Pneumocystis pneumonia (PCP) has historically been one of the leading causes of disease among persons with AIDS. The introduction of highly active antiretroviral therapy in industrialized nations has brought about dramatic declines in the incidence of AIDS-associated complications, including PCP. In the adult population, the incidence of PCP has significantly decreased, but it remains among the most common AIDS-defining infections. Similar declines have been documented in the pediatric population. In much of the developing world, PCP remains a significant health problem, although its incidence among adults in sub-Saharan Africa has been debated. This review discusses the epidemiology of PCP during the current era of the AIDS epidemic. Although fewer cases of PCP occur in the industrialized countries, increasing drug-resistant HIV infections, possible drug-resistant PCP, and to the tremendous number of AIDS cases in developing countries make this disease of continued public health importance.

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone.

Pneumocystis pneumonia (PCP) caused by the opportunistic fungal agent Pneumocystis jirovecii (formerly Pneumocystis carinii) continues to cause illness and death in HIV-infected patients. In the absence of a culture system to isolate and maintain live organisms, efforts to type and characterize the organism have relied on polymerase chain reaction–based approaches. Studies using these methods have improved understanding of PCP epidemiology, shedding light on sources of infection, transmission patterns, and potential emergence of antimicrobial resistance. One concern, however, is the lack of guidance regarding the appropriateness of different methods and standardization of these methods, which would facilitate comparing results reported by different laboratories.

West Nile virus (WNV) is transmitted by mosquitoes and can cause illness in humans ranging from mild fever to encephalitis. In 2002, a total of 4,156 WNV cases were reported in the United States; 329 were in Louisiana. To estimate the economic impact of the 2002 WNV epidemic in Louisiana, we collected data from hospitals, a patient questionnaire, and public offices. Hospital charges were converted to economic costs by using Medicare cost-to-charge ratios. The estimated cost of the Louisiana epidemic was $20.1 million from June 2002 to February 2003, including a $10.9 million cost of illness ($4.4 million medical and $6.5 million nonmedical costs) and a $9.2 million cost of public health response. These data indicate a substantial short-term cost of the WNV disease epidemic in Louisiana.

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). In a longitudinal cross-sectional study, we determined the prevalence of virus in bodily excretions and time of seroconversion in discharged patients with SARS. Conjunctival, throat, stool, and urine specimens were collected weekly from 64 patients and tested for SARS-CoV RNA by real-time polymerase chain reaction; serum samples were collected weekly and tested for SARS-CoV antibody with indirect enzyme immunoassay and immunofluorescence assay. In total, 126 conjunctival, 124 throat swab, 116 stool, and 124 urine specimens were analyzed. Five patients had positive stool samples, collected weeks 5–9. Two patients seroconverted in weeks 7 and 8; the others were seropositive at the first serum sample collection. In this study, 5 (7.8%) of 64 patients continued to shed viral RNA in stool samples only, for up to week 8 of illness. Most seroconversions occurred by week 6 of illness.

Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated with older patients (3.9% in adults and 7.2% in patients >65 years of age), with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and macrolide resistance. Among 14 low-level resistant (MIC 4–8 μg/mL) strains, 1 had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61 high-level ciprofloxacin-resistant (MIC ≥16 μg/mL) strains showed either two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by point mutation (70 strains) or by recombination with viridans streptococci (4 strains) at the topoisomerase II genes. Although 36 pulsed-field gel electrophoresis patterns were observed, 5 international multiresistant clones (Spain^23F-1, Spain^6B-2, Spain^9V-3, Spain¹⁴-5 and Sweden^15A-25) accounted for 35 (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed to prevent the dissemination of these clones.

A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are too heterogeneous (p < 0.001) to warrant a single summary effect estimate. Estimated effects are weaker after 1996 and stronger in studies that included multiple isolates per patient. Five studies examined treatment outcome. The effect of DHPS mutations on treatment outcome has not been well studied, and the few studies that have been conducted are inconsistent even as to the presence or absence of an association.

