Recommendations for policy in the Western Cape Province regarding the prevention of Major Infectious Diseases including hiv/AI



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The Prevention of Mother-to-Child Transmission (PMTCT) can be effectively accomplished through a cost-effective, simple programme that is run through the existing health services. By reducing transmission to less than 5%, the infant morbidity and mortality that may be attributed to HIV infection is significantly lowered. This programme has been successfully implemented in the Western Cape Province, but requires sustained attention and support.
The present drug regimens should be reviewed according to current evidence and adjusted to achive the greatest reduction in the number of mother-to-child transmissions, as well as in the development of resistant mutations in both mothers and infants. There is no current evidence that supports routine, elective Caesarean section as part of PMTCT intervention for those mothers who receive adequate anti-retrovirals during the antenatal and intra-partum periods.

(d) Male Circumcision

Over the past decade, a number of epidemiological analyses have explored the variation of HIV-infection patterns in Africa, leading to the hypothesis that circumcision may be an important factor in reducing HIV-infection risk. Circumcision is practised in many parts of Africa, and there is some correlation between lower levels of circumcision and higher levels of HIV prevalence.

A meta-analysis of 28 studies by Weiss et al (1999) concluded that circumcision was protective for HIV, but raised concerns around the possibility that circumcision might increase risky sexual behaviours as a product of perceived invulnerability, and that there were also inherent risks in the surgical procedures for circumcision. Furthermore, cultural considerations would need to be taken into account if circumcision were to be introduced as an HIV-prevention measure.
A 2003 Cochrane review (Siegfried et al, 2003) found a significant difference (OR 0.58 95% CI 0.36 to 0.96) in HIV-transmission rates between circumcised and uncircumcised men in a single cohort study. A further 14 cross-sectional studies in the review, however, revealed inconsistent results, with circumcision being identified as either a risk factor or a protective factor for the transmission of HIV.

The HIV protective effects of circumcision have been demonstrated in recent randomised and controlled trials, including a South African trial (Auvert et al, 2005), which found that circumcision had a protective effect of 61%. Adverse events, including pain, excessive bleeding and haematoma, were reported to occur in 3.8% of circumcisions. An acceptability study in South Africa (Lagarde et al, 2003) found that perceptions of protection among circumcised men translated into unsafe practices, and that this would be an important area to address in interventions.

While male circumcision clearly reduces the risk of HIV infection among men through female-to-male transmission, risk reduction in the reverse direction, male-to-female, has not been found to be protective (Bonner, 2001). At best, epidemiological impacts of male circumcision on females, who presently remain at higher overall incident risk as a product of a wide range of biological and social factors, would be cumulative as a product of relatively slow reductions in male HIV prevalence. As Williams et al (2006) observe through the modelling of a progressive roll-out of male circumcision over the next decade, there is potential to reduce overall incidence with only an immediate impact on HIV-negative men, and broader impacts would only be realised in ten to twenty years.

Generally speaking, circumcision provides only partial protection, and all circumcised men would need to continue to practise other risk-reducing strategie, including consistent condom use, as well as limiting their number of sexual partners, limiting partner turnover, and other strategies. It remains unclear as to whether promotion of circumcision as an HIV-protective measure would result in higher risk behaviours among men as a product of perceived invulnerability to infection.


While findings of RCTs are promising, there remains disagreement as to the potentials for the ”‘mass roll-out” of male circumcision programmes with issues of concern including:

  • the complexity of the procedure;

  • the need for specialised training;

  • the risks of complications;

  • the possibility of misperceptions of invulnerability; and

  • the limited impact on the high incidence among girls and women.

These considerations suggest that circumcision be considered as an ‘add-on’ prevention measure, rather than a primary approach to reducing HIV prevalence in the short to medium term. It remains that prevention interventions should focus on short-term impacts through other interventions ­– particularly limiting partner turnover, avoiding concurrent sexual partners, and delayed debut among young people who are not yet sexually active.

Implications

Trials have shown a reduction in the risk of male HIV acquisition as a result of circumcision. Concerns about i) logistical challenges and ii) perceived invulnerability on the part of those circumcised, warrant further investigation before initiating policy changes.
1.2. Tuberculosis
The risk of TB is usefully conceptualised as the product of three sequential probabilities

(a) The probability of exposure to Mycobacterium tuberculosis

This translates to the risk of encountering an airspace that contains M. tuberculosis. As such it has both a spatial and a temporal component. The likelihood of this risk is proportional to three major factors (Hans & Rieder, 1999).

