- Email: [email protected]
Preventing HIV infection: lessons from Mwanza and Rakai
COMMENTARY
objective benefits obtained at the price of significant operative mortality, laser therapy is unlikely to occupy anything but a restricted place in clinical practice, and the temptation to substitute it for recognised treatment should be strongly resisted. Surgeons with a large practice in coronary artery surgery have often expressed their stupefaction at the high proportion of “inoperable” patients reported by some units. Minimally invasive surgery, which enables targeted revascularisation of the myocardium with low mortality and morbidity, could be better applied. This limited revascularisation is especially appropriate for patients who have had bypass surgery, the largest group of patients enrolled in laser trials. Likewise, fine adjustment of medical therapy is commonly neglected. It has been acknowledged that 50% of patients referred for laser therapy could be stabilised with intensification of antianginal therapy only.10 If laser can be applied with negligible mortality (perhaps by use of the less invasive thoracoscopic or percutaneous approaches), laser therapy might be considered for its analgesic effect in patients with intractable angina pectoris. Until better knowledge of the damage created by the laser beam and of the presumed subsequent benefits to the heart is obtained, the machine should be used sparingly and preferably only in the few centres that integrate the results into prospective trials. Referral of patients to these centres should accelerate and provide the necessary recruitment for definition of the ranges of beneficial applications, and greatly reduce costs associated with unchecked proliferation of this expensive technique. By relegating laser to merely an expensive analgesic device, the UK trial might be ruining most of the expectations placed in transmyocardial laser revascularisation. To patients with end-stage coronary artery disease, and to their doctors, the information will be extremely disappointing. To them, the moon will still seem far away.
René Prêtre, Marku I Turina, Department of Cardiovascular Surgery, University Hospital, 8091 Zurich, Switzerland 1
Frazier OH, Cooley DA, Kadipasaoglu KA, et al. Myocardial revascularization with laser: preliminary findings. Circulation 1995; 92 (suppl I): 58–65. 2 Cooley DA, Frazier OH, Kadipasaoglu KA, et al. Transmyocardial laser revascularization: clinical experience with twelve-month follow-up. J Thorac Cardiovasc Surg 1996; 111: 791–97. 3 Horvath KA, Cohn LH, Cooley DA, et al. Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease. J Thorac Cardiovasc Surg 1997; 113: 645–53. 4 Vincent JG, Bardos P, Kruse J, Maass D. End stage coronary disease treated with the transmyocardial CO2 laser revascularization: a chance for the ‘inoperable’ patient. Eur J Cardiothorac Surg 1997; 11: 888–94. 5 March RJ.Transmyocardial laser revascularisation with the CO2 laser: one year results of a randomized, controlled trial. Semin Thorac Cardiovasc Surg 1999; 11: 12–18. 6 Mueller XM,Tevaearai HH, Genton CY, Bettex D, von Segesser LK. Transmyocardial laser revascularisation in acutely ischaemic myocardium. Eur J Cardiothorac Surg 1998; 13: 170–05. 7 Malekan R, Reynolds C, Narula N, Kelley ST, SuzukiY, Bridges CR. Angiogenesis in transmyocardial laser revascularization: a nonspecific response to injury. Circulation 1998; 98 (suppl I): 62–65. 8 Kwong KF, Kanellopoulos GK, Nickols JC, et al.Transmyocardial laser treatment denervates canine myocardium. J Thorac Cardiovasc Surg 1997; 114: 883–89. 9 Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting of randomized controlled trials: the CONSORT Statement. JAMA 1996; 276: 637–39. 10 Nägele H, Stubbe HM, Nienaber C, Rödiger W. Results of transmyocardial laser revascularization in non-revascularizable coronary artery disease after 3 years follow-up. Eur Heart J 1998; 19: 1525–30.
