Chapter 9
Venereal Diseases
Colonel John J. Deller, Jr., MC, USA (Ret.), Dallas E. Smith, M.D., David
T. English, M.D., and Edward G. Southwick, M.D.
HISTORY AND INCIDENCE
Venereal diseases have always played a major role in the history of military medicine. In the U.S. Army during World War I, they ranked second only to influenza as a cause of disability and absence from duty, being responsible for the loss of 6,804,818 days and the discharge of more than 10,000 men (Dunham 1923). During World War II, the incidence of VD varied widely among the theaters of operation. Between 1941 and 1945, worldwide incidence in the Army averaged 42.9 per 1,000 strength per year. This figure doubled during the postwar period (1946 to 1950) to 82.3 per 1,000 strength per year. With the troop buildup in Korea, the case rate once again doubled, to 184.0 per 1,000 average strength per year for the period 1951 to 1955. The incidence in American troops in Korea remained at a consistently high rate in the ensuing 10 years, exceeded only by that of American troops in Thailand (Greenberg 1972).
Similar high rates of venereal disease appeared in Vietnam as substantial troop concentrations occurred in 1963. The overall average incidence was 261.9 per 1,000 strength per year during the period of 1963 to 1970 (Greenberg 1972, p.1095). In comparison with other common diseases, venereal disease was the number one diagnosis from 1965 to the conclusion of the war, as reflected in monthly morbidity reports. Table 31 shows the incidence rates of all venereal disease in the Army, worldwide, in CONUS (continental United States), and in Vietnam, from 1963 to 1972. Table 32 gives the rates for the three general categories of venereal disease (gonorrhea, syphilis, and "other") as reflected in the USARV (U.S. Army, Vietnam) monthly morbidity reports.
These data reveal that approximately 90 percent of all venereal disease cases reported were cases of gonorrhea, as were the majority of hospitalized cases. However, despite the high prevalence of venereal disease, and especially of gonorrhea, only about 1 percent of all cases required hospitalization for treatment. The admission rates for all venereal diseases among Army personnel in Vietnam, compared with those worldwide and in CONUS, are shown in table 33. Most venereal disease cases were managed at division-level medical facilities, but the magnitude of the problem was such that significant numbers of patients required hospitalization for primary treatment of venereal disease or its complications.
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TABLE 31.-Incidence rates for all venereal diseases among U.S. Army personnel, 1963-June 1972 [Rates per 1,000 average strength per year]
TABLE 32-Incidence rates for types of venereal disease among U.S. Army personnel in Vietnam, 1963-June 1972 [Rates per 1,000 average strength per year]
Although the medical aspects of the venereal diseases will be emphasized in this chapter, it seems appropriate first to review the basic problems predisposing to high venereal disease rates--the obvious failure of adequate control measures.
CONTROL OFDISEASE
The control and management of venereal disease in the U.S. Army in recent years have been based upon five principal measures: education, prophylaxis,
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detection, early treatment, and suppression of prostitution. The earlier emphasis on punishment of the individual soldier or the unit commander has not in recent years been an acceptable policy.
The basic venereal disease policy of the armed forces at the time of the Vietnam war was published in a technical bulletin (TB MED). The degree to which the measures set forth in this document could be effected during a combat situation, however, remained a critical problem throughout the war. The overall case rate in Vietnam during the conflict was reportedly higher than that of any previous war (Greenberg 1972, p.1095).
One of the best documented studies attempting to resolve some of the problems of venereal disease control within a combat division was carried out in the 25th Infantry Division early in 1970 by Happer, Kerschbaum, and Reid.* The basic principles of venereal disease control, as set forth in Technical Bulletin 230 (TB MED), had been adhered to by personnel of the division. Troops were exposed to education programs on at least three separate occasions during their tour: an initial briefing upon arrival, an intensive lecture series from unit surgeons once they reached their unit assignment, and a subsequent briefing before departure on R&R (rest and recuperation) or leave. Despite this approach, venereal disease remained at a high level. To investigate the failure of VD control, questionnaires were completed for every case within the division during a 4-month study period; 465 cases were then reviewed. The distribution of types of venereal disease was comparable to that throughout the country (USARV-CHR): gonorrhea accounted for nearly 92 percent of the cases, syphilis for slightly less than 1 percent, and other venereal diseases for the remaining 7 percent. The study also revealed that 88 percent of all venereal disease oc-
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1 Lt. Col. Robert L. Reid, MC: Personal communication to Lt. Col. Andre J. Ognibene, MC, 1970.
