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Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Hepatitis B virus (HBV) reactivation in patients with resolved HBV infection was found in 23 (4%) of 552 newly hepatitis B surface antigen – positive patients in Japan. Because one-fourth of cases develop into fulminant hepatic failure and mortality is 100%, management of HBV reactivation in patients with resolved HBV infection should be discussed. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Background.  Burkholderia pseudomallei is endemic in northern Australia, and melioidosis is a common cause of sepsis in the region. Methods.  We summarized the cutaneous manifestations of melioidosis from a prospective cohort of 486 patients with culture-confirmed melioidosis in northern Australia, and we compared those who had primary skin melioidosis with those who had other forms of melioidosis. Results.  Primary skin melioidosis occurred in 58 patients (12%). Secondary skin melioidosis — multiple pustules from hematogenous spread — was present in 10 patients (2%). Patients with primary skin melioidosis were more likely to have chronic presentations (duration, ?2 months). On multivariate analysis, patients with primary cutaneous melioidosis were more likely to be children aged ?15 years (adjusted odds ratio, 8.50; 95% confidence interval [CI], 3.24 – 22.28) and to have a history of occupational exposure to B. pseudomallei (adjusted odds ratio, 3.12; 95% CI, 1.56 – 6.25) but were less likely to have typical risk factors — including diabetes (adjusted odds ratio, 0.26; 95% CI, 0.12 – 0.56), excessive alcohol intake (adjusted odds ratio, 0.45; 95% CI, 0.22 – 0.90), and chronic lung disease (adjusted odds ratio, 0.26; 95% CI, 0.10 – 0.67). Of those patients with primary skin melioidosis, 1 patient was bacteremic and none had severe sepsis or died from melioidosis. Four (7%) of the 58 patients presenting with primary skin melioidosis had disseminated melioidosis, and 1 (2%) experienced a relapse of melioidosis. Nine patients (16%) were cured with a regimen of oral antibiotics alone, and 1 recovered with no therapy. Conclusion.  In our cohort, patients with primary skin melioidosis were younger, had fewer underlying medical conditions, and had better outcomes than did those with other forms of melioidosis. There may be a role for exclusive oral antibiotic therapy for some cases of primary skin melioidosis. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Background.  Patients may experience multiple episodes of bacterial meningitis. Information from large studies of recurrent meningitis is limited. We evaluated the incidence of recurrent bacterial meningitis and the distribution of causative organisms in The Netherlands. Methods.  Data for patients with bacterial meningitis were prospectively collected nationwide for the period 1988 – 2005. Recurrent meningitis was defined as an episode of meningitis that either occurred ?28 days after a previous episode or occurred <28 days after a previous episode but was caused by a different pathogen or different subtype of the same pathogen. Results.  Of 18,915 patients, 202 (predominantly male) patients had recurrent bacterial meningitis ($P< .01$). Prevailing causative organisms were Streptococcus pneumoniae (40% of cases), Neisseria meningitidis (22%), and non – type b Haemophilus influenzae (9%). Pneumococci serotypes included in the heptavalent vaccine caused only 36% of cases of recurrent pneumococcal meningitis. The proportion of episodes caused by meningococcus serogroups W135, Y, and Z was higher among patients with recurrent meningitis than among those with nonrecurrent meningitis (odds ratio, 12.8), and the proportion caused by nontypeable and type f H. influenzae was also higher among patients with recurrent meningitis (odds ratio, 3.8 and 5.6, respectively). Conclusions.  In The Netherlands, the prevalence of recurrent bacterial and fungal meningitis is low. The distribution of causative microorganisms differs between cases of recurrent meningitis and cases of nonrecurrent meningitis; this could be associated with vaccination. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Background.  Primary liver abscess caused by Klebsiella pneumoniae is an infection that is emerging worldwide and that is associated with severe morbidity and considerable mortality. Methods.  A retrospective analysis of 110 episodes of primary liver abscess caused by K. pneumoniae that required hospitalization during 2001 – 2002 was conducted to identify predictors of metastatic infection, mortality, and the efficacy of first-generation cephalosporins and percutaneous drainage. The potential role of Klebsiella rmpA and magA genes was also evaluated. Results.  