(i) The number of incident cases within a population

The more new cases of infectious disease there are, the greater the likelihood that a susceptible will inhale the organism in a given space. Nevertheless, there are modifiers of this rule for any fixed number of incident cases. They are principally: how “infectious” a case is and how “susceptible” an individual (or population) is.

(ii) The duration of infectiousness of the individual case

Rouillon et al (1976) demonstrated that around 30-40% of contacts were found to be infected around the time of diagnosis of a sputum smear-positive index case. Early intervention with chemotherapy reduces the time of infectiousness and, conversely, inadequate treatment can both prolong infectiousness and contribute to drug resistance. A separate study estimated that a single patient may infect ~10 contacts before receiving treatment (Styblo, 1980).

(iii) The number of case-contact interactions per unit time

This is determined mainly by factors that create an increased population density and create circumstances in which people are more likely to share indoor, poorly ventilated spaces. Well recognised among these factors are immigration, socioe-conomic deprivation, unemployment and poverty (Ponticello et al, 2005; Mangtani et al, 1995; Nishiura, 2003; Barr et al, 2004; Spence et al, 1993). Another factor is family size and social arrangements within families (Rieder, 1999). Climate plays a role, too, with a sunny climate more likely to result in people socialising outdoors where bacilli are dispersed rapidly and killed by ultra-violet rays. Winter is associated with an increased likelihood of indoor congregation and subsequent acquisition of the organism (Rieder, 1999).



(b) The probability of infection becoming established

This relates to the innoculating dose of the organism and innate (“first contact”) host defences within the lung parenchyma. A number of established risk factors have a bearing on this:

(i) Air density of Mycobacterium tuberculosis

To be transmissible through the medium of air, TB must remain airborne after being expelled from an infectious case. Droplets containing Mycobacterium TB can remain suspended in air for several hours (Sonkin, 1951).

(ii) Nature of the infectious case

The standard TB epidemiology model generally limits infectiousness to smear-positive TB of the respiratory tract, with greater infectiousness attributed to those with a higher smear-positive rating. Various studies have demonstrated, however, that patients classified as smear-negative can also transmit disease, at a rate of approximately one fifth of that of smear-positive cases (Behr et al, 1999).

(iii) Air circulation and ventilation

The probability of infection being established is related to proximity to a source case and inversely related to the size of the shared air space (Houk et al, 1968a; Houk et al, 1968b). This has clear implications for transmission of disease in institutional settings. Adequate ventilation can play an important role in diluting the concentration of bacilli.

(iv) Reducing expulsion of infectious material from source cases

The most effective intervention is treatment of active cases. Covering of the mouth and nose will also contribute to reducing the number of infectious droplets that can reach the air (Rieder, 1999).

(v) Host immune response

The macrophage is the first cell from the immune system to encounter and ingest the TB bacillus. Macrophage function may vary due to genetic or acquired factors (Rieder, 1999).



(c) The probability of infection progressing to disease

This can be thought of as how well a localised infection is kept “in check” and is associated with the following recognised risk factors:

(i) HIV

HIV is the strongest risk factor yet identified for the progression of infection to disease. Estimates of the annual risk of active infection in HIV-positive people (compared to HIV-negative people) range from a 20-fold increase to 170-fold higher among those with advanced immuno-suppression (Zumla et al, 2000). This is discussed further in the section on HIV/TB interaction on page [XXX].

(ii) Time since infection

In the absence of HIV, recent infection is 10 times more likely to result in the development of disease than a long-standing infection (Rieder, 1999).

(iii) Age

In the absence of HIV, there is a general trend of increasing incidence of disease with increasing age, although it is noted that adolescents and young adults seem particularly prone to progression from latent to active infection (Comstock et al, 1974).

(iv) Genetic factors

Sex, body build, HLA type and blood groups have all been noted to be associated with differential rates of disease. (Rieder, 1999).

(v) Environmental factors

Smoking, alcohol abuse, injecting drug use, silica exposure, malnutrition and diet (lacking in vitamin D) have all been associated with an increased risk of disease. (Rieder, 1999).

(vi) Medical conditions

Silicosis, diabetes mellitus, malignancies, renal failure, measles, gastro-intestinal surgery and corti-costeroid medication have been identified as risk factors (Rieder, 1999).

