Skip to main content
Top
Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Opinion

Integrated fever management: disease severity markers to triage children with malaria and non-malarial febrile illness

Authors: Chloe R. McDonald, Andrea Weckman, Melissa Richard-Greenblatt, Aleksandra Leligdowicz, Kevin C. Kain

Published in: Malaria Journal | Issue 1/2018

Login to get access

Abstract

Febrile symptoms in children are a leading cause of health-care seeking behaviour worldwide. The majority of febrile illnesses are uncomplicated and self-limited, without the need for referral or hospital admission. However, current diagnostic tools are unable to identify which febrile children have self-limited infection and which children are at risk of progressing to life-threatening infections, such as severe malaria. This paper describes the need for a simple community-based tool that can improve the early recognition and triage of febrile children, with either malarial or non-malarial illness, at risk of critical illness. The integration of a disease severity marker into existing malaria rapid diagnostic tests (RDT) could enable detection of children at risk of severe infection in the hospital and community, irrespective of aetiology. Incorporation of a disease severity marker could inform individualized management and early triage of children at risk of life-threatening infection. A child positive for both malaria and a disease severity marker could be prioritized for urgent referral/admission and parenteral therapy. A child positive for malaria and negative for a disease severity marker could be managed conservatively, as an out-patient, with oral anti-malarial therapy. An RDT with a disease severity marker could facilitate an integrated community-based approach to fever syndromes and improve early recognition, risk stratification, and prompt treatment of severe malaria and other life-threatening infections.
Literature
1.
go back to reference de Bont EG, Lepot JM, Hendrix DA, Loonen N, Guldemond-Hecker Y, Dinant GJ, et al. Workload and management of childhood fever at general practice out-of-hours care: an observational cohort study. BMJ Open. 2015;5:e007365.CrossRefPubMedCentral de Bont EG, Lepot JM, Hendrix DA, Loonen N, Guldemond-Hecker Y, Dinant GJ, et al. Workload and management of childhood fever at general practice out-of-hours care: an observational cohort study. BMJ Open. 2015;5:e007365.CrossRefPubMedCentral
2.
go back to reference WHO. Informal consultation on fever management in peripheral health care settings: a global review of evicence and practice. Geneva: World Health Organization; 2013. WHO. Informal consultation on fever management in peripheral health care settings: a global review of evicence and practice. Geneva: World Health Organization; 2013.
3.
go back to reference Hay SI, Guerra CA, Tatem AJ, Noor AM, Snow RW. The global distribution and population at risk of malaria: past, present, and future. Lancet Infect Dis. 2004;4:327–36.CrossRefPubMedCentral Hay SI, Guerra CA, Tatem AJ, Noor AM, Snow RW. The global distribution and population at risk of malaria: past, present, and future. Lancet Infect Dis. 2004;4:327–36.CrossRefPubMedCentral
4.
go back to reference Christensen SS, Eslick GD. Cerebral malaria as a risk factor for the development of epilepsy and other long-term neurological conditions: a meta-analysis. Trans R Soc Trop Med Hyg. 2015;109:233–8.CrossRefPubMedCentral Christensen SS, Eslick GD. Cerebral malaria as a risk factor for the development of epilepsy and other long-term neurological conditions: a meta-analysis. Trans R Soc Trop Med Hyg. 2015;109:233–8.CrossRefPubMedCentral
5.
go back to reference Bangirana P, Menk J, John CC, Boivin MJ, Hodges JS. The association between cognition and academic performance in Ugandan children surviving malaria with neurological involvement. PLoS One. 2013;8:e55653.CrossRefPubMedCentral Bangirana P, Menk J, John CC, Boivin MJ, Hodges JS. The association between cognition and academic performance in Ugandan children surviving malaria with neurological involvement. PLoS One. 2013;8:e55653.CrossRefPubMedCentral
6.
go back to reference Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res. 2010;68:267–74.CrossRefPubMedCentral Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res. 2010;68:267–74.CrossRefPubMedCentral
7.
go back to reference WHO. World malaria report 2017. Geneva: World Health Organization; 2017. WHO. World malaria report 2017. Geneva: World Health Organization; 2017.