The study included 59 men and 51 women, with a mean age of 61.8 years. Diabetes was noted in 67 patients (60.9%). Metastatic infection occurred in 17 patients (15.5%), with meningitis accounting for 11 patients (64.7%) and endophthalmitis accounting for 4 patients (23.5%). The overall mortality rate was 10.0% (11 patients). Most of the severe complications occurred within the first 3 days after hospital admission. Ninety-two patients (83.6%) received treatment with cefazolin for >3 days. Four patients (4.3%) of the group who received cefazolin had metastatic infection, 1 patient (1.1%) experienced septic shock, and 3 (3.3%) experienced acute respiratory failure. Five (5.4%) of those 92 patients died. Multivariable analysis revealed that rmpA (odds ratio [OR], 28.85), Acute Physiologic and Chronic Health Evaluation (APACHE) II score ?20 (OR, 8.08), and septic shock (OR, 4.33) were statistically significant predictors of metastatic infection. Metastatic infection (OR, 6.73), severity of disease (APACHE II score ?16; OR, 11.82), septic shock (OR, 8.30), acute respiratory failure (OR, 69.92), and gas formation revealed on imaging (OR, 13.26) predicted mortality. Pigtail drainage protected against both metastatic infection (OR, 0.25) and mortality (OR, 0.14). Conclusion.  Management of primary liver abscess caused by K. pneumoniae with use of first-generation cephalosporins and percutaneous drainage was associated with low rates of mortality, metastatic infection, and complications. These rates are comparable to those reported for third-generation cephalosporins. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
AIDS [Acquired Immunodeficiency Syndrome] Drug Assistance Programs, operating within the larger Ryan White Program, are state-based, discretionary programs that provide a drug 'safety net' for low-income and uninsured individuals infected with human immunodeficiency virus (HIV). Although the AIDS Drug Assistance Programs and the primary care system that provides care for patients with HIV infection are already financially stressed, the Centers for Disease Control and Prevention recently issued guidelines recommending universal HIV testing to help identify the estimated 300,000 individuals in the United States who are unaware that they are infected with HIV. As the number of people living with HIV/AIDS who are coinfected with hepatitis C virus has grown and the cost and complexity of care have increased, the sustainability of the current HIV care system requires a reevaluation in light of the new testing guidelines. We examine the current state of the AIDS Drug Assistance Programs, discuss the implications of the Centers for Disease Control and Prevention guidelines for the already overstretched Ryan White Program, and consider a federally supported national program to ensure high-quality, efficient HIV care for low-income HIV-infected Americans. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Background.  Recurrent genital herpes is a major problem for patients worldwide. Early episodic treatment with short-course therapy is effective, often stopping progression of outbreaks. This study is the first head-to-head comparison of single-day famciclovir (1000 mg administered twice daily) versus 3-day valacyclovir (500 mg administered twice daily) for episodic therapy in immunocompetent patients. Methods.  In this multicenter, multinational, double-blind, parallel-group study, 1179 adults with a history of recurrent genital herpes were randomized 1:1 to receive either famciclovir or valacyclovir. Patients initiated treatment within 6 h after a recurrence. The primary objective was to establish noninferiority of single-day famciclovir, compared with a 3-day course of valacyclovir, in time to healing of all nonaborted lesions in a modified intent-to-treat population. Results.  This study established that single-day famciclovir therapy was noninferior to 3-day valacyclovir therapy in reducing time to healing of all nonaborted genital herpes lesions (median time to healing, 4.25 days vs. 4.08 days). Approximately one-third of patients in each treatment group had aborted genital herpes episodes, suggesting that both treatments have similar efficacy in preventing outbreaks or progression of lesions beyond the papule stage. There was no significant difference in time to resolution of symptoms associated with recurrence. The overall incidence of adverse events was similar (23.2% for the famciclovir group vs. 22.3% for the valacyclovir group), with headache, nausea, diarrhea, vomiting, and abdominal pain reported most often. Conclusions.  