The economic case for investment in the prevention of vertical (mother to child) transmission of HIV and syphilis is easily made – even in low resource settings.  Yet the virtual elimination of maternal HIV transmission remains a goal still to be achieved in many regions, while syphilis in pregnant mothers is often unaddressed with tragic consequences in terms of peri-natal mortality.

The final resolution of these problems will no doubt require a multi-dimensional and holistic approach of the kind recommended by the UNAIDS report.  Yet a recently trialled technology, designed by biomedical engineers from Columbia University, may ease the way to that solution:  it promises to deliver a point-of-care HIV/syphilis test that replicates all the steps of ELISA (enzyme-linked immunosorbent assay), with a sensitivity and specificity to match traditional benchtop assays – but at low cost, with minimal equipment, and requiring no user interpretation (all important considerations in low resource settings).

A recent paper in Nature Medicine describes the technology – the “mChip” assay (mobile microfluidic chip for immunoassay on protein markers), and reports the encouraging results of three trials undertaken in Rwanda.

The device consists in a microfluidic cassette (5.4 cm x 8.5 cm) costing $0.10.  A metal spacer, displacing 6 ml of air in a syringe, is used to draw into the cassette a fluid plug consisting in 14 reagents separated by air spacers.  The procedure produces a signal that can be detected using low cost optics such as light emitting diodes and photodetectors (costing $0.50 and $6.00 respectively).  The test requires less than 1μl of unprocessed whole blood and is complete in 15 minutes.

When tested in Muhima Hospital Kigali on 70 specimens of known HIV status the device demonstrated an overall sensitivity of 100% and a specificity of 96%.  It was also evaluated on 101 archived specimens from couples receiving HIV voluntary counselling, and showed similar levels of sensitivity (100%) and specificity (94%).  Thirdly, the ability of the device to perform a combined HIV-syphilis test was investigated at Project Ubuzima, using 67 serum and plasma samples collected for a separate research study on female sex workers in Kigali.  The duplex test showed sensitivities of 100% and 94% and specificities of 95% and 76% for HIV and syphilis respectively.

A paper covered in a previous blog (Screening for syphilis in pregnancy: evidence for the effectiveness of doing something) reviews the disastrous failure in many low resource contexts to test and treat syphilis in pregnancy.  For all the priority rightly given to the prevention of HIV, the inclusion of syphilis in the duplex test seems a commendable element.

Curtis D Chin et al., “Microfluidics-based diagnostics of infectious diseases in the developing world”, Nature Medicine 17, 1015-1019, 31^st July 2011

http://www.nature.com/nm/journal/v17/n8/full/nm.2408.html

2 million pregnant women, mostly in low and middle-income countries, have syphilis in pregnancy resulting in adverse outcomes in 69% of cases. Given known low costs of screening and treatment, the figures are appalling. Is it really lack of evidence for the effectiveness of interventions that is holding things back?  Yet one can only support the aims of a recent systematic review in the Lancet in seizing any opportunity to attract wider public attention to this issue.
The problem for the reviewers, however, is that randomised controlled trials providing the kind of evidence the authors require would no longer be ethical. Given the low-grade nature of the available evidence, there has been a tendency to conclude that there existed no intervention studies showing the effect of interventions on preterm birth. Not content with this, the authors of this review return again to the evidence in order to glean whatever may be gleaned.
The resulting 10 studies are very heterogeneous. As for the interventions themselves, it is evidently hard to generalize beyond the important common features of decentralized testing and same-day treatment. The outcomes are similarly varied and include, in various combinations: i. proportion of women receiving ante-natal screening (5 studies); ii. proportion of women receiving at least one dose of penicillin (6); iii. infants born with congential syphilis (4); iv. peri-natal deaths (3); v. stillbirths (3). Evidence of increased uptake of testing and treatment (i. and ii.) is disappointingly inconclusive; but evidence of adverse pregnancy outcomes (especially iv. and v. ) is stronger, allowing the inclusion in the headline findings of a figure for reduced peri-natal death (RR) of 0.46, and for still birth of 0.42.
Given the small number of studies and their heterogeneity, would we have learnt more about the components of these studies from a narrative presentation? Is the preference for the systematic review format driven by the need to obtain useful headline figures that would furnish statistical ammunition for the worthy cause of syphilis prevention?
It is interesting that in one study reviewed (Potter et al.) syphilis testing was increased only in an intervention that included improved HIV-PMTCT services.