8.
go back to reference Hopkins H, Bruxvoort KJ, Cairns ME, Chandler CI, Leurent B, Ansah EK, et al. Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings. BMJ. 2017;356:j1054.CrossRefPubMedCentral Hopkins H, Bruxvoort KJ, Cairns ME, Chandler CI, Leurent B, Ansah EK, et al. Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings. BMJ. 2017;356:j1054.CrossRefPubMedCentral
9.
go back to reference Bruxvoort KJ, Leurent B, Chandler CIR, Ansah EK, Baiden F, Bjorkman A, et al. The impact of introducing malaria rapid diagnostic tests on fever case management: a synthesis of ten studies from the ACT Consortium. Am J Trop Med Hyg. 2017;97:1170–9.CrossRefPubMedCentral Bruxvoort KJ, Leurent B, Chandler CIR, Ansah EK, Baiden F, Bjorkman A, et al. The impact of introducing malaria rapid diagnostic tests on fever case management: a synthesis of ten studies from the ACT Consortium. Am J Trop Med Hyg. 2017;97:1170–9.CrossRefPubMedCentral
10.
go back to reference Nolan T, Angos P, Cunha AJ, Muhe L, Qazi S, Simoes EA, et al. Quality of hospital care for seriously ill children in less-developed countries. Lancet. 2001;357:106–10.CrossRefPubMedCentral Nolan T, Angos P, Cunha AJ, Muhe L, Qazi S, Simoes EA, et al. Quality of hospital care for seriously ill children in less-developed countries. Lancet. 2001;357:106–10.CrossRefPubMedCentral
11.
go back to reference Molyneux E, Ahmad S, Robertson A. Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting. Bull World Health Organ. 2006;84:314–9.CrossRefPubMedCentral Molyneux E, Ahmad S, Robertson A. Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting. Bull World Health Organ. 2006;84:314–9.CrossRefPubMedCentral
12.
go back to reference Makumbe B, Tshuma C, Shambira G, Mungati M, Gombe NT, Bangure D, et al. Evaluation of severe malaria case management in Mazowe District, Zimbabwe, 2014. Pan Afr Med J. 2017;27:33.CrossRefPubMedCentral Makumbe B, Tshuma C, Shambira G, Mungati M, Gombe NT, Bangure D, et al. Evaluation of severe malaria case management in Mazowe District, Zimbabwe, 2014. Pan Afr Med J. 2017;27:33.CrossRefPubMedCentral
13.
go back to reference Fernando SM, Rochwerg B, Reardon PM, Thavorn K, Seely AJE, Perry JJ, et al. Emergency Department disposition decisions and associated mortality and costs in ICU patients with suspected infection. Crit Care. 2018;22:172.CrossRefPubMedCentral Fernando SM, Rochwerg B, Reardon PM, Thavorn K, Seely AJE, Perry JJ, et al. Emergency Department disposition decisions and associated mortality and costs in ICU patients with suspected infection. Crit Care. 2018;22:172.CrossRefPubMedCentral
14.
go back to reference Achan J, Tibenderana J, Kyabayinze D, Mawejje H, Mugizi R, Mpeka B, et al. Case management of severe malaria–a forgotten practice: experiences from health facilities in Uganda. PLoS One. 2011;6:e17053.CrossRefPubMedCentral Achan J, Tibenderana J, Kyabayinze D, Mawejje H, Mugizi R, Mpeka B, et al. Case management of severe malaria–a forgotten practice: experiences from health facilities in Uganda. PLoS One. 2011;6:e17053.CrossRefPubMedCentral
15.
