Genital Inflammation Research Articles

Symptomatic Vaginal Discharge Is a Poor Predictor of Sexually Transmitted Infections and Genital Tract Inflammation in High-Risk Women in South Africa

Diagnosis and treatment of sexually transmitted infections (STIs) is a public health priority, particularly in regions where the incidence of human immunodeficiency virus (HIV) infection is high. In most developing countries, STIs are managed syndromically. We assessed the adequacy of syndromic diagnosis of STIs, compared with laboratory diagnosis of STIs, and evaluated the association between STI diagnosis and the risk of HIV acquisition in a cohort of high-risk women. HIV-uninfected high-risk women (n = 242) were followed for 24 months. Symptoms of STIs were recorded, and laboratory diagnosis of common STI pathogens was conducted every 6 months. Forty-two cytokines were measured by Luminex in cervicovaginal lavage specimens at enrollment. Human immunodeficiency virus type 1 (HIV-1) infection was evaluated monthly. Only 12.3% of women (25 of 204) who had a laboratory-diagnosed, discharge-causing STI had clinically evident discharge. Vaginal discharge was thus a poor predictor of laboratory-diagnosed STIs (sensitivity, 12.3%; specificity, 93.8%). Cervicovaginal cytokine concentrations did not differ between women with asymptomatic STIs and those with symptomatic STIs and were elevated in women with asymptomatic STIs, compared with women with no STIs or bacterial vaginosis. Although laboratory-diagnosed STIs were associated with increased risk of HIV infection (hazard ratio, 3.3 [95% confidence interval, 1.5-7.2)], clinical symptoms were not. Syndromic STI diagnosis dependent on vaginal discharge was poorly predictive of laboratory-diagnosed STI. Laboratory-diagnosed STIs were associated with increased susceptibility to HIV acquisition, while vaginal discharge was not.

Vaginal microbicides to prevent human immunodeficiency virus infection in women: Perspectives on the female genital tract, sexual maturity and mucosal inflammation

Topically applied vaginal microbicides to protect against human immunodeficiency (HIV) virus infection offer an important female-controlled prevention strategy. Microbicides have been in development for more than 2 decades, and have included various agents that disrupt cellular and microbial membranes (surfactants), restore the natural acidic protective pH of the vagina (acid buffers), and those that interfere with interactions between HIV envelope proteins and cellular receptors (anionic polymers). Although none of these candidate microbicides have shown significant protection against HIV in clinical trials, a topical gel, including the antiretroviral drug tenofovir (TFV) 1% was the first microbicide to be tested to show some protection against HIV infection. This review explores the effect of female genital tract biology and anatomy, mucosal inflammation, and age on the effectiveness of microbicides to prevent HIV infection.

《상한론(傷寒論)》, 《김궤요략(金匱要略)》의 피부증상(皮膚症狀) 및 질환(疾患)에 대한 연구(硏究)

Objective : The purpose of this study is to investigate the skin disease in Sanghanron"傷寒論" and Geumgweyoryak"金匱要略". Methods : We conducted a study on the original text paragraphs of Sanghanron and Geumgweyoryak containing the skin disease and analysis of Woo, Oh, Sung, Zhang, etc. We drew a parallel between skin disease from Sanghanron and Geumgweyoryak and matching diagnoses from western medicine. Results : The results were as follows. 1. In Sanghanron and Geumgweyoryak pruritus was related to psychogenic pruritus and similar to skin disease caused by decrease of sweating, dry skin in cholinergic urticaria, atopic dermatitis and eczema, etc. in western medicine. 2. In Geumgweyoryak ichthyosis was caused by woman's disease, after menopause, chronic disease and malnutrition and related to winter itch and xerotic eczema in western medicine. 3. In Sanghanron Goose bumps, keratosis follicularis, acute and chronic urticaria and cold urticaria were occurred because of poorly managed fever care and side effect of antibiotic. 4. In Geumgweyoryak red face was similar to face flushing and side effects, which is after drug and laser treatment on face, in western medicine. 5. In Geumgweyoryak urticaria was, in a broad sense, skin disease with pruritus and secondary infection resulted from scratch. Skin diseases with pruritus are similar to urticaria, dermatitis herpetiformis, lichen planus, atopic dermatitis, contact dermatitis, psoriasis, nummular eczema, lichen simplex chronicus, prurigo nodularis, neurodermatitis and internal disease with pruritus in western medicine. 6. In Geumgweyoryak spots in the skin were caused by fever and similar to allergic purpura and SLE symptom in western medicine. 7. In Geumgweyoryak bullous disease with yellowish discharge was similar to eczema, pustule, atopic eczema, etc. in western medicine. 8. In Geumgweyoryak repeated inflammation of oral cavity, genitals, eyes and skin was similar to Behcet's disease in western medicine. 9. In Sanghanron and Geumgweyoryak boil was similar to abscess and acute lymphadenitis in western medicine caused by oily foods and infections. 10. In Geumgweyoryak swelling and boil were occurred in a poor health. Damage from metalic material could cause a convulsion and was similar to tetanus in western medicine. Conclusion : We analyzed the original text paragraphs of Sanghanron and Geumgweyoryak and explanations about skin disease. As a results, we found out etiology, pathogenesis, treatments of the skin disease in Sanghanron and Geumgweyoryak. Further we compared with western medicine to develop better understanding of the skin disease.

