How to determine life expectancy change of air pollution mortality: a time series study.

BACKGROUND: Information on life expectancy (LE) change is of great concern for policy makers, as evidenced by discussions of the "harvesting" (or "mortality displacement") issue, i.e. how large an LE loss corresponds to the mortality results of time series (TS) studies. Whereas loss of LE attributable to chronic air pollution exposure can be determined from cohort studies, using life table methods, conventional TS studies have identified only deaths due to acute exposure, during the immediate past (typically the preceding one to five days), and they provide no information about the LE loss per death. METHODS: We show how to obtain information on population-average LE loss by extending the observation window (largest "lag") of TS to include a sufficient number of "impact coefficients" for past exposures ("lags"). We test several methods for determining these coefficients. Once all of the coefficients have been determined, the LE change is calculated as time integral of the relative risk change after a permanent step change in exposure. RESULTS: The method is illustrated with results for daily data of non-accidental mortality from Hong Kong for 1985 - 2005, regressed against PM10 and SO2 with observation windows up to 5 years. The majority of the coefficients is statistically significant. The magnitude of the SO2 coefficients is comparable to those for PM10. But a window of 5 years is not sufficient and the results for LE change are only a lower bound; it is consistent with what is implied by other studies of long term impacts. CONCLUSIONS: A TS analysis can determine the LE loss, but if the observation window is shorter than the relevant exposures one obtains only a lower bound.

Part 5. Public health and air pollution in Asia (PAPA): a combined analysis of four studies of air pollution and mortality.

BACKGROUND: In recent years, Asia has experienced rapid economic growth and a deteriorating environment caused by the increasing use of fossil fuels. Although the deleterious effects of air pollution from fossil-fuel combustion have been demonstrated in many Western nations, few comparable studies have been conducted in Asia. Time-series studies of daily mortality in Asian cities can contribute important new information to the existing body of knowledge about air pollution and health. Not only can these studies verify important health effects of air pollution in local regions in Asia, they can also help determine the relevance of existing air pollution studies to mortality and morbidity for policymaking and environmental controls. In addition, the studies can help identify factors that might modify associations between air pollution and health effects in various populations and environmental conditions. Collaborative multicity studies in Asia-especially when designed, conducted, and analyzed using a common protocol-will provide more robust air pollution effect estimates for the region as well as relevant, supportable estimates of local adverse health effects needed by environmental and public-health policymakers. SPECIFIC OBJECTIVES: The Public Health and Air Pollution in Asia (PAPA*) project, sponsored by the Health Effects Institute, consisted of four studies designed to assess the effects of air pollution on mortality in four large Asian cities, namely Bangkok, in Thailand, and Hong Kong, Shanghai, and Wuhan, in China. In the PAPA project, a Common Protocol was developed based on methods developed and tested in NMMAPS, APHEA, and time-series studies in the literature to help ensure that the four studies could be compared with each other and with previous studies by following an established protocol. The Common Protocol (found at the end of this volume) is a set of prescriptive instructions developed for the studies and used by the investigators in each city. It is flexible enough to allow for adjustments in methods to optimize the fit of health-effects models to each city's data set. It provides the basis for generating reproducible results in each city and for meta-estimates from combined data. By establishing a common methodology, factors that might influence the differences in results from previous studies can more easily be explored. Administrative support was provided to ensure that the highest quality data were used in the analysis. It is anticipated that the PAPA results will contribute to the international scientific discussion of how to conduct and interpret time-series studies of air pollution and will stimulate the development of high-quality routine systems for recording daily deaths and hospital admissions for time-series analysis. METHODS: Mortality data were retrieved from routine databases with underlying causes of death coded using the World Health Organization (WHO) International Classification of Diseases, 9th revision or 10th revision (ICD-9, ICD-10). Air quality measurements included nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matter with aerodynamic diameter < or = 10 microm (PM10), and ozone (O3) and were obtained from several fixed-site air monitoring stations that were located throughout the metropolitan areas of the four cities and that met the standards of procedures for quality assurance and quality control carried out by local government units in each city. Using the Common Protocol, an optimized core model was established for each city to assess the effects of each of the four air pollutants on daily mortality using generalized linear modeling with adjustments for time trend, seasonality, and other time-varying covariates by means of a natural-spline smoothing function. The models were adjusted to suit local situations by correcting for influenza activity, autocorrelation, and special weather conditions. Researchers in Hong Kong, for example, used influenza activity based on frequency of respiratory mortality; researchers in Hong Kong and Shanghai used autoregressive terms for daily outcomes at lag days; and researchers in Wuhan used additional smoothing for periods with extreme weather conditions. RESULTS AND DISCUSSION: For mortality due to all natural (nonaccidental) causes at all ages, the effects of air pollutants per 10-microg/m3 increase in concentration was found to be higher in Bangkok than in the three Chinese cities, with the exception of the effect of NO2 in Wuhan. The magnitude of the effects for cardiovascular and respiratory mortality were generally higher than for all natural mortality at all ages. In addition, the effects associated with PM10 and O3 in all natural, cardiovascular; and respiratory mortality were found to be higher in Bangkok than in the three Chinese cities. The explanation for these three findings might be related to consistently higher daily mean temperatures in Bangkok, variations in average time spent outdoors by the susceptible populations, and the fact that less air conditioning is available and used in Bangkok than in the other cities. However, when pollutant concentrations were incorporated into the excess risk estimates through the use of interquartile range (IQR), the excess risk was more comparable across the four cities. We found that the increases in effects among older age groups were greater in Bangkok than in the other three cities. After excluding data on extremely high concentrations of PM10 in Bangkok, the effect estimate associated with PM10 concentrations decreased in Bangkok (suggesting a convex relationship between risk and PM10, where risk levels off at high concentrations) instead of increasing, as it did in the other cities. This leveling off of effect estimates at high concentrations might be related to differences in vulnerability and exposure of the population to air pollution as well as to the sources of the air pollutant. IMPLICATIONS OF THE STUDY: The PAPA project is the first coordinated Asian multicity air pollution study ever published; this signifies the beginning of an era of cooperation and collaboration in Asia, with the development of a common protocol for coordination, data management, and analysis. The results of the study demonstrated that air pollution in Asia is a significant public health burden, especially given the high concentrations of pollutants and high-density populations in major cities. When compared with the effect estimates reported in the research literature of North America and Western Europe, the study's effect estimates for PM10 were generally similar and the effect estimates for gaseous pollutants were relatively higher. In Bangkok, however, a tropical city where total exposures to outdoor pollution might be higher than in most other cities, the observed effects were greater than those reported in the previous (i.e., Western) studies. In general, the results suggested that, even though social and environmental conditions across Asia might vary, it is still generally appropriate to apply to Asia the effect estimates for other health outcomes from previous studies in the West. The results also strongly support the adoption of the global air quality guidelines recently announced by WHO.

Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan, and Singapore.

Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine whether an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically linked coronavirus disease 2019 (COVID-19) cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.

Management decision of hospital surge: assessing seasonal upsurge in inpatient medical bed occupancy rate among public acute hospitals in Hong Kong.

BACKGROUND: There were recurrent upsurges in demand for public hospital services in Hong Kong. An understanding of the contribution of some possible factors for the rise in health care burden would help to inform hospital management strategies. AIM: To evaluate the utilization patterns of hospitalizations in medical wards among public acute hospitals in Hong Kong during surge periods. DESIGN: Retrospective study. METHODS: By extracting the information in press releases between 2014 and 2018, descriptive statistics about medical ward occupancy situation during six surge periods were generated. A time series model was constructed to estimate the occupancy rate at each hospital and assess its relationship with the intensity of seasonal influenza activity, extreme weather, day of week and long holidays. RESULTS: There was a significant increase in the number of admissions to medical wards in all six surge periods. A significant variation in occupancy rate between weekdays and geographic regions was observed. The occupancy rate in 10, out of 15, hospitals was significantly associated with the influenza activity, while there was limited effect of weather on the occupancy rate. A significant holiday effect was observed during Christmas and Chinese New Year, resulting in a lower bed occupancy rate. CONCLUSIONS: A differential burden in public hospitals during surge periods was reported. Contingency bed and staff management shall be tailored to individual hospitals, given their differences in the determinants for inpatient bed occupancy.