go back to reference Zurovac D, Machini B, Kiptui R, Memusi D, Amboko B, Kigen S, et al. Monitoring health systems readiness and inpatient malaria case-management at Kenyan county hospitals. Malar J. 2018;17:213.CrossRefPubMedCentral Zurovac D, Machini B, Kiptui R, Memusi D, Amboko B, Kigen S, et al. Monitoring health systems readiness and inpatient malaria case-management at Kenyan county hospitals. Malar J. 2018;17:213.CrossRefPubMedCentral
16.
go back to reference Namuyinga RJ, Mwandama D, Moyo D, Gumbo A, Troell P, Kobayashi M, et al. Health worker adherence to malaria treatment guidelines at outpatient health facilities in southern Malawi following implementation of universal access to diagnostic testing. Malar J. 2017;16:40.CrossRefPubMedCentral Namuyinga RJ, Mwandama D, Moyo D, Gumbo A, Troell P, Kobayashi M, et al. Health worker adherence to malaria treatment guidelines at outpatient health facilities in southern Malawi following implementation of universal access to diagnostic testing. Malar J. 2017;16:40.CrossRefPubMedCentral
17.
go back to reference Conroy AL, Hawkes M, Elphinstone RE, Morgan C, Hermann L, Barker KR, et al. Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality. Open Forum Infect Dis. 2016;3:ofw046.CrossRefPubMedCentral Conroy AL, Hawkes M, Elphinstone RE, Morgan C, Hermann L, Barker KR, et al. Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality. Open Forum Infect Dis. 2016;3:ofw046.CrossRefPubMedCentral
18.
go back to reference Ricciuto DR, dos Santos CC, Hawkes M, Toltl LJ, Conroy AL, Rajwans N, et al. Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis. Crit Care Med. 2011;39:702–10.CrossRefPubMedCentral Ricciuto DR, dos Santos CC, Hawkes M, Toltl LJ, Conroy AL, Rajwans N, et al. Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis. Crit Care Med. 2011;39:702–10.CrossRefPubMedCentral
19.
go back to reference Valim C, Ahmad R, Lanaspa M, Tan Y, Acacio S, Gillette MA, et al. Responses to bacteria, virus, and malaria distinguish the etiology of pediatric clinical pneumonia. Am J Respir Crit Care Med. 2016;193:448–59.CrossRefPubMedCentral Valim C, Ahmad R, Lanaspa M, Tan Y, Acacio S, Gillette MA, et al. Responses to bacteria, virus, and malaria distinguish the etiology of pediatric clinical pneumonia. Am J Respir Crit Care Med. 2016;193:448–59.CrossRefPubMedCentral
20.
go back to reference Erdman LK, Petes C, Lu Z, Dhabangi A, Musoke C, Cserti-Gazdewich CM, et al. Chitinase 3-like 1 is induced by Plasmodium falciparum malaria and predicts outcome of cerebral malaria and severe malarial anaemia in a case-control study of African children. Malar J. 2014;13:279.CrossRefPubMedCentral Erdman LK, Petes C, Lu Z, Dhabangi A, Musoke C, Cserti-Gazdewich CM, et al. Chitinase 3-like 1 is induced by Plasmodium falciparum malaria and predicts outcome of cerebral malaria and severe malarial anaemia in a case-control study of African children. Malar J. 2014;13:279.CrossRefPubMedCentral
21.
go back to reference Erdman LK, Dhabangi A, Musoke C, Conroy AL, Hawkes M, Higgins S, et al. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study. PLoS One. 2011;6:e17440.CrossRefPubMedCentral Erdman LK, Dhabangi A, Musoke C, Conroy AL, Hawkes M, Higgins S, et al. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study. PLoS One. 2011;6:e17440.CrossRefPubMedCentral
22.
go back to reference Mikacenic C, Hahn WO, Price BL, Harju-Baker S, Katz R, Kain KC, et al. Biomarkers of endothelial activation are associated with poor outcome in critical illness. PLoS One. 2015;10:e0141251.CrossRefPubMedCentral Mikacenic C, Hahn WO, Price BL, Harju-Baker S, Katz R, Kain KC, et al. Biomarkers of endothelial activation are associated with poor outcome in critical illness. PLoS One. 2015;10:e0141251.CrossRefPubMedCentral
23.
