Helicobacter pylori and chronic gastroduodenal disease

IIDN1

Infccti()us Diseases Newsletter Volume 9, Number 9, September 1990

Editor

Associate Editors

Charles W. Stratton, MD

Roger G. Finch, FRCP, MRC

Department of Pathology Vanderbilt UniversityMedical Center Nashville, Tennessee

Nottingham City Hospital Nottingham, United Kingdom

Path

R u t h M . L a w r e n c e , MD Veterans AdministrationOutpatient Clinic Sacramento, California

H. Bradford Hawley, MD

John T. Sinnott IV, MD

Wright State School of Medicine Dayton, Ohio

University of South Florida Tampa, Florida

R i c h a r d F. J a c o b s , MD Arkansas Children's Hospital Little Rock, Arkansas

Eontenl

Helicobacter pylori and Chronic Gastroduodenai Disease

Heficobacter pylori and Chronic Gastroduodenal Disease

Nicholas J. Talley, MB, PhD, FACP GastroenterologyResearch Unit, MayoClinic, Rochester, MN 65

Nicholas J. Talley

Helicobacter pylori (formerly Campylobacter pylori) is a gram-negative

Is Oral Acyclovir Effective in Preventing Postherpetic Neuralgia?

spiral-shaped bacterium that was first cultured in 1982. Since then there has been an explosion of data on the microbiology of this organism and its relation to gastroduodenal disease. However, it still remains controversial as to whether this organism is of clinical significance.

67

Mark H. Wilcox Roger G. Finch

CASE REPORT Hilda B. Ratner C O M M E N T S ON CURRENT PUBLICATIONS

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68

Microbiology H. pylori is found in a patchy distri70

bution overlying gastric or gastrictype epithelium; it is virtually never found on nongastric tissue. H. pylori has a smooth outer coating with four to six unipolar, sheathed flagella at one end; although it has some features in common with Campylobacter species, its exceptionally strong urease production, atypical protein content, unique fatty acid profile, and rRNA sequencing studies have led to the classification of this organism as a new genus.

The structural features of H. pylori may enable it to move easily in a corkscrew manner through the mucus layer, which is its preferred ecologic niche. H. pylori is susceptible to acid and cannot survive above the mucus layer; it has a strong affinity for gastric epithelium and tends to congregate around tight junctions of epithelial cells presumably because of increased access to nutrients at these sites. Ultrastructural studies have also indicated that H. pylori may be in intimate contact with surface mucus cells. H. pylori produces a number of enzymes and toxins. Urea amidohydrolase (urease) is particularly important; this may alkalinize the immediate environment around the organism and protect it. The organism also produces a mucolytic protease. Over 50% of H. pylori strains secrete an extracellular protein that produces nonlethal cytopathic effects such as vacuolation in mammalian tissue cul0278-2316 IDINDN9(9) 65-72, 1990

66 Infectious Diseases Newsletter 9(9) September 1990 ture cell lines; toxigenic strains may be associated with more severe disease.

Diagnosis At endoscopy, biopsies of the gastric mucosa can be obtained simply and safely; H. pylori can be identified histologically with sensitivity and specificity ranging from 85% to 100%. Culture remains the definitive gold standard, however, for establishing the diagnosis. H. pylori requires a warm, humid microaerophilic environment to propagate. To optimize culture results, gastric biopsy specimens need to be promptly placed in a transport solution, such as Stuart transport medium or 20% glucose, and should be transported to the microbiology laboratory preferably within 30 minutes. Culture is 100% specific and has a sensitivity ranging from 50% to 95% depending on the expertise of the particular laboratory. Culture allows antibiotic susceptibility to be evaluated; increasing resistance to metronidazole has been reported. Rapid urease tests are also available for biopsy samples; the biopsy can be placed in a urea solution with a pH indicator that changes color if urea is split by the organisms urease activity. This test has the sensitivity and specificity ranging from 80% to 100%. Noninvasive tests such as the C-13 or C-14 urea breath test and serologic tests have also been developed and are becoming routinely available. Epidemiology of H. pylori in Otherwise Healthy Persons Serologic studies have demonstrated that H. pylori is extremely common in the general population. In industrialized nations (including the United States [U.S.]), the prevalence of in-

