Tuberculosis in Oriental Immigrants

Tuberculosis in Oriental Immigrants* A S t u d y in M i l i t a r y

Dependents

Col Richard B. Byrd, MC, USAF, F.C.C.P.; Lt Col David E. Fisk, MC, USAF; Maj Robert A. Roethe, MC, USAF; John N. Glover, M.D., F.C.C.P.; " L. Dwight Wooster, M.D.,t and Maj Norman J. Wilder, MC, USAF 0

T u b e r c u l o s i s i n O r i e n t a l i m m i g r a n t s is l i k e l y to be r e -

7 p e r c e n t (five p a t i e n t s ) . D e s p i t e t h e presence o f d r u g -

sistant to t h e r a p y w i t h c e r t a i n d r u g s . I n 7 3 m i l i t a r y d e p e n -

resistant o r g a n i s m s a n d o f t e n extensive disease, negative

dents w i t h p o s i t i v e c u l t u r e s f o r

cultures were attained i n a l l b u t one patient. Considera-

tuberculosis w h o

im-

m i g r a t e d f r o m six A s i a n c o u n t r i e s , t h e t u b e r c u l o s i s was

t i o n o f t h e h i g h i n c i d e n c e o f d r u g - r e s i s t a n t tuberculosis

f o u n d t o b e resistant to i s o n i a z i d i n 5 8 p e r c e n t ( 4 2 p a -

should be made i n planning a p r o g r a m o f treatment f o r

t i e n t s ) , to s t r e p t o m y c i n i n 3 6 p e r c e n t ( 2 6 p a t i e n t s ) , t o

these p a t i e n t s . R e c o g n i t i o n o f c u l t u r a l differences m a y

p-amino-salicylic

also be o f v a l u e i n t h e successful t r e a t m e n t o f this d i f -

acid i n 14 percent (ten patients),

to

r i f a m p i n i n 7 p e r c e n t (five p a t i e n t s ) , a n d t o e t h a m b u t o l i n

T"|espite earlier optimistic reports, tuberculosis remains a problem in the United States today, particularly in certain subgroups of the population. Oriental immigrants represent one such subgroup in which the incidence of tuberculosis is appreciable and in which drug-resistant isolates may be anticipated. With the change in laws regarding immigration, larger numbers of immigrants are arriving in the United States from the Far East. For these reasons, we believe it would be valuable to characterize tuberculosis in patients of Oriental extraction by its clinical aspects, sensitivities to drugs, and response to medication. The management of the differences in culture and language in these patients also appeared worthy of review. Our designation as the primary world-wide facility for treatment of tuberculosis for the Air Force has provided a unique opportunity to study this problem, since all dependents found to have tuberculosis while living overseas in their home country are referred to our hospital for evaluation. This report surveys data from these referrals and underscores the management and therapeutic problems associated with tuberculosis in this subpopulation. MATERIALS AND METHODS W e reviewed the inpatient and outpatient charts of all " F r o m the Department of Pulmonary Disease, U S A F Medical Center Scott, Scott Air Force Base, Illinois T h e views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air F o r c e or the Department of Defense. ""Presently at Oklahoma City Clinic, Oklahoma City. fPresently at Washington County Hospital, Hagerstown, Md. Manuscript received September 2 5 ; revision accepted December 2 1 . Reprint requests: Col Byrd, USAF Medical Center, Scott AFB, Illinois 62225

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BYRD ET AL

ficult g r o u p o f patients.

Oriental immigrants admitted to our hospital as patients between September 1969 and July 1978 who had a diagnosis of tuberculosis at discharge. These patients were hospitalized initially for periods ranging from one to six months, depending on the severity of their disease. Those who presented particular therapeutic problems were then followed (or are being followed) as outpatients by our center through the full course of treatment. Patients with uncomplicated tubercidosis were discharged after negative cultures of sputum had appeared. These patients were subsequently observed at their local base hospitals in the United States. Data concerning country of origin, age, and the reactivity on the cutaneous test were noted. The organs involved by tuberculosis and the symptoms were also recorded. The extent of the disease in those with pulmonary tuberculosis was classified roentgenographically as minimal, moderately advanced, or far advanced. Therapy with drugs prior to transfer to our institution was also reviewed. While under our care, the patients were managed generally along the guidelines previously outlined by our department.

