Cholera in Louisiana. Widening spectrum of seafood vehicles.

The largest cholera outbreak in the United States in over a century occurred in Louisiana from August through October 1986. Eighteen persons in 12 family clusters had stool culture or serologic evidence of infection with toxigenic Vibrio cholerae 0-group 1. Thirteen of these persons had severe diarrhea, and 4 required intensive care unit treatment. Although all 18 survived, 1 96-year-old woman with suspected cholera died shortly after hospital admission. A case-control study showed that case-patients were more likely than neighborhood control subjects to have eaten cooked crabs or cooked or raw shrimp during the week before illness. Case-patients who ate crabs were more likely than control subjects who ate crabs to have undercooked and mishandled the crabs after cooking. A third vehicle from the Gulf waters, raw oysters, caused V cholerae 01 infection in two persons residing in Florida and Georgia. All three seafood vehicles came from multiple sources. Stool isolates from the Louisiana case-patients were genetically identical to other North American strains isolated since 1973, but differ from African and Asian isolates. While crabs are the most important vehicle for V cholerae 01 infection in the United States, shrimp and oysters from the Gulf coast can also be vehicles of transmission. A persisting reservoir of V cholerae 01 along the Gulf coast may continue to cause sporadic cases and outbreaks of cholera in Gulf states and in states importing Gulf seafood.

How well does physician selection of microbiologic tests identify Clostridium difficile and other pathogens in paediatric diarrhoea? Insights using multiplex PCR-based detection.

The objective of this study was to compare the aetiologic yield of standard-of-care microbiologic testing ordered by physicians with that of a multiplex PCR platform. Stool specimens obtained from children and young adults with gastrointestinal illness were evaluated by standard laboratory methods and a developmental version of the FilmArray Gastrointestinal (GI) Diagnostic System (FilmArray GI Panel), a rapid multiplex PCR platform that detects 23 bacterial, viral and protozoal agents. Results were classified according to the microbiologic tests requested by the treating physician. A median of three (range 1-10) microbiologic tests were performed by the clinical laboratory during 378 unique diarrhoeal episodes. A potential aetiologic agent was identified in 46% of stool specimens by standard laboratory methods and in 65% of specimens tested using the FilmArray GI Panel (p < 0.001). For those patients who only had Clostridium difficile testing requested, an alternative pathogen was identified in 29% of cases with the FilmArray GI Panel. Notably, 11 (12%) cases of norovirus were identified among children who only had testing for Clostridium difficile ordered. Among those who had C. difficile testing ordered in combination with other tests, an additional pathogen was identified in 57% of stool specimens with the FilmArray GI Panel. For patients who had no C. difficile testing performed, the FilmArray GI Panel identified a pathogen in 63% of cases, including C. difficile in 8%. Physician-specified laboratory testing may miss important diarrhoeal pathogens. Additionally, standard laboratory testing is likely to underestimate co-infections with multiple infectious diarrhoeagenic agents.

Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group.

Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

Sex hormones and coronary artery disease.

Previous investigators have found an increased risk of coronary heart disease in men with high levels of circulating estrogens. To elucidate further this relationship, a case-control study of atherosclerotic coronary artery disease (ASCAD) and sex hormones was undertaken in male patients. Hormone levels in men with severe ASCAD documented at angiography were compared with those in men found to be virtually free from disease and with those in a group of control subjects without signs or symptoms of ASCAD. Significantly lower total testosterone levels were observed among men with severe ASCAD compared with either control group; the free testosterone level was significantly lower than in angiographically disease-free control subjects. The same pattern of hormone levels persisted after control of covariates. Epidemiologic analysis demonstrated a fivefold decrease in risk for severe ASCAD between the lowest and the highest quartile of total testosterone. No overall pattern of association was seen between ASCAD and free or total estrogens.

The prophylactic use of low-dose amphotericin B in bone marrow transplant patients.

