Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond.

This review presents evidence-based guidelines for the prevention of infection after blood and marrow transplantation. Recommendations apply to all myeloablative transplants regardless of recipient (adult or child), type (allogeneic or autologous) or source (peripheral blood, marrow or cord blood) of transplant. In Section I, Dr. Dykewicz describes the methods used to rate the strength and quality of published evidence supporting these recommendations and details the two dozen scholarly societies and federal agencies involved in the genesis and review of the guidelines. In Section II, Dr. Longworth presents recommendations for hospital infection control. Hand hygiene, room ventilation, health care worker and visitor policies are detailed along with guidelines for control of specific nosocomial and community-acquired pathogens. In Section III, Dr. Boeckh details effective practices to prevent viral diseases. Leukocyte-depleted blood is recommended for cytomegalovirus (CMV) seronegative allografts, while ganciclovir given as prophylaxis or preemptive therapy based on pp65 antigenemia or DNA assays is advised for individuals at risk for CMV. Guidelines for preventing varicella-zoster virus (VZV), herpes simplex virus (HSV) and community respiratory virus infections are also presented. In Section IV, Drs. Baden and Rubin review means to prevent invasive fungal infections. Hospital design and policy can reduce exposure to air contaminated with fungal spores and fluconazole prophylaxis at 400 mg/day reduces invasive yeast infection. In Section V, Dr. Sepkowitz details effective clinical practices to reduce or prevent bacterial or protozoal disease after transplantation. In Section VI, Dr. Sullivan reviews vaccine-preventable infections and guidelines for active and passive immunizations for stem cell transplant recipients, family members and health care workers.

Rubella seropositivity in the United States, 1988-1994.

Data obtained in the third National Health and Nutrition Examination Survey (NHANES III), conducted during 1988-1994, were analyzed to determine the epidemiology of rubella seropositivity in the United States, including risk factors for low rubella seropositivity. Serological samples obtained from NHANES III study participants > or =6 years of age were tested for rubella IgG antibodies. "Rubella seropositivity" was defined as serum rubella IgG antibody level > or =10 IU by enzyme immunoassay. Overall, rubella seropositivity rates in the United States were 92% in persons aged 6-11 years, 83% in persons aged 12-19 years, 85% in persons aged 20-29 years, 89% in persons aged 30-39 years, and >or =93% in persons aged > or =40 years. The lowest rate (78%) of any United States birth cohort of the 20th century occurred among persons born from 1970-1974. Eliminating rubella and chronic rubella syndrome in the United States will require international efforts, including vaccination of preschool- and school-age children and all susceptible young adults.

Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients.

This article contains highlights of "Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients: Recommendations of the CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation," which was published in the Morbidity and Mortality Weekly Report. There are sections on the prevention of bacterial, viral, fungal, protozoal, and helminth infections and on hospital infection control, strategies for safe living following transplantation, immunizations, and hematopoietic stem cell safety. The guidelines are evidence-based, and prevention strategies are rated by both the strength of the recommendation and the quality of evidence that supports it. Recommendations are given for preventing cytomegalovirus disease with prophylactic or preemptive gancyclovir, herpes simplex virus disease with prophylactic acyclovir, candidiasis with fluconazole, and Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole. Hopefully, following the recommendations made in the guidelines will reduce morbidity and mortality from opportunistic infections in hematopoietic stem cell transplant recipients.

Hospital infection control in hematopoietic stem cell transplant recipients.

Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients contains a section on hospital infection control including evidence-based recommendations regarding ventilation, construction, equipment, plants, play areas and toys, health-care workers, visitors, patient skin and oral care, catheter-related infections, drug-resistant organisms, and specific nosocomial infections. These guidelines are intended to reduce the number and severity of hospital infections in hematopoietic stem cell transplant recipients.

Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: focus on community respiratory virus infections.

Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant (HSCT) recipients, cosponsored by the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, and the American Society for Blood and Marrow Transplantation, were issued in October 2000. The guidelines recommend that to minimize transmission of community respiratory virus (CRV) infection, health care workers and visitors with symptoms of upper respiratory tract infection be restricted from having contact with HSCT recipients and candidates undergoing conditioning therapy. To screen HSCT recipients for CRVs, active clinical surveillance for CRV disease should be conducted on all hospitalized HSCT recipients and candidates undergoing conditioning therapy, including daily monitoring for signs and symptoms of CRV infections. Respiratory syncytial virus (RSV) is the most important CRV because it is the most prevalent and because RSV pneumonia has a high case-fatality rate. For this reason, it is recommended that respiratory secretions of any hospitalized HSCT candidate or recipient with signs and symptoms of CRV infection be tested promptly for RSV. If test results are positive, the patient should be treated early and aggressively. Early preemptive therapy with such treatments as aerosolized ribavirin has been proposed, but limited data preclude a recommendation as to the optimal strategy. Lifelong seasonal influenza vaccination is recommended for all HSCT recipients.

