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Marieclaude Boily - One of the best experts on this subject based on the ideXlab platform.
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heterosexual hiv 1 Infectiousness and antiretroviral use systematic review of prospective studies of discordant couples
Epidemiology, 2013Co-Authors: Rebecca F Baggaley, Richard G White, Deirdre T Hollingsworth, Marieclaude BoilyAbstract:Background: Recent studies have estimated the reduction in HIV-1 Infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 Infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions: ART substantially reduces HIV-1 Infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms.
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Infectiousness of hiv infected homosexual men in the era of highly active antiretroviral therapy
AIDS, 2010Co-Authors: Rebecca F Baggaley, Richard G White, Marieclaude BoilyAbstract:The recent study by Jin et al [1] provides estimates of Infectiousness of anal intercourse (AI, insertive circumcised and uncircumcised; receptive with and without ejaculation) for the male homosexual population of Sydney, Australia in the highly active antiretroviral therapy (HAART) era. There is a lack of estimates of HIV Infectiousness for homosexual men and for AI in general and especially for Infectiousness with treatment. A recent literature review found only four studies reporting estimates of HIV transmissibility per AI act [2]. Therefore the additional data presented by Jin et al [1] are an important contribution to the literature. There are many methodological challenges when quantifying HIV Infectiousness which have been discussed elsewhere [3, 4]. While the best study design for quantifying per-act HIV Infectiousness for heterosexual populations has involved discordant monogamous couples (albeit compromised with its own set of biases), these types of study have been seldom used for homosexual populations. It may be more difficult to recruit such participants if rates of monogamy are lower than among heterosexual populations, and monogamous couples may also not be very representative of the wider male homosexual community. The alternative approach used by Jin et al was to follow up initially HIV seronegative homosexual men, testing annually for seroconversion and interviewing every six months for reports of types and frequencies of sexual exposure and the presumed serostatus of their sexual partners (categorised as HIV negative, positive, unknown). A similar approach has been used before for AI by Vittinghoff et al [5] as well as for female sex workers [6, 7]. However Vittinghoff et al were unable to provide per-act estimates per positive exposure for insertive AI, only providing estimates per-act with an “infected or unknown serostatus” partner and therefore may underestimate Infectiousness per exposure, if HIV prevalence among unknown serostatus partners is low. Jin et al's per-act AI transmission probability estimates for receptive unprotected AI (0.65% 95%CI 0.15-1.53% with withdrawal; 1.43% 95%CI 0.48-2.85% with ejaculation [1]), from a population with high (proposed 70%) HAART coverage, are remarkably similar to those estimates made preceding HAART (summary of four estimates: 1.4% 95%CI 0.2-2.5%, no differentiation by ejaculation [2], see Figure). As the authors note, this result is surprising, given the reduction in community viral load that has been observed in some other homosexual populations following the introduction of HAART [8], and that such reductions in viral load are expected to reduce HIV Infectiousness. Per act HIV Infectiousness for anal intercourse, for the pre-HAART and HAART eras Potential reasons why HIV Infectiousness was not seen to reduce include higher Infectiousness associated with various cofactors (STI prevalence may be higher in male homosexual communities now, perhaps as a result of risk compensation in the HAART era); there may be unreported competing exposures through other routes of transmission, such as intravenous drug use; or the partners of study participants may not have been representative of the wider Australian homosexual population, for example, with lower HAART coverage. It would have been useful to have more information regarding the likely HAART coverage of the infected partners, in order to assess how concerning these unexpectedly high estimates for Infectiousness are. While authors state that 70% of male homosexuals diagnosed in Australia are currently treated, estimates of the proportion of those infected who are diagnosed and also an indication of adherence levels and average viral loads for those individuals receiving treatment are required to improve our understanding. The authors addressed the uncertainty regarding “unknown” serostatus and presumed HIV negative sexual partners by undertaking uncertainty analysis, varying the HIV prevalence of the “unknown” and presumed HIV negative partner populations by 5%-15% and 0.5-2% respectively, based on prevalence studies from the locality. It would be informative if this analysis could be extended to reflect the uncertainty in HAART coverage levels in order to explore how sensitive the HIV Infectiousness estimates are to the assumed proportion of sexual partners on treatment. However, even in the absence of further information, levels of HAART are likely to be substantial and so the authors' observation that their per-act estimates are not markedly different from those made in the absence of HAART remains a concerning finding. Community viral load studies covering the Sydney population may help to explain these findings, although the association between viral load and HIV Infectiousness for sexual transmission, particularly for AI, remains to be definitively proven. It would also be useful, if data are available or for future cohorts, to ascertain the treatment status of infected partners where possible, in order to make estimates of AI Infectiousness stratified by treatment status. This study and our review have clearly highlighted the need for more data on HIV Infectiousness for sexual transmission among homosexual men [1, 2].