fection increases with age; by the fifth decade approximately 20% to 40% of the population have antibodies to H. pylori. These data have been confirmed by endoscopic studies of asymptomatic volunteers. However, the prevalence does vary between regions in the U.S. This variability may partly reflect the ethnic background in different areas; for example, Hispanics in the U.S. have a higher seroprevalence than whites of similar age. The seroprevalence in nonindustrialized nations is strikingly greater than in industrialized countries with children in Third World countries being much more commonly infected. Although person-to-person transmission is suspected based on the higher prevalence of infection in institutionalized subjects and in family members of infected patients, this has not been established.

H. pylori and Gastroduodenal Disease Histologic Gastritis H. pylori is very strongly associated with the histologic presence of active chronic gastritis, where both polymorphonuclear and mononuclear cells are in excess of normal. There is now convincing evidence that H. pylori is of etiologic importance in gastritis and that Koch's postulates have been fulfilled. Moreover, eradication of the organism is associated with reversal of histologic gastritis to near normal, although this may take up to 1 year. Chronic Peptic Ulcer Disease H. pylori is strongly associated with chronic duodenal ulcer (DU); careful studies have suggested that over 95% of patients with DU have H. pylori

infection in the stomach. It has been postulated that H. pylori damages the duodenum by infecting islands of gastric epithelium that can be found in patients with duodenitis or DU; normal duodenal epithelium cannot be colonized by this organism. These islands of gastric metaplasia may be acquired as a conseqence of increased acidity in the duodenum. Preliminary data have shown that in patients with DU H. pylori infection is associated with increased meal-stimulated gastrin release that is reversed with eradication of infection; this suggests that H. pylori may be responsible for acid hypersecretion in this disease. Only a few small randomized controlled studies have specifically evaluated the relation between H. pylori status and ulcer relapse rates in patients with DU disease. The studies all reported DU relapse rates of approximately 80% at 1 year in patients with persistent H. pylori compared with approximately 25% in patients with no evidence of H. pylori after treatment. Although these preliminary data strongly suggest that H. pyIori plays an etiologic role in chronic DU disease, additional studies are required before this can be accepted. Indeed, H. pylori prevalence rates are high in the general asymptomatic population and most of these subjects never develop duodenal ulceration. It is also unclear why ulcer disease tends to come and go periodically whereas infection with H. pylori usually persists once established. There is a weaker association between H. pylori and chronic gastric ulceration. Approximately 60% to 70% of patients with chronic gastric ulcers have H. pylori gastritis, but it remains to be established whether H. pylori plays a role in the pathogenesis of this disease.

NOTE: No responsibility is assumed by the Publisher for any injury andJot damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. No suggested test or procedure should be carried out unless, in the reader's judgment, its risk is justified. Because of rapid advances in the medical sciences, we recommend that the independent verfication of diagnoses and drug dosages should be made. Discussions. views and recommendations as to medical procedures, choice of drugs and dnag dosages are the responsibility of the authors. Infectious Diseases Newsletter (ISSN 0278-2316) is issued monthly in one indexed volume per year by Elsevier Science Publishing Co.. Inc.. 655 Avenue of the Americas. New York, New York 10010 Printed in USA at Hanover, PA 17331. Subscription price per year: institutions. $148.00; individuals. $86.00. For postage outside the U.S., add $ 3 7 0 0 (Canada and Mexico require no additional postage). Second-class postage paid at New York. NY. and at additional mailing offices Postmaster: Send address changes to Infectious Diseases Newsletter Elsevier Science Publishing (!o I n c . 655 Avenue of the Americas, New York, New York IfX)IO. ~

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67 Infectious Diseases Newsletter 9(9) September 1990

Nonulcer Dyspepsia Many patients have ulcer-like symptoms that are not associated with demonstrable peptic ulceration; this has been termed nonulcer dyspepsia (NUD). Approximately 50% of patients with NUD also have H. pylori infection and associated gastritis. On the other hand, H. pylori is also very common in asymptomatic otherwise healthy subjects and no clear-cut symptom profile characterizes those with NUD with H. pylori infection compared with those with NUD without infection. Unfortunately, few studies have been performed using appropriate aged-matched asymptomatic controls. It therefore remains uncertain whether H. pylori plays a major role in the pathogenesis of NUD.