Single-day famciclovir (1000 mg administered twice daily) was similar to 3-day valacyclovir (500 mg administered twice daily) in both efficacy and safety, representing a more convenient treatment for immunocompetent adults with recurrent genital herpes. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Background.  External acuminata condylomata (EAC) are among the most common sexually transmitted diseases. Although it is understood that low-risk human papillomavirus (HPV) genotypes 6 and 11 are associated with EAC, there have only been a few, small, published studies reporting the genotype-specific prevalence of HPV. The objective of our study was to assess the prevalence of HPV genotypes for a large number of cases involving both men and women and to evaluate the potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in France. Methods.  A total of 256 women and 260 men who presented with EAC to French gynecologists, dermatologists, and proctologists were prospectively recruited during the period January through April 2007. Specimens were collected with a cytobrush, and the HPV genotype was determined using the INNO-LiPA assay (Innogenetics), which detects 24 HPV genotypes. Results.  Four hundred twenty-three ß-globin – positive samples could be analyzed. The median age of patients was 30 years (range, 18 – 72 years). The overall prevalence of HPV DNA in patients with EAC was 99% (33% of patients were coinfected with another pathogen). Low-risk genotypes predominated, with a prevalence of 89%. The most prevalent genotypes were 6 (69%) and 11 (16%), followed by 16 (9%), 51 (8%), 52 (7%), 66 (6%) 53 (5%), 31 (3%), and 18 (3%). The cumulative prevalence of genotypes 6 and 11 was 83%, and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 88%. Conclusions.  This study is, to our knowledge, the first large, multicenter survey to provide solid data on HPV genotype distribution among patients with EAC. Our results provide strong evidence that, in France, the most prevalent HPV genotypes in persons with EAC are 6 and 11. Because of its 99% efficacy for the prevention of EAC and a vaccine coverage of 100%, the quadrivalent HPV vaccine could prevent 62% – 87% of EAC cases in France. 

 

Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Background.  Enteroviruses are shed in human stool and can cause a wide spectrum of illness. They are the leading cause of aseptic meningitis. Methods.  In 2004, the Connecticut Department of Public Health investigated a meningitis cluster among persons returning from a school-organized trip to Mexico. Results.  Among 29 travelers (25 teenagers and 4 adult chaperones), 21 became acutely ill. Viral culture and nucleic acid amplification testing of stool ($n=27$) and cerebrospinal fluid ($n=4$) specimens identified enteroviral infection in 20 of 28 travelers from whom any specimen was obtained; 4 had echovirus 30 only, 11 had coxsackievirus (CV) A1 only, 4 had both echovirus 30 and CVA1, and 1 had CVA5 only. Illness onset dates were tightly clustered 4 days after a prolonged swim in the Gulf of Mexico. Time spent swimming was significantly associated with the odds of enteroviral infection (univariate odds ratio for each additional hour swimming, 14.3; 95% confidence interval, 1.3 – 154.3). Headache, fever, vomiting, and nausea occurred more frequently among the echovirus 30 – infected travelers than among the uninfected control subjects ($P< .05$). The most frequent symptoms among travelers infected with only CVA1 identified were nausea and diarrhea (36% each), but neither was significantly associated with CVA1 infection; 5 patients with CVA1 infection were asymptomatic. Conclusions.  We identified multiple enteroviruses among the travelers. Clustered illness onsets suggest point-source exposure, which likely was a sea swim in sewage-contaminated seawater. Novel molecular amplification and sequencing methodologies were required to recognize the rarely identified CVA1, but it is ambiguous whether CVA1 infection caused illness. Travelers should be aware of risks associated with swimming in natural waters when visiting areas where there is limited sewage treatment. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 585-586, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page i, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page iii-iv, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page v-vi, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 439-443, 15 August 2008.
