed to participate were asked to
provide a fresh faecal sample which was examined microscopically by a quantitative ether sedimentation technique (HALL, 1981). Whether the eggs of A. Zum- bricoides were seen in faeces or not, every subject aged 2 1 year was then treated with pyrantel pamoate (Comban- trin; Pfizer, Bangladesh) given as a single dose of 11 mg/kg bodyweight. Pyrantel pamoate paralyses A. lumbricoides so that they can no longer maintain their position in the gut and are expelled intact in the stools (AUDI et aZ., 1995). A single dose of pyrantel pamoate is reported to cure 95% of infections with A. lumbricoides (ELIUNS et al., 1986).
After treatment each subject was provided with a lidded plastic chamber pot containing about 50 mL of a 5% v/v solution of an antiseptic (Sepnil: Square Pharmaceuticals, Bangladesh) in 0.9% saline. This served to keep stools soft and to reduce unpleasant smells, because many households did not have latrines and the pots were usually stored in the small household compound. Each subject was asked to defaecate into the pot at every bowel movement over the next 24 h and mothers were asked to supervise their children’s defaeca- tion. The pot was replaced with a clean one after 24 h, which was also left for 24 h, so that stools were collected for at least 48 h after treatment. If subiects did not nass any stools, either in the 1 st or 2nd 24 h after treatment, the buckets were left for a further 24 h. The number of
504 ANDREW HALL ETAL.
worms recovered from each subject was recorded and is termed the worm burden.
Subjects were excluded from the study for any 1 of the following reasons: if stools were not collected for at least 48 h after treatment or if subjects reported not collecting all their stools; if a subject returned no worms although A. Zumbricoides eggs had been seen in the faecal sample examined before treatment; or if a subject returned only male worms but eggs had been seen in the faecal sample collected before treatment. The subjects not excluded according to these criteria were classified as having been treated satisfactorily.
Analysis of data To examine the relationship between age, sex and
epidemiological parameters the following 11 age classes were used: 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-16, 17-26,27-36,37-46 and 247 years. These 22 age and sex classes gave an average sample size of 80 (range 44- 136). Subjects were also classed as pre-school children (l-4 years), school-age children (5-14 years) or as teenagers and adults (3 15 years).
Because worms were not normally distributed among hosts and because worm burdens could not be trans- formed to a normal distribution, non-parametric tests of statistical significance were applied to the data to exam- ine all differences in worm burdens between groups. x2 tests or Fisher’s exact test were used to compare propor- tions.
In order to evaluate different measures of aggregation of worms in hosts 2 empirical measures were used: the proportion of subjects with moderate-to-heavy infec- tions, defined as 2 15 worms (HALL et al., 1992); and the proportion of subjects who passed an arbitrary 80% of total worms expelled, termed the empirical aggregation index. These proportions were then compared for all age and sex classes with the following: (i) k estimated by the method of maximum likelihood for the full and zero- truncated negative binomial distributions, hereafter called full k and zero-truncated K, using software kindly provided by Dr Brian Grenfell (University of Cambridge, UK); (ii) k estimated from the proportion of uninfected subjects, hereafter called uninfecteds’ K, according to the method described by ELLIOT (1983) in which various values of k are tried in the following equation until the 2 sides are equal
i log( 1 + (F/L, = log( n/ j0) where f = the mean, n = the sample size and j0 = the number ofuninfected subjects; and (iii) k estimated from moments (the mean ?E and variance s’) according to ELLIOTT (1983) for sample sizes of >50 as follows
i = f2/(s2 -Z)
hereafter called moments k; and, finally, (iv) the variance to mean ratio.
In the negative binomial distribution the prevalence of infection, p, is related to the mean intensity of infection, M, in the following way
p = (1 - (1 + M/k)-k) x 100
This equation was used to examine the relationship between the prevalence and mean worm burdens for all 22 groups using either the value of k determined for the total sample studied or values of k which varied as a function of the mean intensity for the 22 age and sex grouns. A linear function gave the best empirical tit. The fines-were fitted using maximum-likelihood techniques (GUYATT et al.. 1990) and the likelihood ratios were tested for statistical significance.
Results Over a period of 6 months 2884 eligible people living in
502 households were asked to take part in the study and
1765 people (61.2%) from 490 households were de- wormed satisfactorily. In all age groups older than I1 years significantly more males participated in the study than females (P < 0.002). The prevalence of infection with A. lumbricoides based on worm recovery was 85.6% while the prevalence based on stool microscopy was 77*4%, indicating that microscopy had missed 144 (8.2%) infections.
Table 1 shows the prevalence and mean worm burdens in the 22 age and sex classes, and Figure la shows separately for each sex the relationship between age and the prevalence of infection. Children in this community acauire A. lumbricoides verv earlv in life: 67% of children agid l-2 years were infected. The prevalence of infec- tion among males was significantly lower than females in the 3 oldest age-groups (all P < 0.05).
Figure lb shows separately for each sex the relation- ship between age and the mean worm burdens. By the age of l-2 years children already had a mean of 7.4 worms (maximum, 43) but the school-age group was, as usual, most heavily infected with a mean of 20.2 worms, and nearly 10% of children passed more than 50 worms. Figure lb also reveals significant differences between the sexes. Among males the peak mean worm burden of 2 1.8 worms was observed in the 9- 10 years age class and was significantly lower in the 3 oldest male age classes, at 9.6 worms (P< 0.001). Among females, in contrast, although the mean worm burden reached a similar peak (23.4 worms), it did so in an older age-group (13-16 years) and nearly 60% of these adolescent girls were moderatelv to heavilv infected (Table 1). Althouah mean worm burdens among older age classes of females were significantly lower than this peak (all P< O.Ol), the difference was much smaller than among males, so that females in each of the 3 oldest age-groups had signifi- cantly larger worm burdens than males in the same age- groups (16.1 vs9.6worms, P<O.OOl).
Table 1 also presents for each age and sex class the values for measures of aggregation calculated in different ways and shows that values of full k calculated by the method of maximum likelihood ranged between about 0.412 and 1.195 among the 22 age and sex classes, an almost 3-fold difference. Although in most of these age and sex classes the distribution of worms was not sianificantlv different from either the full or the zero- t&cated negative binomial distributions, significant differences were found when the observed distribution of worms was compared with the expected distribution among all 1765 subjects (both P<O.OOl). This was largely because considerably more people than predicted passed no worms (254 vs 184) while fewer people than expected passed only 1 (50 vs 124) or 2 (59 vs 102) worms.
Table 1 shows that the empirical aggregation index has a fairly narrow range, from 0.304 to 0.486, indicating that 80% ofworms occur in between about 30% and 50% of subjects in each class. Figure 2a shows that the empirical aggregation index and full k are strongly and significantly linearly correlated over the observed range (r = 0.945, P < O.OOl), but what happens at greater degrees of aggregation (lower values of k) is difficult to say. Table 2 shows that the empirical aggregation index was strongly correlated with k estimated both from moments and from the proportion uninfected indicating that these simpler ways of estimating k were quite good estimates of aggregation, again over the range observed. The values of k estimated from the proportion unin- fected were, however, consistently lower than full k by an averaaeof0.151 (95% CIO.lll. 0*191).Neither knor the empirical aggregation index &as correlated with the variance to mean ratio, and both these indices were more strongly correlated with the median worm burden rather than the mean, probably because the mean is more influenced by outliers.
An examination of the effect of using cut-off points ranging from as low as 60% and as high as 90% to define
Tabl
e 1.
The
ch
arac
teris
tics
of22
ag
e an
d se
x cl
asse
s in
Ban
glad
esh
in t
erm
s of
the
prev
alen
ce
ofin
fect
ion
with
As
cati
hmbr
icoi
des,
th
e in
tens
ity
of in
fect
ion
and
@
mea
sure
s of
agg
rega
tion
(see
tex
t fo
r de
finiti
ons)
2 B h
Age
(y
ears
) l-2
3-4
5-6
7-8
9-10
11-1
2
13-1
6
17-2
6
27-3
6
37-4
6
347 l-4
5-14
a15
All
All
- Se
x
Mea
n ag
e (y
ears
)
Subj
ects
(n)
Infe
cted
(n>
(%I
iii1
k k
k Pe
rcen
t W
orm
bu
rden
Em
piric
al
Varia
nce:
tll.