PURPOSE: To evaluate the efficacy of prophylactic low-dose amphotericin B (0.1 mg/kg per day) (LDA) in preventing fungal infections in patients who have had a bone marrow transplant (BMT). MATERIALS AND METHODS: Double-blind, randomized, controlled trial in which patients undergoing bone marrow transplantation received intravenous LDA or similar-appearing placebo from the onset of neutropenia until the absolute neutrophil count remained > 0.5 x 10(9)/L, or until high-dose amphotericin B was initiated. Weekly surveillance cultures were obtained from all patients. RESULTS: Five of 18 patients (28%) randomized to placebo developed documented systemic fungal infections within the first 30 days after transplantation, compared to none of 17 patients who received LDA (P = 0.045). LDA recipients received fewer days of high-dose amphotericin B (P = 0.04) and fewer days of antibiotics (P = 0.008). There were trends towards fewer days of hospitalization (P = 0.14) and improved survival (P = 0.08); these differences were statistically significant among recipients of allogeneic BMT. No adverse effects occurred with LDA therapy. CONCLUSIONS: LDA appears to be safe and to reduce early systemic fungal infections in BMT recipients. Improved survival was observed among LDA recipients, but this was not directly attributable to the prevention of fungal infection.

A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah.

OBJECTIVE: To determine epidemiologic features, trends in frequency, and predictors of clinical outcome of postdiarrheal hemolytic uremic syndrome (HUS) in Utah. DESIGN: A 20-year population-based study of HUS with a review of the HUS registry, hospital records, transplant registry, and a survey of pediatricians and pediatric nephrologists to ensure completeness of ascertainment. POPULATION: All Utah residents under 18 years of age with HUS occurring after a diarrheal prodrome between 1971 and 1990. OUTCOME MEASURES: Incidence of HUS, severity, complications, and long-term sequelae. RESULTS: There were 157 cases during 20 years; 140 (89%) occurred after a diarrheal prodrome. The mean annual incidence was 1.42/100,000 children (range 0.2 to 3.4/100,000 children/year). Periods of high incidence occurred; however, there was no overall sustained increase in incidence. Escherichia coli O157:H7 was isolated from the stool of 62% of children who had specimens submitted. There were no differences between the first and second decade in the proportion with diarrheal prodrome, bloody diarrhea, most abnormal laboratory values, hospital course, or outcome. However, admission laboratory abnormalities were more severe during the first decade suggesting a delay in diagnosis. Age < 2 years, anuria before admission, and higher white blood cell counts on admission predicted severe disease. Bad outcome (death, end-stage renal disease, or stroke) occurred in 11%; 5% died. Chronic renal sequelae, usually mild, were found on follow-up (median 6.5 years) in 51% of survivors. CONCLUSIONS: HUS has been an important clinical and public health problem in Utah for 20 years. The consistency of the clinical and epidemiologic features over 2 decades suggests that a common etiologic agent has accounted for most cases of HUS in this region since 1971.

Diarrhea among African children born to human immunodeficiency virus 1-infected mothers: clinical, microbiologic and epidemiologic features.

Diarrhea and weight loss are common features of pediatric and adult human immunodeficiency type 1 (HIV-1) infection, particularly in developing countries. We studied prospectively episodes of diarrhea in 559 children, ages 10 to 15 months, participating in a longitudinal study of perinatal HIV-1 infection in Kinshasa, Zaire. Children with HIV-1 infection had more frequent episodes of diarrhea and were more likely to present with fever or moderate or severe dehydration and to have persistent or fatal diarrhea. Of 9 HIV-1-positive infants with diarrhea, 3 had enteroadherence factor-positive Escherichia coli, compared with 5 of 74 HIV-1-negative children with diarrhea (P = 0.04); no other pathogen was associated with HIV-1 infection. In a logistic regression model diarrhea was significantly associated with HIV-1 infection in the child, moderate or severe malnutrition and symptoms of acquired immunodeficiency syndrome in the mother. Diarrhea among children with perinatal HIV infection in Zaire is more severe than among uninfected children and is associated with malnutrition and advanced disease in the mother.

Surveillance cultures in bone marrow transplant recipients: worthwhile or wasteful?

