Professional Documents
Culture Documents
between
measles,
malnutrition,
and blindness:
a prospective
study
in Indian children13
Vinodini
Reddy,
MD, DCH, P Bhaskaram,
Roy C Milton,
PhD, Vithal Rao, MS, DO,
and KV Radha Krishna,
DCH
MD, N Raghuramulu,
J Madhusudan,
DCH,
PhD,
KEY
WORDS
Measles,
malnutrition,
Introduction
resembling
keratomalacia
is
a fre-
quent
complication
of measles
in Nigerian
children
(4, 5). Similar observations
have been
reported
from Asian countries
(6, 7). Some
observers
have attributed
this to specific measles keratitis
while others believe that underlying vitamin
A deficiency
is the primary
cause
of eye lesions.
Protein-energy
malnutrition
is
also considered
to be a significant
background
factor in the pathogenesis
of these lesions.
Most of the earlier studies were conducted
in children
attending
hospital
clinics for treatment of complications
associated
with measles, and little information
is available
on the
sequence
ofevents
related to the disease in the
924
Furthermore,
the relative importance of various
risk factors may vary in different populations.
A prospective
study was
conducted,
therefore,
to assess the significance
of measles
as a cause of corneal
blindness
in
Indian children and to clarify its relationship
with
nutritional
status.
community.
Measles
is one of the most common
infectious diseases
that occur during childhood.
High death rates due to secondary
infection
have been reported
from developing
countries
(1, 2). Measles is considered
to be an important
cause ofchildhood
blindness.
In Zambia it has
been estimated
that 80% of blindness
in children was due to corneal
lesions,
and half of
these were caused by measles (3). Corneal ulceration
blindness
Am J Clin Nuir
1986;44:
924-30.
Printed
Methods
A slum area situated near the airport ofHyderabad
city
was selected for the study. The slum population
was of
low socioeconomic status and the residents were mostly
laborers subsisting on daily wages. Regular health care was
not available and there was no vitamin A prophylactic
program. In December
1982 the total population
residing
Institute of Nutrition
(VRe, PB,
JM, KVRK),
Hyderabad,
India and the NaInstitute (RCM), Bethesda, MD.
conducted as part of INDO-US
collaborative
Nutritional
Blindness.
3 Address
reprint requests to: Dr Vinodini
Reddy, National Institute
of Nutrition, Jamai-Osmania
P0, Hyderabad, 500 007, India.
Received February 3, 1986.
Accepted for publication May 27, 1986.
1
NR, VRa,
tional Eye
2 Study
project on
in USA.
1986 American
Society
for Clinical
Nutrition
ABSTRACT
A prospective study was conducted in slum children to determine the incidence of
post-measles
corneal disease and to clarify its relationship with nutritional
status. A total of318 cases
of measles were identified
over a period of 15 mo; maximum
incidence
was observed
for children
between
1-2 yr. Most of the children showed weight loss and serum proteins decrease
during the
acute stage ofmeasles.
Corneal lesions were observed
in 3% ofthe children, and the lesions responded
well to treatment.
Serum vitamin A and RBP levels were significantly
depressed
during the acute
stage ofmeasles
but were restored to normal 8 wk after recovery. There were no significant differences
in the serum levels for those with and without eye lesions, which suggests that these lesions may not
be mediated simply through the effect ofinfection
on serum concentration ofvitamin
A.
Am J
Clin Nuir 1986;44:924-30.
MEASLES
TABLE
Baseline
Age
1
survey showing
Total
number
prevalence
Kwashiorkor
AND
of nutritional
Marasmus
CHILDHOOD
deficiencies
925
BLINDNESS
in children
Vitamin A
defidency
Conjunctival
xerosis
Bitot
Night
spot
blindness
Comeal
scar
yr
<1
1+
2+
3+
4+
0-4+
330
345
352
315
202
1544
(100%)
1
4
11
3
0
19
(1.2%)
7
23
0
4
0
1
0
3
0
0
0
0
8
3
24
27
14
18
8
16
2
3
13
46
(3%)
17
44
(2.8%)
0
41
(2.6%)
26
81
(5.2%)
1
0
2
(0.1%)
Results
Initial
nutritional
status
At the initial baseline survey, 4% ofthe children showed clinical signs of kwashiorkor
or
marasmus.
Thirty-five
percent
ofthe children
were in grade I, 48% in grade II, and 1 1% in
grade III malnutrition
while 6% ofthe children
were
of normal
nutritional
grade.
Ocular
manifestations
of vitamin
A deficiency
seen
in 5% ofthe children
were mostly conjunctival
lesions (eg, Bitot Spots and conjunctival
xerosis) (Table
1). The prevalence
of corneal
scars was 0.1%.
