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Harms of HSV-2 may include association of latent infection with autism as well as transfer of active infection to the neonate

11 Apr, 17 | by Leslie Goode, Blogmaster

Mahic & Lipkin (M&L) draw attention to a wholly new health concern in relation to Herpes Simplex Virus 2.

The condition is highly contagious, and the symptoms may be very unpleasant especially during the ‘primary outbreak’, the virus is not, in itself, a major public health concern.  Indeed, up until the 1980s, it was rarely mentioned in this journal – perhaps because it was less common before the 1970s, or maybe because the condition was insufficiently severe to warrant much discussion.

HSV-2 owes its status as a serious health problem to two issues that are independent of its impact on the everyday sufferers.  The first concerns the potentially devastating consequences of transmission of HSV-2 to the neonate (generally in the course of birth rather than in utero) (Preventing neonatal herpes (STIs)).  These are so severe as to have led to a considerable debate on the cost-effectiveness of screening in various parts of the world (Mindel & Cunningham (STIs) (Australia);  Barnabas & Garnett (STIs) (US); Sudfeld & Mensch (STIs) (Malawi)).  The second concerns the links between HSV infection and HIV transmission.  This is an issue discussed primary in the sub-Saharan African context, where HSV is particularly prevalent and its treatment could potentially impact the HIV epidemic (White and Glynn (STIs); Lurie & Matthews (STI)) – though also in the Indian context (Foss & Watts (STI)).

To these two serious concerns Mahic & Lipkin, in a paper recently appearing in the microbiology journal mSphere, have added a third of as yet uncertain importance – the possibility of an association with male autism.  Basing their investigation on data from the Norwegian Autism Birth Cohort (comprising mothers, fathers and infants recruited over the period 1999-2008), the researchers compared maternal immunoglobulin (IgG) antibodies to HSV-2 (amongst other viruses), which had been measured in 442 mothers of male offspring with ASD mid-term, against a frequency-matched control of 464 mothers of ASD unaffected offspring.  An increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was found to be associated with a doubling (RR=2.07) in the odds of ASD.  This was not replicated in the case of antibodies to other viruses that were tested for.

The authors suggest that it is the ‘impact of immune activation and inflammation on a vulnerable developing nervous system’ which is likely to be the mechanism here rather than ‘the specific pathogen per se’ – maybe the transfer of maternally produced antibodies and cytokines across the placenta, or the exposure of the fetus to inflammatory molecules produced by the placenta and deciduas in relation to viral shedding.

The question posed by this outcome – should it be confirmed by subsequent research – is whether this third potential harm, when added to the well-established harm of neo-natal infection, might contribute to tipping the balance in favour serological monitoring and suppressive therapy during pregnancy – at least in certain contexts (cf. Barnabas & Garnett (STIs) (US)).

 

Health interventions can change systemic and cultural determinants of STI/HIV transmission

30 Mar, 17 | by Leslie Goode, Blogmaster

The causal pathway linking intimate partner violence (IPV) and health may be two-way.  We are used to thinking of IPV as a determinant of STI; but sexual health also has an impact on IPV.  This, at any rate, is the conclusion of a recently issued working-paper from the US National Bureau of Economic Research uniting a highly interdisciplinary team of researchers from a range of US universities and medical institutions.  The researchers seek to demonstrate that health is kind of human capital, and that a technological advance in medicine can affect ‘some of the most frustratingly persistent social problems’.  This finding will be particularly interesting to readers of this journal.  Health, in the context of this study, happens to be sexual health, and the technological advance is the introduction of HAART in 1996.

Papageorge & Pollack (P&P) base their work on data from the Women’s Intra-Agency HIV Study (WIHS), and compare a cohort of HIV+ women who were, in 1996, just beginning to experience immune system deterioration, with two control cohorts, using a ‘difference in difference’ approach.  One control consisted in HIV+ women not experiencing such effects, another in HIV- women included in the same WIHS data.  Much of the researchers’ task consists in establishing the relative dependence/independence of causal pathways linking IPV with drug use, perceived mental and physical health, and employment.  Their headline finding is a c.10% reduction in IPV a c.15% reduction in IDU attributable to HAART introduction.