Ten Pneumocystis jirovecii pneumonia (PCP) cases were diagnosed in renal transplant recipients (RTRs) during a 3-year period. Nosocomial transmission from HIV-positive patients with PCP was suspected because the these patients shared the same hospital building, were not isolated, and were receiving no or suboptimal anti-PCP prophylaxis. P. jirovecii organisms were typed with the multitarget polymerase chain reaction–single-strand conformation polymorphism method. Among the 45 patients with PCP hospitalized during the 3-year period, 8 RTRs and 6 HIV-infected patients may have encountered at least 1 patient with active PCP within the 3 months before the diagnosis of their own PCP episode. In six instances (five RTRs, one HIV-infected patient), the patients harbored the same P. jirovecii molecular type as that found in the encountered PCP patients. The data suggest that part of the PCP cases observed in this building, particularly those observed in RTRs, were related to nosocomial interhuman transmission.

Four cases of severe acute respiratory syndrome (SARS) that occurred between December 16, 2003, and January 8, 2004, in Guangzhou city, Guangdong Province, China, were investigated. Four cases of severe acute respiratory syndrome (SARS) that occurred from December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong Province, China, were investigated. Clinical specimens collected from these patients were tested by provincial and national laboratories in China as well as members of the World Health Organization SARS Reference and Verification Laboratory Network in a collaborative effort to identify and confirm SARS-associated coronavirus (SARS-CoV) infection. Although SARS-CoV was not isolated from any patient, specimens from three patients were positive for viral RNA by reverse transcription–polymerase chain reaction assay, and all patients had detectable rises in SARS-CoV–specific antibodies. This study shows the effectiveness of a collaborative, multilaboratory response to diagnose SARS.

A Salmonella enterica serovar Enteritidis epidemic in the United States began in 1978, spread to much of the country in the following decade, and began declining in 1996. We examined correlations between annual changes in S. Enteritidis incidence in humans and introductions of egg quality assurance programs (EQAPs) in some states to reduce S. Enteritidis contamination of eggs. Before EQAPs, 62% of the changes in S. Enteritidis incidence were higher than the baseline for each state. After EQAPs, 73%–84% of the changes were below the baseline. Regression analysis showed that a 1% increase in the number of eggs produced under an EQAP was associated with a 0.14% decrease in S. Enteritidis incidence (p < 0.05). These data indicate that EQAPs probably played a major role in reducing S. Enteritidis illness in these states.

Phylogenetic evidence suggests that endemic and epidemic dengue viruses (DENV), transmitted among humans by the anthropophilic mosquitoes Aedes aegypti and Ae. albopictus, emerged when ancestral, sylvatic DENV transmitted among nonhuman primates by sylvatic Aedes mosquitoes adapted to these peridomestic vectors. We tested this hypothesis by retrospectively examining evidence for adaptation of epidemic and endemic versus sylvatic strains of DENV-2 to Ae. albopictus and Ae. aegypti. First and second-generation offspring of mosquitoes from different geographic regions in the Americas and Southeast Asia were tested for their susceptibility to epidemic/endemic and sylvatic DENV-2 isolates from West Africa, Southeast Asia, and Oceania. Both Aedes species were highly susceptible (up to 100% infected) to endemic/epidemic DENV-2 strains after ingesting artificial blood meals but significantly less susceptible (as low as 0%) to sylvatic DENV-2 strains. Our findings support the hypothesis that adaptation to peridomestic mosquito vectors mediated dengue emergence from sylvatic progenitor viruses.

As part of a study to determine the effects of water filtration on the incidence of community-acquired gastroenteritis in Melbourne, Australia, we examined fecal samples from patients with gastroenteritis and asymptomatic persons for diarrheagenic strains of Escherichia coli. Atypical strains of enteropathogenic E. coli (EPEC) were the most frequently identified pathogens of all bacterial, viral, and parasitic agents in patients with gastroenteritis. Moreover, atypical EPEC were more common in patients with gastroenteritis (89 [12.8%] of 696) than in asymptomatic persons (11 [2.3%] of 489, p < 0.0001). Twenty-two random isolates of atypical EPEC that were characterized further showed marked heterogeneity in terms of serotype, genetic subtype, and carriage of virulence-associated determinants. Apart from the surface protein, intimin, no virulence determinant or phenotype was uniformly present in atypical EPEC strains. This study shows that atypical EPEC are an important cause of gastroenteritis in Melbourne.

