A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis.

Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in 601 patients with endoscopically and microbiologically documented esophageal candidiasis. Patients received intravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14-21 days). At the end of therapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found to be statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, -1.6%; 95% confidence interval, -4.1 to 0.8). The safety profile of anidulafungin was similar to that of fluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratory parameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazole for the treatment of esophageal candidiasis, when assessed at the completion of therapy.

Geographic differences in the distribution of intestinal metaplasia in duodenal ulcer patients.

OBJECTIVE: A strong correlation exists between atrophic gastritis and the intestinal type of gastric carcinoma. Duodenal ulcer disease characteristically has an antral predominant gastritis and a lower risk for gastric cancer. The aim of this study was to investigate the extent and distribution of intestinal metaplasia in duodenal ulcer in countries differing in gastric cancer incidence. METHODS: Topographically mapped gastric biopsy specimens (median 11) were obtained from patients with duodenal ulcer in four countries (Korea, Colombia, USA, and South Africa). Sections were stained with a triple stain and evaluated for Helicobacter pylori (H. pylori), active inflammation, and intestinal metaplasia. RESULTS: One hundred and sixty-five patients with duodenal ulcer were examined (29 from Korea, 52 from Colombia, 62 from the USA, and 22 from South Africa). The percentage of biopsies with intestinal metaplasia was significantly greater in Korean patients (86%) compared with that in other countries (50%) (p = 0.0004). Intestinal metaplasia was most prevalent in the antrum lesser curve and greater curve, and the body lesser curve. Intestinal metaplasia was present in the gastric corpus of 38% of duodenal ulcer patients from Korea compared with an average of 10% elsewhere (p = 0.018). No differences were observed in the density or distribution of H. pylori infection or in the degree of active gastritis between countries. CONCLUSIONS: Although antral predominant gastritis is the prevalent pattern of gastritis in duodenal ulcer, intestinal metaplasia in the gastric corpus may be found with geographic differences. These findings suggest that duodenal ulcer and gastric cancer are not mutually exclusive diseases but are rather ends of the spectrum of H. pylori infection.

Triple therapy with clarithromycin, omeprazole, and amoxicillin for eradication of Helicobacter pylori in duodenal ulcer patients in Asia and Africa.

BACKGROUND: Studies assessing the efficacy of triple therapy containing clarithromycin and amoxicillin for the eradication of Helicobacter pylori infection and healing of duodenal ulcers in Asian and African countries are limited. AIM: To determine the efficacy and safety of 1-week triple therapy with omeprazole, amoxicillin and clarithromycin for eradicating H. pylori infection in patients with active duodenal ulcer living in Asian and African regions. METHODS: This was an open-label, multicentre study in 11 centres in Asia and Africa. Patients with endoscopy-proven duodenal ulcer and who were H. pylori-positive were treated with clarithromycin 500 mg, omeprazole 20 mg, and amoxicillin 1000 mg, all given twice daily for 7 days. Upper endoscopy was repeated at week 6 to check for ulcer healing and H. pylori status. RESULTS: A total of 117 patients were recruited. H. pylori eradication rates were 85% by per protocol analysis and 80% by intention-to-treat analysis. Ulcer healing was found in 94% of subjects (per protocol analysis). Clinical success, measured by change of pre-treatment ulcer symptoms, was strongly supported by complete resolution or improvement in 100% of the evaluable patients (per protocol analysis). Since treatment-related adverse events, when present, were largely mild or moderate, the triple therapy regimen was considered safe. CONCLUSION: Seven-day triple therapy with omeprazole, amoxicillin, and clarithromycin was efficacious for treating Asian and African patients with duodenal ulcer disease associated with H. pylori infection, and the treatment regimen was well-tolerated.

Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis-a 2-year follow-up.

BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+-ATPase, necessary for the final step in gastric acid secretion. AIM: To assess safety and efficacy of oral pantoprazole (40 mg o.d.) used as a prophylaxis against relapse in patients with healed reflux oesophagitis during an open-label, 2-year study. METHODS: Outpatients (n=157) with healed stage II or III reflux oesophagitis (Savary-Miller classification) were enrolled into a long-term, multicentre maintenance study. Endoscopy was performed at entry into the study, after 12 and 24 months, or when disease-specific symptoms occurred on more than three consecutive days. Symptoms were assessed at 3-monthly intervals. Endoscopically confirmed relapses (at least stage I) were evaluated as treatment failures. RESULTS: Of the 178 adverse events, experienced by 88 (56%) patients (intention-to-treat population), 12 (7%) were assessed by the investigators as possibly related to the study medication. Median serum gastrin levels increased from a baseline of 46 ng/L to 90 ng/L, reaching a plateau after 9 months. For the intention-to-treat population the endoscopic remission rates after 12 and 24 months were 87% and 76%, respectively (Life-Table survival analysis, Kaplan-Meier). CONCLUSION: Pantoprazole 40 mg proved to be safe and efficacious during a 2-year prophylaxis treatment in patients with healed reflux oesophagitis.

