The Unbearable Lightness of Being Malnourished: Severe Acute Malnutrition Remains a Neglected Tropical Disease

The Unbearable Lightness of Being Malnourished: Severe Acute Malnutrition Remains a Neglected... In a brilliant display of insight, every article in the very first issue of Journal of Tropical Pediatrics, back in 1955, directly addressed malnutrition as the major underlying etiology of morbidity and mortality among children in the tropics. The topics covered by these articles spanned the range of issues in childhood malnutrition, including how health services should best be organized to address malnutrition [1], the influence of maternal malnutrition [2] and low birth weight [3], the importance of breastfeeding [4], effective complementary feeding [5] and the clinical manifestations of kwashiorkor [6, 7]. What was remarkably important for the global health agenda >60 years ago remains, tragically, just as relevant today. While dramatic improvements in childhood survival have been made over the last several decades [8], malnutrition (in all of its various forms) remains the underlying cause of death for nearly half of all children aged <5 years worldwide [9]. The final common pathway for many of these deaths is acute malnutrition, particularly severe acute malnutrition (SAM) [10], consisting of severe wasting (marasmus) and/or edematous malnutrition (kwashiorkor) (Fig. 1). Given the concordance of risk factors such as abject poverty, the lack of a varied high-quality diet, and frequent infections, most often SAM is superimposed on chronic malnutrition [11], which is clinically manifested as underweight and stunting [12]. Remarkable progress has been made in the management of SAM over the last couple of decades, most notably the development of systematic clinical protocols for inpatients that prioritize attention to life-threatening complications [13], and the development and endorsement of the community-based model of management for SAM [14]. When appropriate staffing, supplies, and systems are made available, these models of care can significantly decrease morbidity and mortality among some of the most vulnerable children imaginable [15]. Fig. 1. View largeDownload slide An educational poster at a health center in rural Malawi demonstrating two different forms of SAM: marasmus (left) and kwashiorkor (right). Fig. 1. View largeDownload slide An educational poster at a health center in rural Malawi demonstrating two different forms of SAM: marasmus (left) and kwashiorkor (right). Nevertheless, there is still a tremendous and urgent need for further progress—in an understanding of the underlying pathophysiology, the role of comorbidities, in the evidence base for diagnosis and management, in the development and implementation of improved inpatient and outpatient treatment protocols, and in the expansion of treatment coverage to broader geographic areas where more children can be diagnosed and treated. While the global community has (quite appropriately) brought renewed focus to the overwhelming burden of childhood tuberculosis, malaria, HIV, diarrhea, pneumonia, and a host of neglected tropical diseases, SAM remains tragically neglected in its own right [16]. Exemplifying this was the recent rejection of ready-to-use therapeutic food (RUTF)—the backbone of modern SAM therapies—from the World Health Organization’s Model List of Essential Medicines [17], joining the milk-based formulas F-75 and F-100 (the other cornerstones of SAM therapy) as exclusions from this important international reference. Unlike most diseases in tropical pediatrics, the actual underlying etiology of SAM unfortunately remains poorly understood. A host of recent studies have pointed in different and sometimes contradictory directions, including the role of aflatoxins [18], disruptions in the enteric microbiome [19], and a continued back-and-forth debate about the role of protein insufficiency in the pathogenesis of kwashiorkor [20, 21]. Why some children living in the same impoverished conditions, exposed to the same pathogens and environmental toxins, and eating the same poor diets become severely malnourished, while others in the same community manage to avoid this fate remains enigmatic. While the strengths of modern 21st century science have been brought to bear on the basic biology of tropical pediatric diseases as diverse as malaria, AIDS, and sickle cell anemia, SAM remains neglected in this respect. Such a disregard in