ANNUAL REVIEWS
Annu. Rev. Publ. Health. 1992. 13:1-30
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HIV INFECTION AND AIDS IN CHILDREN! Thomas C. Quinn, Andrea Ruff, and John Modlin Departments of Medicine and Pediatrics, The Johns Hopkins School of Medicine; Department of International Health, The Johns Hopkins School of Public Health and Hygiene; Laboratory of Immunoregulation, National Institute of Allergy and In fectious Diseases, Baltimore, Maryland 21205 KEY WORDS:
pediatrics, diagnosis, therapy, epidemiology
INTRODUCTION
As of January 1990, the World Health Organization (WHO) estimates that 8-10 million persons are infected with human immunodeficiency virus (HIV) worldwide. Approximately 3 million women, mostly of reproductive age, and more than 500,000 infants and children are infected (35). Eighty percent of these infected women and children reside in sub-Saharan Africa, where the estimated prevalence of HIV infection is 2500/100,000 women aged 15-49 (34). In some African cities, HIV prevalence rates of up to 30% have been documented (114, 142). As heterosexual transmission of HIV increases in other areas of the world, the numbers of infected women and, consequently, their children also increase (124). In Latin America, an estimated 200,000 women are infected, with a prevalence of 200/100,000 women aged 15-49 years (34). There is a rapid increase in HlY infection among drug users and prostitutes in some Asian countries (36). In the United States, women com prise 10% of the 171,865 adult cases of AIDS reported to the Centers for Disease Control as of May 1, 1991 (23). In 1991, AIDS was the fifth leading cause of premature death in women aged 15-49; in New York City, AIDS was the leading cause of death for women aged 20-40 (31, 38). 'The US Government has the right to retain a nonexclusive royalty-free license in and to any copyright covering this paper.
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
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QUINN, RUFF & MODLIN
The World Health Organization estimates that the HIV pandemic will kill 3 million or more women and 2.7 million children worldwide during the 1990s (34,37). AIDS will become the leading cause of death for women aged 15-49 in major cities throughout the Americas, western Europe, and �ub-Saharan Africa, with infant and child mortality rates as much as 30% greater than previously projected. In addition, it is estimated that up to 5.5 million children under 15 will be orphaned because of the premature death of their HIV-infected mothers and fathers from AIDS (34, 130). EPIDEMIOLOGY OF HIV IN WOMEN AND INFANTS
Because more than 90% of HIV-infected children acquired their infection perinatally, the incidence of HIV infection in infants and children is de pendent upon the prevalence of HIV infection in women of reproductive age, the fertility rate of these women, and the risk of perinatal transmission. Because the latter two factors appear to be highly variable among women in different populations, the overall rate of perinatal infection is difficult to predict. The following section discusses the prevalence of HIV infection in women, the associated risk factors for HIV acquisition in women, and how these variables influence perinatal transmission of HIV. Acquisition of HIV through contaminated blood or blood products also remains a risk in many parts of the world; therefore, we also present data regarding this additional mode of transmission. AIDS Surveillance Globally, there has been a marked increase in the number of female AIDS cases. In sub-Saharan Africa and some parts of the Caribbean, the male-to female ratio for AIDS cases is 1: 1, primarily as a result of heterosexual transmission (69, 126, 135, 136). In developed countries, such as those in North America and Europe, the number of AIDS cases diagnosed in women is still fewer than male cases; however, the number is increasing at a faster rate each year because of intravenous (IV) drug use and heterosexual transmis. sion. For example, in the US, the number of AIDS cases diagnosed in women aged 18-44 increased 29% from 1988 to 1989, as compared with an increase of 18% in men in the same age group (21). In 1991, 48% of female AIDS cases acknowledged IV drug use; 35% acknowledged heterosexual contact with an individual at risk for HIV; 7% had a history of receipt of blood transfusion; and 11% were listed as other or undetermined (23), including individuals who may have acquired HIV infection within health care settings, whose mode of exposure is unknown, and who may still be under investiga tion, have died, were lost to follow-up, or refused interview. In the U S, more than 3000 children have been reported to the Centers for