Elevated adenosine deaminase activity in patients with HIV and tuberculous peritonitis.

OBJECTIVE: To evaluate the diagnostic potential of the ADA(T), ADA isoenzymes (ADA1 and ADA2) and the interferon-gamma (IFN-gamma) test in HIV-seropositive patients with tuberculous peritonitis. METHODS: Ascitic ADA(T), ADA1, ADA2 and IFN-gamma were prospectively evaluated in HIV-seronegative patients with tuberculous peritonitis (n = 17), HIV-seropositive patients with tuberculous peritonitis (n = 6) and in patients with cirrhosis (n = 22) and malignancy (n = 5). RESULTS: ADA(T) and ADA2 isoenzyme activities of HIV-seronegative (ADA(T) = 109 U/l; ADA2 = 94 U/l) and HIV-seropositive (ADA(T) = 109.5 U/l; ADA2 = 95.5 U/l) patients with tuberculous peritonitis, respectively, were significantly different (P < 0.001) from patients with cirrhosis (ADA(T) = 10.5 U/l; ADA2 = 8 U/l) and malignancy (ADA(T) = 13 U/l; ADA2 = 11 U/l). There was no significant difference in ADA(T) and ADA2 activities between HIV-seropositive and seronegative patients with tuberculous peritonitis. There was no significant correlation between ADA, its isoenzymes and IFN-gamma. CONCLUSIONS: The diagnosis of tuberculous peritonitis can be made by a sensitive, relatively non-invasive procedure in both HIV-seronegative and seropositive patients with minimal risk to the patient and the investigator. The diagnostic value of ADA(T) is not enhanced by measuring ADA isoenzymes or IFN-gamma.

Variable distribution of Cryptosporidium parvum in the intestine of AIDS patients revealed by polymerase chain reaction.

OBJECTIVE: Cryptosporidium parvum is associated with persistent diarrhoea and malnutrition in children, with large waterborne outbreaks and with the diarrhoea-wasting syndrome in AIDS. However, pathophysiology of infection remains to be defined and the reasons for the variability of clinical features are uncertain. The polymerase chain reaction (PCR) is valuable for the analysis of infections with non-culturable organisms because of its high sensitivity, so we compared PCR and microscopy as tools for the analysis of the distribution of infection. DESIGN: PCR was compared with light microscopy (LM) and electron microscopy (EM) in duodenal biopsies from a well characterized series of 75 Zambian AIDS patients. PCR and LM were then used to define the distribution of infection in biopsies from duodenum, ileum, right colon and left colon in eight South African patients with persistent AIDS-related cryptosporidiosis. RESULTS: PCR specifically detected 10 fg of genomic C. parvum DNA. When applied to duodenal biopsies from 75 Zambian AIDS patients, infection was detected in all seven cases of duodenal cryptosporidiosis that were identified by LM or EM and in six additional cases which appeared to be negative by microscopy. Distribution of infection was defined in six of eight South African AIDS patients. Two had pan-enteric infection, three had small bowel infection and one had purely ileo-colonic infection. In two cases infection could not be localized despite using PCR, suggesting that infection was confined to the inaccessible mid-small intestine. CONCLUSIONS: PCR detection of C. parvum DNA demonstrated that infection is highly variable in distribution, which must be taken into account when designing and interpreting studies of pathophysiology.

Seroepidemiological study of Helicobacter pylori infection in South African children.

The seroepidemiology of Helicobacter pylori infection was studied in 681 randomly selected Black children from newborn to 13 years of age (333 boys, mean age 8.05 years, and 348 girls, mean age 7.76 years) in KwaZulu/Natal, South Africa. H. pylori infection was identified serologically using an enzyme-linked immunosorbent assay to detect the presence of immunoglobulin G against H. pylori. Demographic information collected included age, gender, family income, overcrowding, educational level, and possession of domestic pets. The seroprevalence of H. pylori infection was compared to a known faecal-orally transmitted infection, hepatitis A virus (HAV); 66% of the children were seropositive for H. pylori. There was an age-specific increase in H. pylori infection, with more than 80% of children being infected by the age of 10 years. There was no significant difference (P = 0.338) in the seropositivity of H. pylori infection between boys (68%) and girls (64%), nor was there any significant difference in H. pylori infection related to pets, level of parents' education, crowding, and income, by either univariate or multivariate analysis. However, there was a significant association (P < 0.00001) between the seroprevalence of H. pylori and HAV infections, suggesting similar modes of transmission.