A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection

BackgroundVaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV) infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection.MethodsOur study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years). Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types) and low-grade squamous intraepithelial lesions (LSIL), the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit.ResultsDetection of HPV was positively associated with vaginal pH, mainly in women < 35 years (p-trend = 0.009 and 0.007 for women aged < 25 and 25-34 years, respectively). Elevated vaginal pH was associated with 30% greater risk of infection with multiple HPV types and with LSIL, predominantly in women younger than 35 and 65+ years of age. Detection of C. trachomatis DNA was associated with increased vaginal pH in women < 25 years (OR 2.2 95% CI 1.0-5.0).ConclusionsOur findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia.

Correlates of human immunodeficiency virus cervicovaginal shedding among postmenopausal and fertile-aged women

The aims of this study were to compare the intensity of human immunodeficiency virus (HIV)-RNA genital shedding among postmenopausal (PM) and fertile-aged (F) women and to investigate the association between viral shedding and gynecological features, HIV plasma viral loads, and other markers of HIV disease progression. We interviewed 146 HIV-infected women (73 PM/73 F) in search of gynecological complaints and signs and symptoms of HIV disease and obtained additional information concerning HIV infection by medical chart review. Cervicovaginal lavages (CVLs) were collected for assessment of HIV shedding. Laboratory analyses included CD4 cell counts, HIV-RNA quantitation in plasma and CVL, and screening for concurrent genital infections. HIV-RNA genital shedding was detected in 16.4% of PM and 21.9% of F women (P = 0.400), and the intensity of HIV shedding did not differ between both groups (means-PM: 1.4log/mL; F: 1.4log/mL; P = 0.587). Three women (2 PM/1 F) exhibited viral shedding in the absence of detectable viremia. HIV plasma viral loads correlated with HIV shedding in both groups. In multivariable analysis, HIV plasma viral loads were independently associated with HIV shedding in both groups. Moreover, the intensity of shedding was independently associated with vaginal pH, tumor necrosis factor α concentrations in CVL, and HIV plasma viral loads. Despite significant changes that occur in the vaginal mucosa of PM women, HIV cervicovaginal shedding was not significantly influenced by this state in our cohort. In contrast, increased vaginal pH and genital inflammation, evidenced by increased tumor necrosis factor α concentrations in CVL and HIV plasma viral loads, were independently associated with the intensity of HIV shedding in PM and F women.

Genital Tract Inflammation During Early HIV-1 Infection Predicts Higher Plasma Viral Load Set Point in Women

