Immunity in the female sheep reproductive tract

Entrican, Gary; Wheelhouse, Nick

doi:10.1051/vetres:2006002

Cited by 32 publications

(19 citation statements)

References 80 publications

(91 reference statements)

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“…In conclusion, if the venereal transmission of C. abortus seems possible, it does not constitute a main contributing factor in the transmission of the disease. However, C. abortus infection of non-pregnant ewes by a mucosal route, contrary to parenteral inoculation, could allow establishment of a persistent infection that may cause abortion in a subsequent pregnancy (Entrican and Wheelhouse, 2006).…”

Section: Transmissionmentioning

confidence: 99%

Chlamydiaceae and chlamydial infections in sheep or goats

Rodolakis

Laroucau

2015

Veterinary Microbiology

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Section: Transmissionmentioning

confidence: 99%

Chlamydiaceae and chlamydial infections in sheep or goats

Rodolakis

Laroucau

2015

Veterinary Microbiology

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“…Sheep possess several additional advantages and limitations for HIV prophylactic IVR safety and pharmacokinetic evaluation beyond those mentioned above (for a more detailed discussion of the female sheep reproductive anatomy and physiology, the reader is referred elsewhere [10,11,13]). In contrast to the more commonly utilized rhesus and pigtail macaque nonhuman primates (18,22,30,38), most sheep breeds demonstrate similar body mass and vaginal anatomical dimensions to women, allowing for human-sized IVR testing and avoidance of scaling issues when extrapolating ring mechanics, drug dosing, biodistribution, and pharmacokinetics (35,36).…”

Section: Fig 7 Proximal and Distal Tfv Vaginal Tissue Concentrations mentioning

confidence: 99%

A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

Johnson

Clark

Albright

et al. 2012

Antimicrob Agents Chemother

117

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A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 10 4 ng/g, 10 6 ng/g, and 10 1 ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic. R ecent progress in antiretroviral HIV prevention research has advanced the field from concept toward medical practice (46). The CAPRISA 004 study demonstrated that a vaginal gel containing the reverse transcriptase inhibitor tenofovir (TFV) was partially effective in preventing HIV transmission in women (1), with significant protection observed in women who maintained preventative TFV concentrations of at least 1,000 ng/ml in vaginal fluid (23). However, the overall effectiveness (39%) was likely reduced by poor user adherence to the inconvenient before-andafter-sex dosing regimen. The correlation of adherence and TFV vaginal fluid concentrations to protection was a key finding (23,24), indicating the need for vaginal drug delivery systems that attain and maintain elevated user adherence and vaginal drug concentrations. More recently, the VOICE trial tested the same TFV 1% gel formulation as CAPRISA 004 but with a once-daily dosage regimen and failed to show any effectiveness in women. Here, as well, low adherence may have contributed to the gel's inability to prevent HIV transmission (54). As a result, we (6, 21) and others (4,35,36,44,49) aim to develop TFV drug delivery systems to provide sustained protective vaginal tissue concentrations and potentially increase user adherence.The micromolar anti-HIV activity of TFV motivated sel...

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“…Chlamydiaceae have a single genus Chlamydia that includes nine species; among them C. abortus and C. pecorum can cause diseases in sheep [1–3]. In particular, C. abortus is recognized as a major cause of abortion and lamb loss throughout the world, especially in the intensively managed farms [4–6]. C. abortus usually causes ulceration of endometrial epithelium resulting in placental infection if infection was acquired during the early stages of that pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence and Risk Factors ofChlamydia abortusInfection in Tibetan Sheep in Gansu Province, Northwest China

Qin

Yin

Cong

et al. 2014

The Scientific World Journal

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Chlamydia abortus, an important pathogen in a variety of animals, is associated with abortion in sheep. In the present study, 1732 blood samples, collected from Tibetan sheep between June 2013 and April 2014, were examined by the indirect hemagglutination (IHA) test, aiming to evaluate the seroprevalence and risk factors of C. abortus infection in Tibetan sheep. 323 of 1732 (18.65%) samples were seropositive for C. abortus antibodies at the cut-off of 1 : 16. A multivariate logistic regression analysis was used to evaluate the risk factors associated with seroprevalence, which could provide foundation to prevent and control C. abortus infection in Tibetan sheep. Gender of Tibetan sheep was left out of the final model because it is not significant in the logistic regression analysis (P > 0.05). Region, season, and age were considered as major risk factors associated with C. abortus infection in Tibetan sheep. Our study revealed a widespread and high prevalence of C. abortus infection in Tibetan sheep in Gansu province, northwest China, with higher exposure risk in different seasons and ages and distinct geographical distribution.

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Immunity in the female sheep reproductive tract

Cited by 32 publications

References 80 publications

Chlamydiaceae and chlamydial infections in sheep or goats

Chlamydiaceae and chlamydial infections in sheep or goats

A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

Seroprevalence and Risk Factors ofChlamydia abortusInfection in Tibetan Sheep in Gansu Province, Northwest China

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