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV AND AIDS IN CHILDREN
3
Disease Control (CDC) with AIDS: 88% acquired it from birth to " mother known to be at risk for HIV infection, 5% from a blood transfusion con taminated with HIV infection, 4% from factor 9 concentrates, and 4% from an undetermined source. In most other countries, more than 90% of children with AIDS acquired their infection from birth to an infected mother. In countries with evidence of heterosexual transmission and a male-to-female ratio approximating one, infants and children with AIDS may comprise as much as 20% of the total number of AIDS cases reported in national sur veillance (136, 138). The demographic characteristics of AIDS cases in women and in children with perinatally acquired infection primarily reflect the characteristics of groups at risk for infection, especially IV drug users. In the US, 59% of perinatally acquired AIDS cases are among black children and 26% are in Hispanic children; their cumulative AIDS incidence rates are 21 and 13 times, respectively, the incidence rates in white children (25, 29). In parts of New York and New Jersey, most IV drug users in treatment are black or Hispanic and live in poor inner city communities, where the prevalence of H IV infection among these drug users is nearly 50% (28, 44, 45). Fifteen metropolitan areas, mostly along the East Coast, which include only 18% of the US pediatric population, account for 70% of the perinatal cases (25). Although the greatest number of pediatric AIDS cases occurs in the first year of life, the relative impact of AIDS as the cause of death has been most striking in the 1-4 year age group: By 1990, AIDS was the leading cause of death among Hispanic children, and the second leading cause among black children in the US. Increasing AIDS-related adult mortality in Africa, as recently documented (43), is creating a large and growing number of children under age 15 whose mothers have died of AIDS. During the 1990s,AIDS will kill 1.5-2.9 million women of reproductive age in Central Africa, thus producing 3.1-5.5 million AIDS orphans (130), 6-11% of the population under 15. In these countries, where 20% of mothers are HIV-infected, childhood mortality under five years of age will rise from 100/1000 live births to 136/1000, thereby negating or reversing the gains of childhood survival achieved in the past few decades. Similar large numbers of orphans are predicted in the Caribbean and several urban centers of the US. Many of these children will be driven to prostitution for survival, thus enhancing further transmission of HIV in adolescents. They are joining those now referred to by the United Nations Children's Fund as "children in extremely difficult circumstances," which includes children en dangered by armed conflict and other disasters, those exploited by child labor, street children, and children who are victims of abuse and neglect (71, 130). Although the phenomenon of AIDS orphans is also affecting Western cities like New York, the predominance of heterosexual transmission and absolute number of parents infected with HIV make this problem considerably greater
4
QUINN, RUFF & MODLIN
in Africa (34). As a result, national and international government and nongovernment service providers in Africa need to recognize this potential impact of HIV infection on children, expand AIDS prevention efforts, and develop policies and programs to address children's AIDS-related needs.
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV Prevalence in Women Because AIDS case reporting is variable and subject to a variety of problems, such as underreporting and difficulties with case definition, seroprevalence studies better reflect the real magnitude of HIV infection. Knowledge of the general prevalence and possible incidence of HIV infections is essential to monitor the epidemiologic patterns and scope of the HIV pandemic (35). Estimates of the number of future cases of HIV-related disease, including AIDS, will be dependent upon the number of persons currently infected with HIV. However, seroprevalence data must also be interpreted with caution, because of the differences in