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This chapter describes reports of Kaposi’s sarcoma and opportunistic infections (KS/OI) in Haitians residing in the United States, primarily Miami, Florida, and Brooklyn, New York, which CDC began receiving in 1982. An unusual clinical feature was a high prevalence of toxoplasmosis, a parasitic infection, which can involve the brain. Most patients were men who denied homosexual activity and injection drug use. Additional studies done by CDC and others research groups found that KS/OI was also occurring in Haiti. Because studies of Haitians with KS/OI failed to find clear risk factors for the disease, Haitian entrants to the United States were designated as a “risk group” and, like homosexual men and IDUs, were not allowed to donate blood. Although probably justified for public health purposes, this designation undoubtedly led to unintended discrimination against Haitian Americans.

This chapter describes the first cases of what is now known as AIDS, which were reported by Dr. Michael Gottlieb, an immunologist at UCLA Hospital, and published in the Morbidity and Mortality Weekly Report (MMWR) on June 5, 1981. Five previously healthy homosexual men from Los Angeles had developed a life-threatening infection, Pneumocystis carinii pneumonia (PCP), typically seen only in persons receiving immunosuppressive therapy. A month later, the Centers for Disease Control and Prevention (CDC) published a second MMWR describing additional homosexual men from California and New York City diagnosed with PCP, other opportunistic infections (OIs), and a rare malignancy, Kaposi’s sarcoma (KS). To respond to this apparent outbreak, CDC formed a multidisciplinary task force and placed it under the direction of Dr. James (Jim) Curran. The KS/OI Task Force was asked to solve this medical mystery.

This chapter describes the process of making predictions about the magnitude and trajectory of the epidemic in America’s early response to AIDS. Initial modeling efforts used a simple extrapolation method, which assumed that past trends in cases could predict future cases. Subsequent modeling employed a “back-calculation” method to estimate the number of infected persons and project the number who would develop AIDS. Back-calculation models correctly predicted that the incidence of AIDS would peak in the early 1990s and then gradually fall due to “saturation” of individuals at the highest risk for infection as well as behavioral change. But given that newly susceptible individuals would enter the at-risk population each year, the epidemic would not spontaneously disappear.

The history of the CDC, its role in disease prevention, detection, and response, and its unique assets including the Epidemic Intelligence Service (EIS), the agency’s cadre of public health advisors, and the MMWR are presented—setting the scene for CDC’s early actions to determine the cause of the unexplained illnesses occurring in the United States that would become known as AIDS.

This chapter discusses the impact of the epidemic on blood safety. By the end of 1982, evidence had emerged that the putative Kaposi’s sarcoma and opportunistic infections (KS/OI) agent could be transmitted through transfused blood and the blood-clotting factors used to treat persons with hemophilia. In January 1983, CDC met with representatives of the blood banking associations, the National Hemophilia Foundation, and the Food and Drug Administration to discuss measures to protect the safety of the blood supply. CDC presented several options, including testing donated blood for “surrogate markers” of risk, such as antibody to hepatitis B virus. The meeting was very contentious and resulted in no recommendations. Fortunately, subsequent private discussions were more productive, and in March 1983 the US Public Health Service published the first guidelines to prevent what was now called AIDS. The guidelines included the deferral of “risk group” members from blood donation.

This chapter explores efforts to identify a known sexually transmitted infection (STI) that might serve as a model for the spread of the unidentified agent likely causing Kaposi’s sarcoma and opportunistic infections (KS/OI). The best model for KS/OI appeared to be hepatitis B virus (HBV). If this model were correct, KS/OI would be expected to occur in heterosexual men and women as well as in injection drug users (IDUs). Beginning in the summer of 1981, CDC began receiving reports of KS/OI in both heterosexuals and IDUs. Individual case investigations and epidemiologic studies indicated that the infectious agent was being transmitted by needle sharing between IDUs and sexually from bisexual and IDU men to their female partners. The epidemiology of KS/OI appeared to be like that of hepatitis B and suggested that KS/OI would spread to other populations.