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curred within the 18- to 24-year age group (which was the peak age range for assigned personnel). The risk of acquiring venereal disease increased with the length of time in the Republic of Vietnam, and combat support units were at highest risk. Within this particular division, Saigon and two base camps accounted for nearly 50 percent of the cases, while out-of-country R&R centers accounted for over 20 percent. Thus, not unexpectedly, the areas nearest large cities and of greatest troop concentration and least combat activity had the highest venereal disease rate.
Perhaps of greatest significance is that in this study venereal disease education was clearly shown to be ineffective. Only 12 percent of the patients claimed never to have been exposed to a VD education program. Nevertheless, 88 per cent did not use prophylactic measures in their index case and 25 percent never used prophylaxis. What the VD incidence would have been without any education program is impossible to predict. Obviously, well-organized programs do get information to nearly 90 percent of the troops; the problem is how to get the troops to apply the information which is imparted. Education alone apparently is insufficient and other means of control applicable to combat situations must be seriously considered.
In fact, careful evaluation of whether attempts to control venereal disease are worthwhile at all in combat situations is necessary before a future course can be decided upon. A brief review of the history of venereal diseases to date suggests that, despite advances in knowledge and therapies over recent years, the acquisition rate has doubled with each war since World War II. Yet, more importantly, the problem of noneffectiveness has been reduced with each war. From 1929 to 1939, the average time lost because of gonorrhea was 38 to 50 days per case (Greenberg 1972, p. 1099) while today the average time lost because of gonorrhea is but a few hours and only the rare case is complicated.
If continuing to "control" the incidence rate of venereal disease is deemed desirable, then more emphasis must be directed at the ultimate problem, the infected "camp follower," placing importance on regulation of prostitution. This course was attempted on occasion by a number of units in Vietnam but never received overt support and was carried out almost surreptitiously. Thus, data on the results of such an approach in recent times are not available. In the early 1900`s, control of prostitution was officially sanctioned in Cuba and the Philippines, but a change in the VD rate was not effected (Greenberg 1972, p. 1089). Yet, such an approach could be possible in the future, using modern techniques and stripped of the moral encumbrances of the past. Whether this would provide more effective control than the current method is unknown. These and other considerations must be realistically examined if we are not just to record history but to learn from it.
CLINICAL SPECTRUM
The method of recording venereal disease problems in the U.S. armed forces has generally been to divide them into three broad categories: gonorrhea, syphilis, and other venereal diseases. The category of other venereal diseases is
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one of great interest and importance, but gathering exact incidence figures is difficult because a number of diseases were reported together. The venereal diseases are discussed here in two general groups. Group 1 consists of those conditions which are primarily manifested by urethritis: gonorrhea, postgonococcal urethritis, nonspecific urethritis, and Reiter`s syndrome. Group 2 consists of those conditions in which urethritis is not a principal manifestation but in which penile lesions and/or inguinal adenopathy are the major presentations; within this group are lymphogranuloma venereum, chancroid, and syphilis.
Section I. Urethritis Syndromes
Colonel John J. Deller, Jr., MC, USA (Ret.), and Dallas E. Smith, M.D.
GONORRHEA
Etiology
The causative organism of gonorrhea is Neisseria gonorrhoeae, commonly referred to as the "gonococcus." This gram-negative diplococcus belongs to the same genus as the meningococcus. Although the organism is aerobic, it grows best when stimulated with carbon dioxide. Its requirements for growth and survival are stringent, making confirmation by culture techniques difficult, especially under conditions of field medicine. When the gonococcus dies, a highly irritant endotoxin is liberated, producing the purulent discharge and erosive balanitis which are the hallmarks of the clinical infection. Early in the course of infection, the organisms can be seen extracellularly in the urethral discharge and later within the polymorphonuclear leukocytes (Fiumara 1972).
Clinical Features
Clinical manifestations may occur from 1 day to 2 weeks following sexual contact, with an average incubation period for males of 3 to 5 days. The individual usually reports a penile "drip" as the first symptom, although on careful questioning, descriptions of variable sensations in the penis followed by frequent urination, with or without dysuria, are elicited. The discharge is generally cloudy white to creamy (fig. 61). Constitutional symptoms are usually absent in the early, uncomplicated case.
This overt presentation in the male is contrasted by the often silent disease (75 percent of cases) in the female. Early recognition and treatment are therefore more likely in the male. If the urethritis is neglected or inadequately treated, serious complications may occur. The infection may spread locally to involve the prostate, seminal vesicles, and epididymis, or it may produce septicemia with occasional gonococcal arthritis. This latter complication, seen frequently in general hospitals in CONUS, was rarely recorded in Vietnam Weller 1968). Gonococcemia can produce vesicular and pustular eruptions followed by
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petechiae similar to those seen in meningococcemia (Fiumara 1972). Meningitis also may occur but is quite rare and was not a recorded complication of gonococcal infection in Vietnam.
