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A new kind of treatment for multi-resistant gonorrhoea?

31 Jan, 17 | by Leslie Goode, Blogmaster

Recent research at York University (Ward & Lynam (W&L)), UK, suggests the possible efficacity of carbon monoxide-releasing molecules as an antimicrobial against gonorrhoea.  The work is at an early stage – but the urgency of our current situation lends it a heightened interest.

Growing  resistance of Neisseria gonorrhoeae (Ng) to the last-defence antibiotic treatments (Lewis/STIs) – cephixime and ceftriaxone – has placed sexual health policy in a dilemma: to have an impact on the epidemic requires them to  focus treatment on core-groups; yet the treatment of these individuals has to be shown to heighten antibiotic resistance (Chan & Fisman/STIs).   Ison & Unemo/STIs survey the narrowing options, including heightened surveillance (see also Unemo & Khotenashvili/STIs) and the careful stewarding of our remaining antibiotic resources.  Others suggest recourse to less obvious measures, such as the comprehensive treatment of pharyngeal Ng in MSM (Lewis/STIs), or the use of topical antiseptics (Miari & Ison/STIs).  Ultimately, however, the answer will lie in the developments of new antibiotics.

So how about the York researchers’ carbon monoxide-releasing molecules (CORMs)?  Though – to repeat – it is early days, this avenue looks promising.  The agent, tryptophan manganese carbonyl (Trypto-CORM), has been shown by earlier studies to be toxic to Escherichia coli and Staphylococcus aureus through the effect of CO molecules released by Trypto-CORM when irradiated.  W&L report that in the case of Ng, the bacterium appeared to be destroyed even by the very small amounts of CO released before irradiation.  The idea that Ng might be ‘exquisitely sensitive’ to CO would, of course, be good news.  It suggests the levels of CO necessary for efficacity against Ng might be sufficiently low to eliminate undesired toxic effects.  However, the results of W&L  also raise the suspicion that in the case of Ng, the cytotoxic effect might arise from some mechanism other than release of CO.  Fortunately, another innovation of the study appears to eliminate that possibility.  This is the use of extremely high CO affinity leg-haemoglobin (as opposed to the less high affinity deoxy-myoglobin) to ‘rescue’ the Ng culture by ‘scavenging’ the CO.  So it really does seem that the sensitivity of Ng to CO, not some other mechanism, is producing the cytotoxic effect.

A final potentially medically significant element of the study is the effect of culture age.  Cultures that had been stored for are longer time were more sensitive to Trypto-CORM – a finding that turns out not to be attributable to the number of viable cells in the inoculums.  The authors suggest the effect is due to the depletion in the number of active haem-copper oxidase complexes in near dormant cells.  This too could be good news.  Persistent bacteria in an infection that are recalcitrant to treatment are frequently slow-growing or dormant, and could be particularly susceptible to Trypto-CORM.

 

 

Susceptibility of heterosexual sub-Saharan women to HIV could be the result of cervicovaginal microbiome characteristics

30 Jan, 17 | by Leslie Goode, Blogmaster

Could part of the explanation for the apparent susceptibility of sub-Saharan African heterosexual women to HIV infection (eight-fold that of males) lie in the bacterial flora of their female genital tract (FGT)?

Studies published in STI journal have considered the relationship between a certain state of the FGT bacterial microbiome – especially the depletion of lactobacillus (Francis & Grosskurth/STIs) – and the susceptibility to BV (Antonio & Hillier/STIs; Hardy & Crucitti/STIs; Francis & Grosskurth/STIs; Haggerty & Ness/STIs), to pelvic inflammatory disease (Haggerty & Ness/STIs), and to other STIs (Francis & Grosskurth/STIs).  Others have observed the prevalence of Lactobacillus in the healthy FGT microbiome (Madhivanan & Krupp/STIs), and considered the impact on the FGT lining of practices of vaginal douching (Balkus & McClelland/STIs), hormonal contraception (Verwijs & Wijgert/STIs), and sexual debut (Jespers & Crucitti/STIs).