The biggest challenge in human immunodeficiency virus type 1 (HIV-1) prevention in Africa is the high HIV-1 burden in young women. In macaques, proinflammatory cytokine production in the genital tract is necessary for target cell recruitment and establishment of simian immunodeficiency virus (SIV) infection following vaginal inoculation. The purpose of this study was to assess if genital inflammation during early HIV-1 infection predisposes women to rapid disease progression. Inflammatory cytokine concentrations were measured in cervicovaginal lavage (CVL) from 49 women 6, 17, 30, and 55 weeks after HIV-1 infection and from 22 of these women before infection. Associations between genital inflammation and viral load set point and blood CD4 cell counts 12 months after infection were investigated. Elevated genital cytokine concentrations 6 and 17 weeks after HIV-1 infection were associated with higher viral load set points and, to a lesser extent, with CD4 depletion. CVL cytokine concentrations during early infection did not differ relative to preinfection but were elevated in women who had vaginal discharge, detectable HIV-1 RNA in their genital tracts, and lower blood CD4 counts. Genital inflammation during early HIV-1 infection was associated with higher viral load set point and CD4 depletion, which are markers of rapid disease progression. Strategies aimed at reducing genital inflammation during early HIV-1 infection may slow disease progression.

Induction of Cyclooxygenase (COX)‐2 in Human Vaginal Epithelial Cells in Response to TLR ligands and TNF‐α

Mucosal inflammation caused by infections of the female lower genital tract is considered to be an important cofactor for HIV transmission. We hypothesize that COX-2, a key inflammation-related enzyme, is involved in these responses and is upregulated by microbial ligands and pro-inflammatory cytokines. Human vaginal epithelial cells (VK-2/E6E7) and ectocervical biopsy tissues were stimulated with TLR ligands and the cytokine TNF-α, used as surrogates of vaginal infections, and assessed for COX-2 expression and activity by microarray, real-time RT-PCR, immunoblotting, immunohistochemistry, and ELISA. TLR agonists and TNF-α induce transcriptional and translational expression of COX-2 in vaginal cells. TLR ligands, MALP2, Pam3CSK4, LTA, and imiquimod induced high epithelial COX-2 expression, while zymosan and poly dI:dC induced very low enzyme expression. Induced mRNA and protein expression correlated with increased COX-2 activity, which led to increased levels of PGE(2) in the cell culture supernatant. These cell-based findings were confirmed in primary cervicovaginal tissue explants. Induction of COX-2 expression and activity and the consequent increased levels of prostaglandins are common inflammatory pathways in human cervicovaginal epithelial cells and tissues in response to diverse TLR ligands and pro-inflammatory cytokines. These findings are relevant to the understanding of genital mucosal inflammation, its potential treatment, and its possible relationship with increased tissue susceptibility to HIV-1 infection.

Detection and management of acute HIV infections in patients with sexually transmitted infections: a window of opportunity for HIV prevention within South Africa?

Patients with acute human immunodeficiency virus (HIV) infection are highly infectious to their uninfected sexual partners. The level of this infectiousness is thought to be as much as 26 times greater than that observed during chronic HIV infection, and may be further elevated in patients with coexisting sexually transmitted infections (STI). The sexual partners of acute HIV infection patients with STIs may be more vulnerable to HIV acquisition, because of genital tract inflammation and ulcerations. Data from international and South African studies demonstrate that STI patients are a high-risk population for acute HIV infection. However, most acute HIV infection cases remain clinically undiagnosed, and scoring algorithms offer little assistance to physicians and nurses in terms of improving their diagnostic ability. Laboratory testing of blood specimens remains the only effective means of diagnosis. Laboratory costs have been reduced through the use of pooling strategies for HIV nucleic acid detection, and algorithms that incorporate dual HIV rapid tests and ultrasensitive p24 antigen assays. The availability of these diagnostic tools and antiretroviral drugs means that there is a window of opportunity to enhance HIV prevention activities in South Africa. This can be achieved by screening STI patients for acute HIV infection, in order to initiate appropriate medical management, risk reduction counselling and partner notification.

Role of asymptomatic genital tract inflammation in normozoospermic infertile men undergoing intracytoplasmic sperm injection

Role of asymptomatic genital tract inflammation in normozoospermic infertile men undergoing intracytoplasmic sperm injection

Seroprevalence and risk factors of herpes simplex virus type-2 infection among pregnant women in Northeast India

