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Over-diagnosis of UTIs in Emergency Department leads to STIs going untreated

28 Sep, 15 | by Leslie Goode, Blogmaster

The role of generalists in the care of STIs has always been important, and, in certain contexts – like the UK – looks set to increase. So it is no surprise that recent studies have raised the question of their adherence to sexual health policy guidelines in the matter of treatment regimes (Trotter & Okunwobi-Smith (STIs); Can we Ensure Adherence (STIs/blogs)) – especially given the need to steward antibiotic defences in a world of rising antimicrobial resistance (Gonorrhoea Anti-microbial Resistance (STIs/blogs). But the importance of generalists in the care of STIs also lends a heightened interest to the identification of specific clinical practice and diagnostic protocols among generalists that are associated with the misdiagnosis of – or the failure to diagnose – STIs. For instance, in an analysis of data derived from the Australian BEACH (Bettering the Evaluation and Care of Health) programme, Freedman & Mindel (STIs) (F&M) draw attention to the failure of GPs to undertake tests to exclude specific STIs and the reliance on generic symptomatic management.

Insights into the diagnostic practice of generalists in a rather different setting are provided in a recent observational cohort study of adult women over a two-month period either presenting with, or diagnosed with, genitor-urinary infections at a US Emergency Department (ED) (Tomas & Hecker (T&H)). T&H checked hospital diagnoses against the results of the urine cultures and appropriate Nucleic Acid Amplification Testing (NAAT) which they performed on those participants for whom they had not been performed routinely. They discovered an over-diagnosis of urinary tract infections of between 39% and 52% (depending on whether contaminated cultures were taken into account) and an under-diagnosis of STIs of 37%. Of the 24 missed STI diagnoses represented in the latter figure, 14 involved misdiagnosis as UTIs. What appears to be going on here is that care-providers are treating – and mis-treating – with antibiotics for UTI on the sole basis of urinalysis. Consequently, STIs are going untreated. In fact, empirical therapy for UTI is recommended in the US for women with at least one traditional lower UTI symptom and without complicating factors. But, the results of this study show that 24% of the patients diagnosed with UTI had no possible UTI-related symptoms documented. In other words, an abnormal urinalysis result was being routinely equated with the diagnosis of a UTI.

T&H recommend that urinalysis should be eliminated from triage protocols for women present with only genital symptoms. They also express the view that cost savings from not performing urine cultures may be more than outweighed by the costs of unnecessary antibiotic therapy and the longer-term costs of missed STI diagnoses.

More generally, the poor diagnostic practice exhibited in this study may usefully serve to highlight one of the characteristic failures to which the management of genitor-urinary conditions in general practice – and not just in US Emergency Departments – may be prone.


Take a trip to Brisbane – the World STI and HIV Congress

4 Sep, 15 | by Leslie Goode, Blogmaster

Take a trip to Brisbane, Australia in the pages of your STI journal! (ISSTDR Brisbane).

The International Society for STD Research (ISSTDR) is holding its biennial conference down south for the first time ever – 13-16 September 2015.  What’s more, it’s being held back-to-back with the Australasian HIV & AIDS conference (16 -18 September). No surprise, this being the biggest world HIV & STD research event, presentations include papers by a number of September’s STI journal contributors as well as contributors to STI journal Online First.

So, if you don’t belong to an academic institution that will fund your trip, and you can’t afford the air fare, then sit back, and let STI journal blog guide you through some selected highlights!

At the top of the bill for us the issue of PARTNER NOTIFICATION, and – this being a British-based journal – a possible strategy, much discussed in our pages: Accelerated Partner Therapy (APT), involving treatment of contacts, without the latter having to attend a clinic (Patient Delivered v. Accelerated Partner Therapy (STIs/blog); Golden & Estcourt (STIs); Dombrowski & Golden (STIs)).

-Follow the link to find out just how APTHotline (telephone assessment of partners) and APTPharmacy (community pharmacist assessment) compared with standard partner notification in a randomized control trial: BRISBANE: Escourt & Cassell.

Also on the issue of PARTNER NOTIFICATION. Can we predict from certain key facts about contacts, which are most likely to be worth treating presumptively? An Australian cross-sectional questionnaire-based study of 1,500 Chlamydia contacts arriving at a sexual health clinic in Melbourne between 2010 and 2013 investigates predictive factors for transmission.

