VIRUSMYTH HOMEPAGE

PRESIDENTIAL AIDS ADVISORY PANEL REPORT

SURVEILLANCE
Chapter 3

The discussions on surveillance occupied a significant part of the deliberations of the panel with particular emphasis placed on the availability of surveillance data from South Africa and elsewhere and the ability of these data to demonstrate the presence and magnitude of an AIDS epidemic. Several panellists insisted that the unavailability of direct statistical data on how many South Africans have contracted AIDS or have died from AIDS as distinct from the question of how many South Africans were HIV-antibody positive bedevilled any proper discussion on AIDS and its impact on South Africa. These questions were critical given the arguments already advanced in Chapter 2 of this report on the cause of AIDS or whether an HIV antibody positive test could be declared indicative of infection by HIV in the absence of isolation of the virus from seropositive patients. Several panellists argued that the answers to these questions would fundamentally influence the debates as well as any recommendations that could be made on the issue of surveillance.

3.1 What are the questions and issues?

Some key discussion points that were raised with respect to HIV and AIDS surveillance include:

• Whether the AIDS epidemic in South Africa is indeed a reality
• Why the pattern of the epidemic differs so significantly between Africa and Europe/USA
• Whether available data sufficiently demonstrate an AIDS epidemic
• What the standard AIDS-defining criteria are in South Africa
• How reliable serological tests are in assessing HIV
• What elements are necessary to strengthen surveillance in South Africa so as to better plan for the impact of the epidemic

3.2 Overview on the necessity for surveillance

There was widespread agreement that surveillance is a necessary tool for understanding the AIDS epidemic. However, there were two opposing schools of thought on the issue of HIV surveillance. One group subscribed to the argument that HIV surveillance is an exercise in futility as it has not been proved that an individual that is HIV-positive will develop AIDS. Thus a more useful marker is AIDS disease. The opposing school of thought argued for the importance of conducting both HIV and AIDS surveillance. They argued for observed correlation between HIV-positive status and AIDS disease.

Dr Gayle gave an overview of the general principles surrounding current practice in the surveillance of HIV and AIDS as used by agencies such as the CDC, WHO and UNAIDS. She described the history of HIV surveillance in the USA as having started with AIDS case surveillance and case definitions for AIDS on the basis of a cluster of illnesses and symptoms. At that stage, AIDS had been identified mainly in homosexual men, haemophiliacs and other recipients of blood products, intravenous drug users, their partners and infants.

These profiles contributed to the identification of the main modes of transmission – sexual contacts, blood and blood products, perinatal transmission from pregnant women to their infants and the observation of ‘slim’ disease around Lake Victoria.

It was pointed out that the main components of current HIV and AIDS surveillance include:

1. Serological surveillance, the key components of which include sentinel antenatal testing for HIV prevalence using the ELISA HIV-incidence testing (still new but under development are the serological testing algorithms for recent HIV seroconversion – STARHS), as well as testing among TB patients, patients with sexually transmitted diseases and among high-risk population groups
2. Behavioural surveillance for programme monitoring
3. AIDS and HIV mortality surveillance.

Dr Gayle described the purposes of surveillance as being to estimate the magnitude of the epidemic and assess trends.

There was a debate arising largely from the school of thought that questioned the causal link between HIV and AIDS and around the philosophy underlying the current public health surveillance practice. Other concerns that were debated included whether surveillance tools (such as the serological ELISA test) are sufficiently sensitive and specific to accurately detect true HIV-positive status; whether measuring sexual behaviour, for instance, is informative, since the causal link between HIV and AIDS is still in question, and whether mathematical models are reliable predictors of epidemics.

3.3 South African epidemic – Fact or fiction

There were differences of opinion on whether there is an AIDS epidemic in South Africa. Those from the school of thought that argues that HIV does not cause AIDS also argued the futility of discussing an HIV epidemic, as they do not believe that HIV causes AIDS. There were some in this latter group who even argued that there was insufficient evidence to support the notion of an AIDS epidemic in Africa.

This argument was refuted with HIV-prevalence statistics from the South African Department of Health’s national antenatal survey, showing that HIV prevalence amongst women attending antenatal clinics has increased exponentially from 0.73% in 1990 to 22.4% in 1999. Dr Abdool-Karim, preferring to use his own study data, similarly showed antenatal prevalence statistics from Hlabisa (KwaZulu-Natal), which rose from 4.2% in 1992 to 30% in 1998. He indicated that this increase was characteristic only of the Southern African epidemic. He noted the high prevalence rates among young women aged 20 to 24, by showing the rise in 1992, 1995 and 1998 from 7%, 21% and 39% respectively. Data were also presented from Chris Hani Baragwanath Hospital that showed an increase in the incidence of HIV from 26% in 1997 to 30% in 1999 using the unlinked HIV tests.

