D 2 Technological risks
D 3.2.1 HIV/AIDS
In the 1960s, the battle against infectious disease had reached a pinnacle of success, with smallpox eradi-cated by WHO programs and polio and tetanus un-der control by efficient vaccination. However, the limits of infection control were already becoming vis-ible then. They were apparent in the failure of the WHO program to eradicate malaria and in the be-ginning growth of bacterial resistance. In 1979 one of the leading medical journals published an editorial titled “Pandora’s Box reopened?”. The author pre-sented an until then hypothetical scenario of a global resurgence of epidemic diseases. The emergence of
‘new’ epidemics was feared (Schwartz, 1979). By 1983 it was plain that a new epidemic disease of pan-demic potential had indeed emerged, caused by the human immunodeficiency virus type 1 (HIV) and lethal with great certainty.
HIV viruses are retroviruses. They are named af-ter an enzyme (reverse transcriptase) which they contain. Retroviruses were known since 1910 from ani-mal experiment systems, where they were identi-fied as tumor-inducing agents (Peyton Rous, 1966 Nobel Prize). Human-pathogenic retroviruses were described for the first time in 1980 by Gallo (human T-cell lymphotropic virus, HTLV-1 to HTLV-3). Ini-tially, only their tumor-inducing effect was recog-nized (adult T-cell leukemia in the Caribbean popu-lation). It was only later that HTLV-3, renamed HIV-1 (Brun-Vezinet et al., HIV-1984; Gallo and Reitz, HIV-1985), was identified as the pathogen of the AIDS syn-drome. Current knowledge suggests that the HIV-1 infection (termed HIV in the following) had already emerged in the 1940s through a viral change of host from animals (chimpanzees, Central Africa) to
hu-mans by genetic adaptation of the pathogen to the new host (Williams et al., 1983; Zhu et al., 1998).
Of the above human retroviruses, only HIV has at-tained global relevance. It infects cells of the immune system in the blood, lymphatic nodes and spleen.This takes place exclusively via direct contact with infect-ed blood or other infectinfect-ed body fluids. The viral genome, which contains ribonucleic acid, is tran-scribed by viral reverse transcriptase and integrated as a provirus in the genome of the host cell. After HIV infection, the immune reaction of the organism follows a characteristic cyclical course marked by an interplay between virus and immune system. Here both the viral load and the number of immunocom-petent cells in the blood vary intermittently (anti-genic drift), while on the viral side characteristic shifts occur in the antigenic effect of the virus which are partially caused by the formation of HIV mutants (antigenic shift). Thus after infection an evolutionary process between virus and immune system deter-mines the period that elapses between infection and the onset of symptoms of disease (latent period).
Throughout this latent period, the immune system is increasingly weakened by a steady loss of immuno-competent cells. The immune response of the organ-ism is increasingly circumvented by mutation and in-tegration of the virus in the host genome. A crucial aspect is that the weakening of the immune system leads to an increase of so-called opportunistic infec-tions by agents that are normally not pathogenic to humans but if untreated are 100% lethal to people suffering from AIDS (e.g. Pneumocystis carinii).
The HIV/AIDS pandemic is comprised of many regional epidemics. These differ considerably in terms of time of commencement, main transmission pathways and development of new infections. Widely differing damage potentials are thus apparent in dif-ferent parts of the world (Table D 3.2-1). This is con-ditioned by social patterns of behavior (e.g. drug abuse, promiscuity) and - of fundamental importance - major differences in the capacity to educate the public and to implement self-protection measures.
This is very clear for women in Asian and African countries. WHO estimates (WHO, 1997a) suggest that 30.6 million people are infected with HIV or al-ready suffer AIDS worldwide. Of these, 68% live in Sub-Saharan Africa and a further 24% in South Asia, South-East Asia and Latin America. 41% of HIV-in-fected people are women.
Owing to exclusively anthropogenic factors, the propagation pattern of the disease is country-specif-ic, regionally different and modifiable. Apart from transmission by banked blood, it is almost exclusive-ly transmitted by unprotected sexual contacts (in particular where there is promiscuity and prostitu-tion) and by the joint use of injection syringes. In
North America and Europe, mainly high-risk groups have contracted the disease in which these patterns of behavior often occur in combination (homo- and bisexual men, drug addicts). In North Africa, by con-trast, due to regional socio-cultural features one or several of these forms of behavior are also wide-spread among parts of the heterosexual population (WHO, 1997b).
In Europe and North America, the number of peo-ple infected with HIV and suffering AIDS peaked at the end of the 1980s, leveling off in 1993/94 at a prevalence of 0.3–0.6% (Fig. D 3.2-1). This success was brought about by preventive measures such as education and advice on risks and protection options, medical care for those affected, effective treatment of secondary diseases and infections and strict con-trols on blood products. The present course of the pandemic in Europe and the USA illustrates that the spread of the virus can in principle be contained by means of deploying and further developing these measures. Since 1996, mortality has even fallen dis-tinctly in Europe and North America. This is certain-ly maincertain-ly due to the introduction of effective thera-pies, in particular therapies combining chemothera-peutic agents with protease inhibitors. However, in-fection incidence is not dropping to the same degree.
Indeed, in the USA, for instance, the share of hetero-sexual transmission is slowly rising (Fig. D 3.2-2).
In a global perspective, the damage caused by the HIV/AIDS pandemic is on the rise. With an estimat-ed 16,000 new infections per day, more than 40 mil-lion cases are forecast for the year 2000 (WHO, 1997a). The epidemic is currently coming to a head in Sub-Saharan Africa (Table D 3.2-1). The infection rate among adults there has risen to 7.4%. In individ-ual countries such as Uganda, severe societal changes have already occurred (age structure, decimation of the economically and socially active population). In some countries, AIDS has caused life expectancy to plummet, for instance by 22 years in Zimbabwe (UNDP, 1998). In the most densely populated regions of the world, such as South Asia, South-East Asia and China, the infection only began to spread at the end of the 1980s, and is developing a great regional dy-namism. In Vietnam, for instance, the prevalence of HIV escalated within two years from 1% to 44% in certain groups of society. In India, the number of HIV/AIDS cases is currently estimated at 3–5 mil-lion. Among truck drivers in Madras, who systemati-cally infect themselves through prostitutes, a growth in the infection rate was observed from 1.5% in 1995 to 6.2% in 1996.
There are three prime biological risk amplifiers for HIV infection: latency, genetic instability and co-infection.
84 D Risk potentials of global change
Latency
Due to its 10-year latency (the period between HIV infection and clinical manifestation of the AIDS syn-drome) the virus is able to spread unnoticed if HIV infestation is not monitored adequately (a transcon-tinental prevalence of HIV already existed long be-fore the first epidemiological registration of the AIDS syndrome). It follows that exclusively register-ing the incidence of AIDS cases while not registerregister-ing HIV infections in the latency stage leads to a greatly delayed registration of new epidemiological develop-ments. The ‘time window’ between infection and de-tectability of antibodies amounts to several weeks.
This is why schemes for monitoring banked blood and blood products that are based on detecting HIV antibodies continue to be unable to promise absolute safety.
Genetic instability
The genetic instability of the retroviruses is an out-come of their propensity for aberrations in the two central transcription processes in the infection cycle (reverse transcription of the RNA genome and tran-scription of proviral DNA) and of DNA
recombina-tion events among subtypes within an infected or-ganism. The following brief listing of the conse-quences that genetic instability has for the persisten-cy of the virus illustrates impressively that high pri-ority continues to need to be given to basic retrovirus research. Genetic instability permits
• Rapid adaptation of the virus to changing selec-tion pressure;
• Circumvention of effective long-term natural im-munity through rapid changes of immunogenic vi-ral epitopes (components of the virus membrane that stimulate the immune system);
• High probability of the formation of resistance against antiviral drug therapies, and hampered de-velopment of vaccines;
• Transmission across the species barrier (e.g. be-tween apes and humans);
• Further development of the virus and formation of new subtypes with negatively modified charac-teristics (e.g. increased virulence through changed or extended cell specificity).
Table D 3.2-1
Regional HIV/AIDS statistics and attributes.
Source: UNAIDS, 1997
Region Outbreak HIV/AIDS Prevalence Proportion HIV-negative Main
of epidemic infected among of women children having transmitters
adults adults infected lost one or both
and children [%] [%] parents
to AIDS
Africa/ late 1970s, 20,800,000 7.4 50 7,800,000 Heterosexuals
Sub-Sahara early 1980s
North Africa, late 1980s 210,000 0.13 20 14,200 Intravenous drug
Middle East users and addicts
South and South- late 1980s 6,000,000 0.6 25 220,000 Heterosexuals
East Asia
East Asia, late 1980s 440,000 0.05 11 1,900 Intravenous drug
Pacific users and addicts;
homosexuals
Latin America late 1970s, 1,300,000 0.5 19 91,000 Homo- and
early 1980s heterosexuals
Caribbean late 1970s, 310,000 1.9 33 48,000 Heterosexuals
early 1980s
Eastern Europe, early 1990s 150,000 0.07 25 30 Intravenous drug
Central Asia users and addicts
Western Europe late 1970s, 530,000 0.3 20 8,700 Intravenous drug
early 1980s users and addicts
North America late 1970s, 860,000 0.6 20 70,000 Homo- and
early 1980s heterosexuals
Australia, late 1970s, 12,000 0.1 5 300 Homosexuals
New Zealand early 1980s
Total 30,600,000 1.0 41 8,200,000
Accidents HIV Infection Cancer
Heart disease
Suicide Homicide
Liver disease Stroke Diabetes
Year
Deaths per 100,000 Population
1982 1983198419851986 1987 1988 1989 19901991 1992 1993 1994 1995 1996 0
5 10 15 20 25 30 35
Figure D 3.2-1
Development of deaths caused by HIV in the USA (men, age group 25–44).
