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Digestive Disease as a National Problem
Vol. 55, No. I
GASTROENTEROLOGY
Copyright © 1968 b y The Williams & Wilkins Co.
Printed in U.S.A.
DIGESTIVE DISEASE AS A NATIONAL PROBLEM VI. Enteric disease among United States troops in Vietnam THOMA S
w. S HEEHY,
M.D.
Division of Nutrition, Department of Medicine, University of A labama Medical Center, Birmingham, Alabama
Gastrointestinal diseases have been decisive fa ctors in many military campaigns. They decimated the armies of Napoleon in Egypt and Russia, ravaged both forces in our Civil War, immobilized the British at Gallipoli, an d caused a high degree of morbidity among German forces in Egypt and Russia in World War II . More recently (1946 to 1954), the French Expeditionary Force w Indochina suffered seriously from enteric diseases and, in the course of its ill fated campaign, reportedly had over 190,000 C·ases of amebic dysentery along with numerous cases of shigellosis, salmonellosis, cholera, and intestinal parasitic infestations (16,000 cases). These diseases as well as leptospirosis, viral hepatitis, rickettsial diseases, and malaria seriously hampered the military effectiveness of the French and contributed to their eventual defeat.! These ominous sta tistics also led the United States Army's surgeon general to dispatch a survey team composed of civilian members of the Armed Forces Epidemiological Board to the R<'publi c of South Vietnam (RVN) Received March 1, 1968. Accepted March 2, 1968. Address requests for reprints to: Dr. Thomas W. ShePhy, Department of Medicine, University of Alabama Medi cal Center, 1919 Seventh Avenue South, Birmingh am, Alabama 35233. This paper was prepared for presentation at tlH' Conference on Digestive Disease as a National Problem, Bethesda, Maryland, February 5 to 7, 1967. The conference was sponsored jointly by The American Gastroenterological Association, Th e Digestive Disease Foundation, and th e National Institute of Arthritis and Metabolic Diseases.
immediately after large numbers of
105
106
DIGESTIVE DISEASE. VI 1. Enteric disea:;e:;: United States Army active duty personnel in South Vietnam
TABLE
Personnel Percentage of diarrheal diseases
I n all admissions .. . .. . In all diseases .........
1965
1966
Jan.-June 1967
14 .3 19 .5
8.3 11.8
10.2 15
2. Dispensary and clinic visits: United States Army in Republic of South Vietnam
T ABLE
1966
Total visits
Diarrhea Neuroand gastro- psychienteritis
atric
Acute in feetions
Skin disease
- -- - -- - - - - October ... 104,182 5,228 November. 102,040 4,601
843 822
--
5,761 11,002 5,292 10,305
3. Causes of hospital admission": United States Army in Republic of South Vietnam (1966)
T ABLE
Rates/1000 avg strength/annum
Injured result hostile action. . .. . . Nonbattle injuries. . . . . . . . . . . . . . . Fever- undetermined origin. . . . . . Diarrhea/dysentery . . . . . . . . . . . . . . Malaria.. .. .. . .. .. .. .. .. .. .. .. .. Acute respiratory infections .. . . .. Skin diseases. . .. . . .. . .. .. .. . .. . . Neuropsychiatric ill ness.. . ...... . Infectious hepatitis. . . . . . . Venereal disease. ............. Dengue . Scrub typhus .
86.6 75 .3 71.6 60.7 40.9 40 .0 28.9 13.1 4.8 4.6 2.9 0 .4
a Hospital admissions: disease = 70% ; injured result hostile action= 15%; nonbattle injuries = 15%.
The spectrum of diarrheal diseases among our forces is broad. Specific enteric pathogens are observed commonly, but currently protozoal, parasitic, and nonspecific diarrheas are encountered more often than bacterial diarrheas. Bacterial Diarrhea
Shigellosis. Although there is a hi gh incidence of shigellosis among the Vietnamese, the incidence among Americans is low, 1.2 per 1000 average strength. Most out-
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break:,; oeeu r at platoon or eompany level, and usually are due to a breach of water discipline, most notably, the use of nonpotable ice. The current water usage rate for field troops is 10 gallons per day per man, but as this allocation is difficult to obtain in many areas during the dry season, it is often necessary for combat troops to carry three or four canteens of water on some operations. Strict water discipline is also needed in the hot, humid delta area to prevent unauthorized use of nonpotable water. The carrier rate for shigellae is a lso low among troops. Only two positive isolates (Shigella flexneri) were found among 150 returning combat troops who had lived in country villages for periods of 4 to 6 months (T. W. Sheehy, personal observations). Seventy-four per cent of this group had had one or more attacks of diarrhea during this time. Among Vietnamese admitted to Cho Quan Hospital, Saigon, with diarrhea, Gaines et a!. found a shigella-salmonella ratio of 4:1. All the major groups of shigellae have been isolated from the Vietnamese and in most instances the isolates have proved to be highly resistant to antibiotics other than kanamycin, cephalothin, and polymyxin-B. 4 • 5 In contrast, most salmonella isolates have proven to be sensitive to a variety of broad spectrum antibiotics. Salmonellosis. Salmonellae infections express themselves either as an acute gastroenteritis (food poisoning) or as a systemic illness (typhoid or paratyphoid fever). Although a lack of physicians, medical laboratories, and public health facilities invalidate most govemment health statistics, the RVN Ministry of Health reported 770 cases of typhoid fever in the first quarter of 1966. Almost one-half of these cases occurred in the Saigon area, where the local citizen can and often does purchase tetracycline and other antibiotics on the open market to treat his diarrheal illness. Only a few cases of typhoid fever were reported from outlying districts where the incidence of typhoid fever is undoubtedly high. Re-
July 1968
DIGESTIVE DISEASE. VI
ports from the delta area indicate that, because of bowel perforation, t he disease is diagnosed more often as a surgical than as a medical entity. All somatic types of salmonellae, except type A, have been isolated in RVN with type D predominating in frequency .4 A few small outbreaks of salmonella food poisoning have occurred among Americans in port city areas and isolated cases of para typhoid fever have been observed (0.1 per 1000). However, typhoid fever has not been reported, although a number of troops have been held clinically suspect because of scrub typhus, a disease which may cause diarrhea and skin lesions resembling rose spots. Gastrointestinal symptoms may be prominent in patients with scrub typhus. In a study of 54 patients with the di sease, anorexia was observed in 50%, vomiting in 30%, and diarrhea in 15% (T. W. Sheehy, personal observations). Cholera. In 1964, RVN had its first epidemic of cholera in 20 years and a total of 20,000 cases was reported from areas under government control. The disease is still prevalent because 2,831 cases were recorded by the RVN Ministry of Health between .Janu ary and M arch of 1966. According to Vietnamese health authorities, cholera is concentrated in and about Saigon, Nha Trang, Hue, and Da Nang. Cholera is seasonal in RVN and it is due to biotype El Tor. I solates of Vilirio r.holcrae recovered during the 1966 outbreaks showed serotype changes from Ogawa to Inaba as the epidemic progressed, suggesting in vivo mutation of the organisms. 4 Con trollrd trials have shown that cholera vaccine confer:; a significant amount of protection aga inst clinical illness.ll The absence of a sin gle case of cholera among vaccinated Ameri cans tends to support these observations and emphasizes the value of vaccination. In well nourished individuals, cholera may be a mild selflimi ted illne:,;:,; that is easily mist aken for a nonsprcific type di arrhea. T etracycline, a commonly used antidiarrheal agent in