-Follow the link to find out what we can tell from about a contact from certain key facts about them and their behaviour: BRISBANE: Huffam & Chen

Still on the topic of Chlamydia. The emergence of new POINT-OF-CARE DIAGNOSTICS requires us to consider how they should be used in the most effective and cost-effective way. A study investigates use of Gram-stained urethral smear analysis – to see the effect of restricting the test to male patients currently displaying symptoms rather than routinely administering it to all high risk male patients.

-Follow this link to discover what impact this change in diagnostic algorithm had on diagnostic accuracy, loss to follow-up and cost-effectiveness: BRISBANE: Bartelsman & De Vries

Moving from Chlamydia to HIV/AIDS. The topic of DELAYED LINKAGE TO CARE is one that has occupied our contributors (Lee & Gazzard (STIs)) and seems to have recently come to the forefront of attention (Retention in Care rather than Diagnosis (STIs/blogs)). Skarbinski & Mermin make a case for shifting the focus of public health investment, in the US at least, towards retention and linkage, on the grounds that this could have a more significant impact on onward transmission than simply expanding t testing. This is, of course, not only a problem in the US. A recent STIs Online First contributor is presenting to the conference on a study to quantify the problem of delayed linkage to care in the Netherlands, and to pinpoint its social determinants.

-Follow this link to discover what proportion of newly-diagnosed in the Netherlands are linked to care within four weeks, and what social factors confer vulnerability: BRISBANE: Van Veen & Van der Sande


‘Up-stream’ of the above studies that seek to inform clinical practice, the ISSTDR Conference features contributions in the areas of EPIDEMIOLOGY and SOCIAL BEHAVIOUR.

First EPIDEMIOLOGY. The Indigenous peoples of Australia constitute a sub-population with distinct needs which it is no surprise to find receiving some attention at a conference in Brisbane.  A contributor to STIs On Line First addresses the topic of a complication of Gonorrhoea that would be a rarity in other populations, but is apparently “an important differential when dealing with patients with undefined sepsis and associated joint disease” among the Indigenous population of Central Australia: Disseminated Gonococcal Infection (DGI).

-Follow this link to discover how serious a problem Disseminated Gonococcal Infection (DGI) is in this area, and what kind of people are affected: BRISBANE: Tuttle & Maguire

Moving now to SEXUAL BEHAVIOUR . The issue of ‘chemsex’, and its implications for MSM sexual health, has recently been a topical one (Chemsex & HCV Transmission (STI/blogs); Matser & Van der Loeff (STIs)).   A study published On Line First and presented at the Conference traces back an outbreak of Shigella flexneri among MSM to reported social media encounters, chemsex drugs and chemsex parties.

-Follow this link to find out about lifestyle and sexual behaviour factors explored through in-depth quantitative interviews: BRISBANE: Gilbart and Hughes

The final stop in our whistle stop tour is a different kind of SEXUAL BEHAVIOUR study. This is an application of modelling to demographic data relating to non-co-habiting sex partnering in 25 countries of sub-Saharan Africa. What are the roles of men and women, married and unmarried in driving heterogeneity in sexual networks, and how does this vary by country?

-Follow this link for mean values and variances of number of partners by sex, marital status and country: BRISBANE: Omori & Abu-Radadd

A case for immediate ART initiation in all HIV diagnosed, regardless of CD4+ count?

28 Aug, 15 | by Leslie Goode, Blogmaster

The year 2013 saw the WHO recommended threshold for treatment of HIV+ patients with ART rise from a count of 350 CD4+ per mm3 to one of 500 CD4+ per mm3.. The threshold had been fixed as early as three years before (2010) at 350 CD4+ per mm3 (WHO ART recommendations). These recommendations have doubtless been made with a view both to improving individual outcomes and preventing transmission. However, their implementation poses, and will continue to pose, a serious challenge, especially in resource-poor settings. Writing in 2010, Hamilton and Crowley (STIs) estimated that setting the threshold for ART initiation at 250 CD4+ would by 2012 increase the need for treatment by a median of 15%, whereas setting at 350 CD4+ would increase it by 42% and 500 CD4+ by 84%. Contributors like Hallett & Garnett (STIs) (Zimbabwe) and Zwahlen (STIs) have sought to develop projections for individual countries.

