Antiviral Therapy: Respiratory Infections, Genital Herpes, and Herpetic Keratitis

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INFECTIONS AND ANTIBIOTICS

patients regained normal renal function after the drug was discontinued. The authors conclude that the syndrome of interstitial nephritis, renal failure and nephrotic range proteinuria caused by nonsteroidal anti-inflammatory drugs is potentially reversible, and they believe that it is mediated by cytotoxic T cells. This knowledge may be helpful in developing specific therapy for this condition, using monoclonal antibodies directed against T cell subsets. N. S. D. 3 figures, 3 tables, 35 references

Rapidly Progressive Glomerulonephritis in a Patient With Syphilis. Identification of Antitreponemal Antibody and Treponemal Antigen in Renal Tissue

P. D.

WALKER, E. C. DEEVES, G. SAHBA, J. D. WALLIN AND W. M. O'NEILL, JR., Departments of Pathology and

Internal Medicine (Nephrology), Tulane University School of Medicine, New Orleans, Louisiana Amer. J. Med., 76: 1106-1112 (June) 1984 The most common syphilitic nephropathic condition described is membranous glomerulonephritis, although mild proliferative glomerulonephritis also has been reported. However, the incidence of such renal involvement is extremely low. The authors present a hitherto unreported condition of rapidly progressive glomerulonephritis in a 45-year-old man with syphilis. The patient presented with oliguria, bilateral pedal edema, hypertension and lethargy. Urinalysis revealed massive proteinuria, microhematuria and many red blood cell casts. There was laboratory evidence of acute glomerulonephritis, renal insufficiency and syphilis. An open renal biopsy was performed to diagnose the type of the acute glomerulonephritis. The patient received short-term hemodialysis, penicillin, plasmapheresis and methylprednisolone. He improved rapidly, with stabilization of renal function, although he continued to have mildly elevated serum creatinine levels. Light microscopy of the renal biopsy material showed that 54 of the 58 glomeruli contained cellular crescents (93 per cent). The remaining glomeruli demonstrated mesangial and endothelial cell proliferation, and an infiltration of neutrophils. Electron microscopy demonstrated diffuse mesangial and endothelial cell proliferation. Immunofluorescent studies revealed diffuse deposits of lgG and C3 within the capillary loops and fibrinogen in the crescents. The elution studies revealed that citric acid buffer solution could eliminate completely immunofluorescent staining for IgG, and the resultant eluate demonstrated a 4+ reaction with Treponema pallidum. Furthermore, the sections stained with anti-treponemal antibody revealed 2+ granular deposits within the capillary loops. These findings are highly suggestive of the relationship between syphilis and rapidly progressive glomerulonephritis in this patient. N. S. D. 8 figures, 17 references

Antiviral Therapy: Respiratory Infections, Genital Herpes, and Herpetic Keratitis K. G. NICHOLSON, Infectious Diseases Unit, Department of Pharmacology and Therapeutics, Groby Road Hospital, Leicester, England

Lancet, 2: 617-621 (Sept. 15) 1984 As a group, viral upper respiratory tract infections remain a leading cause of acute morbidity and economic loss throughout