107
southeast Asia, may also hinder diagnosis because the drug sterilizes the bowel of V. cholera within two days. Protozoal Diarrhea Amebic dysentery was second to malaria as a cause of morbidity among French forces in Indochina but the incidence has been low among our forces (2 per 1000 in 1966). Explosive outbreaks of amebic dysentery have not occurred and only a few cases of acute hemorrhagic colitis have ended fatally. Most cases of amebic dysentery have been characterized by bloody diarrhea and a paucity of constitutional symptoms. It is often difficult to confirm a clinical diagnosis of amebiasis even in the presence of overt dysentery. The trophozoites of Entamoeba histolytica may be shed irregularly, various forms of treatment may preclude their identification (one wonders about the effect of prophylactic chloroquine base, 300 mg weekly), and aspiration of suspect lesions may prove futil e. In the field hospital, these and other problems make diagnosis more difficult. However, in a careful diagnostic study employing sigmoidoscopic examination, rectal biopsy, and stool studies, Cifarelli was able to find parasites in all but 7 of 30 patients with acute amebic dysentery. 7 Amebiasis may be more common among troops in RVN than is suggested by incidence rates. In the last quarter of 1965, only 21 cases of amebic dysentery were diagnosed in Army hospitals, but in the same period 16 patients were treated for amebic liver disease (T. W. Sheehy, pe1·sonal observations). An increasing number of patients with amebic liver disease have also been evacuated to this country from RVN. These patients have responded well to combined therapy with emetine, chloroquine, and Diodoquine. H epatoscans with radioactive colloidal gold (Au 198 ) have been valuable in helping to establish the diagnosis of amebic liver abscess, the size and number of abscess cavities, and their resolution time. Most amebic abscesses resolve 2 to 4
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DIGESTIVE DISEASE. VI
months after appropriate chemotherapy, but 20% may persist as asymptomatic lesions for as lon g as 7 to 12 months after treatment. 8 Giardiasis . In one screening survey, Giardia lamblia were found in 8% of asymptomatic returnees from RVN. In dispensaries serving large cities in RVN, G. lamblia infections were responsible for about 3% of diarrheal diseases. Atabrine has proved to be highly effective for treatment. Mala ria. In the tropics, malaria is constantly confused with typhoid fever because of associated gastrointestinal symptoms. Diarrhea, abdominal cramps, nausea, and vomiting occur in about onethird of nonimmune individuals with their first attack of falciparum malaria.9 • 10 Engorgement of the intestinal mucosal capillaries with parasitized erythrocytes has been blamed for the diarrhea observed in malarial patients, but autopsy studies have revealed this findin g in patients who never had di arrhea. Intravascular coagul ation has been found to occur frequently in patients with malaria, and t his phenomenon, plus sticky parasitized red cells, may lead to thrombosis of the mucosal capillary bed and, thereby, to intestinal symptoms.11 Parasitic Diarrhea
Ninety per cent of Vietn amese are estimated to harbor one or more intestinal parasites. In a prospective study of 500 American returnees, 15% were found to have parasites. Among those infected, 55% had hookworm (Necator america nus or Ancylostoma duodenale), 19% were infected with S trongyloides stercora lis, 14% had both hookworm and strongyloides, and 12% had Ascaris lumbricoides. 12 Hookworm . The parasite has caused both isolated infestations and small outbreaks in combat units. One need not go barefoot in RVN to acquire infection with hookworm. Troops may acquire infections from mud or muddy water entering the air vents or eyelets of their boots, from digging foxholes, from leaning against parapets, and from other forms of earth contact.
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Gastrointestinal symptoms due to hookworm begin 2 to 3 months after exposure and are often severe. In one out break , 46 men from a unit of the 1st Cavalry Division were admitted to the hospita l because of severe hookworm gastroenteritis. Ninety per cent had diarrhea, 82% had epigastric discomfort, 17% had frank abdominal tenderness, and 22% were vomiting. 13 Hookworm infestation can produce severe and even incapacitating gastrointestinal symptoms in previously unexposed persons who acquire a heavy inoculum with larvae.14 Besides "ground itch" and "foxhole cough," the parasite may cause an acute duodepit is that clinically simulates an ulcer diathesis, except that eating aggravates the pain. In one instance 11 patients with hookworm disease were admitted to the 3rd Field Hospita l within a 5-day period with a diagnosis of peptic ulcer. All had a marked eosinophilia of 12 tD 42% and roentgenographi c examination of their small bowels revealed spasm or dilation of the duodenum.15 Strongyloides stercoralis, first discovered by Norma nd in the diarrheic stools of French troops in Cochin-China, may also cause a duodenitis. This parasite damages the intestinal mu cosa and heavy infestations may lead to malabsorption. Neither stronglyloidosis nor ascariasis has caused s0rious morbidity but both may he associated with serious compli cations. Nonspecific Diarrhea
This is the most common form of di arrhea in Vietnam. Members of new units often deve lop a turista-like illness wi thin the first few weeks of their arri val ; a considerable number have "Monday" mornin g diarrhea due to weekly primaquine prophylaxis; some have it in the initial phase of heat exhaustion , and many acquire it as a result of local cuisine. A striking example of the latter occurred in F ebruary 1966 when a research team arrived at T an -San Nhut air base to study the causes of diarrhea. Prior to their arrival, 10 to 25 patients were seen daily with diarrhea in the base dispensary. Two days after the study was underway ,
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DIGESTI VE DISEASE. VI
July 1963
Saigon was placed "off limits" to American personnel and within 1 week diarrhea almost disappeared from the base (T. W. Sheehy, personal observation) . A quick inspection of the personnel, the dishwashing faci lities, t he food storage areas, and the water source used in local restaurants are sufficient to discourage most from eating in them. It must be emphasized that the nonspecific diarrheas and acute gastroenteritides encountered in RVN have not been studied in detail. Genera lly, t hese entities have been of short duration and can be divided into febrile and nonfebrile illnesses characterized by nausea, vomiting, abdominal cramps, weakness, and diarrhea of varying severity. The afebrile illnesses usually responded to conservative t herapy; the febri le illnesses appeared to subside more rapidly with antibiotic therapy. The latter are often preceded by a short prodromal period and feces may be bloody or mucopurulent, in contrast to the watery stools seen with the milder illness.