Highly relevant to all these discussions is a recently published study by Gosmann & Anahtar of a prospective cohort of 236 young HIV-negative women participating in the South African Ragon Institute’s FRESH study (Females Rising through Educations, Support and Health) in Kwa-Zulu Natal. The researchers were able to follow up their cohort for a total of 198.2 person-years, in the course of which 31 participants acquired HIV.  The researchers distinguish four ‘cervicotypes’ in respect to FGT bacterial flora; then determine their prevalence along with their association with ‘HIV target cells’ (i.e. activated CD4 T cells expressing the HIV co-receptor CCR5) and HIV acquisition.

The four cervicotypes correspond to the dominance of Lactobacillus crispatus and of Lactobacillus iners (CT1 and CT2, respectively), the preponderance of Gardnerella vaginalis (CT3), and a biome showing a far more diverse range of bacterial types (CT4).  Strikingly, the first two cervicotypes (CT1 and CT2) account for only 10% and 32% of women in the cohort; while, among white women in Western countries, the proportion showing Lactobacillus dominance would be c.90%.  The other 58% fall into the categories of high diversity communities with low Lactobacillus abundance (CT3 and CT4).  More interestingly still, none of the 31 HIV sero-conversions took place among the 10% of women with CT1-type bacterial flora.  Rather, sero-conversions were fairly evenly distributed among the other three cervicotypes, with some diminution of relative incidence in the CT2 category (i.e. nine sero-conversions, as opposed to 10 and 12 in CT3 and CT4 respectively).  Researchers observed a 17-fold increase in HIV target cells in women with a CT4-type cervico-vaginal microbiome as against those with CT1-type, and elevated levels of chemokines MIP-α and MIP-β which attract CCR5 expressing cells in women with diverse FGT bacterial communities.

Sadly, regimens aiming to restore Lactobacillus crispatus dominance (e.g. antibiotics or probiotic vaginal suppositories) show significant recurrence rates.  However, modifiable biological and behavioural factors may play a considerable role on Lactobacillus depletion in sub-Saharan African women (e.g. vaginal washing; antibiotic use; recent Trichomonas and HSV-2).  If so, then, as Baeten & McClelland/STIs point out, this would suggest the possibility of effective intervention strategies to reduce HIV transmission by improving vaginal health.

Location of HIV-2 emergence determined by distribution of indigenous cultural practices of male circumcision

16 Jan, 17 | by Leslie Goode, Blogmaster

Sousa & Vandamme demonstrate a robust correlation between HIV-2 prevalence at the time of the 1980s surveys and the absence of indigenous practices of male circumcision earlier in the century.  This is a complex and interdisciplinary study, involving some of the earliest large-scale, West African serological surveys of HIV-2 (1980s) and extensive ethnography of the region throughout the twentieth century.

HIV-2 seems to have crossed the species barrier into humans from a primate called the ‘sooty mangabey’.  The two epicentres of the 1980s HIV-2 epidemic – south-west Côte I’Ivoire and Guinea Bissau – correspond to the two points along the band of sooty mangabey territory where ethnic groups were to be found who did not practice circumcision (Côte I’Ivoire), or performed it only late in life or very intermittently (Guinea Bissau).  The complexity of this study arises from the fact that, thanks to waves of islamicization, male circumcision has been widely adopted across the region even in areas where it was traditionally prohibited.  Hence investigation of the correlation with HIV-2 emergence, probably in the 1940s, required the authors to go back to ethnographic accounts preceding islamicization.

Of course, the certainty of a causal link cannot be established.  But Sousa & Vandamme discover a strong negative correlation between male circumcision and HIV-2 (Spearman rho = -0.546).  Their results are supported by studies that establish the same negative relationship with HIV-1, both in sub-Saharan Africa (Moses and Plummer) and, more recently in Papua New Guinea (MacLaren & Vallely/STIs).  A likely causative mechanism might be the prevalence of ulcerative sexually transmitted infections (Weiss & Hayes/STIs).