THE LANCET • Vol 353 • February 13, 1999
Preventing HIV infection: lessons from Mwanza and Rakai See page 525 From the start of the AIDS epidemic the influence of other sexually transmitted diseases (STDs) on HIV transmission and the progression of HIV disease has been apparent. Importantly, the epidemiological synergy is consistent with the model of Anderson and May1 that describes the forces necessary to establish an HIV epidemic. After the 1992 Amsterdam international AIDS meeting, the late Jonathan Mann argued that the evidence for STDs as cofactors was so strong that further epidemiological research was not necessary—it was time to find out what impact STD prevention and control might have on HIV infection rates. In that spirit, two landmark communitybased intervention trials were undertaken. The first, in Mwanza, Tanzania, focused on enhanced syndromic diagnosis of symptomatic sexually transmitted infections. It involved populations in eight paired villages in a 2-year study. Back in 1992, the HIV epidemic was in its early stages in Mwanza; HIV seroprevalence was estimated at 4%. The study in the Rakai District of Uganda began soon afterwards. It focused on treatment of all members of five clusters of paired communities, including those with symptomatic and asymptomatic sexually transmitted infections. The AIDS epidemic was already well established in Rakai, and 16% of the study population were infected with HIV. In both studies, experimental and control communities were treated similarly with respect to availability of educational materials and condoms. In August, 1995, the first results of the Mwanza study2 revealed that almost 40% of HIV infections had been prevented in the communities receiving the intervention. No other HIV intervention has had such a striking effect on infection rates. The findings of the Rakai study, reported in this week’s Lancet, are also striking—no HIV infections were prevented in the intervention communities. A predictable initial reaction is that one of the studies is wrong. However, the results of both are consistent with Anderson and May’s model and with the STD simulation exercise of Van Vliet and Habbema.3 The AIDS epidemic was at a different stage in the two areas. In both models,2,3 STD interventions are effective early in the AIDS epidemic. However, the Van Vliet and Habbema model predicts an impact of STD prevention and control even if implemented at a mature stage of the epidemic. The Mwanza results could reflect the short-term impact of STD prevention and control in an immature epidemic, whereas the Rakai study reflects the short-term impact in a mature epidemic. Understanding this concept of epidemic “maturity” requires an appreciation of the three factors influencing the generation of an HIV epidemic in a susceptible population—the probability of transmission, the duration of infectiousness, and the number of sexual partners. STDs increase HIV shedding, thereby increasing the likelihood that genital secretions contain the amount of HIV required for transmission. If there are no other risk factors, HIV is easier to transmit from male to female, probably because the volume of ejaculate is larger than the volume of cervical and vaginal secretions. However, female-to-male transmission of HIV is as likely as male-tofemale transmission if the woman has an STD.4,5 In the HIV-negative partner, an STD increases the amount of
513
COMMENTARY
susceptible target tissue and the infectious dose is lowered. Thus, both infectiousness and susceptibility increase. There are two major periods of HIV infectiousness. The first is immediately after HIV infection and the second period is end stage, when high viral loads in blood result in HIV shedding in many body fluids. In between is a latent period of variable duration. Because HIV shedding is increased in people with another STD, the latent period is disrupted and the duration of infectiousness increases.6 The higher the partner number each year, the greater the chance of encountering a partner with an STD. Among people who are sexually highly active, STDs are highly prevalent. Those with many partners will have few acts with each other. Since HIV is not easy to transmit “under normal circumstances”, they would be unlikely to transmit HIV in a single act of intercourse. However, STDs drastically change that balance, so the ability to transmit HIV is amplified every time they have sex with every partner. The size of the core (population with high prevalence of STDs and high rate of change of sexual partner) and the variation of partner number will affect the initial rate of HIV infection in the epidemic and the longterm persistence of infection within communities. The larger the core and the greater the risk factors, the higher the prevalence before the peak occurs—and the size of the peak will also influence the persistence of the epidemic in the population.7 The point that highly sexually active people have fewer acts per partner is important. In the absence of STDs, this group is less likely to transmit HIV. Another important factor is differential mortality.8 It can account for a third of observed change in an HIV core group—ie, a decrease in risky behaviour may reflect not behaviour change but the death of the people who engage in high-risk behaviour. In a mature AIDS epidemic (eg, Uganda), the infection has moved beyond phase 1 (rapid infection of the very susceptible population). Saturation of the very susceptible population and differential mortality define the end of phase 1. This phase is followed by an apparent decline or plateau, when the death rate and the new infection rate are