1

Bacteriologic data included the dates of the first and last positive cultures, as well as the results of tests of the sensitivity of the isolate to drugs. The time from the initiation of therapy until the appearance of negative cultures of sputum was also noted. All mycobacterial isolates were tested for sensitivity to isoniazid, p-aminosalicylic acid, streptomycin, ethambutol, and rifampin. The tests of susceptibility to drugs were performed on agar ( 7 H 1 0 ) using the methods described

in

Handbook

of Tuberculosis

plements. ' 2

the

Veterans

Administration-Armed

Laboratory

Methods

Forces

and its sup-

Only controls with confluent growth over the

3

surface of the medium were considered adequate. Strains requiring greater than 0.1/tg of isoniazid, greater than 2.5/xg of streptomycin, greater than 5.(Vg of ethambutol, or greater than l.Ojug of rifampin per milliliter of medium for inhibition of growth were considered resistant. The data on sensitivity alone from 50 of these patients have been presented previously in an Army-Air F o r c e study of drug-resistant tuberculosis in Orientals.

4

CHEST, 76: 2, AUGUST, 1979

RESULTS

The records of 115 patients were available for review. Mycobacterium bovis was isolated from the sputum of one Filipino woman, and M xenopeii was isolated from the sputum of one Japanese woman. These two patients were not included for further analysis in this study. Only two of the patients were men, since the majority of adult military dependents are women. The nationalities of the 113 patients showed 51 Koreans, 20 Filipinos, 18 Thais, 13 Japanese, five Taiwanese, and six Vietnamese. The mean age of the patients was 27 years (range, 7 to 53 years). Of the 113 patients, 33 were asymptomatic. Their disease was discovered by a chest x-ray film taken in conjunction with applications for visas. Fourteen of these asymptomatic patients had positive cultures. Cutaneous tests with first-strength or intermediate strength tuberculin were positive in all of the 105 patients in whom this information was recorded. Cutaneous tests were apparently not done in the eight additional patients because of bacteriologic proof of disease. The extent of the disease was assessed radiographically. Of the 103 patients with pulmonary involvement, 56 patients had minimal disease, 25 had moderately advanced disease, and 22 had far advanced disease. Extrapulmonary tuberculosis was seen in 18 (16 percent) of the patients. Tuberculous cervical adenitis was the most common form, being seen in six patients. One patient had axillary adenitis. Five patients had tuberculous pleuritis, four had tuberculous spondylitis, and one each had tuberculous enteritis and uterine stenosis. Extrapulmonary tuberculosis appears to be more frequent in the nonwhite population, and our study would tend to support this observation. Bacteriologic studies showed that 40 (35 percent) of the 113 patients had negative cultures, usually a 5

reflection of therapy having been initiated prior to referral to our hospital. In those with negative cultures, a clinical or radiographic response (or both) to therapy with antituberculosis drugs under our observation was noted. Of those patients with positive cultures, all strains were positive for niacin. Testing for sensitivity showed that only 27 of the 73 patients with positive cultures for M tuberculosis had organisms fully sensitive to all of the major antituberculosis drugs. The incidence of resistance to the various drugs is shown by nationality in Table 1. If one considers that all of those patients who had negative cultures at the time that they entered our hospital could have had disease that was sensitive to drugs, the true incidence of resistance to drugs would obviously be lower. In this circumstance, 46 (41 percent) of the 113 patients would have tuberculosis that was resistant to at least one medication, and 26 (23 percent) of the 113 would have disease resistant to multiple medications. Seventy-four patients gave a history of therapy with an antituberculosis drug prior to transfer to our hospital. These details were often obscure, since the patients might have encountered such Asian proprietary preparations as isoniazid-containing cough syrups. In fact, in both Korea and Vietnam, antituberculosis drugs have been available without a prescription, and self-medication had apparently been a common practice. In those patients with positive bacteriologic tests who had known previous therapy, 30 (67 percent) of 45 proved to have drugresistant disease, compared to 16 (57 percent) of 28 who had no known previous therapy. This finding of such a small difference may in part reflect the possibility that a number of the patients had received antituberculosis drugs and been unaware of it. Alternatively, the finding may indicate a high incidence of primary drug-resistant tuberculosis. In any event, the uncertainty in the history of these patients does not allow us to firmly classify these 8