BackgroundHerpes simplex virus type-2 (HSV-2) is one of the most common sexually transmitted infections that facilitate human immunodeficiency virus (HIV) acquisition by over two fold or more. The development of HSV-2 control methods as a measure to control HIV epidemic in high HSV-2/HIV areas has become a priority. Two out of the six high HIV prevalent states of India are located in the Northeastern region of India. Due to lack of documented HSV-2 studies from this part of the country; there was a need for estimating the seroprevalence and risk factors of HSV-2 infection in this defined population.MethodsPregnant women (n = 1640) aged18 years and above attending antenatal clinics of tertiary referral hospitals in five Northeastern states of India were screened for type specific HSV-2 IgG antibodies. Blood samples were collected from all the participants after conducting interviews. Univariate and multivariate analyses were performed to identify the risk factors associated with HSV-2 seropositivity.ResultsOverall seroprevalence of HSV-2 infection was 8.7% (142/1640; 95% CI 7.3-10.0) with a highest prevalence of 15.0% (46/307; 95% CI 11.0-19.0) in the state of Arunachal Pradesh. Higher seroprevalence was observed with increasing age (Adj. Odds Ratio [AOR] 1.9 for 22-25 years old, AOR 2.29 for > 29 years old). The risk factors associated with HSV-2 seropositives were multiple sex partners (AOR 2.5, p = 0.04), condom non-user's (AOR 4.7, p <0.001), early coitarchal age (age of first intercourse) 'less than 18 years' (AOR 9.6, p = 0.04), middle income group (AOR 2.1, p = 0.001) compared to low income group and low level of education (AOR 3.7, p = 0.02) compared to higher education. HSV-2 seropositivity was higher among Christians (12.6%) compared to Muslims (3.8%). The most frequent clinical symptoms among HSV-2 seropositives were excess vaginal discharge in last one year (53.5%, 76/142) and pelvic pain (26.1%, 37/142). While among subjects with genital ulcers, HSV-2 seroprevalence was 36.8% (7/19).ConclusionsOverall seroprevalence of HSV-2 infection among pregnant women of Northeast India is relatively low. The generation of awareness among high risk groups may have played key role to limit the infection. The role of vaccination against HSV-2 in near future and elimination of HSV-2 viral shedding along with genital tract inflammation in high HIV/HSV-2 areas may be an option for initiating successful intervention strategies to reduce the transmission and acquisition of HIV infection in Northeast India.

Effect of vinyl sulfone inhibitors of cysteine proteinases on Tritrichomonas foetus infection

Tritrichomonas foetus is a sexually transmitted protozoon that causes genital inflammation and adverse pregnancy outcomes in cattle. Cysteine proteinases (CPs) released by T. foetus degrade immunoglobulin G (IgG) antibodies, complement component 3 and matrix proteins as well as inducing apoptosis of bovine genital epithelial cells. In this study, the efficacies of the vinyl sulfone CP inhibitors K11777 and WRR-483 were tested against CPs of T. foetus. The activity of secreted T. foetus CPs in culture supernatants was decreased in the presence of vinyl sulfone inhibitors. Inhibitor K11777 reduced the in vitro cytopathogenic effects of T. foetus in bovine foetal trophoblast cells, which are relevant target cells since this pathogen interferes with pregnancy. Pre-treatment of T. foetus prior to intravaginal inoculation diminished genital infection in a murine model. Therefore, vinyl sulfone CP inhibitors reduce several effects of T. foetus-secreted CPs, including cytotoxicity on relevant target host cells and genital infection in a murine model. These inhibitors have potential as chemotherapeutic agents against bovine trichomoniasis. Generalisation to human trichomoniasis requires further study.

CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

In blood, the accumulation of terminally differentiated (TD) T cells during HIV infection is associated with CD4 T cell loss and HIV disease progression. Here, we investigated the maintenance and functional characteristics of memory T cells at the cervix. We found that CD4 T cell depletion at the cervix mirrors CD4 depletion in blood. In all women, depletion of CD4 T cells at the cervix was associated with significant reductions in CD45RA- CCR7+ (central memory [CM]) T cells and the accumulation of CD45RA+ CCR7- (TD T cells). We determined whether inflammation in the genital tract was associated with the local differentiation of T cells at the cervix. In uninfected women, genital tract inflammation was associated with the accumulation of CD45RA- CCR7+ CM CD4 T cells and reduced frequencies of CD45RA+ CCR7- TD cells at the cervix. This finding may reflect the fact that, in the absence of HIV infection, TD T cells may be slowly lost in the presence of genital inflammation, while CD45RA- CCR7+ CM T cells are recruited to replenish the diminishing CD4 T cell pool. Following global stimulation with phorbol myristate acetate (PMA)-ionomycin, we noted a significant interleukin 2 (IL-2) deficit in both cervical and blood CD4 T cells from HIV-infected women compared to uninfected women, while gamma interferon (IFN-γ) production was similar, irrespective of HIV status. Few HIV-infected women had detectable IFN-γ and IL-2 HIV-specific T cell responses at the cervix, and these responses were significantly lower in magnitude than the corresponding responses in blood. These data suggest that CD4 depletion was associated with the accumulation of terminally differentiated T cell phenotypes at the cervical mucosa defective in their ability to produce IL-2. CD4 depletion and compromised immunity at the cervix may be accompanied by progressive decline of central memory-like T cells and development of T cells toward terminally differentiated phenotypes.

