The global epidemiology of HIV infection and AIDS.

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Microbiol. 1990.44:555-77

THE IGLOBAL EPIDEMIOLOGY OF HIV INFECTION AND AIDS!

Annu. Rev. Microbiol. 1990.44:555-577. Downloaded from www.annualreviews.org Access provided by Texas Christian University on 01/28/15. For personal use only.

M. Miles Braun, William L. Heyward, and James W. Curran Division of HIV/AIDS, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia 30333 KEY WORDS:

H IV-l, H IV-2, Africa, world health

CONTENllS INTROD UCTION. . . . . . . . . . . . . . . . . . . . ... . . ... . . . . . . ..... . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . .. . . . . . . .. . . . .

555

ORIGINS OF H IV . . . . .. .... . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . . . . . . . . . . ... . .. .

556

S URV EILLA NCE: MONITOR ING THE PATTER NS A ND PREVALENCE OF H IV INFECTIO N, AIDS, A ND SEVERE ILLNESSES C A USED BY H IV . ... . . ............ .......... . .. . . . . . ............ . . ........ . . . .. . . . . . . . Beginnings of AIDS Surveillance ..............................................................

Uses and Objectives.......... ......... . .... . ..... ............ . . . . ..... ........................... Monitoring HIV Irifection . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitoring AIDS.................................................................................. Surveillance Constraints ............................................. . . . . . . . . . . . .. . . . . . . . . . . . . . . .

GEOGRAPH IC D IFFERENCES IN EPIDEMIOLOGY A ND MODES O F TRANS MIS S IO N . . . .. . . . . . . . . . . . ......... . . . . . . . . . . . . .. ....... . . . . . . . . . ...... . . .. . . . . . . . Americas. . ....... ............................... .... . . . . . . . . . . . . .. ..... . . . . . . . . . . . ...... . . . . . . . . . . . Europe . . . . . . . . . . . . . . . ... . .. . .. . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . Africa................................................................................................ Asia.. . . ......... .......... . ....... . . . . . . ............. ...... . .. . ................ . . . . ............. . .. .. Oceania, Including the Western Pacific......................................................

557 557 558 558 559 56 1 562 562 566 567 570 57 1

H IV -2 . . . . . . . . . . . . . . . . . . . ....... . . . . . . . . . . . . . . . . . . . . . . . ......... . . . . . . . . . . . . . . . ....... . . . . . . . . . . . ..... . . . .

57 1

PRO JECTIONS . . . . . . . ....... . . . . . . . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . ... . .. . . . .

572

PREVENTION A ND CONTROL OF HIV AND A IDS ...... . . . . .. . . . . . . . . .... ... . . . . . . . . . ..

573

CONCLUSIO N . . . . . . . . . . . . . . . . .. ....... .. . . .. . . . . . . . . . . . . . . . . . . . .. ........ . . . . . . . . . . . . .. . .... . . . . . . . ..

573

INTRODUCTION

This review describes the global epidemiology of AIDS and HIV infection, starting with reports of the earliest confirmed and suspected cases of AIDS lThe US Government has the right to retain a nonexclusive royalty-free license in and to any copyright covering this paper.

555

556

BRAUN ET AL


and HIV-l infection. The first reports of AIDS, which began in 1981 ( 16), and the subsequent isolation of the etiologic agent and development of antibody tests for HIV- l in 1983-84 (7, 46) led to widespread surveillance and recognition of AIDS and HIV-1 infection. This review focuses on how surveillance is conducted, its strengths and weaknesses, and what we know about the current determinants and distribution of HIV infection and AIDS in the world. Finally, it reviews projections for the future and prospects for prevention and control. ORIGINS OF HIV

Although controversial and still debated, the virologic and geographic origins of HIV are of more than academic interest. For example, if a state of human immunity to an evolutionary precursor of HIV can be discovered, important advances in vaccine and treatment research would follow (45). When AIDS was first recognized in 1981, investigators began reviews of suspect medical records in the United States, Europe, Africa, and elsewhere. Although they discovered reports of isolated cases of AIDS, they found no evidence of widespread unrecognized AIDS cases. In the United States, the first laboratory-documented case of AIDS was a sexually active 15-year-old male suffering from Kaposi's sarcoma in 1968, whose stored sera and autopsy tissue tested positive for HIV- 1 antibody and antigen (47). The relation to HIV-l of other early cases from the 1950s and 1960s of cytomegaloviral pneumonia, Pneumocystis carinii pneumonia, pro gressive multifocal leukencephalopathy, and other diseases cannot be con firmed because of the absence of stored sera and tissue (51). Because virtually all of the diseases associated with HIV-1 infection and AIDS were known and observed to occur independently before the AIDS epidemic in persons with impaired immunity resulting from other causes (e.g. cancer chemotherapy), one can only speculate whether these isolated cases resulted from HIV- l infection. Not until the late 1970s did clusters of diseases that can retrospec tively be diagnosed as AIDS begin to be identified, which is the case for homosexual men and intravenous drug users in New York (60), and Haitians in New York and Miami (72, 88). The first cases of AIDS recognized in African heterosexual men and women were noted in Belgium in the late 1970s and early 1980s (29). Then reviews of case reports and medical records identified sporadic disease sug gestive of AIDS in the 1960s and 1970s in Africa (81). Soon after the enzyme-linked immunosorbent antibody (ELISA) test for HIV-l antibodies became available in 1985, workers began to test previously collected sera that had been frozen and stored (78). False positive results flawed initial studies ( 1 1). With the development of better ELISA technology


