Jonathan E. Kaplan

Chronic Fatigue Syndrome: A Working Case Definition

The chronic Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias. Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently. Despite the name of the syndrome, both the diagnostic value of Epstein-Barr virus serologic tests and the proposed causal relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome remain doubtful. We propose a new name for the chronic Epstein-Barr virus syndrome--the chronic fatigue syndrome--that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies, and to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.

Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy.

The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and disseminated Mycobacterium avium complex ¿MAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care. Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART. PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care. The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART. Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.

Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003-2008 has been incorporated into this document.

Acquired immunodeficiency syndrome (AIDS) associated with transfusions.

Of 2157 patients with the acquired immunodeficiency syndrome (AIDS) whose cases were reported to the Centers for Disease Control by August 22, 1983, 64 (3 per cent) with AIDS and Pneumocystis carinii pneumonia had no recognized risk factors for AIDS. Eighteen of these (28 per cent) had received blood components within five years before the onset of illness. These patients with transfusion-associated AIDS were more likely to be white (P = 0.00008) and older (P = 0.0013) than other patients with no known risk factors. They had received blood 15 to 57 months (median, 27.5) before the diagnosis of AIDS, from 2 to 48 donors (median, 14). At least one high-risk donor was identified by interview or T-cell-subset analysis in each of the seven cases in which investigation of the donors was complete; five of the six high-risk donors identified during interview also had low T-cell helper/suppressor ratios, and four had generalized lymphadenopathy according to history or examination. These findings strengthen the evidence that AIDS may be transmitted in blood.

Epidemiology of Norwalk Gastroenteritis and the Role of Norwalk Virus in Outbreaks of Acute Nonbacterial Gastroenteritis

Outbreaks of Norwalk gastroenteritis, which may involve persons of all ages, occur during all seasons and in various locations. Waterborne, foodborne, and person-to-person modes of transmission have been described, and secondary person-to-person transmission is common. Outbreaks generally end in about 1 week; longer outbreaks occur only when new groups of susceptible persons are introduced, usually in the setting of a persistent common source of infection. The illness is generally mild and characterized by nausea, vomiting, diarrhea, and abdominal cramps. Vomiting is the predominant symptom among children, whereas diarrhea is commoner among adults. Forty-two percent of 74 outbreaks of acute nonbacterial gastroenteritis investigated by the Centers for Disease Control from 1976 to 1980 were attributed to the Norwalk virus. The rest resembled Norwalk outbreaks clinically and epidemiologically and were probably caused by 27-nm viral agents similar to the Norwalk virus.

The Epidemiology of Antiretroviral Drug Resistance among Drug-Naive HIV-1-Infected Persons in 10 US Cities

BACKGROUND The prevalence and characteristics of persons with newly diagnosed human immunodeficiency virus (HIV) infections with or without evidence of mutations associated with drug resistance have not been well described. METHODS Drug-naive persons in whom HIV had been diagnosed during the previous 12 months and who did not have acquired immune deficiency syndrome were sequentially enrolled from 39 clinics and testing sites in 10 US cities during 1997-2001. Genotyping was conducted from HIV-amplification products, by automated sequencing. For specimens identified as having mutations previously associated with reduced antiretroviral-drug susceptibility, phenotypic testing was performed. RESULTS Of 1311 eligible participants, 1082 (83%) were enrolled and successfully tested; 8.3% had reverse transcriptase or major protease mutations associated with reduced antiretroviral-drug susceptibility. The prevalence of these mutations was 11.6% among men who had sex with men but was only 6.1% and 4.7% among women and heterosexual men, respectively. The prevalence was 5.4% and 7.9% among African American and Hispanic participants, respectively, and was 13.0% among whites. Among persons whose sexual partners reportedly took antiretroviral medications, the prevalence was 15.2%. CONCLUSIONS Depending on the characteristics of the patients tested, HIV-genotype testing prior to the initiation of therapy would identify a substantial number of infected persons with mutations associated with reduced antiretroviral-drug susceptibility.