It may not be so long before the modellers have, once again, to revise their calculations. Results of the Strategic Timing of Antiretroviral Therapy (START) trial, a recent multi-continental RCT, make a case for not deferring ART initiation, regardless of the patient’s CD4+ count. A total of 4,865 patients in 35 countries were randomized to an immediate and a deferred initiation group, and followed over a three-year period. The trial compared primary end-points, including death and serious AIDS-related, and non-AIDS-related, health events, over a three-year period. Among the commonest AIDS-related events were tuberculosis, Kaposi’s sarcoma and malignant lymphoma. Non-AIDS related events included cardio-vascular disease and non-AIDS related cancers. Hazard ratios for serious AIDS-related and non-AIDS related, events were 0.28 and 0.61, respectively. There have been concerns about the negative health impact of ART especially on cardio-vascular disease. But no safety concerns in the immediate-initiation group were identified. However, as the authors recognize, the study was underpowered for investigating the potential negative effects of early ART initiation on individual non-AIDS related events, because of the relatively limited number of events and early termination of the deferred therapy strategy.

In principle, the benefits of raising the threshold for linkage to care are clear. In due course, we may expect to see yet another upward adjustment in the WHO threshold. However, recent studies point to inadequate availability of care, late diagnosis (even by current standards), and poor retention in care as significant factors in suboptimal health outcomes (Mubezi & Shuha (STIs); Hussey (STIs). So what such a change in guidelines would deliver in real terms is hard to evaluate, and no doubt depends on the context of implementation. Yet, even in the relatively more resource rich settings (US), some recent research has argued for the reallocation of resources from linkage to retention in HIV care, in order to optimize utilization of scarce resources (Retention in Care (STI/blogs); Sherer (STIs). This recommendation would seem hard to square with the prioritization of ever lower thresholds for linkage to care.

At all events, this study demonstrates the benefits to the individual of prompt linkage to care whatever the stage in the progression of his/her infection.

Does fear work? New York City experience with “hard-hitting” public health advertising campaigns.

5 Aug, 15 | by Leslie Goode, Blogmaster

“Young gay men glance fearfully (even shamefully) at the camera.  As the sound of a heartbeat quickens,  … the viewer sees … a femur, shown in x-ray, snapping,  … gray matter shrivelling,  … a digitally enhanced internal view of the body fades to a bloody, raw anus, with Frankenstein-like surgery scars, of an African American man”.

This was the “hard-hitting” New York City anti-HIV campaign – “It’s Never Just HIV” – that began December 2010, but seems, as of 2015, to have been shelved in the face of widespread controversy.  Is this kind of thing appropriate?  Does it even work?

Fairchild & Colgrove (F&C) chronicle a decade of “fear-based” public health campaigns in New York City under Mayor Michael Bloomberg, placing the recent HIV campaign in the context of campaigns on tobacco, obesity, and HIV, and focussing on public reactions and the official response to them.  Readers from the UK will be reminded of the famous – or infamous – HIV/AIDS campaigns of 1986-7,  discussed by a number of past contributors to STIs (Nicoll & Catchpole (STIs); Ross & Scott (STIs); Beck & Miller (STIs)).

In NYC, the tobacco campaign, at least, seems to have had some success, being associated with a 35% decline in smoking over the period 2002-2010.  The impact of the obesity and HIV campaigns, launched on the strength of that success, has proved harder to evaluate; but the orthodoxy among health educators of an earlier generation that “fear-arousing messages backfire” seems to have been punctured.  It is noteworthy that the most serious objections to some of the NYC campaigns have concerned not, so much the restriction of individual autonomy, as their stigmatizing affect on socially disadvantaged groups – e.g. black gay men.

The probable impact of the 1986-1987 campaign in the UK is evaluated by Nicoll & Catchpole (STIs) (N&C) in terms of new attendances at GUM clinics requiring diagnosis – which declined by 117/105 in men, and 42/105 in women during the campaign, then plateaued from 1987, only to rise again in the 1990s.  F&C note that the NYC campaign appears to have failed to interrupt the “apparent continuing increase of HIV diagnoses among young men of color having sex with men”.  There is reason to believe that fear can work – “where people believe they have the capacity to act” (see Fairchild & Colgrove, notes 4-9).


Can we ensure adherence to STI treatment guidelines in a world threatened by antimicrobial resistance?