Conventional disease surveillance mechanisms that rely on passive reporting may be too slow and insensitive to rapidly detect a large-scale infectious disease outbreak; the reporting time from a patient’s initial symptoms to specific disease diagnosis takes days to weeks. To meet this need, new surveillance methods are being developed. Referred to as nontraditional or syndromic surveillance, these new systems typically rely on prediagnostic data to rapidly detect infectious disease outbreaks, such as those caused by bioterrorism. Using data from a large health maintenance organization, we discuss the development, implementation, and evaluation of a time-series syndromic surveillance detection algorithm for influenzalike illness in Minnesota.

Clusters of meningococcal disease caused by a hyperinvasive lineage of Neisseria meningitidis, the ST11 complex, bearing a serogroup C polysaccharide capsule, have been prominent in Europe and North America since the early 1990s. This situation has led to expensive public health measures for outbreak control and, finally, to the introduction of a serogroup C glyconjugate vaccine into the primary immunization schedule in the United Kingdom and elsewhere. ST11 complex meningococci may also express serogroup W135 polysaccharide capsules. We investigated the level of population immunity to this hyperinvasive clone in association with the appearance of outbreaks of meningococcal disease in southern British Columbia. We found that most adults and almost all children were apparently susceptible to infection with ST11 complex meningococci bearing both C and W135 polysaccharide capsules, which suggests that a vaccine program directed against only serogroup C meningococci may be insufficient to prevent hyperinvasive ST11 disease.

To look for evidence of intrafamilial infection, we isolated 107 Helicobacter pylori clones from biopsied specimens taken from both parents and four children. We compared the sequences of two housekeeping genes (hspA and glmM) from these clones with those of 131 unrelated strains from patients living in different geographic regions. Strain relationships within the family were determined by analyzing allelic variation at both loci and building phylogenetic trees and by using multilocus sequence typing. Both hspA- and glmM-based phylogenetic trees showed East Asian and African branches. All samples from family members showed natural mixed infection. Identical alleles found in some strains isolated from the children and parents, but not in the strains isolated from unrelated patients, demonstrated that strains have circulated within the family. Several mechanisms, such as point mutations, intragenic recombination, and introduction of foreign (African) alleles, were shown to enhance strain diversity within the family.

From 1992 to 1999, we analyzed >2.5 million cases of influenzalike illness (ILI). Nationwide influenza epidemics generally lasted 3–4 months in winter. Kriging analysis, which illustrates geographic movement, showed that the starting areas of peak ILI activity were mostly found in western Japan. Two spreading patterns, monotonous and multitonous, were observed. Monotonous patterns in two seasons featured peak ILI activity that covered all of Japan within 3 to 5 weeks in larger epidemics with new antigenic variants of A/H3N2. Multitonous patterns, observed in the other five seasons, featured peak ILI activity within 12 to 15 weeks in small epidemics without new variants. Applying the kriging method allowed better visualization and understanding of spatiotemporal trends in seasonal ILI activity. This method will likely be an important tool for future influenza surveillance in Japan.

Healthcare-associated outbreaks of gastroenteritis are an increasingly recognized problem, but detailed knowledge of the epidemiology of these events is lacking. We actively monitored three hospital systems in England for outbreaks of gastroenteritis in 2002 to 2003. A total of 2,154 patients (2.21 cases/1,000-hospital-days) and 1,360 healthcare staff (0.47 cases/1,000-hospital-days) were affected in 227 unit outbreaks (1.33 outbreaks/unit-year). Norovirus, detected in 63% of outbreaks, was the predominant etiologic agent. Restricting new admissions to affected units resulted in 5,443 lost bed-days. The cost of bed-days lost plus staff absence was calculated to be £635,000 (U.S.$ 1.01 million) per 1,000 beds. By our extrapolation, gastroenteritis outbreaks likely cost the English National Health Service £115 (U.S.$ 184) million in 2002 to 2003. Outbreaks were contained faster (7.9 vs. 15.4 days, p = 0.0023) when units were rapidly closed to new admissions (<4 days). Implementing control measures rapidly may be effective in controlling outbreaks.

