Challenges to the census: international trends and a need to consider public health benefits.

The Canadian government decision to cancel the mandatory long-form census in 2010 (subsequently restored in 2015), along with similar discussions in the United Kingdom (UK) and the United States of America (USA), have brought the purpose and use of census data into focus for epidemiologists and public health professionals. Policy decision-makers should be well-versed in the public health importance of accurate and reliable census data for emergency preparedness planning, controlling disease outbreaks, and for addressing health concerns among vulnerable populations including the elderly, low-income, racial/ethnic minorities, and special residential groups (e.g., nursing homes). Valid census information is critical to ensure that policy makers and public health practitioners have the evidence needed to: (1) establish incidence rates, mortality rates, and prevalence for the full characterization of emerging health issues; (2) address disparities in health care, prevention strategies and health outcomes among vulnerable populations; and (3) plan and effectively respond in times of disaster and emergency. At a time when budget and sample size cuts have been implemented in the UK, a voluntary census is being debated in the US. In Canada, elimination of the mandatory long-form census in 2011 resulted in unreliable population enumeration, as well as a substantial waste of money and resources for taxpayers, businesses and communities. The purpose of this article is to provide a brief overview of recent international trends and to review the foundational role of the census in public health management and planning using historical and current examples of environmental contamination, cancer clusters and emerging infections. Citing a general absence of public health applications of the census in cost-benefit analyses, we call on policy makers to consider its application to emergency preparedness, outbreak response, and chronic disease prevention efforts. At the same time, we call on public health professionals to improve published estimates of monetary benefit (via either cost-benefit or cost-effectiveness analysis) to a given public health intervention.

Partial resistance to infection by R5X4 primary HIV type 1 isolates in an exposed-uninfected individual homozygous for CCR5 32-base pair deletion.

It is known that certain individuals remain persistently seronegative despite repeated exposure to HIV-1. Studies have shown that some exposed uninfected (EU) individuals who are homozygous for a 32-bp deletion in the CCR5 gene are resistant to infection with non-syncytium-inducing (R5) viruses. In the present investigation, we provide evidence that a highly exposed-uninfected individual with the CCR5 32-bp deletion (EUdelta32-1) also has partial resistance to syncytium-inducing (R5X4) HIV-1 viruses, when compared with unexposed-uninfected individuals with (UUdelta32-1 and UUdelta32-2) and without (UU-1 and UU-2) the 32-bp deletion. The partial resistance of EU cells was due neither to altered coreceptor expression, nor to specific mutation or deletion in the coding region of chemokine coreceptors CXCR4 and CCR3. While SDF-1, the ligand for CXCR4, blocked entry of R5X4 viruses to a similar extent in EUdelta32 and UUdelta32, there was a differential production of soluble factors by EUdelta32. Both CD4+ and CD8+ cells from EUdelta32-1 produced soluble factors that efficiently suppressed infection by HIV-1 R5X4 viruses when compared with supernatant from UUdelta32. These data provide evidence that additional soluble factors are involved in resistance to infection with R5X4 viruses.

Herpes simplex type II and Mycoplasma genitalium as risk factors for heterosexual HIV transmission: report from the heterosexual HIV transmission study.

OBJECTIVES: Two hundred twenty-four human immunodeficiency virus (HIV) discordant couples (one HIV negative, one HIV positive) were compared with 78 seroconcordant heterosexually infected couples with HIV with regard to sexually transmitted diseases. METHODS: Serologic testing and cultures were used to determine exposure of participants to sexually transmitted pathogens. These data were compared with HIV concordance of partners to investigate possible risk factors for HIV transmission. RESULTS: Syphilis, chlamydia, and hepatitis B virus (HBV) serologies did not distinguish between concordant and discordant couples nor did cultures for Neisseria gonorrhoeae and Trichomonas or Chlamydia enzyme immunoassay (EIA). Risk of transmission increased with positive serologies for herpes simplex virus (HSV)-2 (P = 0.002), cytomegalovirus (CMV) (P = 0.04), and Mycoplasma genitalium (P = 0.01), but not with Mycoplasma fermentans or Mycoplasma penetrans. Cytomegalovirus was not a significant risk factor when controlled for HSV-2 status. Examination by partner status showed increased risk of concordance with: HSV-2 positive serology in both partners (odds ratio [OR] = 3.14; confidence interval [CI] = 1.62-6.09; P = 0.007); HSV-2 in female secondary partner (OR = 2.10; CI = 1.12-3.93; P = 0.02) or the male primary partner (OR = 2.15; CI = 1.15-4.02; P = 0.017); M. genitalium antibody in both partners (OR = 3.44; CI = 1.68-7.04; P < 0.001); M. genitalium antibody in the primary male partner (OR = 2.51, CI = 1. 27-4.91; P = 0.008) and M. genitalium antibody in the secondary female partner (OR = 2.52; CI = 1.21-5.23; P = 0.01). CONCLUSIONS: These data support the role of HSV-2 in transmission of HIV and, for the first time, suggest a role for M. genitalium as an independent risk factor.

Risks and issues for the health care worker in the human immunodeficiency virus era.

The perception of degree of risk can vary markedly from actual risk. About 5% of the cases of AIDS and HIV infection in the United States have occurred in health care workers, a percentage that has remained stable over time. Nearly all of these infections are related to lifestyle factors, not occupational risk. The rise of occupational transmission is greatest with parenteral injuries. If there is an HIV risk to patients, it appears to be very much smaller than the risk to workers although it has received even more publicity. Apprehension exists concerning the future framework of the medical care delivery system and who will care for whom. The sensitive handling of legitimate fears and the balancing of conflicting risks will continue to be a challenging task in the decades ahead.

Mycoplasma genitalium infection and host antibody immune response in patients infected by HIV, patients attending STD clinics and in healthy blood donors.

Prevalence of Mycoplasma genitalium in humans is still not clear. We have developed a sensitive and specific serological assay for M. genitalium using lipid-associated membrane proteins (LAMPs) as antigens. Antibodies to LAMPs from M. genitalium showed little cross-reactivity to LAMPs from antigenically similar M. pneumoniae. For validity testing, urines from 104 patients were tested by PCR for M. genitalium. All 15 PCR+ patients had M. genitalium-LAMPs antibodies. Moreover, none of 64 antibody-negative patients were PCR+. Serological study of 1800 patients of various diseased groups and healthy blood donors showed M. genitalium was primarily a sexually transmitted microbe that infected patients with AIDS (44.0%), intravenous drugs users with or without HIV infection (42.5%), and also HIV- patients attending STD clinics (42.6%). Only 5.5% HIV- healthy blood donors and 1.3% HIV+ hemophiliacs tested positive. M. genitalium has been associated with acute non-gonococcal urethritis in male patients. However, many sexually active men and women appear to be chronically infected or colonized by the microbe without apparent clinical symptoms and may continue to transmit the organism through sexual contacts.

Development of a multiplex PCR assay for the simultaneous detection and discrimination of HIV-1, HIV-2, HTLV-I and HTLV-II.

BACKGROUND: Multiplex polymerase chain reaction (PCR) has been established as a general technique for the simultaneous amplification of different target sequences. Uses of multiplex include pathogens identification, linkage analysis and genetic disease diagnosis. The high sensitivity of PCR may produce false-positive results due to contamination with previously amplified material. OBJECTIVES: To develop a multiplex PCR technique that can simultaneously detect and discriminate human immunodeficiency virus types 1 and 2 (HIV-1/2) and human T-lymphotropic virus types 1 and 2 (HTLV-I/II) proviral sequences. Such a method should incorporate a system that prevents the occurrence of false-positive results. STUDY DESIGN: Combinations of four primer pairs, one for each retrovirus, were assayed in order to determine the combination of oligonucleotides as well as the PCR conditions that yield the most specific and sensitive coamplification of proviral sequences. To prevent contamination with DNA from previous PCR amplifications, the uracil N-glycosylase (UNG) system was incorporated into the coamplification format. RESULTS: A combination of primer pairs from the gag region of HIV-1, env of HIV-2, pol of HTLV-I and tax of HTLV-II yielded specific and sensitive coamplification of proviral sequences. The UNG system was incorporated and shown to be efficient in the degradation of contaminating DNA. In the evaluation of a serologically well established panel of singly and dually infected individuals, the assay detected 20/22 HIV-1, 8/10 HIV-2, 8/8 HTLV-I and 8/8 HTLV-II infections.