methods in the populations surveyed. Local or regional findings regarding HIV seroprevalence cannot be generalized to the national level, and the extraordinary cultural diversity of many countries should limit any unwarranted extrapolations from small, more intensely studied groups to large populations. A variety of seroprevalence studies have attempted to estimate the frequen cy of HIV infection in women of reproductive age (Table 1). Female appli cants for US military service are routinely tested and have shown a fairly stable seroprevalence rate nationally of 0.06%, although rates are much higher in certain inner cities of the Northeast: approximately 0.5% in northern New Jersey, New York City, and San Juan, Puerto Rico (27, 32, 42, 114). Seroprevalence rates in black and Hispanic female military applicants are eight and four times higher, respectively, than those among white applicants. Seroprevalence among first-time female blood donors is approximately 0.01%. Blinded antenatal screening and surveys of women delivering babies have also documented variable rates in different cities (114). However, several of these studies have shown that many seropositive women do not acknowledge or know they have risk factors for infection. For instance, among women delivering babies at a New York City hospital (92) and at the Johns Hopkins Hospital in Baltimore (4,5),between one third and one half o f the seropositive women had n o reported risk for HIV infection. I n other words, they were likely infected through heterosexual contact with a partner they did not recognize to be infected or at increased risk. Similar studies in sexually transmitted disease (STD) clinics have documented increasing rates among women who may have been infected through heterosexual contact with a partner of unknown risk. In the CDC blinded HIV surveys, seroprevalence of HIV in more than 100,000 women attending STD clinics was 2.2% (21). Median seroprevalence rates by clinic type for women attending prenatal,
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV AND AIDS IN CHILDREN
5
family planning, and drug-treatment clinics were 0.9%, 0.5%, and 3.7%, respectively (21). In 1988,a national survey of 2 million childbearing women per year was initiated in 44 states, the District of Columbia, and Puerto Rico to measure the prevalence of HIV infection among women delivering infants over time. These data will be useful in developing, targeting, and evaluating appropriate education and prevention programs. Thus far, the highest sero prevalence rates have been in New York (0.58%, with 1.25% in New York City and 0.16% upstate), the District of Columbia (0.55%), New Jersey (0.49%), and Florida (0.49); most states have overall rates under 0.1 %. The estimated national rate was 0.15%, which corresponds to 5500-6000 HIV infected women delivering liveborn infants in 1989. If 30% is the rate of perinatal transmission, 1600-1800 of these children were infected as a result of maternal infection in 1989. This number is three times the number of children reported with perinatally acquired AID S in 1989,which suggests that the future number of pediatric cases will be even higher. Rates of 1-4% have been documented in blacks and Hispanic childbearing women in these sur veys, which clearly reflect the impact of HIV infection in minority pop ulations. In developing countries, antenatal surveys for HIV among apparently healthy women of childbearing age reveals that a surprisingly large proportion of those women living in urban areas in some countries have high rates of HIV infection. For example, in Port-au-Prince, Haiti, the rate of HIV infection in pregnant women rose from 8% to more than 10% between 1982 and 1988 (14). In African cities, seroprevalence rates of 5-30% have been documented among women who attend antenatal clinics (17, 59, 67, 90, 95, 105, 126, 137,142,143). Rates of HIV infection have risen from 0% in 1980 to 3% in Table 1
Seroprevalence of HIV -I infection
in antenatal women Location
Number tested
Rate 30.3%
Rwanda
900
Uganda
497
24.3%
Rwanda
3891
23 . 1 %
Burundi
1 255
1 7 . 5%
Zambia
1954
1 1 .6%
Kenya
2400
7.1%
Zaire
1 49 1
6.0%
New York
276,609
0.66%
Massachusetts
30,708
0 . 26%
United States
>2 million
0 . 15%
London
114,5 1 5
0 . 1 5%
Italy
23,491
0 . 024%
Sweden
130,508
0 . 0 1 3%
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QUINN, RUFF & MODLIN
1988 in Nairobi (126, 127), and from 0.2% Kinshasa, Zaire (142).