UlC.
es
t. es
t. w
ith
s
aggr
egat
ion
mea
n ne
g.
neg.
fro
m
from
21
5 9
Mea
n M
edia
n in
dex
ratio
bi
nom
ial
bino
mia
l m
omen
ts
unin
fect
ed
wor
ms
M F M
iti F M F M
iG
ic
iG
iti
i&
c F M F M F M F M F
1.6
:::
93
;:;
z:
5.6
94
7.6
97
7.5
101
9.6
73
9.6
11.5
11
.6
14.2
z9
6 14
.4
20.6
:;
22.0
13
2 31
.9
62
32.1
13
6 41
.6
58
41.0
58
.1
;4”
56.9
44
;:;
151
143
8.8
375
3z.0
0 40
0 26
5 31
.7
431
16.4
79
1 18
.1
974
17.3
17
65
72
73
:: 87
90
4:
70
76
53
74
60
106 44
120 47
iz
41
109
112
339
359
213
379
661
850
1511
63.8
6-
9 69
.6
. 77
,4
11.;
83.9
17
.4
89.5
20
.0
90.4
18
.3
89.7
21
.4
89.1
20
.3
87.7
21
.8
90.9
18
.0
95.9
18
.9
88.4
22
.2
89.8
16
.5
91.4
23
.4*
87.0
12
.2
80.3
17
.1
71.0
g&
2**
l;:fj*
* 81
.0
95.0
* g*
**
77.8
9.
4 93
.2*
15.9
***
72.2
11
.4
78.3
13
.7
90.4
20
.2
89.8
20
.2
80.4
10
.8
87.9
* *
17*0
***
83.6
15
.4
87.3
* 17
.8**
*
85.6
16
.7
4.0
3.0
10.0
8.
0 13
.0
11.0
13
.0
16~0
15
.0
14.0
15
.0
13.0
13
.0
17.0
7.
0 11
.0
4.0
11.0
5.
5 13
.0
5.5
12,o
7.0
7.0
13.0
13
.5
6.0
12.0
9-o
12.0
11.0
0.32
8 12
.0
0.30
4 14
.5
0.38
7 16
.5
0.34
5 27
.1
0.38
9 29
.4
0.38
3 35
*3
0,39
2 30
.6
0,45
5 17
.7
0.45
2 23
.0
0.46
8 16
.8
0.48
6 17
.9
O-4
07
25.6
0.
44
1 17
.8
0.45
7 25
.2
0.40
6 14
.1
0.37
1
23.3
0.
306
18.4
0.
419
19.1
0.
379
26.8
0.
438
19.7
0.
370
13,8
0.
454
12.9
0.34
4 16
.5
0.32
2 25
.6
0.42
1
25.4
0.
432
25.1
0.
362
17.6
o-
415
19.9
0.37
7 23
.6
0.40
6 23
.2
0.39
5 23
.5
0.41
2 1.
578
0.62
0 0.
329
0.41
9 0.
669
0.59
3 0.
388
0.54
3+
1.30
0 0.
916
0.41
9 0.
587
0.80
9 0.
664
0.51
5 0.
722
0.85
5 0.
706
0.65
1 0.
765
0.84
9 0.
535
0.71
5 0.
773
1.01
0 0.
721
0.64
3 0,
974
1,71
8 1,
129
0,63
4 0.
880
1.67
2 0.
992
0.57
0 1.
025
1.44
9 1.
138
0.74
3 1.
195
1.26
7 1.
120
1.10
1 0*
800+
1.
275
0.90
0 0.
589
0.97
1
1.43
3 0.
986
0.72
0 1.
011
1.53
8 0.
971
0.68
9 0.
791
1.00
5 0.
935
0.69
9 0.
569+
+ 1.
155+
0.
764
0.43
6 0.
446
0.96
0 0.
552
0.37
8 0.
847
1.21
6 0.
856
0.67
1
0.64
8+
o-88
6+
0.38
0 0.
575
1.07
6 1.
101
0.92
6 1.
