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Pediatric Sepsis in the Developing World

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Pediatric Sepsis in the Developing World Journal of Infection (2015) 71, S21eS26 www.elsevierhealth.com/journals/jinf Pediatric sepsis in the developing world Niranjan Kissoon a,*, Jonathan Carapetis b,c a Global Child Health, Department of Pediatrics and Emergency Medicine, University of British Columbia, Vancouver V6H 3V4, Canada b Telethon Kids Institute, University of Western Australia, West Perth, Western Australia 6872, Australia Accepted 21 April 2015 Available online 24 April 2015 KEYWORDS Summary Sepsis is the leading killer of children worldwide, but this is not reflected in esti- Sepsis; mates of global mortality. While it is important to classify deaths according to specific causes Children; such as pneumonia, malaria and diarrheal diseases, we contend that it is a mistake to ignore Pneumonia; the unifying feature of all of these deaths e they are due to sepsis. The issue of highlighting Malaria; sepsis as the end result of severe infections is not merely cosmetic but is important for a pro- Diarrhea vision of care especially in resource limited environments where skilled healthcare workers are in short supply and care is being delivered by teams with limited training and clinical skills. Highlighting sepsis and the few simple emergency therapeutic interventions needed will focus on the actual problems that confront clinicians in regions with limited resources. ª 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Introduction sepsis.1 While it is important to classify deaths according to specific causes, we contend that it is a mistake to ignore the unifying feature of all of these deaths e that they are Sepsis is the leading killer of children worldwide, but this is due to sepsis. The implications of recognising sepsis as an not reflected in estimates of global mortality, such as in the entity are dramatic, and are more likely to result in prac- Global Burden of Disease study, a systematic analysis of tical interventions to reduce these deaths than a focus on global and regional mortality.1 In this report 17% of specific infectious agents or the major organ system neonatal deaths are classified as “sepsis and infectious dis- involved. orders of the newborn”; however another 15% of neonatal The International Consensus Conference on Pediatric deaths due to infections are not identified as death due Sepsis2 defines sepsis as the Systemic Inflammatory to sepsis The term “sepsis” is also excluded in the under Response Syndrome (SIRS) plus suspected or proven infec- 5 childhood deaths although 61% of deaths are due to infec- tion. From the clinician’s viewpoint, a diagnosis of sepsis tions such as malaria (20.8%), diarrheal diseases (11.9%) recognises that children who die from infections, regardless and lower respiratory infections (12.4%) which all lead to * Corresponding author. Tel.: þ1 604 875 2507. E-mail addresses: [email protected] (N. Kissoon), [email protected] (J. Carapetis). c Tel.: þ61 894897777. http://dx.doi.org/10.1016/j.jinf.2015.04.016 0163-4453/ª 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved. S22 N. Kissoon, J. Carapetis of their source, develop various combinations of septic healthcare workers are in short supply and care is being shock, cardiac failure, acute respiratory distress syndrome, delivered by teams with limited training and clinical skills. or other organ dysfunction. Indeed, the largest study of While recognition of specific diseases is important for children with severe febrile illness and impaired perfusion epidemiology, research and preventative measures in sub Saharan Africa support supports this contention.3 including vaccine development, the failure to highlight All deaths were due to a combination of severe shock and the syndrome of sepsis, regardless of the infecting organ- acidosis with or without respiratory and neurological ism(s), as a major killer and public health issue, is an dysfunction, findings which satisfy all the criteria for severe oversight with serious implications for the clinician because sepsis and septic shock.2 the most important interventions to reduce sepsis morbidity and mortality must be made generically and Clinical pathophysiological rationale for sepsis before a definitive diagnosis is available. Thus, calling attention to the need for time-sensitive treatment in severe infections is unlikely to happen if severe infections That severe infections leads to sepsis or severe sepsis and are compartmentalized in separate silos such as malaria, septic shock is supported by clinical and robust pathophys- pneumonia and diarrheal diseases.21 iologic evidence. From the clinician’s standpoint, it is often While much separation may be necessary to explore difficult to separate the three most common causes of better diagnostic and therapeutic strategies, such separa- death (pneumonia, malaria and diarrheal diseases) in tion is unnecessary for initial evaluation in which severe children with certainty. These conditions often co-exist infections will present with a limited number of danger