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1.  The prevalence of lymphogranuloma venereum infection in men who have sex with men: results of a multicentre case finding study 
Sexually Transmitted Infections  2009;85(3):173-175.
Objective:
To determine the prevalence of lymphogranuloma venereum (LGV) and non-LGV associated serovars of urethral and rectal Chlamydia trachomatis (CT) infection in men who have sex with men (MSM).
Design:
Multicentre cross-sectional survey.
Setting:
Four genitourinary medicine clinics in the United Kingdom from 2006–7.
Subjects:
4825 urethral and 6778 rectal samples from consecutive MSM attending for sexual health screening.
Methods:
Urethral swabs or urine and rectal swabs were tested for CT using standard nucleic acid amplification tests. Chlamydia-positive specimens were sent to the reference laboratory for serovar determination.
Main outcome:
Positivity for both LGV and non-LGV associated CT serovars; proportion of cases that were symptomatic.
Results:
The positivity (with 95% confidence intervals) in rectal samples was 6.06% (5.51% to 6.66%) for non-LGV CT and 0.90% (0.69% to 1.16%) for LGV; for urethral samples 3.21% (2.74% to 3.76%) for non-LGV CT and 0.04% (0.01% to 0.16%) for LGV. The majority of LGV was symptomatic (95% of rectal, one of two urethral cases); non-LGV chlamydia was mostly symptomatic in the urethra (68%) but not in the rectum (16%).
Conclusions:
Chlamydial infections are common in MSM attending for sexual health screening, and the majority are non-LGV associated serovars. We did not identify a large reservoir of asymptomatic LGV in the rectum or urethra. Testing for chlamydia from the rectum and urethra should be included for MSM requesting a sexual health screen, but serovar-typing is not indicated in the absence of symptoms. We have yet to identify the source of most cases of LGV in the UK.
doi:10.1136/sti.2008.035311
PMCID: PMC2683989  PMID: 19221105
2.  Lymphogranuloma Venereum in Australia: Anorectal Chlamydia trachomatis Serovar L2b in Men Who Have Sex with Men▿  
Journal of Clinical Microbiology  2007;45(3):1029-1031.
Lymphogranuloma venereum (LGV) is a sexually transmitted infection that is causing an ongoing epidemic in men who have sex with men (MSM) in Europe, the United Kingdom, and North America. Twenty-nine rectal swabs positive for Chlamydia trachomatis were analyzed by real-time PCR for the presence of LGV serovars. Genotyping revealed an identical L2b serovar from four specimens. All patients were MSM and human immunodeficiency virus infected. Three of the four presented with severe ulcerative proctitis. We report a cluster of rectal LGV serovar L2b infections in Sydney, Australia.
doi:10.1128/JCM.02389-06
PMCID: PMC1829134  PMID: 17251405
3.  Lymphogranuloma Venereum Prevalence in Sweden among Men Who Have Sex with Men and Characterization of Chlamydia trachomatis ompA Genotypes▿  
Journal of Clinical Microbiology  2006;44(11):4066-4071.
An outbreak of lymphogranuloma venereum (LGV) infections has recently been reported from The Netherlands and other European countries. The Swedish surveillance system has identified three LGV cases since 2004, all with clinically suspected infection in men who have sex with men (MSM). In order to assess the prevalence of LGV in a high-risk group of MSM and include clinically atypical cases, retrospective analysis of 197 Chlamydia trachomatis-infected men was performed. Sequencing of the ompA gene showed a different serotype distribution compared to recent Swedish studies in heterosexual populations. The most common types were G (45%), D (27%), and J (26%), whereas the normally predominant type E accounted for only 4% of the chlamydia cases. Furthermore, certain ompA genotype variants of the dominant serotypes were highly prevalent among MSM, and the reason for this is discussed. No additional case of LGV was detected by retrospective analysis of the high-risk MSM population. This indicates that, thus far, LGV in Sweden is only a result of sporadic import from infected MSM clusters abroad.
doi:10.1128/JCM.00574-06
PMCID: PMC1698335  PMID: 16971651
4.  First case of “bubonulus” in L2 lymphogranuloma venerum 
Sexually Transmitted Infections  2007;83(4):337-338.