S. Hawkes, “Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis”, The Lancet, published online 16th June 2011

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70104-9/abstract

The annual report of the UK Health Protection Agency (17th June, 2011) offers a concise and accessible statistical overview of recent trends in STIs (not including HIV/AIDS), as well as details of the UK Chlamydia screening programme and the recent epidemic of lymphogranuloma venereum (LGV).
The overall picture suggests a slight decline (1%) in STIs in 2010, and – for the first time since records began – no rise in chlamydia diagnosis (despite the continued scale-up of testing). The overall decline conceals a continued rise in gonorrhoea (3%) and herpes (8%) diagnosis, partly attributable to more sensitive diagnostic tests.
Those aged under 25 account for 63% of chlamydia diagnosed, 54% of genital warts, 47% of gonorrhoea, 41% of genital herpes. Trends since 2008 differ somewhat according to sex. Among women the 15-24 year olds are very considerably the most severely affected group, and have seen a continued slight decline in gonorrhoea and genital warts diagnosis. Among men cases seems less unevenly spread overall, but with 20-24 years old the most affected. These have seen a continued rise in gonorrhoea diagnosis.
Men who have sex with men (MSM) are the other key population. These account for 64% of syphilis and 40% of gonorrhoea. Here there is less cause for cheer. Gonorrhoea diagnosis has continued to rise (up by a third in the past year), while Syphilis continues on its upward trajectory. Given the high risk of exposure to HIV/AIDS in the MSM population (a dimension of the STIs picture that is absent from this report, which fails to make the link between STI and HIV), these figures are particularly worrying.
The report concludes with statistics for the epidemic of lymphogranuloma venereum (LGV). This began in the late 2004 and has intensified considerably, with a third of the total number of 1,665 cases having been diagnosed since 2010 – largely among white HIV positive MSM.

HPA, Health Protection Report, HIV/Sexually Transmitted Infections (STIs), vol. 5, no.24, 17th June 2011

http://www.hpa.org.uk/hpr/infections/hiv_sti.htm

Almost thirty years exactly after the first official AIDS diagnosis on 1st June 1981, and 10 years since the landmark UN General Assembly Special Session on HIV/AIDS, member countries meet once again to review the global response to HIV AIDS at the UN General Assembly High-Level Meeting on HIV/ AIDS from 8–10 June in New York. Before the national representatives will be a declaration, formulated by UNAIDS (the Joint United Nations Programme on HIV/AIDS). Known as the “zero draft” (zero infections, zero discriminations, zero Aids related deaths), the declaration is publicly available (see below) and has already been widely discussed by member countries. The scale-up of provision envisaged by the declaration has serious cost implications, as well as implications in the realm of intellectual property rights (TRIPS) where these affect pharmaceutical products. Elements of the declaration are known to be strongly resisted by some developed countries. The recently published (2nd June) UNAIDS report AIDS at 30: Nations at the Crossroads (p.105) places a figure on the proposed scale-up of $22-23bn by 2015, as compared with the current $16bn – in other words a global increase of about a third in order to “decisively alter the course of the epidemic in the next decade”. The message coming out of the UNAIDS Report (published a week in advance of the conference) is that the world would be well advised to commit to the financial implications of placing global resourcing on a more rational and sustainable footing. The necessary up-scaling of global and national efforts is a rational investment and will pay off in the middle- to long-term.
Simultaneously with the UNAIDS report there appeared a health policy paper in the Lancet, Towards an improved investment approach for an effective response to HIV/AIDS. The latter is authored by Bernhard Schwartlaender (principal author) of UNAIDS and other researchers from UNAIDS and a wide range of other organizations “on behalf of the Investment Framework Study Group”. Irritatingly for the general medical reader, its natural constituency, the Lancet paper gives no account of the history of this group and fails to make, within the context of the paper itself, any explicit link to UNAIDS or other international organizations. (How, after all, are we to read a “health policy” paper without situating it in the context of contemporary “health policy” developments?) However, the UNAIDS Report (p.105) appears to refer to the framework proposed in the Lancet paper as “a 2011 investment framework proposed by UNAIDS and its partners”.