the world. Coryza and related symptoms are caused by a multitude of viruses and serotypes, some of which are unstable antigenically and most of which are uncontrollable by vaccination. The common cold and influenza have long been major targets for antiviral chemotherapy. This report summarizes data concerning influenza A and B, rhinovirus, coronavirus and respiratory syncytial virus infections, against which antivirals have distinct but limited efficacy. Amantadine and the structurally related compound rimantadine are effective in the prevention of illness caused by HlNl, H2N2 and H3N3 subtypes of naturally acquired and experimentally induced influenza A (but not influenza B) in man. Prophylactic efficacy has been reported in chronically sick and elderly patients (including those in the hospital) and in children, as well as in healthy adults. On the evidence of controlled studies in many thousands of patients amantadine and rimantadine are about 50 per cent effective in the prevention of infection but 70 to 100 per cent effective in the prevention or amelioration of illness: this distinction may be a desirable feature of prophylaxis, since subclinical infection could confer immunity against reinfection. Concern over side effects has cast doubt on the usefulness of amantadine and rimantadine. During an outbreak of influenza A with an attack rate of 5 to 20 per cent, prevention or amelioration of illness with amantadine is accomplished at the expense of minor central nervous system side effects in about the same numbers. Rimantadine is tolerated far better in this respect. Even so, treatment with either drug is restricted best to those at high risk of infection or its consequences. In the treatment of influenza B ribavirin small particle aerosol yields results similar to those in the treatment of influenza A. To date, benefit has been seen only in patients with symptoms less than 24 hours in duration who received 39 hours of treatment in a total of 60 hours. Respiratory syncytial virus: treatment. The therapeutic efficacy of ribavirin by aerosol has been evaluated further in adults infected with respiratory syncytial virus experimentally and infants infected naturally. In the adult volunteers ribavirin or placebo was started 2 days after intranasal inoculation with respiratory syncytial virus and was given for a total of 12 hours each day for 3 days. Ribavirin had no effect on minor upper respiratory tract symptoms (rhinitis, sore throat, sneezing and lymphadenopathy) but did reduce systemic complaints, cough and fever. The drug then was evaluated in a double-blind controlled trial in children 1 week to 2 years old who were hospitalized with respiratory syncytial virus pneumonia. Treatment was initiated a mean of 4½ days after onset of symptoms. Drug or placebo was administered almost continuously during 3 to 6 days into an infant oxygen hood, oxygen tent or inhalation tubing of a respirator at an estimated dosage of 0.82 mg./ kg. body weight per hour. Rhinovirus: prophylaxis. In 1973 Merigan showed that 1.4 X 107 units of partly purified interferon-a given as frequent nasal sprays during 4 days could reduce the symptoms and virus shedding resulting from experimental infection with rhinovirus type 4 on the second day. Several groups have confirmed its efficacy in preventing or ameliorating illness but its influence on the infection rate has varied. Rhinovirus: treatment. Various compounds, including a propanediamine interferon inducer for the treatment of infection due to rhinovirus and vitamin C for the common cold, have yielded disappointing results to date. There is anecdotal evidence that ribavirin by aerosol is useful in life-threatening para-influenza virus infection. A 6-month-

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INFECTIONS AND ANTIBIOTICS

shortened viral shedding and aided healing, and another showed no clinical benefit from 30 per cent idoxuridine in dimethyl sulfoxide for either primary or recurrent episodes. Topically administered 3 per cent vidarabine cream seems equally ineffective. Treatment with oral ribavirin (800 mg. daily for 10 days) reportedly reduces the severity of pain and new lesion formation but the results await confirmation. Similarly, topical 2-deoxyD-glucose, an inhibitor of envelope protein glycosylation, is said to accelerate recovery from initial infections, and reduce the frequency and severity of recurrent episodes of genital herpes, although this agent has no therapeutic efficacy in animal models of infection. G. P. M. 3 tables, 61 references Antiviral Therapy: Varicella-Zoster Virus Infections, Herpes Labialis and Mucocutaneous Herpes, and Cytomegalovirus Infections K. G. NICHOLSON, Infectious Disease Unit, Department of Pharmacology and Therapeutics, Groby Road Hospital, Leicester, England

