A food-based approach to reduce vitamin a deficiency in southern Ethiopia: a cross-sectional study of maternal nutrition and health indicators

One micronutrient essential for proper growth and development is Vitamin A. Children and pregnant women are most susceptible to vitamin A deficiency (VAD) because of the higher intake requirements needed during critical growth periods. Vitamin A deficiency is a serious but preventable public health problem in Ethiopia. In 2012, the International Potato Center (CIP) partnered with the University of Wisconsin-Madison (UW) and local stakeholders in the Southern Nations, Nationalities, and Peoples Region (SNNPR), Ethiopia, to address the issue of VAD among rural SNNPR households by increasing production and consumption of orange fleshed sweet potatoes (OFSP). This paper presents a cross-sectional analysis of vitamin A knowledge, consumption practices, and OFSP agronomic practices from surveys conducted among households who participated in a food-based intervention. The study population consisted of 150 mothers from rural households in five districts in the Sidama and Wolayta zones in the SNNPR. Data were collected during April and May 2013 by trained enumerators in the local language using structured questionnaires. Surveys were adapted from validated instruments, and included questions about household socioeconomic characteristics, agricultural practices, dietary diversity, food security, and general health for women between 20-60 years and children between 6-59 months. Among respondents, 63% of mothers reported knowledge about vitamin A, with responses varying by geographic location. Among those who reported knowledge about vitamin A, 8% identified OFSP as a source, 1% had consumed OFSP in the past 7 days, and 0% reported that they ever prepared OFSP with an animal- or vegetable-based fat. Vitamin A-related health issues reported by mothers include night-blindness (32%), measles (32%) and malaria (72%). Given that existing knowledge, behaviors and production levels of vitamin A rich foods (including OFSP) are limited within the SNNPR study population and vary by geographic location, an integrated, food-based approach to address VAD may be relevant in this context to sustainably support improved health and livelihoods.Key words: Nutrition, orange fleshed sweet potato, behavior change, Ethiopi

Exploring the Mode of Action of Bioactive Compounds by Microfluidic Transcriptional Profiling in Mycobacteria

10.1371/journal.pone.0069191PLoS ONE87-POLN

A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy

Candidate antibacterials are usually identified on the basis of their in vitro activity. However, the apparent inhibitory activity of new leads can be misleading because most culture media do not reproduce an environment relevant to infection in vivo. In this study, while screening for novel anti-tuberculars, we uncovered how carbon metabolism can affect antimicrobial activity. Novel pyrimidine–imidazoles (PIs) were identified in a whole-cell screen against Mycobacterium tuberculosis. Lead optimization generated in vitro potent derivatives with desirable pharmacokinetic properties, yet without in vivo efficacy. Mechanism of action studies linked the PI activity to glycerol metabolism, which is not relevant for M. tuberculosis during infection. PIs induced self-poisoning of M. tuberculosis by promoting the accumulation of glycerol phosphate and rapid ATP depletion. This study underlines the importance of understanding central bacterial metabolism in vivo and of developing predictive in vitro culture conditions as a prerequisite for the rational discovery of new antibiotics

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis