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Clin Infect Dis

First reported outbreak in the United States of cryptosporidiosis associated with a recreational lake.

Kramer MH. Sorhage FE. Goldstein ST. Dalley E. Wahlquist SP. Herwaldt BL.
Epidemic Intelligence Service (Epidemiology Program Office), Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.
In the summer of 1994, an outbreak of cryptosporidiosis occurred among visitors to a state park in New Jersey. We enrolled 185 persons in a cohort study, 38 (20.5%) of whom had laboratory-confirmed cryptosporidiosis or gastrointestinal illness that met our clinical case definition. Having any exposure to lake water (e.g., swimming) was strongly associated with illness (P < .001). The outbreak lasted 4 weeks and affected an estimated 2,070 persons. The most likely sources of the outbreak were contaminated runoff of rainwater and infected bathers. This outbreak of cryptosporidiosis is the first reported to be associated with recreational exposure to lake water. Our investigation shows that even a large and ongoing outbreak may not be detected for several weeks. Health professionals and persons at high risk for severe cryptosporidiosis should be aware that recreational water can be a source of cryptosporidium infection.

Clinical, virological, and histologic evolution of hepatitis C virus infection in liver transplant recipients.

Lumbreras C. Colina F. Loinaz C. Domingo MJ. Fuertes A. Dominguez P. Gomez R. Aguado JM. Lizasoain M. Gonzalez-Pinto I. Garcia I. Moreno E. Noriega AR.
Infectious Diseases Unit, Hospital Universitario Doce de Octubre, Universidad Complutense de Madrid, Spain.
We designed a prospective study to assess the time course and evolution of hepatitis C virus (HCV) infection in 152 patients who underwent a liver transplantation (LT) in our institution. Forty-four recipients (29%) were infected by HCV after transplantation: 40 who developed recurrent infection after LT and four who acquired infection during or after LT. No differences were found in survival actuarial rates at 1, 2, and 4 years after transplantation for patients infected by HCV vs. noninfected ones. Graft hepatitis occurred in 66% of HCV-infected recipients: 18 developed chronic active hepatitis (10 of them with intense fibrosis) and 2 developed cirrhosis during the follow-up. Infection by the HCV-1b genotype was found in 79% of the infected recipients and in 100% of those in whom histologic evolution was worst. Fourteen grafts were lost in 44 HCV-infected recipients, in comparison with 12 in 108 HCV-negative patients (P = .007), mostly because of chronic rejection. HCV infection did not affect life expectancy in the midterm follow-up for LT patients. However, it was often associated with the occurrence of early and severe graft hepatitis and with a higher incidence of graft loss due to chronic rejection.

A prospective nationwide study of Clostridium difficile-associated diarrhea in Sweden. The Swedish C. difficile Study Group.

Karlstrom O. Fryklund B. Tullus K. Burman LG.
Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
Clostridium difficile-associated diarrhea (CDAD) is regarded as an emerging nosocomial infection. All patients positive for C. difficile in Sweden were recorded during 1995, including primary care patients. Those positive for toxin in feces were defined as CDAD cases. A total of 5,133 CDAD cases were recorded (58 per 100,000 inhabitants per year), as compared with 86 cases diagnosed in 1978 and 553 in 1983. CDAD was almost twice as prevalent as all (combined) diagnosed domestic cases of reportable bacterial and protozoal diarrhea. The age-specific incidence was little affected by gender but increased > 10-fold over the age range of 60-98 years. The differences in overall CDAD incidence were sixfold between counties and threefold between major hospitals. Among hospitalized patients the incidences were highest in geriatric/rehabilitation wards, followed by infectious diseases and internal medicine wards; 28% of all cases involved no recent hospitalization and were defined as community-acquired CDAD.

Trends in antibiotic resistance among diarrheal pathogens isolated in Thailand over 15 years.