The idea that the causative link could flow from STIs to IPV, as well as from IPV to STIs, may not be new to our readers.  Indeed, an ongoing concern for sexual health interventions has been that STI/HIV disclosure (a potentially important element of risk reduction) could result in domestic violence (Partner delivered STI self-testing (STI/blogs)).  This has not prevented other studies from pointing to a potentially positive role for sexual health clinics in relation to IPV (Lockart & McNulty (STIs); Decker and Silverman I (STIs); Decker & Silverman II (STIs)).  The nature of IPV itself is not always well understood, and probably varies with social and cultural context.  For example, it is not restricted to short-term or casual relationships (Silverman & Raj (STIs)), and may be reciprocal (Norris & Hindin (STIs)) as well as man-on-woman.  The nature of the causal link with HIV/STI might be expected to vary with the nature of the IPV itself.

So there is nothing new about the idea that a change in respect to sexual health could influence IPV.  What P&P contribute to the debate is genuinely encouraging, for all that.  Recent characterizations of the global efforts to curb the HIV epidemic (e.g. UNAIDS: On the Fast Track) make a two-fold classification of interventions into, on the one hand, biomedical interventions such as PrEP or cART, and, on the other, vaguer, and longer-term non-biomedical interventions such as legislative or attitudinal change.  The latter correspond to systemic or cultural determinants of sexual health that can seem to mark the ultimate limits on sexual health interventions rather than realistic targets for those interventions.  However, P&P point in this report to the case of a biomedical intervention that would, for once, seem to have achieved something more than an immediate biomedical impact.  HAART introduction, on P&P’s interpretation, effectively provided an additional ‘source of human value’ – an enhancement of women’s social ‘capital’.  Thereby, it would seem to have impacted the fundamental social and cultural determinants of sexual health – those ‘frustratingly persistent social problems’ that constitute the constraints within which sexual health is normally compelled to operate.

‘Scoping’ location: the role of ‘place’/’space’ as an influence on HIV outcomes amongst young MSM

14 Mar, 17 | by Leslie Goode, Blogmaster

Bauermeister & Stephenson (B&S) is a scoping review addressing the impact of location – ‘space’ and ‘place’ – on HIV prevention and care outcomes for young MSM (YMSM).  It owes much to Diaz & Ayala and their concern to view human behaviour in terms of ‘social location’ ‘within a context of social oppressive factors’ rather than in terms of ‘individual identity’.  It focuses on 17 studies, selected for inclusion much as in a systematic review, but analyzed according to scoping methodology (i.e. with a view to mapping out the investigative territory rather than addressing a specific question).  Social location is translated by this study into concepts of ‘space’ and ‘place’.  Space here refers to the physical and geographical aspects of location such as proximity to services and transportation, and place to more socially constructed aspects – ‘the interpersonal exchanges and dynamics that result in physical and social resources in space’.

It is perhaps on account of the breadth of these goals and the methodology of scoping that no very conclusive findings emerge.  Where location assumes the more geographically defined characteristics of ‘space’, the findings underscore the importance of geographic information system (GIS) approaches (see also: Simms & Petersen (STIs editorial); Petersen & Simms (STIs)).  But elsewhere – especially where the concept of location shades into less physical definitions of context (i.e. ‘place’) – the evidence is more contradictory and sometimes appears counter-intuitive.   For example, there are studies that find a positive correlation between social disadvantage and higher levels of adherence to HIV prevention and care recommendations.  Apparently, however, income inequality (as measured by Gini ratio or male-to-female ratio of earnings) stands out across studies as an indicator of poorer YMSM outcomes.

In discussing the limitations of their study, the authors make the interesting point that in a field of investigation as hard to define and as open to fresh hypotheses as this, the tendency for studies reporting an insignificant or null finding not to make their way into the literature could contribute to a serious distortion of our understanding (i.e. ‘publication bias’).  As is evident from their discussion of the review findings, well-conducted studies reporting non-significant findings on the influence of location can make a valuable contribution to the debate (such as, for example,  Haley & Cooper (STIs), a paper published online on the related issue of influence of location on STIs).