HIV indicator diseases such as other sexually transmitted infections (STIs) and TB are seen to be useful markers of the burden of HIV-associated disease. Studies show that STIs make individuals more infective and more susceptible to HIV infections. Data obtained from a community-based randomised trial in Mwanza, Tanzania substantiate this position, demonstrating that improved treatment of STIs lowered HIV incidence by 42%.

3.3.1 AIDS mortality

On the issue of whether there is an AIDS epidemic in South Africa, Dr Rasnick argued that no evidence on AIDS had been presented to demonstrate an AIDS epidemic. He emphasised that the evidence required was "not HIV, not antibodies to HIV but people who have died from AIDS".

Prof Duesberg contended that scientists and non-scientists alike typically diagnose an infectious epidemic on the grounds of a sudden increase in the morbidity and mortality of a given population. In the case of an epidemic, the general trend is that the numbers of the affected population would decline significantly, and a relatively immune population would emerge and would be resistant to the new epidemic for a considerable length of time.

It was noted that AIDS is not a notifiable condition in South Africa and thus reliable statistics on AIDS do not exist. Other panellists argued that there is an HIV epidemic in South Africa. In support of his argument, Dr Abdool-Karim cited data from the South African Demographic and Health Survey, which suggests that while infant mortality was on the decline in the mid-1990s, an upward trend in infant mortality had been observed in the 1998 survey.

Further supporting data for this argument were presented from a study conducted at King Edward VIII Hospital in KwaZulu-Natal, showing a 60% death rate among children with HIV infection who were followed up over a two-year period. He indicated that the case fatality rates among HIV-positive infants had increased from 4.5% to 22.6% over a four-year period, and that studies at Chris Hani Baragwanath Hospital had shown that HIV-positive infants had a mortality rate that was double that of infants who were HIV-negative.

Dr Makgoba expanded on this theory by presenting data that demonstrated that the infant mortality rate among HIV-negative infants in Soweto was 17 per 1 000 live births, in comparison with 362 per 1 000 live births among HIV-positive infants. (The national infant mortality rate is 42 per 1 000 live births.) He further discussed paediatric mortality research conducted at Johannesburg General Hospital by Cooper, which showed that mortality trends had remained more or less constant between 1991 and 1996. After 1996, the HIV positivity rate had increased to 48% and continued to rise.

Dr Mhlongo pointed out that increased access to healthcare facilities and the easing of travel restrictions from rural to urban areas as a result of the recent changes in the political climate in South Africa were bound to lead to changes in the profile of patients in clinics and hospitals. Free access to healthcare facilities by pregnant women enabled impoverished people to seek medical attention in hospitals that would previously have denied them access.

With respect to adult mortality, Dr Makgoba presented data from the South African Department of Home Affairs that the Medical Research Council had received only a few days prior to the second meeting of the panel. It was for that reason that he could not make the data available to other members of the panel prior to his presentation. The data had been processed by the Medical Research Council and modelled by the Actuarial Society of South Africa (see Appendix 2). Dr Makgoba made the following observations on the basis of the data:

• The groups most affected by AIDS range between the ages of 20 and 40, with a peak in deaths at the age of 30 for women and 35 for men.
• Total deaths per annum in South Africa for this age group increased by 23% between 1997 and 2000.

He further presented data for the period from April 1999 to May 2000, suggesting an almost exponential rise in AIDS deaths over the four quarters.

The Actuarial Society projected deaths using two scenarios: deaths expected in the absence of HIV and those that had actually occurred. The conclusion drawn was that the deviation of mortality trends from expected trends could be accounted for by HIV/AIDS.

Prof Whiteside confirmed Dr Makgoba's observations and added that in a recent census conducted in Malawi, two million people could not be accounted for. Dr Chalamira-Nkhoma from Malawi shared similar observations, suggesting that HIV would have contributed to a decrease in the growth rate from 3.2% to 1.9% in the 1998 census.

Prof Whiteside further argued that similar observations had been made in the Rakai district of Uganda where the population pyramid had hollowed out. His concluded that these deaths could only be attributed to AIDS deaths.