Towards an improved investment approach for an effective response to HIV/AIDS
The paper points to the shortcomings of the “prevailing commodity approach” which targets discrete interventions rather than overall results. It proposes to replace it with an “investment framework” incorporating a range of social as well as medical interventions synergizing with general development objectives. The first section of the paper describes the investment framework. The second examines the resource implications as these emerge from a modelling exercise based on the investment framework, estimating resource needs and returns on investment for 139 low- and middle-income countries.
The investment framework is characterized by a concern to give due weight to the social and behavioural aspect of programme activities – e.g. behavioural change especially in connection with “key populations” (e.g. men who have sex with men and intravenous drug users) and community approaches in support of HIV testing and ART adherence. In addition, the model factors in complementary strategies (“critical enablers”) – both in the area of wider social policies conducive to “rational HIV/AIDS responses”, such as stigma reduction and human rights advocacy, and in the more health specific area of incentives for programme participation or methods to improve ART adherence. Thirdly, the model factors in synergies with other development goals, such as the potential of HIV funding to act as a catalyst for the promotion of rational investment across various sectors.
Running the model based on this investment framework gives the figure of $22bn at which the authors predict resource needs will peak in 2015. Thereafter, these needs are expected to decline for three reasons: target rates for interventions will have been reached; efficiency gains will be achieved; and new infections will begin to decrease resulting in decreased need for services. The model puts figures on expenditure not only in the area of basic programme activities, but also in the area of critical enablers, and even development synergies. A case is made for the proposed framework in terms of return on the investment: the $46.5bn invested over the period 2011 – 2020 will, according to the authors, be offset by savings incurred from avoidance to treatment costs estimated at a conservative cost of $40bn.

AIDS at 30: Nations at the Crossroads.
Aspects of the proposed up-scaling of the global response, as set out in Chapter 3 of the Report, are in line with the approach already discussed in relation to the investment framework, and build, of course, on existing UNAIDS policies (see below: UNAIDS Strategy:2012-2015:Getting to Zero). In relation to resource implications, the Report actually refers to the investment framework (p.105) and the projections for resource needs given in the Lancet paper. The Report’s articulation of these issues could have been better organized. But the general tenor of what is proposed is captured in the slogan “sustainable outcomes”. The aspect of sustainability reflects the need for an upscale of global funding, and an increased domestic investment on the part of “high-burden” countries, consonant with their ownership of the programmes. (If current domestic investment by countries were in proportion to the disease burden and size of their health budgets, the Report tells us, investment in sub-Saharan Africa would be double what it is). The aspect of outcomes suggests a shift from an “outputs”- dominated mentality. It reflects the aspiration to a more holistic approach and “smarter metrics” which evaluate the true effectiveness of interventions, leading to investment of resources where they will bring most benefit. Ownership of programmes, their integration within the wider context of health and social policy and synergy with related development goals are consistently emphasised.
Chapters 1 and 2 of the Report offer an overview of the past decade. They chart the success of countries in meeting those targets, recording the gains in treatment access, and the reduction of vertical transmission, as well as difficulties encountered in such areas as reducing HIV stigmatization, targeting interventions at “key populations”, and communicating the safe-sex message to those at risk. Chapter 1 offers a global survey; chapter 2 provides a break-down by region (Africa; Asia and the Pacific; Eastern Europe and Central Asia; Latin American; the Caribbean; the Middle East and North Africa). Chapter 4 provides “score-cards” for individual countries in regard to: HIV incidence; ARVs to prevent new child infections; ART coverage; HIV progress indicators.