Background.  Acinetobacter baumannii is increasingly recognized as being a significant pathogen associated with nosocomial outbreaks in both civilian and military treatment facilities. Current analyses of these outbreaks frequently describe patient-to-patient transmission. To date, occupational transmission of A. baumannii from a patient to a health care worker (HCW) has not been reported. We initiated an investigation of an HCW with a complicated case of A. baumannii pneumonia to determine whether a link existed between her illness and A. baumannii – infected patients in a military treatment facility who had been entrusted to her care. Methods.  Pulsed-field gel electrophoresis and polymerase chain reaction/electrospray ionization mass spectrometry, a form of multilocus sequencing typing, were done to determine clonality. To further characterize the isolates, we performed a genetic analysis of resistance determinants. Results and Conclusions.  A 'look-back' analysis revealed that the multidrug resistant A. baumannii recovered from the HCW and from a patient in her care were indistinguishable by pulsed-field gel electrophoresis. In addition, polymerase chain reaction/electrospray ionization mass spectrometry indicated that the isolates were similar to strains of A. baumannii derived from European clone type II (Walter Reed Army Medical Center strain type 11). The exposure of the HCW to the index patient lasted for only 30 min and involved endotracheal suctioning without use of an HCW mask. An examination of 90 A. baumannii isolates collected during this investigation showed that 2 major and multiple minor clone types were present and that the isolates from the HCW and from the index patient were the most prevalent clone type. Occupational transmission likely occurred in the hospital; HCWs caring for patients infected with A. baumannii should be aware of this potential mode of infection spread. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 444-449, 15 August 2008.
Background.  Acinetobacter baumannii is usually associated with nosocomial pneumonia or bacteremia. Reports of A. baumannii skin and soft-tissue infection (SSTI) are uncommon. Methods.  We performed a retrospective review of 57 inpatients admitted to a naval hospital ship and identified 8 patients with A. baumannii – associated SSTI. Demographic and clinical characteristics were compared between these patients and 49 patients with A. baumannii infections that were not SSTIs. We also reviewed 18 cases of A. baumannii – associated SSTI from the literature. Results.  Our 8 cases of A. baumannii – associated SSTI were associated with combat trauma wounds. The median age of the patients was 26 years. Although not statistically significant, A. baumannii – associated SSTIs were more likely to be associated with gunshot wounds (75% vs. 55%) or external fixators (63% vs. 29%), compared with A. baumannii infections that were not SSTIs. Use of a central venous catheter and total parenteral nutrition was also more common for patients with SSTI. Our cases of A. baumannii – associated SSTI presented as cellulitis with a 'peau d'orange' appearance with overlying vesicles and, when untreated, progressed to necrotizing infection with bullae (hemorrhagic and nonhemorrhagic). In our case series, all isolates were multidrug resistant, and clinical success was achieved for 7 of 8 patients with debridement and carbapenem therapy. Conclusions.  A. baumannii – associated SSTI is an emerging infection in patients who experience trauma. Clinicians should be aware of the potential role of A. baumannii as a multidrug-resistant pathogen causing hospital-acquired SSTI, particularly when associated with previous trauma or use of invasive devices. It should be suspected in patients who experience trauma and have edematous cellulitis with overlying vesicles. Early empirical coverage for drug-resistant species (e.g., with carbapenem therapy), combined with debridement, is usually curative. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 450-457, 15 August 2008.
Background.  Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions. Methods.  XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre – XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993 – 2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting. Results.  Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre – extensively drug resistant. The proportion of pre – XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 ($P=.02$). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment. Conclusions.  XDR TB and pre – XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 458-468, 15 August 2008.
Background.  Japanese encephalitis is a major public health problem in Asia. However, there is little data on the long-term outcome of Japanese encephalitis survivors. Methods.  We prospectively evaluated children with serologically confirmed Japanese encephalitis over an 8.3-year period. The patients were assessed and their outcomes were graded with a functional outcome score at hospital discharge and at follow-up appointments. We examined how patient outcome at hospital discharge compared with that at long-term follow-up visits, when changes in outcome occurred, and the prognostic indicators of the eventual outcome. Results.  One hundred and eighteen patients were recruited into the study, and 10 (8%) died during the acute phase of illness. At hospital discharge, 44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae. Eighty six of the 108 patients were followed up for a median duration of 52.9 months (range, 0.9 – 114.9 months). During follow-up, 31 patients experienced improvement, but 15 patients experienced deterioration in their outcome grade. In most cases, assessment during the first 3 – 6 months after hospital discharge was predictive of the long-term outcome. More than one-half of the patients continued to experience neuropsychological sequelae and behavioral disorders. A combination of poor perfusion, Glasgow coma score ?8, and ?2 witnessed seizures predicted a poor long-term outcome with 65% sensitivity and 92% specificity. Conclusions.  Neurological assessment of Japanese encephalitis survivors at hospital discharge does not predict long-term outcome. Seizures and shock are treatable risk factors for a poor outcome at hospital discharge and at long-term follow-up visits. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 469-475, 15 August 2008.
