The goal of this project is to improve newborn survival among low birth weight (LBW) infants through a daily prophylactic dose of bovine lactoferrin (bLF). A two-stage project will be conducted with formative research followed by randomized controlled trial (RCT) to evaluate the appropriate daily dose of bLF and its efficacy in preventing neonatal infections.

PATH's novel infusion pump, the RELI Delivery System, was designed to address many of the barriers surrounding access to infusion pumps in LRS: it does not require electricity or a battery, is inexpensive to manufacture and operate, does not require expensive consumables, and has a simple user interface. We will develop a functional prototype and related job aids to share with stakeholders.

This team proposes to develop and test an innovative microarray patch to deliver a combination of antibiotics for the treatment of neonatal sepsis. An easy-to-use, less-invasive, affordable delivery method for amoxicillin and gentamicin could expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period.

The Safer Deliveries project will improve the ability of nurses and midwives to identify danger signs for a woman and her baby during the critical period of labor and delivery and link these measures to specific decision support rules that guide the health worker in taking corrective action. Using ultra-low-cost disposable ECG leads, D-tree International will build a phone based device that provides continuous tracking of fetal and maternal heart rate and uterine contractions during labor and delivery leading to more timely and effective interventions to save the life of the mother and infant.

PremieBreathe has built a functional infant breathing aid for $450, one tenth the price of commercial models. The device, a humidified high flow nasal cannula (HHFNC), is the gold standard of non-invasive neonatal respiratory care in high-income countries. With the support of Saving Lives at Birth, PremieBreathe will conduct initial trials at Ayder Referral Hospital in the Tigray region of Ethiopia, and identify design, manufacturing, and distribution partners to prepare for scaled production and dissemination.

Lu Lu of Shanghai Medical College, Fudan University in China working with Ling Ye of Emory University in the U.S., will design a potent HIV vaccine using selected sequences of one of the virus's envelope proteins to trigger the production of broadly neutralizing antibodies. This has been problematic due to the diversity of the viral envelope glycoprotein and its glycosylation shield, which prevent the immune system from recognizing it. The membrane-proximal external region (MPER) of the viral envelope protein has been identified as an attractive target for inducing neutralizing antibodies, and they have fused it with another viral protein to form a chimera that can partly neutralize infection. They will build on this result by modifying the structure of the MPER to stabilize it in a more active conformation, and by fusing it with slightly different viral proteins that can then be immunized altogether. They will evaluate whether this vaccine strategy further stimulates broadly neutralizing antibody production and can fully neutralize HIV in several animal models.

The study intends to develop an inter-generational intervention to ameliorate neonatal gut microbiota. It is based on the hypothesis that consuming prebiotic starches such as high amylose maize starch (HAMS) by mothers during the third trimester of pregnancy will modify their fecal microbiota and will subsequently lead to a beneficial variation in the fecal microbiota of the newborn infant. This will consequently guide favorable intestinal activity, thus enhancing growth, and intellectual competence of the infant in the intermediate and long term.

Pamela Schnupf of Paris Descartes University in France will develop an oral vaccine to prevent infectious diarrhea in children by engineering a non-pathogenic bacteria to express pathogen molecules that can be safely delivered in bacterial spores. Diarrheal disease caused largely by Shigella and enterotoxigenic Escherichia coli is a major cause of morbidity and mortality in children under five years of age in low-resource settings. Segmented filamentous bacterium (SFB) is non-pathogenic and normally colonizes the human gut during infancy and stimulates the immune system to protect against infections. They will establish methods to genetically engineer SFB to express selected antigens from enterotoxigenic E.coli and test whether it can stimulate an immune response and protect against infection using established mouse models.

Save the Children proposes an affordable and exclusive point-of-care diagnostic device for accurate measurement and interpretation of key vital signs (oxygen saturation, respiratory rate and temperature) among young infants (0-59 days) and children (2-59 months). It is equipped with a unique universal pulse oximeter sensor. The device will improve the quality of pneumonia case management and possible serious bacterial infections at community and health facility levels in low-resource settings.

Clif Barry of The National Institute of Allergy and Infectious Diseases in the U.S., working with Qian Gao of Shanghai Medical College Fudan University in China, will support a clinical trial to shorten the treatment time for tuberculosis (TB) from six months to four months by helping to identify predictive biomarkers in individuals that only require the shorter treatment. Shortening treatment when possible will substantially reduce costs and the emergence of drug resistance, which is a major barrier to eradicating this deadly disease. The phase 2b clinical trial will recruit 620 TB patients at multiple clinics in South Africa and China who will be monitored for disease burden by PET/CT scans and diagnostic assays during treatment, and will supply blood and sputum samples for testing. He will analyze RNA and inflammatory markers in serum samples from the Chinese trial participants to identify more robust biomarkers for predicting shorter treatments. He will also determine the strains of the causative Mycobacterium tuberculosis, the source of any reinfection (relapse or new infection), and the presence of drug resistant bacteria in these patients, and how these link with treatment duration and disease outcome.

There is international consensus that syringe pumps are an essential medical device to support care of mothers and newborns at district hospitals. Yet, they are often unavailable in low-resource settings because of high cost, technical complexity, and lack of brand name consumables. The project's idea is to scale AutoSyp, a low cost, low power, syringe pump in maternity and neonatal wards of hospitals in Malawi.

Patricia Donahoe and David Pepin of Massachusetts General Hospital in the U.S. are using a cell-based screening platform to develop a new class of hormonal contraceptive that works at the early stage of primordial follicle activation to prolong the contraceptive effect and reduce side effects, thereby promoting wider use particularly in the developing world. This early stage of follicle development in the ovary is suppressed by a hormone (Mullerian inhibiting substance or MIS) to regulate egg production. They considered that a drug that could mimic MIS could completely suppress ovulation and act as a powerful contraceptive. In contrast, most available hormonal contraceptives work once ovulation has begun, thereby requiring daily dosage, and share unwanted side effects including migraine and increased risk of some diseases. In Phase I, they designed a luciferase-based screening platform using engineered mammalian cells and screened 5,500 compounds from which they validated three candidate contraceptive compounds with high specificity and activity and limited toxicity. In Phase II, they will adapt their assay for higher throughput screening and screen 100,000 compounds to identify diverse classes of molecules for evaluation as ovarian suppressants. The contraceptive efficacy of validated candidates with favorable properties will then be tested in mice.