3.1 Background and aims
As has been mentioned in the literature review it now appears that recurrent acute
diarrhoeal diseases are probably not the cause o f long-term growth faltering in the
tropics (Briend et al., 1989, Moy et al., 1994a). However, there is still evidence that
diarrhoeal disease may be the an important cause o f growth faltering (Lutter et al.,
1989). Diarrhoeal episodes however, are still regarded as an important indicator o f
intestinal disease. Poskitt et al (Poskitt et al., 1999) has described a fall in the
prevalence o f acute diarrhoeal disease based on clinic data but we do not know what
the prevalence is from a community based survey. In view o f the fact that there is
evidence that diarrhoeal disease patterns are changing, there is a need to ascertain
whether or not the previously described lack o f association between diarrhoeal disease
and intestinal permeability still holds true.
The aim o f the first section o f this chapter was to use a community based diarrhoea
survey (rather than a clinic based one by Poskitt et al) to estimate the subject
prevalence of diarrhoea for the cohort o f Keneba children and to related this to
intestinal permeability and biochemical markers o f systemic inflammation (acute
phase reactants and immunoglobulins). This would confirm or refute the lack o f
association between growth and acute diarrhoeal disease in Keneba children.
Patients see section 2.1.3
Diarrhoeal survey see section 2.4.2.
Lactulose-mannitol permeability see 2.5.5
Anthropometry see section 2.5.2
Biochemistry see section 2.6
3.1.3 Statistical analysis
The main unit o f measurement to quantify diarrhoea used was the mean monthly
subject diarrhoea prevalence, which is the mean days with diarrhoea for each child
standardised to a 30.45 day month. Diarrhoea was defined as (see section 2.4.2) the
mothers’ (or main child carer’s impression o f change in bowel habit towards increase
in stool frequency and looseness. This definition has been previously used in The
Gambia by Rowland et al (Rowland et al., 1985, Rowland et al., 1986)
Associations between continuous variables were tested using linear regression. Growth
was defined as a change in height or weight standard deviation score over the whole of
the study period (response variable) expressed as a monthly rate and a summary o f
intestinal permeability, acute phase proteins and immunoglobulins were the predictor
variables. Summary of predictor variables was done by taking the mean o f all
measurements across the study period.
Normality was tested using Bartlett’s test. Log transformation was undertaken in non-
parametrically distributed variables.
For all analyses one subject was excluded who had a subject prevalence for diarrhoea
>4 standard deviations from the cohort mean. No specific cause for the very heavy
burden o f diarrhoea in this child was identified, and he subsequently developed
kwashiorkor and died at 18 months o f age. He was negative for HIV antibodies at that
3.1.4 Results
Seventy-one children were studied, but 5 from the study cohort were excluded as they
were followed for less than 3 months. The mean duration o f follow up was 7.5 months
with a standard deviation o f 2.8 (range 13-3.5 months). There was a clear seasonal
pattern to the diarrhoea but this did not strictly follow the rainy season (late June to
September). Fig 3.1 shows the change in diarrhoea prevalence over a 12 month period.
October to February, during the cool dry season, has the lowest rates o f diarrhoea with
the average child having diarrhoea about 5 % o f the time. A sustained rise in diarrhoea
morbidity above the October to February rates is seen between May and June, before
the rains begin but this escapes significance {P = 0.09).
The highest incidence of diarrhoea comes during the heaviest rains in August and
September rising to a peak mean monthly prevalence o f 18 % in August more than 3
fold higher than the period between October to February. However the diarrhoea
prevalence seems to rise at least 4 months before the rains start and not fall until the
August peak has finished.
The mean diarrhoea prevalence across the whole year is 0.83 days per week ( SD 0.67 )
with a range o f 0.1 - 3.6 days / week. This is equal to 12 % o f the time across a
calendar year slightly higher than the value o f 9.8 % previously quoted by Lunn et al
(Downes et al., 1991).
Significant relationships exist between number o f days with diarrhoea (after log
transformation) and number o f days with vomiting (r = 0.49, P < 0.05), but not with
fever, which correlated more strongly with vomiting (r = 0.76, P < 0.001).
Change in weight and height z-score was not significantly associated with the average
There was also no association between the mean monthly subject prevalence for
diarrhoea and the mean L:M permeability over the survey period. This was repeated
for % recovery o f both lactulose and mannitol and again there was no significant
association.
