Kim S. Erlich

Acyclovir-Resistant Herpes Simplex Virus Infections in Patients with the Acquired Immunodeficiency Syndrome

RECURRENT herpes simplex virus (HSV) infections are frequent in patients with the acquired immunodeficiency syndrome (AIDS). Although they are usually self-limiting in the normal host, such infecti...

Foscarnet Therapy for Severe Acyclovir-Resistant Herpes Simplex Virus Type-2 Infections in Patients with the Acquired Immunodeficiency Syndrome (AIDS): An Uncontrolled Trial

STUDY OBJECTIVE To determine whether trisodium phosphonoformate (foscarnet) is efficacious in treating severe mucocutaneous disease due to acyclovir-resistant herpes simplex virus type-2 (HSV-2) infection in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Open-labeled drug administration to patients with AIDS and severe ulcerative disease due to acyclovir-resistant HSV-2 infection. SETTING Medical floors of acute care hospital. PATIENTS Four patients with AIDS who developed progressive ulcerative mucocutaneous lesions of the genitals, perineum, perianal region, or finger due to acyclovir-resistant, thymidine-kinase (TK)-negative strains of HSV-2. INTERVENTION Foscarnet, 60 mg/kg body weight intravenously every 8 hours (with reduced dosage for renal impairment), for 12 to 50 days. MEASUREMENT AND MAIN RESULTS All patients receiving foscarnet had dramatic improvement in their clinical findings with marked clearing of mucocutaneous lesions and eradication of HSV from mucosal surfaces. CONCLUSION Foscarnet may be an effective treatment for severe mucocutaneous disease due to acyclovir-resistant, TK-negative strains of HSV-2.

Effects of L3T4 + Lymphocyte Depletion on Acute Murine Cytomegalovirus Infection

We examined the role of T lymphocytes bearing the L3T4 phenotype in acute murine cytomegalovirus (MCMV) infection. In vivo administration of rat IgG2b monoclonal antibody (MAb) GK 1.5 was used to deplete mice of L3T4+ lymphocytes during acute MCMV infection. Unlike the saline-treated controls that resolved their infections, mice receiving the MAb developed persistent and high levels of virus in the salivary gland, lung and spleen. The production of antibody to MCMV was delayed and the titres achieved were markedly less than in the controls. Despite the higher levels of virus replication, there was no increase in mortality seen in animals treated with the MAb. Following intraperitoneal challenge with MCMV, depletion of L3T4+ lymphocytes was protective, increasing the dose of MCMV required to produce death. These data indicate that T lymphocytes of the L3T4 phenotype influence the degree of MCMV replication during acute infection and may contribute to mortality following intraperitoneal virus challenge.

Importance of circulating antibodies in protection against meningococcal disease

Neisseria meningitidis infection results in life-threatening illnesses, including bacteremia, sepsis and meningitis. Early diagnosis and treatment are a challenge due to rapid disease progression, resulting in high mortality and morbidity in survivors. Disease can occur in healthy individuals, however, risk of infection is higher in patients with certain risk factors. N meningitidis carriage and case-fatality rates are high in adolescents and young adults. The absolute incidence of meningococcal disease has decreased partially due to increasing meningococcal vaccination rates. Maintaining protective levels of circulating antibodies by vaccination is necessary for clinical protection against disease. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidelines recommend vaccination for all individuals aged 11 through 12 years, followed by a booster dose at age 16 years for maintenance of protective antibody levels throughout the high-risk years. Despite these guidelines, many adolescents remain unvaccinated and susceptible to infection and disease.