27 Jul, 15 | by Leslie Goode, Blogmaster

Sexual health care in the UK has traditionally centred on specialist GUM (genitor-urinary medicine) services.  Since the turn of the twenty-first century primary care has played an increasing role, however.  The 2012 Health and Social Care Act is in line with this tendency, with most GP (general practitioner) practices now being commissioned to provide level 1 STI screening.  Questions have recently been raised about the conformity of care provided by GPs to national guidelines, established for the UK by the British Association for Sexual Health and HIV (BASHH) (Trotter & Okunwobi-Smith (STIs)).

So what is currently the extent of GP involvement in the UK in care of infections previously dealt with by specialist services (i.e. Chlamydia and Gonorrhoea), and how is this impacting on the treatment of these conditions?  Wetten & Hughes (W&H), in a population-based study using data from the UK Clinical Practice Research Datalink (CPRD), provide the answers to both questions.  As regards the role of GPs, the proportion of Chlamydia cases they diagnosed varied over the study period (2000-2011) between 16% and 9%, and appeared to be on a downward trajectory, while the proportion of Gonorrhoea cases fluctuated between 6% and 9%.  As for the quality of care received in general practice, there is a marked disparity between the two conditions.  Whereas, in the case of Chlamydia, 90% were prescribed a recommended therapy, of the patients presenting with Gonorrhoea only 40% received the recommended anti-microbial regimen.  Ciprofloxacin continued to used (42% of prescriptions in 2006, 20% in 2011) long after the 2005 change in national treatment guidelines favouring cephalosporins.

These findings appear to corroborate the concerns expressed by UK patients in another recent study that their expectations for appropriate in-house care or referral to specialist services were not always being met (Sutcliffe & Cassell (STIs)).

The issues raised by these UK studies around the adherence to prescribing guidelines by generalist physicians are not, of course, unique to the UK.  Similar concerns have been voiced in studies based on data emerging from the BEACH (Bettering Evaluation and Care of Health) programme in Australia (Santella & Hillman (STIs); Freedman & Mindel (STIs); Johnston & Mindel (STIs), as well as in studies from more diverse settings (Khandwalla & Rahman (STIs)).  Quite apart from the need to optimize patient outcomes and reduce the burden of infection in the population, the problem of adherence by generalists to guidelines raises more general questions.  The issue of antimicrobial resistance has prompted recent national interventions to “steward” our remaining antibiotic defences (Gonorrhoea antimicrobial resistance (STIs/blog).  Such policies will evidently depend on the adherence to guidelines, including by generalists – especially in settings where they are responsible for much of STI care.  In a world where Gonorrhoea – and perhaps one day Chlamydia – is set to become increasingly hard to treat, the problem of ensuring the conformity of generalists to universal standards of treatment is unlikely to go away.



Myth or reality? Are social media triggering an explosion in sexually transmitted infections?

23 Jul, 15 | by Leslie Goode, Blogmaster

On the whole, where STIs are concerned, social media have tended to be considered as a potential force for the good in public health, offering a new resource for the management of HIV patients, or opportunities for disseminating health messages via peer education (Swanton & Mullan (STIs); Peer group education (STIs/blog)).  Recently, however, there have been a number of studies that have drawn attention to the negative implications of social media.  Last June a study by Beymer & Morisky (STIs), based on data on MSM attendees at the Los Angeles Gay and Lesbian Centre, concluded that, among the 7,000 participants, those who had used geo-sexual networking apps to meet up with a partner had greater odds for testing positive for gonorrhoea (OR 1.25) or chlamydia (OR 1.37) than those who employed in-person methods.

Recently, this more negative side has been receiving ever more attention in the US, especially in connection with HIV transmission.  A yet unpublished but widely publicized study, Agarwal and Greenwood (A&G), investigates hospital attendances for asymptomatic HIV (including acute and silent phases of the infection)  in Florida over the period 2002-2006 when the piece-meal introduction of the digital commerce platform, Craigslist, appears to have greatly facilitated on-line social transactions through its “casual encounters” forum.  It has also offered researchers the chance to record what they describe as a “natural experiment”, as successive counties have experienced the effects of entry into the platform.  A&G estimate the health “penalty” of entry into Craigslist at a 13.5% increase in attributable HIV infections – equivalent in financial terms to an additional burden of $592 million on the State of Florida.   This finding has recently been cited in connection with the precipitous rise in STIs in Rhode Island recently reported in an official Rhode Island Goverment press release and in the press coverage (Huffington Post) – 79% in syphilis; 30% in gonorrhoea; 33% in HIV over the year 2013-2014.