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hiv transmission risk through anal intercourse systematic review meta analysis and implications for hiv prevention
International Journal of Epidemiology, 2010Co-Authors: Rebecca F Baggaley, Richard G White, Marieclaude BoilyAbstract:Background The human immunodeficiency virus (HIV) Infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention. Methods Systematic review and meta-analysis of the literature on HIV-1 Infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without highly active antiretroviral therapy (HAART). Results A total of 62 643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% [95% confidence interval (CI) 0.2–2.5)] and 40.4% (95% CI 6.0–74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI–UIAI risk were 21.7% (95% CI 0.2–43.3) and 39.9% (95% CI 22.5–57.4), respectively, with no available per-act estimates. Per-partner combined URAI–UIAI summary estimates, which adjusted for additional exposures other than AI with a ‘main’ partner [7.9% (95% CI 1.2–14.5)], were lower than crude (unadjusted) estimates [48.1% (95% CI 35.3–60.8)]. Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI Infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however, predictions are highly sensitive to Infectiousness assumptions based on viral load. Conclusions Unprotected AI is a high-risk practice for HIV transmission, probably with substantial variation in Infectiousness. The significant heterogeneity between Infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI among heterosexuals suggest a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.
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HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention
International Journal of Epidemiology, 2010Co-Authors: Rebecca Frances Baggaley, Richard G White, Marieclaude BoilyAbstract:Background: The HIV Infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention. Methods: Systematic review and meta-analysis of the literature on HIV-1 Infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without HAART. Results: 62,643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% (95%CI 0.2-2.5) and 40.4% (95%CI 6.0-74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI-UIAI risk were 21.7% (95%CI 0.2-43.3) and 39.9% (95%CI 22.5-57.4) respectively, with no available per-act estimates. Per-partner combined URAI-UIAI summary estimates, which adjusted for additional exposures other than AI with a "main" partner (7.9% [95%CI 1.2-14.5]), were lower than crude (unadjusted) estimates (48.1% [95%CI 35.3-60.8]). Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI Infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however predictions are highly sensitive to Infectiousness assumptions based on viral load. Conclusions: Unprotected AI is a high risk practice for HIV transmission, probably with substantial variation in Infectiousness. The significant heterogeneity between Infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI amongst heterosexuals suggests a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.
Elizabeth M Halloran - One of the best experts on this subject based on the ideXlab platform.
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comparing bounds for vaccine effects on Infectiousness
Epidemiology, 2012Co-Authors: Elizabeth M Halloran, Michael G HudgensAbstract:Halloran and Hudgens1 and VanderWeele and Tchetgen Tchetgen2 (henceforth HH and VT) consider inference about causal vaccine effects for Infectiousness. The two papers make assumptions that result in different bounds. Assume a random sample of N households with two individuals. Let Zij = 1 if individual j in household i receives vaccine and 0 otherwise, i = 1,…, N, j = 1, 2. Let Zi = (Zi1, Zi2) denote the treatment assignment vector for household i, and zi, zij denote possible values of Zi, Zij. Let Yij(zi1, zi2) denote the potential infection outcome for individual j in household i if the two individuals in household i have vaccine status (zi1, zi2). Let Yijobs be the observed value of Yij under an actual assignment, i.e., Yijobs=Yij(Zi). Assume throughout only individual 1 can be assigned to vaccine or control, vaccine assignment is randomized, and there is no interference across transmission units. Let p1=E[Yi2obs∣Zi1=1,Yi1obs=1] and p0=E[Yi2obs∣Zi1=0,Yi1obs=1]. The net vaccine effect on Infectiousness based on the observed data when the exposed individual has vaccine status 0 is RDInet(0)=p1−p0. This net vaccine effect is difficult to interpret without additional assumptions because of selection bias, i.e., households that become infected when randomized to vaccine might not be comparable to households that become infected under control. Let pv = E[Yi2(1, 0)∣Yi1(1, 0) = Yi1(0, 0) = 1] and pu = E[Yi2(0, 0)∣Yi1(1, 0) = Yi1(0, 0) = 1]. The causal risk difference in the stratum of households where individual 1 becomes infected