This chapter describes investigations into unexplained immunodeficiency and opportunistic infections in infants. In 1982, CDC received reports of such cases from San Francisco, New York City, and Newark, New Jersey. The mothers and infants were extensively investigated by local pediatric immunologists, and findings were reviewed by CDC epidemiologists and immunologists. Although a variety of congenital immunodeficiency syndromes are seen in infants, the immunologic profile of these children resembled that seen in adults with Kaposi’s sarcoma and opportunistic infections (KS/OI). Most of the mothers of these infants were either injecting drug users (IDUs) or Haitian. Although clinical data on the mothers were limited, one of the mothers had Pneumocystis carinii pneumonia (PCP). Taken together, the evidence suggested that the causative agent of KS/OI could be transmitted from mother to infant.

This chapter describes the increasing fear of the infection, as the HIV epidemic spread in the United States. Healthcare workers, especially surgeons, worried about the risk of occupational exposure, while public concerns grew about the possibility of HIV transmission through “casual contact” and other routes, such as insect bites. Such fears were allayed by several CDC studies. A large serosurvey of orthopedic surgeons failed to detect infections resulting from occupational exposures to blood. And, studies of family members of AIDS patients living in the Bronx, New York, and of residents of Belle Glade, Florida, found no evidence of HIV transmission through household contact or mosquitoes, respectively. These studies helped inform the landmark 1987 Understanding AIDS brochure, which was mailed to every US household.

This chapter presents the two main theories that were proposed to explain the outbreak of Kaposi’s sarcoma and opportunistic infections (KS/OI) in homosexual men. The first theory was that an infectious agent, possibly sexually transmitted, was causing immunosuppression in these men. The second theory was that an environmental exposure, perhaps to nitrite inhalants (“poppers”), was the cause. Interviews with patients indicated that they were both highly sexually active and used a variety of drugs. CDC conducted a national case-control study to examine risk factors for KS/OI and concluded that the disease was probably caused by a sexually transmitted infection (STI), but the study could not exclude a possible role for drugs. A second major CDC investigation of a sexually linked cluster of forty homosexual men with KS/OI strongly favored the STI theory and suggested that heterosexual men and women would also be at risk for the disease.

Dispatches from the AIDS Pandemic: A Public Health Story examines the history of the AIDS pandemic through the eyes of key individuals, including the authors, who were involved in the response to the disease at the US Centers for Disease Control and Prevention (CDC). Much of the material is based on interviews conducted as part of the CDC’s AIDS oral history project, as well as hundreds of original source documents. The chapters are organized in three sections, reflecting the different tones and viewpoints of the authors and persons quoted. Section I focuses on the United States and takes the reader from the earliest days of the recognized epidemic, starting with the first five cases of Pneumocystis pneumonia in previously healthy, young homosexual men reported in CDC’s Morbidity and Mortality Weekly Report (MMWR) in June 1981. Section II describes CDC’s initial AIDS efforts beyond the United States in Africa and Thailand, along with the World Health Organization’s (WHO) nascent AIDS program. Section III summarizes and comments on scientific and public health advances to date, including the origins of HIV and the development of life-saving treatments. The book’s distinctive and numerous firsthand reports offer a unique opportunity for readers to gain insight into the history and evolution of the pandemic and efforts leading to the global response.

Introduction The US Preventive Services Task Force (USPSTF) recommends select preventive clinical services, including cancer screening. However, screening for cancers remains underutilized in the United States. The Centers for Disease Control and Prevention leads initiatives to increase breast, cervical, and colorectal cancer (CRC) screening. We assessed the number of avoidable deaths from increased screening, according to USPSTF recommendations, for CRC and female breast and cervical cancers. Methods We used model-based estimates of avoidable deaths for the lifetime of single-year age cohorts under the current and increased use of screening scenarios (data year 2016; analysis, 2018). We calculated prevented cancer deaths for each 1% increase in screening uptake and extrapolated to current level of screening (2016), current level plus 10 percentage points, and increasing screening to 90% and 100% of the eligible population. Results Increased use of screening from current levels to 100% would prevent an additional 2,821 deaths from breast cancer, 6,834 deaths from cervical cancer, and 35,530 deaths from CRC over a lifetime of the respective single-year cohort. Increasing use of CRC screening would prevent approximately 8.5 times as many deaths as the equivalent increase in use of breast cancer screening (women only), although twice as many people (men and women) would have to be screened for CRC. Conclusions A large number of deaths could be avoided by increasing breast, cervical, and CRC screening. Public health programs incorporating strategies shown to be effective can help increase screening rates.