Lack of the alpha-1,2-linked N-acetyl-D-glucosamine epitope in the outer core structures of lipopolysaccharides from certain O serogroups and subspecies of Salmonella enterica.

A total of 176 strains of Salmonella enterica representing 116 serotypes were tested for the presence of the T6 epitope of the alpha-1,2-linked N-acetyl-D-glucosamine residue by reaction with a murine monoclonal antibody T6 specific for this structure in the Salmonella Ra core lipopolysaccharide (LPS). All 20 serotypes (70 strains) belonging to serogroups A to E were positive for the T6 epitope while 29% of the 96 serotypes (106 strains) belonging to O serogroups F to 67 were negative; 12 serotypes (12 strains) of subspecies IIIb Salmonella were positive for the T6 epitope, but 10 serotypes (11 strains) of subspecies IIIa Salmonella were found to lack this epitope. In T6-positive strains, the epitope was accessible to antibody binding in both the unsubstituted free rough core LPS and in the rough core LPS substituted with a few repeating units of O side chains. The presence or absence of the T6 epitope in Salmonella strains was not affected by culture conditions, the source of the isolate, the age of the culture or the presence of fimbriae antigens.

Pulmonary melioidosis.

Melioidosis is the name given to all diseases caused by the bacterium Pseudomonas pseudomallei. Melioidosis is a tropical disease and prevails in parts of Southeast Asia, northern Australia, and Central and South America. However, in recent years, cases of melioidosis have been reported in the United States and other areas. The organism can infect any organ system, although the lung is the most common organ affected. Pulmonary melioidosis presents either as an acute fulminant pneumonia or as an indolent cavitary disease. In northeastern Thailand, the incidence of P pseudomallei infection is extremely high with significant mortality. One of the key problems with treating melioidosis is its recalcitrance to therapy and high relapse rate. In addition, this Gram-negative rod is resistant to aminoglycosides. In nonendemic regions, patients with melioidosis more typically present with reactivation disease occurring months to years after initial exposure to the organism. The pulmonary disease is mainly in the apices and resembles tuberculosis. With the increasing mobility of people throughout the world and the influx of immigrants from endemic to nonendemic areas, it is important that clinicians be aware of this disease. This article will review the epidemiology, clinical presentations, diagnosis, and treatment of pulmonary melioidosis.

Correlation of in vitro susceptibility testing results for amoxicillin-clavulanate and ampicillin-sulbactam using a panel of beta-lactamase-producing Enterobacteriaceae.

Correlation between in vitro susceptibility results for amoxicillin-clavulanate (AMC) and ampicillin-sulbactam (SAM) was studied using 136 clinical and control strains of Enterobacteriaceae harboring TEM-1, SHV-1 or OXA-1-like beta-lactamases. Determination of minimal inhibitory concentration of antibiotics was performed by agar dilution. The beta-lactamases were initially characterized using isoelectric focusing. Further identification was done by DNA hybridization with or without prior PCR amplification. All strains sensitive to SAM were found to be sensitive also to AMC. In contrast, among those susceptible to AMC, only 50% were sensitive to SAM while 36% gave intermediate results and 14% were resistant. Major differences were found solely among SHV-producers while minor differences occurred mostly among TEM-producers. This phenomenon is probably related to the differential activities of clavulanate and sulbactam against various beta-lactamases. In conclusion, testing of Enterobacteriaceae isolates for susceptibility to AMC and SAM should be performed and reported individually to avoid erroneous designation of susceptibility.