049
0.64
7 1.
343
0.73
9 0.
506
1,17
1 1.
461
1.33
3 0.
926
0.46
3 1.
231
0.73
4 0.
486
0.69
2 0.
556
0.84
4++
1.11
5 0.
827
0,87
4 1.
283
0.84
0 0.
641+
++
1.06
7 0.
655
O-8
11++
1.
201
0.89
7
0.64
9+++
1.
030+
0.
680
0.76
0+++
1.
141+
0.
802
0*70
5+++
1.
088+
++
0.74
5
0.37
0 33
.1
0.44
1 30
.1
0.68
6 49
.3
0.66
0 49
.5
0.53
2 24
.5
0.63
7 40
.1
0.40
0 37
.4
0.60
3 41
.9
0.56
8 39
.9
37.9
46
.3
38.3
48
.5
52.5
52
,l 46
.8
50.7
45
.3
40.7
58
.0
31.9
38
.6
24.2
37
.5
13-8
43
.8
20.4
38
.6
Sign
ifica
nt
diffe
renc
es
betw
een
the
sexe
s: *
P <
0.05
; **
P <
0.01
; **
*P
< 0.
00 1
. Si
gnifi
cant
ly
diffe
rent
fro
m
the
nega
tive
(neg
.) or
tru
ncat
ed
(mm
c.)
nega
tive
bino
mia
l di
strib
utio
n:
+P
< 0.
05;
++P
< 0.
01;
+++P
<
0.00
1.
506 ANDREW HALL ETAL.
25
(a)
1
0 10 20 30 40 50 60 Mean age of age class (years)
*Males - A- Females
(b)
0: 0 10 20 30 40 50 60
Mean age of age class (years)
Fig. 1. (a) Tire prevalence of infection with Ascaris Zumbricoides, for each of 11 age classes, by sex, in an urban community in Bangladesh. (b) The mean worm burdens with A. lumbricoides, for 11 age classes, by sex, in an urban community in Bangladesh. *P<@O5, **P<O.Ol and *** P < 0.001 in comparisons of prevalences and worm burdens between the sexes for the same age class.
the proportion of worms in hosts used to calculate the empirical aggregation index did not greatly alter the correlation with full K observed using a cut-off point of 80%. This indicates that the arbitrary cut-off point of 80% of worms is quite robust.
1.4
1.2 e
z l’O $ 0.8
.$ 0 0.6
8 3 0.4 rc’
0.2
0.0
00 O&
00
%O 03
O 00
GO
(a)
4
0.0 0.1 0.2 0.3 0.4 0.5 0.6 Empirical aggregation index
1.4 r
1.2 .x 3 1.0
8 3 0.8
.g 0.6 % fi 0.4 = CL’ 0.2 (b)
0.0 1 4
0 10 20 30 40 50 60 70 Percentage with 2 15 worms
0 0
0
0 OOO 0 0
0 0
“00 0 0
@ 0
00 0
Fig. 2. (a) The relationship between the empirical aggregation index (the percentage of subjects who passed 80% of all worms) and full negative binomial k for Ascarij lumbri~oides in 22 age and sex classes in an urban community in Bangladesh. (b) The relationship between the percentage ofsubjects who passed 5 15 worms in the same groups and community with the full negative binomial k.
Table 1 shows that, in contrast to the empirical aggregation index, the percentage of subjects with mod- erate-to-heavy infections ranges more widely, from 155% to 58%, over the same range in prevalence. Figure 2b shows that the percentage of subjects with 2 15 worms was less tightly correlated with full k (r = 0.672,
Table 2. Coefficients of correlation between statistics describing the aggregation ofAscaris lumbricoides in 1765 people in 22 age and sex classes in Bangladesh and parameters ofbotb worm burdens and measures of aggregation
Statistics
Prevalence (worm recovery) Prevalence (eggs in stools)
Empirical Maximum aggregation likelihood
index” full k
0+350*** 0.898*** 0.869*** 0*863***
% having 315 worms
0.764*** 0.793***
Mean worm burden
Worm burden: Arithmetic mean Median Maximum Geometric mean
0.670”** 0.619** 0.940*** 0.863”** 0.795*** 0.950*** 0.92;*** 0.386 0.345 0.655*** 0.796*** 0.834*** 0.805*** 0.938*** 0.959***
Aggregation: Emuirical aearegation index k max. likelyhood full k max. likelihood zero trunc. k est. from moments k est. from no. uninfected Variance:mean ratio
0.945*** 0.599** 0.746***
- 0,672*** _ ~~ 0.599** 0*454* 0.401* 0.823”** 0.796*** 0.653*** 0.780*** 0.908*** 0.502*
-0-020 -0.017 0.333
0.670*** 0.619** 0.282 0.483* 0.459* 0.567**
“The empirical aggregation index is the proportion of subjects who passed an arbitrary 80% of worms. *P<0.05;**P<0.01;***P<0.001.