Background.  An outbreak of chikungunya virus infection occurred on Reunion Island during the period 2005 – 2006. Persistent arthralgia after chikungunya virus infection has been reported, but few studies have treated this aspect of the disease. Methods.  Adult patients with laboratory-confirmed acute chikungunya virus infection who were referred to Groupe Hospitalier Sud Reunion during the period 2005 – 2006 were asked to participate in the study. Patients were assessed a mean of 18 months after acute disease occurred. Assessment consisted of answering questions on a standard form, undergoing a medical examination, and being tested for the presence of IgM antibodies to chikungunya virus. Results.  Eighty-eight patients (mean age, 58.3 years; male-to-female ratio, 1.1:1.0) were included in this study. Fifty-eight patients (65.9%) had been hospitalized for acute chikungunya virus infection, and a history of arthralgia before chikungunya virus infection was reported by 39 patients (44%). Fifty-six patients (63.6%) reported persistent arthralgia related to chikungunya virus infection, and in almost one-half of the patients, the joint pain had a negative impact on everyday activities. Arthralgia was polyarticular in all cases, and pain was continuous in 31 patients (55.4%). Overall, 35 patients (39.7%) had test results positive for IgM antibodies to chikungunya virus. Conclusions.  Persistent and disabling arthralgia was a frequent concern in this cohort of patients who had experienced severe chikungunya virus infection ~18 months earlier. Further studies are needed to evaluate the prevalence of persistent arthralgia in the general population to determine the real burden of the disease. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 476-484, 15 August 2008.
Background.  Prior to the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), the rate of invasive pneumococcal disease (IPD) was 8-fold higher among White Mountain Apache persons of all ages than it was among the general US population, . We aimed to assess the impact of PCV7 and 23-valent pneumococcal polysaccharide vaccine on the rate of IPD among White Mountain Apache persons. Methods.  From 1991 through 2006, we conducted active laboratory- and population-based surveillance among Native American residents of the White Mountain Apache reservation. Charts were reviewed and pneumococcal isolates were collected for serotype testing. Three time periods were defined: the pre-PCV7 baseline period (1991 – 1997), the PCV7 efficacy trial period (1998 – 2000), and the PCV7 routine-use period (2001 – 2006). Results.  We identified 246 cases of IPD; the mean annual IPD rate fell from 126 cases per 100,000 person-years in the period 1991 – 1997 to 87 cases per 100,000 person-years in the period 2001 – 2006 ($P=.01$). The rate of IPD attributable to PCV7 serotypes of Streptococcus pneumoniae decreased by 252 cases per 100,000 person-years (92%) among children aged <5 years, and that attributable to non-PCV7 serotypes of S. pneumoniae decreased by 87 cases per 100,000 person-years (44%) among children aged <5 years. Among adults, the rate of IPD remained unchanged; PCV7 serotypes of S. pneumoniae accounted for only 25% of adult cases during the period 1991 – 1997. Conclusions.  Since the introduction of PCV7, the rate of IPD among White Mountain Apache children aged <5 years has decreased to the lowest rate ever (122 cases per 100,000 person-years), but it remains 5.7-fold greater than the rate of IPD among children in the general US population. In contrast to some other high-risk populations, there is no evidence of non – vaccine-type replacement disease in this age group. Among White Mountain Apache adults, the rate of IPD remains substantially higher than that observed in the general US population. Vaccines with broader serotype coverage are needed to further reduce the disparity in the rate of IPD between the White Mountain Apache and general US populations. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 485-486, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 487-495, 15 August 2008.