Laboratory Diagnosis
In the male with purulent urethral discharge, the diagnosis is not difficult. Gram`s stain of the urethral discharge will show the typical organism within polymorphonuclear leukocytes in nearly 98 percent of cases. Few laboratory procedures have such a fine record.
Ever since the recognition and designation of a group of organisms known as the tribe Mimeae (De Bord 1943), so named because of their similarity to the tribe Neisserieae in clinical, smear, and culture characteristics, concern has arisen that the "nonsophisticated" smear may be an inadequate means of diagnosing gonococcal urethritis. Moreover, since these organisms are not sensitive to penicillin (but rather to tetracyclines), "misdiagnosis" may account for some of the increasing resistance of Neisseria gonorrhoeae to penicillin. In 1967, 376 cultures of material from urethral discharges were performed at the 9th Medical Laboratory. (The results of the fresh Gram`s stains were not reported and no mention was made as to whether an appropriate "transgrow" medium was used to support the fastidious gonococcus during transport to the laboratory.) Two percent of these cultures grew members of the tribe Mimeae (Smith 1968a).
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Most recent studies (Schroeter and Pazin 1970; Holmes et al. 1967) fail to support the contention that these organisms constitute a serious problem in differential diagnosis and thus in accounting for "penicillin-resistant gonococci."
Treatment
After a quarter of a century of antibiotic therapy for N. gonorrhoeae infections, penicillin remained the drug of choice during the Vietnam conflict despite clear documentation of a slowly developing bacterial resistance to the drug. The average sensitivity of gonococcal strains from treatment failures was 0.1 units/ml in 1954; by 1969 it was 0.5 units/ml. During the same period, the MIC (minimal inhibitory concentration) of the most resistant gonococci increased from a high of 0.2 units/ml to 3.5 units/ml (Schroeter and Pazin 1970, p. 555).
This change in sensitivity of the gonococcus to penicillin required a gradual increase in single-dose therapy from 100,000 units before 1950 to 4.8 million units or more in Vietnam in 1970 (Schroeter and Pazin, p. 555). Concern over this problem, augmented by reports indicating that Southeast Asian strains of the gonococcus had even greater resistance than strains isolated from other geographical areas, led to several clinical trials of alternative methods of therapy (table 34).
TABLE 34.-Gonorrhea treatment schedules given clinical trials by the U. S. Army in Vietnam
From these data and studies done elsewhere, it appeared that a single large injection of procaine penicillin G (aqueous), 4.8 million units, plus probenecid to
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retard renal excretion of the penicillin, assured bactericidal blood concentration sufficient to eradicate 99 percent of the organisms. Evidence of even greater resistance did not develop until after cessation of hostilities.
Although only penicillin and tetracyclines received wide usage in Vietnam, other alternatives were available, such as erythromycin and cephaloridine. Recently two new treatment programs were added: doxycycline or minocycline given as a 100-mg capsule twice a day for 3 days; and spectinomycin given intramuscularly in a single dose of 4 g. This latter drug may be the alternate choice in penicillin-sensitive individuals and for penicillin-resistant organisms.
The treatment of the patient with gonorrhea cannot be considered complete unless the patient is reexamined immediately to detect primary treatment failures. Since a few patients in Vietnam with gonorrhea were also found to have syphilis (which may not be eradicated by some gonorrhea treatment schedules), a serologic test for syphilis should have been performed on every patient. Those with positive tests should have received appropriate therapy for syphilis and those with negative results should have had a repeat serologic test at the end of 4 to 6 weeks. Unfortunately, these ideal measures were difficult to effect in combat situations. The practice of providing 2.4 to 4.8 million units of procaine penicillin to patients with gonorrhea, however, effectively eliminated concomitantly acquired syphilis (table 35). The practice of self-administration of tetracycline, however, did little to abort late onset syphilis. Continuous education was needed at all levels to ensure that treatment was obtained from the appropriate medical authority.
TABLE 35.-Relativeefficacy of various schedules of therapy in aborting incubating syphilis 1
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POSTGONOCOCCALURETHRITIS
The syndrome of PGU (post gonococcal urethritis) has received little attention, despite its high prevalence, and very little was recorded about its incidence in the Army Command Health Reports from Vietnam. This was perhaps because of the imprecision of diagnosis and the lack of a firm definition of the syndrome. It remains unclear whether PGU represents persisting gonorrhea, a normal, gradual resolution of urethral inflammation after gonorrhea has been adequately treated, nongonococcal urethritis acquired coincidentally, or secondary infection by the normal urethral flora (Holmes et al. 1967).