similar and the infection is silently moving into the lowerrisk, innately susceptible population. In phase 2, individuals are susceptible to HIV infection to the degree defined by the biology of HIV and the human host. STDs are not needed to drive HIV transmission in this class of susceptibles since the lower-risk individuals have many more acts of intercourse per partner, and sooner or later transmission occurs. Studies on interactions between STDs and HIV and the Mwanza and Rakai findings suggest that prevention and control of STDs before or early in this epidemic will probably reduce STDs in the highly active core population and will have a major impact on the spread of HIV. Once the epidemic has begun, and certainly after it has moved beyond phase 1, short-term STD prevention and control will probably have little impact on the epidemic. Treatment of STDs will undoubtedly reduce the risk in an individual, but at a population level, in a mature epidemic, it will have an impact only after a long time. An alternative explanation for the differences in findings from Mwanza and Rakai could lie in the biology of the HIV clade—if the Mwanza viruses were harder to transmit through vaginal intercourse, treatment of STDs would have a greater effect, but if the viruses in the Rakai were relatively easy to transmit, treatment would have little effect. Incidentally, no intervention trial has yet taken into account three other key 514
factors that might influence the spread of HIV: dry sex and douching, bacterial vaginosis, and genital herpes. All are highly prevalent in the developing world and could influence transmission rates. The scientific evidence supports STD control as an intervention that will have enormous impact in the early phase of the HIV epidemic. Furthermore, on the basis of Nordic experience (where the prevalence of HIV infection is low, and where low prevalence of STDs reflects comprehensive national STD programmes), low levels of STDs in a population could prevent a heterosexual epidemic. Adolescents are continually entering the pool of new susceptibles. In view of the early age at first intercourse, adolescents commonly have many lifetime partners. Prevention of STDs in these populations might shorten the second phase of the HIV epidemic. The Mwanza and Rakai results tell us that STD prevention and control is feasible, effective, and affordable. What next? • STD prevention and control should be implemented in all populations where STD prevalence is high and HIV prevalence is low. • Long-term STD programmes should be implemented where the HIV epidemic is mature (HIV prevalence high, STD prevalence variable). These programmes should focus on adolescents. • STD services must be made available to pregnant women and their partners because STD treatment reduces the likelihood of low birthweight and adverse outcomes of pregnancy. • Any HIV vaccine or topical virucidal agent must be tested in populations where STD prevalence is low, lest the efficacy of these products in normal populations be obscured by the increased risk of HIV infection created by concurrent STDs. Sadly, the opportunity for STD prevention and control to make a difference has come and gone for 30 million HIV-infected people. The obligation that the health professions have is to the countless millions of uninfected people who are at high risk of HIV infection. Safe biomedical and behavioural interventions that reduce the risk of HIV infection are available. Use of the male condom, clean needles, antiretroviral therapy and caesarean section for pregnant women, and synthetic breastmilk are effective and should be fully supported. To that list should be added STD prevention and control. In view of the prevalence of treatable STDs in resourcelimited populations that are vulnerable to the HIV epidemic, anything short of an immediate response and a sustained commitment to STD prevention and control programmes is unthinkable.
*Penny Hitchcock, Lieve Fransen Sexually Transmitted Diseases Branch, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA; and Human Development Unit DG VIII/A2, Commission of European Community, Brussels, Belgium 1 2
3 4
5
Anderson RM, May RM. Epidemiological parameters of HIV transmission. Nature 1988; 333: 514–19. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346: 530–36. The World Bank. Confronting AIDS:public priorities in a global epidemic. NewYork: Oxford University Press, 1998:103–71. Garnett GP, Anderson RM. Strategies for limiting the spread of HIV in developing countries: conclusions based on studies of the transmission dynamics of the virus. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 9: 500–13. Boily MC. Transmission dynamics of coexisting chlamydial and HIV infections in the United States. In: Eng IR, Butler WT, eds. The hidden
THE LANCET • Vol 353 • February 13, 1999
COMMENTARY
6
7
8
epidemic: confronting sexually transmitted diseases.Washington, DC: Institute of Medicine/National Academy of Scientific Press; 1997: 316–29. May RM, Anderson RM. Heterogeneities, cofactors and other aspects of the transmission dynamics of HIV/AIDS. In: Gottlieb MS, ed. Current topics in AIDS, vol II. Chichester:Wiley, 1989: 33–80. Anderson RM. The transmission dynamics of sexually transmitted diseases: the behavioral component. In:Wasserheit JN, Aral SO, Holmes KK, Hitchcock PJ. Research issues in human behaviour and sexually transmitted diseases in the AIDS era. Washington DC: American Society for Microbiology, 1991: 38–80. Blower SM, van Griensven GJP. Effect of differential mortality on risk behavior change in cohort studies. J Acquir Immune Defic Syndr 1993; 6: 1364–67.