Incidence
of measles
TABLE
2
Incidence of complications
No
Age
groups
of
measles
during
measles
with
With
broncho-
cases
pneumonia
<1
1+
2+
69
105
62
24
40
21
3+
47
16
4+
0-4+
35
318
(100%)
109
With
diarrhea
corneal
lesions
yr
(34.3%)
29
45
22
11
11
118
(37.1%)
3
4
0
0
3
10
(3.1%)
intheslumareawas95l0.
Allchildrenaged
< 5 yr(l544)
were registered
for the study.
During the study the registry of children was adjusted
for births, immigrants,
emmigrants,
deaths, and age limit.
Weights were recorded
and clinical examinations
were
conducted
for assessment ofnutritional
status. Nutritional
status was determined
using weight for age as percentage
ofNational
Center for Health Statistics (NCHS) standard
(8). Children
> 90% ofstandard
were classified as normal,
while children between 75-90%, 60-75%, and < 60% were
considered
to be suffering from grades I, II, and III malnutrition, respectively.
After the baseline survey, the children were placed under
close surveillance and morbidity data were collected
by
field workers
by making
weekly
house visits. Three
hundred eighteen cases of measles were detected over the
15-mo period from January 1983 to March 1984. These
children
were examined
clinically daily during the acute
stage, and the associated complications
including eye
changes were recorded. After a portable slit lamp was procured, a more detailed eye examination
was conducted
in
the 125 children with measles seen during the second half
of the study. Patients were given symptomatic
treatment
and those with severe complications
were referred to the
hospital. Only those who had corneal lesions were treated
with vitamin A (IM injection of 100 000 Hi water-miscible
preparation)
and local antibiotic
drops while others did
not receive any specific therapy. Two hundred eighty-one
cases ofmeasles could be followed for 6 mo after recovery.
Children
ofthe same age and sex who did not suffer from
measles during the study period served as controls Weight
changes, morbidity, and nutritional deficiency signs were
recorded
in both groups during the follow-up period.
Blood samples were collected from children with measles, whenever parental consent could be obtained, during
the acute stage and again 8 wk after recovery.
Samples
also were collected from children with no history of measles
and served as controls. Some ofthese children
subsequently
developed measles within a week, and attempts were made
to collect blood samples again during the acute stage and
after recovery. Serum vitamin A concentration
was estimated by high pressure liquid chromatography
(HPLC)
(9), retinol binding protein (RBP) by immunodifusion technique
(10), and serum albumin
by the dye
method (1 1).
The significance of differences between groups was assessed by : test and chi square test.
The protocol was approved by the Ethical Committee
of our institution.
2
7
(0.4%)
926
REDDY
ET
AL
60
50
40
30
10
0
Jan
Feb Mar
Apr
May
FIG
Jun
Jul
1. Monthly
TABLE
Details
Aug Sep
incidence
Oct
Nov
Dec
Jan
Feb Mar
of measles.
Slit lamp
observations
of children
with corneal
lesions
during
measles
Nutritional
Age
grade
no
6
8
12
13
14
I
II
I
I
II
17
22
54
57
58
II
I
II
III
MeanSE
Serum
vitamin
Serum
albumin
zgJdL
g/dL
19.5
6.0
5.5
9.8
15.0
18.6
6.0
12.0
13.8
8.2
3.1
2.7
3.5
3.4
3.2
3.2
3.3
3.5
3.3
3.4
11.51.63
3.30.07
Associated
complications
Bronchopneumonia
Bronchopneumonia
Bronchopneumonia
Bronchopneumonia
Bronchopneumonia
Diarrhea
Bronchopneumonia
Diarrhea
Diarrhea
Bronchopneumonia
+ Diarrhea
+ Diarrhea
20
MEASLES
TABLE 4
Percent distribution of measles cases according
nutritional status at different times
Nuthtional
status
Normal
Grade I
Grade II
Grade III
S Initial
Initialt
(307)
13.7
37.5
43.6
5.2
vs other times, p
<
AND
CHILDHOOD
Morbidity
Dating
3mo
6mo
measles
(307)
Later
(300)
(220)
later
5.2
3.3
1.8
30.9
36.7
32.3
50.8
49.3
54.5
13.0
10.7
1 1.4
0.001. Figures in parentheses
changes
Among
142 children who were registered as
controls
and subsequently
developed
measles
within a week, weights were available
before
and during measles.
The mean weight of this
group was 8.7 0. 17 kg during measles, which
was significantly
lower compared
with 9.1
0. 19 kg before measles.
Children
with measles showed
lower weight
gain in the first 3
months
of the follow-up
period than did agematched control children (0.3 0.06 kg vs 0.5
0.02 kg). These differences
were statistically
significant
(p < 0.001).