Comparisons between permeability values for each child were made by summarising
the serial estimates in to a mean for each child. There was no significant relationship
between permeability and average days with diarrhoea per week by linear regression.
Measurements o f immunoglobulins, albumin, G/art/za-specific IgM, haematocrit,
alpha-1 -antichymotrypsin and GRP estimates were summarised by taking the mean
values for individual subjects across the survey period and compared to the mean
number o f days with diarrhoea per month for each child. Immunoglobulin subclasses
IgG and IgM were significantly related to the diarrhoea morbidity {r = 0.70 P = 0.02;
r = 0.65, P = 0.03 respectively) but IgA was not (P = 0.07). Days with diarrhoea were
not significantly related to mean C-reactive protein haematocrit, ACT but approached
significance for Gzarcfza-specific IgM (P = 0.06).
3.1.5 Discussion
This survey confirms the commonly held belief that diarrhoeal disease is still very
prevalent in West Africa. Published data from similar surveys carried out in the USA
suggest that children between 6-18 months have 1-3 attacks o f diarrhoea per year
lasting up to 3 days giving a total o f 9 days or 2% over one year (Roubenhoff and
Rosenberg, 1991). This is substantially less than the 12 % estimated by this survey.
This study has not shown any evidence o f a decrease in the subject prevalence since
1994 (Lunn et al., 1995) however much o f the reduction reported by Poskitt et al came
diarrhoea may explain the divergence in the results reported by Poskitt et al and this
present study. It is likely that a twice weekly visit to the compound would gain a
higher estimate than at a 2 monthly clinic visit. This study also used a less rigid
definition o f diarrhoea than the study by Poskitt et al, which would tend to lead to a
higher estimate of diarrhoea prevalence.
Seasonal climatic and social changes are important in the pattern o f diarrhoeal
morbidity with peak rates coming during August (the month o f maximal rain fall).
However, the seasonal rise in diarrhoea begins in May and June before the rains
commence, but during the period when mothers are away from the children preparing
the fields for farming. During the pre-rainy season rise in diarrhoea, the young children
are left in the care o f a child nurse maid who may only be 7 years old (Weaver and
Beckerleg, 1993, Beckerleg, 1993). Infants could be left in the care o f nurse maids for
long periods o f time with the food being prepared in the morning and continuing from
the same bowl for the entire day. By evening the bacterial loads are extremely high and
the consumption o f the gruel puts the infant at risk o f gastrointestinal infection
(Rowland and Barrell, 1978).
This study has confirmed the previous reports that there is no association between
diarrhoeal disease and growth and diarrhoeal disease and intestinal mucosal damage
assessed by L:M permeability. There are at least two possible explanations. Firstly
L:M rises in a non-specific way in any small bowel inflammatory condition, but is
probably not affected by colonic pathology (Elia et al., 1991), which may cause
diarrhoeal disease. Secondly, the lack o f diarrhoeal disease in coeliac disease is well
established, so that even histologically grossly abnormal mucosa can exist in a subject
without diarrhoeal symptoms for years. Potentially the same scenario exists for tropical
marker o f small bowel mucosal damage, or that there were other confounding causes
o f acute phase response.
Mean immunoglobulin levels are significantly related to diarrhoeal prevalence with
higher values seen in children with the greater diarrhoea morbidity, indicating that
diarrhoeal disease is associated with detectable systemic inflammatory activity.
However the acute phase proteins CRP and ACT were not related to diarrhoea
prevalence suggesting that full scale activation o f the reticulo-endothelial system does
not occur with most bouts o f common diarrhoea in Gambian children.
Giardia-s^QQiüo IgM mean levels had a positive relationship to subject diarrhoea
prevalence that approaches significance and supports the idea that Giardiasis is an
important cause o f diarrhoeal disease. The role o f Giardia in causing enteropathy and
growth faltering in rural Gambia will be discussed in chapter 4 in more detail.
3.1.6 Conclusion
Diarrhoeal disease is not associated with long-term growth performance in Gambian
infants, neither is it related to the degree o f small bowel mucosal damage as assessed
by the L:M test. However mean levels o f circulating immunoglobulins (IgM and IgG
in particular) are positively related to subject diarrhoea prevalence, indicating that a
U l A
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K aI
Q 20 rMean days with diarrhoea as a percent o f a standardized m onth August '96-Jiilv '97
Jan Fe b Mar Apr May June July Aug S e p t Oct Nov De c