Year 1998
Hoge CW. Gambel JM. Srijan A. Pitarangsi C. Echeverria P.
Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Antibiotic resistance trends were examined for Shigella species, nontyphoidal Salmonella species, enterotoxigenic Escherichia coli (ETEC), and Campylobacter species isolates from indigenous persons and travelers in Thailand for up to 15 years. Resistance to trimethoprim-sulfamethoxazole was found in >90% of Shigella and 40% of ETEC and nontyphoidal Salmonella isolates. Resistance to nalidixic acid was found in 97%-100% of Shigella dysenteriae 1 strains isolated between 1992 and 1995. Ciprofloxacin resistance was detected in 1% of ETEC isolates in 1994 and 1995 and in one of 349 nontyphoidal Salmonella isolates in 1995. Ciprofloxacin resistance among Campylobacter species increased from zero before 1991 to 84% in 1995 (P < .0001). Azithromycin resistance was found in 7%-15% of Campylobacter isolates in 1994 and 1995, as well as 15% of ETEC and 3% of Salmonella isolates in 1995. Enteric pathogens in Thailand have developed resistance to virtually all antibiotics routinely used in the treatment of diarrhea, as well as the newer fluoroquinolone and macrolide classes of drugs.

Isolation of a toxin B-deficient mutant strain of Clostridium difficile in a case of recurrent C. difficile-associated diarrhea.

Year 1998
Cohen SH. Tang YJ. Hansen B. Silva J Jr.
Department of Internal Medicine, University of California-Davis Medical Center, Sacramento 95817, USA.
Clostridium difficile-associated diarrhea (CDAD) recurs in approximately 15%-20% of patients after discontinuation of metronidazole or vancomycin therapy. Most recurrences are believed to be endogenous relapses due to the persistence of spores. However, there is evidence that reinfection with a different strain is a cause of recurrence. We report the case of a patient with a history of multiple episodes of C. difficile colitis. The patient, a 56-year-old female, has had 5 years of repeated recurrences, each shortly after discontinuing vancomycin therapy. During the course of these episodes, three isolates were cultured from her stools at different times. These isolates were analyzed for the presence of toxin A and B gene sequences and genotyped by means of arbitrarily primed polymerase chain reaction (AP-PCR). The original two isolates contained the toxin A and B genes, as determined by PCR, and were of the same AP-PCR type. During her last relapse, a C. difficile strain lacking at least a portion of the toxin B gene was isolated. AP-PCR analysis of this isolate showed a different DNA banding pattern from that of the previous isolates. A vancomycin susceptibility assay revealed a slight decrease in vancomycin activity as compared with that against the prior isolate. This case demonstrates two unique features: (1) recurrent infections can be due to reinfections and (2) toxin B mutants can possibly cause CDAD. This study also raises concerns about long-term vancomycin use and the development of resistance of C. difficile to vancomycin.

Characteristics of patients with chronic infection due to hepatitis C virus of mixed subtype: prevalence, viral RNA concentrations, and response to interferon therapy.

Year 1998
Toyoda H. Fukuda Y. Hayakawa T. Takayama T. Kumada T. Nakano S. Takamatsu J. Saito H.
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
We studied 349 patients with chronic infection due to hepatitis C virus (HCV), including 83 with coagulopathy, 122 with community-acquired infection, 20 with chronic posttransfusion hepatitis C, and 124 for whom the transmission mode was unknown. The prevalence of mixed-subtype HCV infection was investigated in each group of patients. The serum HCV RNA concentration and the response to interferon (IFN) therapy were evaluated. HCV infection with mixed subtypes was more frequent in patients who had been at high risk for exposure to HCV, such as those with coagulopathy or community-acquired infection. HCV RNA concentrations were lower in patients infected with mixed subtypes, except for those with subtypes 1a and 1b. Ten of 11 patients with mixed subtypes (not including those with 1a and 1b) achieved complete clearance of HCV RNA with IFN therapy.

Prevalence and clinical significance of intestinal microsporidiosis in human immunodeficiency virus-infected patients with and without diarrhea in Germany: a prospective coprodiagnostic study.