Protists as opportunistic pathogens: public health impact in the 1990s and beyond.

Protist organisms (protozoa and fungi) have become increasingly prominent as opportunistic pathogens among persons infected with human immunodeficiency virus (HIV) and among organ transplant recipients--two immunocompromised populations that have increased dramatically in the past two decades. Pneumocystis carinii pneumonia continues to be the most common serious opportunistic infection (OI) among HIV-infected persons in the United States, occurring frequently among persons not previously receiving medical care. Toxoplasmosis, cryptococcosis, cryptosporidiosis, and isosporiasis occur frequently in HIV-infected persons in the developing world. Candidiasis and aspergillosis are common OIs in organ transplant recipients. As these populations of immunosuppressed patients continue to expand worldwide new OIs caused by protist pathogens are likely to emerge.

Transmission of measles virus in healthcare settings during a communitywide outbreak.

OBJECTIVE: To describe the epidemiology of measles in medical settings and to evaluate the implementation and effectiveness of the 1989 Advisory Committee on Immunization Practices (ACIP) guidelines for measles immunization in healthcare workers (HCWs). DESIGN: Confirmed cases of measles reported in Clark County, Washington, from March 14 to June 2, 1996, were analyzed for characteristics of cases occurring in medical settings. A questionnaire was used to assess employee immunization (95% response rate). SETTING AND PARTICIPANTS: Reported measles cases and HCWs at community hospitals, primary-care medical facilities, a health-maintenance organization, and a multispecialty group practice. RESULTS: Of 31 cases of measles, 8 (26%) occurred in HCWs, and 5 (16%) occurred in patients or visitors to medical facilities. Cases of measles occurred in HCWs who were not required to have proof of measles immunity as defined by the 1989 ACIP guidelines. The relative risk of measles in HCWs compared to Clark County adults was 18.6 (95% confidence interval, 7.4-45.8; P<.001). A survey of medical facilities revealed that 47% had an employee measles immunization policy; only 21% met ACIP recommendations and enforced their policies. CONCLUSIONS: HCWs were at higher risk of measles than the adult population. Transmission of measles in medical settings was related to both deficiencies in, and lack of implementation of, the ACIP guidelines.

Preventing opportunistic infections in bone marrow transplant recipients.

In 1996, a Center for Disease Control and Prevention (CDC)-sponsored working group began developing guidelines for preventing opportunistic infections (OIs) in bone marrow transplant (BMT) recipients. The purposes of the guidelines are to: a) summarize current data regarding the epidemiology of OIs in BMT recipients; b) produce an evidence-based statement of recommended strategies for preventing OIs in BMT recipients; c) decrease the incidence, morbidity, and mortality of OIs in BMT recipients; and d) define directions for future OI prevention research. Each recommendation is given two ratings: one indicating the strength of the recommendation, and another indicating the strength of evidence supporting the recommendation. The target audience for the guidelines includes transplant and infectious disease physicians and BMT unit and clinic staff. The BMT OI guidelines include sections on viral, bacterial, fungal, protozoal, and helminth infections, immunization, infection control, and blood and stem cell safety. The disease-specific sections address preventing exposure and disease among both adult and pediatric recipients of allogeneic and autologous BMTs. The immunization section addresses: a) immunization of BMT recipients, their household contacts, and health care workers; b) travel immunizations for BMT recipients; and c) passive immunization with immune globulin products. The infection control sections address room ventilation, isolation and barrier precautions, and prevention of nosocomial and other infections (e.g. infections acquired from visitors, plants, food, pets, construction sites, etc.). The blood safety section contains recommendations on preventing transmission of infections to BMT recipients from infected donated cells. After the guidelines are made available for public comment, they will be finalized and published in the Morbidity and Mortality Weekly Report and placed on the CDC web site.

Changing epidemiology of congenital rubella syndrome in the United States.

To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome (CRS) and to identify missed opportunities for maternal vaccination, data from CRS cases reported to the National Congenital Rubella Syndrome Registry (NCRSR) from 1985 through 1996 were analyzed. Missed opportunities for maternal vaccination were defined as missed postpartum, premarital, and occupational opportunities, that is, times when rubella vaccination is recommended but was not given. From 1985 through 1996, 122 CRS cases were reported to the NCRSR. The most frequent CRS-related defect was congenital heart disease. Of the reported infants with CRS, 44% were Hispanic. Of 121 known missed opportunities for rubella vaccination among 94 mothers of infants with indigenous CRS, 98 (81%) were missed postpartum opportunities. CRS continues to occur in the United States. Hispanic infants have an increased risk of CRS. Missed opportunities for postpartum rubella vaccination were identified for 52% of indigenous CRS cases.

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

Kawasaki syndrome in Washington State. Race-specific incidence rates and residential proximity to water.

