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1.
Eval Program Plann ; 95: 102147, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36041241

RESUMO

The Centers for Disease Control and Prevention launched the Laboratory Leadership Service (LLS) Fellowship Program in July 2015 to develop public health laboratory (PHL) leaders who will improve PHL quality and safety. This article describes a retrospective, summative evaluation to determine the extent to which LLS has met its short-term goals for PHL workforce development. The evaluation relied on existing data from routine LLS data collection and reporting, supplemented with a new alumni survey. The purpose of the design was threefold: 1) to reduce data collection burden on program staff and participants, 2) to assess the value and limits of routine fellowship data for comprehensive public health workforce development program evaluation, and 3) to identify ways to improve LLS's routine data collections for program evaluation. We used descriptive statistics, qualitative analysis, and participatory methods (i.e., a data party) to analyze and interpret data. Results show LLS short-term outcome achievement and highlight opportunities for program improvement, particularly related to the design of certain training requirements and for future evaluations. Overall, the evaluation contributes to lessons learned for PHL workforce development efforts, including how routine data collections can contribute to comprehensive public health workforce development evaluations.


Assuntos
Mão de Obra em Saúde , Liderança , Estados Unidos , Humanos , Bolsas de Estudo , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Saúde Pública , Centers for Disease Control and Prevention, U.S.
2.
J Clin Microbiol ; 58(4)2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32024723

RESUMO

U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. In 2016, the CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up the national capacity for detecting several resistance threats including N. gonorrhoeae AR-Ng testing, a subactivity of the CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in Maryland, Tennessee, Texas, and Washington), and the CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and the program Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole-genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 N. gonorrhoeae isolates, respectively, and the CDC received 531 and 646 concerning isolates and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported the laboratory capacity for N. gonorrhoeae AST and associated genetic marker detection, expanding preexisting notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.


Assuntos
Gonorreia , Neisseria gonorrhoeae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Centers for Disease Control and Prevention, U.S. , Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Humanos , Laboratórios , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/genética , Texas , Estados Unidos , Washington
3.
Diagn Microbiol Infect Dis ; 93(4): 369-371, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30552033

RESUMO

Neisseria gonorrhoeae quickly develops drug resistance. Time-kill curves revealed that EDTA and TOL-463 inhibit growth similar to penicillin, ciprofloxacin, and azithromycin. Furthermore, synergistic and additive antimicrobial interactions occurred when EDTA and TOL-463 were combined with penicillin or azithromycin, respectively, suggesting that further investigations into these unconventional antimicrobials may be advantageous.


Assuntos
Antibacterianos/farmacologia , Ácidos Bóricos/farmacologia , Ácido Edético/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/crescimento & desenvolvimento
4.
Am J Obstet Gynecol ; 217(3): 336.e1-336.e16, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28532600

RESUMO

BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race. RESULTS: We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks. CONCLUSION: Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates.


Assuntos
Infecções por Chlamydia/diagnóstico , Doenças das Tubas Uterinas/epidemiologia , Infertilidade Feminina/epidemiologia , Adulto , Alabama/epidemiologia , População Negra/estatística & dados numéricos , Estudos de Casos e Controles , Chlamydia trachomatis/isolamento & purificação , Feminino , Humanos , Estudos Soroepidemiológicos , População Branca/estatística & dados numéricos , Adulto Jovem
5.
J Med Primatol ; 46(5): 218-227, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28488731

RESUMO

BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. RESULTS: Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies.


Assuntos
Infecções por Chlamydia/complicações , Chlamydia trachomatis/fisiologia , Modelos Animais de Doenças , Infecções por HIV/complicações , Macaca mulatta , Infecções Sexualmente Transmissíveis/complicações , Animais , Infecções por Chlamydia/sangue , Infecções por Chlamydia/patologia , Coinfecção , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Reto , Sorogrupo , Infecções Sexualmente Transmissíveis/sangue , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/virologia , Vírus da Imunodeficiência Símia/fisiologia
6.
AIDS ; 31(6): 745-752, 2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28060011

RESUMO

BACKGROUND: Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. METHODS: Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. RESULTS: Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P < 0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (P = 0.07). Plasma TFV and TFV diphosphate concentrations in tissues and vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. CONCLUSION: Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por Chlamydia/complicações , Coinfecção/complicações , Transmissão de Doença Infecciosa/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Tenofovir/administração & dosagem , Vaginite por Trichomonas/complicações , Administração Tópica , Animais , Fármacos Anti-HIV/análise , Fármacos Anti-HIV/farmacocinética , Feminino , Macaca , Placebos/administração & dosagem , Plasma/química , Tenofovir/análise , Tenofovir/farmacocinética , Vagina/química , Cremes, Espumas e Géis Vaginais/administração & dosagem
7.
PLoS Pathog ; 12(9): e1005885, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27658293

RESUMO

Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.


