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.

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 Published and unpublished data were summarized from the scientific literature and experience of participants.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.

The utility of verbal autopsies for identifying HIV-1-related deaths in Haitian children.

OBJECTIVE: To determine whether deaths among Haitian infants born to HIV-1-seronegative women could be distinguished from deaths among children born to HIV-1-seropositive women using the verbal autopsy technique. METHODS: Mothers of 315 Haitian children who died were interviewed about events leading to the child's death. Three physicians independently reviewed interview data and determined the probable cause of death without knowledge of maternal HIV-1 status or hospital records. The underlying causes of death assigned to the infants were analyzed to determine whether maternal HIV status could be predicted. RESULTS: There was good agreement among the physicians (kappa = 0.62) and 90% agreement between hospital records and the verbal autopsy diagnosis. Compared with children born to HIV-1-seronegative women, deaths in children born to HIV-1-seropositive mothers were more likely to be ascribed to a presumptive diagnosis of AIDS (37 versus 21%; P = 0.01). The sensitivity and specificity of verbal autopsies for identifying deaths associated with maternal HIV-1 infection ranged from 37 to 59% and from 69 to 79%, respectively, depending on the classification system used. The predictive positive value of a death believed to be consistent with pediatric HIV-1 infection was 26-30% and the predictive negative value was 85-90%. CONCLUSION: Verbal autopsies may be useful for distinguishing certain causes of death, but have limited utility for distinguishing deaths associated with maternal HIV-1 infection from deaths among children born to HIV-1-seronegative women.

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.

Severe varicella associated with steroid use.

OBJECTIVE: To evaluate whether corticosteroid use is associated with severe varicella. DESIGN: The odds of corticosteroid exposure were compared among 35 children with severe varicella and 10,000 control subjects. RESULTS: Five (26.3%) of 19 case patients without known immunosuppression had received steroids within 30 days prior to the onset of their rash compared with 20 of the 10,000 control subjects (0.2%), giving an odds ratio of 178 (95% confidence interval 59 to 541). If 16 case patients with leukemia or other known immunosuppressive conditions were included, the odds ratio was larger (odds ratio 420, 95% confidence interval 189 to 935). Of the 13 case patients whose dosage was recorded, 7 received less than the equivalent of 2 mg/kg per day of prednisone. The timing of the steroid use in those who had severe varicella clustered within the incubation period for the virus. CONCLUSIONS: Systemic corticosteroid use appears to increase substantially the risk of severe or fatal varicella. The timing of corticosteroid exposure, in addition to dose and duration, may be an important factor in determining vulnerability. Further studies are needed to determine whether short-course, low-dose, or inhaled steroids are associated with similarly increased risk. Physicians should be aware that varicella-susceptible patients receiving corticosteroids are at considerably increased risk for severe varicella and should consider how to counsel their patients.

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.

Treatment of respiratory syncytial virus infection with vitamin A: a randomized, placebo-controlled trial in Santiago, Chile.

BACKGROUND: Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles. In respiratory syncytial virus (RSV) infection, as with measles, low serum vitamin A concentrations correlate with increased severity of illness. METHODS: To determine whether high dose vitamin A treatment is also effective for treating RSV disease, we conducted a randomized, double blind, placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago, Chile. Children with nasal washes positive for RSV antigen were given oral vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n = 89) or placebo (n = 91) within 2 days of admission. RESULTS: There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For the subgroup of children with significant hypoxemia on admission (room air oxygen saturation level < or = 90%), those given vitamin A had more rapid resolution of tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days, P = 0.09). No toxicities were seen, including excess vomiting or bulging fontanel. CONCLUSIONS: If vitamin A has a beneficial effect on the course of RSV disease, it may be seen only in more severely ill children.

Acute otitis media: management and surveillance in an era of pneumococcal resistance--a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group.

OBJECTIVE: To provide recommendations [corrected] for the management of acute otitis media (AOM) and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP). Five questions were addressed: (1) Can amoxicillin remain the best initial antimicrobial agent for treating AOM in the current period of increasing prevalence of DRSP? (2) What are suitable alternative agents for use if amoxicillin fails? (3) Should empiric treatment of AOM vary by geographic region? (4) Where can clinicians learn about resistance patterns in their patient populations? (5) What modifications to laboratory surveillance would improve the utility of the information for clinicians treating AOM? PARTICIPANTS: Experts in the management of otitis media and the DRSP Therapeutic Working Group. This group was convened by the CDC to respond to changes in antimicrobial susceptibility among pneumococci and includes clinicians, academicians and public health practitioners. EVIDENCE: Published and unpublished data summarized from the scientific literature and experience from the experts present. PROCESS: [corrected] After group presentations and review of background materials, subgroup chairs prepared draft responses to the five questions, discussed the responses as a group and edited those responses [corrected]. CONCLUSIONS: Oral amoxicillin should remain the first line antimicrobial agent for treating AOM. In view of the increasing prevalence of DRSP, the safety of amoxicillin at higher than standard dosages and evidence that higher dosages of amoxicillin can achieve effective middle ear fluid concentrations, an increase in the dosage used for empiric treatment from 40 to 45 mg/kg/day to 80 to 90 mg/kg/day is recommended. For patients with clinically defined treatment failure after 3 days of therapy, useful alternative agents include oral amoxicillin-clavulanate, cefuroxime axetil and intramuscular ceftriaxone. Many of the 13 other Food and Drug Administration-approved otitis media drugs lack good evidence for efficacy against DRSP. Currently local surveillance data for pneumococcal resistance that are relevant for the clinical management of AOM are not available from most areas in the United States. Recommendations to improve surveillance include establishing criteria for setting susceptibility breakpoints for clinically appropriate antimicrobials to ensure relevance for treating AOM, testing middle ear fluid or nasal swab isolates in addition to sterile site isolates and testing of drugs that are useful in treating AOM. The management of otitis media has entered a new era with the development of DRSP. These recommendations are intended to provide a framework for appropriate clinical and public health responses to this problem.

Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States.

BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS: We performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection. RESULTS: There were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness. CONCLUSIONS: We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

Lack of association between Kawasaki syndrome and Chlamydia pneumoniae infection: an investigation of a Kawasaki syndrome cluster in San Diego County.

BACKGROUND: The etiology of Kawasaki syndrome (KS), the leading cause of acquired coronary artery disease in children, is unknown. Recent studies have suggested that Chlamydia pneumoniae, a common respiratory pathogen associated with an increased risk of heart disease, might lead to KS. OBJECTIVE: To assess whether KS was associated with an elevated risk of having a current or antecedent infection with C. pneumoniae. METHODS: Blood, urine and pharyngeal specimens from KS patients in San Diego County, CA, during a period of high KS incidence were analyzed for evidence of recent C. pneumoniae infection by culture, PCR and serology. Specimens collected from two control groups, family members of KS patients and age-matched children attending outpatient clinics for well child visits, were similarly analyzed. RESULTS: Thirteen cases were identified. Forty-five outpatient controls and an average of three family members per patient were enrolled in the study. All specimens tested negative for the presence of C. pneumoniae by PCR and culture except for one blood specimen from the mother of a case-patient. Serologic analysis of patients and a subset of outpatient and family controls revealed no evidence of current C. pneumoniae infection; 4 of 13 adult family controls had IgG titers consistent with past exposure to C. pneumoniae. Case patients were no more likely than outpatient controls to have had a respiratory illness in the preceding 2 months (11 of 13 patients vs. 35 of 45 controls; odds ratio, 1.57; 95% confidence interval, 0.3 to 11.9). CONCLUSIONS: We found no evidence that C. pneumoniae infection was associated with KS.

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.

Current attitudes regarding use of antimicrobial agents: results from physician's and parents' focus group discussions.

Antibiotics are widely prescribed for children with nonspecific upper respiratory tract infections, contributing to the recent emergence of resistant pneumococci. To understand the reasons for the overprescription of antibiotics, we conducted focus groups with parents and with pediatricians and family physicians to assess their attitudes regarding the use of antibiotics. Physicians asserted that their own antibiotic prescribing could be safely reduced. Parental expectation to receive antibiotics was a major factor influencing their overuse of antibiotics. Parents indicated that they would be satisfied with the medical visit even if antibiotics were not prescribed, provided the physician explained the reasons for the decision. This study highlights differences in physician and parent perceptions about antibiotic overuse and suggests that educational efforts to narrow this communication gap will be important for improving antibiotic use.

Acute otitis media: management and surveillance in an era of pneumococcal resistance. Drug-Resistant Streptococcus Pneumoniae Therapeutic Working Group.

Experts in the management of otitis media and the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group were convened by the Centers for Disease Control and Prevention to respond to changes in antimicrobial susceptibility among pneumococci. The objective was to provide consensus recommendations for the management of acute otitis media (AOM) and for the surveillance of drug-resistant Streptococcus pneumoniae. After summarizing published and unpublished data from the scientific literature and the experience of the panel members, the group concluded that oral amoxicillin should remain the first-line antimicrobial agent for treating AOM. For patients with clinically defined treatment failure after 3 days of therapy, useful alternative agents include amoxicillin-clavulanate, cefuroxime axetil, and intramuscular ceftriaxone. The group also made recommendations to improve surveillance and to obtain antimicrobial susceptibility patterns for local geographic areas.

Pancreatitis associated with human immunodeficiency virus infection: a matched case-control study.

To determine the frequency of pancreatitis and to define risk factors for pancreatitis in patients with AIDS, we compared patients with pancreatitis to patients without pancreatitis in an urban infectious disease practice. Pancreatitis was defined as at least one clinical sign or symptom (nausea, vomiting, abdominal pain, or tenderness) accompanied by elevation of serum amylase or lipase. Twenty-four (22%) of 105 patients with AIDS, 2 (4%) of 46 patients with AIDS-related complex, 1 (3%) of 39 asymptomatic patients infected with HIV-1, and none of 9 uninfected patients at risk for HIV-1 developed pancreatitis as defined above. Fourteen patients experienced multiple episodes and three were symptomatic for more than 2 months. Pancreatitis was more likely to have occurred in patients with AIDS (P < .001), biliary tract disease (P = .013), and hypertriglyceridemia (P = .032). After matching for these factors and duration of current HIV disease, cryptosporidiosis, intravenous pentamidine, and isoniazid were each associated independently with pancreatitis (P < .05). Before didanosine (ddl) became available, 22% of the patients with AIDS in this practice had pancreatitis. Cryptosporidiosis, isoniazid, and intravenous pentamidine should be considered among the potential etiologies.

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.