The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious and the earliest movements of the virus within the US are unknown. We serologically screened >2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978-1979-eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome 'snapshot' reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location. Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as 'Patient 0' (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.

BACKGROUND: Endemic Kaposi's sarcoma (KS) is a clinically and epidemiologically distinct human immunodeficiency virus negative form of KS occurring in Africa. Kaposi's sarcoma is now the most frequently reported cancer in some areas of Africa. OBJECTIVE: To determine if a KS-associated herpesvirus (KSHV) is present in both endemic HIV-seronegative and HIV-seropositive KS lesions from African patients. METHODS: Paraffin-embedded tissue specimens from Ugandan patients with KS and non-KS tumor control patients attending a university-based oncology clinic were examined in a blinded case-control study. Tissue DNA specimens were examined for detectable KSHV genome by nested polymerase chain reaction performed at two independent laboratories. RESULTS: We identified KSHV in 17 (85%) of 20 KS tissue specimens from HIV-seronegative patients and 22 (92%) of 24 KS tissue specimens from HIV-infected persons. Kaposi's sarcoma lesions from four HIV-infected persons and four HIV-seronegative persons were positive for KSHV. Unlike previous studies in North America and Europe, three (14%) of 22 non-KS cancer control patients' tissue specimens were also positive for KSHV that resulted in an overall odds ratio of 49.2 (95% confidence interval, 9.1 to 335) for detecting KSHV in KS lesions from patients in Uganda. CONCLUSION: As in North America and Europe, KSHV infection is strongly associated with both HIV-seropositive and HIV-seronegative KS in Africa. However, it is likely that infection with this virus is more highly prevalent in Uganda.

Uganda offers a unique setting in which to study the effect of human immunodeficiency virus-1 (HIV-1) on cancer. HIV-1 is prevalent there, and cancers which are known to be HIV-associated, such as Kaposi's sarcoma and Burkitt's lymphoma, are endemic. Adults residing in Kampala, Uganda, presenting with cancer in city hospitals were interviewed and had an HIV test. Of the 302 adults recruited, 190 had cancers with a potentially infectious aetiology (cases). The remaining 112 adults with tumours not known to have an infectious aetiology formed the control group. In addition, 318 children who were also Kampala residents were recruited and tested for HIV: 128 with cancer (cases) and 190 with non-malignant conditions (controls). HIV seroprevalence was 24% in adult controls and 6% in childhood controls. The odds of HIV seropositivity among cases with specific cancers (other than Kaposi's sarcoma in adults) were compared with that among controls, using odds ratios (ORs), estimated with unconditional logistic regression. All ORs were adjusted for age (

Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p < 0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear.

Objective: To explore the extent of the condom gap, investigating the relative roles of supply-side and demand-side factors in determining condom use. Design: GPS mapping of condom outlets, and population-based survey. Methods: An urban and a rural site were selected within the Epidemiological and Demographic Surveillance Site in Kilifi district, Kenya. Potential condom outlets (n ¼281) were mapped and surveyed, and questionnaires on condom access and use (n ¼630) were administered to a random sample of men and women aged 15‐49. Multivariate logistic regression was performed to assess the relative roles of supply-side and demand-side barriers on condom use. Results: The median straight-line distance to free condoms was 18-fold higher in the rural versus urban site. Among sexually active respondents, 42% had ever used a condom, and 23% had used a condom over the past 12 months, with lower levels among rural versus urban respondents (P

OBJECTIVE: African men who have sex with men often sell sex to men and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). DESIGN: Descriptive behavioural study METHODS: : A novel validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. RESULTS: Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence were more likely to only report insertive anal sex roles and reported lower frequencies of condomless receptive anal sex than exclusive MSW. CONCLUSION: Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.