Year 1998
Sobottka I. Schwartz DA. Schottelius J. Visvesvara GS. Pieniazek NJ. Schmetz C. Kock NP. Laufs R. Albrecht H.
Department of Internal Medicine, University Hospital Eppendorf, Germany.
The prevalence of intestinal microsporidiosis among human immunodefiency virus (HIV)-infected persons with chronic diarrhea varies from 7% to 50%; thus, microsporidia are a significant source of morbidity and, occasionally, mortality among these patients. Anecdotal reports suggest that intestinal microsporidiosis is also an important infection in patients with AIDS in Germany. To determine the prevalence of microsporidiosis among HIV-infected patients in Germany, we performed a prospective coprodiagnostic study of 97 consecutive HIV-infected patients. Microsporidia were the most common enteropathogen identified in 18 (36.0%) of 50 patients with diarrhea and 2 (4.3%) of 47 patients without diarrhea (P < .001; chi2 test). Microsporidia were present in 60% of patients with chronic diarrhea and 5.9% of patients with acute diarrhea. The etiologic agent was Enterocytozoon bieneusi in 18 patients and Encephalitozoon intestinalis in two patients. The prevalence of intestinal microsporidiosis in this cohort of German patients with AIDS and diarrhea is one of the highest to be reported anywhere in the world. Microsporidiosis seems to represent one of the most important causes of diarrhea in HIV-infected patients in Germany and thus must be considered in the differential diagnosis for all AIDS patients presenting with diarrhea.

Clinical efficacy of and immunologic alterations caused by interferon gamma therapy for alveolar echinococcosis.

Year 1998
Jenne L. Kilwinski J. Radloff P. Flick W. Kern P.
Section of Infectious Diseases and Clinical Immunology, University Hospital and Medical Clinic of Ulm, Germany.
Alveolar echinococcosis (AE) is a rare and often fatal disease characterized by a tumorlike expansion of the metacestode Echinococcus multilocularis in the liver. Because of the severe side effects of therapy with benzimidazoles, we treated a patient with recombinant interferon gamma at a dose of 250 microg over a 3-day period once a month. Disease progression was not detected during the observed period of 18 months. Following stimulation with crude Echinococcus antigen, mRNA from interleukin 5 was still detected in peripheral blood mononuclear cells by means of reverse transcriptase polymerase chain reaction analysis, and expression of interleukin 10 in T lymphocytes (as measured by fluorescence-associated cell sorting of intracellular cytokines) was elevated. These results indicate that bolus therapy with interferon gamma has some clinical effect but does not result in a change in the T helper 2 lymphocyte-dominated immune response to this parasite.

Prediction of response to hepatitis B vaccine in health care workers: whose titers of antibody to hepatitis B surface antigen should be determined after a three-dose series, and what are the implications in terms of cost-effectiveness?

Year 1998
Alimonos K. Nafziger AN. Murray J. Bertino JS Jr.
Department of Pharmacy Services, Research Institute, Cooperstown, New York, USA.
We identified the demographics of 385 health care workers (HCWs) to identify those whose chance of developing a protective response to a standard primary hepatitis B immunization series was so high that the need for testing for antibodies to hepatitis B surface antigen (anti-HBs) would be obviated following immunization. In addition, using sensitivity analysis, we analyzed the economic consequences of not determining anti-HBs titers for any individual after primary immunization and of using the Centers for Disease Control and Prevention (CDC)-recommended post-hepatitis B exposure prophylaxis for high-risk HCWs. Nonsmoking women < 50 years old with a weight-height index of < 42 had a 98.2 +/- 0.9% chance of developing a protective anti-HBs titer. Male nonsmokers < 50 years old with a weight-height index of < 29 had a 94.7 +/- 1.8% chance of a protective response. Economic analysis revealed that use of the CDC guidelines for post-hepatitis B exposure prophylaxis in male HCWs whose anti-HBs status is unknown is always more cost-effective than determining anti-HBs titers following primary immunization for those at high risk. In female HCWs, post-hepatitis B exposure prophylaxis is more cost-effective until hepatitis B exposure rats are approximately 50%. It is possible to predict who will have a high probability of developing a protective response to hepatitis B vaccine; for these people, determining postimmunization anti-HBs titers is unnecessary and not cost-effective.

