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Emerging Sexually Transmitted Diseases (STDs)

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INDEX

Overview of Sexually Transmitted Diseases
Magnitude of the Problem
Incidence of Curable STD in the World
Top 10 Reportable Infectious Diseases in the U.S.
STD - Direct and Indirect Costs
The Impact of STD on Sexual Transmission of HIV
The Emerging STD's

  • Human papilloma virus (HPV)
  • Human T-cell lymphotrophic virus (HTLV)
  • Micoplasma genitalium
  • Mobilluncus
  • Helicobacter
  • HIV 1 and HIV 2
  • Human herpes virus type 8
    The Good News: Declining Rates of the Curable STD in Industrialized Countries
  • Syphilis
  • Gonorrhea
  • Chlamydia
    The Bad News
  • Continuing Hyperendemic Spread of Viral STD in the U.S.
  • Genital HPV
  • Genital Herpes
  • Hepatitis B
  • Concentration of Endemic STD and HIV Transmission in the Southeastern US
  • Western U.S. Outbreak of Gonorrhea among MSM
  • International Comparisons: US has Highest Industrialized Country Rates of Curable STD
  • Emerging Antimicrobial Resistance
  • N. Gonorrhoeae - Study in the Philippines
  • TetM in Genital Pathogens
  • AIDS Incidence in the United States and Worldwide
    Global Perspectives
  • HIV/AIDS
  • South Africa: Epidemic Spread of HIV and Other STD
  • Former Soviet Union
  • Epidemic STD in China
  • Short Summary
  • Examples of Underlying Factors for these Phenomena
  • The "Tipping Point": A Social Science Perspective
  • Crack Cocaine Epidemic
  • Persisting High Fertility and Urbanization in developing Countries
  • Cultural Differences in Male Circumcision
    Prevention and Control Strategies
  • The STD/HIV Transmission Cycle
  • Piot's Pyramid: A Comprehensive Approach

    Readings


    index


    Overview of Sexually Transmitted Diseases

    The impact of STD can be assessed in terms of the incidence and prevalence of over 30 specific STDs and their early complications and late sequelae at global, regional, national, and local levels; the direct and indirect costs of these diseases and their major complications and sequelae (infertility in women; complications during pregnancy and in the newborn; several types of common cancers, including those involving the cervix, vagina, vulva, penis, anus, and liver; and cancers related to retroviral infections, including T-cell leukemia, Kaposi's sarcoma, and body cavity lymphomas. Further, several STDs appear to increase transmission of HIV infection, and help account for epidemic spread of HIV infection in many parts of the world. The eight major sexually transmitted pathogens (including four bacterial and four viral pathogens), the usual diseases they cause, and their major complications, are summarized here.

    Eight Major Sexually Transmitted Infections

      Usual Disease Main Complications
    Bacteria
    - Gonorrhea
    - Chlamydia
    - Chancroid
    - Syphilis


    Urethritis and cervicitis

    Genital ulcer


    Salpingitis, infertility, and prematurity
    HIV transmission Congenital syphillis, fetal death

    Virus
    - HIV
    - Hepatitis B
    - Herpes Simplex
    - Human Papilloma


    Class I, II, III, IV HIV
    Hepatitis
    Genital herpes
    Genital warts, dysplasia


    AIDS
    Liver cancer, cirrhosis
    Perinatal herpes
    Cervical cancer




    Magnitude of the Problem

    Incidence of Curable STD in the World (Millions)
    The World Health Organization ranks these four bacterial STDs, together with trichomoniasis among the most common curable infections in the world.

    Disease New Cases/Year
    Gonorrhoea 52-122
    Chlamydia 29-72
    Syphilis 10-24
    Chancroid 5-7
    Trichomoniasis 57-102



    index


    Top 10 Reportable Infectious Diseases in the U.S.
    When data were last published by the CDC in 1995, five of the top ten reportable infectious disease were STD: chlamydial infection, gonorrhea, AIDS, primary and secondary syphilis, and hepatitis B. Of the other five, three can be transmitted sexually among men who have sex with other men (MSM): shigella, salmonella, and hepatitis A; and a fourth, tuberculosis, is increasing in incidence in the US, in part because of AIDS.

    Top 10 Reportable Infectious Diseases - 1995
    1. Chlamydia
    2. Gonorrhea
    3. AIDS
    4. Salmonellosis
    5. Shigellosis
    6. Hepatitis A
    7. Tuberculosis
    8. P & S Syphilis
    9. Lyme disease
    10. Hepatitis B
    477,638
    392,848
    71,547
    45,970
    32,080
    31,582
    22,860
    16,500
    11,700
    10,805




    STD - Direct and Indirect Costs
    The Institute of Medicine estimated the direct medical costs and the indirect costs of STDs and AIDS in the US. For STDs excluding AIDS, the costs were about $10 billion per year in 1994.