But A&G are concerned with more than estimating the magnitude of the effect.   The recent paper also claims to be the first study to attempt to determine exactly where that penalty of increased HIV infection due to social networking is actually falling – a question that is evidently of great interest to public health specialists who need to be able to target their interventions.  On the face of it, this is something of a puzzle.  HIV appears to be most heavily concentrated amongst the very sectors of the population who are most digitally disadvantaged.  So what could be going on?  To answer this question, A&G seek to disaggregate the Craigslist effect by ethnicity, income-level (as determined by enrolment in Medicaid) and gender.  What emerges from their analysis is that the effect of Craigslist entry is contained almost exclusively within the Afro-Caribbean (as opposed to Latino or “Caucasian”) population.  A&G seek to explain this apparently disproportionate penalty accruing to the digitally disadvantaged.  They argue that the “digital divide” is probably not “binary”, but more like a continuum.  We should not, in other words, necessarily think of “digital disadvantage” – at least for an important proportion of the disadvantaged – in terms of the total absence of access or skill.  It is therefore conceivable that it should be associated with a negative effect, i.e. the increased HIV incidence following Craigslist entry.  “Digital disadvantage”, they argue, is likely to be a matter of the limited capacity to utilize on-line resources for “welfare-enhancing activities” rather than a total unavailability of those resources.


Incidental gonorrhoea screening in the general population via dual NAAT is no benefit

12 Jun, 15 | by Leslie Goode, Blogmaster

Fifer & Ison (STIs) express concern over the use of the “dual” nucleic acid amplification tests (NAATs) for the detection of chlamydia and gonorrhoea in the context of chlamydia screening in the UK.  Additional testing for gonorrhoea, when the real target is chlamydia, does not necessarily confer an additional net benefit.   This is because even a high specificity test such as Cobas 4800 (Perry & Corden (STIs); Rockett & Limnios (STIs)) will generate a high proportion of false positives when the infection tested for has extremely low prevalence, as in the  case of gonorrhoea in the general population.  And the potential disbenefit of the additional test in terms of the psychological impact, and the impact on relationships, of false positive diagnoses could easily outweigh the medical benefit represented by the diagnoses which are accurate (Dixon-Woods & Shukla (STIs); McCaffery & Wardle (STIs)).

The potential impact of the adoption of the dual NAAT as a stand-alone test – if not confirmed by further testing using either a second NAAT or else culture – is illustrated by a recent Australian study published in the Medical Journal of Australia (MJA).  Chow & Fairley perform a retrospective analysis of insurance and notification data from Melbourne over the years 2008-2013.  They seek to demonstrate that the apparent rise in identified gonorrhoea cases amongst the general female – non-indigenous – population (from 98 to 343) is at least partly an “artefact” of the growing employment by laboratories of the dual NAAT.  They do this by eliminating the alternative possibility of a genuine increase in gonorrhoea in the general population.  To this purpose they use their data to investigate changes in the proportion of positive dual NAAT gonorrhoea diagnoses to the number of dual NAAT test ordered, over the period during which dual NAATs were being introduced.  They also investigate rates of positive gonorrhoea diagnoses over this period at a “sentinel” clinic in Victoria where culture alone was used as a means ofgGonorrhea diagnosis.  They find that the proportion of positive dual NAAT diagnoses in Victoria remained relatively constant over time (around 0.2-0.3%), as did the proportion of positive culture diagnoses at the Melbourne clinic (around 0.4-0.6%).  Of 25 untreated women who had a positive NAAT result for gonorrhoea and were referred to the Melbourne clinic, only 10/25 were confirmed by culture.  The authors comment that this is in line with what might be expected in the light of the published specificity of the various NAAT tests employed.

C&F recommend that laboratories suppress gonorrhoea diagnoses from the dual NAATs.  An MJA editorial in the same issue questions the feasibility of this.  Instead, the editors propose that the NAAT should, in the case of Gonorrhoea, be used as either a triage, with positive diagnoses confirmed by culture, or as an add-on where high prevalence populations are first tested by culture.  They also consider the possibility of confirming the initial NAAT with a NAAT using a different target.  However, they come down in favour of retaining culture in the diagnostic pathway on account of its value as a means of assessing resistance.  They also question whether even the double NAAT would guarantee adequate predictive value in very low prevalence populations.

Evidently, further studies are required.

Why Tanzania seems unlikely to meet UNAIDS targets for HIV/AIDS prevention.

