Infectious Diseases,
Immunology,
and Rheumatology

Contents

• About the Division
• Clinical Programs
• Research Programs
• Training Programs
• Related Links
• Contact List

About the Division

The Division of Infectious Diseases, Immunology, and Rheumatology is committed to providing quality care at Children's Hospital and Regional Medical Center in the areas of infectious diseases, primary immunodeficiency disorders and rheumatic diseases.

Clinical Programs

The Infectious Diseases division provides diagnostic and therapeutic services for children with proven or suspected infectious diseases and treats complicated, chronic or recurrent infections.

The Immunology section provides diagnostic and therapeutic services for children and adults with suspected or known primary immunodeficiency disorders. The practice is limited to diagnosing and treating patients with these serious disorders. Appointments are arranged only by physician referral to the clinic.

The Rheumatology section diagnoses and manages children with rheumatic diseases. We also evaluate children with complex undiagnosed illnesses, and diagnose and manage complications of the medications used to treat these disorders.

Research Programs

Lisa M. Frenkel, MD
Our laboratory focuses on clinically relevant issues related the virology of HIV-1 infection in children and pregnant women. Current projects pertain primarily to HIV-1 drug resistance, however, studies examining immunization of monkeys and human infants to HIV-1 by exposure to virus during chemoprophylaxis are ongoing.

Our current projects focusing on HIV-1 drug-resistance include:

• Characterization of genetic events that precede and result in the evolution of HIV-1 resistant to antiretroviral drugs among children with plasma RNA <50 copies/ml. Detailed studies have demonstrated diverse patterns of viral evolution; ranging from no evolution to ongoing selective pressure without evolution to selection of resistant strains without loss of suppression of viral replication.
• Studies of pregnant women have found independent evolution to drug resistant virus in the genital tract prior to the blood. "Re-seeding" of the blood by genital tract virus or temporally similar selective pressures have resulted in resistant virus appearing shortly thereafter in the blood. Ongoing studies aim to discern if re-seeding, co-evolution or both lead to the apparent spread of HIV-1 drug-resistance.

1. A rapid, sensitive, specific and inexpensive method to detect point mutations conferring HIV-1 resistance to protease inhibitors and to non-nucleoside analogs has been developed. It is similar to an assay for detection of resistance mutations to nucleoside analogs that we developed previously (Edelstein, J Clin Microbiol, 1998). The limitations of this assay have been characterized in preparation for its inclusion in the NIH AIDS Reference and Reagent Program. The assay is more sensitive than consensus sequencing and the utility of the assay in detecting minor population of resistant HIV-1 is under investigation.
2. International collaborations include the training and assistance of colleagues in Honduras and Peru, early diagnosis of HIV-1 utilizing DNA PCR of whole blood from Peru (Beck, J Clin Microbiol, 2000), studies of antiretroviral resistance among chemoprophylaxed HIV-1 exposed infants in Peru, a study of the feasibility of rapid diagnosis of HIV-1 in pregnant women by whole blood or saliva in women who first present for prenatal care in Lima, Peru during labor.

In addition we are investigating a novel strategy of mucosal immunization to lentiviruses. In these studies monkeys were exposed intravaginally to virus during chemoprophylaxis. Sterilizing immunity was demonstrated in half of the experimental animals and disease was attenuated in nearly all the remaining animals. Shortly we will begin to evaluate whether human infants exposed to HIV-1 by breastfeeding during nevirapine chemoprophylaxis will develop neutralizing.

Our studies examining transient HIV-1 infection (Frenkel, Science 1998) have led to many projects investigating the possibility of transient infection and utilization of viral linkage in criminal cases.

Studies of HIV-1 drug-resistance are ongoing for multiple clinical trials done by the Pediatric AIDS Clinical Trials Group. These trials aim to improve the treatment of HIV-1 infected children and adolescents and to prevent transmission of HIV-1 from infected pregnant women to their infants. Viral studies critical to the evaluations of these trials and studies with questions peripheral to the primary objectives of the studies are ongoing with in our laboratory.

Training Programs

The overall goal of our training programs is to train individuals for careers in academic pediatrics who will be skilled investigators and clinical subspecialists. Clinical training is intensive during the first year; our institutions have large patient bases, providing a rich clinical exposure over the six-twelve months of intensive clinical training. Subsequent years are devoted primarily to investigation, with clinics at sufficient frequency to develop a longitudinal perspective on patient management and to maintain clinical skills.

Related Links

• Division of Infectious Diseases at Children's Hospital
• Immunology Section at Children's Hospital
• Rheumatology Section at Children's Hospital
• Training Programs with Children's Hospital and Regional Medical Center in Pediatric Infectious Diseases, Immunology and Rheumatology
• Residencies and Fellowships in Pediatric Infectious Diseases

Contact List