Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985

BACKGROUND: Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a newly discovered virus found in all forms of KS. In the United States, KSHV infection appears to be most common amongst individuals at high-risk for KS. Preliminary data from Africa suggest that KSHV infection may be much more common in the general population. OBJECTIVE: To examine the KSHV seroprevalence and age-specific patterns of infection in an African country with high rates of KS. DESIGN: Cross-sectional seroprevalence study. METHODS: Sera were taken for a hospital-based HIV seroprevalence study conducted in August 1985 in Lusaka, Zambia at a time when HIV was just becoming epidemic in this area. A total of 251 sera were randomly sampled and examined for antibodies against latent and lytic antigens to KSHV. KSHV seroprevalence was compared with demographic and clinical variables using chi2 test for linear trend and odds ratios and 95% confidence intervals. RESULTS: Overall, 58% of persons aged 14-84 years were KSHV-seropositive. KSHV seroprevalence increased linearly with age (P = 0.04) and was inversely related to years of education (P = 0.015). In contrast, HIV infection peaked in those aged 20-29 years and was positively related to years of education (P = 0.01 5). No association between KSHV and gender, marital status, or HIV serostatus was seen. CONCLUSIONS: KSHV infection was significantly more common in this region of Zambia in 1985 than it currently is in the United States. Our data are consistent with KSHV being well-established in this region prior to 1985 and that continued adult transmission of the virus was occurring. The high seroprevalence in the adolescent age-group and the relatively linear increase in prevalence with age suggest that non-sexual modes of transmission may be important for KSHV transmission in Africa.     

Notes on the socio-economic and cultural factors influencing the transmission of HIV in Botswana

Botswana currently has one of the highest recorded incidences of HIV infection in Africa although AIDS was only first publicly recognized in 1985. By this time other countries in the region such as Malawi, Zambia and Uganda were already showing signs of epidemic levels of HIV. The rapid transmission of HIV in Botswana has been due to three main factors; the position of women in society, particularly their lack of power in negotiating sexual relationships: cultural attitudes to fertility; and social migration patterns. These three factors along with other, arguably more minor, ones have been shaped and mediated within the specific context of Botswana's rapid socio-economic development and cultural milieu. This has resulted in a constellation of factors unique to Botswana which accounts for the current high seroprevalence rate in the country.     

Tuberculosis trends in Barcelona (1987-1995). Impact of the human immunodeficiency virus and control measures

BACKGROUND: To study the epidemiology to tuberculosis (TB) in Barcelona, Spain from 1987 to 1995, analyzing the influence of HIV infection and the impact of control measures. PATIENTS, MATERIAL AND METHODS: All cases detected by the Barcelona Tuberculosis Prevention and Control Program were included in the study of the evolution of TB incidence according to different variables. The impact of HIV infection was analyzed through the attributable risk per cent (AR), and control measures through the evolution of the rate of treatment compliance, contact studies, and diagnostic delay. RESULTS: We detected 8,942 patients, 23.2% of whom were found through the active epidemiological surveillance system, representing an average annual incidence of 60.4/100,000. The incidence peaked in 1991 (68.7/100,000) and slowly declined to 55.7/100,000 in 1995. Men showed higher incidence (RR: 2.74; CI 95%: 2.62-2.87), particularly among the young (25-34 years olds), 53.3% of whom were HIV (+). The AR for HIV was 92.7%. In this period there was an increase in TB HIV (+), IVDU, and prisoners. Treatment compliance (80.8% in 1987 to 93.8% in 1995) and contact studies (3.2 studies/case in 1995) evolved favorably, unlike but diagnostic delay (35 days in 1995) did not. CONCLUSIONS: The Active Epidemiological Surveillance System has affored us a clear view of the actual situation regarding TB in Barcelona, Spain. Despite the HIV epidemics and the high number of IVDU, the evolution of TB has shown a steady decline due to improvement in control measures.     

