Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100,000 per year) and in persons aged ≥50 years, influenza virus A (38·8/100,000 per year). These data can help guide health policy towards effective prevention strategies.

Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal.

Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.

Physician control of pediatric antimicrobial use in Beijing, China, and its rural environs.

BACKGROUND: Antibiotic resistance is recognized as an increasing problem in China. It is widely believed that because antibiotics are available without a prescription, changing physician prescribing behaviors will not decrease inappropriate usage. This study identified the sources of antibiotics and the important influence that physicians have on antibiotic use by children in one region of China. METHODS: Trained medical professionals surveyed parents of children attending several kindergartens in urban Beijing and rural Gu'An, Hebei County. Parents completed a questionnaire concerning the children's recent illnesses, care-seeking patterns and antibiotic use. The team also observed hospital- and non-hospital-based pharmacy purchases of antibiotics for children, assessed the proportion accompanied by a prescription and then interviewed parents about factors influencing those purchases. RESULTS: Of 241 urban and 143 rural kindergarten parents, 76 to 82% usually obtained children's antibiotics from a hospital pharmacy (with a prescription). For 84% the first source of care was usually a physician (primarily western medicine, sometimes traditional Chinese medicine). Only 5% of antibiotics were obtained from independent vendors without prior physician consultation. Among 229 observed antibiotic purchases 72% occurred at hospital-based facilities, even after longer observation times at nonhospital pharmacies. Prescriptions accompanied all hospital-based antibiotic purchases, contrasting with 18% of nonhospital transactions (P < 0.001). Together 86% of parents self-reported that the observed purchase stemmed from a doctor's recommendation. CONCLUSIONS: Doctors directly and indirectly controlled the majority of antibiotic usage for childhood illnesses in Beijing and Gu'An (Hebei County). Physician education and implementation of treatment guidelines might substantially reduce inappropriate antimicrobial usage and help prevent antimicrobial resistance in this region.

Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada).

Chlamydia pneumoniae has been associated with atherosclerosis and several other chronic diseases, but reports from different laboratories are highly variable and "gold standards" are lacking, which has led to calls for more standardized approaches to diagnostic testing. Using leading researchers in the field, we reviewed the available approaches to serological testing, culture, DNA amplification, and tissue diagnostics to make specific recommendations. With regard to serological testing, only use of microimmunofluorescence is recommended, standardized definitions for "acute infection" and "past exposure" are proposed, and the use of single immunoglobulin (Ig) G titers for determining acute infection and IgA for determining chronic infection are discouraged. Confirmation of a positive culture result requires propagation of the isolate or confirmation by use of polymerase chain reaction (PCR). Four of 18 PCR assays described in published reports met the proposed validation criteria. More consistent use of control antibodies and tissues and improvement in skill at identifying staining artifacts are necessary to avoid false-positive results of immunohistochemical staining. These standards should be applied in future investigations and periodically modified as indicated.

Reducing antibiotic use in children: a randomized trial in 12 practices.

OBJECTIVE: To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old. METHODS: Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed. RESULTS: The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses. CONCLUSIONS: A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.

Treating cardiovascular disease with antimicrobial agents: a survey of knowledge, attitudes, and practices among physicians in the United States.

To assess physicians' knowledge, attitudes, and prescribing behaviors with regard to the association between Chlamydia pneumoniae and cardiovascular disease, we surveyed 750 physicians in Alaska, 1172 in West Virginia, and 569 infectious disease (ID) specialists in a nationwide network during February-May 1999. Eighty-five percent knew of the association between C. pneumoniae and atherosclerosis, but this awareness was more common among ID specialists and cardiologists than among generalists (96% vs. 77%; P<.001). Knowledge scores were significantly higher among ID specialists and cardiologists (P<.001) and among physicians who saw relatively more patients who had myocardial infarction and/or were at risk of atherosclerotic disease. Four percent of physicians had treated or recommended treating cardiovascular diseases with antimicrobial agents; this percentage was significantly higher among cardiologists, physicians who empirically treat patients with peptic ulcers with antimicrobial agents, and physicians with a relatively high knowledge score.

Seasonal variation in host susceptibility and cycles of certain infectious diseases.