    STD Direct and Indirect
    Costs in 1994

    • STDs other than AIDS
    $ 10 billion
    • Sexually transmitted HIV
    $ 7 billion
    • Total
    $ 17 billion



    For the sexually transmitted component of HIV, the direct and indirect costs were about $7 billion. To further classify the breakdown of the costs for STDs excluding HIV/AIDS, about half is for diagnosis and treatment of gonorrhea, chlamydia and pelvic inflammatory disease; one-third is for diagnosis and treatment of human papilloma virus (HPV) infection and related cervical dysplasia and cervical cancer; and the remainder is for all the other STD's.

    Estimated Costs of Selected STDs and
    Associated Sequelae in U.S. in 1994
    STD Direct Cost
    (1994 $ millions)
    Bacterial Chlamydia
    Gonorrhea
    PID
    Syphilis
    Chancroid

    1,514
    791
    3,119
    79.4
    0.66
    Viral
    HSV
    HPV
    Hepatitis B
    Cervical cancer

    178.3
    2,878
    117
    554

    Subtotal STDs (excluding HIV/AIDS)
    7,484.44
    Sexually transmitted HIV/AIDS
    5,025
    Total (including HIV/AIDS)
    12, 509.44



    index


    The impact of STD on Sexual Transmission of HIV
    Several cohort studies have documented an increased rate of acquisition of HIV infection among individuals following acquisition of another STD, such as genital ulcer disease, cervical infection with gonorrhea or chlamydia, or vaginal infection (trichomoniasis or bacterial vaginosis).

    Results of Major Epidemiological Studies Regarding the Risk of
    Subsequent HIV Infection Among Persons with Existing STDs
    Reference (Study Site: Population) STD: RR or OR (95% CI)
    1. Cameron et al., 1989
        (Nairobi:  Male STD patients)
    2.  Plummer et al., 1991
        (Nairobi:  Female sex workers
    3. Laga et al., 1993
        (Kinshasa:  Female sex workers)
    4. Telzal et al., 1993
        (New York:  Male STD patients)
    5. Kingsley et al., 1990
        (U.S.:  Men who have sex with men)
    6. Nyange et al., 1994
        (Mombasa:  Female sex workers)
    GUD:  4.7 (1.3, 17)

    GUD:  3.3 (1.2, 10.1), Ct:  2.7 (0.9, 7.8)

    Gc:  4.8 (2.4, 9.8), Ct:  3.6 (1.3, 11.0),
    Tr:  1.9 (0.9, 4.1)
    GUD:  3.3 (1.1, 10.1)

    Hs:  1.0 (0.3, 2.9)

    GUD:  4.0 (1.6, 9.9), Sy:  6.5 (1.5, 27.9),
    Gc:  1.8 (1.0, 9.9)

    Ct = chlamydial infection; GUD = genital ulcerative disease; Gc = gonorrhea; 
    Hs = herpes simplex virus type 2 infection; Sy = syphilis; Tr = trichomoniasis
     

    In addition, urethral or cervical infection or genital ulcers increase genital shedding of HIV DNA and/or RNA [Slide 6], probably making the HIV-infected person more likely to transmit HIV sexually.



    The Emerging STD's
    This summarizes the STD pathogens that have been newly discovered or have actually emerged to cause new diseases over the past 20-25 years.

    Newly Recognized and Newly Emergent
    Sexually Transmitted Pathogens, 1976-1998
    STD Pathogens Associated Syndromes
    HPVs (1976 - present)

    HTLV-I (1980)

    HTLV-II (1982)

    Mycoplasma genitalium (1981)

    Mobiluncus sp. (1980, 1983)

    Helicobacter cinaedi and 
     H. fennelliae (1983)

    HIV-1 (1983)

    HIV-2 (1986)

    HHV type 8 (1995)

    Genital & anal warts, dysplasias, and cancers

    T-Cell leukemia/lymphoma;
        tropical spastic paraparesis
    ?

    Nongonococcal urethritis

    BV-associated 

    Proctocolitis
    Cellulitis, fever, bacteremia
        in the immunosuppressed
    AIDS

    AIDS

    Kaposi's Sarcoma, body cavity lymphoma



    index


    - Human papilloma virus (HPV)
    Human papilloma virus (HPV), the most common sexually transmitted pathogen, is shown here in an electron microscopic photo [Slide 7]. The first human papilloma virus was identified by molecular cloning in 1976; over 80 human papilloma virus types have now been cloned and differentiated from each other by their DNA homologies [Slide 8]. Over 20 of them infect the genital tract. Two of them, type 6 and 11, cause most genital warts [Slide 9], while the others tend to cause lesions not visible to the unaided eye. Several HPV types (e.g., types 16,18,45, 56) are strongly linked to the development of cervical cancer. Data from studies led by Dr. Laura Koutsky at University of Washington showed that among female university students, cervical vaginal HPV infection was 8 times as common as all other STD combined.