Role of asymptomatic genital tract inflammation in normozoospermic infertile men undergoing intracytoplasmic sperm injection

Role of asymptomatic genital tract inflammation in normozoospermic infertile men undergoing intracytoplasmic sperm injection

Influence of urogenital infections and inflammation on semen quality and male fertility

Urogenital infections and inflammation are a significant etiologic factor in male infertility. Data for this review were acquired by a systematic search of the medical literature. Relevant cross-references were also taken into account. We address infectious and inflammatory diseases of different compartments of the male genital tract and discuss their andrological sequelae. Chronic urethritis might be responsible for silent genital tract inflammation with negative impact on semen quality. In chronic pelvic pain syndrome, morphological abnormalities of spermatozoa and seminal plasma alterations are detectable. In the majority of men with epididymitis, a transient impairment of semen quality can be found during the acute infection. However, persistent detrimental effects are not uncommon, even after complete bacteriological cure. The relevance of chronic viral infections as an etiologic factor in male infertility is believed to be underestimated. Data concerning the impact of HIV infection on male fertility are of increasing interest as with the improvement in life expectancy, issues of sexuality and procreation gain importance. Moreover, effects of noninfectious systemic inflammation on the male reproductive tract have to be considered in patients with metabolic syndrome, a disorder of growing relevance worldwide. Finally, microbiological and related diagnostic findings in urine and semen samples are reviewed according to their relevance for male infertility. Available data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

O3-S5.02 Frequent breakthrough genital HSV-2 shedding on standard and high dose valacyclovir

BackgroundShort, rapidly cleared, subclinical shedding episodes are the predominant form of HSV-2 reactivation in the genital tract. Valacyclovir 500 mg once daily (SD-VAL) reduces the risk of sexual transmission of...

Study on the efficacy of Saururaceae lotion in treatment of gynecological genital tract inflammation

Objective To investigate the efficacy of Saururaceae lotion in treatment of gynecological inflammation ( chronic cervicitis,vaginitis).Methods 90 patients with gynecological inflammation(chronic cervicitis,vaginitis) were randomly divided into two groups,and each group 45 cases.The observation group was administered with Saururaceae lotion treatment, and the control group was treated with Jieeryin.Clinical efficacy and relapse situation were observed.Results The total effective rate of the observation group was 95.6% , higher than that of the control group(77.8% )(x2 = 5.362.P <0.05) ;The gynecological inflammation recurrence rate the observation group was 4.4% ,lower than that of the control group(33.3% )(x2 = 16.312,P <0.05).Conclusion Saururaceae lotion in treatment of gynecological inflammation was effective,and had low recurrence rate,and it was worthy of clinical application. Key words: Saururaceae lotion; Gynecological inflammation; Efficacy

Activation of the immune system and sperm DNA fragmentation are associated with idiopathic oligoasthenoteratospermia in men with couple subfertility

Ejaculates from men without known causes for male subfertility and asymptomatic for genital tract inflammation showed infiltration of macrophages, and their activation state (HLA-DR(+)) was negatively correlated with semen parameters and positively correlated with sperm DNA damage. An activation of the immune system is thus detectable in idiopathic oligoasthenoteratozoospermia of unknown origin.

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4(+) T cells with a strong concomitant increase in the number of regulatory T cells (CD4(+)CD25(+)Foxp3(+)) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1-stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.

