Volume 100, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



We aimed to identify clinical and laboratory predictors of mortality in children from a malaria-endemic area of Papua New Guinea hospitalized for severe illness. Children aged 0.5–10 years presenting with any WHO-defined feature of severe malarial illness were eligible for recruitment. Each child was assessed with a detailed clinical examination, blood film microscopy, malaria rapid diagnostic testing (RDT), a full blood examination, and blood glucose and lactate concentrations. Clinical care was coordinated by local medical staff in accordance with national guidelines. Daily study assessments were conducted until death or discharge. Other biochemical tests and malaria polymerase chain reaction (PCR) tests were performed subsequently. Logistic regression identified independent predictors of death. Of 787 evaluable children with severe illness, 336 had confirmed severe malaria (microscopy and PCR positive) and 58 (6.6%) died during hospitalization. The independent predictors of mortality were hyperlactatemia (adjusted odds ratio [95% CI]: 2.85 [1.24–6.41], = 0.01), malnutrition (2.92 [1.36–6.23], = 0.005), renal impairment (3.85 [1.53–9.24], = 0.002), plasma albumin (0.93 [0.88–0.98] for a 1 g/L increase, = 0.004), and Blantyre coma score (BCS) ≤ 2 (10.3 [4.77–23.0] versus a normal BCS, < 0.0001). Confirmed severe malaria (0.11 [0.03–0.30] versus non-malarial severe illness, < 0.0001) was independently associated with lower mortality. Although established risk factors were evident, malaria was inversely associated with mortality. This highlights the importance of accurate diagnosis through blood film microscopy, RDTs, and, if available, PCR to both guide management and provide valid epidemiological data.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Duke T, , 2004. Slow but steady progress in child health in Papua New Guinea. J Paediatr Child Health 40: 659663. [Google Scholar]
  2. Wang H, 2014. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study. Lancet 384: 957979. [Google Scholar]
  3. World Health Organization, 2018. Child Mortality Estimates–Papua New Guinea. Available at: http://www.childmortality.org/index.php?r=site/graph#ID=PNG_Papua%20New%20Guinea. Accessed December 3, 2018. [Google Scholar]
  4. Naraqi S, Feling B, Leeder SR, , 2003. Disease and death in Papua New Guinea. Med J Aust 178: 78. [Google Scholar]
  5. Duke T, Michael A, Mgone J, Frank D, Wal T, Sehuko R, , 2002. Etiology of child mortality in Goroka, Papua New Guinea: a prospective two-year study. Bull World Health Organ 80: 1625. [Google Scholar]
  6. World Health Organization, 2012. Scaling up Diagnostic Testing, Treatment and Surveillance for Malaria. Available at: http://www.who.int/malaria/publications/atoz/test_treat_track_brochure.pdf. Accessed December 3, 2018. [Google Scholar]
  7. Berkley JA, Ross A, Mwangi I, Osier FH, Mohammed M, Shebbe M, Lowe BS, Marsh K, Newton CR, , 2003. Prognostic indicators of early and late death in children admitted to district hospital in Kenya: cohort study. BMJ 326: 361. [Google Scholar]
  8. National Statistical Office of Papua New Guinea, 2002. Papua New Guinea 2000 Census. Port Moresby, Papua New Guinea: Government of Papua New Guinea. [Google Scholar]
  9. Michon P, 2007. The risk of malarial infections and disease in Papua New Guinean children. Am J Trop Med Hyg 76: 9971008. [Google Scholar]
  10. Manning L, Laman M, Townsend MA, Chubb SP, Siba PM, Mueller I, Davis TM, , 2011. Reference intervals for common laboratory tests in Melanesian children. Am J Trop Med Hyg 85: 5054. [Google Scholar]
  11. Yenchitsomanus PT, Summers KM, Bhatia KK, Cattani J, Board PG, , 1985. Extremely high frequencies of alpha-globin gene deletion in Madang and on Kar Kar Island, Papua New Guinea. Am J Hum Genet 37: 778784. [Google Scholar]
  12. UNAIDS, 2010. Global Report Fact Sheet—Oceania. Available at: http://www.unaids.org/en/media/unaids/contentassets/documents/factsheet2010/20101123_FS_oceania_em_en.pdf. Accessed June 27, 2011. [Google Scholar]
  13. Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, , 1989. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. QJM 71: 441459. [Google Scholar]
  14. World Health Organization, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl 1): S1S90. [Google Scholar]
  15. Laman M, 2010. Lumbar puncture in children from an area of malaria endemicity who present with a febrile seizure. Clin Infect Dis 51: 534540. [Google Scholar]
  16. World Health Organization, 2009. AnthroPlus for Personal Computers Manual: Software for Assessing Growth of the World’s Children and Adolescents. Geneva, Switzerland: WHO. [Google Scholar]
  17. Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN, , 1993. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol 58: 283292. [Google Scholar]
  18. Schwartz GJ, Haycock GB, Edelmann CM, Jr. Spitzer A, , 1976. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58: 259263. [Google Scholar]
  19. Paediatrics Society of PNG, 2005. Standard Treatment for Common Illnesses of Children in PNG. Port Moresby, Papua New Guinea: Government of Papua New Guinea. [Google Scholar]
  20. R Development Core Team, 2012. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. [Google Scholar]
  21. Honaker J, King G, Blackwell M, , 2011. Amelia II: a program for missing data. J Stat Software 45: 147. [Google Scholar]
