Publications

OBJECTIVES

Recently developed genotyping tools allow better understanding of Trichomonas vaginalis population genetics and epidemiology. These tools have yet to be applied to T vaginalis collected from HIV+ populations, where understanding the interaction between the pathogens is of great importance due to the correlation between T vaginalis infection and HIV transmission. The objectives of the study were twofold: first, to compare the genetic diversity and population structure of T vaginalis collected from HIV+ women with parasites from reference populations; second, to use the genetic markers to perform a case study demonstrating the usefulness of these techniques in investigating the mechanisms of repeat infections.

METHODS

Repository T vaginalis samples from a previously described treatment trial were genotyped at 11 microsatellite loci. Estimates of genetic diversity and population structure were determined using standard techniques and compared with previously reported estimates of global populations. Genotyping data were used in conjunction with behavioural data to evaluate mechanisms of repeat infections.

RESULTS

T vaginalis from HIV+ women maintain many of the population genetic characteristics of parasites from global reference populations. Although there is evidence of reduced diversity and bias towards type 1 parasites in the HIV+ population, the populations share a two-type population structure and parasite haplotypes. Genotyping/behavioural data suggest that 36% (12/33) of repeat infections in HIV+ women can be attributed to treatment failure.

CONCLUSIONS

T vaginalis infecting HIV+ women is not genetically distinct from T vaginalis infecting reference populations. Information from genotyping can be valuable for understanding mechanisms of repeat infections.

Muscle extracellular matrix (ECM) plays an important role in maintaining muscular integrity and force transduction. However, the role of ECM in skeletal muscle atrophy remains unknown. In this study, we employed two clinically relevant mouse models of Achillotenotomy and hindlimb suspension to simulate Achilles tendon rupture and hindlimb disuse. The gastrocnemius was harvested following two weeks of treatment. We hypothesized that degradation of muscle ECM basement membrane lead to dysfunction of muscle contractility. Our results demonstrated a significant reduction of gastrocnemius single twitch force, isometric tetanic force, and contraction velocity following tendon rupture (p<0.001), but not disuse. Additionally, up-regulation of matrix metalloproteinase-2 (MMP-2) was observed only after tendon rupture (p=0.00234). These findings suggest that ECM remodeling and basement membrane degradation due to MMP-2 may be responsible for declined muscle contractibility. Inhibiting ECM degradation enzymes may be a potential treatment strategy for skeletal muscle atrophy after tendon rupture.

BACKGROUND

Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear.

METHODS

Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding [NLB]) for 1 week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) in nociception was evaluated through behavioral and enzyme-linked immunosorbent assays, surgical interventions, and intrathecal antisense treatments.

RESULTS

Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6 receptor subunit gp130 (gp130), but not to tumor necrosis factor receptor type 1 (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared with control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNFα, whereas sound stress increases IL-6 plasma levels in control rats but not in NLB rats.

CONCLUSIONS

Early-life stress induces a persistent elevation of IL-6, hyperalgesia, and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and proinflammatory cytokines acting at muscle nociceptor level.

OBJECTIVE

Many people living with HIV in sub-Saharan Africa desire biological children. Implementation of HIV prevention strategies that support the reproductive goals of people living with HIV while minimizing HIV transmission risk to sexual partners and future children requires a comprehensive understanding of pregnancy in this population. We analyzed prospective cohort data to determine pregnancy incidence and predictors among HIV-positive women initiating antiretroviral therapy (ART) in a setting with high HIV prevalence and fertility.

METHODS

Participants were enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort of HIV-positive individuals initiating ART in Mbarara. Bloodwork (including CD4 cells/mm(3), HIV viral load) and questionnaires (including socio-demographics, health status, sexual behavior, partner dynamics, HIV history, and self-reported pregnancy) were completed at baseline and quarterly. Our analysis includes 351 HIV-positive women (18-49 years) who enrolled between 2005-2011. We measured pregnancy incidence by proximal and distal time relative to ART initiation and used multivariable Cox proportional hazards regression analysis (with repeated events) to identify baseline and time-dependent predictors of pregnancy post-ART initiation.

RESULTS

At baseline (pre-ART initiation), median age was 33 years [IQR: 27-37] and median prior livebirths was four [IQR: 2-6]. 38% were married with 61% reporting HIV-positive spouses. 73% of women had disclosed HIV status to a primary sexual partner. Median baseline CD4 was 137 cells/mm(3) [IQR: 81-207]. At enrolment, 9.1% (31/342) reported current pregnancy. After ART initiation, 84 women experienced 105 pregnancies over 3.8 median years of follow-up, yielding a pregnancy incidence of 9.40 per 100 WYs. Three years post-ART initiation, cumulative probability of at least one pregnancy was 28% and independently associated with younger age (Adjusted Hazard Ratio (AHR): 0.89/year increase; 95%CI: 0.86-0.92) and HIV serostatus disclosure to primary sexual partner (AHR: 2.45; 95%CI: 1.29-4.63).

CONCLUSIONS

Nearly one-third of women became pregnant within three years of initiating ART, highlighting the need for integrated services to prevent unintended pregnancies and reduce periconception-related risks for HIV-infected women choosing to conceive. Association with younger age and disclosure suggests a role for early and couples-based safer conception counselling.