A. LUMBRICOIDES IN BANGLADESH 507
P < 0.00 1) but indicates that as the degree of aggregation decreases the proportion of moderately to heavily in- fected subjects increases in a linear fashion. At a K of around 1 about 60% of subjects are likely to be moder- ately or heavily infected (2 15 worms). This threshold is arbitrary, and the degree of morbidity is also related to the age and current health of subjects. If morbidity was experienced by children aged l-4 years with 210 worms, by children aged 5- 14 years with ~20 worms and by adults with 230 worms then 28.7% of the sample would be diseased.
Figure 3a shows how full K varies with the prevalence of infection and indicates that the degree of aggregation decreases 3-fold from about O-4 to 1.2 over a narrow 30% range in prevalence, from 64% to 95%. The relationship between iz and prevalence is not likely to be linear and indicates that at prevalences lower than 60% the degree of aggregation is less than 0.4.
The relationship between prevalence and the degree of aggregation of worms is perhaps easier to predict from Figure 3b, which shows that the prevalence and empiri- cal aggregation index are linearly correlated (r = 0.85, P < O.OOl), and that the regression line points towards the origin. At the highest prevalences the empirical aggregation index approaches around 0.50. Figure 3c shows the relationship between the prevalence and the percentage of subjects who passed 215 worms. The percentage of subjects with more than 15 worms rises exponentially at prevalences above 60% and above a prevalence of 80% there is a wide degree of scatter which indicates that between 30% and 60% of people may be moderately to heavily infected.
The relationship between the same 3 measures of
.a 1.4 $ 1.2
3 A::
.6 0.6
yj 0.4
: 0.2
Lz 0.0
4 0.6 .9 2 0.5
‘2 0.4 F & 0.3 2 3 0.2
:& O’l $ 0.0
ii ‘O 8 60
3 50 2 A 40 & 30 s20
2 10
(4
0 20 40 60 80 100
(b) 20.6 ,- (b)
003 -0
t
0 20 40 60 80 100 $ 0 5 10 15 20 25
(cl
o $0 0 oo&oO
0 ,” O.
E 01 , 0 20 40 60 80 100
Percentage infected
Fig. 3. The relationship between the prevalence of infection with Ascans lumbtioides in 22 age and sex classes in an urban community in Bangladesh and (a) k of the negative binomial distribution; (b) an empirical aggregation index (the percentage ofsubjects who passed 80% ofall worms); and (c)the percentage of subjects who passed 5 15 worms.
aggregation and the mean worm burden are shown in Figure 4, and all are roughly linear over the range of values observed. The relationship between the mean worm burden and the empirical aggregation index (Figure 4b) is unlikely to be linear at lower mean worm burdens, and a logarithmic function (not shown) em- pirically gives a fit that would converge with the origin. Only in Figure 4c does the trend point towards the origin and if the equation for the line is constrained through zero (which makes a negligible change in the correlation coefficient, of 0.002) then for every increase in the mean burden of 1 worm the percentage of hosts with 215 worms increases by abour 2.4% (y = 2,386~; I = 0.939; P<O.OOl).
Figure 5 shows the relationship between the preva- lence of infection and the mean worm burden among the 22 classes. The Figure shows that the maximum like- lihood fit using K as a linear function of the mean worm burden (k = a + bM; a = 0.3035, b = 0.0299) gave a significantly better fit than using a single value of k of 0.705 derived from the total population (x2 = 27-9, P < 0.001).