The South African HIV epidemic, reflected by nine provincial epidemics, 1990-1996

OBJECTIVES: To determine by serological examination the annual point prevalence rates of infection with the human immunodeficiency virus (HIV) in representative samples of subjects in the nine provinces of South Africa, 1990-1996. DESIGN: Annual cross-sectional point prevalence surveys conducted in October/November of each year. SETTING: South Africa, including areas that used to be known as self-governing and independent National States. SUBJECTS: Pregnant women in the age group 15-49 years who attend antenatal clinic services provided by the public health services, and who act as an indicator group of the HIV epidemic among the heterosexually active population. OUTCOME MEASURES: HIV positivity as determined serologically; done consistently over several years, this serves to monitor the distribution and trend of the HIV epidemic in each of the nine provinces of South Africa. RESULTS: Empirical data gained from seven annual, consecutive countrywide surveys demonstrate a wide geographical variation in the point prevalence rates of HIV infection. In October/November 1996 the point prevalence rates (%) were as follows: Western Cape 3.09, Northern Cape 6.57, Northern Province 7.96, Eastern Cape 8.10, Gauteng 15.49, Mpumalanga 15.77, Free State 17.49, KwaZulu-Natal 19.90 and North West 25.13. The weighted national average was 14.17%. There are indications that some of the provinces (KwaZulu-Natal and possibly Mpumalanga) might have passed a point of inflection suggesting deceleration in their specific rates of increase. These results are, however, counterbalanced by the exponential growth still being experienced in provinces with large populations such as Gauteng and the Eastern Cape. It is concluded that the net effect of these divergent trends currently affects the national figure only marginally. A major deflection from the exponential growth patterns seen hitherto can be anticipated only once all or most of the highly populated provinces have traversed their respective points of inflection. The exponential model significantly explains the HIV epidemics in the provinces. The combination of these provincial epidemics describes the initial exponential phase of the epidemic.     

Tuberculosis 1992: current clinical aspects, epidemiology and diagnosis

We review four different aspects of tuberculosis (TB), a disease which is making a comeback as a focus of medical attention. The diagnosis of TB in HIV infected individuals can be very challenging for the clinician and an increased number of side effects complicates treatment. Updated information in this area appears necessary for physicians who are in charge of HIV-infected patients. The "cursed duet" of TB and HIV infection is also responsible for the increase of TB in subsaharan Africa. Recent data are discussed in relation to this issue. Another problem for developing countries is the diagnosis and treatment of children's TB, which involves particular features as compared to the adult form of the disease. Finally, new diagnostic methods are now available from the laboratory. The detection of mycobacteria with the polymerase chain reaction has proven very useful in the diagnosis of tuberculous meningitis. Detection of tuberculostearic acid and mycobacterial antigen also represent important advances. The role of these techniques in the diagnosis of TB forms other than meningitis will need to be defined in the near future.     

Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant

OBJECTIVES: To investigate the magnitude and the time course of the HIV epidemic in the provinces of South Africa from the antenatal clinic HIV surveys. DESIGN: We analysed the data on the provincial prevalences of HIV infection from 1990 to 1996 using maximum likelihood methods to determine the intrinsic growth rate and probable asymptotic prevalence of HIV among women attending antenatal clinics. SUBJECTS: Women attending antenatal clinics and included in the national HIV prevalence surveys conducted by the Department of Health. RESULTS: 1. In KwaZulu-Natal the epidemic is likely to peak at a prevalence of about 23% (95% confidence interval (CI) 19-36%). 2. The intrinsic doubling time does not differ significantly among the provinces. 3. The average length of the intrinsic doubling time is 12.0 months (95% CI 11.3-12.8 months). 4. The force of infection is approximately 1.00/year at age 16 years and declines at a rate of about 5% per year of age above 16 years. CONCLUSIONS: South Africa is likely to experience one of the worst HIV epidemics in Africa. The lack of statistically significant differences between the growth rates of the epidemic in the various provinces constrains the possible explanations that can be advanced to explain the time course of the epidemic and may in part be a consequence of migrancy. The intrinsic growth rate is higher than previous estimates and it is possible that in those provinces where the prevalence is still low it will eventually reach the same levels as in KwaZulu-Natal.     