and any or all, when severe, lead to sepsis and septic shock. signs and symptoms (Table 1, Fig. 1). The initial treatment For instance, cerebral malaria is associated with pneu- options for most of the severe infections that can lead to monia in 26e63% of cases as well as systemic activation of sepsis are also limited and are likely to include antimicro- the coagulation cascade.4 In addition, translocation of bac- bial administration (based on local infectious agents pro- terial components from the gut has been postulated for the file), fluid administration (based on ultra vascular volume endotoxemia, immune paralysis and increased risk of inva- status), blood products (based on hemoglobin levels), oxy- sive bacterial diseases with its increased morbidity and gen administration (based evaluation on oxygenation sta- mortality in malaria.5,6 Diarrheal illness beyond 14 days in- tus) and close monitoring.22 The WHO pocketbook creases the risk of pneumonia and 26% percent of pneu- Integrated Management of Childhood Illness uses this monia may be associated with recent diarrhea.7,8 Indeed, approach by highlighting danger signs and therapies rather pneumonia and diarrhea commonly coexist in children in than individual diseases. Highlighting sepsis and the few low income countries, and are frequently associated with e simple emergency therapeutic interventions needed will malnutrition with consequent high mortality.9 15 Diarrheal focus on the actual problems that confront clinicians in re- disease is also commonly associated with severe sepsis gions with limited resources. and septic shock with high mortality rates of 14% and 67% respectively.16 Thus clinicians require an approach that manages the complex syndrome (sepsis) rather than The stark reality for children in the developing focusing on a single disease entity which may result in world with severe infections another equally dangerous, condition being missed. A child presenting in shock may have any or all of pneumonia, ma- While sepsis accounts for a high proportion of under 5 laria, severe gastroenteritis, or other invasive bacterial deaths, most of these deaths occur in Sub Saharan Africa infection. Indeed, the best predictor of death of under 5 and Asia, areas in which the resources are fairly limited children with diarrhea following adequate vascular replen- (22,23 Fig. 2). However, financial resources, as reflected by ishment is classical severe sepsis: fever or hyperthermia the gross national income per capita, are not the only fac- associated with high leukocyte counts with immature leu- tor that determines under 5 mortality in children worldwide 17 kocytes in the blood and multi organ dysfunction. (24, Fig. 3). For instance, the gross national incomes of That many children with diarrheal disease are septic is not surprising because intestinal barrier dysfunction is associated with diarrheal infection. This dysfunction may Table 1 Signs and symptoms leading to suspicion of result in translocation of infectious by products which can infection. incite systemic cytokine production leading to SIRS and Any newborn Any child sepsis18,19 and T and B cell activation20 in children after e Feels feverish (hot) or cold e Not feeding natural cholera. Moreover, tumor necrosis factor alpha e Peri-umbilical pus, e Feeling cold (TNF Alpha) and interferon gamma (IFY) was increased in swelling or redness e Convulsions children with acute diarrhea as compared to uninfected e Poor or no sucking e Disoriented, difficult controls which results in a systemic inflammatory response (not feeding) to engage and sepsis.8 e Feeble or no cry e Repeated vomiting e Drowsy, difficult to arose e Severe breathing e Importance of highlighting sepsis Convulsions difficulties e Repeated vomiting e Severe breathing Highlighting sepsis as the end result of severe infections is difficulties not merely cosmetic but important for the provision of care especially in resource limited environments where skilled Pediatric sepsis in the developing world S23 This is not surprising when one considers the major barriers to care that face children with infections in resource limited areas in developing countries. In many cases a parent with a sick child has to walk several miles to a district clinic in which there may be a medical assistant or a nurse with two years training and with limited ability to provide care beyond antibiotics or antimicrobials and treatment of seizures with rectal medications. It is in the district hospital that the general practitioner and a nurse may be able to do simple tests such as malaria and parasite screening tests and provide intravenous medications and oxygen.28 Thus, there is a need to address the barriers to access as well as provision of care in district clinics and hos- pitals for children with serious infections leading to sepsis. Figure 1 Pathophysiology of severe infections leading to sepsis. The need for a broader conceptual framework South Africa and Malaysia are very similar, yet the under 5 Sepsis has clinical, social, economic and political origins mortality in South Africa is ten times that of Malaysia.
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