GLOBAL EPIDEMIOLOGY OF

HIV AND AIDS

557

and use of Western blot serologic assays for confirmation of ELISA-positive specimens, however, more reliable results have been obtained. The earliest stored sample from Africa shown to contain HIV -1 antibody dates from 1959 from Zaire: (62). This sample had been obtained for immunogenetic studies, and the identity of the donor is no longer known. The earliest viral isolate of HIV -1 was from one of 659 frozen stored serum samples obtained during an unrelated {:pidemiologic investigation of Ebola virus hemorrhagic fever in the Equateur province of Zaire in 1976 (67, 83). Social, cultural, economic, and technologic changes have played an impor tant role in propagating the global epidemic. In Africa, the disruption of the more traditional lifestyles, the building of roads, and the social, behavioral, and economic changes that have accompanied urbanization may be important contributing factors in the spread of HIV -1 (67). Increasing domestic and international travel and population mobility-whether by road, air, or wa ter-has ol;curred at a time when many populations were experiencing a rapid increase in sexual promiscuity and sexually transmitted diseases. For ex ample, truck routes between central and East Africa, and the multiple sexual contacts bl�tween workers and prostitutes that occur at truck stops along the way, help,�d to create an "ecologic corridor" that may have facilitated the spread of HIV -1. In the US many of the earliest cases of AIDS included highly sexually active gay men, some of whom were involved in international travel (38). Dissemination of HIV -1 has been inadvertently aided by advances in medical therapeutics. The development, high volume production, and international distribution of clotting factor concentrates used in the treatment of hemophilia A and B, a process made possible by technologic advances in the 1960s (49), has been a vehicle for HIV-l transmission. In addition, the transfusion of blood and blood products were initially a major route of HIV- l infection. Although elaborate serologic testing and donor deferral has es sentially eliminated this route of transmission in industrialized countries, other less developed countries continue to have transfusion-associated HIV- l transmission. Moreover, intravenous drug use with the sharing of needles, associated with the socioeconomic problems of urban ghettos, has played an important wle in the epidemic in the US, Europe, and Southeast Asia (36, 86, 87). SURVEILLANCE: MONITORING THE PATTERNS AND PREVALENCE OF HIV INFECTION, AIDS, AND SEVERE ILLNESSES CAUSED BY HIV

Beginnings of AIDS Surveillance In June 1981, the Centers for Disease Control (CDC) was alerted to AIDS by reports of;a rare pneumonia caused by P. carinii. Five cases, all in homosex ual men, had been diagnosed over an eight month period in the Los Angeles


558

BRAUN ET AL

area. At about the same time, the CDC received reports of an increase in the incidence of Kaposi's sarcoma in homosexual men in New York and Califor nia. The common underlying factor between these two diseases was a severe ly impaired immune system, with an unknown cause. Subsequently, clinical conditions such as toxoplasmosis of the central nervous system, esophageal candidiasis, disseminated herpes simplex virus infections, and others were noted in the same population and were also associated with immune de ficiency. In late 1982, this constellation of clinical diseases came to be called the acquired immune deficiency syndrome, or AIDS. By then, groups other than homosexual men were reported with AIDS : persons with hemophilia, drug injectors who shared needles, heterosexual contacts of persons with AIDS, transfusion recipients, and infants born to female drug injectors. This epidemiologic pattern of cases strongly suggested transmission by blood or sexual contact; by late 1982, the cause of AIDS was thought by most investigators to be an infectious agent, most likely a virus. The AIDS agent, now called HIV-1 and shown to cause AIDS , was discovered in 1983-84 (7, 46). In 1985, a serologic test to determine whether a person, even if asymptomatic, had been infected with HIV -1 became commercially available, and research showed that the presence of confirmed antibodies indicated persistent viral infection. The commercial availability of a serologic test made possible for the first time confirmation of HIV-1 infection in a person with AIDS or AIDS-like illness and serologic surveys of persons at risk to de termine the prevalence, incidence, and natural history of HIV-l infection.

Uses and Objectives Currently, surveillance for HIV infection and AIDS involves determination of the demographic and clinical characteristics of cases, and identification of associated risk factors for infection. In addition, collection and analysis of surveillance data permits calculation of incidence of new infections over a given time period, projections of numbers of persons with AIDS, and predic tion of future health care resource needs. In contrast to HIV infection sur veillance, AIDS surveillance permits quantitation of the incidence of AIDS related mortality and the current disease burden on the health care system.