whether receiving vaccine or control is CRDI(0) = pv − pu. The CRDI(0) is not subject to selection bias. Even though this causal effect is not identifiable, the observable data provide information such that bounds can be estimated. Monotonicity assumes the vaccine does not increase the risk that individual 1 becomes infected. HH develop bounds on CRDI(0) assuming monotonicity. Under monotonicity, there are three principal strata based on the joint potential outcomes under vaccine and control of person j = 1 (eTable 1), namely the immune stratum (never infected), the protected stratum (not infected if vaccinated, infected if not vaccinated), and the doomed stratum (always infected). Under monotonicity, p1 = pv. Given the observed data, the proportion ρ of households where individual 1 is randomized to control and becomes infected that is in the doomed principal stratum is identifiable, just not which ones. Thus the HH bounds on CRDI(0) are CRDIH H,low(0)=p1−min{1,p0/ρ}, (1) CRDIH H,up(0)=p1−max{0,(p0−(1−ρ))/ρ}. (2) In contrast, VT make the additional assumption that in the absence of vaccination, individuals who become infected regardless of whether they are vaccinated are more infectious than individuals who are protected by the vaccine. Under this assumption, VT show the net risk difference is an upper bound for the causal risk difference. The net risk difference is always less than or equal (2). The main difference between the VT and HH bounds is the reliance on this assumption, which is untestable. Consider the study of 3000 households with two individuals in Table 1. The net vaccine effect on Infectiousness is RDInet(0)=0.2−0.4=−0.2. Because p0 = 0.4 and ρ = 0.5, min{1, p0/ρ} = 0.8 and max{0, (p0−(1−ρ))/ρ} = 0. Thus CRDIH H,low(0)=0.2−0.8=−0.6 and CRDIH H,up(0)=0.2−0=0.2. The HH upper bound is positive, allowing that vaccination might actually enhance Infectiousness. The VT upper bound is RDInet(0)=−0.2, indicating that, ignoring statistical variability, vaccination decreases Infectiousness. Thus, in contrast to the HH bounds, the VT bound leads to the conclusion the vaccine is beneficial in reducing secondary transmissions. The different bounds could lead to different qualitative conclusions about whether the vaccine decreases, or possibly increases, Infectiousness. Thus, one needs to examine critically the underlying biological and selection assumptions when determining bounds. Rather than relying on untestable assumptions, the bounds (1) and (2) can be combined with a sensitivity analysis (as in Hudgens and Halloran3) to make clear the degree to which conclusions about the vaccine having an effect on Infectiousness depend on merging the data with strong prior beliefs. Further details are in the Online Supporting Material. Table 1 Identifiability and bounds on the causal risk difference CRDI(0). 3000 households of size 2 with individual 1 randomized to vaccine or control 1:1. In the 1500 households with Zi = (0, 0), individual 1 became infected in 1000, and individual 2 became ...
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causal inference for vaccine effects on Infectiousness
The International Journal of Biostatistics, 2012Co-Authors: Elizabeth M Halloran, Michael G HudgensAbstract:If a vaccine does not protect individuals completely against infection, it could still reduce Infectiousness of infected vaccinated individuals to others. Typically, vaccine efficacy for Infectiousness is estimated based on contrasts between the transmission risk to susceptible individuals from infected vaccinated individuals compared with that from infected unvaccinated individuals. Such estimates are problematic, however, because they are subject to selection bias and do not have a causal interpretation. Here, we develop causal estimands for vaccine efficacy for Infectiousness for four different scenarios of populations of transmission units of size two. These causal estimands incorporate both principal stratification, based on the joint potential infection outcomes under vaccine and control, and interference between individuals within transmission units. In the most general scenario, both individuals can be exposed to infection outside the transmission unit and both can be assigned either vaccine or control. The three other scenarios are special cases of the general scenario where only one individual is exposed outside the transmission unit or can be assigned vaccine. The causal estimands for vaccine efficacy for Infectiousness are well defined only within certain principal strata and, in general, are identifiable only with strong unverifiable assumptions. Nonetheless, the observed data do provide some information, and we derive large sample bounds on the causal vaccine efficacy for Infectiousness estimands. An example of the type of data observed in a study to estimate vaccine efficacy for Infectiousness is analyzed in the causal inference framework we developed.
