New Ways to Reduce Pneumonia Fatalities Through Timely, Effective Treatment of Children (Round 14)

Opportunity:

Over 1.2 million children died from pneumonia in 2011. Ninety percent of child deaths from pneumonia occur in sub-Saharan Africa and South Asia where the proportion of deaths among children with pneumonia can reach as high as 30%. The Foundation’s pneumonia strategy is a 3-pronged approach - Protect, Prevent, Treat with key emphasis on vaccines including pneumococcal conjugate vaccine and other vaccines aimed at protecting young infants through a maternal immunization platform. 

However, given the currently high levels of child mortality attributable to pneumonia as well as limits of vaccines in preventing all cases of pneumonia, we also work to improve mortality-impacting treatment inputs or commodities, and ensure their inclusion on key global and national policies. Where such commodities exist – such as amoxicillin dispersible tablets – we are working on increasing their availability and use with a primary focus on the countries with highest burden of child pneumonia mortality.

The Challenge:

Children with pneumonia in highest burden countries face many risks and obstacles that impede their access and adherence to timely and appropriate treatment. Such obstacles can vary from caregivers failing to recognize signs and symptoms of deterioration, lack of access to appropriate care or absence of appropriate treatments and services at treatment facilities. Successful execution of our Treatment Innovation and Delivery Initiative within the pneumonia strategy will require new innovation around critical treatment components. We are therefore focusing our explorations topic on finding novel ideas that will help diminish mortality among children with pneumonia leveraging known potential for amoxicillin treatment, pulse oximetry and oxygen supplementation through oxygen concentrators. 

We are looking for innovative ideas in the following specific areas of interest under this exploration:

1. Child friendly formulations of amoxicillin
2. Optimizing Oxygen concentrators
3. Devices for measuring oxygen saturation (or optimizing pulse oximetry)

Examples of ideas we will consider funding:

Child friendly formulations of amoxicillin

Amoxicillin is an effective beta lactam antibiotic with activity against the pneumococcus. The World Health Organization recommends amoxicillin dispersible tablets as the first line antibiotic for outpatient treatment of children with pneumonia. However, the availability and use of this formulation as treatment for pneumonia in high burden countries remains limited. Many countries only have the capsule and powder for suspension formulations on their licensed medicines register, while others continue to recommend cotrimoxazole as front-line treatment. 

The capsule is difficult to administer to children, while the suspension is bulky, requires clean water to reconstitute, is costly, and may require refrigeration in locations with extremely high temperatures. Also, liquid dosage forms, such as syrups and suspension are usually not amenable to long-term storage or transport under high temperature conditions common in many low and middle income countries and must be consumed once opened or reconstituted. Dispersible tablets have improved shelf life and cost but continue to have associated challenges including time to dispersal and requirement for clean liquid. 

The ideal oral pediatric dosage form is tasteless/taste-masked and orally dissolvable or easy to swallow. We are looking for innovative ideas on dosage formulation of amoxicillin for children between birth and 5 years of age (the most affected age group). Ideas such as orally disintegrating tablets (not requiring dispersal in liquid prior to consumption), or transdermal patches will be accepted. While established techniques exist for disintegrating tablets including freeze drying, molding, spray drying, sublimation, direct compression, cotton candy process, mass extrusion, and melt granulation, we are looking for formulations that are user friendly, simpler than dispersible tablets, and of equivalent or lower cost to current amoxicillin formulation.

Things we will not consider funding:

• Formulations that lead to a higher pill burden
• Chewable formulation acceptable only for older children
• Modest improvements in dispersible tablet formulation

Optimizing Oxygen concentrators

Oxygen is a life-saving intervention, yet many hospitals and health centers do not have access to reliable oxygen supply. Cylinders are costly to refill and logistically challenging to transport especially to rural areas with poor road access. Therefore, many low resource settings rely on oxygen concentrators, where facilities have access to grid power or reliable backup power. In settings where electricity is not reliable however, current oxygen concentrators are less suitable. 

We are looking for innovations that would improve the adaptability of oxygen concentrators to low resource settings including improving power or maintenance requirements of the equipment. Power supply is a major known challenge, and we are therefore looking for systems that have low power needs, increased storing capacity or are able to operate continuously from grey power or alternative energy sources. Other improvements to reduce maintenance needs are also encouraged as are improvements to system efficiency. 

Things we will not consider funding: 

• Modifications of oxygen cylinder delivery systems
• Oxygen concentrator modifications which result in a decreased liters per watt output compared to currently available stationary concentrators
• Modifications which limit adaptability to limited resource settings

Devices for measuring oxygen saturation (or optimizing pulse oximetry)

Hypoxemia (low oxygen level in the blood) is associated with mortality. Identifying children with hypoxemia is a key step to provision of life saving oxygen supplementation. Hypoxemia is difficult to detect using clinical signs alone because they lack sensitivity^[1] The primary method for measuring oxygen saturation at the point of care is pulse oximetry, however its availability is highly limited in the developing world due to cost. The initial investment is considerable, and the maintenance costs have been reported to be as high as 50% of the initial capital costs on an annual basis.^[2] The low longevity and high costs of parts particularly the finger sensors constrain their use in low resource settings.

The last few years has seen innovations around mobile devices that can potentially measure oxygen saturation. Examples of such devices are limited and remain costly. We are looking for innovations that will deliver reliable devices or tools for measuring and monitoring of oxygen saturation in children with pneumonia in low resource settings. These innovations should be of lower cost than existing devices, require less frequent and affordable maintenance, and be usable with limited or no training by non-professional health providers. The ideal device would have a long sensor life without disposable parts and be able to communicate with or integrate into a mobile technology (cell phone) platform. 

Things we will not consider funding: 

• Devices or tools that have lower sensitivity and specificity to existing devices
• Devices that cannot measure oxygen saturation in young infants and children
• Devices that require complex ecosystems to run including access to regular maintenance, or access to the internet as examples

We will also not consider funding for:

1. Ideas that are not directly relevant to developing countries;
2. Ideas without a clearly articulated and testable hypothesis and metrics;
3. Ideas for which a relevant indicator of success cannot be demonstrated within the scope of the GCE Phase 1 award ($100,000 over 18 months);
4. Basic research without clear relevance to the goals of this topic;
5. Solely infrastructure or capacity-building initiatives.

References

^[1] Weber MW, Usen S, Palmer A, Jaffar S, Mulholland EK. Predictors of hypoxaemia in hospital admissions with acute lower respiratory tract infection in a developing country. Archives of disease in childhood 1997; 76(4): 310-4.

^[2] Weber MW, Mulholland EK. Pulse oximetry in developing countries. Lancet 1998; 351(9115): 1589.