M Hamill and colleagues believe the UK could do more to ensure people know their HIV status

Following its recognition in 1981, the HIV/AIDS epidemic has evolved to become the greatest challenge in global health, with some 34 million persons living with HIV worldwide. Early epidemiologic studies identified the major transmission routes of the virus before it was discovered, and enabled the implementation of prevention strategies. Although the first identified cases were in MSM in the United States and western Europe, the greatest impact of the epidemic has been in sub-Saharan Africa, where most of the transmission occurs between heterosexuals. Nine countries in southern Africa account for less than 2% of the world's population but now they represent about one third of global HIV infections. Where broadly implemented, HIV screening of donated blood and antiretroviral treatment (ART) of pregnant women have been highly effective in preventing transfusion-associated and perinatally acquired HIV, respectively. Access to sterile equipment has also been a successful intervention for injection drug users. Prevention of sexual transmission has been more difficult. Perhaps the greatest challenge in terms of prevention has been in the global community of MSM in which HIV remains endemic at high prevalence. The most promising interventions are male circumcision for prevention of female-to-male transmission and use of ART to reduce infectiousness, but the extent to which these interventions can be brought to scale will determine their population-level impact.

TOC summary: Although the end of the epidemic is not yet in sight, the remarkable response has improved health around the world., June 2011 marks the 30th anniversary of the first description of what became known as HIV/AIDS, now one of history’s worst pandemics. The basic public health tools of surveillance and epidemiologic investigation helped define the epidemic and led to initial prevention recommendations. Features of the epidemic, including the zoonotic origin of HIV and its spread through global travel, are central to the concept of emerging infectious diseases. As the epidemic expanded into developing countries, new models of global health and new global partnerships developed. Advocacy groups played a major role in mobilizing the response to the epidemic, having human rights as a central theme. Through the commitments of governments and private donors, modern HIV treatment has become available throughout the developing world. Although the end of the epidemic is not yet in sight and many challenges remain, the response has been remarkable and global health has changed for the better.

OBJECTIVE Given the well documented occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients who recently started combination antiretroviral therapy (cART), we examined whether cART initiation increased the risk of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) using data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration. DESIGN A nested matched case-control study design was used to assess the effects of individual CD4 cell trajectories and exposure to cART close to the time of cancer diagnosis. METHODS Cases were patients diagnosed with either cancer during follow-up with a minimum of two consecutive CD4 cell readings within the year preceding diagnosis. For each case, up to 10 controls, matched by sex and cohort, were selected by random sampling. Changes in CD4 cell count, calculated by simple and piecewise linear regression, and recent exposure to cART were compared within matched case-control sets using conditional logistic regression. RESULTS Using data on 689 cases and 4588 controls, we found that an initially low and decreasing CD4 cell count during the year prior to cancer diagnosis is predictive of both Kaposi sarcoma and NHL. Most of this cancer risk is explained by the immunodeficiency characteristic of the period before cART initiation; however, an increased cancer risk was seen in patients who initiated cART in the previous 3 months (odds ratio 2.31; 95% confidence interval 1.33, 4.00). CONCLUSION Although IRIS may transiently increase the risk of Kaposi sarcoma or NHL in HIV-infected patients, the timely initiation of cART remains the best strategy to avoid the development of these malignancies.

To reduce the spread of the human immunodeficiency virus (HIV), Granich et al.1 (2009) have proposed a new strategy for universal voluntary HIV testing immediately followed by antiretroviral therapy. Although this proposal is likely to benefit the partners of those affected and thus promote public health, it is by no means clear that it benefits the infected people themselves and indeed it may be harmful. Since the proposal involves an intervention that is not clinically indicated, it falls foul of the normal ethical standards of clinical medicine, which is to act in the best interests of patients. Neither is it a measure that would be imposed under the protection of public health law on people who are seen as representing such danger to others that significant restrictions in liberty are appropriate. Thus, the proposal represents a third category of public health measure. We argue that a coherent ethical framework including a robust process is appropriate to proposals of this kind and that medical research offers a useful model since some research, like this proposal, is motivated not by the interests of the individual participants but by the common good. We outline some possible elements of such an ethical framework. © The Author 2010. Published by Oxford University Press.

Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

The diagnosis of HIV infection is the point of entry for treatment and prevention services, yet many infected persons in both developed and developing countries remain undiagnosed. To reduce the number of undiagnosed infections, a variety of expanded testing policies have been recommended, including opt-out testing. This testing model assumes that in populations of increased HIV prevalence, voluntary testing should be offered to all patients seen in healthcare settings and performed unless patients specifically decline. While this approach raises ethical issues concerning “voluntariness”, access to care, and stigma, the potential benefits of opt-out testing far outweigh its potential adverse effects.