Link between psychiatric dysfunction and dizziness Primary-care patients who complain of dizziness have been found by L Yardley and colleagues to have a significantly higher rate of psychiatric disorder than agematched controls who do not report this symptom.1 Some patients had mild abnormalities of auditory, vestibular, and oculomotor functioning, but these abnormalities were found in a similar number of controls. Dizziness was associated with a trend towards abnormalities of the balance system, although the extent of these changes was mild. Thus, a community-based group of patients with dizziness was more typically characterised by psychological dysfunction, particularly symptoms of anxiety and depression, than by neurootological disturbance. The association between negative affectivity (a psychological trait with high levels of anxiety and depression) and physical symptoms is not restricted to dizzy patients. This combination is also seen in general epidemiological health surveys and syndromes such as chronic fatigue syndrome, irritable bowel syndrome, and chronic pain.2,3 Similarly, the finding that mild physical abnormality can occur without symptoms is also not unique to Yardley and colleagues’ study. Many people without back pain have abnormalities in their lumbar spine that are similar to those found in people who complain of chronic low back pain.4 How can the association between negative affectivity and dizziness be explained? One possible explanation is that both arise from a common neurophysiological mechanism.5 However, if the relation is essentially biologically driven, symptom reports should be in keeping with laboratory findings. Whereas Yardley and colleagues did not investigate this association, studies of patients’ reports of fatigue and neuropsychological problems have consistently shown no association between objective laboratory findings and symptoms.6,7 Another possible explanation is that psychological distress causes biological changes that lead to dizziness. However, this hypothesis does not take into account those patients who have neuro-otological abnormalities but no symptoms. Perhaps, the link operates the other way round. Repeated episodes of dizziness may increase psychological distress. Arguments against this disability hypothesis are found in prospective studies that show that premorbid psychological distress is a strong predictor of chronic fatigue and chronic pain—distress precedes rather than predates chronic somatic complaints.8,9 Also, patients with chronic medical disorders report different degrees of psychological distress, and there is little evidence to support the hypothesis that health problems lead to negative
THE LANCET • Vol 353 • February 13, 1999
affectivity.3 Clearly, these hypotheses are unlikely to provide a complete explanation for the relation between dizziness and psychological dysfunction, because some patients with dizziness do not have comorbid psychological problems. Therefore psychological distress may be a sufficient but not a necessary factor in the development of dizziness. Any explanation should also be able to account for people who do not report symptoms, but have similar clinical signs to those who do. Another way to look at this problem is to regard the reporting of symptoms as a reflection of self-focused attention and symptom interpretation. Individuals with a high degree of negative affectivity tend to be self-focused and to look out for somatic sensations. When a new sensation is detected, these people tend to interpret the symptom more negatively than would individuals with a low degree of negative affectivity. If a sensation, such as dizziness, is thought to be a sign of illness, it is more likely to be reported than if it were thought to be a normal response to a stressful situation. The interpretation of symptoms is guided by personal ideas about symptoms, as well as by situational factors such as the relative intensity of external and internal stimuli.10,11 This hypothesis on self focusing and symptom interpretation could account for Yardley and colleagues’ findings. Psychological dysfunction has been consistently associated with high degrees of self-focusing.12 Thus, the presence of psychological changes in the dizzy patients suggests that this group has a higher propensity to notice internal stimuli and sensations. Most of the dizzy patients in Yardley and colleagues’ study met criteria for an anxiety-related condition. Anxiety-related autonomic arousal may also enhance the experience of minor neurootological sensations. In addition, these signs of arousal might be misinterpreted as signs of illness that lead to the reporting of symptoms. In conclusion, studies investigating the pathogenesis of dizziness, such as that by Yardley and colleagues,1 are important because they confirm that the treatment of patients who present with symptoms such as dizziness needs to focus on both the physical and psychological aspects. This approach should not be restricted to tertiary care, because patients with dizziness in primary care have similar degrees of psychopathological abnormalities. Future studies should focus on the mechanisms of the association between symptoms and psychological disorders so that better integrated treatment programmes can be developed.
*Rona Moss-Morris, Keith J Petrie Department of Psychiatr y and Behavioural Science, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92 019, Auckland, New Zealand 1
2
3
4
5
Yardley L, Burgneay J, Nazareth I, Luxon L. Neuro-otological and psychiatric abnormalities in a community sample of people with dizziness: a blind, controlled investigation. J Neurol Neurosurg Psychiatry 1998; 65: 679–84. Hudson JO, Pope HG. The concept of affective spectrum disorder: relationship to fibromyalgia and other syndromes of chronic fatigue and chronic muscle pain. Baillière’s Clin Rheumatol 1994; 8: 839–56. Watson D, Pennebaker JW. Health complaints, stress, and distress: exploring the central role of negative affectivity. Psychol Rev 1989; 96: 234–54. Jensen MC, Brant-Zawadzki MN, Obuchowski N, et al. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med 1994; 331: 69–73. Brandt TH. Neuro-otological and psychiatric abnormalities. J Neurol Neurosurg Psychiatry 1998; 65: 619.
