Subclinical malabsorption in Thailand. II. Intestinal absorption in ...

Subclinical II. Intestinal

malabsorption absorption

and

Corps

Gerald

T.

Peace Keusch,2

M.D.,

in Thailand. in American personnel’

Andrew

G.

Plaut,3

M.D.,

Prior to 1966 it was not known with certainty that subclinical malabsorption was acquired in the tropics. The presence of sufficient numbers of young adult Americans living in the manner of the indigenous population in several countries in Asia has allowed this question to be tested. Prospective studies in a group of United States military personnel in Thailand (1) have shown that absorptive defects are indeed acquired, and Lindenbaum and colleagues (2) have determined that intestinal abnormalities developing in Peace Corps volunteers during their stay in India or Pakistan reverse when they return to the United States. Tropical sprue was not detected in our military group in Thailand, whereas several of the Peace Corps volunteers had overt sprue by the criteria of Klipstein and Baker (3). The data from Thailand (1) were of interest because acquired subclinical malabsorption was present without overt disease. One interpretation of this might be that adaptation to the tropical environment results in asymptomatic malabsorption unrelated to tropical sprue, the common features of these enteropathies being the consequence of the limited range of responses the gastrointestinal tract can make to a variety of stresses (4). On the other hand, if overt sprue is the end result of multiple interacting factors, one or more of these hypothetical factors might not be prevalent in Thailand; therefore, subclinical sprue would rarely become overt. A larger prospective study was undertaken in Thailand to document the extent of the acquired lesions. From an epidemiological standpoint, the subjects to be studied also represented

tropical

“sentinels”

sprue

The American

for

the

surveillance

of

in Thailand. Journal

of Clinical

military

Nutritio,z

25:

OCTOBER

and

Materials

Frank

J.

and

Troncale,4

M.D.

methods

Forty-five young Americans comprised the voluntary study group. Thirteen were military personnd (mean age 21.3 years) and were reported in part in a previous communication (1). They were stationed at a United States military installation situated in rice paddy lowlands north of Bangkok, not far from the region where the previously reported Thai patient with tropical sprue lived (5). Their food was primarily American in content, style, and quantity, although they all frequently sampled the local fare. The 32 remaining subjects (30 men, 2 women; mean age 23.2 years) were Peace Corps personnel. They had all spent a period of several weeks at the Peace Corps training center in Hilo, Hawaii, or in Manila, the Philippines, before coming to Bangkok.

Consistent

with

the Peace

Corps

philosophy,

they

lived and worked in the field under conditions similar to those experienced by the local population. Many used a multivitamin preparation without folic acid issued by the Peace Corps on a regular basis. Shortly after arrival in Thailand (within 2 weeks in most cases) a history was taken and physical examination and base-line studies were performed. These included complete blood count, urinalysis, stool examination for ova and parasites, serum total protein and A/G ratio, carotene, vitamin A, cholesterol, calcium, phosphorus, and folate levels (6). Gastrointestinal function was assessed as previously described (7) with the 25-g n-xylose test, Schilling test with added intrinsic factor, and lactose tolerance test. The proximal intestinal mucosa 1

From

the

Clinical

Research

Asia

Treaty Organization ratory, Bangkok, Thailand.

Center,

Medical

Research

Southeast Labo-

‘Formerly Research Associate, International Research Career Development Program, National Institutes of Health, Bethesda, Maryland. Current address: Mount Sinai Hospital, Division of Infectious Diseases, New York, N. Y. 10029. 8Current address: Department of Medicine, State University of New York at Buffalo, New York 14215. Current address: Division of Gastroenterology, Yale University School of Medicine, New Haven, Connecticut 06510. 1972.

PP.

1067-1073.

Printed

in U.S.A.

1067

KEUSCH

1068

ET

are summarized in Table 1 . The military personnel had higher initial levels of serum cholesterol, carotene, and albumin. In the Peace Corps personnel these serum values were lower on first examination and did not change with time. The xylose tolerance test showed a decrease in the 5-hr urinary pentose excretion without any change in the 2-hr serum level in both groups. A significantly lower mean maximal rise in blood sugar during a lactose tolerance test was observed in Peace Corpsmen, but not in the soldiers. There were no significant differences between mean values for the two groups at the end of 1 year in Thailand. Jejunal disaccharidase assays in the Peace Corps volunteers were performed in different laboratories in 1 966 and 1968. Lactase activity correlated well with tolerance test data (Fig. 1), although the slopes of the regression lines for the 2 years were different. Although a direct comparison of lactase activity was therefore precluded, these data validated use of the tolerance test results as an indirect measurement for amount of enzyme. In contrast to the 13 soldiers, in whom there was no consistent alteration in maximum rise in blood sugar (seven decreased, five increased, one no change), it decreased significantly in the Peace Corps volunteers (Table 1, Fig. 2). Table 2 shows mean serum folic acid levels in the two groups (normal, 2.0 to 10.6 ng/ ml). Folate levels in the Peace Corps subjects

was biopsied capsule. When

perorally with the Crosby-Kugler the specimen was adequate, one portion was frozen at -60 C for later determination of disaccharidase activity (8). The second and larger portion was fixed in buffered neutral 10% formalin or Bouin’s solution for histologic study. Biopsies were coded and then read by the pathologist without knowledge of the clinical history, laboratory data, or date of the biopsy. Not all the studies were performed in all subjects. Follow-up in the 13 soldiers was accomplished after 8 months in Thailand. The Peace Corps workers were restudied after 1 and 2 years in Thailand. Clinical summaries in the latter subjects, prepared on the basis of the three yearly medical interviews and records kept by the Peace Corps physician, were independently sorted on a blind basis by two of the authors into three clinical groups, i.e., 1) asymptomatic, 2) mild to moderate, and 3) severe gastrointestinal symptoms. The criteria employed for separating groups 2 and 3 were not strict. Volunteem with severe symptoms in general experienced diarrhea several times per month, lasting several days each time, often resulting in absence from work. Subjects in group 2 had less frequent attacks, often associated with a specific environmental change such as alcohol ingestion, travel, or western-type food. Diarrhea tended to be of short duration and did not result in time loss from work. There was excellent observer agreement on the classification of asymptomatic and severe groups and sufficient disagreement in the mild to moderate classification to warrant grouping the latter two

together. Results Selected ject

laboratory

groups

TABLE Laboratory

during

the

data

for

first

year

the

two

in

AL.

sub-

Thailand

I studies

in two

groups

of Americans

before

and

after Subject

Test

U.S. Initial

Fasting serum Cholesterol Carotene Albumin Globulin Xylose tolerance Urine,g/5 hr Serum, mg/lOOml Lactose tolerance, mg/l00ml a

values

P

=

Data

from

by analysis 0.05 level.

(I).

b

Eight

of variance.

±

164

±

4.3 2.7

±

12.6’ 14.4 0.1 0.1

7.5 36.7 32.6

± ± ±

0.7 3.0 5.8

±

months

later. d

Twelve

in Thailand

group

military4

Peace

Repeat1’

211

residence

184 1 93 ± 3.9 ± 2.7 ± 5.7 32.3 29.7

± ± ±

c

Initial

PC