Lymphocyte immunoregulatory cells present in semen from human immunodeficiency virus (HIV)-infected individuals: a report from the HIV Heterosexual Transmission Study.

The purpose of this study was to determine the types and distribution of immune subsets present in semen from human immunodeficiency virus (HIV)-infected (HIV+) individuals and to compare these values with those measures in semen from HIV-negative (HIV-) individuals. To accomplish this, a direct three-color monoclonal antibody labeling technique was employed to identify immune cells in fresh ejaculates. Once labeled, the percent of each immune subset present in the ejaculate was determined by flow cytometric analysis. The percent of CD3+ cells present in the semen of the HIV+ group showed no significant difference when compared with semen from the HIV- group. Analysis of the CD4+ subset yielded a significantly lower percent in the HIV+ group than in the HIV- group. The analysis of the CD8+ subset yielded a higher percent of cells present in semen from HIV+ individuals. The CD8 higher value along with lower CD4 value results in a lower CD4/CD8 ratio in the HIV+ group. Further subset studies showed that the percent of cells expressing naive (CD4+ CD45RA+) and memory (CD4+ CD45RO+) markers was lower in the HIV+ group. This study provides additional data supporting the utility of flow cytometry and monoclonal antibodies to immunophenotypic cells present in semen ejaculates. It is also the first reported application of the technique to a disease-based model and may be useful to better understand issues of mucosal immunity and transmission of sexually transmitted diseases such as HIV.

Human immunodeficiency virus type 1 (HIV-1)-seronegative injection drug users at risk for HIV exposure have antibodies to HLA class I antigens and T cells specific for HIV envelope.

The question of whether persistently seronegative persons at high risk for human immunodeficiency virus type 1 (HIV-1) infection exhibit HIV-1-specific T cell responses and antibodies to HIV-1 envelope epitopes shared with selected HLAs was assessed. These antibodies are not detectable by conventional serologic methods. Envelope-specific helper T (Env-Th) cell responses and antibodies specific for the HIV/HLA epitopes were studied in 21 HIV-1-negative injection drug users (IDUs). HIV/HLA antibodies were detected in 7 (33.3%) of 21 IDUs and 4 (4.3%) of 94 low-risk controls. Env-Th cell responses were detected in 16 (76.2%) of 21 IDUs and in 2 (3.1%) of 65 low-risk controls. All HIV/HLA antibody-positive IDUs also had Env-Th cell responses. These findings confirm the presence of HIV-1-specific immunity in conventionally seronegative individuals. Further characterization of these responses could provide the basis for new preventive strategies.

Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users.

Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV-II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV-II, and HTLV-II infection is associated with HIV-1 and sociodemographic background.

Viral variability and serum antibody response in a laboratory worker infected with HIV type 1 (HTLV type IIIB).