A trial of lansoprazole in refractory gastric ulcer.

BACKGROUND: The proton-pump inhibitor, lansoprazole, a more potent gastric acid inhibitor with a longer action than H2-receptor antagonists, should heal refractory gastric ulcers more effectively. METHODS: Lansoprazole's efficacy in healing refractory gastric ulcer(s) (i.e. after 6 weeks of treatment with H2-receptor antagonists, antacids or sucralfate at recommended dosages, and/or a relapse within 1 year of documented gastric ulcer), was compared by a two-dose regimen in a four-centre, randomized, parallel group study. One hundred and eighteen patients (59 per group) with an endoscopically confirmed gastric ulcer > or = 3 mm, received lansoprazole 30 or 60 mg daily. We assessed efficacy endoscopically at 4 and 8 weeks, and again after documented healing during a maintenance phase of lansoprazole 30 mg/day at 2 and 4 months. RESULTS: Demographic and anthropometric data were comparable. Healing rates at 4 weeks were 63% (30 mg) vs. 66% (60 mg) (95% CI, -14 to 21%) and cumulatively at 8 weeks, 83% (30 mg) vs. 81% (60 mg) (95% CI, -12 to 16%). Two and 4 months after documented healing, 86% and 78% of intention-to-treat patients remained in remission. CONCLUSION: Lansoprazole 30 or 60 mg/day appear equally effective in healing refractory gastric ulcers, while maintenance therapy of 30 mg/day effectively prevented an ulcer relapse.

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+-ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel-Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.

Hepatitis C virus infection in chronic liver disease in Natal.

The aim of this cross-sectional seroprevalence study was to determine the prevalence of antibodies to hepatitis C virus (HCV) (anti-HCV) in patients with cirrhosis, hepatocellular carcinoma (HCC) and chronic active hepatitis (CAH) attending a referral hospital in a hepatitis B virus (HBV)-endemic area in South Africa. One hundred and ten patients with suspected cirrhosis, 44 with suspected HCC and 6 with chronic hepatitis were initially included. The diagnoses were confirmed in 77 patients with cirrhosis (histologically or macroscopically at peritoneoscopy), 33 patients with HCC (histologically or elevated alpha-fetoprotein levels plus focal lesion on hepatic imaging) and 6 patients with CAH (histologically) without antinuclear antibodies. All patients were tested for anti-HCV with the Abbott second-generation enzyme immunoassay combined with a supplemental neutralisation assay, and hepatitis B surface antigen (HBsAg). Anti-HCV seroprevalence for cirrhosis, HCC and CAH were 18/77 (23%), 8/33 (24%) and 2/6 (33%) respectively. HBsAg was detected in serum in 16 (21%), 15 (46%) and 1 (17%) patient respectively. Only 1 patient (with cirrhosis) was positive for both anti-HCV and HBsAg. Of those who were anti-HCV-positive, 4/18 (22.2%) cirrhotics, none with HCC and 1/2 (50%) with CAH, had previously received blood transfusions, resulting in a cumulative frequency of 5/28 (18%). Our results indicate that HCV is an important aetiological agent in the pathogenesis of chronic liver disease in our patients. In the majority of patients (82%), the infection was not transfusion-related. Thus, screening of blood donors for anti-HCV would not prevent the majority of cases of chronic liver disease secondary to HCV. It appears as if HCV and HBV have different modes of transmission in southern Africa.

Ascitic fluid gamma interferon concentrations and adenosine deaminase activity in tuberculous peritonitis.

The gamma interferon (gamma-IFN) concentration and the adenosine deaminase (ADA) activity were evaluated in 30 patients with tuberculous peritonitis, 21 patients with ascites due to a malignant disorder, and 41 patients with cirrhosis. The gamma-IFN concentrations were significantly higher (p < 0.0001) in tuberculous peritonitis patients (mean: 6.70 U/ml) than in the malignant (mean: 3.10 U/ml) and cirrhotic (mean: 3.08 U/ml) groups. Use of a cut off value of > or = 3.2 U/ml gave the assay a sensitivity of 93% (25 of 27), a specificity of 98% (54 of 55), positive (P+) and negative (P-) predictive values of 96% and a test accuracy of 96%. The ADA activity was significantly (p < 0.0001) higher in the tuberculous peritonitis group (mean: 101.84 U/l) than in the control groups (cirrhosis (mean: 13.49 U/l) and malignancy (mean: 19.35 U/l)). A cut off value of > 30 U/l gave the ADA test a sensitivity of 93% (26 of 28) a specificity of 96% (51 of 53), a (P+) value of 93%, a (P-) value of 96%, and a test accuracy of 95%. There was a significant (p < 0.0001) correlation (r = 0.72) between ADA activity and gamma-IFN values in patients with tuberculous peritonitis. These results show that a high concentration of gamma-IFN in ascitic fluid is as valuable as the ADA activity in the diagnosis of tuberculous peritonitis. Both are rapid non-invasive diagnostic tests for tuberculous peritonitis.

