Role of serology in monitoring treatment for 'Helicobacter pylori' infection in elderly patients

Age and Ageing,  July, 1993  by A.F. Safe,  B. Warren,  A. Corfield,  C.A. McNulty,  B. Watson,  R.A. Mountford,  A. Read

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Introduction

Several reports have confirmed the link between Helicobacter pylori infection and the recurrence of duodenal [1, 2] and gastric ulcers [3]. Recently, eradication of H. pylori infection has been proposed as the mainstay of peptic ulcer treatment [4]. Several studies have shown that after eradication of H. pylori, ulcers only returned after the patients became reinfected with the bacteria [5, 6]. Repeated endoscopy to monitor treatment is expensive and undesirable for the patients and a noninvasive method would be preferable. Urea breath tests are useful in this role but they require very expensive equipment ([C.sup. 13] urea) or involve a small radiation dose ([C.sup. 14 urea). Serological tests may be useful for monitoring treatment [7, 8].

Two groups of elderly patients (treated and untreated for H. pylori infection) were followed up for 3 months to assess whether monitoring for treatment by serology was informative with regard to eradication of H. pylori infection.

Patients and Methods

Fifteen elderly patients with dyspeptic symptoms and H. pylori detected by histology were treated with triple therapy consisting of amoxycillin 500 mg TDS, metronidazole 400 mg TDS for 14 days and de-Noltab (tripotassium dicitratobismuthate 20 mg) two tablets bd for 28 days. All patients had significantly raised serum IgG antibodies against H. pylori determined by ELISA. The patients were followed up and their serology repeated after 6 weeks and 3 months. They also had repeated endoscopy after 3 months. On each endoscopic examination, biopsies were taken, two from the antrum and two from the gastric body. These were stained with modified Giemsa stain and biopsies were cultured using nitrogen atmosphere containing 8%, C[O.sub.2] and 6% [O.sub.2] for 5 days. The bacteria were identified as H. pylori on the basis of their morphology, oxidase, catalase and urea production.

Fifteen patients with H. pylori positive gastritis (matched for age and sex) (Table I), who received no antibacterial treatment, were also followed up by means of serology. This group served as a control group and received [H.sub.2] antagonist treatment.

Results

One of the treated group failed to attend the follow-up appointment and was withdrawn. Eradication treatment was confirmed by culture and histology in 12 treated patients (85%). In the control group, two patients failed to keep the follow-up appointments. The characteristics of the two groups are shown in Table I.

Table I. Clinical details of the patients
                    Treated group      Control group
Age mean (range)     73 (65-83)         74 (62-85)
M:F                  6:9                5:10
No. of smokers       4                  5
  Statistical analysis: Results are presented as
medians with quartiles. The results of the two group
were compared using the Wilcoxon signed rank test
for paired nonparametric data (C stat statistical
package).

The eradication regimen was tolerated by most of the patients but five patients developed nausea and diarrhoea. These symptoms were mild and stopped when treatment ended. Renal functions were monitored for all the patients for 3 months after treatment and showed no deterioration.

The ELISA results for specific IgG anti-H. pylori antibodies in the triple therapy and in the control groups are shown in Table II. There was a significant decrease in IgG titre in the treated group after 3 months compared with the untreated group (Z--3.06, p[equals]0.002). The dyspeptic symptoms improved in ten patients.

Table II. Medians (Med) and interquartile range
(IQR) of antibody titres in treated and control
groups, before treatment and at 6 and 12 weeks
                       Treated          Control
                    Med      IQR     Med      IQR
Before treatment    81      60-101   96      75-110
6 weeks             42      22-49    94      72-112
12 weeks            17      10-28    96      70-110

Discussion

Several reports have shown that specific anti-H. pylori antibodies decrease following eradication treatment [7, 9]. Our results showed a similar pattern in the elderly patients. Although anti-H. pylori IgG antibodies remain raised after successful treatment, there is a marked and consistent fall in antibody levels. This fall is usually detectable by 1 month after treatment but is most reliable by 3 months [7]. The fall of specific IgG antibodies over a 3-month period from the start of treatment is a good predictor of successful therapy [7, 8]. Follow-up studies of longer than 12 months are needed to establish whether a true serological cure of H. pylori infection is possible and whether it will result in normalization of specific antibodies in all patients.

Graham et al. studied the in-vivo susceptibility of H. pylori to various drugs [10]. It was susceptible to bismuth subsalicylate, bismuth subcitrate and furazolidone but not to anti-ulcer agents (cimetidine, ranitidine, misoprostol and sucralfate), NSAIDs or oral penicillin. Various eradication regimens have been proposed. The most widely used eradication regimen consists of amoxycillin or tetracycline 500 mg four times a day, metronidazole 400 mg three times a day and tripotassium dicitratobismuthate 20 mg two tablets twice daily for 14 days. Eradication results vary from 60% to 95% [11, 12]. Success depends on the patient's compliance and bacterial resistance to metronidazole [13]. Metronidazole resistance is seen more in women who have been exposed to the drug for gynecological infections [14]. Shorter courses of triple therapy may overcome some of the problems of poor compliance which may occur with unpleasant medications [15], but large prospective studies are needed to assess efficacy.