Since 2003, an ongoing lymphogranuloma venereum (LGV) proctitis outbreak has been reported in industrialised countries with a new variant designated L2b. Only men who have sex with men (MSM) are affected and most are HIV co‐infected; delayed or incorrect diagnoses are frequent. We report a rare clinical case of LGV primary stage called “bubonulus” with penile adenopathy and secondary local acute lymphoedema in an MSM seropositive man. This is the first case described of this clinical presentation with a L2b genovar strain, occurring immediately after use of a sex toy. It suggests that this presentation is favoured by host immunity and behavioural factors. These factors may also play a part in the new outbreak of LGV.
doi:10.1136/sti.2007.025395
PMCID: PMC2598664  PMID: 17664360
sexually transmitted disease; lymphogranuloma venereum; bubonulus; chlamydia trachomatis; penile adenopathy
5.  The potential role of serology in diagnosing chronic lymphogranuloma venereum (LGV): a case of LGV mimicking Crohn's disease 
Sexually Transmitted Infections  2006;82(2):139-140.
We present the case of a 26 year old HIV positive homosexual man who was managed for suspected Crohn's disease for over 1 year before lymphogranuloma venereum (LGV) was clinically diagnosed. He had presented with constipation, secondary to acute haemorrhagic proctitis, and subsequently had two chlamydia negative rectal smears, using direct fluorescent antibody (DFA) Chlamydia trachomatis staining. Positive chlamydial serology guided retrospective testing of an early rectal biopsy, which was found to have C trachomatis by polymerase chain reaction (Roche Cobas) and identified as LGV serovar L2 by the Sexually Transmitted Bacteria Reference Laboratory (STBRL), Health Protection Agency (HPA), Colindale, London. Chlamydial serology may have a role in identifying late stage LGV infection. Although no standardised test currently exists, consideration should be given to evaluating the role of chlamydial serology in establishing a diagnosis of LGV.
doi:10.1136/sti.2005.016667
PMCID: PMC2564686  PMID: 16581740
lymphogranuloma venereum; chlamydia; Crohn's disease; serology; proctitis
6.  Lymphogranuloma venereum proctosigmoiditis is a mimicker of inflammatory bowel disease 
There has been an increasing prevalence of lymphogranuloma venereum (LGV) or Chlamydia trachomatis (C. trachomatis) cases among the men who have sex with men (MSM) population, particularly in Europe and North America. These cases may present with an incomplete or undisclosed history and proctosigmoiditis without characteristic adenopathy syndrome. During the initial evaluation and colonoscopy, there is a strong clinical and endoscopic suspicion of inflammatory bowel disease (IBD) by virtue of presentation and endoscopic and histological findings. The diagnosis of IBD is subsequently modified to LGV proctosigmoiditis when one or more of the following transpire: (1) there is failure of response to IBD therapy; (2) additional components of history (MSM/travel) may be identified; (3) return of initially performed Chlamydia antibody test is positive; and (4) response to antibiotics effective against Chlamydia. We describe three such cases initially suspected to be an inflammatory bowel disease and subsequently identified as C. trachomatis proctosigmoiditis.
doi:10.3748/wjg.v18.i25.3317
PMCID: PMC3391771  PMID: 22783058
Lymphogranuloma venereum; Chlamydia trachomatis; Proctitis; Proctosigmoiditis; Men who have sex with men; Crohn’s disease; Inflammatory bowel disease
7.  Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L2) and D Lineages 
mBio  2011;2(3):e00045-11.
ABSTRACT
Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation.
IMPORTANCE
Lymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L2 and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.
doi:10.1128/mBio.00045-11
PMCID: PMC3088116  PMID: 21540364
8.  The use of serological titres of IgA and IgG in (early) discrimination between rectal infection with non‐lymphogranuloma venereum and lymphogranuloma venereum serovars of Chlamydia trachomatis 
Sexually Transmitted Infections  2007;83(4):330-334.
Objectives
To investigate whether serological titres of species‐specific IgA and IgG antibodies in patients with rectal chlamydial infection could discriminate between infection with serovar L2 lymphogranuloma venereum (LGV) and infection with non‐LGV serovars.
Methods
A total of 39 male patients with chlamydial infection of the rectum were tested for titres of IgA and IgG antibodies within 14 days after detection of the infection and 6 and 12 months after adequate treatment. Data were collected regarding demographics, sexual orientation, HIV serostatus, history of chlamydial infection, concomitant sexually transmitted infection (STI) or HIV infection, hepatitis C virus antibodies and new STIs during follow‐up.