    The clinical course of female STD clinic patients who have acquired the types of HPV most closely linked to cervical cancer is shown in this slide [Slide 10]. For those who acquired HPV 16 or 18 (shown in yellow and green), 38-48% had developed moderate or severe dysplasia within 1-2 years. Not all type 16 HPV are equally likely to be associated with moderate to severe dysplasia (known as cervical intraepithelial neoplasia grade 2 or 3, or CIN 2-3). Variant (non-prototype-like, or NPL) HPV16 has been over 6 times more likely than the common prototype strains to be associated with CIN 2-3.

    Risk for Biopsy-Confirmed CIN 2-3 
    Associated with HPV16 Variants
    Variant No. of CIN 2-3/
    No. of Subjects (%)
    RR* 95% CI
    HPV16 PL 4/45 (8.9%) 1.0
    HPV16 NPL 5/12 (41.7%) 6.5 1.6-27.2
    * Adjusted for lifetime number of sexual partners, HPV16 status at entry, ethnic group, and number of visits positive for HPV16

    index


     

    Ninety percent or more of invasive cervical cancers are also associated with cervical HPV, especially with types 16, 18, 45, and 56. Cervical cancer has been the most common cause of STD-related death among women through the early 1990s. In the US, the age-specific incidence of genital HPV infection and of cervical carcinoma-in-situ (CIS) peaks in the mid 20s; the incidence of invasive cervical cancer is much lower than that of CIS, and peaked later ages than CIS [Slide 11].

    - Human T-cell lymphotrophic virus (HTLV)
    This virus infects human lymphocytes [Slide 11a], and is related to HIV, but causes different complications. HTLV I causes a type of T-cell leukemia, and also a neurologic syndrome called tropical spastic paraparesis (paralysis). HTLV II is a similar virus, not yet clearly associated with any definite syndrome. HTLV-I is both sexually and perinatally transmitted, while HTLV-II is more common in IV drug users worldwide.



    - Mycoplasma genitalium
    Mycoplasma genitalium a relatively new pathogen, is still in search of a disease.[Slide 11b] However, evidence is growing that this organism causes some cases of non-gonococcal urethritis and perhaps some cases of pelvic inflammatory disease, but it is difficult to culture and has not yet been extensively studied. It has the smallest genome of any free-living bacterium at at 500-600 kilobase pairs compared to 700-800 for Mycoplasma pneumoniae. Because of this it was the first bacterium totally sequenced. It is very difficult to grow.

    Our Seattle isolates fall in two genetic clusters: one related but not identical to the prototypic strain G-37 and another group which differ from G-37 by a 11 or more bases. It is still unknown whether the disease manifestations of this organism are different for the two variants.

    - Mobilluncus
    Two species of this genus were characterized during the 1980s. This anaerobic bacterium is a curved rod (uncus) that swims (mobile), hence the name Mobiluncus. It is associated with bacterial vaginosis, the most common cause of vaginal discharge.


    - Helicobacter
    A recently discovered pathogen - Helicobacter pylori - causes stomach and duodenal ulcers as well as other diseases of the stomach. Although this pathogen is not thought sexually transmitted, other newly discovered bacteria in the Helicobacter genus have been associated with diarrheal diseases in gay men, previously called the "Gay Bowel Syndrome." When the epidemic of intestinal infections in MSM was at its peak in the early 1980ís, two curved gram negative rods were discovered in rectal cultures from 20% of gay men with this syndrome and 10% of gay men who were asymptomatic. It was not seen in heterosexuals. The two species found in gay men were given the names Helicobacter cinaedi and Helicobacter fenelliae.

    H. cinaedi and H. fennelliae
    • Found commonly associated with proctocolitis in MSM in 1980-82, a period when proctocolitis, syphilis, HIV, and other STDs were epidemic problems.
    • With advent of AIDS, and rapid decline in risk taking behaviors, came an abrupt decline in STD, and disappearance of the proctocolitis syndrome among MSM.
    • With increasing AIDS, a new syndrome appeared, predominantly in men with AIDS (22 blood isolates submitted to CDC from 1/82 - 8/90).