in Americans. Tropical sprue may be clinically silent for long periods and it is often insidious in onset. Hence, it could be more common than we suspect. T able 4 lists the results of intestinal absorption and biopsy studies in 75 Americans after 6 months of duty in RVN. Twenty-one had a jejunitis (28%) and 3 had intestinal mucosal lesions characteristic of tropical sprue. Among those with jej unitis, 10 had malabsorption of xylose, 8 had abnormal mucosal lactase levels, 6 had low serum carotene levels, and 4 had low serum folate levels. The low incidence of clinical sprue among Americans may be due to: (1) use of excellent fie ld rations; serum folate levels fell significantly among British field troops living on pack rations in Malaya 17 ; (2) fa ilure to recognize mild forms of the disease in an area where diarrhea is common; (3) the frequent use of tetracycline for nonspecific diarrhea; and (4) the relatively short period of service in RVN; most cases of the disease occur in the 2nd or 3rd year of residency in endemic areas.
Tropical Sprue
Tropical sprue posed a serious medical problem for the British army in I ndia and Burma in World War II. It has a lso been observed among Americans living in Puerto Rico, in the hill country of RVN, and in Pak istanP· 16 Although tropical sprue is endemic to southeast Asia, only 20 cases have been confirmed
Other Gastrointestinal Diseases
L eptospirosis. Leptospirosis is endemic in the Red River Delta and the marshy "le plaine des Jones" of North Vietnam. French operations in these areas were compromised repeatedly by leptospirosis. Since the clinical spectrum of this infec-
TAnLE 4. Intestinal biopsy findings and absorption studies in 75 Americans after 6 months in
the Republic of South Vietnam Jejunal biopsy
Abnormal•
Histological appearance
Dissecting appearance
Jejunitis
Villous
No.
Normal
Fingers . ................ Fingers and t.ongues . . . .. .. Tongues. . . . . . . . . . . . . . . . . . T ongues and ridge ........ Ridge and convol utions ....
25 11 27 10 2
23 8 18 5 0
2 3 9 5 2
0 0 1 2 2
Total. . . . .. .. . . . .... .. ... .
75
54
21
5
- --
Mucosal lactase
Serum
Serum
carotene
fo late
1 0 5 2 2
0 0 2 4 2
1 1 3 1
1 1 2
10
8
G
4
Xylose
changes ---
• Xylose, <1 .0 g pe r 5 h r ; carotene, <70.0 m1-1g p er 100 m l ; lactase, <0.7 un its per g wet weight; folate, <4.0 m1-1g pe r 100 mi.
DIGESTIVE DISEASE. VI
110 TABLE
5. Admissions to hospital: United States Army ln South Vietnam• Viral Hepatitis
1965 1966 Jan.-June 1967
RVNb
Europe
u.s.
5.7 4.1 6.7
0.4 0.5 0.3
0 .5 0.6 0.9
• Expressed as rates per 1000 average strength per year. b Republic of South Vietnam.
tion varies greatly, the disease is often missed, but Deller and Russell failed to find a single case of leptospirosis among 110 Americans studied clinically and serologically for fevers of undetermined origin. 3 A second survey of this type carried out for 3 months at the 93rd Evacuation Hospital revealed only 7 patients with serological evidence of the disease. In French and American studies, L eptospira icterohaemorrhagiae, L eptospira canicola, Leptospira bataviae, and Leptospira australis have been the organisms most commonly responsible for infections in Vietnam. Infectious hepatitis. Table 5 lists the rates for infectious hepatitis observed among Army troops in R VN, Europe, and the United States in 1965 and 1966. All troops assigned to RVN in 1965 received immune human serum y-globulin (0.5 ml per lb body wt) on their arrival and again 4 or 5 months later. This practice was discontinued in April 1966. Throughout the remainder of t he year, the incidence of viral hepatitis remained stationary but in the first 6 months of 1967 it rose from 4.1 to 6.7 per 1000 average strength. A prospective study of the value of prophylactic immune human serum y-globulin for infectious hepatitis is now underway in Korea. Infectious hepatitis is usually a mild disease in RVN where it has been the practice to return troops to duty after clinical and laboratory evidence of recovery. Between July 1, 1966, and April 30, 1967, 208 patients with viral hepatitis were observed at the 6th Convalescent
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Hospital Center. The mean period of hospitalization was 46 days. Only 22 patients were evacuated: 12 for discharge, 4 for other medical problems, 4 because of deteriorating liver function after initial improvement, and 2 because of severe liver degeneration. 18 In its initial phase, falciparum malaria may simulate viral hepatitis. Nonimmune patients may develop jaundice suddenly (0.5%) and biopsies of their livers may reveal fatty degeneration, fatty necrosis, and some parenchymal cell destruction. However, the jaundice associated with malaria is usually due to red blood cell destruction and it can be distinguished from viral hepatitis by the presence of red cell schizonts, eosinophilia, positive serology, clinical course, and clinical response to antimalarial therapy. Peptic ulcer. H. W . Boyce (personal communication) estimated the annual cost of duodenal ulcer disease to the United States Army was 4Y2 million dollars. Duodenal ulcer disease is relatively common in RVN; indeed, the number of ulcer patients in hospitals often exceeded the combined number with amebic and bacillary dysentery. About 8% of these patients had a past history of ulcer disease. Summary
The gastrointestinal diseases encountered by the military in the Republic of South Vietnam serve to emphasize several important points. Among these is the observation that the bacterial diarrheas no longer rank as the major cause of morbidity (table 6). Undoubtedly, this change is due to improved bacteriological support and diagnostic capabilities within the field hospitals, to a greater understanding of the pathophysiology and treatment of these diseases, and to a greater awareness of the constant need for unit sanitation. Even the dread cholera, once a godrevered illness in Asia, has lost much of its mystery as a result of the intensive research directed against it and other bacterial diarrheas during the past two decades. These efforts have been rewarding but they have not vanquished the bacterial