the study of the fundamental risk factors, mechanism, and pathophysiologic changes associated with SAM necessarily hampers our ability to optimally prevent and treat SAM. Particularly important going forward would be a better understanding of the immunologic deficiencies and the role of acute infections in triggering acute relapses after SAM [22], as both early and delayed mortality because of infection remain disproportionately high. Given the myriad challenges in conducting high-quality clinical research in resource-limited hospitals throughout Africa and Asia, it is not surprising that the evidence base for the inpatient management of SAM remains relatively weak [23], with many recommendations outdated and lacking specific clinical trial evidence to support their use [24]. Improved attention to—and funding of—rigorous clinical trials can help challenge established dogma and advance practice that incorporates recent developments in critical care and takes advantage of modern therapeutic feeding products. Controversies and uncertainties linger about fluid resuscitation, antimicrobial usage, optimal feeding regimens, and a host of other issues. An example of important dilemmas in the management of SAM that have been successfully addressed with high-quality clinical trials and rigorous quality improvement methodologies is the appropriate use of RUTF in inpatient settings [25, 26]. The overwhelming majority of children with SAM can (and should) be successfully managed as outpatients in a community-based program using RUTF [27] and a short empiric course of antibiotics [28]. The maturation and spread of these programs has made it possible to reach orders of magnitude more children than could previously access care using traditional inpatient treatment protocols, which should now be restricted to those children with acute medical complications and/or difficulty accessing outpatient care [10]. However, as these programs have expanded, a number of important questions and challenges have emerged that provide the opportunity to more effectively identify and treat even more patients. This is one aspect of SAM that (relatively at least) has not been quite as neglected, with a number of recent high-quality trials that have helped inform optimal care and respond to some of the challenges reported by frontline health workers. One notable and encouraging aspect is that these studies are being conducted just as often by international nongovernmental organizations as by traditional academic researchers. This has, appropriately, meant that the dominant theme has been to improve the geographic coverage of care and accessibility to therapeutic food products in order to maximize the number of children that are identified and treated [29]. Among the major challenges in this field has been the need to develop new formulations of RUTF that are locally sustainable and culturally acceptable in diverse settings and appealing to diverse populations of children without compromising recovery rates. A number of new formulations have been tried with varying degrees of success [30–32], leading to growing optimism that we may be at the beginning of an era of more affordable foods customized and proven effective in local contexts. Streamlining service delivery for children with SAM at the community level has also been an important area of recent inquiry, with significant advances demonstrating the effectiveness of lower doses of RUTF in times of supply shortage [33] and the effectiveness of integrated programs that manage SAM and moderate acute malnutrition jointly [34]. In an important advance, it was demonstrated recently that access to care can also be improved for rural populations without significantly sacrificing outcomes in a treatment model that decreases the frequency of visits [35]. As community-level care for children with SAM proves its effectiveness, it becomes all the more important to identify malnourished children early. Several promising developments in this domain have been made as well, including developing diagnostic criteria for children <6 months of age [36] and those >5 years of age [37]. The expanded use and acceptance of the mid-upper arm circumference for screening and diagnosis has also meant that it may now be possible for mothers and other caregivers to diagnose many cases of SAM on their own at home, bringing their children to medical attention sooner and before they are as wasted or suffering from as many