Investigations of Persons Treated by HIV-Infected Health-Care Workers -- United States

Previous reports have described transmission of human immunodeficiency virus (HIV) to five persons (patients A, B, C, E, and G) during receipt of care from an HIV-infected dentist in Florida (1-3) and other investigations of patients who were treated by HIV-infected health-care workers (HCWs) (4). This report updates these investigations and presents evidence that a sixth patient (patient I) became infected with HIV while receiving care at the Florida dental practice, the only practice in which HIV transmission from an infected HCW to patients has been documented. Investigation of Patients of HIV-Infected HCWs (Excludes Florida Dental Practice)

As of March 31, 1993, HIV tests were completed for 19,036 persons treated by 57 HIV-infected HCWs. These results include findings in published reports (4-7) and unpublished investigations reported to CDC.

No seropositive persons were reported among 11,529 patients tested from the practices of 46 HCWs, including 23 dentists and dental students, 12 physicians and medical students, seven surgeons and obstetricians, and four others. For the remaining 11 HCWs (six dentists and five surgeons and obstetricians), 7507 patients were tested, and 92 seropositive patients were identified. Follow-up investigations have been completed for 86 (94%) of these 92 patients: eight patients were documented to be infected before receiving care from the HIV-infected HCW; 54 had established risk factors for HIV; 19 may have had other opportunities for exposure to HIV (i.e., exchange of sex for drugs or money and/or multiple sex partners); and five had no risks identified. Investigations are in progress for six patients of two HCWs.

Genetic sequencing was performed on HIV strains from 29 of the 92 seropositive patients from the practices of three HCWs. Eleven of these 29 had established risks, 15 had other opportunities for exposure to HIV, and three had no identified risk. Sequencing was not performed on the isolates for the remaining two of the five patients with no identified risk because one patient died before a blood sample could be collected, and the other refused to provide a sample. The degree of genetic similarity of viruses from the patients and the infected HCWs was in the range previously reported for persons with epidemiologically unrelated infections (5,6; CDC, unpublished data). Thus, follow-up to date has not demonstrated transmission from an HCW as a source of HIV infection for any of the patients tested. Epidemiologic and Laboratory Investigation of Patient I

Patient I, a teenaged female, was HIV seropositive when tested as an applicant for military service in late 1992. She had not previously been tested for HIV infection, although she was notified in December 1990 by the Florida Department of Health and Rehabilitative Services (HRS) that, as a former patient of the dentist, she should consider such testing.

Multiple interviews with the patient and her family and review of her medical records did not identify another mode of exposure to HIV. She denied previous injecting-drug use, receipt of blood or blood products, a history of sexually transmitted diseases, or sex with persons infected with HIV or at increased risk for HIV infection. She did not recall, nor did review of her medical records reveal, an illness compatible with an acute retroviral illness. Five of her six lifetime sex partners were tested and were negative for HIV antibody. The sixth sex partner, with whom the patient reported a single sexual contact using a condom, has not been located. The patient's CD4+ T-lymphocyte count at the time of HIV diagnosis was 429 cells/uL. Serologic tests for syphilis and hepatitis B were negative.

Interviews with the patient and her parents indicated she was a patient in the dental office during the summers of 1987, 1988, and 1989 for examinations, radiographs, prophylaxes, and restorative fillings under local anesthesia. Her dental records from the practice cannot be located; therefore, whether she shared a visit date with any of the other five infected patients is unknown. An insurance record documented a visit in August 1988 for an examination, radiographs, and prophylaxis. Bitewing radiographs taken in 1990 by another dentist indicate that single surface restorative fillings had been placed in three permanent molars. Before 1987, the patient had received no other dental care since the eruption of her permanent teeth. She did not recall any injury to the dentist or other unusual events during the dental procedures or whether the dentist or the hygienist performed the prophylaxes.

Peripheral blood mononuclear cells were obtained from patient I, and proviral DNA was extracted, amplified, cloned, and sequenced (2) to determine the relatedness of the HIV strain from patient I to those of the dentist and patients A, B, C, E, and G. A direct sequence of amplified DNA and nine cloned sequences each included approximately 325 nucleotides of the C2-V3 region of the env gene. In addition, six shorter clone sequences were produced. Sequence analyses were performed at Los Alamos National Laboratory and at CDC.

The genetic divergence (i.e., intrapatient nucleotide sequence distances) among the nine complete C2-V3 clones from patient I averaged 3.2% (range: 0.3%-5.0%). The viruses of the dentist and patient I were closely related, with an average genetic divergence of 4.3% (range: 2.8%-7.8%), and the viruses of patient I and patients A, B, C, E, and G also were closely related, with an average divergence of 4.9% (range: 2.1%-8.1%). In comparison, the sequences of patient I were distinct from those of the 34 local controls (2), with an average genetic divergence of 12.0% (range: 6.8%-17.9%). Based on direct sequences of 186 nucleotides from the viruses infecting patients A, B, C, E, G, and 28 of the 34 local controls, the HIV strains from patients A, B, C, E, and G were significantly closer in their DNA sequences to patient I's virus than the control patients (p<0.0001, Wilcoxon rank sum test).