So Sousa & Vandamme offer an additional ‘ecological’ reinforcement of the public health rationale for encouraging voluntary male medical circumcision (VMMC).  Yet what is also interesting, from a public health perspective, is the importance their study attributes to culture in the adoption of a practice like male circumcision.  In the present case, for once, the impact would appear to have been very positive from the medical point of view. The authors speak, for example, of islamicization, along with ethnic intermarriage in the cities, as having given rise to ‘social pressure to be circumcised in order to be accepted by women’, and the ‘abandonment of traditional prohibitions of male circumcision’. Of course, the impact of indigenous culture may often be less benign from a medical point of view – as the source of conservative attitudes that tend to hold back and limit the uptake of VMMC.  As, for example, where males have seen male circumcision as the practice of potentially hostile neighbouring groups (Cultural constraints on uptake of circumcision/STI/blogs), or as a practice uniquely suited to those younger age groups on whom it was traditionally performed (Mbabazi/STIs).  But, either way, it is noteworthy that the influence of local culture would often seem to be so decisive.  So there may be an argument, for electing to promote infant circumcision, as an evidently medical practice that runs less risk of falling foul of prevailing cultural attitudes that restrict ‘demand’ (Gray & Kigozi/STIs; Feasibility of infant circumcision/STIs/blogs).

 

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Revised UK NICE Guidelines for HIV testing: why local prevalence based targeting by GPs and hospitals makes sense

11 Jan, 17 | by Leslie Goode, Blogmaster

November 2016 saw the publication of revised UK NICE Guidelines for HIV testing (last updated 2011) – only a few weeks before the appearance of the annual Public Health England Report: HIV in the UK/2016.  The latter highlights the estimated level of still undiagnosed HIV in the UK (which, at 13,500/101,000, places us 3% short of the UNAIDS 90:90:90 target) and the proportion of late diagnoses (approx. two/five thousand).  It also draws attention to the ‘diversity’ of the epidemic, and the relatively poor levels of diagnosis amongst the 16,500 infected non-black African heterosexuals (approx. 1/4, as opposed to 1/7 for MSM or 1/8.5 for black African heterosexuals).

In the light of these findings, we can appreciate the move in the NICE Guidelines, regarding opportunistic testing in primary and secondary care, towards an approach that, first, makes absolutely clear its basis in regional prevalence rather than any other factor, and, second, is more specific – and more demanding – about the occasions when testing is recommended.  We find a new distinction of two levels of high local risk: high (0.2-0.5%) and extremely high (>0.5%).  This determines whether testing should be offered on specified occasions, namely, in primary care, at registration and the performance of any blood test, and, in secondary care, at admission and performance of a blood test (‘high’ prevalence areas); or whether there should be universal opportunistic testing (‘extremely high’ prevalence areas).  As compared with the 2011 guidelines, an insistence on local prevalence as the determining factor replaces the specification of multiple high-risk groups (e.g. MSM or black Africans).

The danger with routine HIV testing is well illustrated by a 2011 study of screening in 29 Paris emergency departments: Wilson d’Almeida & Cremieux/STIs/blogs.  This trial seems to have spectacularly failed to pick up any HIV infections that would not have been detected even without the intervention.  By contrast, what is proposed by the NICE Guidelines is routine testing in areas of extremely high prevalence.  Of course, patients may still refuse testing (Dhairyawan & Orking/STIs) – and appear to do so all the more frequently where they belong to groups, like non-African heterosexuals, that the authors of the 2016 guidelines are so anxious to include (Mohammed & Hughes/STIs).  Nevertheless, the 2014 HINTS study (HIv testing in Non-Traditional Settings) of the acceptability of routine HIV testing has demonstrated encouraging levels of uptake (c.65%) in UK Emergency Departments, Acute Care Units, Primary Care Centres, and dermatology outpatients (Rayment & Sullivan; see also Mohammed & Hughes/STIs).  Conversely, there is evidence, where primary care is concerned, that practitioners may be capable of missing opportunities for testing even where their patients present with indicator conditions for HIV infection (Agusti & Casabona/STIs).