T a b l e 1—Patterns of Sensitivity to Drugs in 73 Oriental Immigrants Data Patients with positive cultures**

Korean

Thai

Japanese

with

Tuberculosis*

Filipino

Vietnamese

Chinese

Total

37

9

10

8

6

3

73

12 (32)

0

6 (60)

7 (88)

1(17)

1(33)

27 (37)

8 (22)

5(56)

3 (30)

0

3 (50)

1 (33)

20 (27)

Resistance to multiple drugs

1 7 (46)

4 (44)

1 (10)

1 (13)

2 (33)

1 (33)

26 (36)

Resistance to specific drugs Isoniazid Streptomycin p-Aminosalicylic acid Ethambutol Rifampin

2 5 (68) 14 (38) 7(19) 5 (14) 3(8)

7 (78) 6 (67) 2(22) 0 1 (11)

4 (40) 0 0 0 1(10)

103) 103) 0 0 0

3(50) 4(67) 1 (17) 0 0

2 (67) 1 (33) 0 0 0

42 (58) 26 (36) 10(14) 5(7) 5 (7)

Fully sensitive to drugs Resistance to one drug only

T a b l e values are numbers of patients; numbers within parentheses are percentages. " P o s i t i v e for M tuberculosis,

CHEST, 76: 2, AUGUST, 1979

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resistances as primary or secondary. Four of the patients had been treated with chemoprophylaxis with isoniazid in the year prior to their development of active disease. All four of these individuals had isoniazid-resistant organisms on testing of sensitivity. Excluding the five patients who had been receiving therapy for less than three months at the time of this analysis, 57 patients had negative cultures of sputum appear in the first three months, five patients in the second three-month period, one patient in the third three-month period, and four patients in the fourth three-month period of treatment. One patient with tuberculosis that was resistant to nine antituberculosis drugs still has positive cultures, with a bronchopleural fistula and empyema. This patient has undergone debridement of the pleural space, with drainage through an open thoracostomy. Only one other patient in our study with pulmonary tuberculosis was treated surgically, this patient undergoing right upper lobectomy and thoracoplasty for a persistent cavitary lesion in 1970. DISCUSSION

In certain populations of immigrants, tuberculosis has a high incidence of resistance to drugs and presents a significant challenge to public health in the United States today. Schiffman and his co-workers have pointed out the problems of drug-resistant tuberculosis in Mexican immigrants, with 39 percent of those patients having tuberculosis that was resistant to one or more medications. Our study confirms that a similar problem exists among Oriental military dependents entering this country. In those 73 patients with positive cultures, resistance of the isolate to at least one drag was documented in 63 percent (46 patients) and to multiple drugs in 36 percent (26 patients). If those with active disease but negative cultures were considered to have tuberculosis that was sensitive to drugs, then the incidence of resistance for our entire group would still be high, showing 41 percent (46/113) with tuberculosis resistant to one drug and 23 percent (26/113) with tuberculosis resistant to multiple drags. Considering the ready availability of isoniazid for many years in most Asian countries, it was not surprising that isoniazid was the most common medication to which our patients' organisms were resistant. The 58 percent incidence (42/73) of resistance to this drug in these Orientals contrasts sharply with that seen in natives of the United States who have tuberculosis. Resistance to isoniazid has been noted to occur at an incidence of 2.8 to 4.4 percent over recent years in American veterans with tuber7