Results
Between May 2003 and November 2005, 24 men with confirmed L2 proctitis and 15 men with non‐LGV rectal chlamydial infection were recruited. In multivariable analyses, both high titre of IgA within 14 days after detection of the infection and older age of the individual were found significantly associated with L2 proctitis (p<0.001 and p = 0.001, respectively). A total sum score of seven times IgA titre and individual's age ⩾50 years resulted in an overall sensitivity of 92% and specificity of 100%. This total sum score was highly accurate for detection of LGV proctitis, with an area under the curve in a receiver operating characteristic curve of 0.989.
Conclusions
An increased IgA antibody response and the age of the infected individual are of possible diagnostic value for (early) detection of LGV proctitis.
doi:10.1136/sti.2006.024372
PMCID: PMC2598666  PMID: 17475689
9.  Anal infections with concomitant Chlamydia trachomatis genotypes among men who have sex with men in Amsterdam, the Netherlands 
Background
Lymphogranuloma venereum (LGV) proctitis is caused by Chlamydia trachomatis (Ct) genotype L and is endemic among men who have sex with men (MSM) in western society. Genotype L infections need to be distinguished from non-LGV (genotypes A-K) Ct infections since they require prolonged antibiotic treatment. For this purpose, an in-house developed pmpH based LGV polymerase chain reaction (PCR) test is used at the Amsterdam STI outpatient clinic. We investigated retrospectively the anal Ct genotype distribution, and the frequency of concomitant genotype infections in MSM infected with LGV and non-LGV Ct infections. To detect concomitant Ct genotype infections, the pmpH LGV PCR and genoTyping Reverse Hybridization Assay (Ct-DT RHA) were used.
Methods
A total of 201 Ct positive rectal swabs from MSM were selected, which were previously diagnosed as either LGV (n = 99) or non-LGV Ct infection (n = 102) according to the algorithm of Ct detection by the commercially available Aptima Combo 2 assay followed by an in-house pmpH LGV PCR. The samples were retested with the commercially available Ct-DT RHA, which differentiates between 14 major genotypes and is able to detect concomitant Ct genotypes.
Results
Excellent genotyping agreement was observed between the Ct-DT RHA and the pmpH LGV PCR (Kappa = 0.900, 95%CI = 0.845-0.955, McNemar's p = 1.000). A concomitant non-LGV genotype was detected in 6/99 (6.1%) LGV samples. No additional LGV infections were observed with the Ct-DT RHA among the non-LGV Ct group. In the non-LGV group genotype G/Ga (34.3%) was seen most frequent, followed by genotype D/Da (22.5%) and genotype J (13.7%). All LGV infections were caused by genotype L2.
Conclusions
Concomitant non-LGV genotypes do not lead to missed LGV proctitis diagnosis. The pmpH LGV PCR displayed excellent agreement with the commercially available Ct-DT genotyping RHA test. The genotypes G/Ga, D/Da and J were the most frequent non-LGV Ct strains in MSM.
doi:10.1186/1471-2334-11-63
PMCID: PMC3068958  PMID: 21401939
10.  Update on lymphogranuloma venereum in the United Kingdom 
Sexually Transmitted Infections  2007;83(4):324-326.
Objectives
This report updates the UK epidemiology of lymphogranuloma venereum (LGV) to the end of April 2007.
Methods
The Health Protection Agency's Centre for Infections undertakes laboratory testing for LGV and subsequent epidemiological investigation of cases after laboratory confirmation of the LGV serovars (L1–3). Data analysis of enhanced surveillance and laboratory reports was undertaken.
Results
From October 2004 to end April 2007, 492 cases of LGV have been diagnosed and enhanced surveillance forms have been returned for 423. Cases peaked in the third quarter of 2005 with an average of 32 cases per month, while in 2006 this fell to 12 cases per month. Nationally, the outbreak is focused in London, Brighton and the North West. All cases are in men, 99% of whom are MSM, with a median age of 40 and predominantly white ethnicity (91%). Co‐infection remains considerable: HIV (74%); hepatitis C (14%); syphilis (5%); and other STIs including gonorrhoea, genital herpes and hepatitis B. The number of men reporting greater than 10 sexual contacts in the previous 3 months has reduced from 23% (47) to 13% (15) from 2005–2006.
