Browsing Posts in Diseases

    In recent decades, clinical and public health efforts to reduce the burden of cardiovascular disease have emphasized the importance of calculating global, short-term (generally 10-year) risk estimates. However, the majority of adults in the United States who are considered to be at low risk for cardiovascular disease in the short term are actually at high risk across their remaining lifespan. Estimates of the lifetime risk of cardiovascular disease provide a more comprehensive assessment of the overall burden of the disease in the general population, now and in the future, because they take into account both the risk of cardiovascular disease and competing risks (e.g., death from cancer) until participants reach an advanced age. Such estimates can help guide public health policy, allowing projections of the overall burden of cardiovascular disease in the population.

    Most estimates of the lifetime risk of cardiovascular disease have been derived from analyses restricted to risk factors measured at a single age in a predominantly white population.6,7 These estimates do not account for the potential effects of birth cohort that may arise from secular changes in risk-factor levels8,9 or for the widespread use of medical treatment, which has translated into marked reductions in rates of cardiovascular events in the United States.10

    The Cardiovascular Lifetime Risk Pooling Project was designed to collect and pool data from numerous longitudinal epidemiologic cohort studies conducted in the United States over the past 50 years. This pooling approach provides an opportunity to calculate estimates of the lifetime risk of cardiovascular events according to age, sex, race, and other risk factors across multiple birth cohorts that would not be feasible within any one data set alone.

    Study Sample

    We included data sets in the Cardiovascular Lifetime Risk Pooling Project if they met the following criteria: they represented either community-based or population-based samples or large volunteer cohorts, they included at least one baseline examination with direct measurement of physiological and anthropometric (e.g., weight) variables, and they included 10 or more years of follow-up for fatal or nonfatal cardiovascular events or both. Data from 18 unique cohorts were included in the study, 17 of which were included in the pooled analysis. Because of the large size of one study, the Multiple Risk Factor Intervention Trial (MRFIT), relative to the other 17 studies, this cohort was analyzed separately. All data were appropriately de-identified, and all study protocols and procedures were approved by the institutional review board at Northwestern University.

    Ascertainment of Baseline Measures and Follow-up Events

    The protocols used to obtain data on demographic characteristics, personal and medical history, physical examination, laboratory results, and follow-up procedures for ascertainment of vital status and events for all cohorts included in the study have been published elsewhere. Blood pressure and serum cholesterol levels were measured directly in all participants; data on smoking status were self-reported, as were data on diabetes status, the latter derived from records of self-report, use of medication for diabetes, or both. Events were ascertained with the use of strategies selected by each cohort’s investigator group and included death from cardiovascular disease, from coronary heart disease, or from any cause and nonfatal events of interest, including myocardial infarction and stroke.

    Preliminary data on correlates of protection against HSV-1 are available. Antibody, but not cellular immunity, was correlated with protection against HSV-1. Among the HSV vaccinees tested in the immunogenicity cohort, 8 were subsequently infected by HSV-1 and 10 by HSV-2. Subjects with HSV-1 infection had significantly lower gD-2 ELISA antibody titers at month 7 (mean titer, 3561) than subjects who remained uninfected (mean titer, 6875; P=0.04). This was not the case for subjects with HSV-2 infection (mean titer, 6339; P=0.78). Cellular immune responses at month 2 or month 7 did not differ significantly between subjects who subsequently became infected with HSV-1 or HSV-2 and vaccinees who remained uninfected (see the Supplementary Appendix for details).

    The efficacy of the gD-2 candidate vaccine against HSV-1 is important because epidemiologic studies suggest that sexual transmission of HSV-1 is increasing in the United States,1 although its prevalence among U.S. children is decreasing.11 Among control subjects in the present study, 60% of the cases of genital disease and two thirds of the infections (with or without disease) were caused by HSV-1. These data are similar to the finding that HSV-1 is the most common cause of genital herpes in college students and young heterosexual women, and similar trends are reported in other countries. HSV-1 now rivals HSV-2 as a cause of neonatal herpes disease. Public health officials and researchers will need to closely monitor seroprevalence trends as future herpes vaccines are developed and assessed.

    Although the development of a vaccine that provides protection against HSV-1 genital disease is a substantial step forward, additional progress is needed before a herpes vaccine is likely to be approved for general use. Any candidate vaccine will probably have to have proven efficacy against both HSV-1 and HSV-2 disease. Prevention of infection (with or without disease) is also an important goal, because asymptomatic genital shedding of HSV may lead to the spread of the virus to newborns or sexual partners. This is a more difficult goal to achieve and may require approaches such as live attenuated vaccines or vaccine vectors to generate protection.

    Solicited reports of adverse events included redness, swelling, and pain at the injection site, as well as fatigue, fever, headache, and malaise. The HSV vaccine was more reactogenic and was associated with local pain, redness, and swelling more often than was the control vaccine. There was a small but significant increase in systemic symptoms, including fatigue, fever, headache, and malaise, in the HSV-vaccine group (Table 3). Dose 2 and dose 3 of the HSV vaccine were not associated with increased reports of adverse events; in contrast, reactogenicity decreased slightly with additional vaccination.


    The HSV vaccine was immunogenic and stimulated ELISA and neutralizing antibodies. As expected, control subjects did not have antibody to gD-2 on ELISA or neutralization of HSV-2. Geometric mean gD-2 ELISA titers were 21 at baseline and 6809 at month 7 after three doses of HSV vaccine; ELISA titers waned to 769 by month 20. HSV-2 neutralizing antibodies developed after two doses of HSV vaccine, but the median value fell to an undetectable level by study month 6 (see the Supplementary Appendix for details). After dose 3, HSV-2 neutralizing antibodies were again above the limit of detection (the mean titer at month 7 was 29) but fell to a median value that was undetectable by study month 16.


    Our findings of vaccine efficacy against HSV-1 and lack of efficacy against HSV-2 are puzzling in view of the previous two studies involving discordant couples that showed efficacy of this gD-2 vaccine against HSV-2.4 The difference in efficacy is likely to be due to some factor in the two populations studied. The distinguishing feature of discordant couples is that they are a highly selected group in which the uninfected partner is potentially repeatedly exposed to HSV by the infected partner. Attack rates of HSV-2 genital disease in the prior studies of gD-2 vaccine were high among uninfected women in discordant couples (13.9% for 19 months or 8.4% per year) and were reduced significantly by the vaccine (efficacy, 73% and 74% in the two trials; P=0.01 and P=0.02, respectively).4 Too few cases of HSV-1 genital disease occurred in women in the two previous studies to assess efficacy against HSV-1 (one case in each study among women who were seronegative at study entry).4 Potential reasons for vaccine efficacy in the discordant-couple population include selection bias for a population of women with relative resistance to HSV-2, with added benefits from a subunit vaccine; an undefined immunologic priming event from chronic sexual exposure to HSV-2 viral antigens from the infected partner; and less frequent sexual activity due to the long-term nature of the relationship as compared with sexual activity by couples in new relationships.

    It is not apparent why the biologic characteristics of HSV-1 are different from those of HSV-2; the gD-2 vaccine induces significant protection against genital HSV-1 disease as well as HSV-1 infection, but not against disease or infection caused by HSV-2. Genital HSV-1 may be acquired primarily through oral–genital sex (although a history of oral sex was not a risk factor for HSV-1 acquisition in our study); a lower inoculum, an oral–genital route (possibly less traumatic sex), and a less suitable environment for HSV-1 replication are all possible explanations for protection by the vaccine against HSV-1 but not HSV-2. The gD-2 antigen is derived from HSV-2, but 89% amino acid homology is shared with gD-2 from HSV-1, which may explain the protection against HSV-1. Type-specific immune responses to vaccine antigen may reveal differences in antibody activity against HSV-1 and HSV-2. Whether HSV-1 is more easily neutralized by vaccine-induced antibodies must be determined by further laboratory studies.

    Self-reported behaviors and demographic factors were analyzed for association with HSV-1 or HSV-2 infection in the per-protocol cohort for months 2 through 20. Analysis of self-reported behavioral risk factors was restricted to 5980 sexually active subjects. An increased risk of HSV-1 infection was associated with 6 or more lifetime sexual partners (hazard ratio, 2.2; 95% CI, 1.3 to 3.8) and more than 1 partner in the previous 12 months (hazard ratio, 1.9; 95% CI, 1.4 to 2.7). Subjects who were 23 years of age or older were less likely to acquire HSV-1 than 18-to-22-year-olds (hazard ratio for subjects 23 to 26 years of age, 0.6; 95% CI, 0.4 to 0.8; hazard ratio for subjects 27 to 30 years of age, 0.4; 95% CI, 0.3 to 0.8). Factors not associated with an increased risk of HSV-1 infection included race or ethnic group, country of residence (United States or Canada), having a current partner with herpes, ever having a partner with herpes, condom use, history of any sexually transmitted infection (STI), and oral sex.

    An increased risk of HSV-2 infection was associated with having 6 or more lifetime sexual partners (hazard ratio, 2.0; 95% CI, 1.1 to 3.8), having 6 or more partners in the previous 12 months (hazard ratio, 2.7; 95% CI, 1.3 to 5.5), ever having a partner with herpes (hazard ratio, 3.0; 95% CI, 1.7 to 5.3), having a current partner with herpes (hazard ratio, 3.4; 95% CI, 1.8 to 6.4), a history of any STI (hazard ratio, 3.3; 95% CI, 2.2 to 5.0), nonwhite race (hazard ratio, 3.1; 95% CI, 2.1 to 4.6), and U.S. residence (hazard ratio, 2.7; 95% CI, 1.2 to 6.2). Factors not associated with increased risk of HSV-2 infection included age, ethnic group, condom use, and oral sex. Initiation of sexual activity after 15 years of age was associated with a decreased risk of both HSV-1 infection (hazard ratio for initiation at 16 to 18 years of age, 0.6; 95% CI, 0.4 to 0.8; hazard ratio after 18 years of age, 0.3; 95% CI, 0.2 to 0.6) and HSV-2 infection (hazard ratio for initiation at 16 to 18 years of age, 0.5; 95% CI, 0.3 to 0.8; hazard ratio after 18 years of age, 0.3; 95% CI, 0.2 to 0.6).

    Genital Shedding of HSV-2

    Forty-three subjects (30 in the HSV-vaccine group and 13 in the control group) with HSV-2 infection collected anogenital swabs on 60 consecutive days, beginning 3 to 6 months after disease onset (15 subjects in the HSV-vaccine group and 9 in the control group) or seroconversion (15 subjects in the HSV-vaccine group and 4 in the control group). Analysis of these swabs showed that the rate of viral shedding was higher among the HSV-vaccine recipients than among controls (29% vs. 19%; relative risk, 1.55; 95% CI, 1.28 to 1.86). The mean quantity of HSV DNA on days with shedding did not differ between the two groups.

    Statistical Analysis

    The trial was designed to have 80% power to detect a vaccine efficacy of 75% with 45% as the lower limit of the 95% confidence interval. It met the information goal, observing 70 of a planned 72 cases of genital herpes disease in the per-protocol cohort. The trial was monitored by an independent data safety and monitoring board sponsored by the National Institute of Allergy and Infectious Diseases, which met quarterly and reviewed the study for safety. At a prespecified interim analysis, the board also reviewed the trial for futility. The sample size was extended once in response to higher-than-anticipated attrition. Vaccine efficacy was estimated as 1 minus the relative risk from a Cox proportional-hazards model fit to the time to first acquisition of each study end point. Rates of loss-to-follow-up were similar between the two study groups, and noninformative censoring was assumed. A post hoc assessment of demographic and behavioral risk factors for HSV acquisition was performed with the use of a Cox proportional-hazards model adjusted for the receipt of HSV vaccine. All reported P values are two-tailed and have not been adjusted for multiple testing. The per-protocol and intention-to-treat cohorts are defined in the legend for Figure 1.
    Characteristics of the Study Population

    Fifty clinical sites in the United States and Canada screened a total of 31,770 women for antibodies to HSV-1 and HSV-2; 12,468 women were seronegative for both HSV-1 and HSV-2, of whom 8323 met the other eligibility criteria and were enrolled between January 14, 2003, and November 19, 2007.

    Vaccine Efficacy

    In the control group, HSV-1 was a more common cause of genital disease than HSV-2 (21 cases caused by HSV-1 vs. 14 cases caused by HSV-2). Efficacy against genital disease caused by HSV-1 was observed (vaccine efficacy, 58%; 95% CI, 12 to 80) (Figure 2B), but efficacy was not observed against HSV-2 disease (−38%; 95% CI, −167 to 29) (Figure 2C). Three doses of vaccine were associated with efficacy against HSV-1 (77%; 95% CI, 31 to 92) but not HSV-2 (−40%; 95% CI, −234 to 41). An analysis in which the case definition was limited to culture-positive cases (excluding HSV cases diagnosed according to clinical and serologic criteria) also showed efficacy against HSV-1 (two-dose efficacy, 69%; 95% CI, 25 to 87; three-dose efficacy, 82%; 95% CI, 35 to 95).

    The HSV vaccine provided protection against infection caused by HSV-1 or HSV-2 (efficacy, 22%; 95% CI, 2 to 38). This overall finding of protection against infection was driven by efficacy against HSV-1 infection (35%; 95% CI, 13 to 52), whereas efficacy against HSV-2 infection was not observed (−8%; 95% CI, −59 to 26).

    The control vaccine, inactivated hepatitis A vaccine (Havrix, GlaxoSmithKline), was formulated as 720 enzyme-linked immunosorbent assay (ELISA) units of inactivated hepatitis A virus combined with 0.5 mg of alum, in a volume of 0.5 ml. For the study to be blinded, the control vaccine was given at 0, 1, and 6 months in doses containing one half the usual volume and one half the usual amount of antigen.

    Study Design

    The double-blind, randomized field trial was designed in collaboration among the trial sponsors, the National Institutes of Health (NIH) and GlaxoSmithKline; the study chair; the executive committee; and the scientific leadership group. Data were collected with the use of the GlaxoSmithKline remote data-entry system and were monitored by GlaxoSmithKline. All the authors and the trial sponsors vouch for the accuracy and completeness of the data. Data were electronically transferred to EMMES, a contract research organization, where they were analyzed according to the analysis plan prepared by biostatisticians at GlaxoSmithKline and EMMES, with input to the analysis plan from the NIH, the study chair, and the executive committee. The manuscript was drafted by the first author, with input from the biostatisticians at EMMES and from the executive committee.

    Study End Points

    The primary end point of the study was prevention of genital herpes disease caused by HSV-1, HSV-2, or both from month 2 (1 month after vaccine dose 2) through month 20. Genital disease was defined as clinically compatible signs and symptoms confirmed by viral culture, seroconversion, or both within 6 months after disease onset. Secondary end points included prevention of HSV-1 or HSV-2 infection (with or without disease) from month 2 through month 20 (two-dose efficacy) or month 7 through month 20 (three-dose efficacy) and prevention of genital herpes disease caused by individual HSV types. Cases of infection and disease were determined centrally by an independent, blinded end-point review committee with the use of documented criteria.

    Substudy of Viral Shedding

    Subjects identified as having acquired genital HSV-2 disease or HSV-2 infection during the study were invited to participate in an evaluation of viral shedding. Subjects were instructed to collect daily swabs from the anogenital area for 60 consecutive days and to maintain a diary of genital signs and symptoms, as previously described, beginning 3 to 6 months after HSV-2 seroconversion or disease onset.

    Laboratory Studies

    Western blot analysis (University of Washington Clinical Virology Laboratory at Seattle Children’s Hospital) was used to confirm HSV-1– or HSV-2–seronegative status at study entry and seroconversion during the follow-up period.6 Seroconversion to HSV-1 or HSV-2 was defined as a positive Western blot analysis in a subject with a previously negative analysis for the corresponding HSV type.

    Serum specimens from a random subset of 611 subjects in the HSV-vaccine group and 223 subjects in the control group were assessed for the development of antibodies to vaccine antigens with the use of ELISA4,7 for gD-2 and virus neutralization of HSV-2 at 0, 2, 6, 7, 12, 16, and 20 months. Long-term genital shedding of HSV-2 DNA was assessed with the use of a quantitative, real-time, fluorescence-based polymerase-chain-reaction assay, as described previously, with a positive result defined as 150 copies per milliliter.

    Both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can cause primary infection of the genital tract, and HSV-1 infection has become an increasingly frequent cause of genital disease. The majority of HSV infections are asymptomatic, and only 10 to 25% of persons with HSV-2 antibodies have recurrent genital disease. Transmission of HSV from infected women to neonates may lead to severe neurologic disease or death in the newborn. Strategies to control genital herpes infection and disease have mainly focused on antiviral chemotherapy, education, and the use of condoms. The availability of an effective prophylactic vaccine would help control genital herpes.

    In two previous efficacy trials of an HSV-2 glycoprotein D–based subunit (gD-2) vaccine in discordant couples in which one partner had recurrent HSV genital disease, the subset of seronegative women (negative for both HSV-1 and HSV-2 antibodies) was significantly protected against HSV-2 disease by the vaccine (73% and 74% efficacy, respectively); efficacy was not shown in either men or HSV-1–seropositive women.4 To further evaluate the gD-2 vaccine as a potential public health tool, we evaluated this vaccine in a cohort of women who were screened and found to be antibody-negative for HSV-1 and HSV-2.

    Study Population

    Women 18 to 30 years of age who were seronegative for HSV-1 and HSV-2 were recruited from 40 sites in the United States and 10 in Canada. Other inclusion criteria were written informed consent, the absence of serious health problems, a willingness to use effective methods of birth control throughout the period from 30 days before vaccination to 2 months after receipt of the third dose of vaccine, and a negative pregnancy test.

    Vaccines and Adjuvants

    The HSV-2 vaccine (GlaxoSmithKline) contained 20 μg of truncated glycoprotein D from HSV-2 strain G. The gD-2 vaccine antigen was combined with an adjuvant that consisted of 0.5 mg of aluminum hydroxide (alum) and 50 μg of 3-O-deacylated monophosphoryl lipid A. The vaccine was administered by injection at a dose of 0.5 ml at 0, 1, and 6 months.

    Current policies have been criticized as not meeting the needs of victims or public health, focusing on short term crisis interventions that are not likely to solve complex problems (Chuang, 2005; Stolz, 2005). There is a lack of attention to the social and economic conditions throughout the world that leave people vulnerable to trafficking. Immigration policies contribute to potential for exploitation by disallowing legal means for better opportunities. There is a need to look at root causes, including supply and demand factors that contribute to high numbers of trafficking victims (Chuang, 2005, Naim, 2005). The current policies do not look at push and pull factors that make people vulnerable to trafficking, including employment opportunities, high potential for profit for those involved in trafficking. Neither employers utilizing trafficking victims or traffickers face serious penalties. Little has been done to address the gender, racial, and economic oppression that makes the situation possible to begin with (Stolz, 2005). While health education may provide some protection for trafficking victims and potential victims, there is a need for macro level interventions and changes in public policies. Levitra no prescription needed

    Marisol desperately and knowingly entered the United States illegally in hopes of better opportunities and to escape abuse in her home country. Attempts to “rescue” her did not consider Marisol’s needs, wants, or long term remedies to her initial problem, leaving her in an abusive situation with limited opportunities. The lack of effective interventions have resulted in a situation where Marisol’s current and future American citizen children are at much greater risk of HIV/AIDS infection, as well as Marisol’s sexual partners. The fiscal, social, and emotional costs to Marisol, her children, and society at large, are enormous. Current policies and practices in regards to trafficking victims do little to remedy the root circumstances of the problem. “Crisis” centered interventions emphasizing criminal justice system needs while neglecting vulnerable victims are not likely to have an impact on human trafficking. The best interests of individuals, human rights, or public protection are not served under existing programs. There is a need to look at larger issues including economic inequities, gender and racial discrimination, if there is to be any real reduction in human trafficking. Existing policies do little for victims, public protection, or vulnerable groups and may actually contribute to public health risks.

    Potential Solutions/Ethical Dilemmas

    Public health has a tradition of protecting communities from communicable diseases. An ongoing dilemma is the need to balance person rights with the need for protection of the larger society. A difficult question for even the most committed advocates of HIV/AIDS immigrants and trafficking victims is how to achieve this balance. Some communicable diseases including drug-resistant tuberculosis, malaria, and polio are believed to be on the increase in the United States due to the presence of illegal immigrants (Pelner, 2005). The possibility of HIV/AIDS infected sex workers with to potential spread the disease to others including their own unborn children has ethical, medical, and financial implications. There is a need to consider the risk factors in planning successful interventions that might protect both individuals and the larger society.

    It is known that certain policy interventions, including tighter border controls and the legalization of prostitution fail to reduce the incidence of human trafficking. More restrictive immigration laws and the legalization of prostitution may actually provide greater opportunities for traffickers (Chuang, 2005; Dougherty, 2006; Webber & Shirk, 2005).

    Persons desperate to escape lack of opportunities or violence in their home countries are much more vulnerable when their presence and activities are hidden.

    At the most basis level, interventions can begin with provision of information about human trafficking and more specifically, HIV/AIDS risks and prevention. Some programs, including prevention efforts in Korea, have demonstrated effectiveness through public information (Schuckman, 2006). Potential victims and professionals likely to come in contact with potential victims are provided with information about human trafficking, cautioning about potential risks. On a domestic level, health care providers, shelter workers, and law enforcement personnel likely to encounter trafficking victims need training in how to recognize and assist victims (Maxell, Cravioto, Galvan, Ramirez, Wallisch, & Spense, 2005; Webber & Shirk, 2005). Knowledgeable and resourceful professionals might help trafficking victims access legal, health, and social support systems. Connection to resources is not only essential for individual victims, but for the protection of society, including potential unborn children of trafficking victims. On a global level, potential trafficking victims can be provided with information in their home countries that may help lessen vulnerability to exploitation. Human rights, as well as individual needs, are public health concerns (de Caralho, Ayres, Paiva, Franca, Gravato, Lacerda, Negra et al., 2006).