515
objective benefits obtained at the price of significant operative mortality, laser therapy is unlikely to occupy anything but a restricted place in clinical practice, and the temptation to substitute it for recognised treatment should be strongly resisted. Surgeons with a large practice in coronary artery surgery have often expressed their stupefaction at the high proportion of “inoperable” patients reported by some units. Minimally invasive surgery, which enables targeted revascularisation of the myocardium with low mortality and morbidity, could be better applied. This limited revascularisation is especially appropriate for patients who have had bypass surgery, the largest group of patients enrolled in laser trials. Likewise, fine adjustment of medical therapy is commonly neglected. It has been acknowledged that 50% of patients referred for laser therapy could be stabilised with intensification of antianginal therapy only.10 If laser can be applied with negligible mortality (perhaps by use of the less invasive thoracoscopic or percutaneous approaches), laser therapy might be considered for its analgesic effect in patients with intractable angina pectoris. Until better knowledge of the damage created by the laser beam and of the presumed subsequent benefits to the heart is obtained, the machine should be used sparingly and preferably only in the few centres that integrate the results into prospective trials. Referral of patients to these centres should accelerate and provide the necessary recruitment for definition of the ranges of beneficial applications, and greatly reduce costs associated with unchecked proliferation of this expensive technique. By relegating laser to merely an expensive analgesic device, the UK trial might be ruining most of the expectations placed in transmyocardial laser revascularisation. To patients with end-stage coronary artery disease, and to their doctors, the information will be extremely disappointing. To them, the moon will still seem far away.
René Prêtre, Marku I Turina, Department of Cardiovascular Surgery, University Hospital, 8091 Zurich, Switzerland 1
Frazier OH, Cooley DA, Kadipasaoglu KA, et al. Myocardial revascularization with laser: preliminary findings. Circulation 1995; 92 (suppl I): 58–65. 2 Cooley DA, Frazier OH, Kadipasaoglu KA, et al. Transmyocardial laser revascularization: clinical experience with twelve-month follow-up. J Thorac Cardiovasc Surg 1996; 111: 791–97. 3 Horvath KA, Cohn LH, Cooley DA, et al. Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease. J Thorac Cardiovasc Surg 1997; 113: 645–53. 4 Vincent JG, Bardos P, Kruse J, Maass D. End stage coronary disease treated with the transmyocardial CO2 laser revascularization: a chance for the ‘inoperable’ patient. Eur J Cardiothorac Surg 1997; 11: 888–94. 5 March RJ.Transmyocardial laser revascularisation with the CO2 laser: one year results of a randomized, controlled trial. Semin Thorac Cardiovasc Surg 1999; 11: 12–18. 6 Mueller XM,Tevaearai HH, Genton CY, Bettex D, von Segesser LK. Transmyocardial laser revascularisation in acutely ischaemic myocardium. Eur J Cardiothorac Surg 1998; 13: 170–05. 7 Malekan R, Reynolds C, Narula N, Kelley ST, SuzukiY, Bridges CR. Angiogenesis in transmyocardial laser revascularization: a nonspecific response to injury. Circulation 1998; 98 (suppl I): 62–65. 8 Kwong KF, Kanellopoulos GK, Nickols JC, et al.Transmyocardial laser treatment denervates canine myocardium. J Thorac Cardiovasc Surg 1997; 114: 883–89. 9 Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting of randomized controlled trials: the CONSORT Statement. JAMA 1996; 276: 637–39. 10 Nägele H, Stubbe HM, Nienaber C, Rödiger W. Results of transmyocardial laser revascularization in non-revascularizable coronary artery disease after 3 years follow-up. Eur Heart J 1998; 19: 1525–30.