Discussion
The epidemic continues in the mostly white MSM population of the UK. The demographics of LGV remain similar to those previously described and high levels of HIV co‐infection continue. Reduced numbers of sexual contacts might be contributing to the reduced numbers of LGV seen in 2006 but could simply mean that LGV is moving out of the highest risk groups.
doi:10.1136/sti.2007.026740
PMCID: PMC2598681  PMID: 17591663
11.  Systemic Chlamydia trachomatis infection in mice: a comparison of lymphogranuloma venereum and trachoma biovars. 
Infection and Immunity  1985;48(1):78-82.
We developed a murine model of systemic infection with Chlamydia trachomatis biovar lymphogranuloma venereum (LGV). The pathological features of this infection resemble those of human LGV infection since both are characterized by granuloma formation. Mice developed resistance to reinfection with LGV, and this resistance was based on cellular immune mechanisms since it was transferable with immune spleen cells but not with immune serum. Resistance required viable organisms for induction. We compared LGV biovar infection with trachoma biovar infection. Trachoma biovar produced similar but less marked microbiological and pathological features. Cross-immunity was less apparent between serovars from trachoma and LGV biovars than it was between serovars within the same biovar. This model of systemic C. trachomatis infection will be useful in exploring virulence features of LGV.
PMCID: PMC261917  PMID: 3980097
12.  Lymphogranuloma venereum presenting as a rectovaginal fistula. 
Lymphogranuloma venereum (LGV) is a rare form of the sexually transmitted disease caused by Chlamydia trachomatis. In the United States, there are fewer than 350 cases per year. In a review of the world's literature, there has not been a case reported in the last thirty years of a case of LGV presenting as a rectovaginal fistula. We present a case of an otherwise healthy American woman who presented with a rectovaginal fistula. Although uncommon, LGV does occur in developed countries and may have devastating tissue destruction if not recognized and treated before the tertiary stage.
doi:10.1002/(SICI)1098-0997(1999)7:4<199::AID-IDOG7>3.0.CO;2-K
PMCID: PMC1784745  PMID: 10449269
13.  Contrast of Glycogenesis and protein synthesis in monkey kidney cells and HeLa cells infected with Chlamydia trachomatis lymphogranuloma venereum. 
Infection and Immunity  1978;20(3):632-639.
Glycogen metabolism of monkey kidney (LLC-MK-2) cells and HeLa 229 cells infected with a Chlamydia trachomatis lymphogranuloma venereum 440 L (LGV) was studied. The growth cycle of LGV in both host cells was similar; however, a greater number of infectious organism developed intracellularly and were released into the medium during LGV infection of HeLa 229 cells than MK-2 cells. A rapid infection accompanied by a high rate of glycogen synthesis and a short period of accumulation was found in GeLa 229 cells infected with LGV. LGV infected MK-2 cells started to accumulate glycogen about the same time as HeLa 229 cells; however, the rate of glycogen synthesis was lower and the period of accumulation was longer. The LGV agent grew in cycloheximide-treated cells in the absence of host cell protein synthesis. Protein synthesis associated with LGV throughout the developmental cycle was similar in both cell types and could be abolished by chloramphenicol. The continued synthesis of glycogen in the presence of cycloheximide suggested that the synthesis of glycogen was directed by the organism in both MK-2 cells and HeLa 229 cells.
PMCID: PMC421905  PMID: 669815
14.  Lymphogranuloma Venereum II. Characterization of Some Recently Isolated Strains 
Journal of Bacteriology  1969;99(3):636-638.
Five Bedsonia (Chlamydia) isolates from lymphogranuloma venereum (LGV) patients were tested for inclusion type, sulfonamide sensitivity, and mouse virulence. Two matched the classical description of LGV agents. Two were not virulent for mice by the intracerebral route, therefore fitting the description for trachoma-inclusion conjunctivitis agents. One was highly virulent for mice and sulfonamide-resistant, and produced inclusions that did not stain with iodine, all characteristics generally associated with avian bedsoniae. A sixth isolate could not be adequately tested due to poor infective yields. Because of this variety of properties within the Bedsonia group, the term LGV might more appropriately be reserved for clinical disease rather than to describe a particular bedsonial agent.
PMCID: PMC250073  PMID: 4905529
15.  New Lymphogranuloma Venereum Chlamydia trachomatis Variant, Amsterdam 
Emerging Infectious Diseases  2005;11(7):1090-1092.