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effects of pertussis vaccination on transmission vaccine efficacy for Infectiousness
Vaccine, 2003Co-Authors: Mariepierre Preziosi, Elizabeth M HalloranAbstract:We estimated the effect of pertussis vaccination on reducing transmission from vaccinated breakthrough cases from a comprehensive follow-up of a community of 30,000 residents in Niakhar, Senegal. Using a wide spectrum of case definitions, vaccine efficacy was estimated as 1 - the ratio of secondary attack rates (SAR) in all households with cases during the calendar year 1993, a pertussis epidemic year. Vaccine efficacy for Infectiousness (VEi) was 85% (95% confidence interval (CI), 46-95%) for children vaccinated with three doses of a whole-cell (WC; 94%) or an acellullar (6%) pertussis vaccine, with pertussis defined as a cough >/=21 days with paroxysms confirmed by culture, serology, or contact with a culture-confirmed person. It was high for all case definitions. Partial vaccination reduced Infectiousness. Pertussis vaccination is highly effective in reducing transmission from vaccinated breakthrough cases.
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optimal vaccine trial design when estimating vaccine efficacy for susceptibility and Infectiousness from multiple populations
Statistics in Medicine, 1998Co-Authors: Ira M Longini, Karen Sagatelian, Wasima Rida, Elizabeth M HalloranAbstract:Vaccination can have important indirect effects on the spread of an infectious agent by reducing the level of Infectiousness of vaccinees who become infected. To estimate the effect of vaccination on Infectiousness, one typically requires data on the contacts between susceptible and infected vaccinated and unvaccinated people. As an alternative, we propose a trial design that involves multiple independent and interchangeable populations. By varying the fraction of susceptible people vaccinated across populations, we obtain an estimate of the reduction Infectiousness that depends only on incidence data from the vaccine and control groups of the multiple populations. One can also obtain from these data an estimate of the reduction of susceptibility to infection. We propose a vaccination strategy that is a trade-off between optimal estimation of vaccine efficacy for susceptibility and of vaccine efficacy for Infectiousness. We show that the optimal choice depends on the anticipated efficacy of the vaccine as well as the basic reproduction number of the underlying infectious disease process. Smaller vaccination fractions appear desirable when vaccine efficacy is likely high and the basic reproduction number is not large. This strategy avoids the potential for too few infections to occur to estimate vaccine efficacy parameters reliably.
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augmented hiv vaccine trial design for estimating reduction in Infectiousness and protective efficacy
Statistics in Medicine, 1998Co-Authors: Susmita Datta, Elizabeth M Halloran, Ira M LonginiAbstract:It is important to design HIV vaccine trials to estimate the efficacy of a vaccine in reducing Infectiousness in addition to the protective efficacy. Currently planned phase III HIV vaccine field trials in which at-risk individuals are randomized and followed over time do not permit estimation or testing of the vaccine's effect on reducing Infectiousness of vaccinees who become infected. We suggest an augmentation of these field trials that recurits steady sexual partners of the primary participants into the trial as far as they are willing to participate. This study design would allow estimation of the efficacy of the vaccine on reducing Infectiousness as well as the protective efficacy. We compare the classical design that does not include partners to two different types of augmented design. In the first type of augmentation, called the non-randomized partner design, the steady sexual partners are not randomized to vaccine or placebo. In the second type of augmentation, called the randomized partner design, the steady sexual partners are also randomized to vaccine or placebo. We present a probability model based on infection status at the end of the trial that provides maximum likelihood estimates of the protective efficacy of the vaccine, VE s , and the efficacy of the vaccine on reducing Infectiousness, VE l . Wald statistics are used for one degree of freedom tests on VE s and VE,. With the augmented design, a likelihood ratio test is used to test whether the vaccine has any effect at all. The randomized partner design has more power and provides narrower confidence intervals than does the non-randomized partner design.
Ricardo E Gurtler - One of the best experts on this subject based on the ideXlab platform.