Clinical features of infections due to Escherichia coli producing heat-stable toxin during an outbreak in Wisconsin: a rarely suspected cause of diarrhea in the United States.

Year 1998
Roels TH. Proctor ME. Robinson LC. Hulbert K. Bopp CA. Davis JP.
Bureau of Public Health, Wisconsin Division of Health, Madison 53703-3044, USA.
In September 1994, a foodborne outbreak of enterotoxigenic Escherichia coli (ETEC) infection occurred in attendees of a banquet in Milwaukee. E. coli was isolated from stool specimens from 13 patients that were comprehensively tested; isolates from five patients were positive for E. coli producing heat-stable toxin, were biochemically identified and serotyped as E. coli O153:H45, and were all resistant to tetracycline, ampicillin, sulfisoxazole, and streptomycin. Diarrhea (100%) and abdominal cramps (83%) were the most prevalent symptoms in 205 cases; vomiting (13%) and fever (19%) were less common. The median duration of diarrhea and abdominal cramps was 6 days and 5 days, respectively. In the United States, health care providers rarely consider ETEC as a possible cause of diarrhea in their patients, and few laboratories offer testing to identify ETEC. Hence, outbreaks of ETEC infection may be underdiagnosed and underreported. As in this outbreak, the relatively high prevalence of diarrhea and cramps lasting > or = 4 days and the low prevalence of vomiting and fever can help distinguish ETEC infection from Norwalk-like virus infection and gastroenteritis due to other causes with incubation times of > or = 15 hours and can provide direction for confirmatory laboratory testing.

Increases in levels of antibody to hepatitis B surface antigen in an immunized population.

Year 1998
Bulkow LR. Wainwright RB. McMahon BJ. Parkinson AJ.
Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska.
Hepatitis B vaccine is effective in preventing infection with hepatitis B virus (HBV), but its duration of protection is unknown. To examine the effect of exposure to HBV on an immunized population, data were analyzed from a cohort of Alaska Natives who were immunized and then followed up annually for 10 years. A boost in antibody to hepatitis B surface antigen (anti-HBs) was defined as a fourfold rise in levels to > or = 20 mIU/mL that was not accompanied by the presence of antibody to hepatitis B core antigen or attributable to interim vaccination. During 10 years of follow-up, 8.2% of 1,595 vaccines had boosts in anti-HBs. Persons with boosts did not differ significantly from those without boosts in terms of age, gender, village, initial level of anti-HBs, or level of anti-HBs before the boost. These results underscore the continued exposure to HBV among vaccinees and the continued protection against disease that the vaccine provides.

Risk factors for early recurrent Clostridium difficile-associated diarrhea.

Year 1998
Do AN. Fridkin SK. Yechouron A. Banerjee SN. Killgore GE. Bourgault AM. Jolivet M. Jarvis WR.
Hospital Infections Program, Centers for Disease Control, Atlanta, Georgia 30333, USA.
Recurrence is a common sequela of Clostridium difficile-associated diarrhea (CDD) and may increase morbidity, costs, and treatment-related antimicrobial resistance. Because recurrent CDD (RCDD) frequently occurs very soon after an initial episode, our goal was to determine the risk factors for early RCDD (occurring < or = 45 days after the initial episode). We conducted a case-control study, comparing 13 patients with early RCDD (case patients) with 46 patients who had only one CDD episode (control patients) at Centre Hospitalier Angrignon (Quebec) during January 1993 through November 1994. Risk factors for early RCDD included a history of chronic renal insufficiency, a white blood cell count of > or = 15 x 10(3)/mm3, and community-acquired diarrhea with the first CDD episode. For seven of eight case patients, C. difficile strains from the first and second CDD episodes were identical, suggesting that relapse is more common than reinfection. These results suggest that treatments should be directed at preventing relapses in patients at high risk for early RCDD.

Epidemiology of severe hospital-acquired infections in patients with liver cirrhosis: effect of long-term administration of norfloxacin.