    When AIDS and its associated symptoms were recognized among gay men, there was a significant change in sexual behavior. STD cases decreased as did the incidence of intestinal infections in general, and more specifically of Helicobacter-associated diarrhea in gay men. However, as more HIV-infected men became immunosuppressed, Helicobacters reappeared as a cause of bacteremia associated with dermatitis. So Helicobacter has gone through 3 phases: emergence as a cause of diarrhea during a period of epidemic spread of many STDs among MSM during the 1970s; disappearance with reduced risk-taking behavior; and reemergence as a new syndrome in immunosuppressed persons with HIV infection.

    - HIV 1 and HIV 2
    The major new sexually transmitted disease, AIDS, which newly emerged in the 1970s and was newly recognized in the 1980s, will be discussed later in the lecture.


    - Human herpes virus type 8
    Human herpes virus type 8 (HHV8), also called Kaposi's sarcoma-associated virus, is most prevalent in HIV-infected individuals; the mechanism of transmission is still being elucidated, but transmission during sex and/or kissing seems likely. Researchers at Columbia University found the association of HHV-8 with Kaposi sarcoma; the virus has also been associated with a rare neoplasia-body cavity lymphoma, and with a condition called Multicentric Castleman's Disease.


    The Good News: Declining Rates of the Curable STD in Industrialized Countries

  • Syphilis
    Overall the rates of syphilis have been declining steadily in the US since the early 1990ís. [Slide 13] In 1997, 75% of the counties in the United States had no reported primary or secondary syphilis cases. In most other industrialized countries of the West, endemic transmission of syphilis has been eliminated, and the current emphasis is on containment of outbreaks resulting from imported syphilis. For example, in King County, Washington, the annual number of locally-acquired cases of primary and secondary (P&S) syphilis fell to zero in 1996, but this was followed by an outbreak of P&S syphilis among MSM during 1997-98. [Slide 13a)

  • Gonorrhea
    Gonorrhea (GC) rates increased dramatically during and after World War II, due in part to the effects of war per se on patterns of sexual behaviors and sexual mixing. A subsequent major epidemic followed beginning in the 1960s with the sexual revolution and the use of oral contraceptive pills. Rates in the US started declining in the 1970ís due to the introduction of intervention programs, including introduction of cervical culture tests for women, and the routine treatment of sex contacts. [Slide 14] This trend has continued and the GC rates in men, in 1997, were lower than ever before in US history.


  • Chlamydia
    Although reported cases of chlamydial infection increased through the 1990s in the US, this is largely due to increased testing and an increasing number of states reporting cases to the Centers for Disease Control and Prevention [Slide 15]. In fact, there are areas of the country where chlamydia rates are decreasing due to implementation of widespread screening for chlamydia in family planning clinics and later, STD clinics. This [Slide 16] shows declining rates of chlamydia from 9-12% down to 3-4% after the implementation of the screening programs in the Pacific Northwest States. This type of serial prevalence monitoring has become the most effective method for monitoring trends in chlamydia morbidity in women in all regions of the US [Slide 17].


    The Bad News

  • Continuing Hyperendemic Spread of Viral STD in the U.S.
    In addition to the new epidemic of HIV/AIDS, three other viral STDs remain major problems in the US.  

    - Genital HPV infection
    As noted above, genital HPV infection is by far the most common STD in the US, probably in the world. Based upon use of sensitive DNA amplification tests for detecting subclinical HPV infection of the genital tract, and of newly developed serologic tests for antibody to genital types of HPV, Koutsky et al have estimated the cumulative prevalence of genital HPV infection in the US probably approximates 75%
    [Slide 18].

     - Genital herpes
    The age-specific prevalence of serum antibodies to herpes simplex virus type 2 - the usual cause of genital herpes - has risen in prevalence over the past decade despite widespread AIDS-prevention health education efforts. Data from a 1991 National Health and Nutrition Examination Survey reveals that 20% of persons over the age of 12 in the United States, have antibody to herpes simplex virus type 2, with higher rates among blacks than among whites. [Slide 19] A very surprising finding is that data from two NHANES surveys (midpoints 1978 and 1991) showed a 27% increase in prevalence in men and a 32% increase in women - an increase that occurred during the AIDS era, when safer sex practices were widely promoted [Slide 20].

      - Hepatitis B Sexual transmission of hepatitis B virus has decreased during the past decade, both in terms of absolute members and in terms of the relative proportion of cases attributable to sexual transmission; transmission among MSM has declined in particular. Although sexual transmission of hepatitis C virus does not seem to be a efficient as for hepatitis B virus, the role of sexual transmission requires more study.


