A. F. B. Cheng

Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus

BACKGROUND Human infection with an avian influenza A virus (subtype H5N1) was reported recently in Hong Kong. We describe the clinical presentation of the first 12 patients and options for rapid viral diagnosis. METHODS Case notes of 12 patients with virus-culture-confirmed influenza A H5N1 infection were analysed. The clinical presentation and risk factors associated with severe disease were defined and the results of methods for rapid virus diagnosis were compared. FINDINGS Patients ranged from 1 to 60 years of age. Clinical presentation was that of an influenza-like illness with evidence of pneumonia in seven patients. All seven patients older than 13 years had severe disease (four deaths), whereas children 5 years or younger had mild symptoms with the exception of one who died with Reyes syndrome associated with intake of aspirin. Gastrointestinal manifestations, raised liver enzymes, renal failure unrelated to rhabdomyolysis, and pancytopenia were unusually prominent. Factors associated with severe disease included older age, delay in hospitalisation, lower-respiratory-tract involvement, and a low total peripheral white blood cell count or lymphopenia at admission. An H5-specific reverse-transcription PCR assay (RT-PCR) was useful for rapid detection of virus directly in respiratory specimens. A commercially available enzyme immunoassay was more sensitive than direct immunofluorescence for rapid viral diagnosis. Direct immunofluorescence with an H5-specific monoclonal antibody pool was useful for rapid exclusion of H5-subtype infection. INTERPRETATION Avian Influenza A H5N1 virus causes human influenza-like illness with a high rate of complications in adults admitted to hospital. Rapid H5-subtype-specific laboratory diagnosis can be made by RT-PCR applied directly to clinical specimens.

Pathology of fatal human infection associated with avian influenza A H5N1 virus

Eighteen cases of human influenza A H5N1 infection were identified in Hong Kong from May to December 1997. Two of the six fatal cases had undergone a full post‐mortem which showed reactive hemophagocytic syndrome as the most prominent feature. Other findings included organizing diffuse alveolar damage with interstitial fibrosis, extensive hepatic central lobular necrosis, acute renal tubular necrosis and lymphoid depletion. Elevation of soluble interleukin‐2 receptor, interleukin‐6 and interferon‐γ was demonstrated in both patients, whereas secondary bacterial pneumonia was not observed. Virus detection using isolation, reverse transcription‐polymerase chain reaction and immunostaining were all negative. It is postulated that in fatal human infections with this avian subtype, initial virus replication in the respiratory tract triggers hypercytokinemia complicated by the reactive hemophagocytic syndrome. These findings suggest that the pathogenesis of influenza A H5N1 infection might be different from that of the usual human subtypes H1‐H3. J. Med. Virol. 63:242–246, 2001.

Antibacterial Treatment of Gastric Ulcers Associated with Helicobacter pylori

BACKGROUND There is a strong association between infection with Helicobacter pylori and gastric ulcers that are unrelated to the use of nonsteroidal antiinflammatory medications. We studied the efficacy of antibacterial therapy without medication to suppress gastric acid for the treatment of patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal agents. METHODS Patients with gastric ulcers seen on endoscopy and with H. pylori infection confirmed by smear or culture were randomly assigned to receive either a one-week course of antibacterial agents (120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, each given orally four times a day) or a four-week course of omeprazole (20 mg orally per day). Follow-up endoscopies were performed after five and nine weeks. The patients and their physicians were aware of the treatment assignments, but the endoscopists were not. RESULTS A total of 100 patients were randomly assigned to treatment, and 85 completed the trial. At five weeks, H. pylori had been eradicated in 41 of the 45 patients in the antibacterial-treatment group (91.1 percent; 95 percent confidence interval, 82.9 to 99.3) and in 5 of the 40 in the omeprazole group (12.5 percent; 95 percent confidence interval, 2.3 to 22.7; P < 0.001). The gastric ulcers were healed in 38 of the patients treated with antibacterial drugs (84.4 percent; 95 percent confidence interval, 73.9 to 95.0) and in 29 of those treated with omeprazole (72.5 percent; 95 percent confidence interval, 58.6 to 86.4; P = 0.28). At nine weeks, ulcer healing was confirmed in 43 of the patients receiving antibacterial therapy and in 37 of those receiving omeprazole (P = 1.0). The mean (+/- SD) duration of pain during the first week of treatment was 1.9 +/- 2.6 days in the omeprazole group, as compared with 3.6 +/- 3.0 days in the antibacterial-treatment group (P = 0.004). One year after treatment, recurrent gastric ulcers were detected in 1 of 22 patients (4.5 percent) in the antibacterial-treatment group and in 12 of 23 (52.2 percent) in the omeprazole group (P = 0.001). H. pylori was detected in the 1 patient with a recurrent ulcer who had received antibacterial treatment and in 10 of the 12 patients with recurrent ulcers who had received omeprazole. CONCLUSIONS In patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal antiinflammatory drugs, one week of antibacterial therapy without acid suppression heals the ulcers as well as omeprazole and reduces the rate of their recurrence.

Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial

Randomised trials have shown that duodenal ulcers treated by H2 blockers heal faster if Helicobacter pylori is eradicated concurrently. It remains unknown whether eradication of H pylori without suppression of acid-secretion, is sufficient to allow healing. 153 patients with H pylori infection and duodenal ulcer were randomised to receive either a 1-week course of bismuth subcitrate, tetracycline, and metronidazole (76), or omeprazole for 4 weeks with the same three-drug regimen for the first week (77). Endoscopy and antral biopsies were done at entry and 4 weeks after treatment. 132 patients were suitable for analysis. Duodenal ulcers healed in 60 (92%; 95% CI 86-100%) patients taking bismuth, tetracycline, and metronidazole compared with 63 (95%; 88-100%) taking omeprazole in addition to the three other drugs. H pylori was eradicated in 61 (94%; 88-100%) who received only three drugs compared with 66 (98%; 96-100%) who received omeprazole as well. Symptoms were reduced more effectively during the first week in patients who received omeprazole (p = 0.003). We conclude that a 1-week regimen of bismuth, tetracycline, and metronidazole for patients with H pylori and duodenal ulcer eradicates the organism and heals the ulcer in most patients. Concurrent administration of omeprazole reduces ulcer pain more rapidly but has no effect on ulcer healing.

Hong Kong strains of methicillin-resistant and methicillin-sensitive Staphylococcus aureus have similar virulence

While most authorities agree that methicillin-resistant Staphylococcus aureus (MRSA) are as pathogenic as methicillin-sensitive strains (MSSA), some believe that MRSA are relatively avirulent opportunists, and that their importance has been exaggerated. We present evidence that Hong Kong strains of MRSA and MSSA are equally pathogenic: they have similar virulence in animal models; they are isolated in similar proportions from both deep and superficial clinical sites including blood; in patients with hospital-acquired bacteraemias mortality rates are similar when adjusted for clinical factors; and in both animals and patients with systemic MRSA infection, mortality rates are significantly reduced by vancomycin therapy. Efforts to control the spread of MRSA are justified, and in invasive sepsis early treatment with vancomycin may be life-saving.

SARS Transmission among Hospital Workers in Hong Kong

Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection.

Multiplex PCR Amplimer Conformation Analysis for Rapid Detection of gyrA Mutations in Fluoroquinolone-Resistant Mycobacterium tuberculosis Clinical Isolates

ABSTRACT A new strategy known as multiplex PCR amplimer conformation was developed for detection of mutation in the gyrA gene of 138 clinical isolates of Mycobacterium tuberculosis. The method generated a single-stranded and heteroduplex DNA banding pattern of multiplex PCR amplimers of the region of interest that was extremely sensitive to specific mutations, thus enabling much more sensitive and reliable mutation analysis compared to the standard single-stranded conformation polymorphism technique. The genetic profiles of the gyrA gene of the 138 isolates as detected by MPAC were confirmed by nucleotide sequencing and were found to correlate strongly with the in vitro susceptibilities of the mutant strains to six fluoroquinolones (ofloxacin, levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, and sitafloxacin). All 32 isolates that contained gyrA mutations exhibited cross-resistance to the six fluoroquinolones (ofloxacin MIC for 90% of strains > 16 mg/liter), although moxifloxacin, gatifloxacin, and sitafloxacin (MIC for 90% of strains ≤ 4 mg/liter) were apparently more active than ofloxacin, levofloxacin, and sparfloxacin (MIC for 90% of strains ≥ 16 mg/liter). All gyrA mutations were clustered in codons 90, 91, and 94, and aspartic acid 94 was most frequently mutated. Twenty-three isolates without gyrA mutations were also found to exhibit reduced susceptibility to ofloxacin (MIC for 90% of strains = 4 mg/liter), but largely remained susceptible to other drugs (MIC for 90% of strains ≤ 1 mg/liter). Another 83 isolates without mutations were fully susceptible to all six fluoroquinolones (ofloxacin MIC for 90% of strains = 1 mg/liter). In conclusion, high-level phenotypic resistance to fluoroquinolones among M. tuberculosis clinical isolates, which appears to be predominantly due to gyrA mutations, may be readily detected by genotyping techniques such as multiplex PCR amplimer conformation.