Year 1998
Campillo B. Dupeyron C. Richardet JP. Mangeney N. Leluan G.
Service d'Hepato-Gastro-Enterologie et Reeducation Digestive and Laboratoire de Bacteriologie, Hopital Albert Chenevier, Creteil, France.
We performed a 5-year retrospective study to evaluate the effect of long-term administration of norfloxacin on the epidemiology of severe hospital-acquired infections in patients with advanced cirrhosis. Sixty-seven episodes of spontaneous bacterial peritonitis and 60 episodes of bacteremia occurred in, respectively, 46 patients (group 1a) and 52 patients (group 1b) who did not receive norfloxacin, while 23 and 17 episodes occurred in 21 patients (group 2a) and 17 patients (group 2b) during or within 10 days after long-term administration of norfloxacin. Enterobacteriaceae were more prevalent in groups 1a and 1b than in the other two groups (P < .001 and P < .01, respectively); conversely, staphylococci were more prevalent in groups 2a and 2b (P < .001 and P < .05, respectively). The rate of staphylococcal resistance to methicillin was 53.6% in groups 1a and 1b and 77.3% in groups 2a and 2b. We conclude that long-term norfloxacin administration to cirrhotic patients reduces the risk of gram-negative infections but increases the risk of severe hospital-acquired staphylococcal infections and of high-level resistance to antibiotics.

Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience and review of the literature.

Year 1998
Iwen PC. Rupp ME. Langnas AN. Reed EC. Hinrichs SH.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-6495, USA.
A 12-year retrospective analysis was done to identify and evaluate in detail cases of invasive pulmonary aspergillosis (IPA) caused by Aspergillus terreus. We identified 13 A. terreus infections among 133 total cases of confirmed invasive aspergillosis; 11 were IPA and 2 were primary peritoneal infections. Of the 11 patients with IPA, 7 developed neutropenia during hospitalization, and the remaining four were receiving immunosuppressive agents. Ten patients with IPA died; one liver transplantation patient without neutropenia survived after treatment with amphotericin B, itraconazole, and a pulmonary lobectomy. Six patients developed disseminated disease, with the heart the most common extrapulmonary site identified (four patients). These cases demonstrate that IPA caused by A. terreus rapidly progresses in immunocompromised patients receiving amphotericin B and illustrate the need for sensitive diagnostic tests and more effective antifungal agents.

Tritherapy for human immunodeficiency virus infection does not modify replication of hepatitis C virus in coinfected subjects.

Year 1998
Zylberberg H. Chaix ML. Rabian C. Rouzioux C. Aulong B. Brechot C. Viard JP. Pol S.
Unite d'Hepatologie, Hopital Necker, Paris, France.
Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis for human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. In an attempt to evaluate the impact of anti-HIV triple combination therapy on the course of hepatitis C virus (HCV)-related chronic hepatitis and on HCV replication, we studied the biological and virological characteristics of 22 HCV/HIV-coinfected patients who were given triple combination therapy. In comparison with baseline values, there was (1) a significant increase in the CD4 and CD8 cell counts and a decrease in the HIV RNA load and (2) no significant variation in aminotransferase activities or the HCV RNA load at 3, 6, or 9 months of tritherapy. Antiretroviral tritherapy seems to modify neither the biological activity of HCV-related chronic hepatitis nor the HCV load, despite immune restoration. Hepatic histopathologic analysis is warranted to assess the impact of immune restoration on liver lesions.

Hepatic penicilliosis in patients without skin lesions.

Year 1998
Kantipong P. Panich V. Pongsurachet V. Watt G.
Department of Medicine, Chiangrai Regional Hospital, Thailand.
Penicillium marneffei is a common cause of opportunistic fungal infection in patients with AIDS in Thailand. The diagnosis of penicilliosis is easily made when typical skin lesions appear but is frequently missed in their absence. We therefore attempted to identify noncutaneous indicators of P. marneffei infection in order to provide early curative treatment. We recognized a characteristic syndrome in six AIDS patients with penicilliosis involving primarily the liver but not the skin who presented with fever of short duration, hepatomegaly, and markedly elevated serum alkaline phosphatase levels. The diagnosis was confirmed by demonstrating the causative organism in the liver or in the blood. Increased awareness of hepatic penicilliosis and more-rapid diagnostic methods are needed to reduce the high mortality rate associated with this syndrome. P. marneffei is predominantly an Asian pathogen, but as a result of international travel, the need for increased awareness of penicilliosis is worldwide.