Seasonal cycles of infectious diseases have been variously attributed to changes in atmospheric conditions, the prevalence or virulence of the pathogen, or the behavior of the host. Some observations about seasonality are difficult to reconcile with these explanations. These include the simultaneous appearance of outbreaks across widespread geographic regions of the same latitude; the detection of pathogens in the off-season without epidemic spread; and the consistency of seasonal changes, despite wide variations in weather and human behavior. In contrast, an increase in susceptibility of the host population, perhaps linked to the annual light/dark cycle and mediated by the pattern of melatonin secretion, might account for many heretofore unexplained features of infectious disease seasonality. Ample evidence indicates that photoperiod-driven physiologic changes are typical in mammalian species, including some in humans. If such physiologic changes underlie human resistance to infectious diseases for large portions of the year and the changes can be identified and modified, the therapeutic and preventive implications may be considerable.

Evaluation of Binax NOW, an assay for the detection of pneumococcal antigen in urine samples, performed among pediatric patients.

In our evaluation of a new assay for the detection of pneumococcal antigen in urine (Binax NOW; Binax), the test result was no more likely to be positive among 88 children with radiographically confirmed pneumonia than among 198 control subjects; however, it was significantly more likely to be positive among children who were nasopharyngeal carriers of pneumococci. This test is not likely to be useful for distinguishing children with pneumococcal pneumonia from those who are merely colonized.

Analysis of immunoreactivity to a Streptococcus equi subsp. zooepidemicus M-like protein To confirm an outbreak of poststreptococcal glomerulonephritis, and sequences of M-like proteins from isolates obtained from different host species.

The etiologic agent of a large 1998 outbreak of poststreptococcal acute glomerulonephritis (PSGN) in Nova Serrana, Brazil, was found likely to be a specific strain of Streptococcus equi subsp. zooepidemicus from contaminated cheese (S. Balter et al., Lancet 355:1776-1780, 2000). In the present study, we used a serologic screen for a known surface-exposed virulence factor to confirm the epidemiologic findings. Using primers flanking a previously characterized M-like protein gene (J. F. Timoney et al., Infect. Immun. 63:1440-1445, 1995), we amplified and sequenced the M-like protein (designated Szp5058) gene and found it to be identical among four independent acute-phase PSGN patient isolates. Convalescent-phase sera from 33 of 44 patients in the PSGN outbreak were found to contain antibodies highly reactive to a purified Szp5058 fusion protein, compared with 1 of 17 control sera (P < 0. 0001), suggesting that Szp5058 was expressed during infection and further implicating this strain as the cause of the PSGN outbreak. The predicted signal sequence and cell wall association motif of Szp5058 were highly conserved with the corresponding sequence from S. equi subsp. zooepidemicus SzpW60, while the predicted surface-exposed portions differed markedly between these two proteins. The 5' end of the szp5058 gene, including its variable region, was identical to the szp gene from another strain associated with a previous PSGN outbreak in England (M. Barham et al., Lancet i:945-948, 1983), and the corresponding szp sequence found from the Lancefield group C type strain isolated from a guinea pig. In addition, the hypervariable (HV) portion of szp5058 was identical to a previously published HV sequence from a horse isolate (J. A. Walker and J. F. Timoney, Am. J. Vet. Res. 59:1129-1133, 1998). Three other strains of S. equi subsp. zooepidemicus, including another strain previously associated with a PSGN outbreak, were each found to contain a distinct szp gene. Two of these szp genes had HV regions identical to szp regions from isolates recovered from different host species.

Limiting the spread of resistant pneumococci: biological and epidemiologic evidence for the effectiveness of alternative interventions.

Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an "antiresistance vaccine" that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.

Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group.