In addition to the genetic divergence analysis, signature pattern analysis of both amino acids and nucleotides * (2,8) and phylogenetic tree analysis (2) each independently showed the similarity of patient I's sequences and those of the dentist and patients A, B, C, E, and G. Analyses of the six shorter clone sequences and the direct amplification product from patient I were consistent with this finding.

Reported by: JJ Witte, MD, Florida Dept of Health and Rehabilitative Svcs. Los Alamos National Laboratory, New Mexico. Div of HIV/AIDS, and Hospital Infections Program, National Center for Infectious Diseases; Div of Oral Health, National Center for Prevention Svcs; National Institute for Occupational Safety and Health, CDC.

Editorial Note

Editorial Note: The results of the epidemiologic and laboratory investigation of patient I indicate that she became infected with HIV while receiving care from an HIV-infected dentist. She had had no other confirmed exposures to HIV. In addition, DNA sequence analysis showed her HIV strain had a high degree of similarity to that of the dentist and the five other infected patients. The precise event(s) resulting in HIV transmission in this practice remain(s) unknown (1). Unlike the other five infected patients, patient I had neither dental extractions nor root canal therapy. Opportunities for injuries to the dentist were limited. However, exposure of patient I to the dentist's blood cannot be ruled out (e.g., related to use of the anesthetic syringe).

Approximately 1100 patients of the dentist are known to have been tested for HIV. In late 1990, HRS used available records to compile a partial list of the patients in the dental practice and notified those patients who had not been tested. Former patients who have not yet been tested should contact their local health department or private physician to discuss HIV testing.

Among the 58 investigated practices described in this report, the dental practice in Florida remains the only documented instance of HIV transmission from an HCW to patients. The risk for transmission of a bloodborne pathogen from an HCW to a patient is associated with the circulating titer of the pathogen in blood, the procedures performed, techniques and infection-control precautions used, and the medical condition of the HCW (9).

The results presented in this report are consistent with previous assessments that the risk for HIV transmission from an infected HCW to patients during invasive procedures is small and can be reduced with appropriate use of infection-control precautions (9,10).

References

1. Ciesielski C, Marianos D, Ou CY, et al. Transmission of human immunodeficiency virus in a dental practice. Ann Intern Med 1992;116:798-805.

2. Ou CY, Ciesielski C, Myers G, et al. Molecular epidemiology of HIV transmission in a dental practice. Science 1992;256:1165-71.

3. Gooch B, Marianos D, Ciesielski C, et al. Lack of evidence for patient-to-patient transmission of HIV in a dental office. J Am Dent Assoc 1993;124:38-44.

4. CDC. Update: investigations of patients who have been treated by HIV-infected health-care workers. MMWR 1992;41:344-6.

5. Dickinson GM, Morhart RE, Klimas NG, Bandea CI, Laracuente JM, Bisno AL. Absence of HIV transmission from an infected dentist to his patients. JAMA 1993;269:1802-6.

6. Rogers AS, Froggatt JW III, Townsend T, et al. Investigation of potential HIV transmission to the patients of an HIV-infected surgeon. JAMA 1993;269:1795-1801.

7. von Reyn CF, Gilbert TT, Shaw FE, Parsonnet KC, Abramson JE, Smith MG. Absence of HIV transmission from an infected orthopedic surgeon: a 13-year lookback study. JAMA 1993;269:1807-11.

8. Korber B, Myers G. Signature pattern analysis: a method for assessing viral sequence relatedness. AIDS Res Hum Retroviruses 1992;8:1549-60.

9. Bell DM, Shapiro CN, Gooch BF. Preventing HIV transmission to patients during invasive procedures. J Public Health Dent (in press).

10. Bell DM, Shapiro CN, Culver DH, Martone, WJ, Curran JW, Hughes JM. Risk of hepatitis B and human immunodeficiency virus transmission to a patient from an infected surgeon due to percutaneous injury during an invasive procedure: estimates based on a model. Infectious Agents and Disease 1992;1:263-9.

• Patient I's viral C2-V3 amino acid sequences were characterized by a stringently defined signature pattern, A-A-G-E-V-I-H; these seven, atypical amino acid residues were found by computer analysis in each of the nine viral clone sequences consisting of approximately 108 deduced amino acids. The dentist's viral C2-V3 amino acid sequences were characterized by a stringently defined signature of eight noncontiguous residues, A-I-A-G-A-E-V-H, and a majority signature, present in most of the viral clone sequences from the dentist, consisting of 10 noncontiguous residues, A-I-A-G-A-E-E-V-I-H. Of the seven residues in patient I's signature, five were found in the stringently defined dentist signature and all seven were present in the majority signature of the dentist's viruses. Patient I's stringently defined nucleotide signature pattern consisted of 12 atypical, noncontiguous residues detected in each of the nine viral clone sequences of approximately 325 nucleotides. All 12 of these nucleotides were present in five of the six dentist's clone sequences; 11 of these nucleotides were found in the remaining dentist clone sequence. No sequence from any local control or any other sequence in the HIV Sequence Database contained more than five of these 12 signature nucleotides (most had 1 3). In contrast, all 34 clone sequences from patients A, B, C, E, and G had at least 11 of the signature nucleotides.

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