Although diarrhea is a major cause of mortality in young children in developing countries, few studies comprehensively examine infectious diarrheal etiologies associated with death 
. Our study is unique because it examines risk factors for childhood diarrheal mortality including a range of diarrheal etiologies in a setting of a high infant and child mortality, and high malaria and HIV prevalence. Rotavirus was the most common etiology of diarrhea in hospitalized children in this rural area but was not the most frequently identified pathogen among in-hospital fatalities. The pathogen-specific CFR for rotavirus was lower than for other enteric pathogens, particularly nontyphoidal Salmonella
species. Children who died were more likely to have had nontyphoidal Salmonella
, or Shigella
infections than children who survived.
The children who died while hospitalized for diarrhea were vulnerable for several reasons. They had a significantly longer duration of diarrhea before reaching the hospital, and were more likely to be returning to the hospital, a marker for severe illness, or inadequate treatment/premature discharge on previous admission, as observed in previous studies 
. The median age of death was 9 mo old. Those with nontyphoidal Salmonella
infections, which were associated with 22% of all deaths, were particularly young (median age 7 mo). This young age coincides with the critical weaning period when foods are introduced and Salmonella
-specific maternal antibody is lost with consequent elevated risk of diarrhea 
. Children who died had other co-morbidities, which were identified as independent risk factors for death, such as malnutrition, oral thrush (which can be associated with HIV/AIDS infection), and dehydration, as has been previously documented 
. In general, all children in this study had substantially more stunting and wasting and a higher proportion were underweight than children in communities in Nyanza Province 
. Of note, a lower or similar prevalence of a diarrheal pathogen among children who died compared to survivors does not necessarily indicate that infection did not contribute to mortality, but that the CFRs were lower for such pathogens than for others.
Most cases of non-bloody, non-septic bacterial diarrhea do not require antimicrobial therapy and resolve with symptomatic support (e.g., oral rehydration); however, >75% of enrolled children were treated in-hospital with an antimicrobial drug. It has been demonstrated in a previous study 
and in the current study (unpublished data) that the utility of the commonly available antimicrobials for treating bacterial diarrhea in this area is substantially limited by reduced antimicrobial susceptibility, particularly for Shigella
and nontyphoidal Salmonella
. Training and oversight on judicious use of antimicrobial drugs, and enhanced access to laboratory diagnostics for diarrheal diseases, including capacity for blood culture, are warranted to appropriately treat potentially fatal diarrhea.
The study hospitals intermittently ran out of stocks of many critical and life-saving supplies for the treatment of diarrhea, such as ORS, and pediatric intravenous (IV) fluids, needles, or tubing during the study. In addition, in a study assessing community availability of ORS carried out in the area during the same time period, there was a documented lack of widespread availability of ORS packets with only 4% of shops and 48% of pharmacies in the area having ORS available for sale, resulting in very limited community access to life-saving treatment for dehydration outside of the health facility 
This study was subject to several important limitations. It only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home. In resource-limited settings there are inherent biases in studying the etiology of diarrheal deaths in hospitals because rotavirus can be successfully treated with hydration relative to bacterial agents, which may require effective antimicrobial therapy, necessitating knowledge of the causative agent and its antimicrobial susceptibility, which is often not feasible in such settings. Since most diarrheal deaths occur at home where rehydration is less accessible, the etiologic picture of overall childhood diarrheal deaths could be different if community deaths were assessed. HIV counseling and testing were not routinely offered at the time of the study; therefore HIV testing results are not available for participants. Where available, we relied on HIV diagnosis based on clinical features, which may be subject to biases in assessing the factors contributing to diarrheal disease among participants since HIV infection at early stages may have been missed and not all data were routinely captured. Also, given the number of infectious enteric pathogens and clinical factors assessed our model may not have been able to differentiate between clinical factors that had similar effect sizes. The study did not capture other potentially relevant information, such as whether illness was associated with bacteremia (blood cultures were not done), breastfeeding status, and did not specifically ask about pre-hospitalization ORS use. Assessing the prognostic performance of the factors associated with mortality in the detection of patients at high risk of death, as has been carried out in previous mortality studies 
, would be important in future analysis, as would expanding the testing panel to include Cryptosporidium
, and other enteric agents. With regard to the sensitivity of the tests used, culture is the gold standard for the detection of bacterial agents, and the limit of detection of the viral RT-PCR assays ranges from 10–100 viral particles/reaction.
Since vaccines for most bacterial diarrheal diseases are in the distant future, and roll-out of rotavirus vaccines worldwide is as yet limited, expedited implementation of the new Kenyan Ministry of Public Health and Sanitation (MoPHS) policy on the control and management of diarrheal diseases in children <5 y old is critical 
. The strategy focuses on home-based case management, including promotion of ORS and zinc use, prompt and effective health facility-based case management, diarrhea prevention through improved nutrition, water, sanitation, and hygiene, and the introduction of rotavirus vaccine, behavior change communication, and logistics management.
The national supply chain management of critical diarrhea treatment supplies such as ORS, pediatric IV fluids, and zinc, should be strengthened, and enforced systematic inventory monitoring of these supplies should take place at health facilities. The implementation of an improved supply chain, which is contained in the new MoPHS policy 
, will help improve the quality of inpatient pediatric care and prevent unnecessary diarrheal deaths.
The findings of particular clinical relevance are that immediate priority should be given to the management of children presenting to the hospital with diarrhea who are at high risk of death, including those who have previously sought care at a health facility for their illness, are dehydrated, have oral thrush, and are malnourished. In addition to receiving appropriate diarrhea case management, malnourished children with diarrhea should be provided nutritional rehabilitation. Further to identifying children at high risk for death from diarrhea in the hospital, this study can help inform policy makers on priority areas for interventions to reduce childhood diarrhea requiring hospitalization or resulting in death, such as the use of zinc for diarrhea management, reemphasis on community level promotion of ORS, water, sanitation and hygiene interventions, and the development and roll-out of new enteric vaccines.