Estimating the Timing of Mother-to-Child Transmission of the Human Immunodeficiency Virus Type 1 Using a Viral Molecular Evolution Model

Background: Mother-to-child transmission (MTCT) is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT. Materials and Methods Six-hundred and twenty-two clonal env sequences from the RNA and DNA viral population were longitudinally sampled from nine HIV-1 infected mother-and-child pairs [range: 277–1034 days]. For each transmission pair, timing of MTCT was determined using a coalescent-based model within a Bayesian statistical framework. Results were compared with available estimates of MTCT timing obtained with the classic biomedical approach based on serial HIV DNA detection by PCR assays. Results: Four children were infected during pregnancy, whereas the remaining five children were infected at time of delivery. For eight out of nine pairs, results were consistent with the transmission periods assessed by standard PCR-based assay. The discordance in the remaining case was likely confused by co-infection, with simultaneous introduction of multiple maternal viral variants at the time of delivery. Conclusions: The study provided the opportunity to validate the Bayesian coalescent approach that determines the timing of MTCT of HIV-1. It illustrates the power of population genetics approaches to reliably estimate the timing of transmission events and deepens our knowledge about the dynamics of viral evolution in HIV-infected children, accounting for the complexity of multiple transmission events

First Report of Widespread Wild Populations of Triatoma infestans (Reduviidae, Triatominae) in the Valleys of La Paz, Bolivia

Wild populations of Triatoma infestans, the main vector of Chagas disease in the Southern Cone countries, may be involved in reinfestation of human dwellings, limiting the success of vector-control campaigns in Bolivia. Knowledge of the distribution of these populations remains incomplete. We report here the detection of T. infestans wild populations in large areas in the department of La Paz, Bolivia. Among 18 sylvatic areas investigated, 17 were positive with T. infestans specimens. The infection rate of captured T. infestans with Trypanosoma cruzi was 85.7% in adult specimens. These results expand the geographical distribution of wild populations of T. infestans; it may be distributed throughout the Inter-Andean Dry Forest eco-region of Bolivia. The current information allows us to propose the hypothesis that a sylvatic origin of the reinfestation is located in the valleys of La Paz

Effect of different factors (mother-infant pair, duration of follow up and DNA/RNA origin of the viral sequences) on molecular variance analyzed by AMOVA.

<p>*p<0.001.</p><p>AMOVA: analysis of the molecular variance.</p

Pairs sampling informations.

<p>IU: <i>in utero</i> transmission - IP: <i>intrapartum</i> transmission.</p

Bayesian MCMC phylogenetic trees.

<p>Maternal and child sequences are represented by diamonds and triangles respectively. Filled and unfilled symbols refer to DNA and RNA samples respectively. Time scale expressed in days is indicated below each tree. Posterior probabilities of the main lineages are indicated at the root.</p

Comparative TMRCA posterior distributions.

<p>Red curves correspond to posterior distribution of children-only data. Black curves refer to posterior distribution of pair (mother and child) data. Dashed lines represent the 95% confidence interval. Median (hashed line) is indicated. The blue vertical line indicates birth and times on the x axis are expressed in days since birth. Y axis: TMRCA density; X axis: time in days. a to e: infants infected <i>intrapartum</i>. f to i: infants infected <i>in utero</i>.</p

Boxplots of the TMRCA posterior distributions.

<p>Dashed lines represent the 95% High Posterior Density (HPD). First (25%) and third (75%) quartiles (limits of the rectangle) and median (thick line) are also indicated. According to the biomedical reference diagnostic method, the four top infants with white boxplots were infected <i>in utero</i>, whereas the five bottom infants with grey boxplots were infected <i>intra partum</i>. Vertical red lines indicate the maximum estimates of TMRCA.</p