Evaluation of the "one-minute" test for detecting Helicobacter (Campylobacter) pylori infection.

The "one-minute" urease test to detect Helicobacter (Campylobacter) pylori infection was evaluated using histology and culture as the "gold standard". The test was performed in a blinded manner and compared with the conventional Christensen's urease test. Helicobacter pylori was detected in 88 of 100 consecutive patients attending the gastrointestinal clinic for upper endoscopy. Although the "one-minute" urease test was more sensitive [86% (76/88)] than the conventional Christensen's urease test [70% (62/88)], this difference was not statistically significant (P = 0.22). Histology was the most sensitive [97% (85/88)] whilst culture was 80% (70/88) sensitive. All tests exhibited specifications of 100%. The "one-minute" urease test is a simple, rapid and highly specific test to detect Helicobacter pylori which can be performed at endoscopy.

Racial differences in the seroprevalence of hepatitis A virus infection in Natal/KwaZulu, South Africa.

The age- and race-specific seroprevalence of hepatitis A virus (HAV) infection was determined by radioimmunoassay (RIA) in 786 subjects between the ages of 6 months to 60 years. More than 50% of African children were seropositive by the age of 5 years. In blood donors (17-60 years), 50% (93/187) of Whites, 67% (110/163) of Indians, 85% (117/137) of Coloureds, and 91% (115/127) of Africans were seropositive. There was a significant difference in the seroprevalence of HAV infection between White blood donors and blood donors from the other three racial groups [Coloureds (P < 0.0001), Africans (P < 0.0001), and Indians (P < 0.001)] and between Indians and Coloureds (P < 0.0001) and Indians and Africans (P < 0.0001). There was no significance difference in HAV infection between Coloureds and Africans (P < 0.200). Eighty-seven per cent (32/37) of rural Africans had previous infection. In the African population HAV infection is acquired in childhood. There are significant racial differences in the seroprevalence of HAV infection. The surveillance of HAV infection may be used as a valuable yardstick to monitor the changing standards of hygiene and socioeconomic conditions of a community in transition in South Africa and to make rational public health decisions regarding a hepatitis A vaccination policy.

Hepatitis C virus antibodies among risk groups in a South African area endemic for hepatitis B virus.

The prevalence of anti-HCV was studied in a South African area endemic for hepatitis B virus. A total of 35,685 volunteer blood donors (22,034 whites, 9,218 Asians, 3,077 Africans, 1,356 coloureds), 71 haemophiliacs, 84 chronic dialysis patients, 100 antenatal attenders, 212 nurses, and 20 HIV-positive male homosexuals were tested for anti-HCV. Repeat positive second generation Ortho HCV EIA was used to determine HCV status for the blood donors; Abbott-II HCV EIA combined with a neutralisation test was used for the other risk groups. Antibody to hepatitis B core antigen (anti-HBc) was also tested in the haemophiliacs, nurses, and chronic dialysis patients. Seroprevalence for the blood donor population was 0.16, 0.34, 0.75, and 0.22% for whites, Asians, Africans, and coloureds, respectively. Of the risk groups tested, 39.4% of haemophiliacs and 4.8% of chronic dialysis patients were positive; of the remainder tested none was positive. Fifty percent of nurses, 47.9% of haemophiliacs, and 22.6% of dialysis patients had serological evidence of past exposure to hepatitis B virus (anti-HBc positive). These findings indicate a low prevalence of anti-HCV in the blood donor population, thus probably resulting in a low prevalence in groups exposed to blood and blood derivatives. The overall difference in prevalence between the race groups was significant (P < 0.0001). The high prevalence of hepatitis B virus compared to the low prevalence of HCV suggests that the main modes of transmission of the two viruses are probably different.

Asymptomatic intestinal colonization by pathogenic Entamoeba histolytica in amebic liver abscess: prevalence, response to therapy, and pathogenic potential.