A prospective study of the value of surveillance cultures was performed in a bone marrow transplant (BMT) unit among 48 consecutive patients. All patients were admitted to laminar airflow or high-efficiency particulate air (HEPA) filtered rooms, maintained on reduced microbial diets and received oral non-absorbable antibiotics. With the onset of neutropenia, all patients received imipenem/cilastatin and 17 patients received low-dose amphotericen B 0.1 mg/kg/day. Pre-transplant and weekly post-transplant cultures of the stool, throat and urine were obtained on all patients. Nasal and vaginal cultures were performed on 26 patients. Sixteen patients developed 23 documented infections. The sensitivity of surveillance cultures for all infections was 38%, specificity 25%, positive predictive value 20% and negative predictive value 44%. When stratified by organisms, the sensitivity, specificity, positive predictive value and negative value were: Gram positive infections, 33%, 36%, 11%, 70%, Gram negative infections, 17%, 88%, 17%, 88%; fungal infections 37%, 50%, 11%, 75%; and Candida albicans, 100%, 57%, 14%, 100%. These data suggest that surveillance cultures may be useful to exclude C. albicans infections but are of limited value in predicting other types of infections in recipients of BMT.

Bacillus cereus infections among oncology patients at a children's hospital.

BACKGROUND: Bacillus cereus can cause severe infections in immunocompromised persons. METHODS: We report 3 cases of bacteremia/septicemia (1 fatal) among oncology patients in a children's hospital. Because all cases occurred during a 10-day period, a common source outbreak was suspected. An epidemiologic investigation was performed. Molecular comparison of patient and environmental isolates was performed by using pulsed-field gel electrophoresis. RESULTS: After an extensive investigation, no common hospital source could be found. Pulsed-field gel electrophoresis proved that the isolates were not related. CONCLUSION: Sporadic infections in immunocompromised persons do occur and can be associated with significant morbidity.

Hemolytic-uremic syndrome in adolescents.

OBJECTIVE: To compare the epidemiological characteristics, clinical features, and outcome of adolescents with hemolytic-uremic syndrome (HUS) with those of children with HUS. DESIGN: A retrospective descriptive study using data stored in the computerized Utah HUS registry. SETTING: The HUS registry contains data on postdiarrheal and nondiarrheal HUS cases since 1970 in which the patients were younger than 18 years of age at the time of diagnosis and includes virtually all Utah cases as well as those referred from surrounding states. PATIENTS: Seventeen adolescents (age, 12-17 years) and 276 younger patients from September 30, 1970, through December 5, 1993, who met the diagnostic criteria for HUS. MAIN OUTCOME MEASURES: Age, sex, seasonality, prodromal features (eg, antecedent diarrhea), laboratory values, hospital course, outcome, and chronic sequelae. RESULTS: The 17 adolescent patients, who composed 5.8% of the study population, experienced a course of the disease that was similar to that of the younger patients. Diarrhea preceded HUS in approximately 90% of the patients in both groups. Laboratory values were similar in teenagers and younger patients. The hospital courses were also similar; seizures occurred in almost 20%, and hypertension and oligoanuric renal failure occurred in most. Two (12%) of the teenagers and 7 (2.4%) of the younger patients died during the acute phase of the syndrome (P = .09); almost 50% of both groups experienced 1 or more chronic renal sequelae. End-stage renal disease has occurred in 1 (5.8%) of the teenagers and 6 (2.2%) of the children. At follow-up, 1 or more years (median, 5 years) after the onset of HUS, hypertension was present in 22% of the teenagers and 6.7% of the preteens (P = .14). A below-normal glomerular filtration rate was seen in approximately 30% of both groups; proteinuria was noted in approximately 25% of both groups. Approximately 10% of both groups had a combination of proteinuria and a low glomerular filtration rate and are, therefore, at risk for eventual end-stage renal disease. CONCLUSIONS: In our region of the Intermountain West, HUS in adolescents closely resembles that seen in children and the outcome is more favorable than that experienced by adults.

Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir.

BACKGROUND: Molluscum contagiosum virus (MCV) causes cutaneous skin growths that mainly affect children, sexually active adults, and immunocompromised individuals. Lesions of MCV in patients infected with human immunodeficiency virus can be large and numerous, and response to available treatments is often unsatisfactory. OBSERVATIONS: We describe 3 men infected with human immunodeficiency virus who presented with extensive MCV lesions that were not responsive to various treatments. Patient 1 demonstrated dramatic clearing of his MCV lesions when intravenous cidofovir therapy was started for his treatment-resistant bilateral CMV retinitis and because of cidofovir's possible activity against MCV. In case 2, cidofovir was compounded as a 3% cream in a combination vehicle (Dermovan) for extensive facial involvement, and complete resolution of MCV was seen after 1 month of therapy. In case 3, intravenous cidofovir therapy was started both for CMV retinitis and in an attempt to clear 90% facial MCV involvement; after 1 month of treatment, all clinical evidence of MCV had resolved. All 3 patients remain clear of recurrence. CONCLUSIONS: Cidofovir, a nucleotide analog of deoxycytidine monophosphate, appears to have contributed to clearing of advanced MCV lesions in these 3 patients, thus providing suggestive evidence of clinical activity against MCV. Controlled trials of cidofovir therapy for MCV in persons infected with human immunodeficiency virus are warranted.