July 1968
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DIGESTIVE DISEASE. VI
diarrheas and dysenteries. Indeed, the discovery that certain bacterial enteropathogens can transfer resistance factors is proof of their constant dangers. The recognition of nonspecific gastroenteritis and diarrhea as major causes of disability brings into focus how little we know about them. These are the same vague illnesses that strike the tourist, or sweep a community as "intestinal flu," or disrupt a factory as "viral enteritis"-so vague, indeed, that the viral origin of any of these entities is in debate and so obscure that repeated attempts to identify an etiological factor have usually failed. This fact stands in sharp contrast to identification of the bacterial, rickettsial, and viral agents responsible for 74% of fevers of undetermined etiology in field hospitals in RVN. The causes, mechanisms, and pathophysiology of the nonspecific enteritides are virtual blanks in our knowledge. Like the protozoal and parasitic enteritides, they lack glamor and they are not comparable in lethality to malaria; nonetheless, they are causes for enormous loss of duty time among the military services and for absenteeism in civilian life, and their appearance among combat units at a critical time can be disastrous. This is an area worthy of intensive study and research. The Medical Corps of the respective services have committed sizeable portions of their medical research funds for gastrointestinal research. The Army and Navy have each established research laboratories overseas specifically for the purposes of studying certain model gastrointestinal diseases (such as, cholera, tropical sprue, shigellosis, and schistosomiasis) that permit investigations of many parameters of bowel function. Some of the studies done in these laboratories have contributed significantly to our knowledge of intestinal function. Research funds have also been provided by the United States Army Medical Corps for the support of numerous civilian research projects concerned with infectious diarrhea ($1.2 million-fiscal year, 1969). In collaboration with a number of civilian institutions, the Army has also
6. Specified gastrointestinal diseases in comparison to fevers of undetermined origin: United States Army in Republic of South Vietnam (January-June 1967)
TABLE
Admissions
Food infection and poisoning ... Dysentery, bacillary and unspecified . Amebiasis. Other enteric infections. Infectious hepatitis. Serum hepatitis Fever, undetermined etiology .. ... .............
Rate/1000
34
0.25
169 471 6,610 892 8
1.22 3.41 47.87 6.46 0.06
10,022
72.58
undertaken a broad program designed to isolate and to characterize the virus or viruses responsible for infectious hepatitis, with the development of an effective vaccine as its ultimate goal. Army support for these two categories has been greatest because, in 1966 alone, diarrheal diseases and viral hepatitis, respectively, were responsible for 25,400 and 20,100 man days of hospitalization in RVN'. In an effort to develop a realistic gastrointestinal research program designed for their needs, the services have sought the guidance and advice of numerous senior civilian mvestigators. The generous advice and counsel of these men, many of whom serve as members of military advisory boards, have been invaluable and are essential to this end. REFERENCES 1. "Le Sr ~ rvicc De Sante En Indochine 19461954." 2. Hardy, A. V. 1967. Cmrent problems in the enteric infections. Mcd. Clin. N. Amer. 51: 609-615. 3. Deller, J. J., and P. K Russell. 1967. An analysis of fevers of unknown origin in American soldiers in Vietnam. Ann. Intern. Med . 66: 1129-1143. 4. Gaines, S., Nhu Tuan, Nguyen, Thi. 1966. Types and distribution of bacterial enteropathogens among diarrhea patients in Vietnam. Annual Progress Report, p. 65-81. U . S. Army Medical Research Team (WRAIR) , Vietnam, and Institute Pasteur of Vietnam.
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DIGESTIVE DISEASE. VI
5. Higgins, J . P., and C. D. Smith. 1967. Sensitivity of shigellae to various antibiotics. U. S. Army in Republic of South Vietnam. Med. Bull. 2: 53. 6. Philippines Cholera Committee. 1965. A controlled field trial of the effectiveness of cholera and cholera El T or vaccines in the Philippines. Bull. W. H. 0. 32 : 603-625. 7. Cifarelli, P. S. 1967. Acute amebic colitis. U. S. Army in Republic of South Vietnam Med. Bull. 2: 19-26. 8. Sheehy, T. W., L. F. Parmley, Jr., G. S. Johnston, and H. W. Boyce. 1968. Resolution time of an amebic liver abscess. Gastroenterology 55: 26-34. 9. Sheehy, T. W., and R. C. Reba. 1967. Complications of falciparum malaria and their treatment. Ann. Intern. Med. 66: 807-809. 10. Bartelloni, P. J., T. W. Sheehy, and W. D. Tigertt. 1967. Combined therapy for chloroquine-resistent plasmodium falciparum infection. J. A.M. A. 199: 173-177. 11. Spitz, S. 1946. The pathology of acute falciparum malaria. Milit. Surg. 99: 555-572.
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12. Sheehy, T. W., W. C. Cohen, D. K. Wallace, and L. J. Legters. 1965. Tropical sprue in North Americans. J. A.M. A . 194: 1069-1076. 13. Vandevelde, A. G. 1966. Hookworm epidemic in 1st. Cavalry Division. U. S. Army in Republic of South Vietnam. Med. Newsletter 1: 48-49. 14. Rodgers, A. M., and G. J. Dammin. 1946. Hookworm infection in American troops in Assam and Burma. Amer. J. Med . Sci. 211: 531-538. 15. Rowland, H. A. K. 1966. Dyspepsia, duodenitis and hookworm infection. Trans. Roy. Soc. Trop. Med . Hyg. 60 : 481-485. 16. Lindenbaum, J., T. H. Kent, and H . Sprinz. 1966. Malabsorption and jej unitis in American P eace Corps Volunteers in Pakistan. Ann. Intern. Med. 65: 1201-1209. 17. O'Brien, W., and M. W. J. England. 1966. Military tropical sprue from southeast Asia. Brit. Med. J . 2: 1157-1162. 18. Rogoway, W. M., and W. H. Bailey. 1967. Infectious hepatitis in Vietnam. U. S. Army in R epublic of South Vietnam. Med. Bull. 2: 12-14.