We retrospectively conducted a study of men who have sex with men who visited the Amsterdam, the Netherlands, sexually transmitted diseases clinic from January 2002 to December 2003 and had rectal Chlamydia trachomatis infections. We found that symptomatic (73%) as well as asymptomatic (43%) patients were infected with a new C. trachomatis LGV variant.
doi:10.3201/eid1107.040883
PMCID: PMC3371808  PMID: 16022786
Chlamydia trachomatis; genotype; LGV; omp A gene; L2 variant; L2b
16.  Lipid Metabolism of Monkey Kidney Cells (LLC-MK-2) Infected with Chlamydia trachomatis Strain lymphogranuloma venereum 
Infection and Immunity  1974;10(3):464-470.
Lipid metabolism of monkey kidney (LLC-MK-2) cells and cells infected with a Chlamydia trachomatis strain lymphogranuloma venereum (LGV) was studied. The protein-to-lipid ratio of normal MK-2 cells was found to increase linearly over a 60-h period of incubation. The protein-to-lipid ratio of the infected cells was similar to that in normal cells until 36 h after infection, when a plateau in the ratio was observed. Lipid synthesis of the infected cells was found to be inhibited after 48 h of infection. Turnover of host lipids did not appear to be markedly altered by infection with LGV over a 48-h period of incubation. An anteiso branched chain of 15:0 fatty acid was found in infected cells but not in normal cells. The appearance of this fatty acid, correlated with a rise in the infectivity of LGV, suggests that synthesis of specific lipids was associated with the infection.
PMCID: PMC422976  PMID: 4214771
17.  Cytotoxic and immunoregulatory function of intestinal lymphocytes in Chlamydia trachomatis proctitis of nonhuman primates. 
Infection and Immunity  1987;55(5):1137-1143.
To study the role of natural killer cells and immunoregulatory T cells in the pathogenesis of proctitis due to Chlamydia trachomatis (L2 serovar), lymphocytes were obtained from the rectal mucosa and other sites of nonhuman primates and studied by using phenotypic and functional assays. In animals with lymphogranuloma venereum (LGV) proctitis, the percentage of lymphocytes with the natural killer cell phenotype (Leu-11+) was not significantly higher at any site in LGV infection, and natural killer cell function of lymphocytes isolated from the rectum was lower during LGV infection. This was not due to the suppressive effect of factors in serum, rectal lymphocytes, or LGV elementary bodies. In studies of regulatory T cells, the Leu-3+/Leu-2+ ratio was lower in the peripheral blood and the spleen during LGV infection, but the ratio did not decrease in lamina propria T cells. Both peripheral blood and rectal lymphocytes had higher helper T-cell function for polyclonal immunoglobulin G (IgG) synthesis in pokeweed mitogen-stimulated cultures 2 weeks following LGV infection. Increased suppressor T-cell function for pokeweed mitogen-stimulated IgG synthesis was found only in the peripheral blood of animals 2 weeks after infection, but not in isolated rectal lymphocytes. These results indicate that in LGV proctitis natural killer cells are not an important component of the inflammatory infiltrate at the site of infection, and helper T-cell function increases in peripheral blood and rectal lymphocytes.
PMCID: PMC260481  PMID: 2952593
18.  Lymphographic studies in acute lymphogranuloma venereum infection. 
Lymphography, a radiological method of demonstrating lymphatic channels and nodes, has been used to investigate three cases of acute bubonic lymphogranuloma venereum (LGV). There is general agreement that LGV has a predilection for lymphatic channels and lymph nodes. However, very little is known of the extent of lymph node involvement in the early bubonic stage and whether there is merely a lymphangitis or complete lymphatic obstruction. The present study was undertaken to determine the lymphographic appearance in acute bubonic LGV, the extent of lymphatic node involvement in early LGV, and the usefulness of the procedure in the management of LGV patients. The buboes were not outlined by this procedure. The vessel phase of the lymphogram appeared normal, while the nodal phase showed a gradient of pathological involvement from the inguinal region lessening towards the lumbar nodes. The main drawbacks of lymphography in LGV are the difficulty of visualizing the lymphatics in the negroid skin and the lack of diagnostic criteria for inflammatory diseases of the lymphatic system. The lymphographic findings in LGV as described here may be regarded as typical of LGV but cannot be accepted as specific for LGV with a high degree of confidence. It is suggested that the procedure could be used for monitoring patients with the severe and late sequelae of LGV infection.
Images
PMCID: PMC1045319  PMID: 1009421
19.  Elevated Risk for HIV Infection among Men Who Have Sex with Men in Low- and Middle-Income Countries 2000–2006: A Systematic Review 
PLoS Medicine  2007;4(12):e339.