Since the application of isoenzyme electrophoresis to the study of Entamoeba histolytica, the prevalence and natural history of asymptomatic intestinal colonization in patients with amebic liver abscess (ALA) has not been addressed. We prospectively evaluated this enteric phase in 50 patients with ALA, using two dosage regimens of metronidazole. The overall prevalence of asymptomatic colonization was 72% (36/50). All these isolates, without exception, proved to express pathogenic zymodemes. Despite a 100% clinical response of the hepatic lesions, failure to eradicate the organism from the bowel occurred in 20 of these 36 subjects. During longitudinal posttreatment surveillance, three carriers returned with second bouts of invasive disease: one with dysentery and two with liver abscesses. Thus, in patients with ALA, there is a high prevalence of intestinal colonization with exclusively pathogenic strains, and treatment with metronidazole frequently results in a continued carrier state. These carriers have a propensity for developing recurrent invasive disease and constitute a public health hazard.

Chronic pancreatitis with biliary obstruction.

In a 4-year review of 509 patients with chronic pancreatitis, the incidence of clinically manifest fixed common bile duct (CBD) stenosis was 9% (45 patients). In 76% this was alcohol related, and pancreatic calcification was present in 51%. All patients presented with unrelenting jaundice and five (11%) had cholangitis. The mean serum bilirubin (165 +/- 108, normal 0-17 mumol/l), alkaline phosphatase (1790 +/- 1143, normal 73-207 U/l) and gamma glutamyl transferase (798 +/- 660, normal 7-64 U/l) were markedly raised. Diabetes occurred in 8 (18%). A biliary drainage operation was performed in 43 patients and 11 had concomitant pancreaticojejunostomy. Endoscopic retrograde cholangiopancreatography (ECRP) provided valuable information preoperatively in outlining both biliary and pancreatic disease in selecting patients for dual ductal drainage. Minor complications not related to biliary anastomosis occurred in 14%. Four patients died (9%), two from pseudocyst-related haemorrhage. Jaundice was successfully relieved in all and did not recur during follow-up. No secondary biliary cirrhosis was encountered, but varying degrees of portal fibrosis were present in 75% of liver biopsies. The commonest biliary pathogen was E. coli. It is recommended that a biliary bypass operation be performed when the diagnosis is radiologically confirmed and no improvement occurs within 1 month.

Evaluation of various laboratory techniques to diagnose Helicobacter pylori in patients with upper gastro-intestinal tract symptoms.

Helicobacter (Campylobacter) pylori is strongly associated with type B gastritis. The detection of H. pylori, which entails histological examination and culture of gastric biopsy specimens, takes several days. There has been much interest in developing more rapid tests, including non-invasive ones. Using histology and/or culture as the 'gold standard', several methods to detect H. pylori were compared and evaluated. The organism was detected in 84 of 100 consecutive patients attending the Gastrointestinal Unit of King Edward VIII Hospital for upper gastrointestinal tract endoscopy. Histological examination was the most sensitive (98%) and specific (100%) method used in detecting H. pylori in gastric biopsy specimens. An enzyme-linked immunosorbent assay to detect specific IgG antibodies to whole H. pylori organisms is a moderately sensitive (82%), non-invasive method but it is nonspecific (38%). Although culture was specific (100%), it was less sensitive (68%) than histological examination. The 'conventional' urease assays must be performed under controlled conditions (37 degrees C) for optimal results (sensitivity, 71%).

Alterations in the cytological composition of the juxta-scar villous mucosa after ulcer therapy with sucralfate or cimetidine.

A comparative light-microscopic morphometric analysis of non-metaplastic mucosa obtained from the pretreatment juxta-duodenal ulcer (DU) villous mucosa of 10 patients and from the first part of the duodenum of 5 normal volunteers revealed a significant increase (P less than 0.01) in the number of goblet cells (GCs) per 100 microns of villous mucosa (GC/100 microns). Such an increase was thought to represent a mucoprotective response by the mucosa to the corrosive lumenal factors that may cause or maintain ulceration. A similar morphometric analysis was performed on the endoscopically healed juxta-scar villous mucosa of 11 patients successfully treated for 6 weeks with sucralfate (5 patients) or cimetidine (6 patients). After treatment with cimetidine, GC/100 microns was reduced to near-normal levels, whereas after sucralfate therapy it was significantly raised (P less than 0.05). The difference in GC/100 microns after treatment with either sucralfate or cimetidine was significant at the P less than 0.02 level. The apparent drug-mediated difference in the cytological composition of the healed mucosa was thought to be a function of the pharmacodynamic mechanisms of action of the two drugs in promoting DU healing. It is proposed that the retention of GC hyperplasia after curative therapy with sucralfate may predisposed patients so treated to extended periods of remission.