Hepatocellular carcinoma presenting as pyogenic liver abscess: characteristics, diagnosis, and management.

Year 1998
Yeh TS. Jan YY. Jeng LB. Chen TC. Hwang TL. Chen MF.
Department of Surgery and Pathology, Chang-Gung Memorial Hospital, Chang-Gung University, Taipei, Taiwan.
We performed a 17-year retrospective analysis of 10 cases of hepatocellular carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and biliary obstruction caused by tumor thrombi, superimposed with bacterial infection, were the two major pathogeneses. Exact diagnosis of the underlying hepatocellular carcinoma was made for five of the 10 patients before management was attempted. Main clinical manifestations included fever, chills, right-upper-quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis C, chronic liver disease, unexplained anemia, marked weight loss, and a severely inversed albumin/globulin ratio raise suspicions about the underlying hepatocellular carcinoma. Management strategies included percutaneous drainage (n = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to administration of parenteral antibiotics in all cases. The prognosis was dismal, with a mean survival of 3.5 months (range, 8 days to 6 months).

Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum.

Year 1998
Okhuysen PC. Chappell CL. Crabb J. Valdez LM. Douglass ET. DuPont HL.
Division of Infectious Diseases, University of Texas Health Science Center, Houston, USA.
Bovine hyperimmune anti-Cryptosporidium colostrum immunoglobulin (BACI) decreases the intensity of Cryptosporidium parvum infection in vitro. We investigated the prophylactic effect of BACI in healthy adults challenged with C. parvum. After we established an oocyst dose that resulted in 100% infection in four volunteers (baseline group), 16 volunteers were randomized to receive (1) BACI prior to C. parvum challenge (BACI group) and a nonfat milk placebo 30 minutes later, (2) BACI prior to and 30 minutes after challenge (reinforced BACI group), or (3) nonfat milk placebo prior to and 30 minutes after challenge. Subjects received BACI (10 g) or nonfat milk placebo three times a day for a total of 5 days and were followed for clinical symptoms and oocyst excretion for 30 days. A trend toward less diarrhea (P = .08) was observed for subjects receiving BACI in comparison with occurrences in placebo recipients. Subjects receiving BACI or nonfat milk placebo had a 100-fold reduction in oocyst excretion as compared with excretion in the baseline group.

Primary liver abscess due to Klebsiella pneumoniae in Taiwan.

Year 1998
Wang JH. Liu YC. Lee SS. Yen MY. Chen YS. Wang JH. Wann SR. Lin HH.
Department of Internal Medicine, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China.
Pyogenic liver abscess is an uncommon complication of intra-abdominal or biliary tract infection and is usually a polymicrobial infection associated with high mortality and high rates of relapse. However, over the past 15 years, we have observed a new clinical syndrome in Taiwan: liver abscesses caused by a single microorganism, Klebsiella pneumoniae. We reviewed 182 cases of pyogenic liver abscess during the period September 1990 to June 1996; 160 of these cases were caused by K. pneumoniae alone, and 22 were polymicrobial. When patients with K. pneumoniae liver abscess were compared with those who had polymicrobial liver abscess, we found higher incidences of diabetes or glucose intolerance (75% vs. 4.5%) and metastatic infections (11.9% vs. 0) and lower rates of intra-abdominal abnormalities (0.6% vs. 95.5%), mortality (11.3% vs. 41%), and relapse (4.4% vs. 41%) in the former group. Liver abscess caused by K. pneumoniae is a new clinical syndrome that has emerged as an important infectious complication in diabetic patients in Taiwan.

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