Molecular clones of HIV-1 were obtained from isolates cultured from peripheral blood mononuclear cells (PBMCs) and directly from uncultured PBMCs from a laboratory worker accidentally infected with the HIV-1 laboratory strain, HIV-1(HTLV-IIIB). Envelope sequences corresponding to the first 752 amino acids of HIV-1(HTLV-IIIB) clone BH10 were obtained from clones of cultured virus and sequenced. Three env clones obtained shortly after infection differed among themselves at only seven nucleotide positions, resulting in one amino acid substitution and one frameshift mutation. These envelope sequences were as similar to the envelope sequences of various IIIB clones as the latter were to each other. env divergence increased over the course of infection. However, the overall diversity in env clones obtained two or more years after infection was still comparable to that among IIIB env clones from the original IIIB culture. Multiple clones of partial env gene sequences containing the V3 loop were also obtained directly from uncultured PBMCs by polymerase chain reaction amplification. The env sequences of these clones were generally similar to those of the cultured viruses. Within the V3 region, the earliest isolates retained the sequence of the HXB2 clone from IIIB. Clones obtained later showed a progressive divergence in V3. An A-to-T substitution within the GPGRAF sequence at the tip of the V3 loop was observed within 1 year after infection, and this mutation predominated in all subsequent isolates. Antibodies against the V3 loops of IIIB and divergent 1987 and 1990 LW isolates appeared simultaneously in laboratory worker serum and persisted with no significant differences in titer. Furthermore, neutralization studies with autologous sequential sera suggested selection for the A-to-T change in V3 was not due to V3-directed antibodies. These results demonstrate a surprising homogeneity among env sequences of HIV-1 from an infected laboratory worker, perhaps because the initial infection originated from a relatively homogeneous population of tissue culture-adapted virus.

Quo vadis: perinatal AIDS issues--2004.

The HIV problem will inexorably increase over the next decade, with an increasing proportionate impact upon women and children over the next decade. HIV will become endemic, essentially worldwide. Some regions in the developed world may be relatively spared if current trends continue. This may reduce the willingness to expend necessary resources, particularly if trends toward increasing isolationism continue. There are already signs of a world becoming "bored" with AIDS and the chronicity of a difficult problem. This engenders an atmosphere ripe for increasing discrimination, with the development of loopholes in protective legislation. Already in the United States, some lawsuits concerning health care access among employees have been decided in the employer's favor, permitting them to restrict access to health insurance, despite other regulations which might have protected such workers. Similarly, some HIV-infected health care workers have been dismissed or lost their privileges in the 1990s, despite passage of the Americans with Disabilities Act as well as preceding legislation. It remains to be seen how society will cope with these complicated issues. The view of AIDS in 2004 presented above is pessimistic. There are some important rays of hope. Recent innovative vaccine work and new theoretical models may put us on the road to success, both with preventive and therapeutic vaccines. In particular, the first success in eliciting protection against vaginal HIV exposure, albeit partial, was reported in mid 1993. In a simian immunodeficiency virus (SIV) in vivo experimental model, cellular immunity to SIV was induced in macaques without their developing any signs of SIV infection. These macaques after rechallenge with low-dose SIV remained free of detectable SIV, so there may be an element of protection associated with specific cellular immune responses to immunodeficiency viruses. However, very high-dose SIV rechallenge experiments in similar macaques still led to acquisition of active SIV infection, suggesting that any such protection was only partial. It is also possible that cellular immune protection may be of varying efficacy against different types of exposure, particularly parenteral versus mucosal (such as sexual) exposures. There is also reason for specific optimism concerning interventions that might directly reduce the risk of perinatal transmission. Data from studies of twins suggest that a substantial proportion of perinatal transmission does not occur until after labor has commenced. Thus, caesarian sections may potentially reduce the risk of transmission to the fetus in some cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Mycoplasma penetrans infection in male homosexuals with AIDS: high seroprevalence and association with Kaposi's sarcoma.

Antibodies to Mycoplasma penetrans were found at an unusually high frequency in male homosexuals with AIDS (55 of 149; 37%) and in human immunodeficiency virus (HIV)-infected asymptomatic homosexuals (13 of 49; 26.5%) but not in intravenous drug users (3 of 308; 1%) and hemophiliacs (1 of 165; 0.6%) with or without HIV-1 infection. Thus, both M. penetrans and Kaposi's sarcoma (KS) occur primarily in male homosexuals and rarely in other groups of patients at high risk of AIDS. Among 414 HIV-1-infected patients, statistical analysis revealed those with M. penetrans antibody were 11.7 times more likely to develop KS. Furthermore, among 198 HIV-infected homosexuals (149 with AIDS and 49 without AIDS), those with KS had M. penetrans-specific antibody at a significantly higher frequency (28 of 47; 59.6%) than did those without KS (27 of 102 with AIDS [26.5%] as well as 13 of 49 without AIDS [26.5%]; odds ratio = 4.1, P < .001). M. penetrans is apparently transmitted sexually through homosexual activity and is epidemiologically linked to formation of KS in homosexual men with AIDS. Parallel tests with M. genitalium revealed no similar link to KS in the same study sample.

Safe sex? Misconceptions, gender differences and barriers among injection drug users: a focus group approach.

Heterosexual transmission is one factor involved in the spread of the human immunodeficiency virus (HIV) within the injection drug use (IDU) population and between IDU and non-IDU individuals. Insufficient information is currently available to reduce this heterosexual transmission. As a basis for designing a questionnaire aimed at the IDU population, we conducted 5 focus groups to collect information on knowledge of and attitudes toward safe sex as held by male and female IDUs in methadone treatment. We identified misconceptions related to HIV infection, condoms, and sexual behavior. We also found gender-based differences in knowledge and learning style. Also, while individuals felt a responsibility to prevent HIV transmission, they lacked sufficient control to do so. The wide range of responses on questions concerning sexually transmitted diseases (STDs), condoms, reproductive decisions, and methods of promoting safe sex provides a basis for developing a questionnaire designed to identify and target specific subgroups for educational intervention.

PIP: Five focus groups were formed among 22 male and 16 female heterosexual intravenous drug users (IDUs) in February and March, 1991, at three methadone treatment centers in northern New Jersey. Discussion among seven to eight participants was stimulated by questions on attitudes toward and knowledge of sexual practices and sexually transmitted diseases, particularly HIV infection. The information served as part of preparations for the design of an HIV questionnaire for the IDU population. This paper reports on the focus group findings and identifies three areas of importance for questionnaire design and educational efforts: 1) misconceptions about HIV infection, condoms, and sexual terms; 2) gender differences in knowledge and learning style; and 3) the juxtaposition of awareness of responsibility with the lack of ability to use appropriate judgement. Participant characteristics were as follows: 59% Black males, 27% White males, and 14% Hispanic males, aged 20-43 years (mean of 35 years). Of the females aged 20-43 years (mean of 29 years), 44% were Black, 37% were White, and 19% were Hispanic. Most were HIV seronegative. Misconceptions existed about condoms and HIV transmission. Misconceptions traveled easily among peers. The answers to questions reflected a diversity of understanding. A variety of educational messages and approaches must be designed for specific subgroups within the drug using population. The recommendations are to use a variety of educational messages, to try to reach men, and to conduct research for finding out common characteristics of intravenous drug users who do not use condoms. Findings are reported by each of the ten questions asked. Questions pertain to why people do not use health care, what are sexual diseases, what is sexual protection, what is a condom, how to use or request use of condom, how to prevent having children, what protection is possible for couples when one member is HIV positive, what are some common sexual terms, and what can be done to prevent HIV infection.

Evaluation of human T cell lymphotropic virus infection in a cohort of injecting drug users.

The diagnosis and confirmation of human T cell lymphotropic virus (HTLV) type II infection has proven difficult, since most assays depend on antigenic cross-reactivity between HTLV-I antigens and HTLV-II antibodies. Type-specific HTLV infection rates were evaluated in a cohort of 233 injecting drug users screened with an HTLV EIA. Of the 52 EIA-reactive specimens, 48 were indeterminate or negative by standard Western blot. Type-specific HTLV results determined by polymerase chain reaction (PCR) were 0, HTLV-I; 92%, HTLV-II; 6%, type indeterminate; and 2%, negative. Among 42 EIA-reactive, HTLV-II-PCR-positive individuals tested by a p21 envr Western blot, all were positive and 74% had antibodies to the tax protein. This study found a high rate (22.3%) of HTLV reactivity, with HTLV-II usually the sole responsible agent; shortcomings in standard HTLV-I-based diagnostics but usefulness of PCR and p21 envr Western blots for typing and confirmation of HTLV reactivity; and a high prevalence (74%) of anti-tax antibody among HTLV-II-seropositive subjects, suggesting increased potential for infectivity.