Background.  Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission. Methods.  A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Löwenstein-Jensen medium. These were compared with the widely used indirect proportion method on Löwenstein-Jensen medium. Results.  All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Löwenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively). Conclusion.  Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 496-502, 15 August 2008.
Background.  Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. Methods.  This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. Results.  Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index ?18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of >4 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. Conclusions.  Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 503-509, 15 August 2008.
Background.  Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis. Methods.  We analyzed the impact of delaying effective amphotericin B – based therapy on outcome among 70 consecutive patients with hematologic malignancy who had zygomycosis in our institution during the period 1989 – 2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment. Results.  Delayed amphotericin B – based therapy (i.e., initiating treatment ?6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7 – 38.2; $P=.008$) in multivariate analysis. Active malignancy ($P=.003$) and monocytopenia ($P=.01$) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy ($P=.01$) and neutrophil recovery ($P=.009$) were predictive of a favorable outcome. Conclusions.  Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 510-516, 15 August 2008.
Background.  Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously defined, and associations with sepsis outcomes have not been subjected to multivariable analysis. Methods.  We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection. Results.  XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 µg/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30 – 3.43). In intensive care unit – based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90 – 2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27 – 24.92) after adjustment for bacteremia, comorbidities, and age. Conclusions.  We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 517-518, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 519-527, 15 August 2008.
Accurate diagnosis of osteomyelitis underlying diabetic foot ulcers is essential to optimize outcomes. We undertook a meta-analysis of the accuracy of diagnostic tests for osteomyelitis in diabetic patients with foot ulcers. Pooled sensitivity and specificity, the summary measure of accuracy (Q*), and diagnostic odds ratio were calculated. Exposed bone or probe-to-bone test had a sensitivity of 0.60 and a specificity of 0.91. Plain radiography had a sensitivity of 0.54 and a specificity of 0.68. MRI had a sensitivity of 0.90 and a specificity of 0.79. Bone scan was found to have a sensitivity of 0.81 and a specificity of 0.28. Leukocyte scan was found to have a sensitivity of 0.74 and a specificity of 0.68. The diagnostic odds ratios for clinical examination, radiography, MRI, bone scan, and leukocyte scan were 49.45, 2.84, 24.36, 2.10, and 10.07, respectively. The presence of exposed bone or a positive probe-to-bone test result is moderately predictive of osteomyelitis. MRI is the most accurate imaging test for diagnosis of osteomyelitis. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 528-530, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 531-534, 15 August 2008.
The retrospective study of 34 patients with Hodgkin lymphoma – associated hemophagocytic syndrome led us to define this association as a specific disorder. Its characteristics are male predominance (male-to-female sex ratio, 3.3:1), immunodeficiency-like histological features (lymphocyte depletion, 45% of cases; mixed cellularity Hodgkin lymphoma subtype, 40%), and strong association with Epstein-Barr virus (94%). 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 535-539, 15 August 2008.
By use of an automated polymerase chain reaction test of plasma and a qualitative polymerase chain reaction assay on polymorphonuclear leukocytes, we identified a subgroup of hematopoietic cell transplant recipients who were able to control cytomegalovirus infection early after hematopoietic cell transplantation without antiviral therapy. Thirty-one percent of patients had cytomegalovirus DNA detected by qualitative polymerase chain reaction assay but had no cytomegalovirus DNA detected by the automated test; this group maintained a lower peak cytomegalovirus load, compared with the group of patients who had cytomegalovirus DNA detected by both tests ($P=.03$), suggesting a greater degree of functional immune reconstitution. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 540-541, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 542-553, 15 August 2008.
Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 554-566, 15 August 2008.
Acute infection with Toxoplasma gondii during pregnancy and its potentially tragic outcome for the fetus and newborn continue to occur in the United States, as well as worldwide, despite the fact that it can be prevented. The infection can be acquired through ingestion of infected, undercooked meat or contaminated food or water. Transmission to the fetus occurs almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss, mental and psychomotor retardation, seizures, hematological abnormalities, hepatosplenomegaly, or death. Systematic education and serological screening of pregnant women are the most reliable and currently available strategies for the prevention, diagnosis, and early treatment of the infection in the offspring; this is largely because toxoplasmosis in pregnant women most often goes unrecognized. Treatment of the infection in the fetus and infant during the first year of life has been demonstrated to significantly improve the clinical outcome. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 567-574, 15 August 2008.