Burkitt lymphoma a childhood tumor common in parts of sub-Saharan Africa has been directly associated with Epstein-Barr virus (EBV) and indirectly with prevalence of malaria. We studied antibodies to both EBV and malaria in children diagnosed with this cancer in Uganda. We performed a case-control study of HIV-seronegative children (less than or equal to 15 years) admitted to hospital. Cases were diagnosed with Burkitt lymphoma and controls with nonmalignant conditions or non-lymphatic cancers. Interviews were conducted and serological samples collected and when possible tested for both EBV and malaria. Adjusted odds ratios (ORs) for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex age residential district household income and tribe. The mean age of cases was 7 years and 61% were male. Compared to controls cases were more likely to be reported having received more frequent treatment for malaria in the past year (OR = 2.0; p = 0.001) and less likely to be living in a home where insecticides were used (OR = 0.2; p less than 0.0001). Odds ratios for Burkitt lymphoma in children increased with increasing antibody levels against EBV (p less than 0.0001) and malaria (p 5 0.05). Findings were similar for children residing in districts close to the capital city and in remote areas. Cases were 5 times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 5.0; p = 0.003). Our findings suggest that EBV and malaria may act synergistically in the pathogenesis of childhood Burkitt lymphoma. Malaria prevention measures may also prevent this childhood cancer. (authors)

OBJECTIVE We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8). METHODS Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies. RESULTS The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid. CONCLUSIONS We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.

In a case-control study in Uganda, we examined associations between different cancer sites or types in relation to antibodies against human papillomaviruses (HPV)-16, -18 and -45. For each cancer site or type, the controlgroup comprised all other cancers excluding those known, or thought to be associated with HPV infection (cancers of the uterine cervix, penis and eye). Among controls the seroprevalence of antibodies was 11% (68/616) against H PV-16, 5% (29/605) against HPV-18 and 6% (35/605) against HPV-45. Antibodies against HPV-16 were significantly associated with only two cancers: uterine cervix [prevalence of antibodies 27% (51/191); odds ratio (OR) 2.0, 95% confidence interval (Cl) 1.2-3.1, P=0.011 and penis [prevalence of antibodies 27% (4/15); OR 6.4, 95% Cl 1.7-24.3, P=0.01]. For both cancers, the risk Increased with increasing anti-HPV-16 antibody titre (P t r e n d =0.01 for each). No cancer site or type was significantly associated with antibodies against HPV-18 and -45.

Human immunodeficiency virus (HIV) type 1 subtype B sequences (whole envelope and the p17 region of gag ) were obtained from peripheral blood mononuclear cell samples collected in 1981 from seven HIV-infected U.S. individuals and in 1982 from one infected Canadian resident. Phylogenetic and nucleotide distance analyses were performed by using database sequences representing North American strains collected from 1978 to 1995. The estimated phylogeny was starlike, with early strains represented on different lineages. When sequences were grouped by years of collection, nucleotide distance comparisons demonstrated an increase in diversity over time and indicated that contemporary strains are more closely related to early epidemic strains than to each other. Using a recently developed likelihood ratio reduction procedure, the date of origin of the U.S. epidemic was estimated to be 1968 ± 1.4 years. A coalescent approach was also used to estimate the population history of the U.S. subtype B epidemic. Our analyses provide new information that implies an exponential growth rate from the beginning of the U.S. HIV epidemic. The dating results suggest a U.S. introduction date (or date of divergence from the most recent common ancestor) that precedes the date of the earliest known AIDS cases in the late 1970s. Furthermore, the estimated epidemic growth curve shows a period of exponential growth that preceded most of the early documented cases and also indicates a leveling of prevalence rates in the recent past.

Objective: To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV. Design: Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have sex with men (57 with KS), and 70 controls at lower risk for KS. Methods: Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed. Results: Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS [35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9–39.9]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5–3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4–14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0–10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2–78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0–1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0–1.6) or oral fluids (OR, undefined; P = 0.001). Conclusions: In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.