A second intriguing question is raised by this review, even if it is perhaps not adequately discussed in it: whether social context is always translatable in terms of ‘geospatial’ location.  Does the concept of ‘place’, for example, really extend to the case of ‘virtual space’ – or does virtual space effectively break free of any geospatial definition?  The question is, of course, very pertinent, given the importance for this population in particular, of dating apps.  Interestingly, Yu & Shang (STIs), in a paper published online, make a case for characterizing an important category of YMSM (occupying a specific ‘place’ in contemporary China society) in terms of extreme geospatial mobility.  One would like to know how B&S would accommodate the paradoxical existence of social ‘places’ defined by the loss of geospatial definition.  Are we still really talking about place?

The PrEP ‘care continuum/cascade’: how would it look?

8 Mar, 17 | by Leslie Goode, Blogmaster

We take for granted the value of the care continuum (or ‘cascade’), now increasingly seen as the key measure of health system response to HIV (Cassell (STIs editorial)).   The application of this model to HIV has provided a benchmark for evaluation in contexts as diverse as Moscow (Wirtz & Beyrer (STIs)), South Africa (Schwartz & Baral (STIs)) or the Netherlands (van Veen & van der Sande (STIs)).   But could the same model also offer a means of evaluation in the case of other complex sexual health interventions such as PrEP (Pre-Exposure Prophylaxis)?

An on-line soon-to-be-published paper by Nunn & Chan (N&C), building on an earlier attempt by Kelley & Rosenberg (K&R), does precisely this.  An important difference from the earlier paper seems to be the more concrete definition of a larger number of steps (nine as against five) – especially in the central area of ‘uptake’ and engagement in care.  Here K&R define three stages: ‘need for awareness of PrEP and willingness to use it’, ‘need for good access to healthcare’, and ‘need for a prescription for PrEP.  N&C replace these with a more concrete conceptualization of the process in five stages involving: an occasion where PrEP access is facilitated (4); an appointment arising from that occasion where the assessment is performed (5); the prescription of PrEP, where indicated (6); the actual initiation of PrEP (i.e. when the client starts taking the pills) (7).  Also important is N&C’s substitution of two final steps – adherence (8)) then retention (9) for K&R’s single final step of ‘adherence’.  N&C point out that, whereas, with ART, ‘adherence’ is once-and-for-all and secures the ultimate goal of viral suppression, in the case of PrEP, we can envisage multiple trajectories depending on whether PrEP continues to be indicated (e.g. the client may no longer be exposed to risk).  Finally, K&R’s first step – ‘identifying at risk MSM’ – gives way to three: identifying at risk individuals (1), enhancing HIV awareness (2), enhancing PrEP awareness (3).

Is this nine-stage definition of a PrEP cascade overly “complex” (EECAAC2018)?

Answering such a question requires us to reflect on the function that the ‘cascade model’ is called upon to perform.  If the model divides up the total course of an intervention into a series of staged tasks, this is presumably because the health benefit depends on the completion of the whole intervention, yet the accomplishment of each step is necessary to the achievement of subsequent ones.  The idea of the cascade can provide a fair way of evaluating the progress of an intervention before its potential health benefits have been delivered – and can also identify the precise points at which the intervention is failing (i.e. where clients become ‘disengaged’).

It follows that each step should correspond to a potential outcome that is not inferable from previous or later outcomes but is worthy of independent evaluation.  If everyone who accesses PrEP (4) also attends an appointment at which suitability of PrEP is discussed (5), or everyone who adheres to PrEP (8) is also retained in PrEP (9), then steps (4) and (5), or steps (8) and (9), can be merged.  This is not stated in so many words by the authors of the model.  However, I would assume that it must lie at the basis of their thinking.

BASHH Centenary Vignette series: Culture of the gonococcus – some historical details

28 Feb, 17 | by flee

Culture of the gonococcus – some historical details

The 43 year period between two BJVD articles1, 2 incubated improvements in the diagnosis of gonorrhoea by laboratory culture. The following 47 gave birth to alternative tests (NAATs), more simple to administer, but whose automation brought loss of personnel and possibly skills: perhaps in microscopy, perhaps in laboratory culture.