Source: CDC, 1996
Homosexual contact, men
Homosexual contact and injecting drug use Injecting drug use
Heterosexual contact
Year of Report
Percent of Cases
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 0
10 20 30 40 50 60 70 80
Figure D 3.2-2
Development of HIV infections in various risk groups in the USA.
Source: CDC, 1997
86 D Risk potentials of global change
Co-infection
The weakening of the immune system by HIV leads not only to an increase of opportunistic infections, but also favors ‘old’ pathogens, particularly tubercu-losis.This is the most frequent cause of death of HIV-infected individuals (40% in North Africa, and 30%
of all HIV cases). Two thirds of all tuberculosis cases in the world are located in Asian countries, with their large conurbations and rising levels of HIV infection.
In fact, here the two epidemics combine synergisti-cally, which not only considerably amplifies the mag-nitude of damage of HIV infection, but is presently also massively influencing the epidemiology of tu-berculosis.
It has recently become apparent that the strong spread of conventional sexually transmitted diseases (STDs), e.g. syphilis and gonorrhea, enhances the probability of HIV virus transmission by a factor of 10–100. Owing to their inadequate treatment in de-veloping countries, STDs thus constitute a key mech-anism in the rapid heterosexual spread of AIDS. A study in Mwanza, Tanzania, observed a 42% drop in the rate of new HIV infections in a rural population thanks to the early treatment of STDs (WHO, 1997b).
The anthropogenic risk amplifiers lead to a high division rate, with a corresponding selection pressure among HIV subtypes. This in turn harbors a biologi-cal risk potential, for in view of the known muta-genicity of the virus it is possible that new subtypes can form with modified virulence behavior. Such a scenario also entails the possibility of new waves of infection in countries where the incidence of infec-tion has currently been brought under control.
Measures
The present anti-retroviral drug therapy is undoubt-edly a breakthrough, as it considerably reduces the number of opportunistic infections. It costs at least US-$ 12,000 per person annually and is thus not ac-cessible to most of the HIV-infected people of this world. In a North African country, in which typically approximately 10% of the population is infected with HIV, only about US-$ 10 is spent for health care per inhabitant and year. At the current cost of therapy, treating the HIV-infected inhabitants alone would exceed the health budgets of these countries by a fac-tor of more than 100.
Thanks to extensive epidemiological studies, the transmission pathways of HIV/AIDS are now well known and an array of effective preventive measures have proven themselves in practice. However, in many countries a lack of effective implementation remains. In India, health system expenditure is ex-pected to rise by 30% by the year 2010 if the spread of HIV infection continues at its present rate
(Ainsworth, 1998). Evidently the way in which the HIV/AIDS risk is handled differs widely around the world and requires regionally appropriate strategies.
It is essential that states set priorities. Developing countries should concentrate their scarce resources for containing the AIDS epidemic upon prevention, particularly upon developing efficient infection pre-vention. Here tools of global relevance include statu-tory regulations aimed at prevention, educating the public about the risks of infection and the options for protection in order to preclude new infection, and advice aimed at strengthening the responsible behav-ior of individuals. Programs that have concentrated preventive measures upon those at a high risk of transmission have proven highly effective (e.g. use of condoms among prostitutes in Nairobi or Thailand) and should therefore have priority (Ainsworth, 1998). Epidemiological surveillance of the HIV/AIDS epidemic that identifies new and old high-risk groups and is continuous and as compre-hensive as possible is an absolutely essential precon-dition to effective countermeasures of this kind.
The Centers for Disease Control and Prevention (CDC) in Atlanta, USA offer an excellent example of possible nationally and internationally institution-alized surveillance tools with regard to new and al-ready existing epidemiological risks. CDC routinely collates surveillance data from medical reports that it receives from local health authorities and checks data quality by comparing different sources. It is thanks to CDC that it was rapidly understood that the newly observed symptoms were in fact a spread-ing epidemic syndrome. CDC defined AIDS in 1981 on the basis of the occurrence of rare opportunistic illnesses and infections (e.g. Kaposi’s sarcoma and Pneumocystis carinii pneumonia) in groups of young, homosexual men on the American west coast.
Mandatory registration was introduced in the USA for newly diagnosed AIDS cases, involving the preparation of uniform case reports. These contain data on demography, the name of the diagnosing lab-oratory, the risk history and clinical status of the pa-tient and information on therapy. Studies have shown that 90% of all illnesses meaning AIDS under the CDC definition are actually registered. On the basis of the almost complete epidemiological data and the transmission pathways deduced from these, the pub-lic health services of the USA were already able to is-sue recommendations for prevention of infection in 1983.