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is the Infectiousness of dogs naturally infected with trypanosoma cruzi associated with poly parasitism
Veterinary Parasitology, 2016Co-Authors: Gustavo Fabian Enriquez, Graciela Garbossa, Natalia Paula Macchiaverna, Hernan Dario Argibay, Jacqueline Elena Bua, Ricardo E GurtlerAbstract:Interactions among different species of parasites co-infecting the same host could be synergistic or antagonistic. These interactions may modify both the frequency of infected hosts and their Infectiousness, and therefore impact on transmission dynamics. This study determined the Infectiousness of Trypanosoma cruzi-seropositive dogs (using xenodiagnosis) and their parasite load (quantified by qPCR), and tested the association between both variables and the presence of concomitant endoparasites. A cross-sectional serosurvey conducted in eight rural villages from Pampa del Indio and neighboring municipalities (northeastern Argentina) detected 32 T. cruzi-seropositive dogs out of 217 individuals examined for infection. Both the Infectiousness to the vector Triatoma infestans and parasite load of T. cruzi-seropositive dogs examined were heterogeneous. A statistically significant, nine-fold higher mean Infectiousness was registered in T. cruzi-seropositive dogs co-infected with Ancylostoma caninum and a trematode than in T. cruzi-seropositive dogs without these infections. The median parasite load of T. cruzi was also significantly higher in dogs co-infected with these helminths. An opposite trend was observed in T. cruzi-seropositive dogs that were serologically positive to Toxoplasma gondii or Neospora caninum relative to dogs seronegative for these parasites. Using multiple logistic regression analysis with random effects, we found a positive and significant association between the Infectiousness of T. cruzi-seropositive dogs and co-infections with A. caninum and a trematode. Our results suggest that co-infections may be a modifier of host Infectiousness in dogs naturally infected with T. cruzi.
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high levels of trypanosoma cruzi dna determined by qpcr and Infectiousness to triatoma infestans support dogs and cats are major sources of parasites for domestic transmission
Infection Genetics and Evolution, 2014Co-Authors: Gustavo Fabian Enriquez, Ricardo E Gurtler, Jacqueline Bua, Maria Marcela Orozco, Sonia Alejandra Wirth, Alejandro G Schijman, Marta Victoria CardinalAbstract:Abstract The competence of reservoir hosts of vector-borne pathogens is directly linked to its capacity to infect the vector. Domestic dogs and cats are major domestic reservoir hosts of Trypanosoma cruzi , and exhibit a much higher Infectiousness to triatomines than seropositive humans. We quantified the concentration of T. cruzi DNA in the peripheral blood of naturally-infected dogs and cats (a surrogate of intensity of parasitemia), and evaluated its association with Infectiousness to the vector in a high-risk area of the Argentinean Chaco. To measure Infectiousness, 44 infected dogs and 15 infected cats were each exposed to xenodiagnosis with 10–20 uninfected, laboratory-reared Triatoma infestans that blood-fed to repletion and were later individually examined for infection by optical microscopy. Parasite DNA concentration (expressed as equivalent amounts of parasite DNA per mL, Pe/mL) was estimated by real-time PCR amplification of the nuclear satellite DNA. Infectiousness increased steeply with parasite DNA concentration both in dogs and cats. Neither the median parasite load nor the mean Infectiousness differed significantly between dogs (8.1 Pe/mL and 48%) and cats (9.7 Pe/mL and 44%), respectively. The Infectiousness of dogs was positively and significantly associated with parasite load and an index of the host’s body condition, but not with dog’s age, parasite discrete typing unit and exposure to infected bugs in a random-effects multiple logistic regression model. Real-time PCR was more sensitive and less time-consuming than xenodiagnosis, and in conjunction with the body condition index, may be used to identify highly infectious hosts and implement novel control strategies.
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domestic dogs and cats as sources of trypanosoma cruzi infection in rural northwestern argentina
Parasitology, 2007Co-Authors: Ricardo E Gurtler, Marta Victoria Cardinal, Maria C Cecere, Marta A Lauricella, Uriel Kitron, Joel E CohenAbstract:The reservoir capacity of domestic cats and dogs for Trypanosoma cruzi infection and the host-feeding patterns of domestic Triatoma infestans were assessed longitudinally in 2 infested rural villages in north-western Argentina. A total of 86 dogs and 38 cats was repeatedly examined for T. cruzi infection by serology and/or xenodiagnosis. The composite prevalence of infection in dogs (60%), but not in cats, increased significantly with age and with the domiciliary density of infected T. infestans. Dogs and cats had similarly high forces of infection, prevalence of infectious hosts (41–42%), and Infectiousness to bugs at a wide range of infected bug densities. The Infectiousness to bugs of seropositive dogs declined significantly with increasing dog age and was highly aggregated. Individual dog Infectiousness to bugs was significantly autocorrelated over time. Domestic T. infestans fed on dogs showed higher infection prevalence (49%) than those fed on cats (39%), humans (38%) or chickens (29%) among 1085 bugs examined. The basic reproduction number of T. cruzi in dogs was at least 8·2. Both cats and dogs are epidemiologically important sources of infection for bugs and householders, dogs nearly 3 times more than cats.