Assuntos
Interações Hospedeiro-Patógeno/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Mucosa/efeitos dos fármacos , Progestinas/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vagina/efeitos dos fármacos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Colo do Útero/efeitos dos fármacos , Colo do Útero/imunologia , Colo do Útero/metabolismo , Colo do Útero/virologia , Preparações de Ação Retardada , Feminino , Injeções Intramusculares , Ativação Linfocitária/efeitos dos fármacos , Macaca mulatta , Macaca nemestrina , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/virologia , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/uso terapêutico , Ciclo Menstrual , Mucosa/imunologia , Mucosa/metabolismo , Mucosa/virologia , Progestinas/administração & dosagem , Progestinas/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Vagina/imunologia , Vagina/metabolismo , Vagina/virologia , Internalização do Vírus/efeitos dos fármacos
8.
Diagn Microbiol Infect Dis ; 86(2): 144-7, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27489119

RESUMO

Four commercial transport systems for the recovery of Neisseria gonorrhoeae were evaluated in support of the need to obtain culture isolates for the detection of antimicrobial resistance. Bacterial recovery from the InTray GC system was superior with minimal loss of viability in contrast to non-nutritive transport systems.


Assuntos
Técnicas Bacteriológicas/métodos , Neisseria gonorrhoeae/isolamento & purificação , Manejo de Espécimes/métodos , Gonorreia/diagnóstico , Humanos , Masculino , Viabilidade Microbiana , Neisseria gonorrhoeae/fisiologia
9.
J Infect Dis ; 213(10): 1541-5, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26743846

RESUMO

Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally. All animals in the placebo group were infected with SHIV, while 4 of 6 PrEP recipients remained uninfected (P= .03). Oral FTC/TDF maintains efficacy in a macaque model of sexually transmitted coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por Chlamydia/complicações , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vaginite por Trichomonas/complicações , Animais , Chlamydia trachomatis/isolamento & purificação , Coinfecção , Modelos Animais de Doenças , Feminino , Humanos , Macaca mulatta , Profilaxia Pré-Exposição , Vagina/microbiologia , Vagina/virologia
10.
J Med Primatol ; 44(5): 286-95, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26238265

RESUMO

BACKGROUND: Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility. METHODS: Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks. RESULTS: All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 µm in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 µm for the descending doses, respectively. CONCLUSIONS: All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Macaca nemestrina , Acetato de Medroxiprogesterona/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Vagina/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças/virologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ciclo Menstrual/efeitos dos fármacos , Mucosa/efeitos dos fármacos , Progesterona/metabolismo , Vagina/anatomia & histologia
11.
AIDS Res Hum Retroviruses ; 31(11): 1166-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26165400

RESUMO

Vaginal SHIVSF162P3 acquisition in pigtail macaques (Macaca nemestrina) is dependent on time point during the menstrual cycle. Susceptibility is higher around menstruation and lower at ovulation in mid cycle. This complicates the design of repeat low-dose (RLD) SHIV exposure studies because virus challenges given during low susceptibility periods have lower chances to infect. To account for fluctuating susceptibility, we analyzed menstrual cycles rather than exposures until infection following virus challenges. We first reanalyzed infection data of 41 macaques receiving placebo or no treatment during once (n=18) or twice (n=23) weekly virus exposures. The same number of cycles was required for infection with either challenge frequency, while it took a median four or six challenges for once or twice weekly exposures, respectively. More virus challenges to infection likely reflect frequent unsuccessful exposures in frequently exposed animals. When reanalyzing two previously reported biomedical HIV intervention studies, we found 1% tenofovir gel was 74% or 86% efficacious based on cycles or exposures (p=0.019 or p=0.003, respectively, Fisher's exact test), while 1% raltegravir gel was 84% or 89 % efficacious, respectively (p=0.047 or p=0.031). Evaluating the number of menstrual cycles rather than exposures until infection can account for varying susceptibility during the menstrual cycle. Our observations have implications for future study designs such as planning the frequency of virus exposures. Menstrual cycle analysis may also avoid potential overestimation of efficacy against vaginal challenges during low susceptibility periods in the cycle that are unlikely to cause infection.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Antirretrovirais/administração & dosagem , Transmissão de Doença Infecciosa/prevenção & controle , Ciclo Menstrual/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Administração Tópica , Animais , Suscetibilidade a Doenças , Feminino , Macaca nemestrina , Placebos/administração & dosagem , Resultado do Tratamento
12.
Virol J ; 12: 90, 2015 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-26070461