complications [38]. Nonetheless, better and more precise tools should be developed to detect and quantify the exact degree of malnutrition in each individual patient. Successes in decreasing mortality from SAM should not make the tropical pediatric community complacent, as effective methods to decrease relapse following recovery remain relatively lacking [39] and interventions to protect cognitive development among malnourished children only recently starting to be developed [40]. Discussions around childhood malnutrition are inherently fraught with political undertones [41], linked as the conversation is with agricultural interests, foreign aid, economic development, and ultimately conflicting perspectives on equity and inclusion for the most vulnerable members of society. SAM remains additionally marginalized and neglected from a scientific perspective. While some progress has been made in an understanding of the pathophysiology of the disease and in both inpatient and outpatient treatment programs, it is startling how little we still know about SAM considering how important a contributor it is to childhood morbidity and mortality worldwide. If ever there were a neglected tropical disease, it would be SAM. Following in the footsteps of our predecessors at the launch of this journal, we are not the first to argue that SAM needs more urgent consideration, nor—tragically—are we likely to be the last. Complacency is not an acceptable option. REFERENCES 1 Williams CD. The organisation of child health services in developing countries. J Trop Pediatr  1955; 1: 3– 8. Google Scholar CrossRef Search ADS   2 Sharma DC. Mother, child and nutrition. J Trop Pediatr  1955; 1: 47– 53. Google Scholar CrossRef Search ADS   3 Salber EJ. The significance of birth weight: as illustrated by a comparative study of South African racial groups. J Trop Pediatr  1955; 1: 54– 60. Google Scholar CrossRef Search ADS   4 Matthews DS. The ethnological and medical significance of breast feeding: with special reference to the Yorubas of Nigeria. J Trop Pediatr  1955; 1: 9– 24. Google Scholar CrossRef Search ADS   5 Welbourn HF. The danger period during weaning. J Trop Pediatr  1955; 1: 34– 46. Google Scholar CrossRef Search ADS   6 Jelliffe DB. Hypochromotrichia and malnutrition in Jamaican infants. J Trop Pediatr  1955; 1: 25– 33. Google Scholar CrossRef Search ADS   7 Mukherjee KL, Jelliffe DB. Clinical observations on kwashiorkor in Calcutta. J Trop Pediatr  1955; 1: 61– 6. Google Scholar CrossRef Search ADS   8 United Nations Children's Fund, World Health Organization, World Bank Group. Levels and Trends in Child Malnutrition—UNICEF/WHO/World Bank Group Joint Child Malnutrition Estimates . New York, NY: UNICEF/WHO/World Bank Group, 2017. 9 Black RE, Victora CG, Walker SP, et al.   Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet  2013; 382: 427– 51. Google Scholar CrossRef Search ADS PubMed  10 Bhutta ZA, Berkley JA, Bandsma RHJ, et al.   Severe childhood malnutrition. Nat Rev Dis Primers  2017; 3: 17067. Google Scholar CrossRef Search ADS PubMed  11 Khara T, Mwangome M, Ngari M, et al.   Children concurrently wasted and stunted: a meta-analysis of prevalence data of children 6-59 months from 84 countries. Matern Child Nutr  2018, in press. doi: 10.1111/mcn.12516. 12 Bose A. Let's talk about stunting. J Trop Pediatr  2018, doi: 10.1093/tropej/fmx104. 13 WHO. Management of Severe Malnutrition: A Manual for Physicians and Other Senior Health Workers . Geneva: World Health Organization, 1999. 14 WHO, WFP, UNSCN, UNICEF. Community-Based Management of Severe Acute Malnutrition . Geneva: World Health Organization, World Food Programme, United Nations System Standing Committee on Nutrition, United Nations Children's Fund, 2007. 15 Hossain M, Chisti MJ, Hossain MI, et al.   Efficacy of World Health Organization guideline in facility-based reduction of mortality in severely malnourished children from low and middle income countries: a systematic review and meta-analysis. J Paediatr Child Health  2017; 53: 474– 9. Google Scholar CrossRef Search ADS PubMed  16 Gross R, Webb P. Wasting time for wasted children: severe child undernutrition must be resolved in non-emergency settings. Lancet  2006; 367: 1209– 11. Google Scholar CrossRef Search ADS PubMed  17 Williams PCM, Berkley JA. Severe Acute Malnutrition Update: Current WHO Guidelines and the WHO Essential Medicine List for Children . Geneva: World Health Organization Department of Maternal, Newborn, Child and Adolescent Health, 2016. 