Quality of Care for Pelvic Inflammatory Disease: Room for Improvement

Pelvic inflammatory disease (PID) is a clinical syndrome characterized by upper genital tract inflammation and frequently associated with sexually transmitted or genital tract microorganisms. The Centers for Disease Control and Prevention (CDC) has developed STD treatment guidelines intended to assist health care providers in selecting antibiotic treatment strategies based on objective clinical evidence.1 Several studies over the past 2 decades have demonstrated poor provider adherence to recommended treatment for PID.2‐5 The authors of these reports called for aggressive quality improvement measures to improve adherence to PID treatment guidelines. With an ongoing focus on improving quality of care, one would expect to see improvement in provider adherence to PID antibiotic regimens over the past decade. In this issue, Shih and colleagues report on provider adherence to CDC guidelines for outpatient treatment of PID in emergency and urgent care settings. 6 The authors used data from a national database (National Hospital Ambulatory Medical Care Survey; NHAMCS) to determine whether provider selection of antibiotics for outpatient PID was consistent with CDC guidelines during the 1999‐2006 period. The authors concluded that a guideline-recommended antibiotic regimen was provided only 30% of the time, with partially appropriate antibiotics provided 47% of the time, and completely inconsistent treatment (or no treatment) provided 22% of the time. The authors conclude that provider adherence to PID antibiotic treatment guidelines remains low and has not improved significantly since the previous studies on this topic. Why is adherence to the guidelines so low? Although research has consistently shown poor adherence to PID antibiotic treatment guidelines, little is actually known about why providers are not adherent. It could be that many providers are not aware of the latest guidelines from CDC or other major organizations. Ubiquitous internet access now provides healthcare providers with nearly immediate access to latest treatment guidelines (one needs only to type “PID treatment guidelines” into an internet search engine, and the latest CDC guidelines will be the first link). However, many providers may use other sources of information (eg, review articles or text books) or may continue to practice in a manner that they learned previously. Alternatively, it could be that providers either do not agree with the guidelines, find them impractical, or are aware of new data that has emerged since the latest version of the guidelines were written. For example, the Shih study found that one of the most common reasons for provider nonadherence was the provision of azithromycin, rather than doxycycline, as part of the outpatient antibiotic regimen. Although azithromycin was not included as a recommended treatment for PID in the 2006 CDC guidelines, it appears to be an effective treatment option (although the optional dose and duration remains unknown). 1,7 The recommended oral regimens for PID generally require twice-daily medication for 2 weeks, and young women with PID often have significant challenges with adherence to these antibiotic regimens.8 Another possible explanation for the low adherence rates in the Shih study could be measurement error related to misclassification of PID and/or the antibiotic regimens used. In the NHAMCS survey, use of provider-coded diagnosis of PID has not been validated against actual medical records or other means; thus, providers completing the survey could have indicated a PID diagnosis for a variety of pelvic complaints. However, other studies that used chart review or questionnaires to identify PID have found similar rates of nonadherence to CDC guidelines. 2,4,5 Some providers in the NHAMCS did not report providing any antibiotics for PID, and while failure to provide any antibiotics is clearly inappropriate, it is possible that either the PID diagnosis was not correct or that the provider did not accurately list all medications provided on the survey form. Should antibiotic treatment that is only partially in agreement with guidelines always be classified as poor quality of care? Recent clinical trials provide evidence of efficacy for several

Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians

BackgroundPolymorphisms in chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load (VL) and heterosexual transmission in an African cohort. Between 1995 and 2006, cohabiting Zambian couples discordant for HIV-1 (index seropositive and HIV-1 exposed seronegative {HESN}) were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques, controlling for non-genetic factors, we estimated the effects of these haplotypic variants on a) index partner VL, b) seroconverter VL, c) HIV-1 transmission by index partners, d) HIV-1 acquisition by HESN partners.ResultsAmong 567 couples, 240 virologically linked transmission events had occurred through 2006. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta = -0.58, log10 P = 0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta = 0.54, log10 P = 0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by the HESNs (HR = 2.0, 95% CI = 1.20-3.43, P = 0.008), after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD/HHE effect was stronger in exposed females (HR = 2.1, 95% CI = 1.14-3.95, P = 0.018).ConclusionsAmong Zambian discordant couples, HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-1 acquisition by HESNs. These associations replicate or resemble findings reported in other African and European populations.