Dr Fiala and other panellists responded to the South African mortality data presented by Dr Makgoba with the argument that they were unable to analyse and adequately comment on the statistics as they had not been presented with the information prior to the verbal presentation (in the second panel discussions) and had therefore not been afforded the opportunity to apply their minds to the data. Dr Bialy's views were that if South Africa had not already determined the epidemic before external influence, the observations made on the epidemic might not be real. He suggested that Dr Duesberg's hypothesis of a chemical causal agent for AIDS be closely examined.

3.4 Epidemiological Theory of Causal Inference

The concept of causal inference is critical to epidemiological practice because theory on causal inference in the context of a particular disease sets ‘standards’ on whether a specific infection could or does result in disease. Various theories and hypotheses on the cause of AIDS are presented in Chapter 2 (sections 2.2–2.4) of this report.

Prof Root-Bernstein explored the theory in a discussion paper on the aetiology of HIV in AIDS. In this aetiological theory he distinguished three hypotheses:

• That HIV is both ‘necessary’ and ‘sufficient’ to cause AIDS
• That HIV is sufficient but not necessary to cause AIDS
• That HIV is neither necessary nor sufficient to cause to cause AIDS.

The debate was therefore whether HIV is both necessary and sufficient to cause AIDS. Some panellists argued that it has not been proved that HIV does cause AIDS and that, while HIV can be present in individuals that develop AIDS, it cannot be proved that HIV caused AIDS. Dr Stein argued that in standard epidemiological practice, causes do not need to be ‘necessary’ and ‘sufficient’ to cause disease. She quoted from Dr M Sussers' manuscript for a forthcoming encyclopaedia on public health: "HIV is (and can be so regarded) as a cause of AIDS even if everyone who has HIV does not get AIDS".

This is similarly the case with conditions related to syphilis and tuberculosis. She explained that modern-day epidemiologists share a multi-causal perspective that deviates somewhat from Galileo's seventeenth century formulation that causes should be necessary and sufficient, and Koch's subsequent postulates, which served to guide the search for specific organisms as one-to-one causes of given diseases. Thus, in her view, HIV does not need to be necessary and sufficient to cause AIDS.

This view was challenged by Dr Papadopoulos-Eleopoulos, who turned the argument around to support an alternative theory (that AIDS may be caused by another agent e.g. Chemical agent) by concluding that, if a factor can cause disease without necessarily being sufficient, then we can have AIDS without HIV. Scientifically that is the only conclusion that can be drawn. Dr Fiala contributed to this debate a presentation of data published in the European Journal of Epidemiology, which demonstrated that of a total of 465 patients with clinical AIDS, 40% were found not to be HIV-positive. Views expressed by panellists in other discussion suggest that this may not necessarily be unusual and could be influenced by the progression of disease state or tests used.

3.5 Socio-economic risk factors

There were two opposing views on the debate around risk factors that are critical for the transmission and spread of AIDS. One school of thought argued that poor economic status was a sufficient risk factor in the acquisition of AIDS. Another argued that low socio-economic status and poverty contributed to circumstances that would increase the risk of acquiring AIDS, but that these factors are not in themselves sufficient in the acquisition and spread of AIDS.

Scientists of the former school, notably Prof Duesberg and Dr Giraldo, argued that poverty is an important risk factor for AIDS.

An opposing view was expressed Dr Bertozzi, who argued that higher HIV and AIDS cases do not necessarily correlate with low socio-economic status. Dr Bertozzi cited Mohanda and Allan, who wrote on the basis of their research in Tanzania, Rwanda, Zimbabwe and Zaire that the initial spread of HIV and the initial cases of AIDS that were identified in the population were not correlated with lower socio-economic status, rather the opposite was true, they were correlated with higher incomes and higher educational achievement. This position was supported by observations made by Dr Mugwera, who demonstrated that the earlier cases of HIV were in men from Rakai district who were involved in trade with Tanzania and whose socio-economic status was relatively higher than those who had not initially contracted HIV.

Discussing paediatric mortality and the work done by Professor Cooper in Johannesburg, Makgoba said that mortality trends had remained more or less constant between 1991 and 1996. After 1996, the HIV positivity rate had increased to 48% and continued to rise. Dr Bialy challenged the paediatric mortality data and asked to know what proportion of those infants had received AZT. The response to this was that the two groups were comparable with respect to socio-economic status and caesarean section rates of 23%, and that the only difference was the presence of HIV by antibody test and PCR. Dr Makgoba challenged the panellists to devise a general predictive model that explains such figures. He was convinced that poverty, malnutrition, TB, malaria, stress and chemical toxins would not explain these data.