Responding to the new NICE guidelines, a GPs’ representative stresses the existing workload of GPs and the sensitivity of sexual health issues, but broadly welcomes the new emphasis.

 

 

 

UNAIDS 2016 Report: How a ‘life-cycle’ approach can help the world ‘get on the fast track’ to HIV prevention

7 Dec, 16 | by Leslie Goode, Blogmaster

‘Get on the Fast Track: a Life-cycle Approach to HIV’ is the latest UNAIDS report, following on from the UN Assembly’s 2016 declaration of commitment to ‘Fast Track’ goals for ending the HIV/AIDS epidemic. The major theme of the ‘life-cycle’ appears to owe much to the findings of the South African CAPRISA study – above all, the idea of a transmission cycle between younger (25 year-old) women and older (>25 year-old) men.  Broadly, phylogenetic analysis reveals that the prevailing pattern of transmission is as follows.  Younger women appear to get infected through casual relationships with considerably older men, who have, in turn, been infected by their longer-term partners; in time, the younger women grow up and form longer-term relationships – and the cycle is repeated.  The former group – younger (≤25 year-old) women – appear to be more vulnerable to infection than men of the equivalent age due to complex social factors, and have recently seen only c. 6% declines in annual incidence; older (>25 year-old) men have incidence rates that have remained obstinately high despite all recent efforts to reduce them.  These are best explained by poor rates of testing, integration into treatment, and viral suppression making them a potential risk to non-HIV-infected partners.

Diagnosing a problem is one thing; framing the solution quite another.  In case of the younger women, the dominant factors appear to be structural and societal – e.g. gender inequalities.  These are difficult to address without major social and political change.  The authors suggest a number of prevention tools, including sexual education in schools, the introduction of pre-exposure prophylaxis (PrEP), and social transfers.  However, recent trials of PrEP in sub-Saharan Africa do not bode well for this intervention (STI/blogs/’Failed PrEP trial’; STI/blogs/‘Another failed PrEP trial’); while the evidence for the effectiveness of sexuality education and ‘social transfers’ is far from conclusive (School-based Sexuality Programmes/STI/blogs; STI/Galarraga & Sosa-Rubi; STI/Minnis & Padian; STI/Khan & Khan).  However, in the case of the other group – i.e. older men – the obstacles to HIV prevention (poor rates of testing and viral suppression) may be less intractable, and the report proposes a number of very practical measures that could help, including: distribution of self-test kits through female partners attending ante-natal clinics (STI/blogs/’Partner-delivered STI testing’); simplifying ART regimens so individuals have to take just one tablet a day; shifting from CD4 count testing to viral load testing.

The report also has much to say about other phases of the life-cycle, as well as about ‘key populations’ (estimated 45% of new infections).  Regarding the latter, the authors report the stability, or even rise, in new infections amongst sex-workers, drug-users and MSM. They emphasize the negative impact of criminalization of key populations and same-sex relations (73 countries) (see STI/blog/’HIV criminalization’/; STI/blog/’Health workers violate human rights’), the very low levels of domestic funding (on average, only 12% of total spending on MSM prevention), and the relatively young age of many in the ‘key populations’.  The authors recommend ‘comprehensive’ programmes for these populations incorporating access to a range of health care programmes, such as the Red Umbrella programme for sex workers in South African, and the ‘Targeted Strategy Plan’ for the transgender population in Lima, Peru.