Monitoring HIV Infection To serologically test an entire population of a country for HIV-1 infection is usually impossible. To monitor the levels and trends of HIV- 1 infection, one can more efficiently collect detailed information in a number of smaller well-defined popUlation groups. These population groups may be considered as sentinel populations and collectively representative of the trends of the total population (44). In practice, the approaches taken by a country's public health authorities are usually tailored to their specific circumstances. For example, Thailand has concentrated their initial HIV-1 seroprevalence studies in in-


GLOBAL EPIDEMIOLOGY OF HIV AND AIDS

559

travenous drug users and prostitutes, the highest risk groups in this society (43,86). The Soviet Union first tested immigrants, students, then homosexual men in an effort to track introduction of HIV- I into the population. Later, following a nosocomial outbreak of HIV-1 in Elista, more widepread sur veillance f,or HIV-1 infection was instituted there (73). In the US, large population groups tested include many generally healthy persons: volunteer military recruits, blood donors, pregnant women present ing for delivery or prenatal care, and newborn infants. Other groups studied are at increased risk of HIV infection because of certain behavioral risk factors: prostitutes, intravenous drug injectors, or patients at sexually trans mitted disease clinics. A third category consists of outpatients being treated for tuberculosis-an opportunistic infection that is associated with HIV. HIV testing may be voluntary or "blinded." Confidential voluntary HIV testing involves pre- and post-test counselling and testing of blood. Hull et al (50) demonstrated considerable distortion in HIV-l prevalence rates de termined from voluntary testing of sexually transmitted disease clinic patients. Blood from persons who had refused confidential voluntary testing was stripp1ed of all personal identifiers and then tested blindly. HIV-l seropositivity was more than fivefold greater in those who had refused compared to those who had voluntarily consented to HIV-l testing (50). While providing less detailed patient information, blinded testing may pro vide a mOfl� accurate estimate of HlV-I seroprevalence in a population (44). Blinded testing is anonymous and unlinkable to any identifiable individuals whose blood is tested. It makes use only of available serum specimens as well as demographic and historical data; the investigators and the people whose serum specimens are being tested do not interact.

Monitoring AIDS AIDS represents a spectrum of diseases that occur as a result of HIV-induced immunosuppression; AIDS is not a single clinical entity that can be readily diagnosed. The sophisticated tests or procedures necessary to diagnose HIV infection or the associated opportunistic infections are often not available in many areas of the world. For example, to fulfill CDC criteria for the diagnosis of toxoplasmosis of the brain, a patient must undergo either a brain biopsy, radiography with injected contrast media, computed tomography, or nuclear magnetic fI�sonance imaging. Where such technology is unavailable, the criteria cannot be met. Therefore, definitions of AIDS should be adapted to the level of technology available to diagnose HIV-associated disease. The CDC has conducted surveillance for AIDS in the UNITED STATES United Statles since 1981. The case definition of AIDS has been revised and expanded as diagnostic tests for HIV infection were introduced and as other

560

BRAUN ET AL


diseases and conditions associated with AIDS were recognized (17-19). Currently, 23 different indicator diseases are associated with AIDS in adults (see Table I). A slightly modified definition is employed for children younger than 13 years old. Reports of AIDS from developed countries in North America, Europe, and Oceania have consistently employed the CDC case definition-which was adopted for international application by WHO in 1986 (26). SUB-SAHARAN AFRICA In Bangui, central Africa,in 1985, a World Health Organization (WHO) workshop developed, as an interim measure, an AIDS clinical case definition primarily for use in sub-Saharan Africa, where the lack of technical and laboratory resources largely precludes diagnosis of HIV seropositivity as well as diagnosis of the serious diseases comprising the CDC AIDS case definition. The WHO definition (Table 2),which has in practice in sub-Saharan Africa been utilized to varying degrees, requires simply a brief medical history and bedside physical exam (92). The definition is met when a patient suffers from two major and one minor criteria, or the patient has Kaposi's sarcoma or cryptococcal meningitis. Kaposi's sarcoma may be

Table 1

Diseases indicative of AIDS in adults'

Candidiasis of bronchi. trachea, or lungs Candidiasis, esophageal Coccidioidomycosis, disseminated or extrapulmonaryb Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision)b HIY encephalopathyb Herpes simplex: chronic ulcer(s) (> I month duration); or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonaryb Isosporiasis, chronic intestinal (> I month duration)b Kaposi's sarcoma Lymphoma, Burkitt'sb Lymphoma, immunoblasticb Lymphoma, primary in brainb Mycobacterium avium complex or Mycobacterium knnsasii. disseminated or extrapulmonary Mycobacterium of other species or unidentified species, disseminated or extrapulmonaryb Mycobacterium tuberculosis, disseminated or extrapulmonaryb Pneumocystis carinii pneumonia

Progressive multifocal leukencephalopathy Salmonella septicemia, recurrentb Toxoplasmosis of brain Wasting syndrome due to HIyb •

According to the CDC AIDS case definition.

b Laboratory evidence of HIV infection required.