GASTROENTEROLOGY
Copyright © 1968 b y The Williams & Wilkins Co.
Printed in U.S.A.
DIGESTIVE DISEASE AS A NATIONAL PROBLEM VI. Enteric disease among United States troops in Vietnam THOMA S
w. S HEEHY,
M.D.
Division of Nutrition, Department of Medicine, University of A labama Medical Center, Birmingham, Alabama
Gastrointestinal diseases have been decisive fa ctors in many military campaigns. They decimated the armies of Napoleon in Egypt and Russia, ravaged both forces in our Civil War, immobilized the British at Gallipoli, an d caused a high degree of morbidity among German forces in Egypt and Russia in World War II . More recently (1946 to 1954), the French Expeditionary Force w Indochina suffered seriously from enteric diseases and, in the course of its ill fated campaign, reportedly had over 190,000 C·ases of amebic dysentery along with numerous cases of shigellosis, salmonellosis, cholera, and intestinal parasitic infestations (16,000 cases). These diseases as well as leptospirosis, viral hepatitis, rickettsial diseases, and malaria seriously hampered the military effectiveness of the French and contributed to their eventual defeat.! These ominous sta tistics also led the United States Army's surgeon general to dispatch a survey team composed of civilian members of the Armed Forces Epidemiological Board to the R<'publi c of South Vietnam (RVN) Received March 1, 1968. Accepted March 2, 1968. Address requests for reprints to: Dr. Thomas W. ShePhy, Department of Medicine, University of Alabama Medi cal Center, 1919 Seventh Avenue South, Birmingh am, Alabama 35233. This paper was prepared for presentation at tlH' Conference on Digestive Disease as a National Problem, Bethesda, Maryland, February 5 to 7, 1967. The conference was sponsored jointly by The American Gastroenterological Association, Th e Digestive Disease Foundation, and th e National Institute of Arthritis and Metabolic Diseases.
immediately after large numbers of
105
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DIGESTIVE DISEASE. VI 1. Enteric disea:;e:;: United States Army active duty personnel in South Vietnam
TABLE
Personnel Percentage of diarrheal diseases
I n all admissions .. . .. . In all diseases .........
1965
1966
Jan.-June 1967
14 .3 19 .5
8.3 11.8
10.2 15
2. Dispensary and clinic visits: United States Army in Republic of South Vietnam
T ABLE
1966
Total visits
Diarrhea Neuroand gastro- psychienteritis
atric
Acute in feetions
Skin disease
- -- - -- - - - - October ... 104,182 5,228 November. 102,040 4,601
843 822
--
5,761 11,002 5,292 10,305
3. Causes of hospital admission": United States Army in Republic of South Vietnam (1966)
T ABLE
Rates/1000 avg strength/annum
Injured result hostile action. . .. . . Nonbattle injuries. . . . . . . . . . . . . . . Fever- undetermined origin. . . . . . Diarrhea/dysentery . . . . . . . . . . . . . . Malaria.. .. .. . .. .. .. .. .. .. .. .. .. Acute respiratory infections .. . . .. Skin diseases. . .. . . .. . .. .. .. . .. . . Neuropsychiatric ill ness.. . ...... . Infectious hepatitis. . . . . . . Venereal disease. ............. Dengue . Scrub typhus .
86.6 75 .3 71.6 60.7 40.9 40 .0 28.9 13.1 4.8 4.6 2.9 0 .4
a Hospital admissions: disease = 70% ; injured result hostile action= 15%; nonbattle injuries = 15%.
The spectrum of diarrheal diseases among our forces is broad. Specific enteric pathogens are observed commonly, but currently protozoal, parasitic, and nonspecific diarrheas are encountered more often than bacterial diarrheas. Bacterial Diarrhea
Shigellosis. Although there is a hi gh incidence of shigellosis among the Vietnamese, the incidence among Americans is low, 1.2 per 1000 average strength. Most out-
Vol. 55, No. 1
break:,; oeeu r at platoon or eompany level, and usually are due to a breach of water discipline, most notably, the use of nonpotable ice. The current water usage rate for field troops is 10 gallons per day per man, but as this allocation is difficult to obtain in many areas during the dry season, it is often necessary for combat troops to carry three or four canteens of water on some operations. Strict water discipline is also needed in the hot, humid delta area to prevent unauthorized use of nonpotable water. The carrier rate for shigellae is a lso low among troops. Only two positive isolates (Shigella flexneri) were found among 150 returning combat troops who had lived in country villages for periods of 4 to 6 months (T. W. Sheehy, personal observations). Seventy-four per cent of this group had had one or more attacks of diarrhea during this time. Among Vietnamese admitted to Cho Quan Hospital, Saigon, with diarrhea, Gaines et a!. found a shigella-salmonella ratio of 4:1. All the major groups of shigellae have been isolated from the Vietnamese and in most instances the isolates have proved to be highly resistant to antibiotics other than kanamycin, cephalothin, and polymyxin-B. 4 • 5 In contrast, most salmonella isolates have proven to be sensitive to a variety of broad spectrum antibiotics. Salmonellosis. Salmonellae infections express themselves either as an acute gastroenteritis (food poisoning) or as a systemic illness (typhoid or paratyphoid fever). Although a lack of physicians, medical laboratories, and public health facilities invalidate most govemment health statistics, the RVN Ministry of Health reported 770 cases of typhoid fever in the first quarter of 1966. Almost one-half of these cases occurred in the Saigon area, where the local citizen can and often does purchase tetracycline and other antibiotics on the open market to treat his diarrheal illness. Only a few cases of typhoid fever were reported from outlying districts where the incidence of typhoid fever is undoubtedly high. Re-
July 1968
DIGESTIVE DISEASE. VI
ports from the delta area indicate that, because of bowel perforation, t he disease is diagnosed more often as a surgical than as a medical entity. All somatic types of salmonellae, except type A, have been isolated in RVN with type D predominating in frequency .4 A few small outbreaks of salmonella food poisoning have occurred among Americans in port city areas and isolated cases of para typhoid fever have been observed (0.1 per 1000). However, typhoid fever has not been reported, although a number of troops have been held clinically suspect because of scrub typhus, a disease which may cause diarrhea and skin lesions resembling rose spots. Gastrointestinal symptoms may be prominent in patients with scrub typhus. In a study of 54 patients with the di sease, anorexia was observed in 50%, vomiting in 30%, and diarrhea in 15% (T. W. Sheehy, personal observations). Cholera. In 1964, RVN had its first epidemic of cholera in 20 years and a total of 20,000 cases was reported from areas under government control. The disease is still prevalent because 2,831 cases were recorded by the RVN Ministry of Health between .Janu ary and M arch of 1966. According to Vietnamese health authorities, cholera is concentrated in and about Saigon, Nha Trang, Hue, and Da Nang. Cholera is seasonal in RVN and it is due to biotype El Tor. I solates of Vilirio r.holcrae recovered during the 1966 outbreaks showed serotype changes from Ogawa to Inaba as the epidemic progressed, suggesting in vivo mutation of the organisms. 4 Con trollrd trials have shown that cholera vaccine confer:; a significant amount of protection aga inst clinical illness.ll The absence of a sin gle case of cholera among vaccinated Ameri cans tends to support these observations and emphasizes the value of vaccination. In well nourished individuals, cholera may be a mild selflimi ted illne:,;:,; that is easily mist aken for a nonsprcific type di arrhea. T etracycline, a commonly used antidiarrheal agent in