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culosis. Resistance to streptomycin in our Oriental patients was also quite frequent and correlated with the fact that many of our patients gave a history of having received an injectable drug for their tuberculosis prior to immigration. 8

It should be noted that the high incidence of drugresistant tuberculosis seen in this military dependent subset of the Oriental population might be different from that seen in the population at large. These patients may come from a higher economic class, with greater access to antituberculosis medications in their own countries; however, the incidence of drug-resistant tuberculosis in our Vietnamese patients compares closely to those found by a study by the World Health Organization of 290 consecutive patients with positive cultures who were admitted to the National Tuberculosis Hospital, Cholon, Republic of Vietnam, in the late 1960s. This study found organisms resistant to streptomycin in 71 percent, to isoniazid in 64 percent, to p-aminosalicylic acid in 27 percent, and to all three drugs in 19 percent. 6

Recent studies by others have also shown a high incidence of drug-resistant tuberculosis among Orientals immigrating to North America. A Canadian investigation found that Oriental immigrants who have arrived in that country over the last 12 years have an incidence of 11.7 percent for primary resistance to drags and 43 percent for secondary resistance. A study by the Public Health Service on patterns of primary resistance in the United States for 1975 to 1977 showed an incidence of 21 percent for drug-resistant tuberculosis in 111 Asian immigrants who allegedly had not received previous therapy.' These investigators suggested that one possible explanation for the high rate of resistance in these individuals might relate to this ethnic group settling in areas where a high prevalence of drugresistant tuberculosis already exists. Our study would better support the concept that these dragresistant strains are imported, since our patients came directly to our hospital from their countries. 9

0

This problem of the importation of drug-resistant disease has apparently been solved, at least in part, in the state of Hawaii by not generally allowing those with active disease to enter the state. Despite a high rate of Oriental immigration, the incidence of resistance to isoniazid, streptomycin, and paminosalicylic acid in Hawaii is less than 2 percent and has changed little from 1957 to 1977; however, the control measures used in Hawaii cannot be applied to illegal immigrants and possibly will not be applied toward the increasing numbers of refugees from southeast Asia who are being admitted to the continental United States. 11

The importance of a program of screening for CHEST, 76: 2, AUGUST, 1979

tuberculosis in Oriental immigrants is emphasized by the finding that 33 ( 29 percent) of the 113 patients in our study were asymptomatic. The cutaneous test with tuberculin does appear to be very sensitive in this group of patients, since no falsenegative results occurred in the 105 patients tested. The striking absence of false-negative results on cutaneous tests might be genetic but more likely reflects the relatively young age of the population studied; however, one cannot generalize that this would apply to all Oriental populations, since those marrying American servicemen may be better nourished than the average Oriental and thus more likely to have competent immune systems. Lester has pointed out that barriers of language and culture contribute to the difficulty in managing drug-resistant tuberculosis. In consideration of this fact, an organized educational effort was made to acquaint our patients with their disease and with American culture. Formal and informal briefings on tuberculosis and the importance of taking medications were given by the staff. Also, regular visits with a native from the patient's country of origin was arranged. This appeared to reduce the cultural shock and also provided us with an interpreter to ensure that our instructions were being understood. Furthermore, most of those providing this assistance were patients previously cured of tuberculosis who further reinforced our goals. Many patients considered American food unpalatable. Provisions were made for the patients to cook their native foods, which improved their nutrition and also their tolerance of various medications. 12

All of our patients eventually had negative cultures of sputum appear, except for one patient with a chronic bronchopleural fistula and tuberculosis that was resistant to multiple drugs. W e do not have follow-up data after the initial appearance of negative cultures of sputum in some patients with less complicated disease who were discharged to other military installations; however, the patients with more difficult disease did well in prolonged followup, thus suggesting that all patients are excellent candidates for curative therapy. The most important conclusion from our study is that the Oriental immigrant with tuberculosis should be considered to have potentially drug-resistant disease. It is obvious that testing for sensitivity to drugs should be done on the initial isolates of the organism in all such patients. It would be unwise to determine sensitivities only on those with a previous history of treatment with drugs, as suggested by some authorities, since many of our patients were unsure of this facet of their history.