18 McMillan A, Renaud JB, Burgess KMN, et al.   Aflatoxin exposure in Nigerian children with severe acute malnutrition. Food Chem Toxicol  2017; 111: 356– 62. Google Scholar CrossRef Search ADS PubMed  19 Million M, Diallo A, Raoult D. Gut microbiota and malnutrition. Microb Pathog  2017; 106: 127– 38. Google Scholar CrossRef Search ADS PubMed  20 Coulthard MG. Oedema in kwashiorkor is caused by hypoalbuminaemia. Paediatr Int Child Health  2015; 35: 83– 9. Google Scholar CrossRef Search ADS PubMed  21 Golden MH. Nutritional and other types of oedema, albumin, complex carbohydrates and the interstitium—a response to Malcolm Coulthard's hypothesis: oedema in kwashiorkor is caused by hypo-albuminaemia. Paediatr Int Child Health  2015; 35: 90– 109. Google Scholar CrossRef Search ADS PubMed  22 Ibrahim MK, Zambruni M, Melby CL, Melby PC. Impact of childhood malnutrition on host defense and infection. Clin Microbiol Rev  2017; 30: 919– 71. Google Scholar CrossRef Search ADS PubMed  23 Webb P. How strong is our evidence for effective management of wasting? A review of systematic and other reviews. Food Nutr Bull  2015; 36: S65– 71. Google Scholar CrossRef Search ADS PubMed  24 Tickell KD, Denno DM. Inpatient management of children with severe acute malnutrition: a review of WHO guidelines. Bull World Health Organ  2016; 94: 642– 51. Google Scholar CrossRef Search ADS PubMed  25 Lanyero B, Namusoke H, Nabukeera-Barungi N, et al.   Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda. Nutr J  2017; 16: 52. Google Scholar CrossRef Search ADS PubMed  26 Versloot CJ, Voskuijl W, van Vliet SJ, et al.   Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi. BMC Pediatr  2017; 17: 112. Google Scholar CrossRef Search ADS PubMed  27 Trehan I, Manary MJ. Management of severe acute malnutrition in low-income and middle-income countries. Arch Dis Child  2015; 100: 283– 7. Google Scholar CrossRef Search ADS PubMed  28 Million M, Lagier JC, Raoult D. Meta-analysis on efficacy of amoxicillin in uncomplicated severe acute malnutrition. Microb Pathog  2017; 106: 76– 7. Google Scholar CrossRef Search ADS PubMed  29 Action Against Hunger. SAM 2020: An Agenda for Scaling-up the Management of Severe Acute Malnutrition by 2020 . New York, NY: Action Against Hunger, 2015. 30 Bahwere P, Balaluka B, Wells JC, et al.   Cereals and pulse-based ready-to-use therapeutic food as an alternative to the standard milk- and peanut paste-based formulation for treating severe acute malnutrition: a noninferiority, individually randomized controlled efficacy clinical trial. Am J Clin Nutr  2016; 103: 1145– 61. Google Scholar CrossRef Search ADS PubMed  31 Weber JM, Ryan KN, Tandon R, et al.   Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India. Matern Child Nutr  2017; 13: e12250. Google Scholar CrossRef Search ADS   32 Bahwere P, Akomo P, Mwale M, et al.   Soya, maize, and sorghum-based ready-to-use therapeutic food with amino acid is as efficacious as the standard milk and peanut paste-based formulation for the treatment of severe acute malnutrition in children: a noninferiority individually randomized controlled efficacy clinical trial in Malawi. Am J Clin Nutr  2017; 106: 1100– 12. Google Scholar CrossRef Search ADS PubMed  33 James PT, Van den Briel N, Rozet A, et al.   Low-dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar. Matern Child Nutr  2015; 11: 859– 69. Google Scholar CrossRef Search ADS PubMed  34 Maust A, Koroma AS, Abla C, et al.   Severe and moderate acute malnutrition can be successfully managed with an integrated protocol in Sierra Leone. J Nutr  2015; 145: 2604– 9. Google Scholar CrossRef Search ADS PubMed  35 Isanaka S, Kodish SR, Berthe F, et al.   Outpatient treatment of severe acute malnutrition: response to treatment with a reduced schedule of therapeutic food distribution. Am J Clin Nutr  2017; 105: 1191– 7. Google Scholar CrossRef Search ADS PubMed  36 Mwangome M, Ngari M, Fegan G, et al.   Diagnostic criteria for severe acute malnutrition among infants aged under 6 mo. Am J Clin Nutr  2017; 105: 1415– 23. Google Scholar PubMed  37 Mramba L, Ngari M, Mwangome M, et al.   A growth reference for mid upper arm circumference for age among school age children and adolescents, and validation for mortality: growth curve construction and longitudinal cohort study. BMJ  2017; 358: j3423. Google Scholar CrossRef Search ADS PubMed  38 Ale FG, Phelan KP, Issa H, et al.   