We propose to develop a rapid, low-cost and effective method for detecting sepsis in early stages. We will take advantage of the potential of histones to be sensitive and effective biomarkers for sepsis, and of the versatility, simplicity and low-cost of test strips. The diagnostic test will be simple, comfortable, easy to interpret and low-cost for prognosis/early diagnosis of sepsis based on histone expression. The test can be used by non-technical experts in any hospital or health center worldwide, though it has been designed intentionally for low-resource countries. Proof-of-concept of this diagnostic test will be performed in Uganda, in order to analyze benefits and reduction in mortality of pregnant women and infants in that country. The innovative combination of histones and strips make this diagnostic test a significant improvement over the inefficient methods currently used for sepsis diagnosis, such serum lactate measurement, microbiological sampling, etc.

Our proposal will provide this life-saving treatment to isolated, extremely resource poor people by obviating the need for electricity. This will be achieved by applying recently developed hydrological engineering approaches to extract the pressure differential required for the adsorption process exploited by Oxygen concentrators. This project aims to develop and test an electricity free Oxygen concentrator suitable for a developing world health facility. This represents a major paradigm shift, as to-date the problem has been interpreted as how to supply electricity to an Oxygen concentrator. In comparison with solar and generator based approaches the prototype will require significantly less capital cost and maintenance. Further, construction out of locally available components will empower the community to independently and sustainably access this life-saving treatment.

Effective resuscitation could reduce intrapartum related neonatal deaths by 30%, and deaths from prematurity by 10%, creating the potential to save 347,200 babies annually. However, one in five trained healthcare professionals (HCPs) fail to perform the resuscitation technique correctly, and those that do, often experience a rapid decline in proficiency. Our Augmented Infant Resuscitator's advanced training capabilities, instant feedback mechanism, and objective self-audit and retraining abilities will maximize and sustain gains from effective resuscitation. The AIR prototype provides instant feedback to users about effective ventilation. This is measured using inexpensive instrumentation that calculates ventilation rate, air volume and air pressure delivered by the bag-valve-mask (BVM) across the resuscitation face-mask. These parameters correlate with the four most common mistakes that result in ineffective resuscitation: 1) Failed seal at the face-mask interface resulting in failure to inflate the lungs; 2) Blocked airways; and 3) Wrong ventilation frequency 4) Insufficient/shallow lung inflation. Each of these mistakes can cause death or brain damage. AIR also records performance on an internal memory card for future feedback, improving HCPs training by identifying persistent gaps in technique.

Rodolfo de Carvalho Pacagnella from the Universidade Estadual de Campinas in Brazil will perform two randomized clinical trials across 15 obstetric clinics in Brazil to evaluate treatment with progesterone in the presence or absence of a cervical pessary for preventing spontaneous preterm birth. Both cervical pessary and progesterone are individually considered to be effective preventative treatments for preterm birth, which is one of the most common complications seen in pregnancy and can cause severe complications for the premature infant. The causes of preterm birth are mostly unknown, although incidence does increase with cervical shortening during the mid stages of pregnancy. They will also analyze the prevalence of a short cervix in Brazilian pregnant women, and determine how well it predicts preterm birth. Their approach to screen for cervix length and then treat high-risk individuals with the combination therapy will also be evaluated for cost-effectiveness.

Bernardo Jefferson de Oliveira from the Universidade Federal de Minas Gerais in Brazil will develop an interactive exhibit including images, audio, games, and theatre to encourage natural childbirth and perform a pilot study to evaluate its effect on changing public perception of labor and birth. They aim to reduce unnecessary cesarean sections in Brazil where the incidence of preterm births, which can cause severe disabilities, has been increasing. This is thought to be due in part to the negative perception of normal birth and the assumption that cesarean sections are safer and more convenient. The exhibit will focus on producing sensations and emotions to teach participants about the experience, risks and benefits of both cesarean section and natural childbirth. They will present the exhibit over 12 months in three major cities, which should reach around 30,000 people, and use interviews and questionnaires before and after participants visit the exhibit to measure its effect on knowledge and attitudes.