    Empowerment models allow for the development of interventions based on stated needs and desires of those impacted versus the agendas of organizations providing care. Some note that “rescue efforts” are not likely to be successful if a holistic approach including specialized shelter, case management, legal and practice services are not provided. Effective interventions need to consider the actual wants and needs of trafficking victims. Care should be taken to avoid further exploitation and trauma by promoting organizational agendas with little input from trafficking victims themselves (Davies, 2004). Cultural and language barriers may impair advocacy efforts, thus need to be addressed in intervention strategies (Gavagan & Brodyaga, 1998). Legal representation is essential, given the complexity of laws and policies, as well as discretion within systems. Services and advocacy may be limited in rural areas, resulting in a need for creative networking and information sharing (Chuang, 2004).

    Although policies are sympathetic to undocumented persons working in the sex industry, cultural stigma against illegal immigrants and prostitutions are realities for trafficking victims, both in the United States and in their home countries (Stuckman, 2006). Despite current emphasis on victim protection as opposed to old “victim blaming” policies and practices, there is evidence that reality falls short of ideology. Trafficking victims, given their limited education, work options, and historical trauma, may be vulnerable to “secondary trafficking” (Chuang, 2004). Trafficking victims may be among the most vulnerable and disadvantaged persons in society, likely to have experienced poverty, trauma, and desperation prior to trafficking (Bales, 2005; Coonan, 2004; Schuckman, 2006). Previous experiences, limited education, lack of fluency in host language and culture may cause victims to avoid seeking or utilizing help. Some researchers have noted correlations and similarities to victims of domestic violence including self blame, shame, lack of emotional and social support as factors (Gavagan & Brodyaga, 1998; Hopper, 2004). Because most victims are in the United States illegally, fear of deportation may be valid concern. Even for victims who are willing to come forward and cooperate with law enforcement, the process of applying for benefits and protections can be very long, stressful, and potentially risky. Despite protections, victims may be charged with crimes, including prostitution, and face incarceration or deportation (Bales & Lize, 2005; Pendleton, 2004; Webber & Shirk, 2005). Despite the high amounts of money provided to combat the problem of human trafficking, little change has occurred in terms of prosecutions of traffickers or protections for victims(Chuang, 2004).

    An Unsuccessful Intervention
    Marisol was identified as a potential “trafficking victim” by a trusted health care worker. The worker convinced Marisol that she might be able to obtain legal immigration status, public benefits, and even be reunified with her daughter, Serena, under the TVPA policies. Marisol reluctantly agreed to cooperate with law enforcement against “Uncle Ned,” resulting in greater alienation from her family of origin, as well as the local community. “Uncle Ned” was highly respected by Marisol’s family and peers. Her willingness to work with U.S. law enforcement was perceived by many as a betrayal. Programs, shelters, and legal resources specific to trafficking victims were limited or non-existent in the small rural community where Marisol and Sergio had been residing. Marisol’s worker made arrangements for Marisol to and Sergio to be placed in a shelter/advocacy program for victims of domestic violence. Life in the shelter failed to provide Marisol and Sergio with support and security. Once again perceived as an “other,” Marisol was shunned by the other residents. Few spoke her language, and many labeled her a “whore.” Separated from what she had perceived as support and special treatment from “Uncle Ned,” Marisol became increasingly lonely and afraid. She felt little in common with her housemates, many of whom had mental health and substance abuse problems. Sergio was exposed to viral infections and subjected to minor injuries from other children in the shelter. Marisol decided her best option was to run away. Given her lack of resources, education, and skills, Marisol soon found herself dependent on a man who put her back to work as a prostitute. She now keeps her HIV status hidden and avoids interactions with social service agencies or health care providers. Marisol is pregnant again, but her fears, previous experiences, and now, her current captor, keep her from accessing prenatal care or treatment for HIV/AIDS. Her lack of access to health care and information puts others, including her unborn child, at high risk of contracting HIV/AIDS.