Practising obstetrics and gynaecology in areas with a high prevalence of HIV infection

What is it like to practise obstetrics and gynaecology in a country with a high prevalence of HIV infection? My experience relates especially to Zimbabwe, but the same factors apply equally well to Zambia, Zaire, Uganda, Kenya, Tanzania, Malawi, and Mozambique. Within a population of 11 million in Zimbabwe, at least 1 million are HIV positive according to the official figures. AIDS often means "home-based care"; the nearest clinic or hospital, which has very little to offer, may be 3 hours away by wheelbarrow. Many patients who die with chronic diarrhoea lack a piped water supply nearby, an indoor toilet, or even a waterproof sheet. Every year in Zimbabwe there are 120,000 confinements of HIV-positive women compared with 7000 HIV-positive pregnancies in the USA. Transmission of the virus in Africa is mainly heterosexual and vertical, although blood transfusion still plays a part. Intravenous drug use is not a problem but alcohol is, by way of promoting risky behaviour. A secondary epidemic of tuberculosis (TB) (also among HIV-negative persons) adds to the difficulties in sub-Saharan Africa.     

HIV-associated tuberculosis in Africa exemplified by Zimbabwe

In Africa, a rapid increase of human immunodeficiency virus (HIV)-associated tuberculosis cases has been observed; 80% of a worldwide 6 million dually infected persons live in this part of the world. The annual risk of progression to clinically overt tuberculosis in dually infected persons approaches the lifetime risk in persons with tuberculosis but no HIV infection. Zimbabwe is an example which illustrates the rapid increase in notified tuberculosis cases since 1985, accounted for primarily by HIV-associated tuberculosis cases. In sputum-smear positive HIV-associated tuberculosis, classical symptoms are reported with the same frequency as in HIV negative cases. Thus, case-finding activities need not be altered. In sputum-smear negative patients, reliable diagnostic tests are not available. Therapeutic trials are widely used and this causes overdiagnosis of tuberculosis. Extrapulmonary manifestations are common in HIV-associated tuberculosis. A majority of lymph node enlargements, pleurisy and pericarditis in Africa are now due to tuberculosis. If compliance is ensured, response to chemotherapy is excellent, but overall case fatality and relapse rates are increased. The cost-effectiveness of tuberculosis control programmes using directly observed therapy for at least the first 2 months of treatment is well established. With the prominent global significance of tuberculosis and the possibility of cost-effective interventions, a commitment to the fight against the worldwide epidemic is more important than ever before.     

Prospective study of tardive dyskinesia in the elderly: rates and risk factors

Estimated incidence rates are presented for three human immunodeficiency virus (HIV)-associated cancers [Kaposi's sarcoma (KS), Burkitt's lymphoma (BL) and other non-Hodgkin's lymphomas (NHLs)] from across the African continent, based on data collected before the HIV epidemic. Mapping of the rates and comparisons with a range of geographical variables indicate completely different distributions for KS and BL but a degree of similarity in the occurrence of Burkitt's lymphoma and other NHLs. Comparisons with rates elsewhere in the world suggest, most notably, that KS was as common in some regions of sub-Saharan Africa as was cancer of the colon in much of Western Europe. Comparison with data from the era of AIDS indicates 20-fold increases in the occurrence of Kaposi's sarcoma in Uganda and Zimbabwe. The highest rates for BL were three to four times the rates for leukaemia at young ages in Western populations, but the general incidence of other NHL was no higher than in the West and very low rates were indicated for much of southern Africa.     

Prevention and control of tuberculosis in the 1990s

Beginning in 1984, the long-term decline in tuberculosis (TB) cases stopped, and since 1985 the number of cases has actually increased by 18%, from 22,201 new cases in 1985 to 26,283 in 1991. The change in the morbidity trend appears to be primarily due to three factors: HIV coinfection, TB occurring in persons from countries where this disease is prevalent, and deterioration of the health care infrastructure with resultant outbreaks of TB. This article presents six interventions that address major areas where action is needed. These efforts will require coordinated action by health care providers, public health departments, and other public and private organizations. Protection of all workers and patients in health care settings is one important goal of these efforts.     