An evaluation of susceptibility testing methods for ampicillin-sulbactam using a panel of beta-lactamase-producing bacteria.

Bacteria possessing TEM-1-like beta-lactamases are generally regarded as susceptible to ampicillin-sulbactam (SAM), while those harboring OXA-1 enzymes are considered resistant. The current study was undertaken to compare susceptibility testing using various combinations of ampicillin and sulbactam to improve clinical correlation. Members of the Enterobacteriaceae family harboring TEM-1, SHV-1 or OXA-1-like beta-lactamases were tested using the agar dilution method. A substantial proportion of strains harboring OXA-1-like beta-lactamases showed false susceptibility to SAM at the 1:1 ratio or fixed sulbactam concentration of 8 microg/ml. At a fixed sulbactam concentration of 4 microg/ml, the activity of ampicillin-sulbactam appeared to be reduced, with large numbers of TEM-1 producers becoming frankly resistant. Results obtained with the 2:1 ratio exhibited the closest correlation with that obtained by the currently recommended disk diffusion test. However, very major errors were still found between the disk diffusion test and agar dilution test, suggesting the necessity for consideration of a change in criteria for interpretation of disk diffusion test results. In conclusion, SAM susceptibility testing by agar dilution using other than a 2:1 ratio is not recommended and results should be interpreted with caution.

A one-day selective migration procedure for detecting salmonellae in faeces.

A one-day procedure for detecting salmonellae was developed and evaluated with clinical faecal specimens. The procedure was based on the selective retardation of enterobacteria in their migration through a semi-solid enrichment medium. It was shown that a pure or almost pure growth of salmonella could often be obtained within 16 to 24 hours by this method. The culture thus obtained could then be used directly for serological confirmation. The method was rapid, economical, and efficient. Clinical trials indicated an increase of 28% in the frequency of positive isolations of salmonella with this procedure as compared with the conventional multistep cultural procedures with no false-positive results. However, the method was unsatisfactory for detecting Salmonella typhi due to its slow migration through the semi-solid medium.

Further study of strontium selenite and selenite F broths for the isolation of Salmonella typhi.

The efficiency of strontium selenite and selenite F broths in the isolation of S. typhi from 625 clinical stool specimens were compared. A total of 126 strains of S. typhi were detected. Of these, 96 (76%) were isolated with selenite F broth and 118 (94%) were isolated with strontium selenite broth. At the same time, the number of false positive isolates accruing to strontium selenite broth was less than that accruing to selenite F broth. The superiority of strontium selenite broth over selenite F broth was more obvious when relatively few typhoid bacilli were present in faeces, eg, after antibiotic therapy, or when stools had been left for prolonged periods at room termperature. In the isolation of S. typhi with strontium selenite broth, salmonella-shigella agar was found to be a better plating medium than xylose lysine desoxycholate agar.

Use of PCR in routine diagnosis of treated and untreated pulmonary tuberculosis.

AIMS: To assess the routine use of a polymerase chain reaction (PCR) assay for the direct detection of Mycobacterium tuberculosis in expectorated sputum specimens. METHODS: A pair of primers (20-mer) were designed to amplify the 38 kilodalton protein of M tuberculosis. The specificity of the assay was evaluated in 31 M tuberculosis strains, 15 atypical mycobacterium species, and several commensal bacteria of the upper respiratory tract. The assay was subsequently applied to 519 sputum specimens from 85 inpatients of a chest hospital in Hong Kong. RESULTS: An amplified product of 239 base pairs was found in all M tuberculosis strains, standard strains of M bovis, and M africanum but not in the other bacterial strains tested. For the 51 patients with pulmonary radiographic lesions, the diagnosis of pulmonary tuberculosis was subsequently confirmed by both culture and PCR in 41 of them. Five patients who were treated before admission were positive by PCR alone. All but one patient in the control group (patients with acute exacerbation of chronic obstructive airway diseases) or those with atypical mycobacterial diseases were PCR negative. The PCR remained positive after four weeks of anti-tuberculosis treatment in 29 patients, 16 of whom had become culture negative. CONCLUSION: This PCR assay is a useful technique for the diagnosis of untreated and recently treated cases of pulmonary tuberculosis.