The association between the prevalence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) and sociodemographic, sexual, reproductive and lifestyle factors was investigated in a study of adults presenting with cancer at hospitals in Kampala, Uganda. Patients were interviewed and tested for antibodies against KSHV (using an indirect immunofluorescent assay). Data are presented for 607 patients who were not infected with the human immunodeficiency virus-1 (HIV) and who did not have Kaposi's sarcoma (these included people with cancers of the uterine cervix [140], breast [58], liver [41], oesophagus [36], lymphoma [47], other cancers [285] and benign tumours [63]). The prevalence of anti-KSHV antibodies was 50% overall (302/607) and did not differ significantly by cancer site (p = 0.4) or sex (p = 0.2), but increased linearly with age from 35% in those under 25 years to 55% in those 45 years and over (chi(2) trend [1 df] = 9.1; p < 0.001). After adjusting for age and sex, anti-KSHV antibodies were more common in tribal groups other than the Baganda tribe (54% vs. 45% among Baganda; p = 0.02), but there was no significant (p > 0.05) variation in seroprevalence by district of birth, region of residence prior to becoming ill or various measures of wealth. The prevalence of anti-KSHV antibodies decreased with increasing number of older siblings, although this may be due to chance (p = 0.05) and was higher among people who had ever been married (p = 0.03). There was no significant association (p > 0.05) between the presence of antibodies against KSHV and other sexual and reproductive factors. Among the 302 patients with anti-KSHV antibodies, the proportion with high titres increased linearly with increasing age (p = 0.03) and was higher among those reporting having had a blood transfusion (p = 0.03). In conclusion, in this population in Uganda, where KSHV is relatively common, the prevalence of anti-KSHV antibodies increased with age but showed little association with nearly 50 other factors studied.

As part of a larger investigation of cancer in Uganda, we conducted a case-control study of Kaposi's sarcoma in human immunodeficiency virus-1 (HIV)-seronegative adults presenting at hospitals in Kampala. Cases comprised 117 HIV-seronegative patients with Kaposi's sarcoma and controls comprised 1,282 HIV-seronegative patients with a provisional diagnosis of cancer other than Kaposi's sarcoma. Study participants were interviewed about social and lifestyle factors, tested for HIV and, if there was sufficient sera, for antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 [HHV8]), using an immunofluorescent assay. Independent effects of these factors were identified using unconditional logistic regression, after adjusting for age group (

As part of a larger investigation of cancer in Uganda, we conducted a case–control study of conjunctival squamous cell carcinoma in adults presenting at hospitals in Kampala. Participants were interviewed about social and lifestyle factors and had blood tested for antibodies to HIV, KSHV and HPV-16, -18 and -45. The odds of each factor among 60 people with conjunctival cancer was compared to that among 1214 controls with other cancer sites or types, using odds ratios, estimated with unconditional logistic regression. Conjunctival cancer was associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2–19.4; P

In 2010, the top five causes of death in the United States were 1) diseases of the heart, 2) cancer, 3) chronic lower respiratory diseases, 4) cerebrovascular diseases (stroke), and 5) unintentional injuries. The rates of death from each cause vary greatly across the 50 states and the District of Columbia (2). An understanding of state differences in death rates for the leading causes might help state health officials establish disease prevention goals, priorities, and strategies. States with lower death rates can be used as benchmarks for setting achievable goals and calculating the number of deaths that might be prevented in states with higher rates. To determine the number of premature annual deaths for the five leading causes of death that potentially could be prevented ("potentially preventable deaths"), CDC analyzed National Vital Statistics System mortality data from 2008-2010. The number of annual potentially preventable deaths per state before age 80 years was determined by comparing the number of expected deaths (based on average death rates for the three states with the lowest rates for each cause) with the number of observed deaths. The results of this analysis indicate that, when considered separately, 91,757 deaths from diseases of the heart, 84,443 from cancer, 28,831 from chronic lower respiratory diseases, 16,973 from cerebrovascular diseases (stroke), and 36,836 from unintentional injuries potentially could be prevented each year. In addition, states in the Southeast had the highest number of potentially preventable deaths for each of the five leading causes. The findings provide disease-specific targets that states can use to measure their progress in preventing the leading causes of deaths in their populations.