(vii) Pregnancy

The postpartum period might increase the risk of progression to disease (Rieder, 1999).


Implications

The single biggest risk factor for being exposed to TB is overcrowding in a high incidence area. HIV is the biggest risk factor for the development of tuberculosis disease.
By lowering the number of incident TB cases, and by early diagnosis and treatment of these cases, the probability of exposure of individuals to TB is reduced. Increased awareness of the probability of infection among vulnerable individuals, especially among those who are immuno-compromised and among other risk groups, will aid this initiative. Also crucial to this approach is the density of populations in which an infectious case occurs. Thus adequate space and accommodation with sufficient ventilation are necessary to lower the risk of infection.

2. Individual factors related to infection
2.1. HIV - Sexual behavioural risks

(a) Sexual debut and age mixing

Early sexual debut is correlated with higher rates of HIV prevalence. Early debut increases the length of time of sexual activity, as well as the likelihood of higher numbers of lifetime sexual partners (Pettifor et al, 2004b). A study of young males in rural Kwazulu-Natal found that those who had started sex before age fifteen were more likely to report risk behaviours at first sex, but also were ten times more likely to have had more than three partners in the past three years (Harrison, 2005).

Similar findings were made by Shisana et al (2005) including a much higher likelihood of females being HIV positive when sexual partners were five or more years older than themselves – for example, among females aged 15-19, 29.5% who had partners five or more years older than themselves were HIV positive, in comparison to 17.2% who had partners within a five year age range.

In essence, while behavioural risk factors for females are generally lower than those of males, females have a higher overall risk of HIV infection. In a study of HIV differentials in relation to sex, Glynn et al (2005) explored factors that increased female vulnerability in communities in Kenya and Zambia. They concluded that young males and females generally had similar risk exposures on average – male’s exposure being enhanced as a product of higher partner numbers, and females exposure being enhanced as a product of exposure to older partners who have had other partners. Differences in prevalence were linked to higher susceptibility among females, as well as the presence of other STIs – in particular, genital herpes. HIV positivity was also noted to occur in some females after only a few episodes of sexual intercourse.



Implications

HIV prevalence among young people in South Africa and the Western Cape is high. Earlier sexual debut increases risk to HIV. For males and females this is related to a greater likelihood of exposure to multiple partners over time, while for females, risk is additionally linked to factors that include biological vulnerability and vulnerability as a product of having older sexual partners. Country and site-level declines in HIV prevalence have also been associated with increases in age of sexual debut. Promoting delayed debut, particularly in a context of high HIV prevalence, is a crucial strategy for the Western Cape.

(b) Partner turnover / concurrency

Sexual transmission of HIV is the predominant mode of infection in South Africa. The probability of infection is related to the infectiousness of the sero-positive individual, the mechanisms of sexual contact, and the susceptibility of the sero-negative partner (Vernazza et al, 1999). Females are biologically more susceptible to the virus and, in South Africa, female HIV-prevalence levels are considerably higher than those of males in similar age groups. HIV-prevalence of females in 15-19, 20-24 and 25-29 year age groups in South Africa, for example, are three to four times higher than for males in the same age groups (Shisana et al, 2005). While part of this difference is accounted for by age differentials between sexual partners, with females tending to have older partners, peak prevalence levels for males remain lower than for females: 23.3% for males in the 30-34 and 35-39 year age groups, in comparison to 33.3% for females aged 25-29.

Low average rates of HIV infectivity are unlikely, on their own, to sustain a high-level HIV epidemic, and other factors related to transmission need to be taken into account. Increased genital shedding of HIV-1 in early stages of infection has been observed in a number of studies. Pilcher et al (2004), noting that viral load in semen is estimated to be much higher during a six-week period of acute infection. It was found that — with “conservative” estimates for sub-Saharan African men — 7-24% of female partners would be infected in the first two months of infection, with an estimated increase to 50%, if one partner also had an STI (Pilcher et al, 2004). Chakroborty et al (2001) attributed high HIV prevalence in sub-Saharan African epidemics to the greater efficiency of HIV infection during the acute phase of infection. Acute infection is asymptomatic, apart from flu-like symptoms in some cases (Daar et al, 2001).