 

School-based sexuality programmes fail to demonstrate an influence on STI and pregnancy outcomes

7 Dec, 16 | by Leslie Goode, Blogmaster

The 2016 UNAIDS Report – Get on the Fast Track: a Life-Cycle Approach to STI Prevention/STI/blogs – underlines the particular vulnerability to infection of women at a relatively early phase of the life-cycle, especially in limited resource settings such as sub-Saharan Africa as a result of structural factors .  These can seem intractable, but the authors of the report propose a number of practical measures for this group that include sexuality education in schools, social transfers and PrEP.  So the recent publication of a Cochrane Review of studies assessing the effectiveness of two of these interventions – sexuality education in schools and social transfers in the form of material incentives for girls to remain in school – is very timely – especially as five of the eight studies included in the analysis are based in the limited resource settings of sub-Saharan Africa that are the focus of the UNAIDS report.

A number of both European and non-European countries have incorporated some form of sexuality education into their school syllabuses, and there have been attempts to investigate their effectiveness in a number of places, including the UK (Stephenson & Johnson/STIs; Stephenson & Oakley; Henderson & Hart).  Unfortunately many of these trials rely on self-reported data, a tendency that has been shown to be problematic in this area (Langhaug & Cowan/STIs; Plummer & Hayes/STIs). The importance of the recent Cochrane Review is that it focuses largely on biological outcomes: namely, rates of STIs and pregnancy at follow-up.  The studies of sexuality education that are based on these outcomes have been undertaken in sub-Saharan Africa: Ross & Hayes (R&H,Tanzania); Cowan & Pascoe (C&P, Zimbabwe); Duflo & Kremer (D&K, Kenya). The same applies to studies of social transfers based on biological outcomes (Baird & Oezler (B&O) and Duflo & Kremer (D&K)).  (The non-African studies in the analysis use pregnancy prevalence as their preferred outcome (Cabezon & Garcia (C&G, Chile); Stephenson & Oakley (S&O, England); Henderson & Hart) (H&H, Scotland)).)

So what biological evidence do we find of the effectiveness of school-based education interventions? Practically none, say the reviewers.  No difference was reported between intervention and control groups for HIV or for other STIs – except in the case of R&H for syphilis prevalence at the end of follow up (RR 0.81: CI 0.47-1.39).  Even the statistically significant aggregate outcome for long-term pregnancy prevalence (0.55: CI 0.34-0.91) (C&G, S&O, H&H, D&K) seems largely accounted for by the results of C&G, which were at particularly high risk of bias.  When the latter were excluded, differences in pregnancy prevalence dropped to 0.93.

When it came to the other element of this survey, social transfers (B&O and K&K), only B&O reported a significant effect for HIV prevalence and HSV-2 prevalence.  This evidence was considered weak because, in the former case, it concerned data for school ‘drop-outs’ which, say the reviewers, the B&O study was not powered to detect, and, in the latter, because there was no measurement of prevalence at baseline.  As for pregnancy outcomes, both studies reported a reduction in short-term prevalence (0.76).

The trials of educational interventions may simply have been underpowered to detect small, but clinically important effects (especially with HIV).  On the other hand, the authors of the review also point to a growing consensus among experts that the determinants of sexual health outcomes and sexual risk-taking are wider structural factors such as poverty and cultural gender norms that lie beyond the capacity of school-based education programmes to influence.  The evidence for the effectiveness of incentives to stay at school, though as yet very inadequate, seems more encouraging.  This is evidently a field that requires further research.

Criminalizing HIV transmission: Is imprisonment ever the right response?

28 Nov, 16 | by Leslie Goode, Blogmaster

This month sees the publication of a ‘Consensual Statement’  by Australian medical professionals on ‘Sexual Transmission and the Law’.  This draws on a similar Canadian ‘Consensus Statement’  issued in 2014.

The involvement of the law in this area remains a highly controversial matter.  It is easy to assume that UNAIDS policies underlining the public health disbenefits of “overly broad criminalization” largely concern those African nations which have recently adopted draconian legal previsions in response to the HIV crisis (Kpanake & Mullet/STIs; Stackpole-Moore/STIs).  Yet we should not forget that prosecution and imprisonment for transmission of HIV continues to occur in first-world countries as well (e.g. 16 custodial sentences in England over the period 2001-2012 (Phillips & Sukthankar/STIs)).  National jurisdictions differ in respect to whether, in order to be subject to prosecution, the transmission must be intentional or reckless.