Joao Guilherme Bezerra Alves from the Instituto de Medicina Integral Professor Fernando Figueira in Brazil will perform a randomized controlled trial to assess whether a daily oral supplement of magnesium citrate can prevent placental vascular disease, which can lead to preterm birth. Placental vascular disease restricts the flow of nutrients to the fetus and can cause growth restriction and maternal hypertensive disorders. Magnesium is known to promote placental vascular flow, and magnesium citrate is safe, inexpensive and easily absorbed in the body. They will perform a clinical trial in two large hospitals in Brazil in which 3,000 pregnant women will be offered a daily magnesium supplement or a placebo control starting from up to 20 weeks of gestation and continuing until birth. The effect on various outcomes including placental function, preterm labor, and mother and child health will be evaluated.

Jose Simon Camelo Junior from the Universidade Federal de São Paulo in Brazil will test a method for producing a lyophilized human milk concentrate for feeding very low birth weight newborns that can be implemented in developing countries. Very small premature babies of less than 1,500 grams require large quantities of proteins, calories, minerals, micronutrients and electrolytes to survive and thrive. However, breast milk alone is not concentrated enough. Supplements derived from cow’s milk have been used but appear to inhibit particularly the immunological quality of human breast milk, which helps block infection. Human milk additives have now also been tested and show promising results, but they are prohibitively expensive to produce in developing countries. They will use a simple method involving evaporation, centrifugation and lyophilization to produce a concentrated form of human milk that can be implemented in Brazilian milk banks. The milk product will be evaluated for stability and safety and for nutritional content to ensure it contains adequate concentrations of essential nutrients within manageable volumes to support very low weight newborns.

Silvia Regina Dias Medici Saldiva from the Instituto de Saúde in Brazil will determine whether and which physical, social and cultural aspects of urban environments can increase the incidence of preterm birth. Prematurity is a major cause of childhood mortality and disability, and levels are high in Brazil. Preterm birth is likely caused by combinations of factors that, particularly in urban locales, might include environmental factors such as the quality of housing, proximity to health facilities and pollution levels, which then interact with social and cultural factors. They will identify spatial clusters of premature births from 2012 in the city of São Paulo to define suitable regions for performing case-control studies. The studies will involve face-to-face interviews at selected households by trained interviewers to assess environmental and social factors such as income, education, health and sanitation. These data will be supplemented with available or modeled meterological and pollutant data, and data from tree rings, which can provide climate information as well as levels of toxins. They will then perform hierarchical modeling to identify environmental factors associated with preterm births.

Renato Soibelmann Procianoy from the Universidade Federal do Rio Grande do Sul in Brazil will analyze the association between bacterial populations in the vagina and gut of mothers in their third trimester and in the meconium of very preterm newborns, with risk of preterm delivery. It was previously assumed that microbes from the mother are first transferred to the fetus during delivery. However, it was recently shown that this could happen already in the uterus, triggering a possible immune response by the fetus that may lead to premature birth, which is a leading cause of infant morbidity and mortality. They will use 16S rRNA-based bacterial sequencing technology on around 600 samples to compare the types of bacteria present in preterm infants with that in healthy term infants in a neonatal unit in the Clinicas Hospital in Porto Alegre. They will also track the changes in bacterial composition in healthy and sick newborns during their hospital stay, to identify types of bacteria associated with specific diseases such as diarrhea. All samples will be stored in a repository for future case-controlled studies.

Brian Lilly of Ergo-Tech Inc. in the U.S. will design and build a water irrigation pump from inexpensive and widely available automobile parts to decrease labor and increase production of women smallholder farmers in Africa. Irrigation is one of the most time-consuming and labor-intensive activities of women farmers. Making an irrigation system from automobile parts is useful because the parts are well tested and mass-produced in Africa, and expertise on their repair and maintenance is readily available. Lilly will build an irrigation system from automobile parts using different designs for the pump and battery charger components, and test the interchangeability of different parts. Once the design is finalized, he will build 10 machines and test them in Africa to evaluate performance.

Matthew Bonds of Harvard University in the U.S. will quantify the economic burden of disease using a combined metric to incorporate disease impact on both human and animal health. Current measures of economic burden consider humans and animals independently, yet they are both influenced by disease and by the health of each other. They will develop an integrated model combining epidemiology and economic growth to uncover links between disease impact and income in both human and livestock systems. Their model will be tested in the field using target human and wildlife populations in Madagascar to quantify the overall economic burden of disease.