561

diagnosed by biopsy or visual inspection of mucous membranes and skin. The diagnosis of cryptococcal meningitis is made by microscopic inspection of cerebrospinal fluid. Several studies evaluating the definition have found sen sitivity of 52-59% and specificity of 78-90% for HIV-1 infection (30, 40, 91). Though not highly sensitive, the definition's relatively good specificity (which can be further improved by HIV-l antibody testing) makes it useful for surveillance of AIDS in countries with endemic HIV -1 infection where diagnostic capabilities are limited. For example, in a study of Ugandan inpatients and outpatients with an overall HIV-1 seroprevalence determined using ELISA of 42%, fewer than 50% of patients that fulfilled the WHO AIDS case definition had been diagnosed as having AIDS at recent medical evaluations (91). South and Central American countries have insufficient technical support to widely apply the CDC case definition but can often provide HlV serologic tes ting and some laboratory diagnostic ,evaluation of diseases associated with AIDS. These countries have therefore adopted a modified AIDS case definition, first implemented in 1 989, that incorporates technical and laboratory resources intermediate to the CDC and the more rudimentary WHO AIDS case definition. In addition, this new definition includes pulmonary tuberculosis, which is commonly associ ated with HIV infection in developing countries but is not included in the CDC case definition. There has not yet been a propsective evaluation of this new definition to determine its sensitivity and specificity (42, 69b, 90). OTHER SURVEILLANCE DEFINITIONS OF AIDS

Surveillance Constraints Three basic problems hinder surveillance for HIV-related diseases and other medical conditions. First, the lack of a public health infrastructure in many developing countries makes surveillance and reporting of AIDS cases diffi cult, or in some cases, impossible. The second problem is that the limited Table 2

Major and minor criteria of the WHO AIDS clinical case definition" Minor criteria

Major crite ria Weig ht loss

;"

10% of body weig ht

C hroni c diarrhea for more than one month P rolonged fever fo r more than one month

Persistent cough for more than one month Generalized pruriti c dermatitis Re current he rpes zos ter Oropharyngeal can di diasis Chronic p rogressive and disseminated herpes simplex virus infection Generali ze d lymp ha denopathy

a

From Ref. 92.


562

BRAUN ET AL

availability and high cost of diagnostic radiology, bronchoscopy, sterile surgical instruments and anaesthesia to perform biopsies, clinical laboratory facilities to analyze specimens, and other technical resources makes it diffi cult to definitively diagnose HIV-associated diseases. In addition, HIV serologic testing, including the easily performed rapid field tests, may be too expensive for wide utilization in many developing countries. Third, and currently less important, some countries were initially unwilling to report all cases of AIDS for social, political, or economic reasons. However, this reluctance is decreasing with the realization of the global scope of the problem and increasing availability of resources to diagnose, treat, and control AIDS. GEOGRAPHIC DIFFERENCES IN EPIDEMIOLOGY AND MODES OF TRANSMISSION As of December 1989, the World Health Organization had received a cumula tive total of more than 198,000 AIDS case reports from 152 countries on all five continents (Table 3). However, because of underreporting and un derrecognition of AIDS, the WHO estimated the actual number of cumulative AIDS cases to be approximately 600,000 (J. Chin, personal communication).

Americas The United States has one of the most accurate and STATES complete AIDS reporting systems in the world (26). It also has reported the most cases of AIDS of any country in the world, with 125,000 cases reported between June 1981 and February 1990 (23). Homosexual and bisexual men (in a homosexual:bisexual ratio of 4: 1) have accounted for 68% of the cumulative AIDS cases in men in the United States. However, this percentage declined from 69% of cases reported before 1985 to 63% in 1988. This change results mostly from the increased sensitivity of the revision of the CDC AIDS case definition (Table I), which effectively UNITED

Table 3

Global distributions of HIV infections, reported AIDS, and estimated!

projected AIDS, December 1989

Area

Estimated HIV

Cumulative AIDS

Cumulative AIDS cases

infection prevalence

cases reported

estima�ed by WHO

> 3,000,000

36,486

320,000

2,000,000

1 3 1 ,250

220,000

Asia

1 00,000

481

1 ,000

Europe

500,000

28,247

36,000

30,000

1,701

2,200

> 5,630,000

1 98 , 1 65

579,200

Africa Americas

Oceania Total a

Adapted from

J.

Chin, personal communication.

563

GLOBAL EPIDEMIOLOGY OF HlV AND AIDS

increased the proportion of AIDS cases comprised by intravenous drug users. More recently, cases in homosexual/bisexual men have increased more slowly because of behavioral changes that result in decreased incidence of HIV - l infection; AZT antiviral therapy and pentamidine prophylaxis o f

P. carinii

pneumonia, resulting in slowed progression to AIDS; changes in reporting; or several or all of these factors

(10, 19, 3 1).

Intravenous drug users, their sex partners

(75% of intravenous drug users

are heteros1exuaI), and infants born to women who are intravenous drug users

30% of all cumulative 33% of the total cases reported in 1988 . Some data suggest


or sexual partners of intravenous drug users comprise AIDS cases, and

that significant behavioral change has occurred in intravenous drug users to reduce the incidence of HIV-1 infection. Cocaine injection may lead to a higher risk of HIV-l infection than heroin injection

(24).