Many in sexual health, I suspect, would reject the idea of involving the criminal law in such cases.  Stackpole-Moore/STIs, for example, argues that its use “in order to guide normative behaviour” is irreconcilable with the concern to avoid internalized stigma among at risk populations.  According to S, employing criminal sanctions in this area involves promoting just the kind of social stigma that health policy makers have found so counter-productive in fighting the epidemic.  However, this side-steps the question whether there might ever be a moral argument for legal sanctions regardless of their impact on behaviour.  Phillips & Sukthankar/STIs, in their theoretical examination of traditional justifications for sentencing to imprisonment, recognize the possibility that ‘retributive justice’ could provide some genuine justification for imprisonment for HIV transmission.  This might explain why those African legislators responsible for passing the recent severe previsions, tend, when asked about their motivations, to revert to the argument of retribution – even where that is not the ‘official’ justification (Stackpole-Moore/STIs and Kpanake & Mullet/STIs).

To come at last to the recent Australian and Canadian statements – these discourage, even if they don’t quite exclude, the involvement of the law.  However, they do so not on the grounds of a principled rejection of all justifications for criminalization (such as advocated by Stackpole-Moore/STIs), but on the grounds of the changing reality, and changing perceptions, of HIV.  They specify the risk of per sex-act transmission – in the case of penal-vaginal transmission, rated low (0.4%-1.4%) – and point to the effectiveness and tolerability of treatment.  If HIV is no longer a ‘death-sentence’, then transmitting HIV to a partner can hardly be considered ‘killing’.  Still more conclusively, perhaps, they point to the inadequacy of phylogenetic analysis as forensic evidence, which, they argue, “simply cannot determine beyond reasonable doubt that the reference samples are linked”.

Yet it should be remembered that the first two of these three considerations (unlike the claims of retributive justice) are context-dependent.  Whether or not HIV amounts to a ‘death sentence’ may depend on where you live.  Were the same kind of arguments to be applied in the case of the African countries discussed by S and K&M, they would need to take account of the very different health realities obtaining in those countries.

Partner-delivered HIV self-testing through antenatal clinics: the way ahead for partner notification in low-resource settings?

23 Nov, 16 | by Leslie Goode, Blogmaster

A recently published, Kenya-based, randomized controlled study (Masters & Thirumurthy/STIs) (M&T) evaluates a novel intervention that appears to combine in a fresh way elements of various innovative interventions for HIV prevention.  Recently published studies (e.g. Kissinger/STIs; Estcourt & Cassell/STIs) have explored the potential of ‘expedited’, or ‘accelerated’ partner therapy – where the partner of an index STI-infected individual is offered therapy through the infected individual directly, without a clinic attendance, or with only a telephone interview. They have also evaluated the benefits of ‘self-testing’ for HIV (e.g. Pai & Dheda/STIs).  The intervention trialled by M&T – partner delivered HIV self-testing – combines elements of these two types of interventions.  A third crucial element is that it takes advantage of the unique opportunity offered by antenatal and postpartum clinics in low resource settings (see Azeze & Haile/STIs; Sombie & Dabis/STIs; Ganiyu & Mason/STIs) to make contact with HIV-infected individuals who might otherwise have little access to health services.

In M&T’s study, participants attending antenatal and postpartum clinics (ANC) who were assigned to the intervention arm of the study (n=284/570) were offered two oral-fluid-based HIVselfing kits, one for themselves, one for their partner.  Discussion about HIV, self-testing, couple testing, and awareness of partner’s result were subsequently reported by index patients at monthly follow-up meetings over a three-month period.  This ANC-based, partner-delivered HIV self-testing intervention was evaluated against a control group (n=286/570) who were given an invitation card for conventional clinic-based HIV testing and encouraged to distribute the card to partners.

The primary outcome was reported partner HIV testing which was 91% for the intervention as against 52% for the control.  The intervention looked at couple testing (42% difference between intervention group and control), and awareness of partner’s HIV status (difference=39%).  0% participants in either group reported intimate partner violence (IPV) as a consequence of HIV testing.