Recent Studies on Possible Pathogenesis
The study by Holmes and coworkers (1967) raised two significant considerations concerning the possible etiology of this syndrome. First, a far greater number of cases of PGU were found in patients whose original gonococcal organisms demonstrated in vitro resistance than in patients whose organisms showed a more "normal" sensitivity pattern. Such an association could be taken as evidence that, although all the patients were treated "successfully" for their acute gonococcal urethritis with penicillin, a suboptimal dose (for the more resistant strains) could induce gonococcal L-forms which then might be responsible for the PGU syndrome. The second finding was that a definite relationship could be shown between PGU and the presence of urethral mycoplasma in patients initially treated with penicillin. It might thus be concluded that the simultaneous acquisition of mycoplasma and gonococcus organisms is frequent and that mycoplasmas may produce post gonococcal urethritis as a direct consequence of the concomitant urethral mucosal damage produced by gonorrhea itself. The accumulating evidence that much nonspecific (nongonococcal) urethritis may be caused by mycoplasma supports this contention.
Therapeutic Implications
If gonococcal L-forms are responsible for PGU, then low-dose penicillin regimens may induce the syndrome, especially when dealing with relatively resistant strains of N. gonorrhoeae. If mycoplasmas are acting as secondary in vaders and are responsible for PGU, no penicillin regimen, without a tetracycline, will be effective in eradicating this syndrome. More careful scrutiny of the cases during the immediate followup period will be required before the magnitude and importance of this syndrome can be clarified.
NONSPECIFICURETHRITIS
Etiology and Incidence
Data from the Army monthly morbidity reports are insufficient to define
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either the magnitude of the problem of NSU (nonspecific urethritis) or its etiology. Since Guiard`s original description (1897), there have been many studies in search of a cause of nonspecific urethritis, and a number of agents have been implicated. These include various bacteria and mycotic agents, Trichomonas vaginalis, TRIC (trachoma inclusion conjunctivitis) agent, and mycoplasma (King 1972). Studies in England and in U.S. naval personnel in the Philippines suggest that the incidence of NSU is at least equal to, if not greater than, that of gonococcal urethritis (Frederick 1972).
Clinical Course
Nonspecific urethritis usually presents in the male in "subacute" form, with a low-grade urethritis, variable dysuria, and a scanty mucopurulent discharge. The "acute" form is clinically indistinguishable from gonorrhea when a profuse urethral discharge, urinary frequency, and dysuria occur. The symptoms usually appear within 5 to 14 days after intercourse. Subclinical infection is thought to be common. Prostatitis is an infrequent complication. Association with Reiter`s syndrome will be discussed separately.
Diagnosis and Treatment
The diagnosis of NSU is one of exclusion. The Gram`s stain of the NSU exudates should reveal abundant polymorphonuclear leukocytes without gram negative intracellular diplococci and should be free of trichomonads and yeasts.
Nonspecific urethritis does not respond to penicillin therapy at any dose level. Most cases are treated with tetracycline, but as the entity probably has more than one causative factor, response to therapy is not always dramatic. Search for a specific agent is required. Many studies have attested to the superiority of tetracyclines over penicillin, placebo, and spontaneous remission with "cure rates" ranging from 59 to 94 percent (Frederick 1972). Both dosage and duration of therapy appear to be important in achieving a "cure": a minimum of 1 g per day in divided dosage for a minimum of 10 days is necessary. The best results from a particular treatment program were reported by John (1971). In a comparative study using 500 mg of oxytetracycline three times daily for 5 days, 500 mg four times daily for 10 days, and 250 mg four times daily for 21 days, he reported successes of 55 percent, 72 percent, and 87.5 percent, respectively, after 3 months. The longer the duration of therapy, the lower is the relapse rate.
The proven value of tetracycline therapy in the treatment of both PGU and NSU seems to strengthen the contention that mycoplasmas (cultured from significant numbers of patients with both these syndromes) may well be the major etiologic agent in these infections.
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REITER`S SYNDROME
History and Military Significance
Hans Reiter (1916) first described the triad of urethritis, arthritis, and conjunctivitis in young males in the German Army. Other manifestations, such as distinctive lesions of the buccal mucosa, of the glans penis (circinate balanitis), and of the skin (keratoderma blennorrhagicum) may also occur, singly or in varying combinations. Although the syndrome may appear following epidemics of shigella dysentery (Noer 1966), the vast majority of cases appear to be venereally transmitted.