The example of the CDC illustrates clearly the key position that attaches to specialized, internationally operating surveillance institutions that use the analy-sis of epidemiological data at a high scientific level and with high efficiency to exercise control functions.
Such institutions are successful in controlling global
risks if they form an interface between basic scientif-ic research and national and supranational authori-ties.
In structurally weak countries, in particular, devel-oping and implementing the epidemiological surveil-lance of preventive measures and research projects requires support by international institutions or bi-lateral assistance. The global monitoring of the HIV/AIDS pandemic is conducted by WHO and UNAIDS (Joint United Nations Programme on AIDS). Epidemiological data are notified by region-al offices and by the heregion-alth ministries of the member states. Under WHO’s Global Programme on AIDS (GPA), financial assistance was provided for activi-ties against AIDS in more than 150 countries.The ob-jectives were to establish national AIDS programs, to improve management capacities and to coordinate international research tasks.The program terminated formally with the establishment of UNAIDS in 1996.
WHO supports and collaborates with UNAIDS through its Office of AIDS and Sexually Transmitted Diseases (ASD), which was also established in 1996.
UNAIDS further receives support from UNDP, UNICEF, UNESCO, UNFPA and the World Bank.
WHO’s global epidemiological surveillance is de-pendent upon the completeness and reliability of the data delivered by the national monitoring systems.
Estimates of infection rates in regions without effec-tive infectious disease surveillance are based on model calculations which, in turn, are based on infor-mation from countries which have relatively compre-hensive data. WHO nonetheless found itself com-pelled to correct its estimate of HIV/AIDS infections for the year 1996 upwards from 22.6 to 27 million and its estimate of new infections in 1996 from 3.1 to 5.3 million. This was mainly due to the erroneous esti-mate of the development in Sub-Saharan Africa. The model calculation had been based on relatively ex-tensive data from Uganda, where in past years infec-tion rates have been brought under control by means of successful preventive measures. However, the cal-culations were confounded by the situation in Nige-ria and South Africa, where robust data have only re-cently become available (WHO, 1997a). These events illustrate that the collection of complete epidemio-logical data is indispensable for high-quality risk characterization.
D 3.2.2
‘Hong Kong bird flu’ (avian influenza)
Influenza viruses comprise a large group of different subtypes, which cause grippal clinical pictures with infections of the upper respiratory tract through to severest lethal pneumonia. Humans are infected by
types of the influenza A and B viruses. Influenza A further infects pigs, horses, marine mammals and birds. Influenza A subtypes differ by structures on their surface that have been identified biochemically as glycoproteins. The influenza subtypes are named according to these glycoproteins, which function as binding proteins for the attachment of the virus to the body cells that it infects. They thus determine the spread of the pathogen in the organism, its virulence and consequently its hazard potential. The hemag-glutinins H1–H15 and neuraminidases 1–9 are such glycoproteins. In birds, all of these types can lead to infection. In humans, epidemics are caused by the in-fluenza A subtypes H1, H2 and H3 and by inin-fluenza B. The subtypes H5 and H7 occasionally lead to very severe epidemics in birds, particularly chickens and turkeys.
Influenza A infections have a relatively high cata-strophic potential, as they very regularly lead to ma-jor epidemics or pandemics at intervals of about 15–20 years. In the past these have been associated with a widely varying and partly high mortality rate, and thus constitute a major risk potential. Larger epi-demics have been attributed retrospectively to dif-ferent, mostly completely unknown influenza A sub-types. The influenza A H3N2 subtype was thus iden-tified for the first time in the 1968 epidemic in Hong Kong. Influenza A H2N2 was identified and charac-terized for the first time as a causal agent in connec-tion with another epidemic in 1957. Phylogenetic studies have shown that these newly formed subtypes came from avian influenza A and entered the human population after recombination with a human in-fluenza virus strain (Webster and Laver, 1972;
Influenza A infections have a relatively high cata-strophic potential, as they very regularly lead to ma-jor epidemics or pandemics at intervals of about 15–20 years. In the past these have been associated with a widely varying and partly high mortality rate, and thus constitute a major risk potential. Larger epi-demics have been attributed retrospectively to dif-ferent, mostly completely unknown influenza A sub-types. The influenza A H3N2 subtype was thus iden-tified for the first time in the 1968 epidemic in Hong Kong. Influenza A H2N2 was identified and charac-terized for the first time as a causal agent in connec-tion with another epidemic in 1957. Phylogenetic studies have shown that these newly formed subtypes came from avian influenza A and entered the human population after recombination with a human in-fluenza virus strain (Webster and Laver, 1972;