To return to the population from which the data on the degree of aggregation of A. lumbricoides were derived, Figure 6 shows how full K, the empirical aggregation index and the percentage with 2 15 worms vary with age and by sex. Figure 6a shows among males a convex pattern in which k increases 3-fold to reach a peak in boys aged 1 1 - 12 years and is lower among the 3 oldest age- groups. Among females the pattern is different and suggests that k rises to a similar peak but shows much less convexity so that values of k for the 2 oldest female age classes are around twice the values for males of the
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Fig. 4. The relationship in 22 age and sex classes in an urban community in Bangladesh between the mean worm burden of Ascaris lumbricoides and (a) k of the negative binomial distribu- tion; (b) an empirical aggregation index (the percentage of subjects containing 80% of all worms); and (c) the percentage of subjects who passed 2 15 worms.
fl 0
-Lineark varies with mean
- - - Constanr k = 0.705
0 5 10 15 20 25 ‘\ Mean worm burden
Fig. 5. The relationship between the mean worm burden with Ascati lumbri-coides and the prevalence of infection in 22 age and sex classes in an urban community in Bangladesh. Also shown are a maximum-likelihood fit using k as a linear function of the mean worm burden (see Fig. 4a) and a fit for constant k derived from the total sample (see Table 1).
~ 1.4
2 1.2
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.$ 0.6 0 .g 0.4
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(b)
,
0 10 20 30 40 50 60
*Males - A- Females
60 -
50 -
40 -
10 f
z ol 4 0 10 20 30 40 50 60
Mean age of age class (years)
Fig. 6. The relationship between age and sex for 11 age classes of subjects living in an urban community in Bangladesh and (a) full k of the negative binomial distribution; (b) an empirical aggregation index (the percentage of subjects who passed 80% of all worms); and (c) the percentage of subjects who passed 3 15 worms.
same age and are similar to the peak reached during late childhood. The empirical aggregation index (Fig. 6b) shows a similar pattern but the range in values is much narrower. Figure 6c shows clearly how adult women are more likely than men to have moderate-to-heavy infec- tions and the degree of convexity is much smaller than for
ANDREW EL%LL ETAL.
men, if it is convex at all. Table 1 shows that a third of children aged l-4 years and nearly a half of all school-age children had 2 15 worms.
Discussion This is the largest study of its kind to date which has
carefully quantified burdens with an intestinal worm in a population of hosts in which there was no previous parasite control programme, so worm populations were probably at equilibrium. In many communities the mean burden of A. lumbricoides tends to be lower among adults than children, and the cross-sectional relationship bet- ween age and intensity is typically convex. The smaller average worm burdens in adults has been explained by 2 main factors: as a result of changes in behaviour with age that reduce exposure to infective stages, perhaps because adults are more careful than children in their personal hygiene; as a result of acquired resistance to infection which prevents the establishment or survival ofworms; or perhaps as a combination of both exposure and immu- nity (ANDERSON & h4AY, 1991). Three observations from the present study suggest that exposure plays a large role in generating the pattern of infection observed here. First, the highest mean worm burdens were observed in different age-groups in males and females: among males aged 9- 10 years and among females aged 13- 16 years (Fig. lb). Second, both the prevalence and intensity of infection were significantly lower among adult males than among adult females (Fig. l), and the 3 groups of adult males had mean worm burdens not much higher than the youngest children in the study, an age-group which is likely to have had much less exposure to the eggs of A. lumbricoides. Third, adult women in the 2 oldest age classes, who might be expected to have experienced considerable previous exposure to A. lumbricoides, had mean worm burdens and values of full k as high as most groups of school-age children, indicating that these groups were most heavily infected and that worms were least aggregated.
To explain these observations in immunological terms it would be necessary to conclude that in this community males are able to mount a significantly more effective immune response against A. lumbricoides than females, and at an earlier age as well. There is some evidence for differences between adolescent boys and girls in the intensity of reinfection with Schistosoma spp., and hor- monally mediated differences in immunity have been proposed as an explanation (FULFOFCD et al., 1998), but this theory has been questioned for Schistosoma haema- tobium at least (FELDMEIER et al., 1998).