Dr Reddy cautioned against interpretation of the mortality data for causality of death without taking socio-economic and political parameters into consideration. She proposed that the data be studied by a trans-disciplinary team which included Social Scientists.

3.6 Differences in the African epidemic, compared with Europe and the USA

Several panellists presented the issues surrounding why and how the South African epidemic differs from the epidemic in Europe and the USA. According to one group, the similarities are that initially AIDS occurred predominantly among homosexuals and haemophiliacs in the USA, Europe and South Africa, and that subsequent heterosexual spread and perinatal transmission were predominantly low among all socio-economic groups in all regions.

One of the differences is that in Africa and South Africa in particular, the epidemic has been explosive, with considerable perinatal transmission, probably through breast-feeding. Survival time appears to be shorter and the spectrum of disease differs due to local infections. Factors that contribute to the differences and the larger epidemic in Africa include poverty and infections, severe manifestations of sexually transmitted disease, higher diversity in HIV clades on account of migration, and the ccr5 gene being much rarer in Africa, thereby making more rare the possibility of natural immunity to the disease.

A distinguishing feature of the African epidemic has been in the area of transmission dynamics, host biological factors, and behavioural and viral factors. A high level of heterosexual transmission is one important factor. While most scientists who ascribe to the theory that HIV infection leads to AIDS argue that HIV is sexually transmitted, Dr Giraldo, in his submissions on the Internet debate, challenged this position and argued that there was no logical reason why HIV would be transmitted heterosexually in the South and homosexually in the North.

Dr Sonnabend's contribution to the debate on the differences between Africa and countries such as the USA relates to the issue of HIV transmission. Whereas heterosexual transmission of AIDS from women to men is inefficient in the USA, it seems to be efficient in Africa. The explanation provided is that the HIV inoculum in female to male transmission is very small and is transmitted very inefficiently. The situation in Africa, however, is different because of the high incidence of sexually transmitted diseases and other infections.

Dr Abdool-Karim argued that the most important factors include:

• The way the epidemic was introduced
• The South African strain – the phylogenetic tree analysis. While in India, the viruses that have been isolated and sequenced are ‘related to one another’, the South African isolate shows much more diversity. The close relationship between the Indian strains suggests a single introduction and subsequent spread (clonal epidemic) whereas the high genetic diversity in South Africa is suggestive of multiple introductions. The latter would confirm the importance of migration in fuelling the epidemic.
• The fact that sexually transmitted infections are so highly prevalent
• With the migrant labour system, various strains are brought together, causing multiple epidemics in South Africa.

A study comparing 70 couples where one partner was a migrant and 50 couples where both were non-migrants showed that the level of HIV discordance (where one person is positive and the other negative) is 30% in migrant couples and 12% in non-migrant couples.

3.7 The role of mathematical models in forecasting the epidemic

Data obtained through mathematical modelling were presented to support the argument that AIDS deaths are on the increase. This argument was supported by data from the national population register of the Department of Home Affairs (see section 3.3.1). While the CDC documentation and other official statistics including the South African Department of Health apply models to forecast events and the epidemic, information published by WHO, UNAIDS and other agencies were widely criticised by panellists such as Prof Duesberg and Drs Fiala and Giraldo. Prof Abdool-Karim expressed a concern about the use of mathematical models.

In a critique, Prof Root-Bernstein discussed mathematical models of AIDS, saying that they could be used in addition to experimental and clinical studies to investigate and compare theories of AIDS pathogenesis. He categorised them into two groups:

1. Models of the epidemiological behaviour of the epidemic
2. Models of the effect of HIV and cofactors on the immune system. The principal limitation of statistical and mathematical models is that such "models are actually an assortment of assumptions and simplifications that reflect the collective understanding and disposition of investigators concerning the natural history of disease and how it is spread".

It was widely recognised that there are inherent limitations in the use and application of mathematical models. These limitations result from the wide number of assumptions, and sometimes simplifications, that are made. The point of departure seemed to be the extent to which different individuals and groups are prepared use data obtained from models in spite of their limitations. While panellists suggest that using models is unhelpful, and even misleading, others ascribe to the position (evident from their continued use of models) that models have their usefulness in situations where planning data are required and unavailable and that they should continue to be used with caution.