107
southeast Asia, may also hinder diagnosis because the drug sterilizes the bowel of V. cholera within two days. Protozoal Diarrhea Amebic dysentery was second to malaria as a cause of morbidity among French forces in Indochina but the incidence has been low among our forces (2 per 1000 in 1966). Explosive outbreaks of amebic dysentery have not occurred and only a few cases of acute hemorrhagic colitis have ended fatally. Most cases of amebic dysentery have been characterized by bloody diarrhea and a paucity of constitutional symptoms. It is often difficult to confirm a clinical diagnosis of amebiasis even in the presence of overt dysentery. The trophozoites of Entamoeba histolytica may be shed irregularly, various forms of treatment may preclude their identification (one wonders about the effect of prophylactic chloroquine base, 300 mg weekly), and aspiration of suspect lesions may prove futil e. In the field hospital, these and other problems make diagnosis more difficult. However, in a careful diagnostic study employing sigmoidoscopic examination, rectal biopsy, and stool studies, Cifarelli was able to find parasites in all but 7 of 30 patients with acute amebic dysentery. 7 Amebiasis may be more common among troops in RVN than is suggested by incidence rates. In the last quarter of 1965, only 21 cases of amebic dysentery were diagnosed in Army hospitals, but in the same period 16 patients were treated for amebic liver disease (T. W. Sheehy, pe1·sonal observations). An increasing number of patients with amebic liver disease have also been evacuated to this country from RVN. These patients have responded well to combined therapy with emetine, chloroquine, and Diodoquine. H epatoscans with radioactive colloidal gold (Au 198 ) have been valuable in helping to establish the diagnosis of amebic liver abscess, the size and number of abscess cavities, and their resolution time. Most amebic abscesses resolve 2 to 4
108
DIGESTIVE DISEASE. VI
months after appropriate chemotherapy, but 20% may persist as asymptomatic lesions for as lon g as 7 to 12 months after treatment. 8 Giardiasis . In one screening survey, Giardia lamblia were found in 8% of asymptomatic returnees from RVN. In dispensaries serving large cities in RVN, G. lamblia infections were responsible for about 3% of diarrheal diseases. Atabrine has proved to be highly effective for treatment. Mala ria. In the tropics, malaria is constantly confused with typhoid fever because of associated gastrointestinal symptoms. Diarrhea, abdominal cramps, nausea, and vomiting occur in about onethird of nonimmune individuals with their first attack of falciparum malaria.9 • 10 Engorgement of the intestinal mucosal capillaries with parasitized erythrocytes has been blamed for the diarrhea observed in malarial patients, but autopsy studies have revealed this findin g in patients who never had di arrhea. Intravascular coagul ation has been found to occur frequently in patients with malaria, and t his phenomenon, plus sticky parasitized red cells, may lead to thrombosis of the mucosal capillary bed and, thereby, to intestinal symptoms.11 Parasitic Diarrhea
Ninety per cent of Vietn amese are estimated to harbor one or more intestinal parasites. In a prospective study of 500 American returnees, 15% were found to have parasites. Among those infected, 55% had hookworm (Necator america nus or Ancylostoma duodenale), 19% were infected with S trongyloides stercora lis, 14% had both hookworm and strongyloides, and 12% had Ascaris lumbricoides. 12 Hookworm . The parasite has caused both isolated infestations and small outbreaks in combat units. One need not go barefoot in RVN to acquire infection with hookworm. Troops may acquire infections from mud or muddy water entering the air vents or eyelets of their boots, from digging foxholes, from leaning against parapets, and from other forms of earth contact.
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Gastrointestinal symptoms due to hookworm begin 2 to 3 months after exposure and are often severe. In one out break , 46 men from a unit of the 1st Cavalry Division were admitted to the hospita l because of severe hookworm gastroenteritis. Ninety per cent had diarrhea, 82% had epigastric discomfort, 17% had frank abdominal tenderness, and 22% were vomiting. 13 Hookworm infestation can produce severe and even incapacitating gastrointestinal symptoms in previously unexposed persons who acquire a heavy inoculum with larvae.14 Besides "ground itch" and "foxhole cough," the parasite may cause an acute duodepit is that clinically simulates an ulcer diathesis, except that eating aggravates the pain. In one instance 11 patients with hookworm disease were admitted to the 3rd Field Hospita l within a 5-day period with a diagnosis of peptic ulcer. All had a marked eosinophilia of 12 tD 42% and roentgenographi c examination of their small bowels revealed spasm or dilation of the duodenum.15 Strongyloides stercoralis, first discovered by Norma nd in the diarrheic stools of French troops in Cochin-China, may also cause a duodenitis. This parasite damages the intestinal mu cosa and heavy infestations may lead to malabsorption. Neither stronglyloidosis nor ascariasis has caused s0rious morbidity but both may he associated with serious compli cations. Nonspecific Diarrhea
This is the most common form of di arrhea in Vietnam. Members of new units often deve lop a turista-like illness wi thin the first few weeks of their arri val ; a considerable number have "Monday" mornin g diarrhea due to weekly primaquine prophylaxis; some have it in the initial phase of heat exhaustion , and many acquire it as a result of local cuisine. A striking example of the latter occurred in F ebruary 1966 when a research team arrived at T an -San Nhut air base to study the causes of diarrhea. Prior to their arrival, 10 to 25 patients were seen daily with diarrhea in the base dispensary. Two days after the study was underway ,
109
DIGESTI VE DISEASE. VI
July 1963
Saigon was placed "off limits" to American personnel and within 1 week diarrhea almost disappeared from the base (T. W. Sheehy, personal observation) . A quick inspection of the personnel, the dishwashing faci lities, t he food storage areas, and the water source used in local restaurants are sufficient to discourage most from eating in them. It must be emphasized that the nonspecific diarrheas and acute gastroenteritides encountered in RVN have not been studied in detail. Genera lly, t hese entities have been of short duration and can be divided into febrile and nonfebrile illnesses characterized by nausea, vomiting, abdominal cramps, weakness, and diarrhea of varying severity. The afebrile illnesses usually responded to conservative t herapy; the febri le illnesses appeared to subside more rapidly with antibiotic therapy. The latter are often preceded by a short prodromal period and feces may be bloody or mucopurulent, in contrast to the watery stools seen with the milder illness.