  22. Rubin D, , 1987. Multiple Imputation for Nonresponse in Surveys. New York, NY: Wiley. [Google Scholar]
  23. Manning L, 2011. Features and prognosis of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed Plasmodium species in Papua New Guinean children. PLoS One 6: e29203. [Google Scholar]
  24. Bhutta ZA, Nizami SQ, Thobani S, Issani Z, , 1997. Risk factors for mortality among hospitalized children with persistent diarrhoea in Pakistan. J Trop Pediatr 43: 330336. [Google Scholar]
  25. Demers AM, Morency P, Mberyo-Yaah F, Jaffar S, Blais C, Somse P, Bobossi G, Pepin J, , 2000. Risk factors for mortality among children hospitalized because of acute respiratory infections in Bangui, Central African Republic. Pediatr Infect Dis J 19: 424432. [Google Scholar]
  26. Shann F, Barker J, Poore P, , 1989. Clinical signs that predict death in children with severe pneumonia. Pediatr Infect Dis J 8: 852855. [Google Scholar]
  27. Imbert P, Gerardin P, Rogier C, Ka AS, Jouvencel P, Brousse V, Guyon P, , 2002. Severe falciparum malaria in children: a comparative study of 1990 and 2000 WHO criteria for clinical presentation, prognosis and intensive care in Dakar, Senegal. Trans R Soc Trop Med Hyg 96: 278281. [Google Scholar]
  28. Marsh K, 1995. Indicators of life-threatening malaria in African children. N Engl J Med 332: 13991404. [Google Scholar]
  29. Mockenhaupt FP, 2004. Manifestation and outcome of severe malaria in children in northern Ghana. Am J Trop Med Hyg 71: 167172. [Google Scholar]
  30. Schapira A, Solomon T, Julien M, Macome A, Parmar N, Ruas I, Simao F, Streat E, Betschart B, , 1993. Comparison of intramuscular and intravenous quinine for the treatment of severe and complicated malaria in children. Trans R Soc Trop Med Hyg 87: 299302. [Google Scholar]
  31. Rosanas-Urgell A, 2012. Reduced risk of Plasmodium vivax malaria in Papua New Guinean children with Southeast Asian ovalocytosis in two cohorts and a case-control study. PLoS Med 9: e1001305. [Google Scholar]
  32. Mitra AK, Rahman MM, Fuchs GJ, , 2000. Risk factors and gender differentials for death among children hospitalized with diarrhoea in Bangladesh. J Health Popul Nutr 18: 151156. [Google Scholar]
  33. Black RE, Morris SS, Bryce J, , 2003. Where and why are 10 million children dying every year? Lancet 361: 22262234. [Google Scholar]
  34. Manning L, Laman M, Rosanas-Urgell A, Turlach B, Aipit S, Bona C, Warrell J, Siba P, Mueller I, Davis TM, , 2012. Rapid antigen detection tests for malaria diagnosis in severely ill Papua New Guinean children: a comparative study using Bayesian latent class models. PLoS One 7: e48701. [Google Scholar]
  35. Chang TH, Wu ET, Lu CY, Huang SC, Yang TI, Wang CC, Chen JM, Lee PI, Huang LM, Chang LY, , 2018. Pathogens and outcomes in pediatric septic shock patients supported by extracorporeal membrane oxygenation. J Microbiol Immunol Infect 51: 385391. [Google Scholar]
  36. Lowlaavar N, 2016. Pediatric in-hospital death from infectious disease in Uganda: derivation of clinical prediction models. PLoS One 11: e0150683. [Google Scholar]
  37. Yang SD, 2018. Factors associated with fatal outcome of children with enterovirus A71 infection: a case series. Epidemiol Infect 146: 788798. [Google Scholar]
  38. Sypniewska P, Duda JF, Locatelli I, Althaus CR, Althaus F, Genton B, , 2017. Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis. BMC Med 15: 147. [Google Scholar]
  39. Manning L, Laman M, Davis WA, Davis TM, , 2014. Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis. PLoS One 9: e86737. [Google Scholar]
  40. O'Reilly CE, 2012. Risk factors for death among children less than 5 years old hospitalized with diarrhea in rural western Kenya, 2005–2007: a cohort study. PLoS Med 9: e1001256. [Google Scholar]
  41. Carcillo JA, Halstead ES, Hall MW, Nguyen TC, Reeder R, Aneja R, Shakoory B, Simon D, Eunice Kennedy Shriver National Institute of Child H, Human Development Collaborative Pediatric Critical Care Research Network I; , 2017. Three hypothetical inflammation pathobiology phenotypes and pediatric sepsis-induced multiple organ failure outcome. Pediatr Crit Care Med 18: 513523. [Google Scholar]
  42. Weizman Z, Binsztok M, Fraser D, Deckelbaum RJ, Granot E, , 2002. Intestinal protein loss in acute and persistent diarrhea of early childhood. J Clin Gastroenterol 34: 427429. [Google Scholar]
  43. Downie ML, Gallibois C, Parekh RS, Noone DG, , 2017. Nephrotic syndrome in infants and children: pathophysiology and management. Paediatr Int Child Health 37: 248258. [Google Scholar]
  44. Zappitelli M, , 2008. Epidemiology and diagnosis of acute kidney injury. Semin Nephrol 28: 436446. [Google Scholar]
  45. Krishna S, 1994. Lactic acidosis and hypoglycaemia in children with severe malaria: pathophysiological and prognostic significance. Trans R Soc Trop Med Hyg 88: 6773. [Google Scholar]
  46. Evans JA, 2006. Capillary refill time as an independent prognostic indicator in severe and complicated malaria. J Pediatr 149: 676681. [Google Scholar]
  47. Anil N, , 2017. Importance of measuring lactate levels in children with sepsis. Nurs Child Young People 29: 2629. [Google Scholar]

Data & Media loading...

  • Received : 22 Sep 2018
  • Accepted : 10 Dec 2018
  • Published online : 18 Feb 2019

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error