12 Jun, 15 | by Leslie Goode, Blogmaster

The UNAIDS 90-90-90 Target has set the goal that, by 2020, 90% of the HIV infected should know their status, 90% of those diagnosed should be in treatment, and 90% of those in treatment should achieve viral suppression.  The  UNAIDS GAP Report (2014) presses the need for countries to achieve a major redeployment of effort and resources towards tackling HIV among at-risk populations with a view to achieving that target (UNAIDS (STI/blog)).

Redeployment, a report by Congressional staff delegates on a visit to Tanzania hosted by the Infectious Diseases Society of America’s (IDSA) Global Education and Research Foundation gives a detailed account of the practical problems facing the attempt to make such ambitions a reality on the ground – even where UNAIDS recommendations are embedded in official government planning policy.  Evidence from visits of the staff delegates to Dar-es-Salaam, Zanzibar and Mbeya in the rural highlands is illustrated with well-chosen photographs.   These problems fall into three general categories.

First, there is a human resource problem.  At present, there is a 65% vacancy rate for health-care positions in the public sector.  According to the government figures, health workforce capacities have steadily declined from 67,000 in 1994/5 to 54,245 in 2002 to 48,000 in 2015.  The PEPFAR (President’s Emergency Plan For AIDS Relief) operational plan attributes this in some measure to gaps in Tanzania’s education capacities with large classes and poorly trained teachers, leading to pupils leaving school without adequate study, problem solving and analytic skills.

As regards redeployment of these limited resources in line with UNAIDS recommendations, this is hindered by the fact that at risk groups may be criminalized (e.g. drug-users, sex workers, MSM) and are certainly stigmatized.  Much of the outreach to them is through civil society organizations.  While the government has policies to support and defend their efforts, there is little in the way of financial investment.  Civil society organizations are hampered by the largely voluntary nature of their workforce, and the absence of adequate data concerning the size and whereabouts of at-risk populations (though it is estimated that between 2010 and 2015 the number of IDU rose from 25,000 to 50,000).  The prison population seems to be altogether inaccessible.

Thirdly, HIV transmitted to children born to infected mothers is often ignored, and the number of adolescents dying of AIDS has risen by a third since 2005.  This is partly because stigma surrounding a disease associated with IDUs, sex-workers MSM prevents parents from seeking diagnoses for their children.  The situation is not helped be the frequently poor state of record-keeping with no digitalization and folders “jammed into, stacked on top of, and spilling out of record cabinets”.

Though no doubt inadequate, data on “at risk” populations is not altogether absent.  Studies published in STI journal relevant to populations in specific places visited by delegates include an evaluation of surveys of MSM in Zanzibar, Haji & Kibona (STIs), and a discussion of the socio-demographic context of the epidemic in Mbeya, Riedner & Groskurth (STIs), focussing on female bar-workers.  As a poor but high-mobility rural population, Mbeya appears to share some socio-demographic characteristics with Mzanza province in the NW (bordering Lake Victoria) which has figured in a number of studies at the beginning of the last decade.  A number of these focus on barmaids as a particularly high-risk population (Hoffmann & Hoelscher(STIs); Boerma & Mwaluko (STIs); Bloom & Boerma (STIs)).


Increased HIV infectivity in the acute phase of infection may be a less important factor in HIV transmission than we thought

12 Jun, 15 | by Leslie Goode, Blogmaster

Assessing, as far as we can, the preventative impact of ART on HIV transmission dynamics is evidently very important – both to inform judgments about ART initiation (Wayal & Hart (STI); Cohen (STI)), and also, at the policy level, to be able to evaluate the possible preventative gains of ART scale-up (Shafer & White (STI); Boily & Mishra (STI)).   One important piece of the jigsaw is the impact of ART on sexual behaviour.  This has been discussed by a number of recent studies (Wayal & Hart (STI); Hogben & Ford (STI); Shafer & White (STI)).  Another piece of the jigsaw is the impact of ART on HIV infectivity.  Of particular concern here are the relatively high levels of infectivity that occur in the period immediately after infection.  In view of this, investigators have stressed the importance of the earliest possible initiation of therapy, if the full preventative benefits of ART are to be enjoyed (Cohen (STI)).