go back to reference Poukoulidou T, Spyridaki A, Mihailidou I, Kopterides P, Pistiki A, Alexiou Z, et al. TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen. BMC Infect Dis. 2011;11:309.CrossRefPubMedCentral Poukoulidou T, Spyridaki A, Mihailidou I, Kopterides P, Pistiki A, Alexiou Z, et al. TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen. BMC Infect Dis. 2011;11:309.CrossRefPubMedCentral
24.
go back to reference Xing K, Murthy S, Liles WC, Singh JM. Clinical utility of biomarkers of endothelial activation in sepsis–a systematic review. Crit Care. 2012;16:R7.CrossRefPubMedCentral Xing K, Murthy S, Liles WC, Singh JM. Clinical utility of biomarkers of endothelial activation in sepsis–a systematic review. Crit Care. 2012;16:R7.CrossRefPubMedCentral
25.
26.
go back to reference Leligdowicz A, Richard-Greenblatt M, Wright J, Crowley VM, Kain KC. Endothelial activation: the Ang/Tie axis in sepsis. Front Immunol. 2018;9:838.CrossRefPubMedCentral Leligdowicz A, Richard-Greenblatt M, Wright J, Crowley VM, Kain KC. Endothelial activation: the Ang/Tie axis in sepsis. Front Immunol. 2018;9:838.CrossRefPubMedCentral
27.
go back to reference Kim H, Higgins S, Liles WC, Kain KC. Endothelial activation and dysregulation in malaria: a potential target for novel therapeutics. Curr Opin Hematol. 2011;18:177–85.CrossRefPubMedCentral Kim H, Higgins S, Liles WC, Kain KC. Endothelial activation and dysregulation in malaria: a potential target for novel therapeutics. Curr Opin Hematol. 2011;18:177–85.CrossRefPubMedCentral
28.
go back to reference Ghosh CC, David S, Zhang R, Berghelli A, Milam K, Higgins SJ, et al. Gene control of tyrosine kinase TIE2 and vascular manifestations of infections. Proc Natl Acad Sci USA. 2016;113:2472–7.CrossRefPubMedCentral Ghosh CC, David S, Zhang R, Berghelli A, Milam K, Higgins SJ, et al. Gene control of tyrosine kinase TIE2 and vascular manifestations of infections. Proc Natl Acad Sci USA. 2016;113:2472–7.CrossRefPubMedCentral
29.
go back to reference Page AV, Kotb M, McGeer A, Low DE, Kain KC, Liles WC. Systemic dysregulation of angiopoietin-1/2 in streptococcal toxic shock syndrome. Clin Infect Dis. 2011;52:e157–61.CrossRefPubMedCentral Page AV, Kotb M, McGeer A, Low DE, Kain KC, Liles WC. Systemic dysregulation of angiopoietin-1/2 in streptococcal toxic shock syndrome. Clin Infect Dis. 2011;52:e157–61.CrossRefPubMedCentral
30.
go back to reference Higgins SJ, Purcell LA, Silver KL, Tran V, Crowley V, Hawkes M, et al. Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria. Sci Transl Med. 2016;8:358ra128.CrossRefPubMedCentral Higgins SJ, Purcell LA, Silver KL, Tran V, Crowley V, Hawkes M, et al. Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria. Sci Transl Med. 2016;8:358ra128.CrossRefPubMedCentral
31.
go back to reference David S, Mukherjee A, Ghosh CC, Yano M, Khankin EV, Wenger JB, et al. Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis. Crit Care Med. 2012;40:3034–41.CrossRefPubMedCentral David S, Mukherjee A, Ghosh CC, Yano M, Khankin EV, Wenger JB, et al. Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis. Crit Care Med. 2012;40:3034–41.CrossRefPubMedCentral
32.