Background
Recent reports of high HIV infection rates among men who have sex with men (MSM) from Asia, Africa, Latin America, and the former Soviet Union (FSU) suggest high levels of HIV transmission among MSM in low- and middle-income countries. To investigate the global epidemic of HIV among MSM and the relationship of MSM outbreaks to general populations, we conducted a comprehensive review of HIV studies among MSM in low- and middle-income countries and performed a meta-analysis of reported MSM and reproductive-age adult HIV prevalence data.
Methods and Findings
A comprehensive review of the literature was conducted using systematic methodology. Data regarding HIV prevalence and total sample size was sequestered from each of the studies that met inclusion criteria and aggregate values for each country were calculated. Pooled odds ratio (OR) estimates were stratified by factors including HIV prevalence of the country, Joint United Nations Programme on HIV/AIDS (UNAIDS)–classified level of HIV epidemic, geographic region, and whether or not injection drug users (IDUs) played a significant role in given epidemic. Pooled ORs were stratified by prevalence level; very low-prevalence countries had an overall MSM OR of 58.4 (95% CI 56.3–60.6); low-prevalence countries, 14.4 (95% CI 13.8–14.9); and medium- to high-prevalence countries, 9.6 (95% CI 9.0–10.2). Significant differences in ORs for HIV infection among MSM in were seen when comparing low- and middle-income countries; low-income countries had an OR of 7.8 (95% CI 7.2–8.4), whereas middle-income countries had an OR of 23.4 (95% CI 22.8–24.0). Stratifying the pooled ORs by whether the country had a substantial component of IDU spread resulted in an OR of 12.8 (95% CI 12.3–13.4) in countries where IDU transmission was prevalent, and 24.4 (95% CI 23.7–25.2) where it was not. By region, the OR for MSM in the Americas was 33.3 (95% CI 32.3–34.2); 18.7 (95% CI 17.7–19.7) for Asia; 3.8 (95% CI 3.3–4.3) for Africa; and 1.3 (95% CI 1.1–1.6) for the low- and middle-income countries of Europe.
Conclusions
MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as general population prevalence increases, but remain 9-fold higher in medium–high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.
From a systematic review, Chris Beyrer and colleagues conclude that men who have sex with men in the Americas, Asia, and Africa have a markedly greater risk of being HIV-infected than does the general population.
Editors' Summary
Background.
AIDS (acquired immunodeficiency syndrome) first emerged in the early 1980s among gay men living in New York and California. But, as the disease rapidly spread around the world, it became clear that AIDS also affected heterosexual men and women. Now, a quarter of a century later, 40 million people are infected with human immunodeficiency virus (HIV), the organism that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner and in sub-Saharan Africa, the region most badly hit by HIV/AIDS, heterosexual transmission predominates. However, globally, 5%–10% of all HIV infections are thought to be in men who have sex with men (MSM, a term that encompasses gay, bisexual, transgendered, and heterosexual men who sometimes have sex with men), and in several high-income countries, including the US, male-to-male sexual contact remains the most important HIV transmission route.
Why Was This Study Done?
In the US, the MSM population is visible and there is considerable awareness about the risks of HIV transmission associated with sex between men. In many other countries, MSM are much less visible. They remain invisible because they fear discrimination, stigmatization (being considered socially unacceptable), or arrest—sex between men is illegal in 85 countries. Consequently, MSM are often under-represented in HIV surveillance systems and in prevention and care programs. If the AIDS epidemic is going to be halted, much more needs to be known about HIV prevalence (the proportion of the population that is infected) among MSM. In this study, the researchers have done a systematic review (a type of research where the results of existing studies are brought together) on published reports of HIV prevalence among MSM in low- and middle-income countries to get a better picture of the global epidemic of HIV in this population.
What Did the Researchers Do and Find?
The researchers found 83 published studies that reported HIV prevalence in 38 low- and middle-income countries in Asia, Africa, the Americas, and Eastern Europe. When the results were pooled—in what statisticians call a meta-analysis—MSM were found to have a 19.3-times greater chance of being infected with HIV than the general population. This is described as a pooled odds ratio (OR) of 19.3. The researchers also did several subgroup analyses where they asked whether factors such as injection drug use (another risk factor for HIV transmission), per capita income, geographical region, or the HIV prevalence in the general population were associated with differential risk (increase in odds) of HIV infection compared to the general population. They found, for example, that in countries where the prevalence of HIV in the general population was very low (less than 1 adult in 1,000 infected) the pooled OR for MSM compared to the general population was 58.4; where it was high (more than 1 adult in 20 infected), the pooled OR for MSM was 9.6.