IS6110 based amplityping assay and RFLP fingerprinting of clinical isolates of Mycobacterium tuberculosis.

AIMS: To evaluate the usefulness of two IS6110 based typing methods, an amplityping assay and restriction fragment length polymorphism (RFLP) analysis, for fingerprinting respiratory isolates of Mycobacterium tuberculosis. METHODS: For amplityping, a pair of primers which amplify the intervening sequence between the repetitive insertion sequence IS6110 was used to generate a banding pattern which was confirmed by hybridisation. This assay was compared with conventional chromosomal DNA RFLP typing in the evaluation of 110 epidemiologically diverse isolates. RESULTS: Polymerase chain reaction (PCR) amplityping generated a single pattern in Hong Kong Chinese strains, but two and four diverse patterns in Filipino and Vietnamese strains, respectively, and could be completed within four days. When compared with chromosomal DNA RFLP typing, which took three weeks to complete, four different RFLP patterns could be seen among the Chinese strains, while seven patterns were found in the Filipino and Vietnamese strains. No change in amplityping or RFLP patterns was found in 36 sequential isolates from the same patients after anti-tuberculosis treatment for up to 12 months, despite the emergence of resistance in three of these strains. No specific amplityping or RFLP pattern could be related to different patterns of drug susceptibility. CONCLUSION: PCR amplityping could be used initially as a rapid typing method to distinguish strains originating from different localities. This could be important for investigation of outbreaks of tuberculosis--for example, in refugee camps.

Worldwide variation in chloramphenicol utilization: should it cause concern?

Per capita sales of chloramphenicol in Hong Kong (which presumably reflect adult and pediatric consumption in the community) are between about 11 to 442 fold greater than in several western countries and Australia. Despite such relatively excessive exposure to a potentially marrow-damaging drug, the certified death rate from aplastic anemia in Hong Kong was only 0.4 per 1000 deaths compared with 1.0 per 1000 in England and Wales. Nor was there any other evidence to indicate that Hong Kong residents suffered an excessive incidence of aplastic anemia. Wherever chloramphenicol use is widespread, prospective investigations should be undertaken in the local population to evaluate the alleged high risks of producing aplastic anemia.

Characterization and application of a murine monoclonal antibody that reacts specifically with the serogroup D1 Salmonella.

A murine hybridoma cell line that produces monoclonal antibody (mAb) against the serogroup D1 Salmonella lipopolysaccharide (LPS) antigen was established. The trisaccharide tyvelose alpha 1----3 mannose alpha 1----4 rhamnose was shown to be involved in the reactive epitope of the mAb since this mAb reacted strongly with strains of serogroup D1 Salmonella but not with Salmonella strains from the O serogroups of A, B, and D2, and sodium meta-periodate was found to destroy the reactivity of the serogroup D1 O-antigen with the mAb. As such this mAb was found to be a useful serotyping reagent for the identification of serogroup D1 Salmonella, and for the differentiation of strains of serogroups D1 and D2 Salmonella which have identical flagellar H antigens.

Inhibition of Cryptococcus neoformans by Pseudomonas aeruginosa.

Pseudomonas aeruginosa was found to produce a factor or factors that inhibited Cryptococcus neoformans and appeared to be extracellular because the anti-C. neoformans activity was readily demonstrable in medium after the removal and killing of Pseudomonas organisms. Production of the inhibitor material was greatest in DST Agar after prolonged incubation and was reduced in the presence of glucose. A part of the inhibitory material was found to be chromatographically distinct from pyocyanin.

Melioidosis: a serological survey in a tuberculosis sanatorium in Hong Kong.