We report the first case of primary amebic meningoencephalitis in Italy, in a 9-year-old boy. Clinical course was fulminant, and diagnosis was made by identifying amebas in stained brain sections and by indirect immunofluorescence analysis. Naegleria fowleri was characterized as genotype I on the basis of polymerase chain reaction test results.

In October 2001, an outbreak of febrile illness began in the southwest islands group of the Republic of Palau. Through October 2003, a total of 15 southwest islanders experienced fever >39.5°C and abdominal distress, both lasting >7days. Orientia tsutsugamushi, the agent of scrub typhus, was subsequently identified as the cause.

This study investigated the long-term excretion of severe acute respiratory syndrome–associated coronavirus in sputum and stool specimens from 56 infected patients. The median (range) duration of virus excretion in sputa and stools was 21 (14–52) and 27 (16–126) days, respectively. Coexisting illness or conditions were associated with longer viral excretion in stools.

Independent risk factors for campylobacteriosis (eating raw, rare, or undercooked poultry; consuming raw milk or raw milk products; and eating chicken or turkey in a commercial establishment) account for <50% of cases in Québec. Substantial regional and seasonal variations in campylobacteriosis were not correlated with campylobacter in chickens and suggested environmental sources of infection, such as drinking water.

We report two laboratory-acquired Brucella melitensis infections that were shown to be epidemiologically related. Blood culture isolates were initially misidentified because of variable Gram stain results, which led to misdiagnoses and subsequent laboratory exposures. Notifying laboratory personnel who unknowingly processed cultures from brucellosis patients is an important preventive measure.

Escherichia coli strains of nonenteropathogenic serogroups carrying eae but lacking the enteropathogenic E. coli adherence factor plasmid and Shiga toxin DNA probe sequences were isolated from patients (children, adults, and AIDS patients) with and without diarrhea in Brazil. Although diverse in phenotype and genotype, some strains are potentially diarrheagenic.

We investigated a multistate cluster of Escherichia coli O157:H7 isolates; pulsed-field gel electrophoresis subtyping, using a single enzyme, suggested an epidemiologic association. An investigation and additional subtyping, however, did not support the association. Confirmation E. coli O157 clusters with two or more restriction endonucleases is necessary before public health resources are allocated to follow-up investigations.

Mycobacterium triplex, a recently described, potentially pathogenic species, caused disease primarily in immunocompromised patients. We report a case of pulmonary infection due to this mycobacterium in an immunocompetent patient and review the characteristics of two other cases. In our experience, Mycobacterium triplex pulmonary infection is unresponsive to antimycobacterial chemotherapy.

During an 8-year study period, Arcobacter butzleri was the fourth most common Campylobacter-like organism isolated from 67,599 stool specimens. Our observations suggest that A. butzleri displays microbiologic and clinical features similar to those of Camplobacter jejuni; however, A. butzleri is more frequently associated with a persistent, watery diarrhea.

From February to October 2003, Mycobacterium goodii wound infections were identified among three patients who received surgical implants at a Colorado hospital. This report summarizes the investigation of the first reported nosocomial outbreak of M. goodii. Increased awareness is needed about the potential for nontuberculous mycobacteria to cause postoperative wound infections.

Recent transmission of dengue viruses has increased in tropical and subtropical areas and in industrialized countries because of international travel. We describe a case of nosocomial transmission of dengue virus in Germany by a needlestick injury. Diagnosis was made by TaqMan reverse transcription–polymerase chain reaction when serologic studies were negative.

We determined the complete genome sequences of two sapovirus strains isolated in Thailand and Japan. One of these strains represented a novel, naturally occurring recombinant sapovirus. Evidence suggested the recombination site was at the polymerase-capsid junction within open reading frame one.