This may be due to

the short half-life of cocaine, which leads to more daily injections, sharing of injection equipment, and the use of "shooting galleries." HIV-1 seropreva lence in intravenous drug users still varies widely by geographic region in the US, from

0% to nearly 70% (20, 37). Wide variations in HIV- l seropreva

lence may also be seen between intravenous drug users and homosexual/ bisexual men living in the same geographic area

(10). In New York City, a

recent study demonstrated that, for intravenous drug users, heterosexual contact with other intravenous drug users was independently associated with HIV-1 seropositivity, showing the potential for two different modes of transmission of and infection with HIV-l. A drug user's risk of HIV-l infection results from a complex interrelation of drug-use and sexual be haviors that vary according to socioeconomic status and race or ethnic back ground (79). Blood or blood products served as the vehicle of HIV -1 infection in

3% of

the AIDS cases reported in the United States; persons with hemophilia hemophilia B accounted for an additional 1 %

A

or

(10). Since early 1985, dona

tions of blood and plasma have been screened for antibody to HIV -1, and clotting factor concentrates used to treat hemophilia have been subjected to viral inactivation. Thus, these modes of transmission of HIV-l have been greatly reduced, and in the case of clotting factor concentrate, have virtually ceased. However, transfusion-associated AIDS cases will continue to occur because seven years elapse before transfusion develop AIDS

(89).

50% of a cohort infected with HIV -1 by 70% of persons with mod

Approximately

erate to severe hemophilia A and 35% with hemophilia B who received concen trates before

1985

are seropositive for HIV-l; seroprevalence varies little geo

graphically because the clotting factor concentrates implicated in transmission prior to

1985

were distributed nationally and internationally

(20).

Persons with AIDS acquired through heterosexual contact with a person at risk for HIV-I infection increased from 4% to

5% of AIDS cases in 1988. The

demographic composition of this group has changed as well. Between

1981


564

BRAUN ET AL

and 1985, persons born in Haiti or central Africa comprised three-fourths of heterosexually transmitted AIDS cases, whereas in 1988 only one fouth were from these areas. In contrast, the proportion of US-born AIDS cases attribut able to heterosexual contact has increased from 1% before 1985 to 4% after 1985. Moreover, this percentage is likely an underestimate because some cases categorized in the unidentified risk and intravenous drug user transmission categories may actually have acquired HIV-1 infection heterosexually (79). Recent increases in syphilis among heterosexuals, parti cularly among prostitutes, drug users, and their sexual contacts suggest that HIV risk reduction in heterosexuals is lagging (21). Pediatric cases of AIDS represent 2% of total AIDS cases in the US. The two major risk categories are children who have acquired HIV from infected mothers in the perinatal period (8 1%) and children infected through receipt of HIV -1 infected blood or blood products ( 16%) (23). To date, the majority of children with perinatally acquired AIDS were born to mothers who are either intravenous drug users or sex partners of intravenous drug users (21). The median period between infection and diagnosis of AIDS has been 8 months for infants with perinatally acquired AIDS and 19 months for children receiv ing transfusions (76). These incubation periods are much shorter than the observed incubation period for adults ( 10). CANADA As of December 1989 , 2,996 cases of AIDS were reported. In Canada, as in the US, homosexual/bisexual males represent the largest pro portion of AIDS cases (83%). However, in contrast to the US, intravenous drug users comprise only 1% of AIDS cases. Persons originating from countries where AIDS is primarily heterosexually transmitted comprise 5% of cases and are reported primarily from Quebec (2). ENGLISH-SPEAKING CARIBBEAN COUNTRIES Through December 1989, AIDS surveillance in the 18 English-speaking countries in the Caribbean reported 1,3 16 cases of AIDS to WHO. Whereas in 1983-84, 100% of the cases were reported in homosexual or bisexual males, by 1987, heterosexual transmission accounted for greater than one half of the cases (8). Consistent with these numbers is the finding that the proportion of AIDS cases reported in females increased from 0% in 1984 to 29% in 1987. Many factors have been posited to explain the rapid transition to heterosexual transmission of HIV -1, including low homosexual: bisexual ratio (2 : 1), social unacceptability of overt homosexuality, multiple sexual partners, heterosexual intravenous drug use, and immigration of heterosexuals infected with HIV -1. Intravenous drug use has been implicated in 8% of cumulative cases and, according to available surveillance data, does not represent an increasing proportion since 1985. Blood and blood products account for 2% of cases. HIV-l seropreva-


565

lence studies in several countries have documented elevated rates among homosexual men (15-40%), prisoners (4-10%), and prostitutes (0-13%), while the prevalence among blood donors in most countries in 1987 ranged from 0.04% to 0.5% (63). Intravenous drug use plays a very significant role in the HIV epidemic in this commonwealth of the United States. As of December 1989, 4,212 AI DS cases have been reported to CDC from Puerto Rico. Of these, 60% were heterosexual intravenous drug users, 8% were homosexual or bisexual intravenous drug users, and 8% were infected heterosexually; in contrast, homosexual/bisexual men comprised only 17% of persons with AIDS. Puerto Rico has close links with New York City, where HIV- l seroprevalence in intravenous drug users is among the highest in the United States, sometimes exceeding 50% (10). Given the high proportion of AIDS cases occurring in heterosexuals, AIDS in women and infants, now compris ing 17% and I % of cases, respectively, can be expected to grow.