THE LANCET • Vol 353 • February 13, 1999
Preventing HIV infection: lessons from Mwanza and Rakai See page 525 From the start of the AIDS epidemic the influence of other sexually transmitted diseases (STDs) on HIV transmission and the progression of HIV disease has been apparent. Importantly, the epidemiological synergy is consistent with the model of Anderson and May1 that describes the forces necessary to establish an HIV epidemic. After the 1992 Amsterdam international AIDS meeting, the late Jonathan Mann argued that the evidence for STDs as cofactors was so strong that further epidemiological research was not necessary—it was time to find out what impact STD prevention and control might have on HIV infection rates. In that spirit, two landmark communitybased intervention trials were undertaken. The first, in Mwanza, Tanzania, focused on enhanced syndromic diagnosis of symptomatic sexually transmitted infections. It involved populations in eight paired villages in a 2-year study. Back in 1992, the HIV epidemic was in its early stages in Mwanza; HIV seroprevalence was estimated at 4%. The study in the Rakai District of Uganda began soon afterwards. It focused on treatment of all members of five clusters of paired communities, including those with symptomatic and asymptomatic sexually transmitted infections. The AIDS epidemic was already well established in Rakai, and 16% of the study population were infected with HIV. In both studies, experimental and control communities were treated similarly with respect to availability of educational materials and condoms. In August, 1995, the first results of the Mwanza study2 revealed that almost 40% of HIV infections had been prevented in the communities receiving the intervention. No other HIV intervention has had such a striking effect on infection rates. The findings of the Rakai study, reported in this week’s Lancet, are also striking—no HIV infections were prevented in the intervention communities. A predictable initial reaction is that one of the studies is wrong. However, the results of both are consistent with Anderson and May’s model and with the STD simulation exercise of Van Vliet and Habbema.3 The AIDS epidemic was at a different stage in the two areas. In both models,2,3 STD interventions are effective early in the AIDS epidemic. However, the Van Vliet and Habbema model predicts an impact of STD prevention and control even if implemented at a mature stage of the epidemic. The Mwanza results could reflect the short-term impact of STD prevention and control in an immature epidemic, whereas the Rakai study reflects the short-term impact in a mature epidemic. Understanding this concept of epidemic “maturity” requires an appreciation of the three factors influencing the generation of an HIV epidemic in a susceptible population—the probability of transmission, the duration of infectiousness, and the number of sexual partners. STDs increase HIV shedding, thereby increasing the likelihood that genital secretions contain the amount of HIV required for transmission. If there are no other risk factors, HIV is easier to transmit from male to female, probably because the volume of ejaculate is larger than the volume of cervical and vaginal secretions. However, female-to-male transmission of HIV is as likely as male-tofemale transmission if the woman has an STD.4,5 In the HIV-negative partner, an STD increases the amount of
513
COMMENTARY
susceptible target tissue and the infectious dose is lowered. Thus, both infectiousness and susceptibility increase. There are two major periods of HIV infectiousness. The first is immediately after HIV infection and the second period is end stage, when high viral loads in blood result in HIV shedding in many body fluids. In between is a latent period of variable duration. Because HIV shedding is increased in people with another STD, the latent period is disrupted and the duration of infectiousness increases.6 The higher the partner number each year, the greater the chance of encountering a partner with an STD. Among people who are sexually highly active, STDs are highly prevalent. Those with many partners will have few acts with each other. Since HIV is not easy to transmit “under normal circumstances”, they would be unlikely to transmit HIV in a single act of intercourse. However, STDs drastically change that balance, so the ability to transmit HIV is amplified every time they have sex with every partner. The size of the core (population with high prevalence of STDs and high rate of change of sexual partner) and the variation of partner number will affect the initial rate of HIV infection in the epidemic and the longterm persistence of infection within communities. The larger the core and the greater the risk factors, the higher the prevalence before the peak occurs—and the size of the peak will also influence the persistence of the epidemic in the population.7 The point that highly sexually active people have fewer acts per partner is important. In the absence of STDs, this group is less likely to transmit HIV. Another important factor is differential mortality.8 It can account for a third of observed change in an HIV core group—ie, a decrease in risky behaviour may reflect not behaviour change but the death of the people who engage in high-risk behaviour. In a mature AIDS epidemic (eg, Uganda), the infection has moved beyond phase 1 (rapid infection of the very susceptible population). Saturation of the very susceptible population and differential mortality define the end of phase 1. This phase is followed by an apparent decline or plateau, when the death rate and the new infection rate are similar and the infection