The HIV-epidemic among drug addicts in Norway

Up to 1996, 368 persons in Norway (population 4.3 million) had been reported as being HIV-infected because of intravenous drug use. 72 of these had developed AIDS and 59 had died from AIDS. HIV-testing is very common among drug users in Norway and new cases are rarely detected at treatment centres or at autopsy. Some 15-30 cases may still be undiagnosed. HIV spread very rapidly among drug users in Norway in 1984 and 1985, by around 100 new cases per year. Since then, the annual incidence has decreased from 30-40 cases in 1986 to 10-15 in 1995. Although the drug users seldom shared syringes even before the advent of the HIV epidemic, we believe that the public rehabilitation programmes, needle exchange programmes and health information have contributed to control HIV in this group. We expect an annual incidence of 10-15 cases the next five years.     

Association of non-acquired immunodeficiency syndrome-defining cancers with human immunodeficiency virus infection

Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for an association with Hodgkin's disease, with lower relative and absolute risks than for non-Hodgkin's lymphoma. Anogenital intraepithelial neoplasia also appears to be HIV associated, but increases of invasive disease are still uncertain for both cervical and anal cancers. Various studies have suggested associations with testicular seminoma, multiple myeloma, oral cancer, and melanoma, but the data are inconsistent. Leiomyosarcoma and benign leiomyomas have increased in incidence in HIV-infected children but are unusual in HIV-infected adults. Conjunctival carcinoma is seen in HIV-infected individuals in sub-Saharan Africa but it is uncommon in Western countries. Most other cancers do not seem to have increased incidences in HIV infection. The etiologic mechanisms of HIV-related cancer likely differ among these diverse cancers and do not globally increase cancer risk.     

Tuberculosis. The old and the new

BACKGROUND: The overall incidence of tuberculosis (TB) in the general Australian population is low and has been stable over the past 10 years. The incidence is, however, much higher in certain subgroups of the population and these include overseas-born people (especially from countries in Asia) and Aboriginal and Torres Strait Islander populations. Other groups regarded as at increased risk of TB are nursing home residents, the homeless, prison populations and immunosuppressed patients, especially those who are HIV positive. OBJECTIVE: Patients regarded as high risk should be investigated promptly if they present with signs or symptoms suggestive of TB. DISCUSSION: The best method of preventing the transmission of TB and preventing the emergence of drug resistant strains of the organism are by ensuring that sputum smear positive patients are isolated till non-infectious; that any patient with TB receives prompt and adequate treatment; that all patients with TB comply with a full course of treatment till cured: and that contact tracing is undertaken to detect newly infected patients so as to offer chemoprophylaxis and to detect previously unrecognised cases.     

Shock. Physiological principles for resuscitation

As the epidemic of the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa enters its second decade, much has been learned about the distribution and determinants of the disease and its causative agent, the human immunodeficiency virus (HIV). Over 6 million people, or 2.5% of the adult population, are thought to be infected with HIV. The distribution of HIV is largely determined by sexual behavior; as for other sexually transmitted diseases, the characteristics of sexual networks determine the extent and rate of spread of HIV. Female sex workers and their male clients are at high risk for HIV and have been important in initiating the epidemic in many African countries. The dynamics of HIV in the rest of the population are complex; men with multiple sexual partners are largely responsible for transmission of HIV to women in the general population. Other sexually transmitted diseases and lack of male circumcision may increase the probability of transmission of HIV during sexual intercourse and probably are partially responsible for the rapid diffusion of HIV in Africa. Interventions among high-risk groups are needed, but they must be accompanied by attempts to induce behavior change among men and women in the general population. Epidemiologic studies of the determinants of sexual behavior and sexual contact patterns, as well the design and evaluation of interventions, are urgently needed. Key areas for development are the study of behavioral exposures and outcomes, the evaluation of interventions, developing new methods for conducting interventions in resource-poor environments, and increasing the number of African scientists with the skills and resources to conduct epidemiologic studies.     