Concerns around interventions of this kind tend to centre upon two things.  First, the absence of any direct contact between partner and health services, and consequent loss of an opportunity to test for the full range of STIs and help ensure integration into treatment (Estcourt & Cassell/STIs).  Second, worries as to the likelihood of IPV related to testing.  On the first, concern may be less where the self-test is for HIV, and the partner misses out on testing for the other STIs (Kissinger/STIs), than it would be where, as in many non-African settings, the self-test would generally be for Chlamydia or gonorrhoea and HIV could remain undiagnosed.  Regarding IPV, the authors note its lack of association with testing in the study (despite base-line reported rates of 27%).  They also point to the large proportion of eligible declining to participate (715/1,315).  This – taken together with zero cases of IPV – they interpret as a possible indication of the ‘agency’ of these women, and their capacity to make their own judgments regarding the possible impact of participation on their relationships.  The problem of ensuring engagement with care among those self-tested for HIV, however, is one that the authors acknowledge as still needing to be resolved.

As for the study itself, a primary limitation is self-reporting.  But here the authors note that misreporting is hardly likely to account for the differences between intervention and control arm – which is the evidence that the authors principally emphasize.

 

Where HPV vaccination loses the battle for public support: calculating the health implications for Japan

9 Nov, 16 | by Leslie Goode, Blogmaster

A recent brief contribution to The Lancet-Oncology (Tanaka & Ueda) uses predictions of the probable health outcomes of the suspension of the Japanese HPV vaccination programme to make the case for an urgent reassessment of the current policy.  This intervention is very timely.  The approved age for HPV vaccination for Japanese girls is a window of four years from 13-16 yrs, and the current year (2016-17) constitutes the fourth since the suspension of the programme (June 2013); so the current year is the last opportunity for a return to the initial HPV vaccination policy before the effects of the suspension (for the oldest in the cohort) become irrevocable.   From the following year on (2017-8), the authors argue, every additional year of suspension will exclude an additional age group from the protective effects of HPV vaccination – unless, that is, the eligibility period is extended to include older girls).  With a view to maximizing the impact of this message, they assess the impact of restarting vaccination in 2020 as against restarting in the current year.  They do this on two scenarios depending on whether or not vaccination, when resumed, is given to those who would have missed out in 2013-2017 as well as to those currently eligible.

So how great are these effects?   On the first scenario (no catch-up for missed years), risk of HPV 16/18 infection at 20yrs is estimated for the 2013-6 year groups at around a steady 1.0%, given resumption of vaccination 2020, as against the 0.3-0.4% risk, with resumption in 2016; on the second, that steady 1% risk over the four missed years is replaced by an evenly paced decline from 1.0% to previous levels (0.3-0.4%) over the four-year period.

Of course, it is the long-term health impact of these HPV infections that constitutes the cost of the current Japanese policy, and, were it recognized, the strongest incentive for a resumption of vaccination.  Unfortunately, the full impact is very long term, and hard to quantify.  But some advanced indication of its potential scale is provided by the recent Finish ‘FUTURE’ trial that demonstrated an absence of CIN3 and ICC lesions in vaccinated participants (Paavonen/3/STIs), as well as, more indirectly, the enormous (c.90%) declines in genital wart presentations in Australia (Chow & Fairley/STIs; Ali & Donovan (STIs)) and New  Zealand (Wilson & Baker/STIs).  The benefits foregone by the unvaccinated will also include protection against head and neck – especially oropharyngeal – cancers (Field & Lechner/STIs; King & Sonnenberg/STIs), and against a small, but significant range of anogenital cancers in women (Prevention of anogenital cancers in women/STIs/blogs).  On a more positive note, however, there is some evidence for the benefit of ‘catch-up’ and incomplete vaccination (“Catch-up” and incomplete vaccination/STIs/blogs) as against those who have hitherto put this in doubt (STs/Chesson & Markowitz).