Mothers screening for malnutrition by mid-upper arm circumference is non-inferior to community health workers: results from a large-scale pragmatic trial in rural Niger. Arch Public Health  2016; 74: 38. Google Scholar CrossRef Search ADS PubMed  39 Berkley JA, Ngari M, Thitiri J, et al.   Daily co-trimoxazole prophylaxis to prevent mortality amongst children with complicated severe acute malnutrition: a randomised, double-blind, placebo controlled trial. Lancet Glob Health  2016; 4: e464– 73. Google Scholar CrossRef Search ADS PubMed  40 Roberts SB, Franceschini MA, Krauss A, et al.   A pilot randomized controlled trial of a new supplementary food designed to enhance cognitive performance during prevention and treatment of malnutrition in childhood. Curr Dev Nutr  2017; 1: e000885. Google Scholar CrossRef Search ADS PubMed  41 Nisbett N, Gillespie S, Haddad L, et al.   Why worry about the politics of childhood undernutrition? World Dev  2014; 64: 420– 33. Google Scholar CrossRef Search ADS   © The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Tropical Pediatrics Oxford University Press

The Unbearable Lightness of Being Malnourished: Severe Acute Malnutrition Remains a Neglected Tropical Disease

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Abstract

In a brilliant display of insight, every article in the very first issue of Journal of Tropical Pediatrics, back in 1955, directly addressed malnutrition as the major underlying etiology of morbidity and mortality among children in the tropics. The topics covered by these articles spanned the range of issues in childhood malnutrition, including how health services should best be organized to address malnutrition [1], the influence of maternal malnutrition [2] and low birth weight [3], the importance of breastfeeding [4], effective complementary feeding [5] and the clinical manifestations of kwashiorkor [6, 7]. What was remarkably important for the global health agenda >60 years ago remains, tragically, just as relevant today. While dramatic improvements in childhood survival have been made over the last several decades [8], malnutrition (in all of its various forms) remains the underlying cause of death for nearly half of all children aged <5 years worldwide [9]. The final common pathway for many of these deaths is acute malnutrition, particularly severe acute malnutrition (SAM) [10], consisting of severe wasting (marasmus) and/or edematous malnutrition (kwashiorkor) (Fig. 1). Given the concordance of risk factors such as abject poverty, the lack of a varied high-quality diet, and frequent infections, most often SAM is superimposed on chronic malnutrition [11], which is clinically manifested as underweight and stunting [12]. Remarkable progress has been made in the management of SAM over the last couple of decades, most notably the development of systematic clinical protocols for inpatients that prioritize attention to life-threatening complications [13], and the development and endorsement of the community-based model of management for SAM [14]. When appropriate staffing, supplies, and systems are made available, these models of care can significantly decrease morbidity and mortality among some of the most vulnerable children imaginable [15]. Fig. 1. View largeDownload slide An educational poster at a health center in rural Malawi demonstrating two different forms of SAM: marasmus (left) and kwashiorkor (right). Fig. 1. View largeDownload slide An educational poster at a health center in rural Malawi demonstrating two different forms of SAM: marasmus (left) and kwashiorkor (right). Nevertheless, there is still a tremendous and urgent need for further progress—in an understanding of the underlying pathophysiology, the role of comorbidities, in the evidence base for diagnosis and management, in the development and implementation of improved inpatient and outpatient treatment protocols, and in the expansion of treatment coverage to broader geographic areas where more children can be diagnosed and treated. While the global community has (quite appropriately) brought renewed focus to the overwhelming burden of childhood tuberculosis, malaria, HIV, diarrhea, pneumonia, and a host of neglected tropical diseases, SAM remains tragically neglected in its own right [16]. Exemplifying this was the recent rejection of ready-to-use therapeutic food (RUTF)—the backbone of modern SAM therapies—from the World Health Organization’s Model List of Essential Medicines [17], joining the milk-based formulas F-75 and F-100 (the other cornerstones of SAM therapy) as exclusions from this important international reference. Unlike most diseases in tropical pediatrics, the actual underlying etiology of SAM unfortunately remains poorly understood. A host of recent studies have pointed in different and sometimes contradictory directions, including the role of aflatoxins [18], disruptions in the enteric microbiome [19], and a continued back-and-forth debate about the role of protein insufficiency in the pathogenesis of kwashiorkor [20, 21]. Why some children living in the same impoverished conditions, exposed to the same pathogens and environmental toxins, and eating the same poor diets become severely malnourished, while others in the same community manage to avoid this fate remains enigmatic. While the strengths of modern 21st century science have been brought to bear on the basic biology of tropical pediatric diseases as diverse as malaria, AIDS, and sickle cell anemia, SAM remains neglected in this respect. Such a disregard in the study of the fundamental risk factors, mechanism, and pathophysiologic changes associated with SAM necessarily hampers our ability to optimally prevent and treat SAM. Particularly important going forward would be a better understanding of the immunologic deficiencies and the role of acute infections in triggering acute relapses after SAM [22], as both early and delayed mortality because of infection remain disproportionately high. Given the myriad challenges in conducting high-quality clinical research in resource-limited hospitals throughout Africa and Asia, it is not surprising that the evidence base for the inpatient management of SAM remains relatively weak [23], with many recommendations outdated and lacking specific clinical trial evidence to support their use [24]. Improved attention to—and funding of—rigorous clinical trials can help challenge established dogma and advance practice that incorporates recent developments in critical care and takes advantage of modern therapeutic feeding products. Controversies and uncertainties linger about fluid resuscitation, antimicrobial usage, optimal feeding regimens, and a host of other issues. An example of important dilemmas in the management of SAM that have been successfully addressed with high-quality clinical trials and rigorous quality improvement methodologies is the appropriate use of RUTF in inpatient settings [25, 26]. The overwhelming majority of children with SAM can (and should) be successfully managed as outpatients in a community-based program using RUTF [27] and a short empiric course of antibiotics [28]. The maturation and spread of these programs has made it possible to reach orders of magnitude more children than could previously access care using traditional inpatient treatment protocols, which should now be restricted to those children with acute medical complications and/or difficulty accessing outpatient care [10]. However, as these programs have expanded, a number of important questions and challenges have emerged that provide the opportunity to more effectively identify and treat even more patients. This is one aspect of SAM that (relatively at least) has not been quite as neglected, with a number of recent high-quality trials that have helped inform optimal care and respond to some of the challenges reported by frontline health workers. One notable and encouraging aspect is that these studies are being conducted just as often by international nongovernmental organizations as by traditional academic researchers. This has, appropriately, meant that the dominant theme has been to improve the geographic coverage of care and accessibility to therapeutic food products in order to maximize the number of children that are identified and treated [29]. Among the major challenges in this field has been the need to develop new formulations of RUTF that are locally sustainable and culturally acceptable in diverse settings and appealing to diverse populations of children without compromising recovery rates. A number of new formulations have been tried with varying degrees of success [30–32], leading to growing optimism that we may be at the beginning of an era of more affordable foods customized and proven effective in local contexts. Streamlining service delivery for children with SAM at the community level has also been an important area of recent inquiry, with significant advances