go back to reference Hendrickson CM, Matthay MA. Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS. Pulm Circ. 2018;8:2045894018769876.CrossRefPubMedCentral Hendrickson CM, Matthay MA. Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS. Pulm Circ. 2018;8:2045894018769876.CrossRefPubMedCentral
33.
go back to reference Lee WL, Liles WC. Endothelial activation, dysfunction and permeability during severe infections. Curr Opin Hematol. 2011;18:191–6.CrossRefPubMedCentral Lee WL, Liles WC. Endothelial activation, dysfunction and permeability during severe infections. Curr Opin Hematol. 2011;18:191–6.CrossRefPubMedCentral
34.
go back to reference Lovegrove FE, Tangpukdee N, Opoka RO, Lafferty EI, Rajwans N, Hawkes M, et al. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS One. 2009;4:e4912.CrossRefPubMedCentral Lovegrove FE, Tangpukdee N, Opoka RO, Lafferty EI, Rajwans N, Hawkes M, et al. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS One. 2009;4:e4912.CrossRefPubMedCentral
35.
go back to reference Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Piera K, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci USA. 2008;105:17097–102.CrossRefPubMedCentral Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Piera K, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci USA. 2008;105:17097–102.CrossRefPubMedCentral
36.
go back to reference Barber BE, William T, Grigg MJ, Parameswaran U, Piera KA, Price RN, et al. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria. PLoS Pathog. 2015;11:e1004558.CrossRefPubMedCentral Barber BE, William T, Grigg MJ, Parameswaran U, Piera KA, Price RN, et al. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria. PLoS Pathog. 2015;11:e1004558.CrossRefPubMedCentral
37.
go back to reference Barber BE, Grigg MJ, William T, Piera KA, Boyle MJ, Yeo TW, et al. Effects of aging on parasite biomass, inflammation, endothelial activation, microvascular dysfunction and disease severity in Plasmodium knowlesi and Plasmodium falciparum malaria. J Infect Dis. 2017;215:1908–17.CrossRefPubMedCentral Barber BE, Grigg MJ, William T, Piera KA, Boyle MJ, Yeo TW, et al. Effects of aging on parasite biomass, inflammation, endothelial activation, microvascular dysfunction and disease severity in Plasmodium knowlesi and Plasmodium falciparum malaria. J Infect Dis. 2017;215:1908–17.CrossRefPubMedCentral
38.
go back to reference Conroy AL, Phiri H, Hawkes M, Glover S, Mallewa M, Seydel KB, et al. Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study. PLoS One. 2010;5:e15291.CrossRefPubMedCentral Conroy AL, Phiri H, Hawkes M, Glover S, Mallewa M, Seydel KB, et al. Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study. PLoS One. 2010;5:e15291.CrossRefPubMedCentral
39.
go back to reference Hahn WO, Mikacenic C, Price BL, Harju-Baker S, Katz R, Himmelfarb J, et al. Host derived biomarkers of inflammation, apoptosis, and endothelial activation are associated with clinical outcomes in patients with bacteremia and sepsis regardless of microbial etiology. Virulence. 2016;7:387–94.CrossRefPubMedCentral Hahn WO, Mikacenic C, Price BL, Harju-Baker S, Katz R, Himmelfarb J, et al. Host derived biomarkers of inflammation, apoptosis, and endothelial activation are associated with clinical outcomes in patients with bacteremia and sepsis regardless of microbial etiology. Virulence. 2016;7:387–94.CrossRefPubMedCentral
40.
go back to reference Han S, Lee SJ, Kim KE, Lee HS, Oh N, Park I, et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med. 2016;8:335ra355.CrossRef Han S, Lee SJ, Kim KE, Lee HS, Oh N, Park I, et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med. 2016;8:335ra355.CrossRef
41.