When the children
were classified by various
nutritional
grades
on the basis of weight for
age, it was observed
that the prevalence
of
grades
II and HI malnutrition
was significantly
higher during measles than during the initial
survey.
This difference
persisted
up to 6 mo
after measles (Table 4).
deficiency
measles
signs
Out of 28 1 cases
of measles
followed,
12
children
(4.3%) developed
clinical signs of severe PEM-like
edema and wasting of muscles.
In the age-matched
controls,
the incidence
was
only 1.3%. Conjunctival
signs of vitamin
A
deficiency
(eg, xerosis and Bitot spots) were
noted in 1. 1% of children
following
measles
compared
with 0.5% in control children.
There
was no case of corneal
xerophthalmia
during
the follow-up
period.
changes
levels ofalbumin
and vitamin A were
low in most ofthe slum children,
but the mean
levels were found to be significantly
lower in
children
with measles than in the control children (Table 6 and Table 7). In children whose
serum level tests were repeated
8 wk later, all
the biochemical
parameters
were restored
to
normal
after recovery
even without
vitamin
A supplementation.
Serum
TABLE 5
Post-measles
period
morbidity
during
the 6 mo follow-up
Measles
281
Noofchildren
respiratory
infection
Percent of children
affected
No of episodes/
child
Duration/episode
(days)
Percent incidence
of
hospitalization
Control
819
Lower
Diarrhea
Percent of children
affected
No of episodes/
child
Duration/episode
(days)
Percent
incidence
t p <0.001.
6.2
0.5 0.04t
0.08 0.01
6.80.24
5.5
0.12
2.9t
0.4
76.9t
48.7
2.3 0. 1 3t
1.4
0.07
4.30.20
3.7 0.10
of
dehydration
a
34.2t
1.1
0.5
the cornea.
None of these cases progressed
to
macroerosions
or ulceration.
Fine punctate
keratopathy
was seen in 15%
of the patients.
The lesions appeared
first in
the lower and nasal part of the cornea and in
two patients
progressed
to corneal xerosis detected by clinical examination.
Nutritional
during
to
Weight
927
BLINDNESS
928
REDDY
TABLE 6
Biochemical
parameters
(Cross-sectional
ET
AL
data)*
Serum levels
Group
Control
Albumin
Retinol
g/dL
,g/dL
I 17
3.6 0.03
153
108
significance:
3.4 0.03
3.5 0.05
C vs Ml, p < 0.001
(C)
Measles
During infection (M 1)
After recovery (M2)
Values are Mean SE. Statistical
<
Vitamin
deficiency
is
major
public
that
influence
vitamin
A metabolism,
such as protein-energy
malnutrition
and infection, also contribute
to the disease process.
Results of the present survey showed
that
TABLE
7
Biochemical
children)
parameters
(Longitudinal
Retinol
<
for retinol,
0.001
p <0.001
reported
that
keratomalacia
is a frequent
complication
of measles in Indian children.
In developing
countries
where measles vaccine is not given routinely,
virtually
all children suffer from the disease before they reach
5 yr of age.
However,
severity
of the
disease
gJdL
,g/dL
16.5 1.75
11.11.10
19.2 1.68
RBP
in measles according
No of
children
grade
to
Albumin
Retinol
RBP
gm/dL
eJdL
mgJdL
mg/dL
2.40.14
2.20.17
2.3 0.15
Levels
Albumin
3.60.07
3.40.08
3.70.07
2. 1 0.07
2.5 0.06
-5%
of the preschool
children
had
ocular
signs of vitamin
A deficiency
confirming
that
xerophthalmia
is a significant
health problem
in the slum population.
Acute corneal lesions
were not observed
though
healed scars were
seen in 0.1% ofthe population.
In measles the
incidence
was high; --3.0% of the patients
showed
changes
resembling
corneal
xerophthalmia.
Krishnamurthy
and Anantharaman
Nutrition
Premeasles(PM)
Measles(Ml)
Postmeasles(M2)
1 1.5 0.44
19.8 0.69
TABLE 8
Biochemical
parameters
nutritional status*
data on 32
Serum
Group
2.5 0.06
for albumin,
0.001 fo r RBP.
(7)
Discussion
17.9 0.8 1
Normal
+ Grade
58
Grade II
74
21
Grade III
a valurs are Mean
t
p < 0.05
p<0.02
compared
compared
3.4 0.05
12.5
0.80
2.0 0.80
3.4
1 1.3 0.60
2.2 0.09
0.05
3.20.07t
8.30.75t
SE.
with Normal
with Normal
+ Grade
I.
+ Grade I.
2.2
0.15
During
measles,
mean serum vitamin
A
levels were not significantly
different
in children with or without
secondary
infections.