OBJECTIVE: To provide recommendations for the management of community-acquired pneumonia and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP). METHODS: We addressed the following questions: (1) Should pneumococcal resistance to beta-lactam antimicrobial agents influence pneumonia treatment? (2) What are suitable empirical antimicrobial regimens for outpatient treatment of community-acquired pneumonia in the DRSP era? (3) What are suitable empirical antimicrobial regimens for treatment of hospitalized patients with community-acquired pneumonia in the DRSP era? and (4) How should clinical laboratories report antibiotic susceptibility patterns for S pneumoniae, and what drugs should be included in surveillance if community-acquired pneumonia is the syndrome of interest? Experts in the management of pneumonia and the DRSP Therapeutic Working Group, which includes clinicians, academicians, and public health practitioners, met at the Centers for Disease Control and Prevention in March 1998 to discuss the management of pneumonia in the era of DRSP. Published and unpublished data were summarized from the scientific literature and experience of participants. After group presentations and review of background materials, subgroup chairs prepared draft responses, which were discussed as a group. CONCLUSIONS: When implicated in cases of pneumonia, S pneumoniae should be considered susceptible if penicillin minimum inhibitory concentration (MIC) is no greater than 1 microg/mL, of intermediate susceptibility if MIC is 2 microg/ mL, and resistant if MIC is no less than 4 microg/mL. For outpatient treatment of community-acquired pneumonia, suitable empirical oral antimicrobial agents include a macrolide (eg, erythromycin, clarithromycin, azithromycin), doxycycline (or tetracycline) for children aged 8 years or older, or an oral beta-lactam with good activity against pneumococci (eg, cefuroxime axetil, amoxicillin, or a combination of amoxicillin and clavulanate potassium). Suitable empirical antimicrobial regimens for inpatient pneumonia include an intravenous beta-lactam, such as cefuroxime, ceftriaxone sodium, cefotaxime sodium, or a combination of ampicillin sodium and sulbactam sodium plus a macrolide. New fluoroquinolones with improved activity against S pneumoniae can also be used to treat adults with community-acquired pneumonia. To limit the emergence of fluoroquinolone-resistant strains, the new fluoroquinolones should be limited to adults (1) for whom one of the above regimens has already failed, (2) who are allergic to alternative agents, or (3) who have a documented infection with highly drug-resistant pneumococci (eg, penicillin MIC > or =4 microg/mL). Vancomycin hydrochloride is not routinely indicated for the treatment of community-acquired pneumonia or pneumonia caused by DRSP.

Mortality from pneumonia in children in the United States, 1939 through 1996.

BACKGROUND AND METHODS: Pneumonia remains an important cause of childhood deaths throughout the world, but in developed countries, the mortality rate is decreasing. We reviewed death records for children in the United States from 1939 through 1996. A plot of the annual rates of change in the number of deaths from pneumonia was used to generate hypotheses about the influence of various events and interventions. We used data from the National Hospital Discharge Survey, the Medicaid program, and published reports to test these hypotheses. RESULTS: During the 58-year study period, the number of children who died from pneumonia declined by 97 percent, from 24,637 in 1939 to 800 in 1996. During the same period, the rate of mortality from other causes declined by 82 percent. There were steep declines in the mortality rates for pneumonia from 1944 to 1950, although the rate increased among older children in 1957, and there were sustained declines in all age groups from 1966 to 1982. From 1966 to 1982, the mortality declined by an average of 13.0 percent annually, and these decreases coincided with increases in the proportion of poor children covered by Medicaid, increases in rates of hospitalization for pneumonia, a narrowing of the gap between the mortality rate for black children and the rate for white children, and a convergence between the mortality rate in the South and the rates in the other three census regions. CONCLUSIONS: Since 1939, the rate of mortality from pneumonia in children in the United States has declined markedly. We hypothesize that the steep declines in the late 1940s are attributable to the use of penicillin, that the peak in 1957 was due to the influenza A pandemic, and that the sustained decline from 1966 through 1982 may be attributable in part to improved access to medical care for poor children.

Severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection.

An outbreak of severe pneumococcal pneumonia among children occurred in Iowa from November 1995 through January 1996. An associated outbreak of influenza disease was predominantly caused by influenza A (H1N1) for the first time since 1989. We conducted a case-control study to determine whether preceding influenza infection was directly associated with pneumococcal illness. We identified 13 children with severe pneumococcal pneumonia. Patients were more likely than control subjects to report experiencing an influenza-like illness in the 7-28 days preceding admission (matched odds ratio [OR], 12.4; 95% confidence interval [CI], 1.7-306). Likewise, family members of patients were more likely than those of control subjects to report experiencing an influenza-like illness in the 28 days preceding their admission date (OR, 2.6; 95% CI, 1.0-6. 3). Patients were more likely than control subjects to have a positive influenza A (H1N1) convalescent serology (matched OR, 3.7; 95% CI, 1.0-18.1). This study provides direct and indirect evidence that influenza infection led to severe pneumococcal pneumonia among these children. Prevention of pneumococcal disease should be included among the potential benefits of influenza vaccination.