is silently moving into the lowerrisk, innately susceptible population. In phase 2, individuals are susceptible to HIV infection to the degree defined by the biology of HIV and the human host. STDs are not needed to drive HIV transmission in this class of susceptibles since the lower-risk individuals have many more acts of intercourse per partner, and sooner or later transmission occurs. Studies on interactions between STDs and HIV and the Mwanza and Rakai findings suggest that prevention and control of STDs before or early in this epidemic will probably reduce STDs in the highly active core population and will have a major impact on the spread of HIV. Once the epidemic has begun, and certainly after it has moved beyond phase 1, short-term STD prevention and control will probably have little impact on the epidemic. Treatment of STDs will undoubtedly reduce the risk in an individual, but at a population level, in a mature epidemic, it will have an impact only after a long time. An alternative explanation for the differences in findings from Mwanza and Rakai could lie in the biology of the HIV clade—if the Mwanza viruses were harder to transmit through vaginal intercourse, treatment of STDs would have a greater effect, but if the viruses in the Rakai were relatively easy to transmit, treatment would have little effect. Incidentally, no intervention trial has yet taken into account three other key 514
factors that might influence the spread of HIV: dry sex and douching, bacterial vaginosis, and genital herpes. All are highly prevalent in the developing world and could influence transmission rates. The scientific evidence supports STD control as an intervention that will have enormous impact in the early phase of the HIV epidemic. Furthermore, on the basis of Nordic experience (where the prevalence of HIV infection is low, and where low prevalence of STDs reflects comprehensive national STD programmes), low levels of STDs in a population could prevent a heterosexual epidemic. Adolescents are continually entering the pool of new susceptibles. In view of the early age at first intercourse, adolescents commonly have many lifetime partners. Prevention of STDs in these populations might shorten the second phase of the HIV epidemic. The Mwanza and Rakai results tell us that STD prevention and control is feasible, effective, and affordable. What next? • STD prevention and control should be implemented in all populations where STD prevalence is high and HIV prevalence is low. • Long-term STD programmes should be implemented where the HIV epidemic is mature (HIV prevalence high, STD prevalence variable). These programmes should focus on adolescents. • STD services must be made available to pregnant women and their partners because STD treatment reduces the likelihood of low birthweight and adverse outcomes of pregnancy. • Any HIV vaccine or topical virucidal agent must be tested in populations where STD prevalence is low, lest the efficacy of these products in normal populations be obscured by the increased risk of HIV infection created by concurrent STDs. Sadly, the opportunity for STD prevention and control to make a difference has come and gone for 30 million HIV-infected people. The obligation that the health professions have is to the countless millions of uninfected people who are at high risk of HIV infection. Safe biomedical and behavioural interventions that reduce the risk of HIV infection are available. Use of the male condom, clean needles, antiretroviral therapy and caesarean section for pregnant women, and synthetic breastmilk are effective and should be fully supported. To that list should be added STD prevention and control. In view of the prevalence of treatable STDs in resourcelimited populations that are vulnerable to the HIV epidemic, anything short of an immediate response and a sustained commitment to STD prevention and control programmes is unthinkable.
*Penny Hitchcock, Lieve Fransen Sexually Transmitted Diseases Branch, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA; and Human Development Unit DG VIII/A2, Commission of European Community, Brussels, Belgium 1 2
3 4
5
Anderson RM, May RM. Epidemiological parameters of HIV transmission. Nature 1988; 333: 514–19. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346: 530–36. The World Bank. Confronting AIDS:public priorities in a global epidemic. NewYork: Oxford University Press, 1998:103–71. Garnett GP, Anderson RM. Strategies for limiting the spread of HIV in developing countries: conclusions based on studies of the transmission dynamics of the virus. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 9: 500–13. Boily MC. Transmission dynamics of coexisting chlamydial and HIV infections in the United States. In: Eng IR, Butler WT, eds. The hidden
THE LANCET • Vol 353 • February 13, 1999
COMMENTARY
6
7
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epidemic: confronting sexually transmitted diseases.Washington, DC: Institute of Medicine/National Academy of Scientific Press; 1997: 316–29. May RM, Anderson RM. Heterogeneities, cofactors and other aspects of the transmission dynamics of HIV/AIDS. In: Gottlieb MS, ed. Current topics in AIDS, vol II. Chichester:Wiley, 1989: 33–80. Anderson RM. The transmission dynamics of sexually transmitted diseases: the behavioral component. In:Wasserheit JN, Aral SO, Holmes KK, Hitchcock PJ. Research issues in human behaviour and sexually transmitted diseases in the AIDS era. Washington DC: American Society for Microbiology, 1991: 38–80. Blower SM, van Griensven GJP. Effect of differential mortality on risk behavior change in cohort studies. J Acquir Immune Defic Syndr 1993; 6: 1364–67.