Advances in antimicrobial therapy.

Despite several decades of improved therapy and prevention of infectious diseases, infectious pathogens remain major causes of morbidity and mortality in humans worldwide. Among the most complex and daunting problems facing medical science is the evolution of antibiotic resistance among many common and once easily-treated infectious agents. This review summarizes the status of newer antimicrobial agents that have utility against pathogens infecting the central nervous system.

Clustering of post-diarrheal (Shiga toxin-mediated) hemolytic uremic syndrome in families.

AIMS: 1. To study the epidemiological and clinical features of Shiga toxin (Stx)-mediated (post-diarrheal) hemolytic uremic syndrome (HUS) occurring in more than 1 family member. 2. To compare familial with non-familial episodes, and concurrent familial with non-concurrent familial cases. 3. To determine the likelihood of Stx HUS occurring in a second family member. METHODS: A retrospective review from January 1970 through September 2001 of families in whom Stx HUS occurred in more than 1 family member was conducted using a computerized HUS registry. It contains information on 373 episodes that occurred in 356 families from Utah and neighboring states. Cases were categorized as being either concurrent (i.e., occurring within a month of one another) or non-concurrent, and the study was limited to those with typical (post-diarrheal) episodes. RESULTS: HUS occurred in 2 or more family members in 17 (4.8%) of the families in our registry. In 12 (3.4%) of these families episodes occurred with days to weeks of each other; in 5 families (1.4%) episodes were separated by intervals of several years. There were no statistically significant differences in demographic, seasonal, laboratory, clinical, or outcome variables between familial subsets (concurrent versus non-concurrent) or between familial and non-familial cases. CONCLUSIONS: When a child is diagnosed with D+ HUS, there is an increased risk that a second family member will also develop HUS; most often within days to weeks (i.e., within a month), but in some cases episodes may be separated by intervals of years. Non-concurrent cases suggest common environmental risk factors, or perhaps a genetic predisposition. Concurrent cases suggest a common source of infection or person-to-person transmission; a genetic predisposition cannot be excluded. These observations suggest that siblings of an index case who develop diarrhea should be kept under close surveillance.

Spontaneous intestinal perforation in premature infants: a distinct clinical entity associated with systemic candidiasis.

PURPOSE: The aim of this study was to define patient characteristics, risk factors, microbiology, and outcome of spontaneous intestinal perforations (SIP) in premature infants. METHODS: To identify the characteristics and frequency of SIP, the medical records of 94 premature infants were reviewed retrospectively. RESULTS: Eleven infants experienced 12 episodes of SIP and 53 infants had 55 episodes of confirmed necrotizing enterocolitis (NEC). Compared with infants who had NEC, the infants with SIP were smaller and born more prematurely. The onset of illness was earlier and was associated with antecedent hypotension, leukocytosis, and a gasless appearance on abdominal radiograph. Blue abdominal discoloration was present in 11 of 12 babies with SIP, but in only one of the babies with NEC. Infants with SIP were significantly more likely to have systemic candidiasis. When controlling for birth weight and age, early onset, blue abdomen, and a gasless abdominal radiograph continued to be statistically significant markers of SIP. CONCLUSIONS: SIP occurs about 12-fold less frequently than NEC in preterm infants. A combination of clinical, laboratory, and radiological features distinguish very low birthweight infants with SIP from those with NEC. Obvious signs of bowel perforation are infrequent with SIP. SIP is frequently associated with systemic candidiasis.

A new look at typhoid vaccination. Information for the practicing physician.