Richard G White - One of the best experts on this subject based on the ideXlab platform.
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heterosexual hiv 1 Infectiousness and antiretroviral use systematic review of prospective studies of discordant couples
Epidemiology, 2013Co-Authors: Rebecca F Baggaley, Richard G White, Deirdre T Hollingsworth, Marieclaude BoilyAbstract:Background: Recent studies have estimated the reduction in HIV-1 Infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 Infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions: ART substantially reduces HIV-1 Infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms.
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Infectiousness of hiv infected homosexual men in the era of highly active antiretroviral therapy
AIDS, 2010Co-Authors: Rebecca F Baggaley, Richard G White, Marieclaude BoilyAbstract:The recent study by Jin et al [1] provides estimates of Infectiousness of anal intercourse (AI, insertive circumcised and uncircumcised; receptive with and without ejaculation) for the male homosexual population of Sydney, Australia in the highly active antiretroviral therapy (HAART) era. There is a lack of estimates of HIV Infectiousness for homosexual men and for AI in general and especially for Infectiousness with treatment. A recent literature review found only four studies reporting estimates of HIV transmissibility per AI act [2]. Therefore the additional data presented by Jin et al [1] are an important contribution to the literature. There are many methodological challenges when quantifying HIV Infectiousness which have been discussed elsewhere [3, 4]. While the best study design for quantifying per-act HIV Infectiousness for heterosexual populations has involved discordant monogamous couples (albeit compromised with its own set of biases), these types of study have been seldom used for homosexual populations. It may be more difficult to recruit such participants if rates of monogamy are lower than among heterosexual populations, and monogamous couples may also not be very representative of the wider male homosexual community. The alternative approach used by Jin et al was to follow up initially HIV seronegative homosexual men, testing annually for seroconversion and interviewing every six months for reports of types and frequencies of sexual exposure and the presumed serostatus of their sexual partners (categorised as HIV negative, positive, unknown). A similar approach has been used before for AI by Vittinghoff et al [5] as well as for female sex workers [6, 7]. However Vittinghoff et al were unable to provide per-act estimates per positive exposure for insertive AI, only providing estimates per-act with an “infected or unknown serostatus” partner and therefore may underestimate Infectiousness per exposure, if HIV prevalence among unknown serostatus partners is low. Jin et al's per-act AI transmission probability estimates for receptive unprotected AI (0.65% 95%CI 0.15-1.53% with withdrawal; 1.43% 95%CI 0.48-2.85% with ejaculation [1]), from a population with high (proposed 70%) HAART coverage, are remarkably similar to those estimates made preceding HAART (summary of four estimates: 1.4% 95%CI 0.2-2.5%, no differentiation by ejaculation [2], see Figure). As the authors note, this result is surprising, given the reduction in community viral load that has been observed in some other homosexual populations following the introduction of HAART [8], and that such reductions in viral load are expected to reduce HIV Infectiousness. Per act HIV Infectiousness for anal intercourse, for the pre-HAART and HAART eras Potential reasons why HIV Infectiousness was not seen to reduce include higher Infectiousness associated with various cofactors (STI prevalence may be higher in male homosexual communities now, perhaps as a result of risk compensation in the HAART era); there may be unreported competing exposures through other routes of transmission, such as intravenous drug use; or the partners of study participants may not have been representative of the wider Australian homosexual population, for example, with lower HAART coverage. It would have been useful to have more information regarding the likely HAART coverage of the infected partners, in order to assess how concerning these unexpectedly high estimates for Infectiousness are. While authors state that 70% of male homosexuals diagnosed in Australia are currently treated, estimates of the proportion of those infected who are diagnosed and also an indication of adherence levels and average viral loads for those individuals receiving treatment are required to improve our understanding. The authors addressed the uncertainty regarding “unknown” serostatus and presumed HIV negative sexual partners by undertaking uncertainty analysis, varying the HIV prevalence of the “unknown” and presumed HIV negative partner populations by 5%-15% and 0.5-2% respectively, based on prevalence studies from the locality. It would be informative if this analysis could be extended to reflect the uncertainty in HAART coverage levels in order to explore how sensitive the HIV Infectiousness estimates are to the assumed proportion of sexual partners on treatment. However, even in the absence of further information, levels of HAART are likely to be substantial and so the authors' observation that their per-act estimates are not markedly different from those made in the absence of HAART remains a concerning finding. Community viral load studies covering the Sydney population may help to explain these findings, although the association between viral load and HIV Infectiousness for sexual transmission, particularly for AI, remains to be definitively proven. It would also be useful, if data are available or for future cohorts, to ascertain the treatment status of infected partners where possible, in order to make estimates of AI Infectiousness stratified by treatment status. This study and our review have clearly highlighted the need for more data on HIV Infectiousness for sexual transmission among homosexual men [1, 2].