Link between psychiatric dysfunction and dizziness Primary-care patients who complain of dizziness have been found by L Yardley and colleagues to have a significantly higher rate of psychiatric disorder than agematched controls who do not report this symptom.1 Some patients had mild abnormalities of auditory, vestibular, and oculomotor functioning, but these abnormalities were found in a similar number of controls. Dizziness was associated with a trend towards abnormalities of the balance system, although the extent of these changes was mild. Thus, a community-based group of patients with dizziness was more typically characterised by psychological dysfunction, particularly symptoms of anxiety and depression, than by neurootological disturbance. The association between negative affectivity (a psychological trait with high levels of anxiety and depression) and physical symptoms is not restricted to dizzy patients. This combination is also seen in general epidemiological health surveys and syndromes such as chronic fatigue syndrome, irritable bowel syndrome, and chronic pain.2,3 Similarly, the finding that mild physical abnormality can occur without symptoms is also not unique to Yardley and colleagues’ study. Many people without back pain have abnormalities in their lumbar spine that are similar to those found in people who complain of chronic low back pain.4 How can the association between negative affectivity and dizziness be explained? One possible explanation is that both arise from a common neurophysiological mechanism.5 However, if the relation is essentially biologically driven, symptom reports should be in keeping with laboratory findings. Whereas Yardley and colleagues did not investigate this association, studies of patients’ reports of fatigue and neuropsychological problems have consistently shown no association between objective laboratory findings and symptoms.6,7 Another possible explanation is that psychological distress causes biological changes that lead to dizziness. However, this hypothesis does not take into account those patients who have neuro-otological abnormalities but no symptoms. Perhaps, the link operates the other way round. Repeated episodes of dizziness may increase psychological distress. Arguments against this disability hypothesis are found in prospective studies that show that premorbid psychological distress is a strong predictor of chronic fatigue and chronic pain—distress precedes rather than predates chronic somatic complaints.8,9 Also, patients with chronic medical disorders report different degrees of psychological distress, and there is little evidence to support the hypothesis that health problems lead to negative
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affectivity.3 Clearly, these hypotheses are unlikely to provide a complete explanation for the relation between dizziness and psychological dysfunction, because some patients with dizziness do not have comorbid psychological problems. Therefore psychological distress may be a sufficient but not a necessary factor in the development of dizziness. Any explanation should also be able to account for people who do not report symptoms, but have similar clinical signs to those who do. Another way to look at this problem is to regard the reporting of symptoms as a reflection of self-focused attention and symptom interpretation. Individuals with a high degree of negative affectivity tend to be self-focused and to look out for somatic sensations. When a new sensation is detected, these people tend to interpret the symptom more negatively than would individuals with a low degree of negative affectivity. If a sensation, such as dizziness, is thought to be a sign of illness, it is more likely to be reported than if it were thought to be a normal response to a stressful situation. The interpretation of symptoms is guided by personal ideas about symptoms, as well as by situational factors such as the relative intensity of external and internal stimuli.10,11 This hypothesis on self focusing and symptom interpretation could account for Yardley and colleagues’ findings. Psychological dysfunction has been consistently associated with high degrees of self-focusing.12 Thus, the presence of psychological changes in the dizzy patients suggests that this group has a higher propensity to notice internal stimuli and sensations. Most of the dizzy patients in Yardley and colleagues’ study met criteria for an anxiety-related condition. Anxiety-related autonomic arousal may also enhance the experience of minor neurootological sensations. In addition, these signs of arousal might be misinterpreted as signs of illness that lead to the reporting of symptoms. In conclusion, studies investigating the pathogenesis of dizziness, such as that by Yardley and colleagues,1 are important because they confirm that the treatment of patients who present with symptoms such as dizziness needs to focus on both the physical and psychological aspects. This approach should not be restricted to tertiary care, because patients with dizziness in primary care have similar degrees of psychopathological abnormalities. Future studies should focus on the mechanisms of the association between symptoms and psychological disorders so that better integrated treatment programmes can be developed.
*Rona Moss-Morris, Keith J Petrie Department of Psychiatr y and Behavioural Science, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92 019, Auckland, New Zealand 1
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Yardley L, Burgneay J, Nazareth I, Luxon L. Neuro-otological and psychiatric abnormalities in a community sample of people with dizziness: a blind, controlled investigation. J Neurol Neurosurg Psychiatry 1998; 65: 679–84. Hudson JO, Pope HG. The concept of affective spectrum disorder: relationship to fibromyalgia and other syndromes of chronic fatigue and chronic muscle pain. Baillière’s Clin Rheumatol 1994; 8: 839–56. Watson D, Pennebaker JW. Health complaints, stress, and distress: exploring the central role of negative affectivity. Psychol Rev 1989; 96: 234–54. Jensen MC, Brant-Zawadzki MN, Obuchowski N, et al. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med 1994; 331: 69–73. Brandt TH. Neuro-otological and psychiatric abnormalities. J Neurol Neurosurg Psychiatry 1998; 65: 619.
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