  • Concentration of Endemic STD and HIV Transmission in the Southeastern US
    Rates of gonorrhea and syphilis (and other curable STD) are highest in the southeastern US [Slide 21]. This slide shows the correlation geographically between counties that have the highest incidence rates of syphilis and gonorrhea, and those that have had the highest prevalence of HIV in pregnant women. To the extent that STDís facilitate transmission of HIV, then this area of the US has rates of gonorrhea and syphilis as high as many sites in Africa and Asia, and should more urgently address control of curable STD, if only to slow sexual transmission of HIV.

  • Western U.S. Outbreak of gonorrhea among men having sex with men (MSM)
    There is a resurgence of STDís in gay men. This [Slide 22] shows the percentage of urethral gonococcal isolates from men that are from MSM in STD clinics in the western US, who participate in the Gonococcal Isolates Surveillance Project (GISP). Over the past three years, in the STD clinic in Seattle, about half of the gonorrhea cases in men have occurred in gay men. This increase coincides with a 1997-98 outbreak of primary and secondary syphilis in MSM - a return to pre-AIDS syphilis epidemiology [Slide 23]. More alarming is a recent study from San Francisco, which found that 26% of those at risk for HIV said that they no longer felt the need to be careful to prevent HIV because of the availability of highly effective antiretroviral therapy.

  • International Comparisons: US has Highest Industrialized Country Rates of Curable STD
    The US rates of the curable STDís like gonorrhea and syphilis are still much higher than in other industrialized countries. For example, in Sweden, Denmark, England, Wales, Canada and Germany, the rates of gonorrhea and syphilis are at least 10 times lower than the rates in the United States.
    [Slide 24]  [Slide 25]


  • Emerging Antimicrobial Resistance
    Another troubling phenomenon is the development of antimicrobial resistance in several STD pathogens, especially including N. gonorrhoeae, Haemophilus ducreyi (the cause of chancroid),and HIV. During the antimicrobial era, each new antimicrobial introduced for treatment of gonorrhea led to increasing gonococcal resistance to that antimicrobial: Sulfonamides, penicillins, streptomycin, and tetracyclines all became less effective or ineffective because of gonococcal chromosomal mutations, or acquisitions of plasmids that mediated resistance. In 1994, we were invited to the Philippines to study gonococcal resistance to ciprofloxacin, the most widely available and affordable oral antibiotic that is effective for gonorrhea in developing countries. We evaluated 100 consecutive gonococcal isolates from female sex workers in Manila and Cebu City. We found intermediate and high or level resistance to ciprofloxacin in some of these isolates. We therefore returned 18 months later to reexamine resistance to ciprofloxacin. We found a dramatic increase in high level resistance to ciprofloxacin. [Slide 26], due to rapid accumulation of multiple mutations in the topoisomerase genes of the organism.

    Historically, the last big event in gonococcal antibiotic resistance had been the development of a plasmid that encoded resistance to penicillin through production of beta lactamase, an enzyme which destroys penicillin. This plasmid was also first discovered in the gonococcus in the Philippines. Why has the Republic of the Philippines had a higher incidence of these resistant strains than elsewhere? Several factors may play a role:

      1. The commercial sex industry plays a prominent part of the patterns of sexual mixing in the Philippines.

    2. The church has opposed the use of condoms for preventing STD/HIV.

    3. Antibiotics for the prevention and treatment of STD are readily available over-the-counter without prescription. In fact, we implicated prophylactic self-use of antimicrobials by sex workers without prescription as a major risk factor for having infection with a ciprofloxacin-resistant gonococcus. [Slide 27]

    These fluoroquinolone-resistant strains are also being isolated in other countries in Asia and the Western Pacific now - a potential disaster in efforts to control gonorrhea and prevent HIV infection - and it seems inevitable that we may see these increase in other parts of the world which commonly use fluoroquinolones in the United States as well.

    - TetM in Genital Pathogens
    An interesting example of how extensively an antibiotic resistance gene can spread in pathogenic microorganism is provided by the emergence of tetracycline resistance in sexually transmissible urogenital pathogens. We first discovered in 1983 that Mycoplasma hominis, a cause of pelvic inflammatory disease and postpartum infection, was tetracycline resistant, and showed an increase in the prevalence of resistance from the early 70s to the early 80s.

    Tetracycline Resistance in M. hominis from Female STD Clinic Patients, Seattle 1972-1982
    1972 - 73 2/17 (12%)
    1980 - 82 21/59 )36%)
    Koutsky et al. Sex Trans Dis, 1983

    This resistance was found to be due to a gene called TetM. We next found the TetM gene occurring in ureaplasma, a cause of non-gonococcal urethritis and a common organism in the genital tract. Then it was found on a mobilizable plasmid in N. gonorrhoeae and H. ducreyi, and also was found in Gardnerella vaginalis, a bacterium associated with bacterial vaginosis. This gene also is found in Streptococcus group B, a sexually transmissible bacteria that can cause perinatal infection and pelvic inflammatory disease. Fortunately, the TetM gene has not yet been encountered in C. trachomatis; tetracycline is the major drug used for chlamydial infection in most developing countries.