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hiv transmission risk through anal intercourse systematic review meta analysis and implications for hiv prevention
International Journal of Epidemiology, 2010Co-Authors: Rebecca F Baggaley, Richard G White, Marieclaude BoilyAbstract:Background The human immunodeficiency virus (HIV) Infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention. Methods Systematic review and meta-analysis of the literature on HIV-1 Infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without highly active antiretroviral therapy (HAART). Results A total of 62 643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% [95% confidence interval (CI) 0.2–2.5)] and 40.4% (95% CI 6.0–74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI–UIAI risk were 21.7% (95% CI 0.2–43.3) and 39.9% (95% CI 22.5–57.4), respectively, with no available per-act estimates. Per-partner combined URAI–UIAI summary estimates, which adjusted for additional exposures other than AI with a ‘main’ partner [7.9% (95% CI 1.2–14.5)], were lower than crude (unadjusted) estimates [48.1% (95% CI 35.3–60.8)]. Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI Infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however, predictions are highly sensitive to Infectiousness assumptions based on viral load. Conclusions Unprotected AI is a high-risk practice for HIV transmission, probably with substantial variation in Infectiousness. The significant heterogeneity between Infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI among heterosexuals suggest a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.
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HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention
International Journal of Epidemiology, 2010Co-Authors: Rebecca Frances Baggaley, Richard G White, Marieclaude BoilyAbstract:Background: The HIV Infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention. Methods: Systematic review and meta-analysis of the literature on HIV-1 Infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without HAART. Results: 62,643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% (95%CI 0.2-2.5) and 40.4% (95%CI 6.0-74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI-UIAI risk were 21.7% (95%CI 0.2-43.3) and 39.9% (95%CI 22.5-57.4) respectively, with no available per-act estimates. Per-partner combined URAI-UIAI summary estimates, which adjusted for additional exposures other than AI with a "main" partner (7.9% [95%CI 1.2-14.5]), were lower than crude (unadjusted) estimates (48.1% [95%CI 35.3-60.8]). Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI Infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however predictions are highly sensitive to Infectiousness assumptions based on viral load. Conclusions: Unprotected AI is a high risk practice for HIV transmission, probably with substantial variation in Infectiousness. The significant heterogeneity between Infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI amongst heterosexuals suggests a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.
Rebecca F Baggaley - One of the best experts on this subject based on the ideXlab platform.
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heterosexual hiv 1 Infectiousness and antiretroviral use systematic review of prospective studies of discordant couples
Epidemiology, 2013Co-Authors: Rebecca F Baggaley, Richard G White, Deirdre T Hollingsworth, Marieclaude BoilyAbstract:Background: Recent studies have estimated the reduction in HIV-1 Infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 Infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions: ART substantially reduces HIV-1 Infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms.