If the differences between the sexes were to be explained in terms of some sort of ‘peak shift’ phenom- enon (WOOLHOUSE, 1998) this would imply that in the first 10 years of life boys in the same community were exposed to more infective stages than girls, and there is no evidence of a difference in mean worm burdens (Table 1). The shift in the peak intensity of infection to a later age is also usually associated with a lower peak (WOOLHOUSE, 1998), which was not observed either in this community.
The most likely explanation for the observations presented here for A. lumbricoides is that adolescent and adult males are less exposed to infection than females of the same age because of social and cultural practices that separate the sexes at puberty. In Bangladesh adolescent girls and women are traditionally confined to the home and its immediate surrounds to care for the house and their children while males have greater freedom of movement and typically leave the immediate community to work. The evidence presented here of infections in very young children (Fig. l), and the fact that reinfection in the youngest children, who stay in and around the household, occurs very rapidly (HALL et al., 1992), indicate that transmission in this crowded slum is very intense. The absence of drains and the fact that many latrines were simply private places to defaecate, either
A. LUMBRICOIDES IN BANGLADESH 509
directly on to the ground or into shallow pits which overflow during heavy rains, mean that faecal contam- ination of the environment around households is very heavy. Practices such as cleaning and caring for young children, many of whom defaecate directly in the open, are likely to expose women to infection. The fact that the men who provided their faeces for 48 h after treatment were more likely to be those who were not at work (although we tried to deworm adult males over weekends so that they could participate) suggests that mean worm burdens amongst all men in this community may be even lower than recorded. Only 24% of men aged > 17 years passed 2 15 worms compared with 40% ofwomen of the same age range (Fig. 6~).
Differences in mean worm burdens between the sexes have been noted in 1 other study of which we are aware: in southern India EWNS et al. (1986) found that adolescent and adult females passed more A. Zumbricoides after treatment than males. Similar differences in beha- viour between the sexes may also occur in southern India. No differences between the sexes have been reported in other studies which recovered A. lumbricoides after treat- ing people of all ages, including studies in Jamaica (BUNDY et al., 1987), Mexico (FORRESTER et al., 1988), Korea (C~~~etal., 1985) andIran (C~o~~etal., 1982).
The negative binomial probability distribution has proved to be a useful way of describing the characteristic aggregation of worms in hosts, but it is an empirical fit rather than being driven by any known biological me- chanism. The parameters ofthe negative binomial, k and M, are difficult to estimate because it is necessary to expel and recover worms to calculate them. Our data have enabled K to be put in perspective by examining it in comparison with empirical indices, and then to see how they all vary with prevalence, mean worm burdens and with age and sex.
For 19 of the 22 classes defined in the present study the distribution of worms was described by the negative binomial. A S-fold range in full k, from about 0.4 to 1.2, was equivalent to a relatively small increase in the empirical aggregation index from O-30 to 0.49 (Fig. 2a) but was associated with a similar, 3-fold increase in the percentage of subjects in each group with > 15 worms, from 155% to 58.0% (r = 0.672; Fig. 2b). Although the data suggest that even at low values of full K of around 0.4, 80% of all worms were still found in 30% of hosts, Figure 2a indicates that the relationship is not likely to be linear at lower values of both parameters.
Of the trends indicated by the observed points in Figures 3 and 4, which show how the prevalence and mean worm burdens are related to full K, to the empirical aggregation index and to the percentage with 215 worms, only Figures 3b and 4c have trend lines which, if extrapolated, go through zero. Whether K approaches zero at lower values of prevalence and mean worm burden cannot be said from these data, but Figures 3a and 4a are similar in their slope and shape to-Figures shown bv GUYATT et ~2. (1990) who looked at the same relations-hips with K using data’from 6 expulsion studies of A. lumbricoides and covering a wider range in pre- valence and mean worm burdens. GUYA-IT et al. (1990) examined values of k ranging between 0.36 and 0.8 1, and this lowest value was reported from Korea at a prevalence of 16.5% and a mean worm burden of only 0.2 worms/ host (CHAI et al., 1985). It seems that most of the lowest recorded values of k for A. Zumbricoides lie close to 0.3 and it is interesting to note that the plots of both prevalence and worm burden against k shown in the analysis of G~ATT et al. (1990) have an intercept at which k = 0.33. If similar lines are fitted to the data in Figures 3a and 4a, the lines also intercept at k z 0.30. Above a prevalence of 50-60% the values of k shown in Figure 3a increase exponentially, which is similar to the relation- shiu shown bv GUYAIT et aZ. (19901. The common feamres of an analysis of A. &tbri>oides in several communities and the analysis of worms in 22 age and
sex classes within 1 community presented here suggest that the relationships between the prevalence, worm burdens and measures of aggregation are similar both within and between communities.