The recent study, Bellan & Meyers (B&M), addresses itself to this second, important but potentially less easily investigable piece of the jigsaw. They observe that investigators have tended to proceed on the basis of the known relationship between viral load and infectivity. Empirical evidence of relative infectivity of acute versus chronic phases of the infection is practically unobtainable, for various reasons.  For a start, newly-infected individuals are rarely diagnosed in the acute phase and, if infected by stable partners may provide no evidence on onward tradition; if susceptible non-infected partners are at risk, then, clearly, ethical guidelines dictate that further transmission be stopped – not investigated.  According to B&M, most subsequent studies have relied for direct epidemiological measurement of acute phase infectivity and duration on a retrospective cohort in Rakai, Uganda (Wawer & Quinn; Hollingsworth & Fraser). B&M reassess previous analyses of this evidence.  They find significant bias – especially in two areas.  The first has to do with the neglect of the contribution to total risk of couples who were censored from the cohort owing to couple dissolution, loss to follow-up or study termination.  The second concerns the extent to which some of the estimated difference in risk between the acute and chronic phases may reflect heterogeneity in the risk behaviour of those couples entering the study sero-discordant, as against those entering it sero-concordant negative.

The findings of B&M are intriguing. They argue that combined effect of these sources of bias in earlier analysis of the Rakai evidence has been enormously to inflate estimates of relative acute phase – relative to chronic phase – HIV infectivity. B&M estimate the relative hazard of transmission during acute phase at 5.3, the acute phase duration at 1.7 months, and the “extra-hazard months” contributed by the acute phase (a measure adopted by the authors in order to ensure comparability of study results) at 8.4. Previous estimates give levels of increased infectivity due to acute phase which are equivalent to between 31 and 141 hazard months. If the results of B&M are confirmed in subsequent studies, the preventative gains of ART scale-up could be greater than hitherto supposed.

Achieving HPV herd immunity cost-effectively. When does it make sense to allocate resources preferentially to boys?

23 Apr, 15 | by Leslie Goode, Blogmaster

Recent empirical studies of HPV vaccination have provided evidence that marginal vaccination costs increase with coverage.  Let us take into account – they argue – not just the vaccine price, but the cost of education and outreach programmes that would be needed so as to reach the yet unvaccinated population.  If we do so, we are likely to find that raising the vaccination rate for pre-adolescent girls, let us say, from 40-41%, proves considerably more expensive than raising it from 20-21%.  This, in turn, raises the question whether – given the achievement of herd immunity is the ultimate goal – resources are necessarily best allocated when directed to the female rather than the male pre-adolescent population. Could it even be that – at certain levels of coverage and a certain rates of increase in marginal vaccination cost (for girls and for boys) – resources might be more effectively allocated to the vaccination of pre-adolescent boys? Ryser & Myers in a recent study seek to model the impact of marginal cost increase in order to answer this question.  In the case of US, at least – with rates of vaccination standing currently, for girls and boys, at, respectively 37% and 13.9% – they argue in cost benefit terms for re-directing resources to boys.  However, the question is no doubt relevant to other countries in which HPV has been introduced, but levels sufficient for herd immunity, have not yet been achieved.

Optimal allocation of new resources as between girls and boys for a given level of vaccination is indicated in the diagrams on p.40.  Marginal vaccination cost increase is estimated at a higher, a lower, and zero level.  What is striking is the radically different patterns of optimal allocation between girls and boys in those three scenarios.  At the very least, the results challenge the orthodoxy of the superior cost benefit of female vaccination. They also indicate the importance of further empirical research into marginal vaccination cost increase.

The limitations of the study are largely due to the assumption of a closed sexual network of 14-18 yr old heterosexual adolescents.  The attempt is made to factor in the impact of various complicating factors, such as the assortativity of vaccine uptake with sexual activity, the likely presence of additional relationships between females inside, and older males outside, the network, and asymmetric vaccination cost curves as between girls and boys.  But the most serious limitation was beyond the power of the study to address.  This is the restriction of the modelled network to heterosexual relations, and the exclusion from consideration of a large number of HPV-related conditions such as anal and oro-pharyngeal cancers which have higher incidence among MSM and HIV-infected individuals (Lawton & Asboe (STIs); English & Pourbohloul (STIs)).  One wonders, therefore, whether the case for male HPV vaccination is not a great deal stronger than might appear from this paper.  At all events, a case is made that, even when these conditions are excluded, a greater allocation of HPV vaccination resources to males may be justifiable – e.g. currently in the US.  For the impact of the recent extension of the HPV vaccination programme to males in Australia (the first country to have taken this step (2013)), see Korostil & Donovan (STIs).

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