One world, one hope: the cost of providing antiretroviral therapy to all nations

OBJECTIVE: To estimate the potential direct cost of making triple combination antiretroviral therapy widely available to HIV-positive adults and children living in countries throughout the world. METHODS: For each country, antiretroviral costs were obtained by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive persons accessing therapy. Per capita antiretroviral costs were computed by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita. All values are expressed in 1997 US dollars. RESULTS: The potential cost of making triple combination antiretroviral therapy available to HIV-positive individuals throughout the world was estimated to be over US$ 65.8 billion. By far the greatest financial burden was on sub-Saharan Africa. The highest per capita drug cost in this region would be incurred in the subregions of Southern Africa (US$ 149) followed by East Africa (US$ 116), Middle Africa (US$ 44), and West Africa (US$ 42). In the Americas, subregional data indicated the highest per capita drug cost would be in the Latin Caribbean (US$ 22), followed by the Caribbean (US$ 17), Andean Area (US$ 7), the Southern Cone (US$ 6), North America (US$ 6), and Central American Isthmus (US$ 5). In Asia and Europe the percentage of the GNP necessary to finance drug therapy was less than 1% in most countries examined. CONCLUSION: Our results demonstrate that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources.     

Demographic impact of the HIV epidemic in Thailand

OBJECTIVE: To assess the impact of the HIV epidemic on the demographic development of the Thai population. METHODS: A deterministic mathematical model was used to predict simultaneously epidemiological and demographic processes. Partial differential equations express the relationships between biological, behavioural and demographic variables. The model allows the evaluation of different sexual mixing patterns, variable transmission probabilities and incubation times. Validity analysis was performed by generating antecedent HIV prevalence patterns among military recruits and pregnant women. RESULTS: On the national level in Thailand we predict that the cumulative number of people in Thailand with HIV infection will exceed 1 million by 1999; the number of deaths from AIDS will be 555000 by the year 2000 but will not reach 1 million until after the year 2014. Without the HIV epidemic the population growth rate was estimated at 1.3% per annum until 1995, after which a decline to 0.9% by 2005 is predicted. The HIV epidemic started to affect the population growth rate by 0.026% per year in 1991, and the difference is predicted to rise to about 0.12% per year during the period 1995-2000, to decline to 0.06% in 2005 and then to disappear. In the mid-1990s HIV affected mainly the 15-35-year-old age group, but over time younger and older age groups have been affected as a result of perinatal transmission, and a decline in fertility as well as ageing of the 15-35-year-old birth cohort. Because of HIV, in 2000 there will be 612000 (1%) fewer people than expected and by 2010, 1140000 fewer (1.6%). We predict that the demographic impact of the HIV epidemic in the northern region will follow the same pattern, but with greater severity. Here, the effect on the population growth rate and the population age distribution is likely to be twice as high as at the national level. CONCLUSIONS: It is estimated that 1 million Thais will be infected with HIV by the year 2000 and an almost equal number will have died of AIDS by the year 2014. Although these numbers seem high, their direct and indirect effects on the demographic structure of the Thai population are small. However, at a regional level, for example in the northern region, the effect of the HIV epidemic may be more severe.     

Harm reduction in the hills of northern Thailand

The human immunodeficiency virus (HIV) pandemic has swept through injecting drug user (IDU) communities around the world. Once HIV is present in an IDU community, seroprevalence rates escalate rapidly unless immediate and comprehensive prevention methods are put in place. Such measures often include providing IDUs with sterile injecting equipment and dispensing methadone or other opiate substitution formulas. These measures fall under the rubric of harm reduction-an attempt to reduce the harm to drug users, their families, and communities, including preventing or limiting the transmission of HIV and other blood-borne viruses. In Thailand, HIV-1 spread rapidly among IDUs with seroprevalence rates jumping from 1 to 40% in the space of a year. Current incidence rates are estimated at 11 per 100 person years. This paper describes the establishment and implementation of needle and syringe exchanges among injecting drug users in nine Hilltribe communities in Northern Thailand. The exchanges have been operating for between 1 and 3 years and have been effective in limiting the transmission of HIV within these small communities. The needle and syringe exchanges are run by indigenous staff with the cooperation of the community and provide a good example of the feasibility of establishing locally-run, community-based harm reduction programs.     