10
1970 to 8%
10
1986 in
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
Heterosexual Transmission Sexual behavior, exposure to an HIV-infected individual, and a history of STDs appear to be the major risk factors for HIV infection in both men and women. In some developing countries, urban prostitutes, who have a high infection rate (18-86%), played a prominent role in the initial dissemination of HIV in many parts of the world (39, 88, 126-128, 135, 148, 156). However, even among African prostitutes, the presence of STDs appears to be strongly associated with HIV transmission (122). In Nairobi, a prospective study of 124 HIV seronegative African prostitutes documented HIV seroconversion in 83 (67%) (128). Oral contraceptive use, genital ulcers, and Chlamydia trachomatis cervical infection were each independently associated with increased risk of HIV infection. Condom use reduced the risk of HIV infection. Of seroconverting women, 60% experienced one or more episodes of genital ulcers in the period before seroconversion, compared with 45% of HIV seronegative women. This relationship became stronger when the num ber of ulcer episodes was adjusted for length of follow-up. The mean number of annual ulcer episodes was 1.32 ± 0.55 in seroconverting women, com pared with 0.48 ± 0.21 in seronegative women (p < 0.02). The importance of STDs as cofactors was further emphasized among sexual couples in general population surveys. In studies in Rwanda (156) and Kinshasa (125), seropositivity was strongly associated with history of STDs in both men and women. More recently, several US studies have found that a positive serologic test for syphilis (133, 134) and seropositivity to herpes simplex virus type II (31), which is the predominant cause of genital herpes, were strongly associated with HIV infection among women with or without a history of IV drug use. Therefore, STDs appear to be intricately linked to HIV epidemiology and represent one of the major explanations for the heterosexual epidemic in central equatorial Africa, and for the increasing number of heterosexual cases in the US. These findings argue strongly for inclusion of STD control in AIDS prevention programs. The development of programs with an integrated approach to inducing behavioral change, promoting con dom use, and controlling STDs would reduce the infectiousness of HIV transmitters (43) and the susceptibility of HIV-exposed persons (122). Limit ing the transmission of HIV infection among women of reproductive age would obviously have the same impact on preventing perinatal transmission of HIV to infants. Parenteral Transmission In the US, 9% of children acquired HIV infection by receipt of HIV-contami nated blood transfusions or blood components, such as factor 8 and 9
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV AND AIDS IN CHILDREN
7
concentrates for hemophilia. Fortunately, with HIV screening of all blood donations, this mode of transmission has dramatically decreased. In contrast, recent outbreaks of HIV infection in children in the Soviet Union, Romania, and in many developing countries in Africa and Latin America emphasize the risk of nosocomial transmission and the continued need for blood screening and sterilization of medical equipment. For example, among hospitalized children less than 24 months old in Zaire, five (31%) of 16 seropositive infants born to seronegative mothers had been transfused, compared with 15 (7%) of 220 seronegative children in the same age group (100). Also, 147 (14.1%) of 1046 pediatric patients in Kinshasa, Zaire, had a history of blood transfusion. Of these pediatric patients, 40 (3.8%) were HIV seropositive, and there was a strong dose-response association between blood transfusion and HIV seropositivity (58). HIV INFECTION AND PREGNANCY
Studies in Zaire, Zambia, Uganda, Kenya, Haiti, and Malawi have shown highest rates of adverse pregnancy outcomes, such as spontaneous abortion, stillbirth, prematurity, low birth weight, and neonatal mortality in seroposi tive women compared with seronegative controls (17, 59, 67, 90, 95, 105, 143). However, the findings have not been consistent and appear to be related to the severity of maternal HIV disease. In Haiti, children born to HIV seropositive mothers were significantly more likely to be premature, of low birth weight, and malnourished at three and six months of age than were infants born to HIV negative women (62). In Nairobi (17), the mean birth weight of singleton neonates of HIV positive women was significantly lower than that of controls (3090 vs. 3220 g, P 0.005), and birth weight was < 2500 g in 9% of cases and 3% of controls [odds ratio (OR) 3.0, p. 0.007]. Among neonates of HIV seropositive women, birth weight was less than 2500 g in 17% if mothers were symptomatic and 6% if mothers were asymptomatic (OR 3.4, P 0.08). In Malawi, the seroprevalence for HIV infection in 461 consecutive pregnant women was 