PUERTO RllCO

HAITI Haiti was one of the first countries in which AIDS was recognized. As of December 1989, 2,215 cases have been reported to WHO; however, this is thought to represent significant underreporting. Heterosexual activity is believed to be the prominent mode of transmission of HIV-1 in Haiti and for Haitians in the US (32, 70). The current severity of the problem is reflected in a 1988 study showing that 10. 5% of pregnant women residing in an urban slum were seropositive for HIV-I ( 12). These data also suggest a significant perinatal component to the AIDS problem. Intravenous drug use is rare in Haiti. CUBA Cuba has embarked on a controversial national plan, including com pulsory HIV -I testing and quarantine, to diagnose and control AIDS and HIV-I infection (9). As of May 30, 1988, Cuba reported that 2,224,748 Cubans and foreigners, approximately one-fifth of the island's population, had been t(!sted for HIV-l infection. Serosurveys in blood donors, pregnant women, hospital inpatients, and sexually transmitted disease patients all showed HIV-I seroprevalence rates of less than 0. 1%. Of all Cuban residents tested, 227 were identified as seropositive; the male:female ratio was 3: 1 in these persons, and 97% of the infections were reported to be sexually ac quired. Cubans seropositive for HIV-I have been placed in sanatoria; sero positive foreigners have been repatriated (6 1). BRAZIL The second most populous country in the Americas after the US, Brazil has reported the second high�st number of AIDS cases in the Americas. Through December 1989, 9,555 cases of AIDS had been reported; it is


566

BRAUN ET AL

estimated that 30-50% of cases are not reported. Sixty-seven percent of cumulative AIDS cases have resulted from sexual contact: 39% in homosex uals, 18% in bisexuals, and 10% in heterosexuals. Intravenous drug use has accounted for 14% of cases; blood and blood products, 8%; perinatal transmission, 2%; and 9% of cases had multiple risk factors. Since the inception of the AIDS epidemic, there has been an evolution of the proportion of AIDS cases in the various adult transmission categories. Homosexual and bisexual men in 1980 through 1984 accounted for 54% and 23% of AIDS cases, respectively; however, in 1989, these proportions had decreased to 32% and 14%, respectively (excluding persons with multiple risk factors). In contrast, intravenous drug users and those in the heterosexual risk group comprised 2% and 3% of total AIDS cases in 1980 through 1984, respective ly; and by 1989, these proportions had increased to 20% and 14%, respective ly. Changes over time in the other transmission categories were of much smaller magnitude. As in the English-speaking Caribbean countries, the large proportion of homosexual men who have sex with bisexual men (the homosexual:bisexual ratio in men with AIDS is 2: 1 ), as well as the HIV-l infected intravenous drug users, put women at risk of HIV-I infection. As a result, AIDS in women (now 10% of total cases) and perinatally acquired AIDS cases should increase in the near future. In addition, seroprevalences as high as 20-30% in urban homosexual and bisexual men, 37% in urban transvestites, and 3-6% in female prostitutes suggest the potential for future exacerbation of the AIDS problem in Brazil (1, 34, 75). MEXICO Mexico had reported 2,683 cases of AIDS to WHO as of Decem ber 1989. Of total adult cases through April 1989, 72% of cases occurred in homosexual or bisexual men, 14% were acquired heterosexually, and only 0.5% were in intravenous drug users. The male:female AIDS case ratio is 9: 1. The proportion of AIDS cases in Mexico attributed to transfusions (12%) is one of the highest in the world. This may be linked to HIV-I-infected commercial blood and plasma donations. HIV-I seroprevalence of 7% in a group of urban commercial blood and plasma donors was demonstrated in 1986. Epidemiologic evidence suggested that donors had acquired HIV-l through poor infection control techniques at blood and plasma donation centers, such as the reuse in multiple donors of the same plastic tubing used to carry blood from the patient to a storage container. A subsequent 1987 law proscribing paid blood donations and mandating HIV screening of donated blood is believed to have effectively curtailed this problem (3, 33, 85).

Europe As of December 1989, 28,367 cases of AIDS were reported to WHO from 32 European countries. Table 4 lists the ten countries with the largest numbers of reported cases.

GLOBAL EPIDEMIOLOGY OF HIV AND AIDS Table 4

567

AIDS cases reported to WHO from Europe

through December 1 989 Cumulative cases


Country

Rate"

France

8,025

4.5

Italy

4,663

2.9

West Germany

4 ,093

1 .9

Spain

3,965

3.9

United Kingdom

2,649

1.2

Switzerland

1 ,046

5. 1

Netherlands

983

2.0

Belgium

563

1 .2

Denmark

470

2.4

Sweden

346

1 .0

·eases per 100,000 in 1988.

In Italy and Spain, cases in heterosexual intravenous drug users account for

66% and 62% of AIDS cases, and cases in homosexuallbisexual men account for only 1 6% and 18%, respectively. In Belgium, 50% of the cases of AIDS result from heterosexual transmission, most occurring in persons from central Africa. In the seven other countries with the most cases of AIDS, homosexual or bisexua.l men account for

54

to

81% of cases. In all ten countries, 8% or less, and perinatally acquired

transfusion-associated AIDS accounts for AIDS represents

2%

or less of the AIDS cases. Except for Belgium, AIDS

acquired heterosexually does not exceed

10%

of the total. In the remaining

European ,;;ountries with fewer AIDS cases, homosexual and bisexual men

(93). 18 cases of AIDS to WHO,

represent the predominant AIDS transmission category Although the Soviet Union has reported only

a

recent nosocomial outbreak of HIV - 1 highlights the potential for epidemic transmission in an area of low HIV -1 seroprevalence when proper sterile techniques are not used. In this outbreak, an infant with perinatally acquired HIV infection was the index case from whom

4 1 other children with overlap

ping days of hospital admission were infected. HIV transmission occurred through multiple use of syringes into which blood was aspirated between intravenous injections. In Romania, preliminary reports have indicated that many cases of HIV infection in children may be linked to the practice of using blood transfusions that were not serologically tested for HIV -1 antibodies as therapy for a variety of medical conditions such as infection, anemia, and malnutrition. With this practice, a unit of blood from an adult donor is divided into multiple aliquots; therefore, one HIV-infected donor could potentially infect many children

(73).