demonstrating the effectiveness of lower doses of RUTF in times of supply shortage [33] and the effectiveness of integrated programs that manage SAM and moderate acute malnutrition jointly [34]. In an important advance, it was demonstrated recently that access to care can also be improved for rural populations without significantly sacrificing outcomes in a treatment model that decreases the frequency of visits [35]. As community-level care for children with SAM proves its effectiveness, it becomes all the more important to identify malnourished children early. Several promising developments in this domain have been made as well, including developing diagnostic criteria for children <6 months of age [36] and those >5 years of age [37]. The expanded use and acceptance of the mid-upper arm circumference for screening and diagnosis has also meant that it may now be possible for mothers and other caregivers to diagnose many cases of SAM on their own at home, bringing their children to medical attention sooner and before they are as wasted or suffering from as many complications [38]. Nonetheless, better and more precise tools should be developed to detect and quantify the exact degree of malnutrition in each individual patient. Successes in decreasing mortality from SAM should not make the tropical pediatric community complacent, as effective methods to decrease relapse following recovery remain relatively lacking [39] and interventions to protect cognitive development among malnourished children only recently starting to be developed [40]. Discussions around childhood malnutrition are inherently fraught with political undertones [41], linked as the conversation is with agricultural interests, foreign aid, economic development, and ultimately conflicting perspectives on equity and inclusion for the most vulnerable members of society. SAM remains additionally marginalized and neglected from a scientific perspective. While some progress has been made in an understanding of the pathophysiology of the disease and in both inpatient and outpatient treatment programs, it is startling how little we still know about SAM considering how important a contributor it is to childhood morbidity and mortality worldwide. If ever there were a neglected tropical disease, it would be SAM. Following in the footsteps of our predecessors at the launch of this journal, we are not the first to argue that SAM needs more urgent consideration, nor—tragically—are we likely to be the last. Complacency is not an acceptable option. REFERENCES 1 Williams CD. The organisation of child health services in developing countries. J Trop Pediatr  1955; 1: 3– 8. Google Scholar CrossRef Search ADS   2 Sharma DC. Mother, child and nutrition. J Trop Pediatr  1955; 1: 47– 53. Google Scholar CrossRef Search ADS   3 Salber EJ. The significance of birth weight: as illustrated by a comparative study of South African racial groups. J Trop Pediatr  1955; 1: 54– 60. Google Scholar CrossRef Search ADS   4 Matthews DS. The ethnological and medical significance of breast feeding: with special reference to the Yorubas of Nigeria. J Trop Pediatr  1955; 1: 9– 24. Google Scholar CrossRef Search ADS   5 Welbourn HF. The danger period during weaning. J Trop Pediatr  1955; 1: 34– 46. Google Scholar CrossRef Search ADS   6 Jelliffe DB. Hypochromotrichia and malnutrition in Jamaican infants. J Trop Pediatr  1955; 1: 25– 33. Google Scholar CrossRef Search ADS   7 Mukherjee KL, Jelliffe DB. Clinical observations on kwashiorkor in Calcutta. J Trop Pediatr  1955; 1: 61– 6. Google Scholar CrossRef Search ADS   8 United Nations Children's Fund, World Health Organization, World Bank Group. Levels and Trends in Child Malnutrition—UNICEF/WHO/World Bank Group Joint Child Malnutrition Estimates . New York, NY: UNICEF/WHO/World Bank Group, 2017. 9 Black RE, Victora CG, Walker SP, et al.   Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet  2013; 382: 427– 51. Google Scholar CrossRef Search ADS PubMed  10 Bhutta ZA, Berkley JA, Bandsma RHJ, et al.   Severe childhood malnutrition. Nat Rev Dis Primers  2017; 3: 17067. Google Scholar CrossRef Search ADS PubMed  11 Khara T, Mwangome M, Ngari M, et al.   Children concurrently wasted and stunted: a meta-analysis of prevalence data of children 6-59 months from 84 countries. Matern Child Nutr  2018, in press. doi: 10.1111/mcn.12516. 12 Bose A. Let's talk about stunting. J Trop Pediatr  2018, doi: 10.1093/tropej/fmx104. 