Malnourished
children
with measles
had significantly
lower
mean
levels
of albumin
and
serum
vitamin
A than did those with better
nutrition
(Table 8). However,
the biochemical
parameters
showed no correlation
with corneal
changes
(Table 9).
<
RBP
mg/dL
MEASLES
TABLE
9
Serum vitamin
corneal lesions
Corneal
AND
CHILDHOOD
929
of control
A levels in relation
to measles and
No
Albumin
Retinol
g/dL
Nochange
Coarse keratitis
Fine keratitis
Corneal xerosis
47
19
6
10
3.30.09
3.2 0.09
3.2 0. 14
3.3 0.07
,&g/dL
13.7
10.8
1 1.6
1 1.5
1.37
1.09
1.39
1.63
immunosuppression
and
sec-
ondary
infection
with herpes
simplex.
Such
ulcerative
lesions are extremely
rare in Indian
children.
In this study, slit-lamp
examination
revealed
coarse-punctate
lesions in 50% of the
children.
These
lesions
are similar
to the
changes
described
by Dekkers
in measles keratitis (17); however,
they disappeared
spontaneously
after 2-3 wk. On clinical
examination corneal
lesions were observed
in 10 children, but they were mild and responded
well
to treatment.
Haziness
of the cornea disappeared
completely
in all, and only the child
with a corneal ulcer showed
residual opacity
after healing.
The consequences
may be more
serious in untreated
cases and measles
may,
therefore,
be a potential
cause ofblindness
in
Indian children.
Infection
can adversely
affect the nutritional
status by reducing food intake and by causing
malabsorption
and metabolic
losses. The impact ofmeasles
may be more severe compared
with
other infections
because
of secondary
complications
and prolonged
illness.
The effect
may be seen during the acute stage ofthe disease or during
the subsequent
period.
This
longitudinal
study gave us a unique
opportunity to assess
these effects. In children
who
were examined
before and after measles, there
was not only weight loss during infection
but
growth rate afterwards was also lower than that
perhaps because
of immediate
medical
care.
John et al (15) observed
that the case fatality
rate was lower in villages with health-care
supervision
than in areas where such facilities
were not available.
Acute
ulcerative
lesions
of the eye and
mouth have been described
in African children
with measles
(16). The lesions tend to be more
severe in malnourished
children and progress
rapidly
in spite of treatment.
This has been
to
children.
Frequent
occurrence
of
observed
during this period can account for the slower growth. The frequency
of
children
with severe PEM also showed
an increase confirming
the role of measles
in aggravating
malnutrition.
The adverse effect of measles on vitamin
A
status also has been well documented.
Serum
vitamin A levels were significantly
reduced in
all the measles cases studied here confirming
our earlier observations
(18). The reduction
was more marked in those who had associated
malnutrition.
In children
subsisting
on marginal diets, serum vitamin
A levels are low already. An episode
ofinfection
can cause a further drop in vitamin
A levels increasing
the
risk of corneal
xerophthalmia;
however,
this
mechanism
alone cannot
explain
the corneal
lesions associated
with measles. There were no
significant
differences
in the vitamin
levels of
children
with and without
corneal
disease.
Some ofthe children studied here showed fine
punctate
keratopathy
described
in vitamin
A
deficiency
(19), but even these changes showed
no correlation
with vitamin A levels. Furthermore, both the fine and gross lesions of cornea
were seen only during the acute stage of measles and not during the follow-up
period when
the stress of malnutrition
was still present.
Studies in Nigerian
children have shown that
though
plasma
vitamin
A levels were depressed
in measles
there were no differences
between
those with and without
eye lesions
(20). Similar findings have been reported
from
Kenya (17). These observations
suggest that
apart
from hypovitaminosis
A, there may
be other factors that contribute
to corneal
damage.
Both measles and malnutrition
are known
to cause immunosuppression
predisposing
to
secondary
infection.
This can exacerbate
the
epithelial
damage
caused by viral keratitis and
vitamin
A deficiency.
Corneal
ulceration
is
obviously
caused by a variety of interacting
factors, but measles plays the most significant
role in triggering the destructive
changes.
Appreciation
of this fact has important
bearing
on public health policies and programs
for the
control of childhood
blindness.
In India and
other Asian countries
where xerophthalmia
is
common,
efforts are being made to improve
vitamin
A status of the community
through
nutrition
education
and vitamin
A suppleinfections
changes
in measles
attributed
BLINDNESS
930
REDDY
mentation.
The present
study demonstrates
the importance
ofmeasles
as an additional
risk
factor in causing blindness
and emphasizes
the
need for effective
vaccination
programs
for
control of measles.
ET
9.
10.
1 1.
12.
13.
14.
15.
16.
17.
18.
19.
20.
References
AL