Africa SUB-SAHA.RAN AFRICA

Sub-Saharan Africa has probably been impacted

more seve:rely by the HIV/AIDS epidemic than any other region. As of


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BRAUN ET AL

December 1989, 36,279 cases of AIDS have been reported to WHO from 45 African countries; however, these case totals represent a very large un derestimate as several of the African countries hardest hit by AIDS have not reported any cases to WHO since 1987. Despite incomplete reporting, analy sis of reported AIDS cases, along with seroprevalence studies, have resulted in a relatively accurate epidemiologic assessment of HIV transmission in Africa (57). WHO estimates that 320,000 cases have actually occurred through November 1989 (J. Chin, personal communication). Studies in Nairobi have found that frequent sexual contact with prostitutes, lack of circumcision, and the presence of genital ulcer disease are associated with HIV -1 infection in men. Genital ulcer disease is a nonspecific clinical diagnosis that denotes a sexually transmitted disease characterized by ulcera tion of normally intact genital epithelium. In Africa, the specific disease is usually chancroid, syphilis, herpes, or lymphogranuloma venereum; howev er, similarities in clinical presentation of these diseases and unavailability of diagnostic facilities usually preclude making a specific diagnosis. In Nairobi, one study followed 73 HIV- l seronegative men who presented to a sexually transmitted disease clinic. Each of these men reported a single sexual contact with prostitutes who, as a group, have been shown to have an HIV-l seroprevalence of 85%. Six (8%) of the men seroconverted within a mean of 13 weeks follow-up. All the seroconverters had genital ulcers; of 36 men with similar sexual contact and urethritis but without genital ulcers, none serocon verted ( 13, 80). Extensive serosurveys have shown that 2 to 25% of women of child-bearing age in some areas are infected with HIV- 1. This prevalence of infection, along with high fertility rates, result in a large role for AIDS in women and perinatal transmission of HIV -1 in the AIDS epidemic in sub-Saharan Africa ( 14, 7 1). All newborns of HIV- l-infected mothers passively receive maternal antibodies and are HIV-l-seropositive; only about one-third of them will actually be infected with HIV-l; the remainder become seronegative by 12-15 months of age (53). Thus, the proportion of newborns infected with HIV-l will be approximately one-third the seroprevalences observed in pregnant women. In an individual child, the serologic diagnosis of HIV-I infection can usually be made at the age of 15 months or older, when passively acquired maternal antibodies to HIV-l can be expected to have disappeared; however, there have been reports of children with HIV -1 infection demonstrated by culture becoming seronegative after loss of their own or maternal HIV-l antibodies (35). Another mode of transmission of HIV -1 from mother to infant is breast feeding. Although documented in several case reports, breast feeding is thought to play a much smaller role in HIV -1 transmission than perinatal transmission. The importance of breast feeding in infant health and survival in developing countries, and the ready availability of safe alternatives in in-


GLOBAL EPIDEMIOLOGY OF HIY AND AIDS

569

dustrialized countries, has resulted in differing recommendations concerning breast feeding by HIV- l seropositive mothers. Thus, in most cases in de veloping countries, breast-feeding should remain the feeding method of choice for the infants of mothers infected with HIV-l; whereas in the U S, alternative formulas are recommended (69). Screening of the blood supply for HIV infection and single use (or steriliza tion) of an syringes, needles and other medical equipment used parenterally are goals toward which all countries strive. However, limited monetary and technical resources make achievement of these goals difficult in sub-Saharan Africa, especially outside major cities. Iatrogenic HIV transmission by transfusion of unscreened blood, although seldom quantified, still occurrs in much of the developing world. Because of the lack of specific, defined HIV transmission categories, donor deferral is not usually effective. Some rapid screening assays for antibody to HIV-l that are read visually have shown specificity and sensitivity of over 95% in field testing in Africa. This type assay can be implemented in a developing country with limited technical resources; however, the cost of the assays may pose a problem (82). HIV -1 seroincidence and seroprevalence studies indicate the magnitude of the HIV and AID S problem in some areas of central Africa. In Kinshasa, Zaire, studies of the incidence of new HIV-l infections in a large cohort of hospital workers in 1984 to 1986 found a two-year cumulative incidence of HIV-l infection of 3. 2%-which was not associated with nosocomial expo sure (65). Another Kinshasa cohort of 210 prostitutes had an incidence of 14% per woman-year of follow-up, and these HIV- l seroconversions were ' shown to be associated with other sexually transmitted diseases (55). In Kampala, Uganda, serosurveys in 1986--87 found a 24% prevalence of HIV- l in pregnant women and 15% in male blood donors. In nearby Rwanda, in 1986, a nationwide community-based serologic survey found HIV-l serop revalence of 17.8% in urban areas and 1. 3% in rural areas. Figure 1, from the Rwandan survey, demonstrates the typical distribution of HIV-1 seropreva lence by age, and contrasts the severity of the HIV -1 epidemic in urban areas with the much lower seroprevalence in rural areas (77). The rural/urban dichotomy in HIV-l seroprevalence, however, should be considered neither static nor uniform. In certain rural areas, such as the Kagera region of Tanzania and some areas of Uganda, the prevalence of HIV-1 infection exceeds 10% in healthy adults (66). When AID S was first reported in central Africa in 1983, the disease was unknown in East Africa. Through 1989, Kenya has now reported over 6,000 cases of AID S to WHO. The rapid entry and dissemination of HIV-l in the Kenyan population, especially in certain high risk groups, has been documente:d. In Nairobi, the prevalence of HIV-l in prostitutes in an area of low socioe:conomic status increased dramatically from 4% in 1981 to 88% in 1988 (71). Prostitutes such as these, along with their male sexual contacts,