The efficiency of acute infection of CD4+ T cells is markedly enhanced in the setting of antigen-specific immune activation

Human immunodeficiency virus (HIV) disease in sub-Saharan Africa generally differs from that observed in the United States and other developed countries in that the risk of seroconversion after exposure is greater and the rate of disease progression to AIDS and death is faster. One theory that could in part explain this difference is the increased state of immune activation associated with a relatively high rate of parasite infestation and other infections among inhabitants of these regions. Using a model based on the cellular microenvironment of lymphoid organs, the role of exposure to HIV during a state of antigen-specific immune activation was investigated. Dendritic cells and CD4+ T cells are the major cellular components of the paracortical region of lymphoid tissue, the primary site of HIV replication. We analyzed cocultures of HIV-pulsed dendritic cells that had matured in the presence of tetanus toxoid and CD4+ T cells before and after inducing an antigen-specific response by in vivo immunization with tetanus toxoid. During antigen-specific immune activation, 100 times less HIV was needed to initiate a productive infection. These findings provide a model system to further delineate the relationship between immune activation and the propagation of HIV infection and suggest a mechanism for the epidemiologic observations of an increased ease of developing HIV infection and faster progression for HIV disease in geographic areas where immune activation is prevalent.     

Trends in human immunodeficiency virus infection prevalence in homosexual/bisexual men in Madrid (1986-1995)

BACKGROUND: We analysed the trend in seroprevalence for human immunodeficiency virus (HIV) in homosexual or bisexual men who voluntary requested the test in a sexually transmitted disease/HIV clinic in Madrid. PATIENTS AND METHODS: We studied 5,424 homo/bisexual non-injecting drug user (non-IDU) men, who came for the first time since 1986 to 1995. We analysed the HIV seroprevalence taken into account the year, age and exchange of sex by money. A hundred and thirty-six IDU homo/bisexual men were also attended during the same period and they were compared with non-IDU. RESULTS: HIV seroprevalence among the 5,424 non-IDU homo/bisexual men were 20.2%, rising from 19.6% in 1986 to 29.6% in 1990. After then, the trend decreased to 15.3% in 1995 (chi 2 for trend, 66.8; p < 0.0001). Average age was three years higher among seropositives (p < 0.0001), and showed an upward trend from 29.9 in 1986 to 34.6 in 1995 (p = 0.0059). Seroprevalence among homosexuals younger than 25 fell in the last years. One percent of individuals had ever practiced the prostitution. They were younger (average age, 27.6), and their HIV seroprevalence were 25.9%. A hundred and thirty-six IDU homo/bisexual men were also attended for the first time, being 2.4% of overall homo/bisexual men. They had a higher seroprevalence (48.5%) than non-IDU (p < 0.0001), and did not show any significative time-trend. CONCLUSIONS: A favourable evolution can be observed in HIV seroprevalence among homo/bisexual from Madrid, Spain, men who came to be tested, especially among the youngest. Prevention programs should make an effort to maintain this trend.     

Meningococcal disease in Africa

Neisseria meningitidis (the meningococcus) is responsible for endemic and meningococcal disease in Africa. Meningococci are placed into 12 serogroups based on their capsular polysaccharide antigens. Group-B meningococci are responsible for sporadic endemic disease. In the meningitis belt of sub-Saharan Africa, the large spreading epidemics which occur every 5-10 years are usually caused by group-A meningococci, with attack rates of 400-500/100,000 population. In the last epidemic, infection spread from the original meningitis belt to Kenya, Uganda, Rwanda, Zambia and Tanzania. Most cases of meningococcal disease are of meningitis and meningococcal septicaemia is a rare presentation except in South Africa. It is important to exclude meningococcal septicaemia since this carries the highest mortality (up to 75%). Treatment involves intravenous chloramphenicol (or intramuscular, oily chloramphenicol), a drug which is preferable to penicillin because penicillin-resistant meningococci have already emerged in Africa. Dexamethasone treatment of meningococcal meningitis is unproven and may even be deleterious in developing countries. Prevention of epidemic meningococcal disease could be achieved by mass vaccination with protein-conjugate, group-A and -C polysaccharides, but these new vaccines are likely to be expensive.