13 WHO. Management of Severe Malnutrition: A Manual for Physicians and Other Senior Health Workers . Geneva: World Health Organization, 1999. 14 WHO, WFP, UNSCN, UNICEF. Community-Based Management of Severe Acute Malnutrition . Geneva: World Health Organization, World Food Programme, United Nations System Standing Committee on Nutrition, United Nations Children's Fund, 2007. 15 Hossain M, Chisti MJ, Hossain MI, et al.   Efficacy of World Health Organization guideline in facility-based reduction of mortality in severely malnourished children from low and middle income countries: a systematic review and meta-analysis. J Paediatr Child Health  2017; 53: 474– 9. Google Scholar CrossRef Search ADS PubMed  16 Gross R, Webb P. Wasting time for wasted children: severe child undernutrition must be resolved in non-emergency settings. Lancet  2006; 367: 1209– 11. Google Scholar CrossRef Search ADS PubMed  17 Williams PCM, Berkley JA. Severe Acute Malnutrition Update: Current WHO Guidelines and the WHO Essential Medicine List for Children . Geneva: World Health Organization Department of Maternal, Newborn, Child and Adolescent Health, 2016. 18 McMillan A, Renaud JB, Burgess KMN, et al.   Aflatoxin exposure in Nigerian children with severe acute malnutrition. Food Chem Toxicol  2017; 111: 356– 62. Google Scholar CrossRef Search ADS PubMed  19 Million M, Diallo A, Raoult D. Gut microbiota and malnutrition. Microb Pathog  2017; 106: 127– 38. Google Scholar CrossRef Search ADS PubMed  20 Coulthard MG. Oedema in kwashiorkor is caused by hypoalbuminaemia. Paediatr Int Child Health  2015; 35: 83– 9. Google Scholar CrossRef Search ADS PubMed  21 Golden MH. Nutritional and other types of oedema, albumin, complex carbohydrates and the interstitium—a response to Malcolm Coulthard's hypothesis: oedema in kwashiorkor is caused by hypo-albuminaemia. Paediatr Int Child Health  2015; 35: 90– 109. Google Scholar CrossRef Search ADS PubMed  22 Ibrahim MK, Zambruni M, Melby CL, Melby PC. Impact of childhood malnutrition on host defense and infection. Clin Microbiol Rev  2017; 30: 919– 71. Google Scholar CrossRef Search ADS PubMed  23 Webb P. How strong is our evidence for effective management of wasting? A review of systematic and other reviews. Food Nutr Bull  2015; 36: S65– 71. Google Scholar CrossRef Search ADS PubMed  24 Tickell KD, Denno DM. Inpatient management of children with severe acute malnutrition: a review of WHO guidelines. Bull World Health Organ  2016; 94: 642– 51. Google Scholar CrossRef Search ADS PubMed  25 Lanyero B, Namusoke H, Nabukeera-Barungi N, et al.   Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda. Nutr J  2017; 16: 52. Google Scholar CrossRef Search ADS PubMed  26 Versloot CJ, Voskuijl W, van Vliet SJ, et al.   Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi. BMC Pediatr  2017; 17: 112. Google Scholar CrossRef Search ADS PubMed  27 Trehan I, Manary MJ. Management of severe acute malnutrition in low-income and middle-income countries. Arch Dis Child  2015; 100: 283– 7. Google Scholar CrossRef Search ADS PubMed  28 Million M, Lagier JC, Raoult D. Meta-analysis on efficacy of amoxicillin in uncomplicated severe acute malnutrition. Microb Pathog  2017; 106: 76– 7. Google Scholar CrossRef Search ADS PubMed  29 Action Against Hunger. SAM 2020: An Agenda for Scaling-up the Management of Severe Acute Malnutrition by 2020 . New York, NY: Action Against Hunger, 2015. 30 Bahwere P, Balaluka B, Wells JC, et al.   Cereals and pulse-based ready-to-use therapeutic food as an alternative to the standard milk- and peanut paste-based formulation for treating severe acute malnutrition: a noninferiority, individually randomized controlled efficacy clinical trial. Am J Clin Nutr  2016; 103: 1145– 61. Google Scholar CrossRef Search ADS PubMed  31 Weber JM, Ryan KN, Tandon R, et al.   Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India. Matern Child Nutr  2017; 13: e12250. Google Scholar CrossRef Search ADS   32 Bahwere P, Akomo P, Mwale M, et al.   Soya, maize, and sorghum-based ready-to-use therapeutic food with amino acid is as efficacious as the standard milk and peanut paste-based formulation for the treatment of severe acute malnutrition in children: a noninferiority individually randomized controlled efficacy clinical trial in Malawi. 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Journal

Journal of Tropical PediatricsOxford University Press

Published: Jan 5, 2018

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