Treating Opportunistic Infections among HIV- Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America

The National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, and CDC have developed guidelines for treatment of opportunistic infections (OIs) among adults and adolescents infected with human immunodeficiency virus (HIV). These guidelines are intended for clinicians and other health-care providers who care for HIV-infected adults and adolescents, including pregnant women; they complement companion guidelines for treatment of OIs among HIV-infected children and previously published guidelines for prevention of OIs in these populations. They include evidence-based guidelines for treatment of 28 OIs caused by protozoa, bacteria, fungi, and viruses, including certain OIs endemic in other parts of the world but that might be observed in patients in the United States. Each OI section includes information on epidemiology, clinical manifestations, diagnosis, treatment recommendations, monitoring and adverse events, management of treatment failure, prevention of recurrence, and special considerations in pregnancy. Tables address drugs and doses, drug toxicities, drug interactions, adjustment of drug doses in persons with reduced renal function, and data about use of drugs in pregnant women.

Pneumococcal Disease among Human Immunodeficiency Virus-Infected Persons: Incidence, Risk Factors, and Impact of Vaccination

To determine the factors associated with pneumococcal disease (pneumococcal pneumonia or invasive disease) and the impact of pneumococcal vaccine in HIV-infected persons, we analyzed patient data collected by the Adult and Adolescent Spectrum of HIV Disease Project for person-time between January 1990 and December 1998. Among 39,086 persons with 71,116 person-years (py) of observation, 585 episodes of pneumococcal disease were diagnosed (incidence, 8.2 episodes per 1000 py). Factors associated with an increased risk for pneumococcal disease (P < .05) included injection drug use (adjusted relative risk [RR], 1.5) and blood transfusion (RR, 2.0) as the mode of HIV transmission (referent, male-male sex); black race/ethnicity (RR, 1.5; referent, white race); history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness (RR, 2.1); a CD4(+) cell count of 200-499 cells/microL (RR, 2.5) or < 200 cells/microL (RR, 3.7; referent, CD4(+) cell count of > or = 500 cells/microL); and alcoholism (RR, 2.0). Factors associated with a decreased risk included prescription of antiretroviral therapy (RR for monotherapy, 0.6; for dual therapy, 0.7; for triple therapy, 0.5) and pneumococcal vaccination (RR for persons vaccinated at a CD4(+) cell count of > or = 500 cells/microL, 0.5). We recommend that pneumococcal vaccine be given to HIV-infected persons before profound immunosuppression has occurred.

HIV risk factors in three geographic strata of rural Rakai District, Uganda

ObjectivesTo examine risk factors for HIV-1 infection in three geographic strata (main road trading centers that service local and international traffic, small trading villages on secondary dirt roads that serve as foci for local communications, and agricultural villages off main and secondary roads) in Rakai District, Uganda. Design and methodsSerological, sociodemographic, knowledge/hehaviors and health survey conducted in 21 randomly selected community clusters; complete data were collected for 1292 consenting adults. ResultsFifteen per cent of the men and 24% of the women were HIV-1-positive. On univariate analysis, several sociodemographic and behavioral factors were significantly associated with risk of HIV infection, including age, place of residence, travel, occupation, marital status, number of sex partners, sex for money or gifts, history of sexually transmitted disease (STD), and history of injections. On multivariate analysis, age, residence and number of sex partners remained significantly associated with HIV infection in both sexes; a history of STD and not having been circumcised were significant in men. There was a significant interaction between place of residence and reported number of sex partners: for any given level of sexual activity, the risk of HIV infection was markedly increased if the background community prevalence was high. ConclusionSexual transmission appears to be the primary behavioral risk factor for infection, but the risks associated with this factor vary substantially between the three geographic strata. These data can be used to design targeted interventions.

Seroprevalence of HTLV-I and HTLV-II among Intravenous Drug Users and Persons in Clinics for Sexually Transmitted Diseases

Abstract Background. The human T-cell lymphotropic virus Type I (HTLV-I) is associated with adult T-cell leukemia and myelopathy, whereas HTLV-II infection has uncertain clinical consequences. We assessed the seroprevalence of these retroviruses among intravenous drug users and among patients seen at clinics for sexually transmitted diseases (STD clinics). Methods. We used serum samples that were collected in eight cities in 1988 and 1989 during surveys of human immunodeficiency virus infection among intravenous drug users entering treatment and persons seen in STD clinics. The serum samples were tested for antibodies to HTLV, and positive specimens were tested further by a synthetic peptide-based enzyme-linked immunosorbent assay to differentiate between HTLV-I and HTLV-II. Results. Among 3217 intravenous drug users in 29 drug-treatment centers, the median seroprevalence rates of HTLV varied widely according to city (range, 0.4 percent in Atlanta to 17.6 percent in Los Angeles). Seroprevalence increased ...