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Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.

Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle.

The use of recombinant CD4-IgG2 in pediatrie human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log10 copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1—infected children appears to be well tolerated and capable of reducing HIV-1 burden.

Infants born to human immunodeficiency virus type 1 (HIV-1)–infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1SF-2; n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P=.01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission

The goal of this project was to better understand the experiences and impacts of HIV stigma and discrimination on people living with HIV and to co-create knowledge that has the potential to challenge existing stigma within the healthcare, social services, and public policy sectors in the province of Alberta, Canada. We employed community-based participatory research and a mixed methods design (survey methods and qualitative interviews) to address these questions. An online survey was completed by 148 people living with HIV and semi-structured interviews were conducted with an additional 20 participants. The research findings have been conceptualized within a social ecological model. The four main categories that emerged from the data included personal level factors attributed to HIV stigma, interpersonal factors related to HIV stigma, community factors related to HIV stigma, and HIV stigma in systems and institutions. Within each ecological domain we highlight the strengths and coping strategies people living with HIV identified in the study. Results will be of interest to health researchers and HIV service providers.

Neglected and underutilized crops such as bottle gourd [Lagenaria siceraria (Molina) Standl.] are associated with considerable drought tolerance. The objective of this study was to determine variation in the level of drought tolerance among bottle gourd landraces based on photosynthetic efficiency and to identify unique genotypes for breeding. Photosynthetic efficiency of 12 selected bottle gourd landraces were evaluated under controlled environment under drought-stressed (DS) and non-stressed (NS) conditions. A significant genotype × water regime interaction (P < 0.05) was observed for minimum fluorescence (Fm′), maximum quantum efficiency of PS II photochemistry (Fv′/Fm′), the effective quantum efficiency of PS II photochemistry (ΦPSII), photochemical quenching (qP), non-photochemical quenching (qN), linear electron transport rate (LETR), non-cyclic electron transport rate (NCETR), proportion of open PS II reaction centers (1 − qP), photo-inhibition of PS II reaction centers Y (NO), the fraction of photon energy trapped by “open” PS II reaction centers and utilized in PS II photochemistry (P), the portion of the absorbed photon energy that was thermally dissipated (D), rate of photochemistry (RPC) and rate of heat dissipation (RHD) suggesting variation in genotypic response under NS and DS conditions. Principal component analysis under NS and DS conditions identified two principal components (PC’s) which accounted for a total variance of 90 and 96%, respectively. Under DS condition, minimum fluorescence (F0′), Fm′, Fv′/Fm′, qN, NCETR, D, and RHD correlated with PC1 which accounted for 56% of total variation. ΦPSII, qP, LETR, P, RPC and 1 − qP correlated with PC2 which accounted for 40% of total variation. The PC biplot identified landraces BG-27, BG-58 and BG-78 as the most drought tolerant characterized by high values for LETR, qP, P, ΦPSII and RPC under drought stress condition. These landraces could be a useful genetic resource in the development of bottle gourd genotypes with enhanced drought tolerance.