go back to reference Saharinen P, Eklund L, Alitalo K. Therapeutic targeting of the angiopoietin-TIE pathway. Nat Rev Drug Discov. 2017;16:635–61.CrossRefPubMedCentral Saharinen P, Eklund L, Alitalo K. Therapeutic targeting of the angiopoietin-TIE pathway. Nat Rev Drug Discov. 2017;16:635–61.CrossRefPubMedCentral
42.
go back to reference D’Acremont V, Kilowoko M, Kyungu E, Philipina S, Sangu W, Kahama-Maro J, et al. Beyond malaria–causes of fever in outpatient Tanzanian children. N Engl J Med. 2014;370:809–17.CrossRefPubMedCentral D’Acremont V, Kilowoko M, Kyungu E, Philipina S, Sangu W, Kahama-Maro J, et al. Beyond malaria–causes of fever in outpatient Tanzanian children. N Engl J Med. 2014;370:809–17.CrossRefPubMedCentral
43.
go back to reference George EC, Walker AS, Kiguli S, Olupot-Olupot P, Opoka RO, Engoru C, et al. Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) score. BMC Med. 2015;13:174.CrossRefPubMedCentral George EC, Walker AS, Kiguli S, Olupot-Olupot P, Opoka RO, Engoru C, et al. Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) score. BMC Med. 2015;13:174.CrossRefPubMedCentral
46.
go back to reference Keitel K, Kagoro F, Samaka J, Masimba J, Said Z, Temba H, et al. A novel electronic algorithm using host biomarker point-of-care tests for the management of febrile illnesses in Tanzanian children (e-POCT): a randomized, controlled non-inferiority trial. PLoS Med. 2017;14:e1002411.CrossRefPubMedCentral Keitel K, Kagoro F, Samaka J, Masimba J, Said Z, Temba H, et al. A novel electronic algorithm using host biomarker point-of-care tests for the management of febrile illnesses in Tanzanian children (e-POCT): a randomized, controlled non-inferiority trial. PLoS Med. 2017;14:e1002411.CrossRefPubMedCentral
47.
go back to reference Higgins SJ, De Ceunynck K, Kellum JA, Chen X, Gu X, Chaudhry SA, et al. Tie2 protects the vasculature against thrombus formation in systemic inflammation. J Clin Invest. 2018;128:1471–84.CrossRefPubMedCentral Higgins SJ, De Ceunynck K, Kellum JA, Chen X, Gu X, Chaudhry SA, et al. Tie2 protects the vasculature against thrombus formation in systemic inflammation. J Clin Invest. 2018;128:1471–84.CrossRefPubMedCentral
48.
go back to reference Rutherford ME, Dockerty JD, Jasseh M, Howie SR, Herbison P, Jeffries DJ, et al. Access to health care and mortality of children under 5 years of age in the Gambia: a case-control study. Bull World Health Organ. 2009;87:216–24.CrossRefPubMedCentral Rutherford ME, Dockerty JD, Jasseh M, Howie SR, Herbison P, Jeffries DJ, et al. Access to health care and mortality of children under 5 years of age in the Gambia: a case-control study. Bull World Health Organ. 2009;87:216–24.CrossRefPubMedCentral
49.
go back to reference Battle KE, Bisanzio D, Gibson HS, Bhatt S, Cameron E, Weiss DJ, et al. Treatment-seeking rates in malaria endemic countries. Malar J. 2016;15:20.CrossRefPubMedCentral Battle KE, Bisanzio D, Gibson HS, Bhatt S, Cameron E, Weiss DJ, et al. Treatment-seeking rates in malaria endemic countries. Malar J. 2016;15:20.CrossRefPubMedCentral
Metadata
Title
Integrated fever management: disease severity markers to triage children with malaria and non-malarial febrile illness
Authors
Chloe R. McDonald
Andrea Weckman
Melissa Richard-Greenblatt
Aleksandra Leligdowicz
Kevin C. Kain
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-018-2488-x

Other articles of this Issue 1/2018

Malaria Journal 1/2018 Go to the issue