in Americans. Tropical sprue may be clinically silent for long periods and it is often insidious in onset. Hence, it could be more common than we suspect. T able 4 lists the results of intestinal absorption and biopsy studies in 75 Americans after 6 months of duty in RVN. Twenty-one had a jejunitis (28%) and 3 had intestinal mucosal lesions characteristic of tropical sprue. Among those with jej unitis, 10 had malabsorption of xylose, 8 had abnormal mucosal lactase levels, 6 had low serum carotene levels, and 4 had low serum folate levels. The low incidence of clinical sprue among Americans may be due to: (1) use of excellent fie ld rations; serum folate levels fell significantly among British field troops living on pack rations in Malaya 17 ; (2) fa ilure to recognize mild forms of the disease in an area where diarrhea is common; (3) the frequent use of tetracycline for nonspecific diarrhea; and (4) the relatively short period of service in RVN; most cases of the disease occur in the 2nd or 3rd year of residency in endemic areas.
Tropical Sprue
Tropical sprue posed a serious medical problem for the British army in I ndia and Burma in World War II. It has a lso been observed among Americans living in Puerto Rico, in the hill country of RVN, and in Pak istanP· 16 Although tropical sprue is endemic to southeast Asia, only 20 cases have been confirmed
Other Gastrointestinal Diseases
L eptospirosis. Leptospirosis is endemic in the Red River Delta and the marshy "le plaine des Jones" of North Vietnam. French operations in these areas were compromised repeatedly by leptospirosis. Since the clinical spectrum of this infec-
TAnLE 4. Intestinal biopsy findings and absorption studies in 75 Americans after 6 months in
the Republic of South Vietnam Jejunal biopsy
Abnormal•
Histological appearance
Dissecting appearance
Jejunitis
Villous
No.
Normal
Fingers . ................ Fingers and t.ongues . . . .. .. Tongues. . . . . . . . . . . . . . . . . . T ongues and ridge ........ Ridge and convol utions ....
25 11 27 10 2
23 8 18 5 0
2 3 9 5 2
0 0 1 2 2
Total. . . . .. .. . . . .... .. ... .
75
54
21
5
- --
Mucosal lactase
Serum
Serum
carotene
fo late
1 0 5 2 2
0 0 2 4 2
1 1 3 1
1 1 2
10
8
G
4
Xylose
changes ---
• Xylose, <1 .0 g pe r 5 h r ; carotene, <70.0 m1-1g p er 100 m l ; lactase, <0.7 un its per g wet weight; folate, <4.0 m1-1g pe r 100 mi.
DIGESTIVE DISEASE. VI
110 TABLE
5. Admissions to hospital: United States Army ln South Vietnam• Viral Hepatitis
1965 1966 Jan.-June 1967
RVNb
Europe
u.s.
5.7 4.1 6.7
0.4 0.5 0.3
0 .5 0.6 0.9
• Expressed as rates per 1000 average strength per year. b Republic of South Vietnam.
tion varies greatly, the disease is often missed, but Deller and Russell failed to find a single case of leptospirosis among 110 Americans studied clinically and serologically for fevers of undetermined origin. 3 A second survey of this type carried out for 3 months at the 93rd Evacuation Hospital revealed only 7 patients with serological evidence of the disease. In French and American studies, L eptospira icterohaemorrhagiae, L eptospira canicola, Leptospira bataviae, and Leptospira australis have been the organisms most commonly responsible for infections in Vietnam. Infectious hepatitis. Table 5 lists the rates for infectious hepatitis observed among Army troops in R VN, Europe, and the United States in 1965 and 1966. All troops assigned to RVN in 1965 received immune human serum y-globulin (0.5 ml per lb body wt) on their arrival and again 4 or 5 months later. This practice was discontinued in April 1966. Throughout the remainder of t he year, the incidence of viral hepatitis remained stationary but in the first 6 months of 1967 it rose from 4.1 to 6.7 per 1000 average strength. A prospective study of the value of prophylactic immune human serum y-globulin for infectious hepatitis is now underway in Korea. Infectious hepatitis is usually a mild disease in RVN where it has been the practice to return troops to duty after clinical and laboratory evidence of recovery. Between July 1, 1966, and April 30, 1967, 208 patients with viral hepatitis were observed at the 6th Convalescent
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Hospital Center. The mean period of hospitalization was 46 days. Only 22 patients were evacuated: 12 for discharge, 4 for other medical problems, 4 because of deteriorating liver function after initial improvement, and 2 because of severe liver degeneration. 18 In its initial phase, falciparum malaria may simulate viral hepatitis. Nonimmune patients may develop jaundice suddenly (0.5%) and biopsies of their livers may reveal fatty degeneration, fatty necrosis, and some parenchymal cell destruction. However, the jaundice associated with malaria is usually due to red blood cell destruction and it can be distinguished from viral hepatitis by the presence of red cell schizonts, eosinophilia, positive serology, clinical course, and clinical response to antimalarial therapy. Peptic ulcer. H. W . Boyce (personal communication) estimated the annual cost of duodenal ulcer disease to the United States Army was 4Y2 million dollars. Duodenal ulcer disease is relatively common in RVN; indeed, the number of ulcer patients in hospitals often exceeded the combined number with amebic and bacillary dysentery. About 8% of these patients had a past history of ulcer disease. Summary
The gastrointestinal diseases encountered by the military in the Republic of South Vietnam serve to emphasize several important points. Among these is the observation that the bacterial diarrheas no longer rank as the major cause of morbidity (table 6). Undoubtedly, this change is due to improved bacteriological support and diagnostic capabilities within the field hospitals, to a greater understanding of the pathophysiology and treatment of these diseases, and to a greater awareness of the constant need for unit sanitation. Even the dread cholera, once a godrevered illness in Asia, has lost much of its mystery as a result of the intensive research directed against it and other bacterial diarrheas during the past two decades. These efforts have been rewarding but they have not vanquished the bacterial