Despite the importance of Reiter`s syndrome, it was rarely diagnosed in Vietnam. It was usually considered to be nonspecific urethritis and lumped into the "other venereal disease" category or was diagnosed as "nonspecific arthritis." Nevertheless, the syndrome was seen frequently in general hospitals to which patients were referred during the war years. Records kept by the medical consultant in 1969 revealed that up to 13 patients in a single month were evacuated because of manifestations of this syndrome."
Etiology
Because of the clear epidemiological evidence, an infectious cause of Reiter`s syndrome has long been sought. Reiter himself believed it was caused by a spirochete; later, mycoplasma seemed to be the most likely etiologic agent. More recently, evidence has suggested that a Bedsonia [Chlamydia] organism may be the agent (Schachter et al. 1966). However, precise data indicating the exact etiology (if a single agent is responsible) are not yet available. The common occurrence of mycoplasma in the normal urethra and its increased occurrence in patients with "pure" NSU suggest that this agent might be found in patients with Reiter`s syndrome, but whether it is causative remains questionable. The failure of tetracyclines to eradicate the disease can be used as evidence against this etiology. The theory that Bedsonia organisms cause the syndrome is supported by the fact that other Bedsonia infections may be transmitted venereally (TRIC agent urethritis and conjunctivitis, and lymphogranuloma venereum).
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Most of the material under "Reiter`s Syndrome" in this chapter is derived from the following article by the author(1968b): Reiter`s syndrome. Present Concepts Int. Med. 1:46-50.
* Lt. Col. Andre J. Ognibene, MC, USARV Medical Consultant 1969. Unpublished data.
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Clinical Features
The classic case of Reiter`s syndrome consists of the triad of arthritis, urethritis, and conjunctivitis, but most authorities agree that the diagnosis may be made in the absence of the complete triad, especially when mucocutaneous or other manifestations are present. The disease tends to be self-limited, with the average duration of the initial attack being 3 months. However, recurrence in 50 percent of cases studied has been reported by Csonka (1965), and a small percentage of these patients may develop permanent joint and visual disability.
Transient or recurrent nonspecific urethritis may be the initial manifestation. However, gonococcal urethritis is frequently seen in association with Reiter`s syndrome and the diagnosis must be suspected in the patient with arthritis and gonorrhea in whom urethritis and arthritis fail to respond to adequate penicillin therapy. The entire genitourinary tract may be involved, leading to simple cystitis, hemorrhagic cystitis, prostatitis, prostatic abscess, and, rarely, hydronephrosis and nephritis.
A mild, self-limited, bilateral conjunctivitis is the usual ocular manifestation. However, eye symptoms may be minimal and may not be readily volunteered by the patient. Anterior nongranulomatous uveitis may be the first in dictation of Reiter`s syndrome, but it usually follows repeated episodes and, in this setting, may be severe. Keratitis, corneal ulcerations, and cataracts have also been reported.
Arthritis is the most disabling aspect of the syndrome. It is an asymmetric polyarthritis most commonly involving joints of the lower extremities, although almost any joint in the body may be involved. Knees, ankles, toes, heels, and the Achilles tendon insertions are frequent sites. Swelling in the phalanges, similar to that seen in psoriatic arthritis, tends to involve the distal as well as the proximal joints and soft tissues, which gives rise to the phrase "sausage-like swelling." The true incidence of sacroiliac involvement is not known, but it has been reported in up to 50 percent of cases (Csonka 1965, p.147) and tends to be bilateral.
Mucocutaneous lesions are of great diagnostic importance and must be carefully looked for. Circinate balanitis is considered the most diagnostic of all lesions in this syndrome. This consists of discrete, round, shallow ulcers or hyperkeratotic lesions on the head or shaft of the penis (fig. 62). The lesions are asymptomatic and do not tend to become secondarily infected. A nonspecific stomatitis is also quite common. Finally, keratoderma blennorrhagicum, consisting of erythematous based vesicles or pustules, may appear anywhere on the skin but is most common on the palms and soles. Nail changes consisting of subungual accumulation of keratin, which makes the nail appear yellow, opaque, and elevated, may be seen and may result in loss of the nail. The pitting of the nail seen in psoriasis is absent, however (fig. 63).
Involvement of other organ systems has been covered in Csonka`s excellent review. Manifestations include cardiac conduction defects, aortic insufficiency, thrombophlebitis, pulmonary infiltrates, and peripheral neuritis, all of which are quite rare.