In 1927 Colonel Harrison wrote1: “There are differences of opinion as to the value of cultures in the diagnosis of gonorrhoea. Personally I think them indispensable in the case of women and often valuable in male urethritis” (my emphasis).

Laboratory culture of Neisseria gonorrhoeae has always lacked 100% sensitivity. Sampling from multiple sites, on multiple occasions, was necessary to diagnose, to exclude, and, importantly, to monitor any advances, or fluctuations, in the efficiency of laboratory culture. The use of repeated tests to analyse the sensitivity of culture is now impossible, with the universal adoption of epidemiological treatment (before/without diagnosis).

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HIV prevention through HAART: a victim of its own success?

28 Feb, 17 | by Leslie Goode, Blogmaster

A recent study (Kalichman & Allen (K&A)) involving a series of four cross-sectional surveys (1996-2016) at a Gay Pride event in US Atlanta Georgia adds to the mounting body of evidence that substantial changes have occurred in community-held beliefs about the safety of certain sexual behaviours in the era of HIV treatment as prevention.

It might seem surprising, in view of the known effectiveness of ART as a preventative tool, that its deployment has generally failed to deliver the preventative benefits that might have been anticipated.  It is essential to achieve progress right along the ‘treatment cascade’, including, not only access to testing, but integration into treatment and viral suppression, for those benefits to be realized.  The fact remains that levels of infection amongst MSM, even in countries that have scaled up testing and treatment, have remained stable or are actually rising.

The obvious hypotheses, tested by K&A in this study, are that, 1., the perception of safety on the part of MSM has led to an increase in condomless anal sex, and that, 2., the growing incidence of STIs resulting from these sexual practices has itself had a direct impact in reducing the protective effects of ART.  (Of course, this is not to deny that sizeable proportion of the MSM community in the US – as in Australia (Mao & de Wit) – be successfully engaged in deliberate HIV risk-reduction strategies.)  The four surveys adopted identical measures and procedures, and involved ascertaining proportion of condom use during anal intercourse and number partners over the previous six months as well as assessment of beliefs regarding the preventive effectivess of ART (nine items of the questionnaire).

Results were as follows.  For HIV negative men: condomless anal sex (CAS) increased from 43% (1997) to 61% (2015); reporting two or more condomless sex partners from 9% to 33%.  For HIV positive men:  CAS from 25% to 67%; reporting two or more condomless sex partners from 9% to 57%.  As regards beliefs that ART was protective, comparisons across survey times indicate a main effect for year of survey, F(3, 1829) = 6.3,p<0.01, with an effect across survey year for men who engaged in CAS, F(1,1829) = 9.3,p<0.01.  Most evident from figures is a precipitous drop in perception of risk amongst both groups between the third and fourth survey (2006 and 2016).

K&A’s hypotheses (one or both) would seem to be corroborated from another quarter by the observed association with the introduction of HAART of an increased infection rate of gonorrhoea and syphilis (Stolte & Coutinho (STIs)) and of viral STIs (de Laar & Richel (STIs)).  Indeed rates of MSM syphilis increase coinciding with HAART introduction have been so dramatic in some places (e.g. Buenos Aires (Bissio & Cassetti (STIs)) as to lead to a hypothesis that HAART agents may actually be impairing immunity to the virus (Rekart & Cameron (STIs); Tuddenham & Ghanem (STIs)).  Whatever the validity of the latter hypothesis, evidence of STI epidemics is consistent with evidence of attitudinal and behavioural changes, such as those proposed by K&A.