    Tetracycline Resistance and tetM in Pathogenic 
    Urogenital Bacteria
        TcR (MIC > 16)/
    Total (%)
    Tet M/
    TcR (%)
    Ureaplasma urealyticum
    Mycoplasma hominis
    Neisseria gonorrhoeae
    Haemophilus ducreyi
    Streptococcus agalactia
    Gardnerella vaginalis
    ('70-'84)
    ('66-'84)
    ('85 on)
    ('85 on)
    ('84)
    - ('78)
    - ('84)
    14/72 (19.4)
    49/85 (57.6)
    Increasing percentage
    Increasing percentage
    50/50 (100)
    20/39 (25.6)
    21/27 (77.7)
    14/14 (100)
    49/49 (100)
     

    17/50 (34)
    20/20 (100)
    21/21 (100)

    Roberts MC, Kenny GE. AAC, 1986; Roberts MC et al. AAC, 1985;
    Morse SA et al. AAC, 1986; Roberts MC et al. AAC, 1986.


    AIDS Incidence in the United States and Worldwide
    The story of the emergence of human immunodefiency virus (HIV), the virus which causes AIDS, is an emerging story in itself, but a few comments here are possible. It now appears likely from molecular epidemiologic studies that HIV-1 is closely related to, and may have arisen from a simian immunodeficiency virus found in chimpanzees of Central and West Africa. Occasional transmission to humans could have resulted from various exposures related to trauma bites, or eating the meat of chimps as food. HIV-1 has been detected in a human in Zaire as early as the 1950s, but began to spread in Subsaharan only with population growth, urbanization, changing patterns of sexual behavior, and emergence of other STD to facilitate sexual transmission of HIV. When HIV-1 reached industrialized countries, it spread most efficiently and fastest in MSM and IDU. With the advent of highly effective antiretroviral therapy, many HIV-infected persons no longer progress to AIDS. HIV infection is not yet reported in many states in the US. Therefore, the best way to look at the HIV incidence today in the US is to study HIV infections or AIDS in adolescents and very young adults, whose infections tend to reflect recently acquired HIV. The tables below show reported AIDS cases in young adults and adolescents between 1990 and 1995. Among gay men and intravenous drug users reported AIDS declined. However, among AIDS cases attributed to heterosexual contact, there was a 137% increase. The second point is that the incidence in females rose 73%, whereas the number of cases in men was unchanged. The third trend showed an overall decrease among Caucasians but an increase in cases among Mexican Americans and African Americans. So, in the United States, the adolescents and young adults with still rising incidences of AIDS are females, heterosexuals, and African American.

    U. S. Trends in AIDS Incidence in Adolescents and Young Adults
    (Ages 13 - 25 Years)
    No. Reported AIDS Cases
    1990 1995 % Change
    • Males
    • Females

    1800
    550

    1800
    950

    No Change
    + 73%

    Paul Denning, Patricia Fleming. Abstract 375
    4th Conf Retroviruses and OI

    index


    U. S. Trends in AIDS Incidence in Adolescents and Young Adults
    (Ages 13 - 25 Years)
    No. Reported AIDS Cases
    1990 1995 % Change
    • MSM
    • IDU
    • Heterosexual contact

    1400
    600
    380

    1300
    550
    900

    - 7%
    - 8%
    + 73%

    Paul Denning, Patricia Fleming. Abstract 375
    4th Conf Retroviruses and OI

    U. S. Trends in AIDS Incidence in Adolescents and Young Adults
    (Ages 13 - 25 Years)
    No. Reported AIDS Cases
    1990 1995 % Change
    • White
    • Hispanic
    • Black

    950
    500
    850

    800
    600
    1400

    - 16%
    + 20%
    + 150%

    Paul Denning, Patricia Fleming. Abstract 375
    4th Conf Retroviruses and OI



    Global Perspectives

    - HIV/AIDS

    This shows a 1997 UNAIDS estimate of HIV and AIDS worldwide. There are now over 6 million new cases of HIV annually. The largest epidemic is still in Africa, but numbers in Asia are rapidly increasing.