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Infectiousness of hiv infected homosexual men in the era of highly active antiretroviral therapy
AIDS, 2010Co-Authors: Rebecca F Baggaley, Richard G White, Marieclaude BoilyAbstract:The recent study by Jin et al [1] provides estimates of Infectiousness of anal intercourse (AI, insertive circumcised and uncircumcised; receptive with and without ejaculation) for the male homosexual population of Sydney, Australia in the highly active antiretroviral therapy (HAART) era. There is a lack of estimates of HIV Infectiousness for homosexual men and for AI in general and especially for Infectiousness with treatment. A recent literature review found only four studies reporting estimates of HIV transmissibility per AI act [2]. Therefore the additional data presented by Jin et al [1] are an important contribution to the literature. There are many methodological challenges when quantifying HIV Infectiousness which have been discussed elsewhere [3, 4]. While the best study design for quantifying per-act HIV Infectiousness for heterosexual populations has involved discordant monogamous couples (albeit compromised with its own set of biases), these types of study have been seldom used for homosexual populations. It may be more difficult to recruit such participants if rates of monogamy are lower than among heterosexual populations, and monogamous couples may also not be very representative of the wider male homosexual community. The alternative approach used by Jin et al was to follow up initially HIV seronegative homosexual men, testing annually for seroconversion and interviewing every six months for reports of types and frequencies of sexual exposure and the presumed serostatus of their sexual partners (categorised as HIV negative, positive, unknown). A similar approach has been used before for AI by Vittinghoff et al [5] as well as for female sex workers [6, 7]. However Vittinghoff et al were unable to provide per-act estimates per positive exposure for insertive AI, only providing estimates per-act with an “infected or unknown serostatus” partner and therefore may underestimate Infectiousness per exposure, if HIV prevalence among unknown serostatus partners is low. Jin et al's per-act AI transmission probability estimates for receptive unprotected AI (0.65% 95%CI 0.15-1.53% with withdrawal; 1.43% 95%CI 0.48-2.85% with ejaculation [1]), from a population with high (proposed 70%) HAART coverage, are remarkably similar to those estimates made preceding HAART (summary of four estimates: 1.4% 95%CI 0.2-2.5%, no differentiation by ejaculation [2], see Figure). As the authors note, this result is surprising, given the reduction in community viral load that has been observed in some other homosexual populations following the introduction of HAART [8], and that such reductions in viral load are expected to reduce HIV Infectiousness. Per act HIV Infectiousness for anal intercourse, for the pre-HAART and HAART eras Potential reasons why HIV Infectiousness was not seen to reduce include higher Infectiousness associated with various cofactors (STI prevalence may be higher in male homosexual communities now, perhaps as a result of risk compensation in the HAART era); there may be unreported competing exposures through other routes of transmission, such as intravenous drug use; or the partners of study participants may not have been representative of the wider Australian homosexual population, for example, with lower HAART coverage. It would have been useful to have more information regarding the likely HAART coverage of the infected partners, in order to assess how concerning these unexpectedly high estimates for Infectiousness are. While authors state that 70% of male homosexuals diagnosed in Australia are currently treated, estimates of the proportion of those infected who are diagnosed and also an indication of adherence levels and average viral loads for those individuals receiving treatment are required to improve our understanding. The authors addressed the uncertainty regarding “unknown” serostatus and presumed HIV negative sexual partners by undertaking uncertainty analysis, varying the HIV prevalence of the “unknown” and presumed HIV negative partner populations by 5%-15% and 0.5-2% respectively, based on prevalence studies from the locality. It would be informative if this analysis could be extended to reflect the uncertainty in HAART coverage levels in order to explore how sensitive the HIV Infectiousness estimates are to the assumed proportion of sexual partners on treatment. However, even in the absence of further information, levels of HAART are likely to be substantial and so the authors' observation that their per-act estimates are not markedly different from those made in the absence of HAART remains a concerning finding. Community viral load studies covering the Sydney population may help to explain these findings, although the association between viral load and HIV Infectiousness for sexual transmission, particularly for AI, remains to be definitively proven. It would also be useful, if data are available or for future cohorts, to ascertain the treatment status of infected partners where possible, in order to make estimates of AI Infectiousness stratified by treatment status. This study and our review have clearly highlighted the need for more data on HIV Infectiousness for sexual transmission among homosexual men [1, 2].
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hiv transmission risk through anal intercourse systematic review meta analysis and implications for hiv prevention
International Journal of Epidemiology, 2010Co-Authors: Rebecca F Baggaley, Richard G White, Marieclaude BoilyAbstract:Background The human immunodeficiency virus (HIV) Infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention. Methods Systematic review and meta-analysis of the literature on HIV-1 Infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without highly active antiretroviral therapy (HAART). Results A total of 62 643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% [95% confidence interval (CI) 0.2–2.5)] and 40.4% (95% CI 6.0–74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI–UIAI risk were 21.7% (95% CI 0.2–43.3) and 39.9% (95% CI 22.5–57.4), respectively, with no available per-act estimates. Per-partner combined URAI–UIAI summary estimates, which adjusted for additional exposures other than AI with a ‘main’ partner [7.9% (95% CI 1.2–14.5)], were lower than crude (unadjusted) estimates [48.1% (95% CI 35.3–60.8)]. Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI Infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however, predictions are highly sensitive to Infectiousness assumptions based on viral load. Conclusions Unprotected AI is a high-risk practice for HIV transmission, probably with substantial variation in Infectiousness. The significant heterogeneity between Infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI among heterosexuals suggest a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.