CHEST, 76: 2, AUGUST, 1979

Prior to obtaining the results of testing for sensitivities to drugs, these patients should be started on a therapeutic regimen containing medications to which their organisms are unlikely to be resistant. Considering the high incidence of resistance to isoniazid and streptomycin that was found in our patients and also in other studies of Oriental immigrants, rifampin and ethambutol are logical choices for initial therapy in most instances. For those in whom therapy with a third drug appears to be indicated, capreomycin or kanamycin is the logical choice, since the incidence of resistance to streptomycin is also appreciable. In patients where the previous history of medication is particularly confusing, a holding regimen of previously administered drugs may be utilized. Modification of the therapeutic program in any of these patients may be possible when the results of studies of sensitivity to drugs become available.

REFERENCES 1 Byrd R B , Kaplan P D , Gracey D R : Treatment of pulmonary tuberculosis. Chest 6 6 : 5 6 0 - 5 6 7 , 1 9 7 4 2 Handbook of Tuberculosis Laboratory Methods: VAArmed Forces Cooperative Studies of Chemotherapy of Tuberculosis. Washington, D.C., 1 9 6 2 3 Supplements 5 and 6 to the Handbook of Tuberculosis Laboratory Methods: VA-Armed Forces Cooperative Studies of Chemotherapy of Tuberculosis, 1 9 6 8 4 Wilder NJ, Gerace J E , Byrd R B , et al: Patterns of drug resistance in the tuberculous Oriental immigrants ( a b s t r a c t ) . Am Rev Respir Dis 1 1 5 ( s u p p l ) : 4 1 0 , 1977 5 Snider D E J r : Extrapulmonary tuberculosis in Oklahoma, 1 9 6 5 to 1 9 7 3 . Am Rev Respir Dis 1 1 1 : 6 4 1 - 6 4 6 , 1 9 7 5 6 Cowley RG, Briney R R : Pulmonary drug-resistant tuberculosis in Vietnam veterans. Am Rev Respir Dis 1 0 1 : 7 0 3 705, 1970 7 Schiffman PI, Ashkar B, Bishop M, et al: Drug resistant tuberculosis in a large southern California Hospital. Am Rev Respir Dis 1 1 6 : 8 2 1 - 8 2 5 , 1 9 7 7 8 Hobby G L , Johnson P M , Boytar-Papirnyik V : Primary drug resistance: A continuing study of drug resistance in tuberculosis in a veteran population within the United States. Am Rev Respir Dis 1 1 0 : 9 5 - 9 8 , 1 9 7 4 9 Edius L , Jessamine AG, Hershfield E S , et al: A national study to determine the prevalence of drug resistance in newly discovered previously untreated tuberculosis patients as well as in retreatment cases. Can J Public Health 69:146-153, 1978 10 Kopanoff D E , Kilbum JO, Glassroth J L , et al: A continuing survey of tuberculosis primary drug resistance in the United States: March 1 9 7 5 to November 1977. Am Rev Respir Dis 1 1 8 : 8 3 5 - 8 4 2 , 1 9 7 8 11 Pien F D , Michael N L , O w C L , et al: Primary tuberculosis drug resistance in Hawaii ( 1 9 5 7 to 1 9 7 7 ) . Am Rev Respir Dis 1 1 8 : 7 0 1 - 7 0 4 , 1 9 7 8 12 Lester W : Treatment of drug-resistant tuberculosis. D M , April 1 9 7 1 , pp 1-43

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