Antimicrobial use in defined populations of infants and young children.

BACKGROUND: Antimicrobial overprescribing contributes to bacterial resistance, but data on use in infants and young children are limited. OBJECTIVES: To assess antimicrobial use in a defined population of infants and young children and to determine diagnosis-specific prescribing rates for common infections. DESIGN AND SETTING: Retrospective cohort study of children served by 44 practices affiliated with 2 managed care organizations. PATIENTS: Children aged 3 months to 72 months enrolled in either health plan between September 1, 1994, and August 31, 1996. ANALYSIS: Rates of antimicrobial use were calculated as the number of pharmacy dispensings divided by the number of person-years of observation contributed to the cohort in 2 age groups (3 to <36 months and 36 to <72 months). Other outcomes included the distribution of diagnoses associated with antimicrobial dispensing and population-based rates of diagnosis of common acute respiratory tract illnesses. RESULTS: A total of 46477 children contributed 59710 person-years of observation across the 2 health plans. Rates of antimicrobial dispensing for children aged 3 to 36 months were 3.2 and 2.1 dispensings per person-year in the 2 populations. A substantial fraction of younger children (35% in population A and 23% in population B) received 4 or more antimicrobial prescriptions in a single year. For children aged 36 to 72 months, the dispensing rates for the 2 populations were 2.0 and 1.5 antimicrobials per person-year. We found significant differences in rates between the populations studied and a decrease in use at all sites from 1995 to 1996. The diagnosis of otitis media accounted for 56% of antimicrobial drugs dispensed to children aged 3 to 36 months and 40% of those dispensed to children aged 36 to 72 months. Antimicrobial prescribing for colds and upper respiratory tract infections, bronchitis, and sinusitis was less frequent than previously reported but accounted for 10% to 14% of antimicrobial drugs dispensed. CONCLUSIONS: In these populations, otitis media accounted for the largest number of antimicrobial agents dispensed to children younger than 6 years. Clearly inappropriate indications such as cold, upper respiratory tract infection, and bronchitis accounted for smaller fractions of antimicrobial use but may be most amenable to change. However, interventions that encourage use of strict criteria for diagnosis and treatment of otitis media will likely have the greatest impact on overall antimicrobial exposure. Monitoring defined populations longitudinally will allow assessment of the effectiveness of such national and local initiatives.

Haemophilus influenzae type b and Streptococcus pneumoniae as causes of pneumonia among children in Beijing, China.

To determine if Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae could be identified more often from the nasopharynx of patients with pneumonia than from control patients, we obtained nasopharyngeal swab specimens from 96 patients with chest x-ray-confirmed pneumonia and 214 age-matched control patients with diarrhea or dermatitis from the outpatient department at Beijing Children's Hospital. Pneumonia patients were more likely to be colonized with Hib and S. pneumoniae than control patients, even after the data were adjusted for possible confounding factors such as day-care attendance, the presence of other children in the household, and recent antibiotic use. In China, where blood cultures from pneumonia patients are rarely positive, the results of these nasopharyngeal cultures provide supporting evidence for the role of Hib and S. pneumoniae as causes of childhood pneumonia.

Increased carriage of trimethoprim/sulfamethoxazole-resistant Streptococcus pneumoniae in Malawian children after treatment for malaria with sulfadoxine/pyrimethamine.

Treatment of malaria with sulfadoxine/pyrimethamine and of presumed bacterial infections with trimethoprim/sulfamethoxazole (cotrimoxazole) was assessed to see if either increases the carriage of cotrimoxazole-resistant Streptococcus pneumoniae in Malawian children. Children <5 years old treated with sulfadoxine/pyrimethamine, cotrimoxazole, or no antimicrobial agent were enrolled in a prospective observational study. Nasopharyngeal swabs were taken before treatment and 1 and 4 weeks later. Pneumococci were tested for antibiotic susceptibility by broth microdilution. In sulfadoxine/pyrimethamine-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 38.1% at the initial visit to 44.1% at the 4-week follow-up visit (P=.048). For cotrimoxazole-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 41.5% at the initial visit to 52% at the 1-week follow-up visit (P=.0017) and returned to 41.7% at the 4-week follow-up. Expanding use of sulfadoxine/pyrimethamine to treat chloroquine-resistant malaria may have implications for national pneumonia programs in developing countries where cotrimoxazole is widely used.