    A New, Grimmer Portrait of AIDS
    Previous (1996) Revised (1997)
    People with HIV or AIDS 22,600,000 30,600,000
    •  Sub-Saharan Africa
    •  S. and SE Asia
    •  Latin America
    •  North America
    •  Western Europe
    •  E. Asia and Pacific
    •  Caribbean
    •  N. Africa, Middle East
    •  E. Europe, Central Asia
    •  Australia, New Zealand
    20,800,000
      6,000,000
      1,300,000
         860,000
         530,000
         440,000
         310,000
         210,000
         150,000
           12,000
    New Infections per Year
    • Total
    3,000,000 5,800,000
    • Children
    350,000 580,000
    Source: United Nations



    South Africa: Epidemic Spread of HIV and Other STD
    The African epidemic is still increasing as well, in Southern Africa especially. One study done in Botswana showed that in 1990 there were no cases of HIV infection among pregnant women. However, within only 4 years the HIV incidence increased to 44% of pregnant women. The incidence of HIV infection is now increasing rapidly in South Africa, an area originally relatively isolated from other areas of Africa, that had remained relatively free of HIV; as the borders opened and immigration proceeded from areas with higher HIV incidence, the rates increased. Massive migration within the country of the male labor force working in mines also has contributed to rapid spread, once HIV was introduced. Urban migration from villages following the lifting of apartheid represents a new phenomenon. Many feel that the very high rates of other STDís in this region when HIV was introduced further facilitated the rapid sexual transmission of the virus. Others have speculated that the HIV subtype most common in this area (subtype C) may be better adapted to heterosexual transmission than subtype B which predominates in the industrialized countries and in Latin America.

    Since the beginning of the HIV epidemic in humans, the virus has been undergoing continuous genetic diversivation, at the rate of nearly 1% of the viral genome per year. There are by now two major types of HIV (HIV 1 and 2); three major subgroups of HIV 1 (m, n, o); and multiple subtypes of the major subgroup m (including subtypes B and C, for example). The behavior of the pathogen, its virulence and infectivity still remain an issue. Despite the very high incidence of HIV infection in Subsaharan Africa and parts of Asia, a recent World Bank Study emphasizes that only 5% of the population of the world lives in areas where the HIV epidemic is in the generalized stage (25% of the general population); the remaining population can mostly be considered to be in very early stages of the epidemic, where interventions can still have the greatest impact.

    Distribution of Developing Country 
    Population by Stage of Epidemic
    Stage of Epidemic Total Population Percent
    • Nascent
    • Concentrated
    • Generalized
    • Unknown
    2,422
    1,624
      220
      467
       51%
       34%
         5%
       10%
     
    Total  4,733 100%
    Number of countries 135 VanVliet et al. 1997

     


    Former Soviet Union
    An epidemic of STDís and HIV in the former Soviet Union soon followed the fall of the Iron Curtain in 1990. This slide shows annual numbers of syphilis cases in the Russian Federation from 1990-1997. [Slide 35] Although these changes could theoretically reflect improved reporting, additional data are available from annual routine surveillance for syphilis seropositivity in seven occupational groups in Moscow. [Slide 36] This clearly illustrates that the increasing rates of reported syphilis reflect a true epidemic, not simply reporting bias. During the time period evaluated there was a 100-fold increase in prevalence of syphilis antibody in these. Many factors are thought to play a role in this epidemic including 1) the decline of the public health infrastructure, 2) deterioration of the economy, with an increase in prostitution, and 3) increase in movement across borders. Anecdotal reports show a large increase in HIV rates where syphilis rates have been high; and increases in gonorrhea, chlamydial infection and pelvic inflammatory disease, as well.
    China
    In China, rates of reported STD (thought to mostly represent urethritis in men) have doubled annually since the late 70s. The increased rates have been attributed by the Ministry of Health to several factors, including: 1) Opening of borders to the outside; 2) reintroduction of "western bourgeois values"; 3) increased travel within the country from rural to urban areas, especially for the male labor force; 4) the reemergence of prostitution - partly in response to this work-related migration; and 5) the failure to train clinicians in STD management during the period from the mid 50s to the late 70s - a period when STD were said to have been eliminated in China.

    Summary
    Global HIV rates are increasing, and there is HIV subtype diversification. In most of the industrialized countries, especially in Western Europe, HIV incidence and bacterial STD incidence are decreasing. In North America, the incidences of bacterial STDís are declining, but the US still has 10 times the rates of western Europe. In eastern Europe, STD and HIV incidences are increasing. Overall, HIV/AIDS incidence is decreasing among MSM but is still increasing among adolescents, heterosexuals, women, and African Americans.

