Progress in Infectious Disease and Immunology
Authors: Gianna Zuccotti
Journal: JAMA (2011)

INFECTIOUS DISEASES ARE COMMONLY ENCOUNTERED IN VIRtually all areas of health care, can represent potential major threats to communities and public health, and account for substantial morbidity and mortality. On a global level, infectious diseases such as malaria and tuberculosis remain leading causes of death. Among hospitalized patients, infectious complications such as central line– associated bloodstream infections, ventilator-associated pneumonia, and surgical site infections continue to be important causes of morbidity and increased length of stay. Illness related to infectious diseases also accounts for significant numbers of office and emergency department visits as well as substantial heath care costs and leads to losses in productivity among workers. In addition, the management of infectious diseases continues to be challenging, with major concerns about the emergence of multidrug-resistant pathogens and a significant decline in the production of new antimicrobial agents from both research and industry sources. Immunologic disorders also are increasingly prevalent, with improved detection of common immunologic and allergic conditions; expanded numbers of patients living longer with immune-suppressing disorders such as human immunodeficiency virus (HIV) infection and some cancers; and increasing numbers of patients receiving immunemodulating and immunosuppressing medications, such as patients with connective tissue disorders and recipients of organ, tissue, and stem cell transplants. Many of these disorders can take a devastating toll on physical functioning, quality of life, and emotional well-being. This theme issue of JAMA, devoted to infectious diseases and immunology, includes research reports and other scholarly articles that provide new information to help inform clinicians about these issues. Three clinical trials in this issue provide data on approaches to treatment and prevention of 3 relatively common infectious disease processes. In a noninferiority trial of tuberculosis treatment conducted among 1585 adults with newly diagnosed tuberculosis at 11 sites in Africa, Asia, and Latin America, Lienhardt and colleagues demonstrated that compared with a regimen of 4 separately administered medications, a fixed-dose 4-drug combination formulation satisfied noninferiority criteria in 2 of 3 analyses. The authors suggest that even though the results do not demonstrate full noninferiority, the potential advantages related to administration and adherence using the fixed-dose combination over separate drug formulations may make this a preferred approach, particularly in resource-poor settings. In another noninferiority clinical trial evaluating alternative dosing regimens for human papillomavirus (HPV) vaccination among 903 adolescent girls in Vietnam, Neuzil and colleagues found that the use of 2 alternative HPV vaccine dosing schedules (at 0, 3, and 9 months and at 0, 6, and 12 months) compared with the standard vaccine schedule (0, 2, and 6 months) did not result in inferior antibody concentrations, although the yearly vaccination schedule (0, 12, and 24 months) did not meet prespecified noninferiority criteria. The study, however, only addressed immunogenicity and reactivity and does not provide information on the efficacy of these dosage regimens for preventing cervical cancer. In a clinical trial of hepatitis B vaccination conducted at 33 centers in France, Launay and colleagues compared the safety and immunogenicity of a 4-intramuscular doubledose regimen (40 μg at weeks 0, 4, 8, and 24) and a 4-intradermal low-dose regimen (4 μg at weeks 0, 4, 8, and 24) vs the standard regimen (20 μg at weeks 0, 4, and 24) of recombinant hepatitis B virus (HBV) vaccine among 396 HIV1–infected adults with CD4 cell counts greater than 200/μL and who were HBV seronegative. The investigators report that both the 4 intramuscular double-dose regimen and the 4 intradermal low-dose regimen improved serological response compared with the standard HBV vaccine regimen. The findings also suggest that intradermal administration of this regimen may be more efficient than the standard intramuscular administration in achieving immunogenicity. Three observational studies in this issue report novel information on 3 clinically important and prevalent conditions. In a study of 498 immunocompetent adults with serologic evidence of infection with herpes simplex virus type 2 (HSV-2), Tronstein and colleagues measured the rate of viral shedding using polymerase chain reaction (PCR) detection of HSV-2 DNA from self-collected genital swabs obtained on consecutive days. Among 410 symptomatic persons with a history of genital lesions, HSV was detected on