3.8 Surveillance recommendations – what should be done about the South African epidemic?

3.8.1 Deliberations of the panel

The deliberations of the panel were at all times bedevilled by the absence of accurate and reliable data and statistics on the magnitude of the AIDS problem or even HIV prevalence in South Africa. Repeated requests for such data and statistics, particularly by panellists who refuted the causal link between HIV and AIDS, failed to result in the provision of such data by either South African panellists or the officials of the Department of Health.

Recommendation

It is therefore strongly recommended that appropriate measures be taken to establish the necessary infrastructure and provide the necessary expertise and resources to collect the data and develop reliable and up-to-date statistics on the magnitude of AIDS and prevalence of HIV in South Africa. All efforts must be made to ensure AIDS reporting in South Africa is up to the highest standards in the world.

3.8.2 Discussion on mortality data

The discussions around the mortality data presented by Dr Makgoba revealed the necessity for a study to unpack the numbers and gain deeper understanding as to whether the changing mortality profile resulted from AIDS only and/or from factors other than AIDS.

Recommendation

It is recommended that a trans-disciplinary team comprising members from all the relevant branches of science, including social sciences and humanities, other relevant professional spheres and representatives of relevant government departments be constituted to undertake an in-depth study of the mortality trends in South Africa and report on the results of the study to the South African government.

3.8.3 Recommendations from panellists who do not subscribe to the causal linkage between HIV and AIDS

It was recommended that the South African government commit to the folowwing:

1. Suspend the dissemination of the psychologically destructive and false message that HIV infection is invariably fatal and assist in reducing the 'hysteria' surrounding HIV and AIDS
2. Suspend all HIV testing until its relevance is proved especially in the African context, given the evidence of false positive results in the tropical setting and the fact that most assumptions and predictions about AIDS in Africa are based on HIV tests
3. Continue to improve social conditions in South Africa
4. Continue to decrease poverty
5. Continue to control infections and sexually transmitted diseases
6. Continue to increase the nutritional status of the population.

3.8.4 Recommendations from panellists who subscribe to HIV as the cause of AIDS

Dr Gayle and Prof Abdool-Karim, representing panellists who endorse the causal link between HIV and AIDS, reinforced the importance of the following initiatives for the South African government:

1. Continue strengthening the surveillance of risk factors such as the behaviour of youth
2. Surveillance of HIV prevalence in antenatal clinics, blood banks and among workers
3. Conducting incidence surveys
4. AIDS surveillance at health facilities
5. Keeping death registers
6. Standardisation and evaluation of diagnostic criteria and their completeness for reporting purposes
7. Surveillance of antenatal syphilis
8. Laboratory reporting
9. Health facility reporting.

3.8.4.1 Recommendations on surveillance as it pertains to reduction of blood-borne infection

The South African government needed guidance on the following issues:

1. The most appropriate policies on screening and quality assurance for blood safety
2. The most appropriate policy to reduce or prevent needle-stick injury with specific reference to policies on single use needles
3. Policies on the management of occupational HIV exposure, including post-exposure prophylaxis. Research on post-exposure prophylaxis needs to be pursued vigorously.
4. Policies on education and implementation of universal precautions
5. Most appropriate education and training related to reduction of risk of HIV and transmission in nosocomial settings and related to surgical operations.
6. Policies on intravenous drug use

3.8.4.2 Recommendations on surveillance as it pertains to reduction of HIV from Mother to Child

The South African government needed to pay attention to the following issues:

1. The most appropriate policy on voluntary HIV testing and counselling of pregnant women
2. The best policy for contraception promotion, including targeting HIV-positive women
3. The best policy on the use of anti-retroviral drugs to treat HIV-positive pregnant women. There were several research issues that were listed in this regard, including:
• investigating the extent of Nevaripine resistance when used to prevent transmission of HIV from mother to child
• the role of early weaning and non-exclusive breastfeeding
• what other mechanisms can be devised to reduce transmission of HIV from Mother to Child

3.8.4.3 Recommendations on surveillance as it pertains to sexual transmission of HIV

The following issues require attention:

1. The most appropriate policy on safe sex education
2. How best to promote the use of condoms
3. The best policy on the most appropriate and comprehensive treatment of sexually transmitted diseases
4. The most appropriate policy on post-exposure prophylaxis for rape
5. Regulation of commercial sex work and gender equity issues
6. Research into finding an efficacious and effective microbicide and into the development of a vaccine for therapy and prevention needs to be continued vigorously

3.8.5 General recommendation

There was general consensus on the need for the case definition of AIDS to be standardised for clinical practice in South Africa.

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