570

BRAUN ET AL (,0

� 30 CII u c: CII

'ii > � 20 Co


e

CII '" ->

�

10

o-s

Figure

1

16-25

Age Iyr)

>40

HIV-seroprevalence by age in urban and rural samples, Rwanda 1986. From Ref. 77,

with permission.

may serve as a source of infection for larger segments of the population. In a 1987 study, HIY-I seroprevalence in a group of pregnant women in Nairobi was 2.7%; in blood donors, seroprevalences of 1.6 to 3.6% have been reported (15). West Africa was the last major region of sub-Saharan Africa to be affected by the HIY-I epidemic. HIY-I infection and AIDS has rapidly emerged, however, in several countries in the region. In Abidjan, Cote d'Ivoire, the ftrst clinical cases of AIDS were recognized in 1985; however, two years later, HIY-I infection had become widespread. A 1987 seroprevalence study found seropositivity to HIY-I in 1 1% of blood donors, 8% of pregnant women, and 8% of persons coming to a sexually transmitted disease clinic (68). Northern Africa has reported relatively small numbers of cases of AIDS; no country in this region has reported more than 200 cases of AIDS to WHO, and seroprevalence studies in healthy adults have shown HIY-I seroprevalence of well below 1% ( 15). Asia

Of the world total of AIDS cases, only 0.2% (481) have been reported from Asia. Nonetheless, some countries in this region are on the verge of an exponential increase in HIY-I infection and AIDS. In December 1987 in Bangkok, Thailand, HIY-I seroprevalence in intravenous drug users was 1 %. By February 1988, HIY-l seroprevalence had risen to 16%. In September 1988, a sample of 1,8 11 of 15,000 registered intravenous drug users was found to have an HIY-I seroprevalence of 44%. This explosive increase in


GLOBAL EPIDEMIOLOGY OF HlY AND AIDS

571

HIV-1 infection among intravenous drug users has been attributed to wide spread needle sharing (86, 87). In a sample of prostitutes of 14 Thai provinces in 1989, HlV-l infection varied between 0 and 5%, except for one province in which 44% (44/100) of prostitutes were seropositive for HIV-l (43). Until recently, HIV infection in Thailand had been geographically limited; now it has been reported in 70 of the country's 73 provinces. Although Thailand has reported only 22 cases of AIDS to WHO, these seroprevalence data are the harbinger of a rapidly worsening AIDS epidemic. India had reported only 32 cases of AIDS to WHO by December 1989; however, the AIDS situation there may soon worsen as well. Serosurveys in prostitutes in southeastern India have documented HIV-1 seroprevalences between 3 and 7% (57). In addition, evidence of potential HIV-l transmission via commercial blood products has recently been presented (5, 84). China, with a population of more than one billion, has reported three cases of AIDS to WHO. A serosurvey of 16,000 underground prostitutes found none to be seropositive for HIV-l. Four persons with hemophilia who were infected with HIV-l through imported therapeutic blood derived products have been repoited (4).

Oceania, Including the Western Pacific Australia and New Zealand have reported 1,529 and 146 cases of AIDS to WHO, respectively. Their epidemiologic pattern is most similar to northern Europe, with the majority of cases occurring in homosexual men (85%) ( 10). Besides Japan, which has reported 108 cumulative cases of AIDS with an incidence of less than one per million in 1988, no other country in this region has reported more than 30 cases of AIDS. HIV-2

In 1985, researchers reported finding antibodies in serum from healthy female prostitutes in Senegal that cross-reacted with antigens from the virus now called simian immunodeficiency virus (SIV) (6). In 1986, another group (28) isolated the virus, now called HIV-2, from persons with AIDS in Guinea Bissau and Cape Verde who had similar cross-reacting antibodies and were shown serologically and virologically not to be infected with HIV- 1. Now, HIV-2 is recognized as older and more geographically widespread than originally thought. Retrospective serologic studies of stored frozen sera have dated HIV-2 in West Africa from at least the 1960s (54), and persons infected with HIV-2 have now been reported from central Africa, western Europe, the United St

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