RESUMO

There are few nonhuman primate models of enhanced HIV susceptibility. Such models can improve comprehension of HIV acquisition risk factors and provide rigorous testing platforms for preclinical prevention strategies. This paper reviews past, current, and proposed research on macaque HIV acquisition risk models and identifies areas where modeling is significantly lacking. We compare different experimental approaches and provide practical considerations for designing macaque susceptibility studies. Modifiable (mucosal and systemic coinfections, hormonal contraception, and rectal lubricants) and non-modifiable (hormonal fluctuations) risk factors are highlighted. Risk acquisition models via vaginal, rectal, and penile challenge routes are discussed. There is no consensus on the best statistical model for evaluating increased susceptibility, and additional research is required. The use of enhanced susceptibility macaque models would benefit multiple facets of the HIV research field, including basic acquisition and pathogenesis studies as well as the vaccine and other biomedical preventions pipeline.


Assuntos
Modelos Animais de Doenças , Suscetibilidade a Doenças , Infecções por HIV/imunologia , Macaca , Animais , Modelos Estatísticos
13.
J Med Primatol ; 44(5): 301-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26054016

RESUMO

Varying susceptibility during menstrual cycling could be a factor for S(H)IV infection risk in female rhesus macaques. We retrospectively determined vaginal SIV infection time points relative to the menstrual cycle in a group of rhesus macaques (n=11) enrolled in an HIV transmission trial. Eight of nine rhesus macaques became infected around menstruation time.


Assuntos
Macaca mulatta , Ciclo Menstrual , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Vagina/virologia , Animais , Feminino , Estudos Retrospectivos
14.
PLoS One ; 10(4): e0120021, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25853710

RESUMO

BACKGROUND: Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15. METHODS: Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure. RESULTS: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models). CONCLUSIONS: Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.


Assuntos
Lubrificantes/química , Lubrificantes/toxicidade , Reto/efeitos dos fármacos , Reto/virologia , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Animais , Epitélio/efeitos dos fármacos , Feminino , Hemorragia/induzido quimicamente , Concentração de Íons de Hidrogênio , Lubrificantes/administração & dosagem , Macaca fascicularis , Microbiota/efeitos dos fármacos , Concentração Osmolar , Reto/citologia , Reto/microbiologia , Risco , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/fisiologia , Fatores de Tempo , Viremia/induzido quimicamente , Eliminação de Partículas Virais/efeitos dos fármacos , Água/química
16.
AIDS Res Hum Retroviruses ; 30(11): 1125-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25313448

RESUMO

The repeat low-dose virus challenge model is commonly used in nonhuman primate studies of HIV transmission and biomedical preventions. For some viruses or challenge routes, it is uncertain whether the repeated exposure design might induce virus-directed innate or adaptive immunity that could affect infection or viremic outcomes. Retrospective cohorts of male Indian rhesus (n=40) and female pigtail (n=46) macaques enrolled in repeat low-dose rectal or vaginal SHIV(SF162p3) challenge studies, respectively, were studied to compare the relationship between the number of previous exposures and peak plasma SHIV RNA levels or viral load area under the curve (AUC), surrogate markers of viral control. Repeated mucosal exposures of 10 or 50 TCID50 of virus for rectal and vaginal exposures, respectively, were performed. Virus levels were measured by quantitative reverse-transcriptase real-time PCR. The cumulative number of SHIV(SF162p3) exposures did not correlate with observed peak virus levels or with AUC in rectally challenged rhesus macaques [peak: rho (ρ)=0.04, p=0.8; AUC: ρ=0.33, p=0.06] or vaginally challenged pigtail macaques (peak: ρ=-0.09, p=0.7; AUC: ρ=0.11, p=0.6). Infections in these models occur independently of exposure history and provide assurance that neither inoculation route nor number of exposures required for infection correlates with postinfection viremia. These data also indicate that both the vaginal and rectal repeated low-dose virus exposure models using SHIV(SF162p3) provide a reliable system for nonhuman primate studies.