Concurrent sexual partnerships are a risk factor for increased HIV transmission as a result of the risks of new and acute infection of one partner resulting in more efficient transmission to other partners during the first six to eight weeks of infection, with models of concurrency illustrating amplified disease-transmission dynamics (Morris & Kretszchmar, 2000; Wawer et al, 2005). In a microsimulation study for rural Uganda in the 1990s, Morris and Kretszchmar (2000) found that concurrency may have increased HIV prevalence by a factor of two or three, and concluded that prevention messages promoting “one partner at a time” were as important as promoting fewer partners.

A number of recent analyses of HIV prevalence declines in urban Kenya, Malawi, Uganda and in Zimbabwe, concluded that changes in sexual behaviour — particularly delayed sexual debut and lower rates of partner turnover, as well as condom use with non-regular partners — are strongly associated with declines (Hallet et al, 2006; Cheluget et al, 2006; Bello et al, 2006; Kirungi et al, 2006; Mahomva et al, 2006). These studies explored declines in various age groups, with declines among 15-24 year-olds providing a proxy for incidence declines. Moreover, prevalence data have been disaggregated by site or region, and in some analyses, models have been used to identify factors contributing to prevalence and incidence declines.

Declines have been associated with significant changes in high risk behaviours. In Kenya, for example, having more than one partner in the previous 12 months declined between 1998 and 2003 from 4.2% to 1.8% for females, and from 24.1% to 11.9% for males. Condom use at last “higher risk sex” increased for females from 15.1% in 1998 to 23.9% in 2003 (Cheluget et al, 2006). In Zimbabwe, statistically significant declines occurred in a number of non-regular partners in the reported previous 12 months of 15- to 29-year-olds, from 17.2% to 8.2% for females between 2001 and 2003, and from 32.2% to 21.3% for males over the same time period. Antenatal HIV prevalence among 15- to 19-year-olds declined from 19.5% in 2001 to 13.7% in 2004, and for 20-to 24-year-olds, from 28.9% to 24.0% over the same period (Mahomva et al, 2006).

In South Africa 23% of males, and 8.8% of females aged 15-24 reported more than one partner in the past year in 2002. Rates for males aged 25-49 were 11.5%, and 2.5% for females in 2002, increasing for males to 14.4% in 2005, and decreasing for females to 1.8%. (Shisana et al, 2002; Shisana et al, 2005). Higher rates of more than one partner in the past year were found in a survey of 15- to 24-year-olds in 2004 ­— 44% for males and 12% for females (Pettifor et al, 2004). While annual partner turnover rates provide some insight into partner reduction over time, numbers of concurrent partners are less readily defined. A national survey in 2006 explored the numbers of partners reported in the previous month and found that 33.2% of males and 12.6% of females aged 15-24 reported more than one partner in the past year, with around one third of this group — 10.8% of males and 3.6% of females reporting more than one partner in the previous month (Parker, 2006).

Implications

In the context of an advanced HIV epidemic in South Africa, high levels of partner turnover, along with high levels of concurrency, are likely to be driving the epidemic. Although elevated risks of HIV infection occur where there is concurrency, individuals may not necessarily be aware that they are exposed to HIV as a product of concurrent partnerships. Addressing concurrent partnerships should thus be seen as a subset of interventions encouraging the limiting of sexual-partner numbers.

(c) Condom use

Male latex condoms provide an impermeable barrier for the prevention of HIV and other STIs and have been actively promoted as a core strategy in HIV prevention (WHO, 2004). A condom that has passed all quality control tests will not allow passage of HIV contaminated seminal fluid through the latex. Modelled risk for viral transfer relative to non-use (risk = 1.0) was calculated to be 0.0006 in the case of condom breakage, 0.000008 in the case of a visibly detectable hole, and 0.0 in the case of no break or leak (NIH, 2000:7). Consistent and correct condom use thus has a very high efficacy for HIV prevention. It has been recognised, however, that failure may occur in relation to the integrity of the condom, as well as user failure as a product of incorrect use, including contact with seminal, vaginal or other body fluids prior to, or after condom use, as well as condom breakage, slippage and other problems. In addition, condoms may be used inconsistently.