Lancet, 2: 677-682 (Sept. 22) 1984 Primary infection with varicella-zoster virus causes chickenpox (varicella) and reactivation of the virus in dorsal nerveroot ganglia causes shingles. Both diseases are particularly severe in patients with subnormal immunity, in whom the complications include pneumonitis, encephalitis, hepatitis and disordered coagulation. Varicella-zoster virus vaccines are being evaluated but are unlikely to have much impact in the near future. Treatment in the immunocompromised host. Vidarabine, acyclovir and interferon-a all have had good trials in immunosuppressed patients with varicella. A total of 34 patients entered a trial of vidarabine, with disease less than 72 hours in duration. Compared to placebo, intravenous vidarabine (10 mg./kg. per day during 12 hours for 5 days) reduced the time during which new cutaneous lesions appeared (from a median of 5.6 to 3.8 days), accelerated the resolution of fever (p = 0.06) and diminished the incidence of varicella-related complications from 62 to 5 per cent. Passive immunization of exposed normal children with pooled human gamma globulin does not lower the attack rate of varicella but modifies its severity as indicated by fewer pocks and less fever. In contrast, zoster immune globulin protects normally susceptible children from infection if administered within 3 days of exposure. Because of the apparent benefit conferred by zoster immune globulin, investigations among high risk patients have been uncontrolled. Nevertheless, Zaia's review of 2,993 immunosuppressed children who received immune globulin after varicella exposure suggests strongly that passive immunization modifies the course of infection and prevents severe disease (The Human Herpesviruses: An Interdisciplinary Perspective. New York: Elsevier, 1981). The period between exposure and passive immunization seems critical, protection being much reduced when the delay is 5 days or more. There are no published data on chemoprophylaxis of varicella in normal or high risk subjects. Topical treatment. Opinions have differed on the efficacy of idoxuridine in dimethyl sulfoxide for treatment of uncomplicated herpes zoster. In 1 investigation dressings were soaked in a 40 per cent solution of idoxuridine in dimethyl sulfoxide or

in saline and garlic placebo, and applied continuously to the affected dermatome. The median duration of pain was reduced significantly by idoxuridine (from 14.5 to 3 days). Furthermore, 40 per cent idoxuridine applied in this manner provided more pain relief than 5 per cent idoxuridine applied intermittently but neither accelerated healing. In contrast, Wildenhoff and associates found that 40 per cent idoxuridine in dimethyl sulfoxide, although shortening the acute inflammatory response, had no effect on the duration of pain (Scand. J. Infect. Dis., 11: 1, 1979). These investigators then studied patients with trigeminal and thoracic zoster separately because of the differences in their natural history. In patients with thoracic zoster 40 per cent idoxuridine in dimethyl sulfoxide affected neither rate of healing nor duration of pain, whereas in those with trigeminal zoster healing and pain were improved greatly. Since the rate of healing and the duration of pain are related to sex, age, presence of fever and affected dermatome, it is possible that the conflicting judgments on the efficacy of different concentrations of idoxuridine could stem from mismatches between treatment and placebo groups. Irrespective of efficacy, the cost, side effects and inconvenience of topical treatment with idoxuridine limit its usefulness. Moreover, the use of dimethyl sulfoxide is restricted on safety grounds in some countries, including the United States. Primary herpes simplex virus type 1 infections of the mouth often cause no symptoms but may present as severe oropharyngeal ulceration, notably in young children. The infection later recrudesces in about 20 per cent of the immunologically normal population, usually in the form of a painful vesicular eruption at the mucocutaneous junction of the lips, which heals in 8 to 10 days. These same infections in the immunocompromised host account for considerable morbidity and the occasional death of prolonged, extensive oropharyngeal and esophageal ulceration, and viral dissemination to the lung or brain. G. P. M. 2 tables, 67 references Antiviral Therapy: Herpes Simplex Encephalitis, Neonatal Herpes Infections, Chronic Hepatitis B K. G. NICHOLSON, Infectious Diseases Unit, Department of Pharmacology and Therapeutics, Groby Road Hospital, Leicester, England

Lancet, 2: 736-739 (Sept. 29) 1984

Herpes simplex encephalitis. Herpes simplex virus is the most common cause of sporadic encephalitis in temperate climates. In newborns the disease is due to herpes simplex virus type 2 acquired during birth, whereas in infants, children and adults it usually is associated with type 1 virus (either primary or recurrent infection). In untreated cases of herpes simplex encephalitis the mean fatality rate is 70 per cent and many of the survivors are left with severe brain damage. As soon as a presumptive diagnosis of herpes simplex virus encephalitis has been made, acyclovir should be started in the aforementioned dosage and continued for 10 days or until an alternative diagnosis has been reached. Attempts should be made to confirm the diagnosis by serological means but the safety of acyclovir treatment is such that brain biopsy is not essential. In view of the efficacy of acyclovir against herpes simplex virus of other sorts, there' is a temptation to use it in cases of neonatal herpes. However, the decision is not straightforward,