Biomedical subjects
Publications and source records attributed to R Hoff.
Trends in the vertical transmission rate of HIV and evolving antiretroviral usage between 1990 and 1998 within the Women and Infants Transmission Study were evaluated. A decline in mother-infant transmission was temporally associated with advances in therapy, especially when regimens including a protease inhibitor were included in the analysis.
OBJECTIVE: This study examined incarceration rates of users of Department of Veterans Affairs (VA) mental health services in 16 northeastern New York State counties between 1994 and 1997-a time of extensive bed closures in the VA system-to determine whether incarceration rates changed during this period. METHODS: Data were obtained for male patients who used inpatient and outpatient VA mental health services between 1994 and 1997 and for men incarcerated in local jails during this period. For comparison, services use and incarceration data were obtained for all men who received inpatient behavioral health care at community general hospitals and state mental hospitals between 1994 and 1996 in the same counties. Probabilistic population estimation, a novel statistical technique, was employed to evaluate the degree of overlap between clinical and incarceration populations without relying on person-specific identifiers. RESULTS: Of all male users of VA mental health services between 1994 and 1997, a total of 15.7 percent-39.6 percent of those age 18 to 39 years and 9.1 percent of those age 40 years and older-were incarcerated at some time during that period. Dual diagnosis patients had the highest rate of incarceration (25 percent), followed by patients with substance abuse problems only (21 percent) and those with mental health problems only (11 percent). The rate of incarceration among male patients hospitalized in VA facilities was lower than among men in general hospitals or state hospitals (11.6 percent, 23 percent, and 21.7 percent, respectively), but was not significantly different. No significant increase occurred in the annual rate of incarceration among VA patients from 1994 to 1997 (3.7 percent to 4 percent), despite extensive VA bed closures during these years. CONCLUSIONS: Substantial proportions of mental health system users were incarcerated during the study period, especially younger men and those with both substance use and mental health disorders. Rates of incarceration were similar across health care systems. The closure of a substantial number of VA mental health inpatient beds did not seem to affect the rate of incarceration among VA service users.
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There has been considerable debate over what evidence from preclinical and clinical studies is required to advance an HIV vaccine candidate to phase III efficacy testing. Given this situation, conduct of intermediate-size trials is proposed as a method for assessing the plausibility that a vaccine candidate would prevent chronic HIV infection. Designed to observe 45 incident infections in the control group, these preliminary efficacy trials could rule out candidates with low or no efficacy while advancing those candidates with some evidence of protection to definitive trials. In addition, these trials could provide clues about correlates of immunity. A threefold or greater difference in the postvaccination geometric mean titer of neutralizing antibody can be readily detected between infected and uninfected vaccinees. Differences in CD8+ cytotoxic T lymphocytes, however, are more difficult to detect. Intermediate-size trials could also discern a 0.5 log10 or greater difference in plasma HIV-1 RNA levels between infected vaccinees and infected controls. Such differences in viral load might suggest disease amelioration or reduction in infectiousness. Given the large variability in CD4 count and its relatively modest average decline in the year after infection, a slower decline in CD4 count among infected vaccinees would not be detectable. With limited resources, intermediate-size trials could contribute significantly to HIV vaccine development.
Early diagnosis of infection with human immunodeficiency virus type 1 (HIV- 1) in young infants is essential to decisions on their medical and social care. Whereas studies have suggested that polymerase chain reaction (PCR) is a sensitive and timely method of diagnosing HIV infection in children, these evaluations have been limited by the number of specimens studied. Recently, Roche Molecular Systems developed a complete HIV-1 DNA PCR testing kit (from specimen preparation to detection). In this study, use of this PCR test kit was evaluated for the detection of HIV infection in infants of seropositive mothers who were enrolled in the longitudinal, multicenter Women and Infants' Transmission Study. A total of 1209 blood specimens from 483 infants were tested and analyzed. The overall sensitivity and specificity of a single PCR test in determining HIV infection status in infants more than 1 but less than 36 months of age were 95% and 97%, respectively. For infected infants 1 to 6 months of age the sensitivity of the DNA-PCR test was 90% to 100%. In a direct comparison with coculture, the Roche DNA-PCR test was significantly more sensitive than coculture in the detection of HIV-1 in infected infants and was equivalent to coculture for the diagnosis of HIV in infants when a standardized algorithm was used to define infection status.
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Biotops with extreme temperatures such as deserts force animals to avoid or escape high temperatures by biochemical, behavioural or morphological adaptation. In this context we tested the resistance to heat of the oxygen carrier hemocyanin from the ancient tarantula Eurypelma californicum, which is found in arid zones of North America. Differential scanning calorimetry, light scattering, crossed immunogelelectrophoresis and oxygen binding experiments show that the 24-meric hemocyanin is conformationally stable and fully functioning at temperatures up to 90 degrees C. Our results demonstrate that the cation-mediated state of oligomerization is not only crucial for the high cooperativity of oxygen binding of this hemocyanin, but also for its extreme stability in the physiological temperature and pH range.
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In order to prove the efficacy of human immunodeficiency virus (HIV) vaccines, it will be necessary to do large-scale trials in populations at high risk of acquiring HIV infection. The choice of objectives and end points and their measurement will be key to the design of efficacy trials. To address these issues, the National Institute of Allergy and Infectious Diseases convened several workshops and discussions at national meetings. These discussions have concluded that many factors will contribute to the selection of practical primary objectives and end points for efficacy trials of HIV vaccines. For initial trials the objective of preventing the establishment of chronic infection is a reasonable choice, given the current state of knowledge. However, given the complexities of HIV and the acquired immunodeficiency syndrome, it will be important to collect data and evaluate other potential objectives and end points as well.
BACKGROUND: Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. METHODS: In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. RESULTS: Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three). CONCLUSIONS: Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.
The magnitude of HIV pandemic has made the development of HIV vaccines an urgent biomedical research priority. Although the biologic problems in designing a vaccine for a chronic viral infection like HIV are formidable, there has been encouraging progress. More than a dozen first generation prophylactic HIV vaccine candidates have completed phase I human trials that have established the safety and immunogenicity of these products in adults. A phase II trial of two HIV subunit envelope vaccines in adults at high risk of HIV infection is underway in the United States, and preparations for phase III efficacy trials have begun. Preliminary studies are under way to evaluate the potential application of active and passive immunization for preventing vertical transmission of HIV. Because of the higher rate of HIV transmission and a more abbreviated time course to disease, it may be more efficient to evaluate the efficacy of HIV vaccines in HIV infected pregnant women and their offspring than in adults who are exposed sexually to HIV.
In summary, much has been accomplished in the past year, but much still remains to be done before we can embark on an efficacy trial. With the availability of a fully operational network, the NIAID has in place the resources and mechanisms to complete baseline feasibility studies and to conduct the future trials. As presented at the 1993 conference and reported in this supplement, the preliminary data from the current baseline studies indicate that such trials are feasible, although not without considerable problems. To reach our "efficacy trials preparedness" goal, we will need to work especially hard in the coming months to identify and resolve the remaining technical, ethical, legal, and political constraints to initiating trials. We must also listen to community concerns and educate the public about the trials if we expect to gain community support and volunteers for the study. Finally, we must evaluate the supporting data pertaining to candidate products for efficacy trials. These will not be easy tasks or decisions, but we must approach them with vigor.
A perfect serologic test for infection with Trypanosoma cruzi does not exist. This study uses recombinant T. cruzi surface proteins in the antibody capture enzyme linked immunoabsorption assay (ELISA); and compares this approach to the more standard immunofluorescence assay (IFA). Three recombinant antigens are studied: F1-160 corresponding to the 160 kDa flagellar associated surface protein of trypomastigotes (the motile form of T. cruzi in mammalian infections); and SA 85-1.1 and 1.2 corresponding to different members of the 85 kDa family of surface proteins expressed by trypomastigotes and amastigotes (the replicative, non-motile form of T. cruzi in mammalian infections). Each recombinant antigen is found to be highly specific (range 86-94%) but relatively insensitive (range 36-52%) when used to screen for antibodies to T. cruzi. Defining seropositivity as reactivity to any of the three recombinant antigens markedly increases the sensitivity (72%) with only a minor reduction in specificity (82%). Thus, employing recombinant T. cruzi antigens to screen for T. cruzi infection has promise, but improvements in sensitivity must be made before widespread utilization is recommended.
Three nonradioisotopic polymerase chain reaction (PCR)-based detection techniques were evaluated for sensitivity and specificity in detecting human immunodeficiency virus type 1 (HIV-1) proviral DNA in peripheral blood mononuclear cells. The Roche prototype HIV-1 PCR assay, the Du Pont enzyme-linked oligonucleotide sandwich assay (ELOSA), and the Gen-Probe hybridization protection assay (HPA) were compared with a standard radioisotopic oligonucleotide solution hybridization (OSH) technique. A panel of 111 well-characterized clinical samples that included peripheral blood mononuclear cells from 48 healthy, low-risk, HIV-1 antibody-negative subjects, 24 antibody-positive subjects with stable CD4 counts of less than 200/mm3, and 39 antibody-positive subjects with stable CD4 counts of greater than 800/mm3 were studied. Each method demonstrated good specificity, ranging between 96 and 100%; those of the OSH and ELOSA (Du Pont) were 100%, those of the HPA (Gen-Probe) were 100% with one probe and 96% with the other probe, and that of the HIV-1 PCR assay (Roche) was 96%. Sensitivities ranged from 96 to 100% for the low-CD4-count group, with the OSH, the HIV-1 PCR assay (Roche), and the HPA (Gen-Probe) all attaining a sensitivity of 100%. For the high-CD4-count group, sensitivities ranged from 69 to 97%, with the OSH attaining a sensitivity of 97% and the HPA attaining sensitivities of 97% with one probe and 95% with the other probe. These data indicate that the nonradioisotopic techniques are sensitive and specific for the detection of HIV-1 proviral DNA in clinical samples.
Since 1986, all Massachusetts newborn filter paper blood specimens, and some from New Hampshire, have been screened for the presence of IgM antibodies to Toxoplasma gondii using an enzyme-linked IgM capture assay. Among approximately 530,000 infants screened, 40 had serologically confirmed congenital toxoplasma infection, and 4 additional infants had borderline serologies, for an overall identification and treatment rate of 1:12,000. False positive results from the newborn's filter paper specimen occurred in 22 infants (1/24,000); these were clarified by tests for IgM and IgG in serum specimens obtained 2-3 weeks later from the infant and mother. The screening program would have failed to detect 3 infants with severe infection who were diagnosed on clinical grounds prenatally or at birth and lacked IgM. No infants with a later diagnosis of congenital toxoplasmosis that was missed by screening are known to our statewide network of pediatric infectious disease consultants. Follow-up studies are in progress to evaluate more completely the sensitivity of the IgM assay in newborns and the efficacy of treatment.