Background.  Dyslipidemia alone does not fully explain the increase in cardiovascular events among patients receiving protease inhibitor (PI) – based treatment for human immunodeficiency virus infection. Some PIs, such as indinavir, directly induce endothelial dysfunction, an effect that may mediate that portion of the increase in cardiovascular events that is not attributable to dyslipidemia. Methods.  Endothelium-dependent vasodilation, insulin-mediated vasodilation, and whole-body and leg glucose uptake during use of a 1-h euglycemic hyperinsulinemic clamp (insulin infusion, 40 mU/m2/min) were measured in healthy men before and after 4 weeks of treatment with placebo (12 men), with 400 mg atazanavir per day (9 men), or with 400 mg lopinavir and 100 mg ritonavir twice per day (9 men). Results.  Median age (36 years) and mean body mass index ± SD ($23.4\pm 2.6$; calculated as weight in kilograms divided by the square of height in meters) did not differ between groups. Endothelium-dependent vasodilation, expressed as the percentage change in the leg blood flow response to intrafemoral artery infusion of 15 µg/min of the endothelium-dependent vasodilator methacholine, did not change after 4 weeks of treatment in any group: mean percentage change ± SD, $154\pm 102$ from baseline and $242\pm 254$ at week 4 with atazanavir ($P=.36$), $76\pm 62$ and $86\pm 79$, respectively, with lopinavir-ritonavir ($P=.68$), and $111\pm 86$ and $127\pm 153$, respectively, with placebo ($P=.63$; for between-group differences, $P=.55$). The response to the endothelium-independent vasodilator nitroprusside was not different at week 4 for any group, nor was insulin-mediated vasodilation or leg or whole-body insulin-mediated glucose uptake (all within-group P values were >.1). Conclusions.  Unlike the dramatic impairment seen with indinavir, the newer PIs atazanavir and lopinavir-ritonavir do not induce endothelial dysfunction in healthy subjects. Thus, endothelial dysfunction does not appear to be a PI drug class effect. The cause of the non – lipid-mediated increase in cardiovascular events that are reported with PIs remains unclear. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 575-576, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 577-584, 15 August 2008.
Objectives.  We examined the relationship between receipt of medical care for human immunodeficiency virus (HIV) infection and HIV transmission risk behavior among persons who had received a recent diagnosis of HIV infection. Methods.  We enrolled 316 participants from 4 US cities and prospectively followed up participants for 1 year. Generalized estimating equations were used to examine whether having at least 3 medical care visits in a 6-month period was associated with unprotected vaginal or anal intercourse with an HIV-negative partner or partner with unknown HIV status. Results.  A total of 27.5% of the participants (84 of 305) self-reported having unprotected sex with an HIV-negative or unknown status partner at enrollment, decreasing to 12% (31 of 258) and 14.2% (36 of 254) at 6-month and 12-month follow-ups, respectively. At follow-up, people who had received medical care for HIV infection at least 3 times had reduced odds of engaging in risk behavior, compared with those with fewer visits. Other factors associated with reduced risk behavior were being >30 years of age, male sex, not having depressive symptoms, and not using crack cocaine. Conclusions.  Being in HIV care is associated with a reduced prevalence of sexual risk behavior among persons living with HIV infection. Persons linked to care can benefit from prevention services available in primary care settings. 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 587, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 587, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 587-588, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 588, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page 588-590, 15 August 2008.
 

 

Clinical Infectious Diseases, Volume 47, Issue 4, Page e39-e41, 15 August 2008.
We report a case of symptomatic Plasmodium falciparum malaria that manifested 4 years after a visit to an area of endemicity in an 18-year-old male patient with sickle cell disease. The exceptionally long incubation time raises the questions of how and where P. falciparum parasites can reside for several years before suddenly causing disease.