OBJECTIVES: To calculate race-specific incidence rates of Kawasaki syndrome (KS) and to assess the association of KS with residential proximity to water in Washington State. DESIGN: Incidence study over 4 1/2 years, using cases identified with a new statewide hospital data set and a case-control study. SETTING: King, Pierce, and Snohomish counties in Washington State. PATIENTS: One hundred twelve population-based incident cases meeting Centers for Disease Control and Prevention criteria for KS. MAIN OUTCOME MEASURES: Race-specific KS incidence rates and distance to permanent bodies of water among KS cases and matched controls. RESULTS: For the years 1985 through 1986 and 1987 through 1989, the annual KS incidence rates were 6.5 and 15.2 per 100,000 children younger than 5 years, respectively. Rates were highest among Asian Americans (33.3 per 100,000 children younger than 5 years in the 1987-1989 period), followed by blacks and whites (23.4 and 12.7 per 100,000 children younger than 5 years, respectively). The median distance to water did not differ between cases and controls and the proportion of cases living within 150 yd (135 m) of water was no greater than that of controls (odds ratio, 1.0; 95% confidence interval, 0.1 to 20.9). CONCLUSIONS: With complete ascertainment of incident-hospitalized cases of KS, the race-specific rates are among the highest documented in the United States. The rate among Asian Americans was less than that found in Japan, perhaps due to differences in environmental exposures or variations in susceptibility among different Asian ethnic groups. Although we found no association with permanent bodies of water, future studies of KS should include home inspection to assess exposure to temporary collections of standing water.

Lymphocytic choriomeningitis outbreak associated with nude mice in a research institute.

OBJECTIVE: After an employee at a cancer research institute was diagnosed with lymphocytic choriomeningitis, an investigation was performed to determine the extent of lymphocytic choriomeningitis virus (LCMV) infections among the institute's employees and to identify risk factors for infection. DESIGN: Retrospective cohort study. SETTING: A US cancer research institute. PARTICIPANTS: Eighty-two of 90 institute employees. MAIN OUTCOME MEASURES: Serum LCMV antibodies. RESULTS: Seven workers (9%) with definite LCMV infection (LCMV IgG antibody titer greater than or equal to 16) and one worker (1%) with probable infection (IgG titer = 8) were identified (10% overall seroprevalence). All infected employees handled animals or animal tissues and were more likely than other animal handlers to have worked with nude mice (Mus musculus) (P less than .02). Among the 31 employees who worked with nude mice at the institute, infected workers were more likely to clean the cages of nude mice (P much less than .001), change their bedding (P less than .01), and change their water (P less than .001). The institute had been injecting nude mice with LCMV-infected tumor cell lines and had recently increased the nude mouse population and the duration of experiments. These changes would have increased the LCMV burden at the facility and were temporally associated with the cluster of LCMV infections in employees. CONCLUSIONS: This LCMV outbreak, the first reported since 1974, is the first associated with nude mice. It illustrates the ongoing hazard LCMV poses in research laboratories. Since the symptoms of LCMV infection can be nonspecific, clinicians should consider this diagnosis in ill patients who report laboratory rodent exposure.

Virus zoonoses and their potential for contamination of cell cultures.

Silent virus infections of laboratory animals present a human health hazard, from direct exposure and from contamination of biological products for human use. Here we report two recent examples. In 1989, an outbreak of lymphocytic choriomeningitis virus (LCMV) infections was recognized among workers at a cancer research center after an animal caretaker developed viral meningitis. Investigation revealed that multiple tumor cell lines at the facility were infected with LCMV, as were research animals injected with these cell lines. Of 82 workers tested, eight (10%) were found to have been infected. The infected workers were more likely than other animal handlers to report handling athymic (nude) mice (p less than .0.007). The number of nude mice used in this facilty had increased five-fold in the previous year, possibly explaining the timing of the outbreak. This is the first reported LCMV outbreak since 1975, and the first to implicate nude mice as a source of human LCMV infections. In November 1989 and January 1990, infections caused by two distinct Ebola-like filoviruses were discovered in non-human primates at quarantine facilities in Virginia and Pennsylvania. Although 22 persons were considered to have high- or medium-risk exposures for Ebola infection, no Ebola-compatible illnesses occurred. One of the medium-risk persons had Ebola IgG antibodies confirmed by IFA and Western blot. Rigorous use of barrier precautions may have limited exposure and infection with these filoviruses. In February 1990, new groups of filovirus-infected monkeys were identified in Virginia and in Texas. Seroconversion occurred in four animal handlers, including one to very high titer, but again no illness was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of nutritional indices and classifications in predicting death of malnourished children.

The usefulness of nutritional indices and classifications in predicting the death of children under 5 years old was evaluated by comparing measurements of 34 children with diarrhoea who died in a Dhaka hospital with those of 318 patients who were discharged in a satisfactory condition. In a logistic regression analysis mid-upper arm circumference was found to be as effective as other nutritional indices in predicting death. Combinations of different indices did not improve the prediction. Arm circumference might be preferable to more complex criteria for predicting the death of malnourished children.