Bernhard Schwartlaeder et al., “Towards an improved investment approach for an effective response to HIV/AIDS”, The Lancet, published online, 3rd June 2011

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60702-2/abstract

AIDS at 30: Nations at the Crossroads, Joint United Nations Programme on HIV/AIDS, June 2011

http://www.unaids.org/en/resources/unaidspublications/2011/

Zero Draft, 28th April 2011

http://www.aidsactioneurope.org/fileadmin/files/5.News/5a.Announcements/hivaidszerodraftpdf.pdf

Complete HLM HIV/AIDS Zero Draft Compilation 19th May 2011 10:00pm

http://donttradeourlivesaway.files.wordpress.com/2011/05/complete-compilation-zero-draft-19th-may-2011-10pm-1.pdf

Getting to Zero: Strategy 2010-2015: Joint United Nations Policy on HIV/AIDS, 2010

http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2010/JC2034_UNAIDS_Strategy_en.pdf

3rd February saw the publication of the results of a 4 year study to ascertain the efficacy of HPV vaccine for boys against HPV strains 6, 11, 16 and 18 . The sponsors were Merck, producers of the HPV vaccine, Gardasil. The double-blind study included 4,065 healthy men aged 16-26 in 18 countries. Efficacy was 90.5 % against external lesions when offered before exposure, and 65.5% when offered regardless of prior exposure
HPV vaccination of girls is widely practised. The question is: should we be vaccinating boys? The authors stress the potential benefits of preventing HPV transmission to women, especially in the light of the low take-up of teenage girls in the US. They also emphasise reduction of transmission from men to men.
Recent independent studies of the cost-effectiveness of HPV vaccination favour vaccination of pre-adolescent females, but not males www.bmj.com/content/339/bmj.b4127.extract . According to J.J. Kim & S.J. Goldie www.nature.com/bjc/journal/v97/n9/abs/6604023a.html, “only under the most favourable assumptions for the benefits … did the cost per quality adjusted life year fall below $100,000 per QALY”. On one issue at least Kim and Goldie concur with Giuliano and Palefsky: that male HPV vaccination may be cost-effective in situations where the take-up by girls is sufficiently low.
Anna R. Giuliano & Joel M. Palefsky, “Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males”, New England Journal of Medicine, February 2011
http://www.nejm.org

STI surveillance in England has taken a major step forward with the first publication of STI data based on GUMCAD (Genitourinary Medicine Clinic Activity Dataset).   For the first time, the genitourinary medicine(GUM)  clinic data are based on a disaggregate dataset, using pseudonymised individual level data, rather than an aggregate summary.  As a consequence, we now have the ability at local, regional and national level to interrogate the dataset for rates of co-infection, re-infection rates and attendance data.  While this dataset is still confined to the specialist clinics, it is a huge step forward in surveillance.  It remains to be seen how we will develop surveillance spanning the primary care/specialist interface.  Disaggregate datasets in primary care (such as the General Practice Research Database) have been around for a long time, and have been used to explore STI and HIV diagnoses and management.  Although they have been linked to hospital and cancer registry data, a link to specialist GUM services is unlikely to happen in the foreseeable future, so we will continue to rely on a complex admixture of GUMCAD, chlamydia screening, laboratory and ad hoc datasets.  Compared to many other countries, this is pretty good – but a real assessment of what is delivered by our National Health Service will require a bit more “joining the dots”.

Interestingly, epidemiological treatment of suspected gonorrhoea has risen over the past decade – suggesting either better documentation ofpartner notification, or truly improved partner notifications.  Given that the rate of partner change needed to maintain gonorrhoea in a population with developed services and effective antibiotics, this is an important finding.  It may be part of the explanation for declining gonorrhoea diagnoses, since a 2002 peak.

We at STI were delighted to see that  one of our research papers (http://sti.bmj.com/content/early/2010/06/07/sti.2009.041954.short?q=w_sti_ahead_tab )  had been picked up by the British Broadcasting Corporation `s news website ( http://news.bbc.co.uk/1/hi/health/10401029.stm). It reports a dutch study on STI rates amongst “swingers”  ( heterosexual couples who are practising mate swapping, group sex or visit sex clubs for couples). The study looked at rates of gonorrhoea and chlamydia and found that swingers represented more than half of the STI diagnoses in the over 45 years age group. This clinic ( South Limburg) were able to do this analysis because their clinic has been registering surveillance data on swinging since 2007. 12% of their attendees were recorded as belonging to this group.

Certainly this is not data which sexual health clinics in the UK have been obtaining routinely during consultations or reporting for national surveillance programmes. National guidelines for sexual history taking do not include a specific closed question on swinging so we would be reliant on the patient to volunteer that information, or at the least, disclose their total number of partners and concurrency  in the routine sexual history. Does anyone else work in a clinic or STI prevention service which targets this group ?