The statistic k as a measure of aggregation is difficult to grasp and its description sometimes gives the impression that worms are always highly aggregated. The evidence presented here suggests that at prevalences of <50% worms are, indeed, highly aggregated, but above this prevalence the degree of aggregation rapidly diminishes. It seems that the range in values of k is perhaps better captured by expressing it in terms of the percentage of subjects who are moderately to heavily infected than in terms of the percentage of subjects who contain a certain percentage of all worms.
Although it is also known that moderately to heavily infected people are likely to become moderately to heavily reinfected after treatment (KEYMER & PAGEL, 1990), we have shown previously that over 3 rounds of treatment during a period of a year in this same commu- nity, about two-thirds of all subjects had 115 worms at least once (HALL et al., 1992). This means that over the medium-to-long term more people will benefit from treatment of their infections than would be expected from a cross-sectional study of the distribution ofworms.
This analysis shows that the degree of aggregation of worms in hosts varies with age and sex in this community, and worms become more dispersed between hosts with increasing prevalence (exponentially) and mean worm burden (linearly), so that a larger proportion of subjects have moderate-to-heavy infections as full k increases (linearly). In public health terms the school-age group is, as expected, most at risk of disease in this community, but the intensity of infection in pre-school children and their mothers suggests that they too should become targets for parasite control activities in the growing slums of cities such as Dhaka.
Acknowledgements This study was supported by the British Overseas Develop-
ment Administration (now Deoartment for International Development) and the United Staies AID Project Development Fund of the ICDDR,B. A. H. acknowledges current support from donors to the Partnership for Child Development includ- ing the UNDP and the Rockefeller Foundation. We thank Professor Roger Eeckles for his interest, the project staff for their diligence and enthusiasm for collecting worms, Maria- Gloria Basifiez for her help with maximum-likelihood analysis, and the subjects of this studv for their coooeration. The ICDDR. B is supported by countries, international agencies and donors which share its concern for the health problems of developing countries.
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Received 4 May 1999; revised 5 July 1999; accepted for publication 14 July 1999
ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE Denis Burkitt Fellowships
The Denis Burl&t Fund was set up by his family in memory of Denis Burkitt, FRS, who died in 1993; it is administered by the Royal Society of Tropical Medicine and Hygiene.
One Fellowship (maximum value E7000) or two separate Fellowships (of E3500 each) are awarded annually for practical training, travel, or direct assistance with a specific project (preferably clinico-pathological, geographical or epidemiological studies of non-communicable diseases in Africa).
Applications must be made at least six months before the commencement of the proposed study (by 15 March or 15 September in each year). A short report on the study should be submitted, within 3 months of the recipient’s return. Application forms are available from the Administrator, Royal Society of Tropical Medicine and Hygiene, Manson House, 26 Portland Place, London, WlN 4EY, UK; fax +44 (0)20 7436 1389, e-mail [email protected]
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The fund will support travel for l Leprosy workers who need to obtain practical training in field work or in research l Experienced leprologists to provide practical clinical training in a developing country
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Applications must be made at least six months ahead of the proposed trip, sponsored by a suitable representative of the applicant’s employer or study centre and agreed by the host organization. A short report on the travel/study should be submitted, within one month of the recipient’s return. Application forms are available from the Administrator, Royal Society of Tropical Medicine and Hygiene, Manson House, 26 Portland Place, London, WlN 4EY, UK; fax f44 (0)20 7436 1389, e-mail [email protected]