A serological survey of 275 Chinese patients with underlying pulmonary diseases in a tuberculosis sanatorium in Hong Kong showed that 39 (14%) had haemagglutinating antibody (HA) against Pseudomonas pseudomallei in a titre of 1: 80 or above. Only 9 of these 39 patients had travelled to endemic areas, suggesting that at least 30 patients (11%) had been exposed to Ps. pseudomallei locally. Females are affected as often as males, and the seropositive rate is the same whether patients are immunosuppressed or not. Because subclinical melioidosis is prevalent and HA may persist for a long time, even at a high titre, after infection, determination of HA alone cannot differentiate between active melioidosis and its masquerade--active tuberculosis.

First report of septicaemic melioidosis in Hong Kong.

Septicaemia due to Pseudomonas pseudomallei was found in five patients; it complicated pneumonia in three. Four patients were old and had diabetes mellitus; the fifth patient, though young, was immunocompromised by steroid therapy. The clinical features were indistinguishable from those of other Gram-negative septicaemia. Four of the patients died. This was the first report of septicaemic melioidosis in Hong Kong where the disease might be endemic. Soil sampling and serological survey gave further supporting evidence. Early treatment using a bactericidal anti-Pseudomonal cephalosporin, such as ceftazidime, was suggested for this life-threatening infection.

Ofloxacin compared with amoxycillin in treating infective exacerbations in bronchiectasis.

Forty-one hospitalized adult patients of bronchiectasis (non-cystic fibrotic) with infective exacerbations were entered into a randomized, double-blind, placebo-controlled study comparing ofloxacin (200 mg tid) and amoxycillin (1 g tid) both orally for ten days. In the ofloxacin group (20 patients), improvement in sputum purulence was excellent in 14, and fair in five patients with one failure. In the amoxycillin group (21 patients), improvement in sputum purulence was excellent in eight, fair in five and poor in eight patients. Mean drug levels on day 5 were 4.1 mg l-1 for serum (2 h post-dosage) and 4.0 mg l-1 for sputum for ofloxacin, and 18.4 mg l-1 for serum and 0.3 mg l-1 for sputum for amoxycillin. Ofloxacin thus yielded higher sputum concentration and appeared to be more effective and also better tolerated than amoxycillin in infective episodes of bronchiectasis.

An evaluation of inpatient consultations conducted by clinical microbiologists in a teaching hospital.

A systematic procedure for conducting consultations by clinical microbiologists requested by their clinical colleagues is described. The method was evaluated over a period of 17 months and involved sequential consultations related to 229 patients with known or probable infections. An attempt was made to elucidate the contributions of the clinical microbiologists in achieving a better understanding of the problems experienced in this particular setting and which in turn led to improved management of patients. It is hoped that this paper may provide a practical working framework for clinical microbiologists in the care of patients suffering from infection.

Antibiotic susceptibility of pneumococci and Haemophilus influenzae isolated from patients with acute exacerbations of chronic bronchitis: prevalence of tetracycline-resistant strains in Hong Kong.

The susceptibility of 119 respiratory isolates of Haemophilus influenzae and 87 respiratory isolates of Streptococcus pneumoniae to various antibiotics was tested by means of an agar dilution method and an inoculum size of 10(3) colony forming units (c.f.u.). The antibiotics tested included penicillin/ampicillin, erythromycin, tetracycline, chloramphenicol and four third-generation cephalosporins, cefotaxime, cefoperazone, ceftriaxone and moxalactam. Fifty-eight per cent of the pneumococcal strains and 23 per cent of the H. influenzae strains tested were found resistant to tetracycline (MICs = 4-128 mg/l and 4-64 mg/l, respectively). None of the isolates tested was resistant to erythromycin or chloramphenicol. Three per cent of Haemophilus strains tested were beta-lactamase producing and thus resistant to ampicillin (MICs = 2-8 mg/l), while none of the pneumococcal strains tested was penicillin-resistant. Three of the newer third-generation cephalosporins--cefotaxime, cefoperazone and ceftriaxone--were highly active against both H. influenzae and Str. pneumoniae while moxalactam, though also active, was comparatively less effective.