17.6% (104). The estimated annual in cidence of HIV seroconversion in urban pregnant women was 3-4% per annum between 1985 and 1987, and 7-13% between 1987 and 1989. HIV infection was significantly associated with a positive syphilis serology and correlated with history of STDs, although it was not statistically significant. A history of spontaneous abortion was also associated with reactive syphilis serology, HIV infection, and history of STDs; in a logistic regression analy sis, HIV infection remained the only significant variable. Predicting HIV infection in pregnant women without serologic testing has been extremely difficult, even in high prevalence areas. Obstetrical history may be a better predictor of HIV infection in women of childbearing age than socioeconomic and sexual history parameters, with a strong association be=
=
=
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8
QUINN, RUFF & MODLIN
. tween intrauterine fetal death and maternal HIV infection in case-controlled studies performed in Nairobi (152) and in Kigali, Rwanda. The rates of prematurity, low birth weight, congenital malformations, and neonatal mortality and socioeconomic statistics were comparable in the two groups (95). However, infants of HIV positive mothers were a mean birth weight of 130 g lower than the infants of HIV negative mothers (p
Annu. Rev. Publ. Health. 1992. 13:1-30
Further
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Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV INFECTION AND AIDS IN CHILDREN! Thomas C. Quinn, Andrea Ruff, and John Modlin Departments of Medicine and Pediatrics, The Johns Hopkins School of Medicine; Department of International Health, The Johns Hopkins School of Public Health and Hygiene; Laboratory of Immunoregulation, National Institute of Allergy and In fectious Diseases, Baltimore, Maryland 21205 KEY WORDS:
pediatrics, diagnosis, therapy, epidemiology
INTRODUCTION
As of January 1990, the World Health Organization (WHO) estimates that 8-10 million persons are infected with human immunodeficiency virus (HIV) worldwide. Approximately 3 million women, mostly of reproductive age, and more than 500,000 infants and children are infected (35). Eighty percent of these infected women and children reside in sub-Saharan Africa, where the estimated prevalence of HIV infection is 2500/100,000 women aged 15-49 (34). In some African cities, HIV prevalence rates of up to 30% have been documented (114, 142). As heterosexual transmission of HIV increases in other areas of the world, the numbers of infected women and, consequently, their children also increase (124). In Latin America, an estimated 200,000 women are infected, with a prevalence of 200/100,000 women aged 15-49 years (34). There is a rapid increase in HlY infection among drug users and prostitutes in some Asian countries (36). In the United States, women com prise 10% of the 171,865 adult cases of AIDS reported to the Centers for Disease Control as of May 1, 1991 (23). In 1991, AIDS was the fifth leading cause of premature death in women aged 15-49; in New York City, AIDS was the leading cause of death for women aged 20-40 (31, 38). 'The US Government has the right to retain a nonexclusive royalty-free license in and to any copyright covering this paper.
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
2
QUINN, RUFF & MODLIN
The World Health Organization estimates that the HIV pandemic will kill 3 million or more women and 2.7 million children worldwide during the 1990s (34,37). AIDS will become the leading cause of death for women aged 15-49 in major cities throughout the Americas, western Europe, and �ub-Saharan Africa, with infant and child mortality rates as much as 30% greater than previously projected. In addition, it is estimated that up to 5.5 million children under 15 will be orphaned because of the premature death of their HIV-infected mothers and fathers from AIDS (34, 130). EPIDEMIOLOGY OF HIV IN WOMEN AND INFANTS
Because more than 90% of HIV-infected children acquired their infection perinatally, the incidence of HIV infection in infants and children is de pendent upon the prevalence of HIV infection in women of reproductive age, the fertility rate of these women, and the risk of perinatal transmission. Because the latter two factors appear to be highly variable among women in different populations, the overall rate of perinatal infection is difficult to predict. The following section discusses the prevalence of HIV infection in women, the associated risk factors for HIV acquisition in women, and how these variables influence perinatal transmission of HIV. Acquisition of HIV through contaminated blood or blood products also remains a risk in many parts of the world; therefore, we also present data regarding this additional mode of transmission. AIDS Surveillance Globally, there has been a marked increase in the number of female AIDS cases. In sub-Saharan Africa and some parts of the