    The Situation - Summary
    • Global HIV rates increasing, subtype diversification
    • Industrialized countries
      • Western Europe - HIVê , Bacterial STDê , Viral STD?
      • Eastern Europe - STD, HIVé
      • North America
        • Bacterial STDê (but US > 10x W. Europe)
        • Viral STD - ? leveling off
        • HIV/AIDS   ê MSM (but relapsing risk behaviors)
            • é Heterosexual, adolescents, women, Blacks, and Hispanics
      • Vancouver BC - IVDU epidemic



    Examples of Underlying Factors for these Phenomena
    Many socioeconomic factors are responsible for patterns of sexual behavior that directly drive the transmission of STD. These include poverty, the status of women, patterns of migration, wars, the absolute and relative size of the adolescent and young adult population, and many other sociocultural factors. A few of these that are of special interest in the US or in developing countries, and that illustrate the variety of factors that indirectly influence STD rates, are discussed below.

  • The "Tipping Point:" A Social Science Perspective
    Social scientists have postulated a critical threshold percentage of the population that belongs to the middle class and includes social leaders- a threshold of about 5%. When the percentage drops below that critical threshold, it is like pulling the control rods out of a nuclear reactor. That threshold has been called "the tipping point," below which social chaos occurs, with increasing violence and crime, as well as epidemic STD. Rodney Wallace has coined the term "epidemic urban decay" to describe a related phenomenon, when draconian cuts in social support systems (e.g., fire control) lead to out-migration of the middle class.

  • Crack Cocaine Epidemic
    An unexpected brief surge in the US in incidence of STDs such as gonorrhea and syphilis, coming against a background of declining rates of these infections, began in 1985, and was closely linked temporally and geographically to the onset of the crack cocaine epidemic in the US. Although some US surveys, such as the survey of hospital Emergency Room visits for cocaine use, suggest a continued increase in crack cocaine use through 1997 [Slide 38], a separate Department of Justice Survey reported by Johnson and Golub has shown that the prevalence of cocaine in urine among newly arrested individuals has been declining on the East and West Coasts of the US during the 1990s - coincident with a resumption of the decline in gonorrhea and syphilis.


  • Persisting High Fertility and Urbanization in Developing Countries
    In addition to factors noted above, two especially interesting factors that destabilize social relationships include persisting high rates of fertility [Slide 39] in parts of the world - especially Subsaharan Africa - where the resulting burgeoning population of adolescents and young adults increase the size of the population at greatest risk for STD. This is compounded by rural to urban migration of young men, further increasing the ratio of young males to females in cities.

  • Cultural Differences in Male Circumcision
    Male circumcision appears to substantially reduce the risk of acquisition of HIV and of chancroid. Regional differences in cultural practices are highly associated with differences in HIV prevalence.

    index


    Prevention and Control Strategies

    The STD/HIV Transmission Cycle
    The "STD-HIV Transmission Cycle" [Slide 42] identifies the determinants of transmission in a population and the points of intervention. C = rate of exposure, D= duration of infection and B = the probability of transmission from an infected person to a non-infected person. For the epidemic to continue, you have to have a susceptible person exposed to someone who is infectious and then given that exposure, transmission and acquisition of infection have to occur. If each new infection leads to at least one further infection, the epidemic will persist or spread.

     

    As outlined below, the intervention points in the HIV and STD epidemics therefore should ultimately arm to: 1) decrease exposure of susceptibiles to infecteds by behavior changes, such as limiting the number of sexual partners; 2) decrease the efficiency of transmission (given exposure), by promoting condom use for example; and 3) decrease the duration of infectivity (given infection), for example by early diagnosis and treatment of curable STDís.

    Basic Steps in STD/HIV Prevention
    Decrease Exposures of Susceptibles to Infecteds
    • Modify behaviors of susceptibles
    • Modify behaviors of known infecteds
    • Modify behaviors of potentially infecteds
    Decrease Acquisition by Susceptibles
            (decrease efficiency of transmission per exposure)
    Decrease Duration of Infectivity
           (to prevent further transmission and complications)
    • Early detection (case finding)
    • Treatment (curative or suppressive)



    Piot's Pyramid: A Comprehensive Approach [Slide 44]
    This analytic approach takes a step-wise systematic approach to public health interventions. For example, given the ecology of infection, what behaviors should be promoted to avoid exposure to infection? Given exposure, what intervention can reduce transmission? Given infection, only some develop symptoms, so what interventions will detect and treat those who are asymptomatic? Given symptoms, what public health education can improve recognition by individuals of their own symptoms that may possibly indicate an STD? Given symptom recognition, how to promote care-seeking? Given care-seeking, how to provide access to care? Given access, how to ensure adequate diagnosis and effective treatment, and partner treatment to prevent reinfection? Programs that currently focus only on providing expensive multiple-dose prescriptions to symptomatic patients do little for STD prevention or control.


    Readings:

    Holmes, K. "Human Ecology and Behavior and Sexually Transmitted Bacterial Infections". Proceedings of National Academy of Sciences, Vol. 91, March 1994, pp. 2448-2455.


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