Based on studies of sero-discordant couples, various estimates have been made for the relative risk reduction for HIV transmission. In a Cochrane review, Weller & Davis (2002) estimated 80% protection over non-use for consistent condom use, noting that — in the studies reviewed — correct use was not measured. Studies using a micro-simulation model showed incremental benefits of condom use, with the highest risk reduction being achieved through consistent use, while benefits were also being achieved through high use with high-risk partners (Bracher et al, 2004). Holmes et al (2004) note the relevance of condoms for HIV and STI prevention and conclude that condoms should be promoted along with complementary prevention strategies.

Male latex condoms have been extensively promoted and distributed in South Africa, using the public sector; the private, commercial sector; and via social marketing.

Considerable attention has been given to ensuring condom quality assurance and effective distribution and logistics management of high volumes condoms in the public sector. The system follows a demand-based model, ensuring that condoms supplies are only replenished when minimum volumes are reached at primary distribution sites. Volumes have increased each year with 267-million being distributed in 2001 to over 350-million in 2005. Hospitals and clinics serve as primary distribution sites, with secondary distribution extending to NGOs, community-based organisations, taverns, workplaces, transport hubs, and spazas. In June 2004, public-sector condoms were rebranded as ChoiceTM. In 2004, an average of 22 condoms per male aged 15-59 were distributed nationally, with 16.4 per male in this age range being distributed in the Western Cape (Department of Health, South Africa, 2005).

Social marketing of male condoms is used extensively in many African countries, and is conducted in South Africa by the Society for Family Health, a subsidiary of Population Services International (PSI). Lovers Plus and Trust brand names are sold at subsidised prices in a variety of outlets, with approximately 18 million being sold in 2005. Commercial brands such as Durex, Contempo and Lifestyle condoms are estimated to account for only one percent of the total national condom distribution.

Perceived awareness of condom availability in South Africa is high, with more than 90% of respondents aged 15-49 reporting that condoms were easy to access in 2002 (Shisana et al, 2002). Reported condom use at last sex is high throughout the country, with proportions including 72.8% of males and 55.7% of females aged 15-24, and over 30% for males and females aged 25-49 (Shisana et al, 2005). While this indicator provides little insight into consistency of condom use — a “yes” response to a questionnaire is no gurantee of use in prior sex acts — it is a useful indicator for understanding the response to condom-promotion campaigns. Marked increases in reported last sex condom use have occurred over the past decade, and have run in parallel to increases in procurement and logistical distribution efficiencies. Awareness of condoms as a primary means for HIV prevention is also extremely high — over 90% of respondents aged 15-49 mentioned condoms when asked to mention HIV prevention methods they were aware of, while only 18.9% of 15-24 year olds and 28.8% of 25-49 year olds mentioned sticking to one partner or being faithful (Parker, 2006).

While awareness of condoms and reported last sex use of condoms is high for both sexes, less is known about the correct and consistent use of condoms, and — in spite of year-on-year increases in reported condom use at last sex among young people aged 15-19 nationally, for example — there has been no change in HIV prevalence among females under 20 over the past five years (Department of Health, South Africa, 2006). A national survey of youth aged 15-24 found that, among those who were sexually active in the last year, 33% reported always condom use, while 12% reported condom use “more than half the time” with the remaining 55% using condoms half the time, less, or never (Pettifor et al, 2004:45).

Ahmed et al (2001) found consistent condom use was protective for HIV in a rural African setting, but found no protective effect in the case of inconsistent condom use. Condom-related concerns of callers to the national AIDS Helpline included advice on the safety and reliability of condoms; breakage and slippage of condoms; condom myths; storage; disposal; and other factors (Parker et al, 2004). In an analysis of places where people met sexual partners in the Western and Eastern Cape, Wier et al (2003) reported relatively low levels of ever condom use — 33-66% — and of those who said they used a condom at last sex, only a fourth reported carrying a condom, and only a fifth of these respondents showed the condom to the interviewer.

Allen and Heald (2004) compared prevalence declines in Uganda and the lack of decline in Botswana in a context of systematic response in both countries, arguing that the promotion of condoms at an early stage in Botswana was counter-productive to prevalence impacts, while the lack of condom promotion in the early phases of the Ugandan response allowed for an emphasis on other prevention approaches.

Condom use is less likely in the contexts of diminished rationality or control over sexual choices — for example, in relation to alcohol or drug abuse; where imbalances of power exist and where, for example, one partner is resistant to condom use; and in situations of sexual violence including rape, child sexual abuse, and rape in institutional settings such as prisons (Marandu & Chamme, 2004; Pettifor et al, 2004).

Implications


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