What Do These Findings Mean?
These findings indicate that MSM living in low- to middle-income countries have a greater risk of HIV infection than the general populations of these countries. The subgroup analyses indicate that the high HIV prevalence among MSM is not limited to any one region or income level or to countries with any specific HIV prevalence or injection drug use level. Although the small number and design of the studies included in the meta-analysis may affect the numerical accuracy of these findings, the clear trend toward a higher HIV prevalence of among MSM suggests that HIV surveillance efforts should be expanded to include MSM in those countries where they are currently ignored. Efforts should also be made to include MSM in HIV prevention programs and to improve the efficacy of these programs by investigating the cultural, behavioral, social, and public policy factors that underlie the high HIV prevalence among MSM. By increasing surveillance, research, and prevention among MSM in low- to middle-income countries, it should be possible to curb HIV transmission in this marginalized population and reduce the global burden of HIV.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040339.
The International Lesbian and Gay Association provides a world legal map on legislation affecting lesbian, gay, bisexual, and transgendered people
The International Gay and Lesbian Human Rights Commission provides a page called Off the Map: How HIV/AIDS Programming is Failing Same-Sex Practicing People in Africa
The American Foundation for AIDS Research (amfAR) has launched their MSM initiative, which is focused on providing support to front-line community groups working on providing services and doing research focused on HIV among MSM in lower income-settings
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of organizations that provide information for gay men and MSM
Information is available from Avert, an international AIDS charity, on HIV, AIDS, and men who have sex with men
The US Centers for Disease Control and Prevention provides information on HIV/AIDS and on HIV/AIDS among men who have sex with men (in English and Spanish)
doi:10.1371/journal.pmed.0040339
PMCID: PMC2100144  PMID: 18052602
20.  Interaction of Chlamydia trachomatis organisms and HeLa 229 cells. 
Infection and Immunity  1976;13(4):1103-1109.
The infection of HeLa 229 cells in monolayer culture with trachoma (B/TW-5/OT) and lymphogranuloma venereum (LGV) (L2/434/Bu) organism was studied in terms of two parameters: radioactivity counts of cell-associated tritium labeled organisms at the initial stage of inoculation for measurement of attachment, and inclusion counts of infection cells after incubation for measurement of growth. Factors affecting attachment and inclusion formation and correlation of the two are presented. It was shown that attachment is an important initial step in infection by Chlamydia trachomatis. The rate of attachment was temperature dependent. The attachment of LGV organisms was affected more profoundly by temperature than was that of trachoma organisms. Attachment and inclusion formation of trachoma and LGV organisms were inhibited by heparin. Diethylaminoethyl-dextran was again shown to enhance attachment and inclusion formation of trachoma but not LGV organisms. NaF had no effect on attachment, but inhibited inclusion formation of both trachoma and LGV organisms. Both attachment and inclusion formation of trachoma organisms were strongly enhanced by centrifugation of the inoculum onto the cell monolayer. Although inclusion formation of trachoma organism was much greater in susceptible cells (HeLa 229) than relatively insusceptible cells (fetal tonsil), attachment was only slightly greater. The results based on the test of two cell lines suggested that attachment prpbably is not a critical factor in determing a cell line's susceptibility to infection with trachoma organisms.
PMCID: PMC420724  PMID: 179950
21.  Characterization of Chlamydia DNA by restriction endonuclease cleavage. 
Infection and Immunity  1983;41(2):604-608.
The DNA from six serovars of Chlamydia trachomatis, lymphogranuloma venereum (LGV) I, LGV II, LGV III, B, C, and D, and from Chlamydia psittaci was extracted, treated with restriction endonuclease enzymes, and run on agarose gels. By using this technique, the DNA of C. trachomatis could be clearly differentiated from C. psittaci DNA. A comparison of the DNA from the different serovars of C. trachomatis revealed similar patterns with and without detectable differences. LGV I, LGV II, LGV III, B, and C revealed no differences when treated with BamHI, HaeIII, XbaI, and XhoI. LGV III DNA, when cleaved with EcoRI and HhaI, had a major band migrating faster than the other two LGV serovars. Serovar D had a different pattern from all other strains tested when cleaved with BamHI, EcoRI, HhaI, HincI, and XhoI. When treated with SacI and HgaI, LGV II displayed a unique band not seen in the other LGV serovars. Differences in strains could be attributed to both chromosomal and plasmid DNA.