July 1968
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DIGESTIVE DISEASE. VI
diarrheas and dysenteries. Indeed, the discovery that certain bacterial enteropathogens can transfer resistance factors is proof of their constant dangers. The recognition of nonspecific gastroenteritis and diarrhea as major causes of disability brings into focus how little we know about them. These are the same vague illnesses that strike the tourist, or sweep a community as "intestinal flu," or disrupt a factory as "viral enteritis"-so vague, indeed, that the viral origin of any of these entities is in debate and so obscure that repeated attempts to identify an etiological factor have usually failed. This fact stands in sharp contrast to identification of the bacterial, rickettsial, and viral agents responsible for 74% of fevers of undetermined etiology in field hospitals in RVN. The causes, mechanisms, and pathophysiology of the nonspecific enteritides are virtual blanks in our knowledge. Like the protozoal and parasitic enteritides, they lack glamor and they are not comparable in lethality to malaria; nonetheless, they are causes for enormous loss of duty time among the military services and for absenteeism in civilian life, and their appearance among combat units at a critical time can be disastrous. This is an area worthy of intensive study and research. The Medical Corps of the respective services have committed sizeable portions of their medical research funds for gastrointestinal research. The Army and Navy have each established research laboratories overseas specifically for the purposes of studying certain model gastrointestinal diseases (such as, cholera, tropical sprue, shigellosis, and schistosomiasis) that permit investigations of many parameters of bowel function. Some of the studies done in these laboratories have contributed significantly to our knowledge of intestinal function. Research funds have also been provided by the United States Army Medical Corps for the support of numerous civilian research projects concerned with infectious diarrhea ($1.2 million-fiscal year, 1969). In collaboration with a number of civilian institutions, the Army has also
6. Specified gastrointestinal diseases in comparison to fevers of undetermined origin: United States Army in Republic of South Vietnam (January-June 1967)
TABLE
Admissions
Food infection and poisoning ... Dysentery, bacillary and unspecified . Amebiasis. Other enteric infections. Infectious hepatitis. Serum hepatitis Fever, undetermined etiology .. ... .............
Rate/1000
34
0.25
169 471 6,610 892 8
1.22 3.41 47.87 6.46 0.06
10,022
72.58
undertaken a broad program designed to isolate and to characterize the virus or viruses responsible for infectious hepatitis, with the development of an effective vaccine as its ultimate goal. Army support for these two categories has been greatest because, in 1966 alone, diarrheal diseases and viral hepatitis, respectively, were responsible for 25,400 and 20,100 man days of hospitalization in RVN'. In an effort to develop a realistic gastrointestinal research program designed for their needs, the services have sought the guidance and advice of numerous senior civilian mvestigators. The generous advice and counsel of these men, many of whom serve as members of military advisory boards, have been invaluable and are essential to this end. REFERENCES 1. "Le Sr ~ rvicc De Sante En Indochine 19461954." 2. Hardy, A. V. 1967. Cmrent problems in the enteric infections. Mcd. Clin. N. Amer. 51: 609-615. 3. Deller, J. J., and P. K Russell. 1967. An analysis of fevers of unknown origin in American soldiers in Vietnam. Ann. Intern. Med . 66: 1129-1143. 4. Gaines, S., Nhu Tuan, Nguyen, Thi. 1966. Types and distribution of bacterial enteropathogens among diarrhea patients in Vietnam. Annual Progress Report, p. 65-81. U . S. Army Medical Research Team (WRAIR) , Vietnam, and Institute Pasteur of Vietnam.
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DIGESTIVE DISEASE. VI
5. Higgins, J . P., and C. D. Smith. 1967. Sensitivity of shigellae to various antibiotics. U. S. Army in Republic of South Vietnam. Med. Bull. 2: 53. 6. Philippines Cholera Committee. 1965. A controlled field trial of the effectiveness of cholera and cholera El T or vaccines in the Philippines. Bull. W. H. 0. 32 : 603-625. 7. Cifarelli, P. S. 1967. Acute amebic colitis. U. S. Army in Republic of South Vietnam Med. Bull. 2: 19-26. 8. Sheehy, T. W., L. F. Parmley, Jr., G. S. Johnston, and H. W. Boyce. 1968. Resolution time of an amebic liver abscess. Gastroenterology 55: 26-34. 9. Sheehy, T. W., and R. C. Reba. 1967. Complications of falciparum malaria and their treatment. Ann. Intern. Med. 66: 807-809. 10. Bartelloni, P. J., T. W. Sheehy, and W. D. Tigertt. 1967. Combined therapy for chloroquine-resistent plasmodium falciparum infection. J. A.M. A. 199: 173-177. 11. Spitz, S. 1946. The pathology of acute falciparum malaria. Milit. Surg. 99: 555-572.
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12. Sheehy, T. W., W. C. Cohen, D. K. Wallace, and L. J. Legters. 1965. Tropical sprue in North Americans. J. A.M. A . 194: 1069-1076. 13. Vandevelde, A. G. 1966. Hookworm epidemic in 1st. Cavalry Division. U. S. Army in Republic of South Vietnam. Med. Newsletter 1: 48-49. 14. Rodgers, A. M., and G. J. Dammin. 1946. Hookworm infection in American troops in Assam and Burma. Amer. J. Med . Sci. 211: 531-538. 15. Rowland, H. A. K. 1966. Dyspepsia, duodenitis and hookworm infection. Trans. Roy. Soc. Trop. Med . Hyg. 60 : 481-485. 16. Lindenbaum, J., T. H. Kent, and H . Sprinz. 1966. Malabsorption and jej unitis in American P eace Corps Volunteers in Pakistan. Ann. Intern. Med. 65: 1201-1209. 17. O'Brien, W., and M. W. J. England. 1966. Military tropical sprue from southeast Asia. Brit. Med. J . 2: 1157-1162. 18. Rogoway, W. M., and W. H. Bailey. 1967. Infectious hepatitis in Vietnam. U. S. Army in R epublic of South Vietnam. Med. Bull. 2: 12-14.