This chapter reviews the association between the recently recognized virus human herpesvirus 8 (HHV-8) and Kaposi's sarcoma (KS), the most common malignancy seen in persons with AIDS. Other malignancies associated with HHV- 8 are also reviewed. The chapter illustrates the use of epidemiologic methods to indicate an infectious agent as the cause of a disease of unknown etiology and the use of molecular biologic methods to identify infectious agents that may have remained undetectable by more conventional approaches. KS is by far the most common malignancy found in human immunodeficiency virus (HIV)-infected persons. Paucity of KS cases among HIV-infected transfusion recipients, hemophiliacs, and injection drug users argues against KS agent's being a blood-borne pathogen. Even before the increased incidence of KS associated with HIV infection, researchers had been looking for a possible infectious agent as a cause of KS. Use of the polymerase chain reaction (PCR) to detect HHV-8 DNA is one of the primary methods of determining HHV-8 infection. PCR-based studies have also examined the rate of positivity of KS biopsies based on the stage of the lesion. If HHV-8, like many other human herpesviruses, were ubiquitous among American and European adults, questions would remain regarding the connection between HHV-8 and KS. Several epidemiologic studies have examined the effect of antivirals active against herpesviruses on the development of KS. Knowledge about HHV-8 also may provide insights which may be useful to treat existing disease.

Objective: To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998. Methods: Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4 + cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated. Results: There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p = .05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4.1 per 100 py in 1990 to 0.7 per 100 py in 1998; p

Summary Background We used data from Europe, North America, and Australia to assess the effect of exposure category on the AIDS incubation period and HIV-1 survival and whether the effect of age at seroconversion varies with exposure category and with time since seroconversion. Methods 38 studies of HIV-1-infected individuals whose dates of seroconversion could be reliably estimated were included in the analysis. Individual data on 13 030 HIV-1-infected individuals from 15 countries were collated, checked, and analysed centrally. We calculated estimates of mortality and AIDS incidence rates and estimated the proportions of individuals surviving and developing AIDS at each year after seroconversion from the numbers of observed deaths or cases of AIDS and the corresponding person-years at risk. Analyses were adjusted for age at seroconversion, time since seroconversion, and other factors as appropriate. Findings Mortality and AIDS incidence increased strongly with time since seroconversion and age at seroconversion. Median survival varied from 12·5 years (95% Cl 12·1–12·9) for those aged 15–24 years at seroconversion to 7·9 years (7·4–8·5) for those aged 45–54 years at seroconversion, whereas for development of AIDS the corresponding values were 11·0 years (10·7–11·7) and 7·7 years (7·1–8·6). There was no appreciable effect of exposure category on survival. For AIDS incidence, the exposure category effect that we noted was explained by the high incidence of Kaposi's sarcoma in those infected through sex between men. We estimated that among people aged 25–29 years at seroconversion 90% (89–91) and 60% (57–62) survived to 5 years and 10 years, respectively, after seroconversion, whereas 13% (12–15) and 46% (44–49), respectively, developed AIDS (excluding Kaposi's sarcoma). Interpretation Before widespread use of highly-active antiretroviral therapy (before 1996), time since seroconversion and age at seroconversion were the major determinants of survival and development of AIDS in Europe, North America, and Australia.

These two scenarios raise the question of whether male circumcision should be used in the UK as a means to decrease HIV transmission. Lack of circumcision has long been recognised as a risk factor for HIV acquisition in heterosexual men.1 This makes biological sense because superficial Langerhans cells, which express HIV-1 receptors, are more prevalent in the male foreskin than in the remainder of the penis.2 In addition, decreased keratinisation of the foreskin increases susceptibility to minor trauma during intercourse, potentially aiding the passage of HIV.3 Finally, ulcerative sexually transmitted infections, found more commonly in uncircumcised men, are associated with increased rates of HIV transmission.4 The biological plausibility of adult male circumcision to reduce HIV transmission has now been shown to have clinical relevance in three recent large randomised controlled trials conducted in sub-Saharan Africa, in which male circumcision reduced the rate of female-to-male HIV transmission by at least 50%.5–7 Overall, there was little evidence of increased risk-taking behaviour in circumcised men. Here we examine whether the results of the African trials are relevant in the UK. The yearly number of new HIV diagnoses in the UK has increased by 157% since 1997.8 Of the new diagnoses reported in 2006, 12% were in black African men, most of whom were thought to have been infected heterosexually in Africa, whereas 36% were in men who have sex with men (MSM). Indeed, 2006 saw the greatest yearly number of newly diagnosed HIV infections in MSM since the start of the epidemic. New prevention strategies for these groups are urgently needed. Based on …