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PMCID: PMC264685  PMID: 6307876
22.  Isolation and Characterization of a Mutant Chinese Hamster Ovary Cell Line That Is Resistant to Chlamydia trachomatis Infection at a Novel Step in the Attachment Process 
Infection and Immunity  2001;69(9):5899-5904.
Host factors involved in Chlamydia trachomatis pathogenesis were investigated by random chemical mutagenesis of Chinese hamster ovary (CHO-K1) cells followed by selection for clones resistant to chlamydial infection. A clonal mutant cell line, D4.1–3, refractory to infection by the C. trachomatis L2 serovar was isolated. The D4.1–3 cell line appears to be lacking in a previously undescribed temperature-dependent and heparin-resistant binding step that occurs subsequent to engagement of cell surface heparan sulfate by L2 elementary bodies. This novel binding step differentiates the lymphogranuloma venereum (LGV) serovar from other serovars and may contribute the different pathologies associated with LGV and non-LGV strains.
doi:10.1128/IAI.69.9.5899-5904.2001
PMCID: PMC98709  PMID: 11500469
23.  Histological, immunofluorescent, and ultrastructural features of lymphogranuloma venereum: a case report. 
We studied the course of a case of lymphogranuloma venereum (LGV) over two years. The comparative histological, immunological, and ultrastructural studies showed the existence of characteristic granulations within the macrophages of the granuloma. We suggest that direct immunofluorescence is a specific method for diagnosing cutaneous LGV. Some ultrastructural aspects lead us to believe that different chlamydial bodies exist inside the granuloma.
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PMCID: PMC1046388  PMID: 6394098
24.  Genital ulcer disease in men in Durban, South Africa. 
Genitourinary Medicine  1991;67(4):327-330.
OBJECTIVE--To study the microbial aetiology of genital ulcer disease (GUD) in men. DESIGN--Microbiological and clinical assessment of genital ulcers in men. SETTING--City Health sexually transmitted diseases clinic, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS--100 Zulu men with genital ulcers who had not received antibiotics in the previous four weeks. RESULTS--Syphilis was diagnosed in 42%, chancroid in 22%, donovanosis (granuloma inguinale) in 11%, genital herpes in 10% and lymphogranuloma venereum (LGV) in 6%. No pathogens were identified in 24%. Mixed infections were detected in 14 men, in whom 13 had syphilis. Five men had HIV-1 antibodies. Neisseria gonorrhoeae was isolated from the ulcers and urethra in seven men and from the urethra alone in five. Scabies was diagnosed clinically in eight. CONCLUSIONS--All the major causes of GUD are prevalent in Zulu men in Durban. Primary syphilis was the commonest and was invariably present in mixed infections. Donovanosis was under-reported and was associated with a long delay before presentation. In this population, genital ulcers other than superficial lesions should be treated with anti-syphilitic therapy and oral antibiotics effective against chancroid and donovanosis.
PMCID: PMC1194710  PMID: 1655627
25.  Men Who Have Sex with Men and Human Immunodeficiency Virus/Sexually Transmitted Disease Control in China 
Cell research  2005;15(11-12):858-864.
Objectives:
To address the role of men who have sex with men (MSM) in the human immunodeficiency virus (HIV)/sexually transmitted disease (STD) epidemic in China.
Goal:
To explore the prevalence of risky sexual behaviors and the existing prevention efforts among men who have sex with men (MSM) in China.
Study Design:
Review of behavioral and STD/HIV prevention studies addressing MSM in China.
Results:
Sexual risk behaviors including unprotected group sex, anal sex, casual sex, and commercial sex were prevalent among Chinese MSM. Many Chinese MSM also engaged in unprotected sex with both men and women. Most MSM either did not perceive that they were at risk of HIV/AIDS or underestimated their risk of infection. Surveillance and intervention research among these men are still in the preliminary stages.
Conclusions:
Chinese MSM are at risk for HIV/STD infection and potential transmission of HIV to the general population. In addition to sexual risk reduction among MSM, reduction of homosexualityrelated stigma should be part of effective intervention efforts. Volunteers from the MSM community and health care workers in primary health care system may serve as valuable resources for HIV/STD prevention and control among MSM.
doi:10.1038/sj.cr.7290359
PMCID: PMC1791010  PMID: 16354560

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