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Laboratory Findings
There are no characteristic laboratory findings in Reiter`s syndrome although an association with HLA-B27 (histocompatibility leukocyte antigen) has been demonstrated. The white blood count may be normal or show slight leukocytosis. The E.S.R. (erythrocyte sedimentation rate) may or may not be elevated. Sterile pus in the urine is found when urethritis or cystitis is present. Analysis of joint fluid shows acute inflammatory cells in the early stages and chronic inflammatory cells in the later stages of synovitis. The white blood cell count is seldom above 20,000 cells per cubic millimeter, and synovial fluid glucose is not markedly reduced as in bacterial pyarthrosis. Complement fixing antibodies to Bedsonia group antigen ("psittacosis titer") may be present in 37 percent of cases, and isolation of Bedsonia from urethra, conjunctiva, synovial fluid, and synovial membrane has been reported.
Roentgenograms of the feet and sacroiliac joints may be helpful. Erosions
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about the oscalcis at the region of the Achilles tendon and plantar fascia insertion, and periosteal new bone formation about the metatarsal shafts of the proximal phalanges are common. Loss of cortical margin of sacroiliac joints is an early sign of involvement of the joints and may precede by a considerable period of time the gross bony sclerosis and ankylosis characteristic of the later stages.
Treatment
Treatment, in the absence of a confirmed etiology, must be directed at symptomatic relief. Tetracycline has occasionally been beneficial in controlling urethritis, but the arthritis is not responsive. Salicylates, indomethacin, and phenylbutazone may be helpful in controlling acute synovitis, but because of spontaneous remissions, therapy is difficult to evaluate. The use of corticosteroids has given disappointing and irregular results and should be reserved for exceptional cases. Methotrexate has been reported to be effective in some cases (Jetton and Duncan 1969). Iritis, which may result in permanent visual impairment, should be treated by an ophthalmologist. The prognosis in Reiter`s syndrome is generally excellent and, despite even severe involvement, relatively few patients develop permanent disability.
Section II. Nonurethritis Syndromes
David T. English, M.D., Edward G. Southwick, M.D., and Colonel John J. Deller, Jr., MC, USA (Ret.)
LYMPHOGRANULOMAVENEREUM
Incidence and Etiology
LGV (lymphogranuloma venereum) is a systemic venereal disease caused by a member of the Bedsonia group, Miyagawanella [Chlamydia] lymphogranulomatosis. Incidence of LGV is increasing in the United States. Although no accurate statistics are available, recent studies (Abrams 1968; Schachter et al. 1969) indicate that part of this increase was caused by dissemination of the disease by soldiers returning from Southeast Asia. Of 20 patients studied at Letterman General Hospital in 1967-68,18 were recent Vietnam returnees (Abrams 1968).
Clinical Features and Course
After an average incubation period of 10 days, a small papule commonly develops on the external genitalia. This primary chancre is inconspicuous and is
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noticed in less than one-half of the cases(Costello and d`Avanzo 1948).
After a highly variable interval, from 1 week to 6 months, several syndromes ensue. The inguinal syndrome is most frequent in men and is the most common clinical picture of LGV. It is characterized by tender inguinal lymphadenopathy and systemic signs and symptoms. Some nodes have been misdiagnosed and surgically excised as hernias. The tender bubo is irregularly fluctuant. Its long axis is parallel to the inguinal ligament, which occasionally may separate matted groups of glands forming the pathognomonic "groove sign." Spontaneous rupture of fluctuant areas may occur through the overlying violaceous skin and form multiple fistulas (fig. 64).
The rectal syndrome, seen most often in women and male homosexuals, is characterized by a bloody mucopurulent discharge. Abdominal pain and constipation or diarrhea may coexist.
Systemic signs and symptoms accompany the inguinal more frequently than the rectal syndrome; these include fever, headache, weight loss, arthralgia, arthritis, meningismus, conjunctivitis, urethritis, hepatitis, and pneumonitis. Skin manifestations include erythema multiforme, erythema nodosum, scarlatini form eruptions, and a peculiar photodermatitis (Canizares 1954, pp.62-96; Abrams 1968, pp.201-2).
Untreated cases of LGV may resolve spontaneously in 8 to 12 weeks. However, the majority of untreated patients develop chronic complications. The
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rectal syndrome may progress to rectal fistulas, abscesses, or strictures. Such lesions are far more common in the female (Abrams 1968, p. 201). Strictures are associated with an increased incidence of carcinoma of the rectum (Levin et al. 1964). Both rectal and inguinal syndromes may lead to genital elephantiasis.