Caribbean, the male-to female ratio for AIDS cases is 1: 1, primarily as a result of heterosexual transmission (69, 126, 135, 136). In developed countries, such as those in North America and Europe, the number of AIDS cases diagnosed in women is still fewer than male cases; however, the number is increasing at a faster rate each year because of intravenous (IV) drug use and heterosexual transmis. sion. For example, in the US, the number of AIDS cases diagnosed in women aged 18-44 increased 29% from 1988 to 1989, as compared with an increase of 18% in men in the same age group (21). In 1991, 48% of female AIDS cases acknowledged IV drug use; 35% acknowledged heterosexual contact with an individual at risk for HIV; 7% had a history of receipt of blood transfusion; and 11% were listed as other or undetermined (23), including individuals who may have acquired HIV infection within health care settings, whose mode of exposure is unknown, and who may still be under investiga tion, have died, were lost to follow-up, or refused interview. In the U S, more than 3000 children have been reported to the Centers for
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV AND AIDS IN CHILDREN
3
Disease Control (CDC) with AIDS: 88% acquired it from birth to " mother known to be at risk for HIV infection, 5% from a blood transfusion con taminated with HIV infection, 4% from factor 9 concentrates, and 4% from an undetermined source. In most other countries, more than 90% of children with AIDS acquired their infection from birth to an infected mother. In countries with evidence of heterosexual transmission and a male-to-female ratio approximating one, infants and children with AIDS may comprise as much as 20% of the total number of AIDS cases reported in national sur veillance (136, 138). The demographic characteristics of AIDS cases in women and in children with perinatally acquired infection primarily reflect the characteristics of groups at risk for infection, especially IV drug users. In the US, 59% of perinatally acquired AIDS cases are among black children and 26% are in Hispanic children; their cumulative AIDS incidence rates are 21 and 13 times, respectively, the incidence rates in white children (25, 29). In parts of New York and New Jersey, most IV drug users in treatment are black or Hispanic and live in poor inner city communities, where the prevalence of H IV infection among these drug users is nearly 50% (28, 44, 45). Fifteen metropolitan areas, mostly along the East Coast, which include only 18% of the US pediatric population, account for 70% of the perinatal cases (25). Although the greatest number of pediatric AIDS cases occurs in the first year of life, the relative impact of AIDS as the cause of death has been most striking in the 1-4 year age group: By 1990, AIDS was the leading cause of death among Hispanic children, and the second leading cause among black children in the US. Increasing AIDS-related adult mortality in Africa, as recently documented (43), is creating a large and growing number of children under age 15 whose mothers have died of AIDS. During the 1990s,AIDS will kill 1.5-2.9 million women of reproductive age in Central Africa, thus producing 3.1-5.5 million AIDS orphans (130), 6-11% of the population under 15. In these countries, where 20% of mothers are HIV-infected, childhood mortality under five years of age will rise from 100/1000 live births to 136/1000, thereby negating or reversing the gains of childhood survival achieved in the past few decades. Similar large numbers of orphans are predicted in the Caribbean and several urban centers of the US. Many of these children will be driven to prostitution for survival, thus enhancing further transmission of HIV in adolescents. They are joining those now referred to by the United Nations Children's Fund as "children in extremely difficult circumstances," which includes children en dangered by armed conflict and other disasters, those exploited by child labor, street children, and children who are victims of abuse and neglect (71, 130). Although the phenomenon of AIDS orphans is also affecting Western cities like New York, the predominance of heterosexual transmission and absolute number of parents infected with HIV make this problem considerably greater
4
QUINN, RUFF & MODLIN
in Africa (34). As a result, national and international government and nongovernment service providers in Africa need to recognize this potential impact of HIV infection on children, expand AIDS prevention efforts, and develop policies and programs to address children's AIDS-related needs.