Randomised controlled trial of short term treatment to eradicate Helicobacter pylori in patients with duodenal ulcer.

OBJECTIVE--To determine whether one weeks drug treatment is sufficient to eradicate Helicobacter pylori in patients with duodenal ulcer. DESIGN--Single blind, randomised controlled trial. SETTING--Specialised ulcer clinic in a teaching hospital. PATIENTS--155 patients with H pylori and a duodenal ulcer verified endoscopically which had either bled within the previous 24 hours or was causing dyspepsia. INTERVENTIONS--Patients were allocated randomly to receive either omeprazole for four weeks plus bismuth 120 mg, tetracycline 500 mg, and metronidazole 400 mg (all four times a day) for the first week (n = 78), or omeprazole alone for four weeks (n = 77). Further endoscopy was performed four weeks after cessation of all drugs. MAIN OUTCOME MEASURES--Presence or absence of H pylori (by urease testing, microscopy, and culture of antral biopsy specimens), duodenal ulcer, and side effects. RESULTS--Eradication of H pylori occurred in 70 (95%) patients taking the four drugs (95% confidence interval 86% to 97%) compared with three (4%) patients taking omeprazole alone (1% to 11%). Duodenal ulcers were found in four (5%) patients taking the four drugs (2% to 12%) and in 16 (22%) patients taking omeprazole alone (14% to 32%). Mild dizziness was the only reported side effect (six patients in each group) and did not affect compliance. CONCLUSIONS--A one week regimen of bismuth, tetracycline, and metronidazole is safe and effective in eradicating H pylori and reduces the number of duodenal ulcers four weeks after completing treatment.

REPEATED PREVALENCE SURVEYS FOR MONITORING EFFECTIVENESS OF HOSPITAL INFECTION CONTROL

In a 1400-bedded teaching hospital single-day prevalence surveys of hospital infection were done every six months for 3 years. The prevalence of community-acquired infection remained constant; but, after the introduction of a general infection-control policy, the prevalence of hospital-acquired infection (HAI) fell linearly from 10.5% in the second survey to 5.6% in the last. After the introduction of a specific urinary catheter care policy, the prevalence of hospital-acquired urinary tract infection (HAUTI) fell from 3.2% in the first four surveys to 2.0% in the last three. These differences persisted when the results were adjusted by logistic regression for patient risk factors, which varied between surveys: the declines for HAI and HAUTI were then 9.9% to 6.0% and 2.9% to 2.2% respectively. Infection control policies, therefore, can have substantial impact on the prevalence of HAI, and their effectiveness can readily be measured by repeated prevalence surveys.

Evaluation of the VITEK 2 System for Rapid Direct Identification and Susceptibility Testing of Gram-Negative Bacilli from Positive Blood Cultures

ABSTRACT This study explores the possibility of combining the BacT/Alert Microbial Detection System with the VITEK 2 system to achieve rapid bacterial identification and susceptibility testing. Direct inoculation of bacterial suspension to the VITEK 2 ID-GNB card and AST-NO09 card was made by differential centrifugation of blood cultures of organisms with gram-negative enteric bacillus-like morphology. A total of 118 strains were investigated; of these, 97 (82.2%) strains were correctly identified to the species level and 21 (17.8%) strains were not identified; by comparing the results with those of the reference method of API identification systems using a pure culture, it was found that no strain had been misidentified. Among the 21 strains with no identification, 13 (61.9%) strains were nonfermenters. The direct-identification reporting time of VITEK 2 was 3.3 h. Direct testing of susceptibility to 11 antibiotics, i.e., amikacin, cefepime, ceftazidime, ciprofloxacin, gentamicin, imipenem, meropenem, netilmicin, piperacillin, piperacillin-tazobactam, and tobramycin, was also performed by using the broth microdilution (MB) method according to the NCCLS guidelines as a reference. After comparing the MICs of the VITEK 2 system with those obtained by the MB method within ±twofold dilution, it was determined that the 1,067 organism-antibiotic combinations had an overall correct rate of 97.6% (1,041 combinations). The rates of susceptibility to the 11 antibiotics ranged from 88.7 to 100%, respectively. Only two (0.2%) and four (0.4%) combinations of the susceptibility tests gave very major errors (i.e., reported as sensitive by the VITEK 2 system but shown to be resistant by the MB method) and major errors (i.e., reported as resistant by the VITEK 2 system but shown to be sensitive by the MB method), respectively. The reporting time for the direct testing of susceptibility against the 11 antibiotics for 97 blood culture isolates by the VITEK 2 system ranged from 3.3 to 17.5 h. Compared with conventional methods that require 1 or 2 days, this method can make same-day reporting possible and thus permit better patient management.