BASHH Centenary Vignette series: Then and Now

28 Feb, 17 | by flee

Then and Now

As far as I know, Sir Humphry Davy Rolleston, Bart, GCVO, KCB, LLD, MD PRCP, has been the only President of the specialist society, the Medical Society for the Study of Venereal Diseases (MSSVD) to have also been the President of the Royal College of Physicians. He was the son of George Rolleston FRS FRCP, Linacre Professor of Physiology at Oxford and his wife Grace who was the niece of Sir Humphry Davy the chemist after whom he was named. He was a direct descendant of Sir Michael Stanhope, the Groom of the Stool of King Henry VIII and was 22nd in direct line from King Edward I. He was mainly associated with St George’s Hospital in London but became the Regius Professor of Physic at Cambridge. He was the Physician-in-Ordinary and Extraordinary to King George V. He served in the South African War and was Consulting Surgeon to the Royal Navy in the First World War with the rank of Surgeon Rear Admiral. He was the first baronet, the KCB decoration is usually awarded to senior military officers and civil servants, so presumably it was for services to the Navy and the GCVO for services to the Royal Family. The Journal was fortunate indeed to have such an eminent physician write the introduction to its first issue.

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What is the future of cervical screening in the era of HPV vaccination?

20 Feb, 17 | by Leslie Goode, Blogmaster

With the introduction of HPV child vaccination programmes, there will have to be a shift from cytology to HPV testing as the main technology involved in primary cervical screening, say the contributors to an on-coming special issue of Preventive Medicine (Tota & Ratnam I) (T&R). Why?  Well, first, because of the inevitable decline in the positive predictive value of the test (i.e. proportion of positive results that are true positives) that comes with declining prevalence of HPV sequelae.  This is an important consideration given the reality of the potential ‘harm’ resulting from false positive diagnoses.  But it is also necessary to take into account the impact on diagnosis (which, of course, in the case of cytology, takes place through the judgment of fallible human cytotechnologists) of the ever-dwindling proportion of abnormalities – an effect well described by T&R as a reduced ‘signal-to-noise ratio’.  This, our authors argue, will inevitably lead to ‘fatigue’.

Yet the transition to HPV primary screening is very much to be welcomed, it seems.  Tota & Ratnam I comprehensively review recent trials – in Canada, US and Europe – which all demonstrate that primary HPV screening (in combination with various ‘triage’ regimes for positive cases) offers more security, even at more distant testing intervals, than a cytology-based regime.  Also one that is less prone to human error, more cost-effective, as well as capable (unlike cytology) of being adapted to ‘self-testing’ regimes that could allow wider access (especially in limited resource settings).

Another paper in this on-coming special issue reviews trials (Canadian HPV FOCAL, and Montreal-based VASCAR) testing different ‘triage’ regimes (Tota & Ratnam II).  These involve cytology, with or without HPV genotyping.  Genotyping allows the discrimination of different levels of risk according to HPV genotype, giving health services the option of a differentiated approach to more or less ‘high risk’ strains (i.e. retesting after a year, referral to cytology, or to colposcopy). Whether or not genotyping is included in the regime, the combination of primary HPV screening in combination with triage seems to offer a much more reliable test than cytology – at the possible cost of some relatively minor increase in needless colposcopy referral.

Yet cervical screening policy must, in practice, be informed by more than epidemiological evidence – as the editor of this special issue (Schiffman) reminds us.  It will also depend on available resources and the willingness of a particular system to assume a degree of risk.  The US is particularly good example.  As Kinney & Huh show, in another study in this issue same special issue, the very marginal increment in safety demonstrated by five-yearly co-testing over stand-alone HPV is one that US appears not to be willing to relinquish, even at considerable cost both economic and in terms of ‘harms from screening’.

At the other extreme, of course, are the medium and limited-resource settings in which, for various reasons the aspiration to offer affordable protection through traditional forms of screening (e.g.  visual inspection with acetic acid (VIA)), may currently be delivering ‘sub-optimal’ results (see, for example, Sibanda & Cowan (STIs)).  (For an evaluation of HPV screening as against VIA, see Mitchell & Ogilvie (STIs).)  The special issue includes papers that consider the possibility of diverse screening algorithms in limited resource settings (Maza & Gage; Kuhn & Denny).  Where there are problems of access, the self-collection of samples, which becomes a possibility with HPV primary screening may offer a more feasible alternative to clinician based approaches.  Vallely & Caldor (STIs) makes the case for screening based on self-sampling using CepheidXpert.  Nelson & Arnold (STIs)  review 24 studies of HPV self-sampling across five continents.

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.

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