Therapeutic Approaches The treatment of H. pylori infection remains extremely problematic. The organism is sensitive to many antibiotics and bismuth therapy in vitro. Although the organism can be temporarily suppressed with either antibiotics or bismuth therapy, it is rarely eradicated using either alone. Combinations of bismuth and antibiotics have been tested, but significant side

effects have been reported (including C. difficile colitis) and eradication rates have been variable. The best results have been reported with a combination of bismuth, metronidazole, and amoxocillin or tetracycline for which eradication rates have exceeded 90%. It is unclear, however, whether such an aggressive therapeutic approach will be of significant clinical benefit for most patients. Only further controlled trials will help clinicians determine the best course of action. In the meantime, aggressive antimicrobial therapy directed against H. pylori remains inappropriate for those patients who are not enrolled in controlled therapeutic trials.

Conclusions There seems little doubt that H. pylori is the most common cause of histologic chronic gastritis and is highly prevalent in the general population. It also may play an important role in the relapse of chronic duodenal ulceration. H. pylori is often found in patients with gastric ulceration or NUD, but whether it is of pathogenic importance in these diseases remains unclear. Much more needs to be learned about H. pylori. Its reservoir, source,

Is Oral Acyclovir Effective in Preventing Postherpetic Neuralgia? Mark H. Wilcox, MD, Roger G. Finch, FRCP, MRC Path Clinical Microbiology Department, Nottingham City Hospital, Nottingham, United Kingdom

Acyclovir given intravenously to immunocompromised patients with herpes zoster (HZ) shortens the course of the disease, reduces acute pain, and helps to prevent serious complications. It appears more effective than vidarabine. However, immunocompetent patients with HZ do not normally require hospital admission and therefore drug treatment needs to be demonstrably effective when given

orally. In addition, oral therapy should be shown to prevent the often common and debilitating complication, postherpetic neuralgia (PHN). Corticosteroids have frequently been used to prevent PHN despite contradictory results of efficacy studies and their potential for complications. The results of three major trials from the United Kingdom (UK), United States (USA), and New Zea© 1990 Elsevier Science Publishing Co., Inc. 0278-2316/90/$0.00 + 2.20

and mode of transmission remain unknown. The incidence is not established; it is also unclear why infection rates appear to rise with increasing age. It has been suggested that some persons may spontaneously clear the bacteria whereas most do not, but this is not well defined. It is also unclear how the bacterium actually induces damage of the gastric epithelium. Finally, what constitutes optimal therapy is not defined and we lack clear cut indications of when and when not to treat.

Bibliography Dooley CP, Cohen H, Fitzgibbons PL, et al: Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 321:1562-1566, 1989. Graham DY: Campylobacterpylori and peptic ulcer disease. Gastroenterology 96:614-625, 1989. Levi S, Haddad G, Ghosh P, et al: Campylobacter pylori and duodenal ulcers: The gastrin link. Lancet 1:1167-1168, 1989. Ormand JE, Talley NJ: Helicobacterpylori: Controversies and an approach to management. Mayo Clin Proc 65:414426, 1990. Talley NJ: Chronic (nonerosive) gastritis: Pathogenesis and management. Dig Dis 7:61-75, 1989.

land (NZ) concerning the efficacy of oral acyclovir in the treatment of HZ in immunocompetent patients have recently been published. These provide convincing evidence that oral acyclovir has few side effects and does benefit such patients in terms of acute pain and healing when given within 72 hours of disease onset. However, recent promotional claims that acyclovir also "significantly reduces the chances of PHN," and is "the only treatment for shingles clinically proven to be effective in reducing the prevalence of PHN" have been viewed with skepticism. The evidence for these claims is reviewed here. The incidence of HZ is related to