Laboratory Diagnosis
There may be a mild leukocytosis with a relative lymphocytosis or monocytosis. The E.S.R. is elevated and there may be reversal of the albuminglobulin ratio. A high incidence of false positive serologic tests for syphilis has been noted (Canizares 1954, pp.70-71, p. 82).
A positive Frei test (greater than 6 mm induration) occurs in 12 to 40 days and usually remains positive for many years and sometimes for life (Greenblatt, Dienst, and Baldwin 1959). A recent study (Schachter et at. 1969) revealed the Frei test to be insensitive compared to the CF (complement fixation) test (36 percent positive compared to 83 percent). There appears to be no correlation between the skin test reaction or the CF test and the severity of the disease (Abrams 1968).
Treatment
Drugs recommended include tetracyclines, sulfonamides, or both. Tetracycline 500 mg every 6 hours and sulfisoxazole 4 g loading dose and 500 mg every 6 hours were used for therapy in Vietnam. Bed rest and cool compresses offer supportive therapy (Abrams 1968). If bubo aspiration is necessary, an indirect lateral approach through adjacent normal skin greatly lessens the likelihood of the development of a persistent draining sinus. Surgery is required for chronic sequelae, but surgical drainage of the acute bubo is to be avoided.
CHANCROID
Etiology and Incidence
Chancroid is an ulcerating venereal infection caused by the gram-negative bacillus Haemophilus ducreyi. The disease is endemic in tropical climates and therefore was common in U.S. Armed Forces in South Vietnam. Because of the short incubation period of chancroid (2 to 5 days) and the short lapse in travel time from South Vietnam to CONUS (sometimes within 30 hours), many men who acquired the disease during the last few days or hours of their tour first presented with it in CONUS. The disease was second only to gonorrhea among venereal infections early in the war (Kerber, Rowe, and Gilbert 1969). Similar reports during the Korean war suggest that this experience was not unique (Asin 1952).
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Clinical Features
The initial sign of chancroid is a small, red papule which rapidly becomes pustular and then ulcerates (Rook, Wilkinson, and Ebling 1968, pp. 629-30) (fig.65). Often there are several ulcers. These ulcers are characteristically covered with a necrotic grayish exudate and surrounded by an erythematous halo. They are usually tender and painful, in contrast to those of syphilis. In order of frequency, the lesion occurs in the male in the prepuce, frenulum, penile shaft, and anus. In the female it occurs in the labia, clitoris, fourchette, vestibule, anus, and cervix. In about one-half of the cases, inguinal adenitis occurs about 1 week after the appearance of the ulcer. Typically, this is unilateral and painful and may suppurate (Olansky and Norins 1971, pp. 1978-80).
Diagnosis
The diagnosis of chancroid is usually made on a clinical basis rather than by attempting to demonstrate H. ducreyi because of the sometimes misleading or unreliable results obtained from the smears or cultures. Heyman, Beeson, and Sheldon (1945) consider the disease to be most easily and accurately diagnosed by biopsy. A granulomatous reaction is usually sufficiently distinct to permit a diagnosis of chancroid. Biopsy, however, is impractical in many situations. Furthermore, in 50 percent of the cases, a diagnosis can be made by staining a smear of material from an ulcer. Exudate from the undermined border of the ulcer is obtained on a sterile cotton-tipped applicator stick (Borchardt and Hoke 1970). By carefully rolling the stick 180 degrees in one direction (never back and forth)
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onto a glass slide and staining with Gram`s or methyl green-pyronine (Unna Pappenheim) stain, one can see the organisms. They are shown to occur in pairs and short chains and often are parallel to shreds of mucus. A positive culture, when it can be obtained, is the most reliable criterion for the diagnosis; however, this procedure is rarely used.
Kerber, Rowe, and Gilbert (1969) cultured lesions on rabbit and human blood, on EMB (eosin-methylene blue) agar, and on thioglycolate broth. In no instance could they specifically identify H. ducreyi. Deacon et al. (1956) used fresh human clotted blood as a culture medium and obtained positive results in only 18 of 62 patients. Borchardt and Hoke (1970) used heat inactivated serum obtained from a patient as the culture medium and obtained positive results in 21 of 24 patients. Formerly, the Ito-Reenstierna vaccine for skin testing was considered helpful in establishing a diagnosis, but this vaccine is no longer available. It consisted of killed H. ducreyi and, when injected intradermally, produced a reaction in active and remote cases.