Most cases of typhoid fever in the United States occur in international travelers, with the greatest risk associated with travel to Peru, India, Pakistan, and Chile. Laboratory workers and household contacts of long-term carriers are also at greater risk than the general population. Decisions to the use typhoid vaccine involve weighing the risk of illness against the risk of vaccine reactions. Until recently, the only typhoid vaccine commercially available to US civilians was a heat-phenol-inactivated parenteral product that is 51% to 77% effective in preventing typhoid fever but frequently produces local pain and swelling, fever, headache, and malaise. A new orally administered, live-attenuated vaccine, made from the Ty21a strain of Salmonella typhi, has been recently licensed in the United States. This vaccine provides equivalent protection with a much lower incidence of adverse reactions. It is administered in a four-dose series given over 7 days. Since neither vaccine offers total protection, the most important elements in prevention of typhoid fever remain sound biosafety precautions in laboratory workers and care in selecting food and beverages by those traveling to areas where typhoid fever is endemic.

Partner notification for control of HIV: results after 2 years of a statewide program in Utah.

OBJECTIVES: We sought to evaluate the utility of partner notification for control of human immunodeficiency virus (HIV) infection and to identify subgroups in which it may be most effective. METHODS: All persons reported to be HIV-positive during a 2-year period were interviewed. Outcome measures included proportion of index patients cooperating; number of partners named, located, counseled, and tested; number of persons newly testing positive; and costs. RESULTS: Of 308 index patients, 244 (79%) cooperated. They named 890 partners; 499 (70%) of in-state partners were located. Of these, 154 (34%) had previously tested HIV-positive. Of 279 partners tested for the first time, 39 (14%) were HIV-positive. Injecting drug users were significantly more likely to cooperate than persons in other risk groups (93% vs 76%) and named more partners (median 4 vs 1). Women and persons choosing confidential testing were more likely to cooperate and named more partners. The estimated cost of the program was $62,500 per year. CONCLUSIONS: Partner notification identified a group with a high seroprevalence of HIV. It was not successful among populations that may be difficult to reach with other interventions.

Invasive sinonasal disease due to Scopulariopsis candida: case report and review of scopulariopsosis.

Sinonasal infection with fungi of the order Mucorales--termed mucormycosis or zygomycosis--is sometimes seen in immunosuppressed patients, including those with diabetic ketoacidosis and malignancy. We describe a case of invasive sinonasal infection with Scopulariopsis candida (not among the Mucorales organisms) in a 12-year-old girl who was being treated for non-Hodgkin's lymphoma. Only a few cases of invasive infection with Scopulariopsis species have been reported previously; five of six of these cases were associated with persistent or fatal disease. Our patient survived without undergoing radical surgical debridement and was treated with granulocyte colony-stimulating factor, amphotericin B, and itraconazole; chemotherapy was stopped. In vitro susceptibility testing of our patient's Scopulariopsis isolate showed that it was resistant to amphotericin B and that it was relatively susceptible to itraconazole and miconazole. The case described herein demonstrates the expanding spectrum of fungal organisms that may cause invasive sinonasal infection in immunocompromised hosts and the need for reliable antifungal susceptibility testing.

A community-wide outbreak of hepatitis A in a religious community: impact of mass administration of immune globulin.

Community-wide outbreaks of hepatitis A are frequently prolonged and difficult to control. An extensive outbreak of hepatitis A in a religious community provided an opportunity to assess the effect of mass administration of immune globulin on the course of the outbreak. Between July 1, 1988 and May 30, 1989, 204 cases occurred among 3,500 residents (58/1,000), with persons aged 5-19 years having the highest attack rate. It was found that 89% of persons older than age 19, but no persons under age 20, had evidence of prior hepatitis A infection. During a 5-day campaign, immune globulin (0.02 ml/kg) was administered to 2,287 (65%) of the 3,500 residents. The cost of vaccine and syringes was less than $3,500. New cases among immune globulin recipients virtually stopped 2 weeks after the campaign, and the incidence of hepatitis in the community decreased from 9.6/week to 1.9/week. Among persons younger than age 20 years, the efficacy of immune globulin was 88.9% (95% confidence interval 77.9-94.5) for seven months. Although the authors cannot be sure that the outbreak will not recur, they believe that mass administration of immune globulin appears to have been partially effective at controlling this community-wide outbreak.