An important lesson of the Japanese experience for everyone concerned with HPV is the importance of public education.  The very poor levels of understanding revealed by a recent systematic review (Patel & Moss/STIs) amongst European adolescents is a timely warning that uninformed attitudes to HPV vaccination are not restricted to the Japanese.

Feasibility of infant circumcision as an HIV prevention tool

31 Oct, 16 | by Leslie Goode, Blogmaster

Recent trials have shown male circumcision (MC) to be associated with a reduced HIV incidence of up to 60%. For this reason UNAIDS has included ambitious goals for circumcision (20 millions MCs) as a major component of its HIV prevention strategies for 14 priority countries in sub-Saharan Africa (STI/blogs/Roll-out of UNAIDS voluntary male circumcision).  The achievement of this objective has met with considerable obstacles on the supply side – for instance, the lack of trained practitioners (STI/blogs/Roll-out of UNAIDS voluntary male circumcision; Kaufman & Ross/STIs); but constraints on the demand for MC have, if anything, proved still harder to surmount (STIs/blogs/cultural constraints on uptake of circumcision). The existence of circumcision as a traditional cultural practice amongst some populations can lead to its perception in other cultures as alien and externally imposed – even  hostile to one’s own tradition (David/STIs; Madhivanan & Klausner/STIs; STIs/blogs/cultural constraints on uptake of circumcision). Also, its traditional association with a certain phase in the life cycle can give rise to the feeling among older members of the community that it is inappropriate for people of their age (Mbabazi/STIs).

The cultural problems affecting demand have led some to reconsider the possible contribution of early infant circumcision (EIC) as a prevention tool – albeit on a longer view that the one envisaged by existing UNAIDS targets (Gray & Kigozi/STIs).  Kankaka & Gray (K&S), in a recent paper reporting a trial of such an intervention in Rakai Uganda, seem to corroborate (largely) positive findings of earlier investigations of EIC in other sub-Saharan countries (Young & Nordstrom (Y&N) (Kenya); Plank & Lockman (Botswana); Bowa & Stringer (Zambia)) that would indicate EIC could ultimately prove a highly effective form of prevention.  Of course, supply side problems with the recruitment and retention of adequately trained personnel remain.  For this reason, K&S – as indeed Y&N before them – investigated the impact of task-shifting from physicians to less highly trained practitioners; in the Uganda study, infants were randomly assigned to either ‘clinical officers’ (i.e. assistant physicians) or registered nurse midwives (RNMWs). Another feature of this study geared to testing the feasibility of the extension of EIS to remote areas was the decision to substitute topical analgesia for the dorsal penile nerve block used in earlier studies.  The trial assessed the safety of EIS (Mogen Clamp) as performed by more junior cadres of medical staff, and rated the degree of pain/discomfort experienced by the infants in terms of Neonatal Infant Pain scores (NIPS) – as well as testing out, in some rudimentary way, the acceptability of the intervention to mothers.

On all accounts, the trial produced very satisfactory results.  The rate of adverse events with RNMWs was low, and indeed comparable to rates that might be expected with physicians (1.6%), and the NIPS scores suggested that 76% of infants experienced mild pain or less, and only 1.6% experienced severe pain.  So far as the supply-side difficulties are concerned, these results are encouraging.  There could, of course, also be demand-side constraints with EIS, equivalent to those observed with adult circumcision.  Yet, of the 701 infant-mother pairs registered as potential participants, 74% (no.= 525) consented (as compared to 60% in the Botswana study (Plank & Lockman), but only 11% in the Zambia study (Bowa & Stringer)).  Maternal satisfaction rates were 99.6% for clinical officers, and 100% for RNMWs.  The cultural acceptability may vary somewhat between populations – yet, to the extent that EIS remains distinct from cultural practices, its dissemination may be less at risk of being perceived in non-medical terms as an alien or hostile cultural imposition.  Moreover the evidence suggests that experience of pain increases with age.

 

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