The differential diagnosis includes herpes progenitalis which has become secondarily infected, traumatic ulcerations, and primary syphilis. Because syphilis infections may occur simultaneously with chancroid (the mixed ulcer) or subsequent to it, repeated darkfield examinations for Treponema Pallidum are indicated in every genital ulcer, even when the diagnosis of chancroid has been established. Follow up serological tests for syphilis are also indicated (Borchardt and Hoke 1970).
Treatment
The sulfonamides are effective and specific for chancroid. A dose of 4 g daily in divided doses for 7 to 14 days is generally adequate. Tetracycline has also been effective. However, in a study conducted on 90 consecutive patients at the 9th Medical Battalion, Bearcat, Vietnam, in 1968, Kerber, Rowe, and Gilbert (1969) found sulfisoxazole to be more effective than tetracycline, which was inadequate alone. They evaluated the combination of tetracycline and sulfonamide and concluded that it was effective as primary therapy or for the occasional patient who failed to heal promptly on sulfonamide alone.
Based on the study of Kerber et al., the basic regimen used through 1970 consisted of sulfonamide or sulfonamide-tetracycline combination. Marmar (1972), at the 24th Evacuation Hospital in 1970, treated 67 patients who were resistant to these drugs. These patients presented coronal or foreskin ulceration, inguinal adenopathy or abscess, and/or abscess of the penile shaft. Treatment consisted of kanamycin 500 mg twice daily for 6 to 14 days. The lesions were cleansed daily with povidone-iodine surgical scrub, and abscesses were drained by sterile aspiration. All patients responded, but the various lesions healed in differing periods of time. Storey, at the 93d Evacuation Hospital, utilized sodium cephalothin for a similar group of patients.
Resistant chancroid did not become a major disease problem. However, the potential of this disease for significant impact in tropical military operations remains.
252
SYPHILIS
Incidence
The available data from the 10 years of the Vietnam conflict indicate an overall incidence rate of approximately three cases of syphilis per 1,000 average strength per year. During the last 3 years of U.S. involvement (1970 through 1972), the hospital admission rate for syphilis was only 0.2 per 1,000 average strength per year (PAD) which is probably a fair estimate of the total admission rate for the 10 years based on the incidence rates. Thus, syphilis was not a significant medical problem, despite the high rate of gonorrhea and other venereal disease. Why this should have been remains somewhat of a mystery. This is not unique to Vietnam, however, for despite the rapid upswing in gonorrhea worldwide, the incidence of syphilis has barely risen.
Diagnosis
The classic features of primary and secondary syphilis are well recorded and need no further elaboration here. The important aspect to consider is that all patients with genital lesions of any type should have serologic tests to rule out the possibility of syphilis and repeated darkfield examinations (3 consecutive days) before institution of penicillin or broad-spectrum antibiotic therapy. One should suspect syphilis when a typical clean, well-demarcated chancre is found; however, there are many mixed infections (chancroid being the most common associated disease), and in tropical climes, there is often a secondary bacterial infection which masks the typical chancre. A similar alertness to the possibility of secondary syphilis must be maintained when one is confronted with almost any type of generalized skin eruption and, again, a serologic test for syphilis must be obtained (fig. 66).
The serologic screening tests in general usage in Vietnam were the VDRL (Venereal Disease Research Laboratory) slide test and the RPR (Rapid Plasma Reagin) test. In primary syphilis, the VDRL test usually becomes positive about 30 days after infection (7 to 10 days after appearance of a chancre), while the RPR test usually is positive about 14 days after infection.
Two problems may occur in the serodiagnosis of syphilis. First, if the test is done too early and not repeated, the diagnosis may be missed. Second, BFP (biologically false positivity) may occur with the commonly used reagin tests. If a specific treponemal antigen test is not employed for confirmation, a false diagnosis of syphilis may be made, and the disease inducing the BFP may be missed.
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254
In secondary syphilis, there is less problem with diagnosis, since the serologic test is always reactive. The problem of biological false positive reactions remains but can usually be clarified by a treponemal antigen test.
Treatment
The treatment of syphilis remains unchanged from the established therapeutic regimens outlined in Technical Bulletin 230 (TB MED, pp.7-13). The area of greatest concern is whether the low incidence of syphilis in association with the high incidence of gonorrhea in Vietnam can be partially attributed to inadequate follow up practices leading to missed diagnoses. Although it has been reported that in general the treatment schedules used in gonorrhea may also be curative for incubationary syphilis (Schroeter et al.1971), this remains questionable, especially in view of the variety of therapeutic regimens used in treating gonorrhea.
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