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV Prevalence in Women Because AIDS case reporting is variable and subject to a variety of problems, such as underreporting and difficulties with case definition, seroprevalence studies better reflect the real magnitude of HIV infection. Knowledge of the general prevalence and possible incidence of HIV infections is essential to monitor the epidemiologic patterns and scope of the HIV pandemic (35). Estimates of the number of future cases of HIV-related disease, including AIDS, will be dependent upon the number of persons currently infected with HIV. However, seroprevalence data must also be interpreted with caution, because of the differences in methods in the populations surveyed. Local or regional findings regarding HIV seroprevalence cannot be generalized to the national level, and the extraordinary cultural diversity of many countries should limit any unwarranted extrapolations from small, more intensely studied groups to large populations. A variety of seroprevalence studies have attempted to estimate the frequen cy of HIV infection in women of reproductive age (Table 1). Female appli cants for US military service are routinely tested and have shown a fairly stable seroprevalence rate nationally of 0.06%, although rates are much higher in certain inner cities of the Northeast: approximately 0.5% in northern New Jersey, New York City, and San Juan, Puerto Rico (27, 32, 42, 114). Seroprevalence rates in black and Hispanic female military applicants are eight and four times higher, respectively, than those among white applicants. Seroprevalence among first-time female blood donors is approximately 0.01%. Blinded antenatal screening and surveys of women delivering babies have also documented variable rates in different cities (114). However, several of these studies have shown that many seropositive women do not acknowledge or know they have risk factors for infection. For instance, among women delivering babies at a New York City hospital (92) and at the Johns Hopkins Hospital in Baltimore (4,5),between one third and one half o f the seropositive women had n o reported risk for HIV infection. I n other words, they were likely infected through heterosexual contact with a partner they did not recognize to be infected or at increased risk. Similar studies in sexually transmitted disease (STD) clinics have documented increasing rates among women who may have been infected through heterosexual contact with a partner of unknown risk. In the CDC blinded HIV surveys, seroprevalence of HIV in more than 100,000 women attending STD clinics was 2.2% (21). Median seroprevalence rates by clinic type for women attending prenatal,
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
HIV AND AIDS IN CHILDREN
5
family planning, and drug-treatment clinics were 0.9%, 0.5%, and 3.7%, respectively (21). In 1988,a national survey of 2 million childbearing women per year was initiated in 44 states, the District of Columbia, and Puerto Rico to measure the prevalence of HIV infection among women delivering infants over time. These data will be useful in developing, targeting, and evaluating appropriate education and prevention programs. Thus far, the highest sero prevalence rates have been in New York (0.58%, with 1.25% in New York City and 0.16% upstate), the District of Columbia (0.55%), New Jersey (0.49%), and Florida (0.49); most states have overall rates under 0.1 %. The estimated national rate was 0.15%, which corresponds to 5500-6000 HIV infected women delivering liveborn infants in 1989. If 30% is the rate of perinatal transmission, 1600-1800 of these children were infected as a result of maternal infection in 1989. This number is three times the number of children reported with perinatally acquired AID S in 1989,which suggests that the future number of pediatric cases will be even higher. Rates of 1-4% have been documented in blacks and Hispanic childbearing women in these sur veys, which clearly reflect the impact of HIV infection in minority pop ulations. In developing countries, antenatal surveys for HIV among apparently healthy women of childbearing age reveals that a surprisingly large proportion of those women living in urban areas in some countries have high rates of HIV infection. For example, in Port-au-Prince, Haiti, the rate of HIV infection in pregnant women rose from 8% to more than 10% between 1982 and 1988 (14). In African cities, seroprevalence rates of 5-30% have been documented among women who attend antenatal clinics (17, 59, 67, 90, 95, 105, 126, 137,142,143). Rates of HIV infection have risen from 0% in 1980 to 3% in Table 1
Seroprevalence of HIV -I infection
in antenatal women Location
Number tested
Rate 30.3%
Rwanda
900
Uganda
497
24.3%
Rwanda
3891
23 . 1 %
Burundi
1 255
1 7 . 5%
Zambia
1954
1 1 .6%
Kenya
2400
7.1%
Zaire
1 49 1
6.0%
New York
276,609
0.66%
Massachusetts
30,708
0 . 26%
United States
>2 million
0 . 15%
London
114,5 1 5
0 . 1 5%
Italy
23,491
0 . 024%
Sweden
130,508
0 . 0 1 3%
6
QUINN, RUFF & MODLIN
1988 in Nairobi (126, 127), and from 0.2% Kinshasa, Zaire (142).
10
1970 to 8%
10
1986 in
Annu. Rev. Public Health 1992.13:1-30. Downloaded from www.annualreviews.org Access provided by New York University - Bobst Library on 02/03/15. For personal use only.