Assuntos
HIV/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Carga Viral , Animais , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Macaca mulatta , Macaca nemestrina , Masculino , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
J Med Primatol ; 43(5): 310-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24779484

RESUMO

BACKGROUND: Hormonal changes during menstrual cycling may affect susceptibility to HIV. METHODS: We determined the simian human immunodeficiency virus (SHIV) acquisition time point in 43 cycling pigtail macaques infected by repeated vaginal virus exposures initiated randomly in the cycle. RESULTS: SHIV infection was first detected in the follicular phase in 38 macaques (88%), and in the luteal phase in five macaques (12%), indicating a statistically significant timing difference. Assuming a 7-day eclipse phase, most infections occurred during or following a high-progesterone period associated with menstruation, vaginal epithelium thinning, and suppressed mucosal immunity. CONCLUSIONS: This raises questions whether other high-progesterone conditions (pregnancy, hormonal contraception) similarly affect HIV risk.


Assuntos
Suscetibilidade a Doenças/imunologia , Macaca nemestrina , Ciclo Menstrual/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Animais , Suscetibilidade a Doenças/virologia , Feminino , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Fatores de Tempo , Vagina/virologia
18.
J Infect Dis ; 210(8): 1239-47, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24755433

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood. METHODS: Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy. RESULTS: Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤ .05, by the Wilcoxon test). CONCLUSIONS: C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological associations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.


Assuntos
Infecções por Chlamydia/complicações , Chlamydia trachomatis , Coinfecção/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Vaginite por Trichomonas/complicações , Trichomonas vaginalis , Animais , Colo do Útero/microbiologia , Colo do Útero/parasitologia , Colo do Útero/patologia , Colposcopia , Feminino , Macaca nemestrina , Fatores de Risco , Infecções Sexualmente Transmissíveis/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
19.
Am J Reprod Immunol ; 71(6): 513-22, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24716832

RESUMO

PROBLEM: Recent concerns that hormonal contraception (HC) may increase risk of HIV acquisition has led to keen interest in using non-human primates (NHP) to understand the underlying mechanism and the magnitude of the risk. This is, in part, because some experiments which would be difficult or logistically impossible in women are more easily conducted in NHP. METHOD OF STUDY: NHP models of HIV can inform HIV acquisition and pathogenesis research and identify and evaluate biomedical preventions and treatments for HIV/AIDS. Widely used species include rhesus, pigtail, and cynomolgous macaques. RESULTS: This paper reviews past, current and proposed NHP research around the intersection of HIV and HC. CONCLUSION: NHP research may lead to the identification of hormonally regulated biomarkers that correlate with HIV-acquisition risk, to a ranking of existing or next-generation HC along an HIV-acquisition risk profile, and inform research around new biomedical preventions for HIV.


Assuntos
Anticoncepcionais Orais Hormonais/farmacologia , Estradiol/metabolismo , Acetato de Medroxiprogesterona/farmacologia , Progesterona/metabolismo , Vagina/patologia , Animais , Feminino , Infecções por HIV/patologia , Infecções por HIV/transmissão , HIV-1/patogenicidade , Humanos , Macaca , Modelos Animais , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/patogenicidade
20.
J Med Primatol ; 43(3): 135-43, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24460742

RESUMO

BACKGROUND: Rectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C. trachomatis and SHIVSF162p3 infections. METHODS: Four SHIVSF162p3 -positive male cynomolgus macaques were used (n = 3 rectally inoculated with 10(6) IFU; n = 1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real-time PCR and Luminex assays, respectively. RESULTS: Macaques were successfully Chlamydia infected. Rectal SHIV shedding (P = 0.02 χ(2) ) and levels of G-CSF, IL-1ra, IL-6, IL-8, IFN-γ, and TNF-α (P ≤ 0.01, Mann-Whitney) in rectal secretions increased following infection. CONCLUSIONS: These pilot data successfully demonstrate rectal C. trachomatis-SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C. trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs.


Assuntos
Infecções por Chlamydia/complicações , Modelos Animais de Doenças , Infecções por HIV/complicações , Infecções Sexualmente Transmissíveis/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Animais , Infecções por Chlamydia/sangue , Infecções por Chlamydia/patologia , Chlamydia trachomatis , Coinfecção , Citocinas/sangue , Citocinas/urina , Infecções por HIV/sangue , Infecções por HIV/virologia , Macaca fascicularis , Masculino , Projetos Piloto , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Reto/microbiologia , Reto/patologia , Infecções Sexualmente Transmissíveis/sangue , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Vírus da Imunodeficiência Símia , Eliminação de Partículas Virais
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