Heterosexual Transmission Sexual behavior, exposure to an HIV-infected individual, and a history of STDs appear to be the major risk factors for HIV infection in both men and women. In some developing countries, urban prostitutes, who have a high infection rate (18-86%), played a prominent role in the initial dissemination of HIV in many parts of the world (39, 88, 126-128, 135, 148, 156). However, even among African prostitutes, the presence of STDs appears to be strongly associated with HIV transmission (122). In Nairobi, a prospective study of 124 HIV seronegative African prostitutes documented HIV seroconversion in 83 (67%) (128). Oral contraceptive use, genital ulcers, and Chlamydia trachomatis cervical infection were each independently associated with increased risk of HIV infection. Condom use reduced the risk of HIV infection. Of seroconverting women, 60% experienced one or more episodes of genital ulcers in the period before seroconversion, compared with 45% of HIV seronegative women. This relationship became stronger when the num ber of ulcer episodes was adjusted for length of follow-up. The mean number of annual ulcer episodes was 1.32 ± 0.55 in seroconverting women, com pared with 0.48 ± 0.21 in seronegative women (p < 0.02). The importance of STDs as cofactors was further emphasized among sexual couples in general population surveys. In studies in Rwanda (156) and Kinshasa (125), seropositivity was strongly associated with history of STDs in both men and women. More recently, several US studies have found that a positive serologic test for syphilis (133, 134) and seropositivity to herpes simplex virus type II (31), which is the predominant cause of genital herpes, were strongly associated with HIV infection among women with or without a history of IV drug use. Therefore, STDs appear to be intricately linked to HIV epidemiology and represent one of the major explanations for the heterosexual epidemic in central equatorial Africa, and for the increasing number of heterosexual cases in the US. These findings argue strongly for inclusion of STD control in AIDS prevention programs. The development of programs with an integrated approach to inducing behavioral change, promoting con dom use, and controlling STDs would reduce the infectiousness of HIV transmitters (43) and the susceptibility of HIV-exposed persons (122). Limit ing the transmission of HIV infection among women of reproductive age would obviously have the same impact on preventing perinatal transmission of HIV to infants. Parenteral Transmission In the US, 9% of children acquired HIV infection by receipt of HIV-contami nated blood transfusions or blood components, such as factor 8 and 9
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HIV AND AIDS IN CHILDREN
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concentrates for hemophilia. Fortunately, with HIV screening of all blood donations, this mode of transmission has dramatically decreased. In contrast, recent outbreaks of HIV infection in children in the Soviet Union, Romania, and in many developing countries in Africa and Latin America emphasize the risk of nosocomial transmission and the continued need for blood screening and sterilization of medical equipment. For example, among hospitalized children less than 24 months old in Zaire, five (31%) of 16 seropositive infants born to seronegative mothers had been transfused, compared with 15 (7%) of 220 seronegative children in the same age group (100). Also, 147 (14.1%) of 1046 pediatric patients in Kinshasa, Zaire, had a history of blood transfusion. Of these pediatric patients, 40 (3.8%) were HIV seropositive, and there was a strong dose-response association between blood transfusion and HIV seropositivity (58). HIV INFECTION AND PREGNANCY
Studies in Zaire, Zambia, Uganda, Kenya, Haiti, and Malawi have shown highest rates of adverse pregnancy outcomes, such as spontaneous abortion, stillbirth, prematurity, low birth weight, and neonatal mortality in seroposi tive women compared with seronegative controls (17, 59, 67, 90, 95, 105, 143). However, the findings have not been consistent and appear to be related to the severity of maternal HIV disease. In Haiti, children born to HIV seropositive mothers were significantly more likely to be premature, of low birth weight, and malnourished at three and six months of age than were infants born to HIV negative women (62). In Nairobi (17), the mean birth weight of singleton neonates of HIV positive women was significantly lower than that of controls (3090 vs. 3220 g, P 0.005), and birth weight was < 2500 g in 9% of cases and 3% of controls [odds ratio (OR) 3.0, p. 0.007]. Among neonates of HIV seropositive women, birth weight was less than 2500 g in 17% if mothers were symptomatic and 6% if mothers were asymptomatic (OR 3.4, P 0.08). In Malawi, the seroprevalence for HIV infection in 461 consecutive pregnant women was 17.6% (104). The estimated annual in cidence of HIV seroconversion in urban pregnant women was 3-4% per annum between 1985 and 1987, and 7-13% between 1987 and 1989. HIV infection was significantly associated with a positive syphilis serology and correlated with history of STDs, although it was not statistically significant. A history of spontaneous abortion was also associated with reactive syphilis serology, HIV infection, and history of STDs; in a logistic regression analy sis, HIV infection remained the only significant variable. Predicting HIV infection in pregnant women without serologic testing has been extremely difficult, even in high prevalence areas. Obstetrical history may be a better predictor of HIV infection in women of childbearing age than socioeconomic and sexual history parameters, with a strong association be=
=
=
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QUINN, RUFF & MODLIN
. tween intrauterine fetal death and maternal HIV infection in case-controlled studies performed in Nairobi (152) and in Kigali, Rwanda. The rates of prematurity, low birth weight, congenital malformations, and neonatal mortality and socioeconomic statistics were comparable in the two groups (95). However, infants of HIV positive mothers were a mean birth weight of 130 g lower than the infants of HIV negative mothers (p
