Berkley J, Mwarumba S, Bramham K, Lowe B, Marsh K, 1999. Bacteraemia complicating severe malaria in children. Trans R Soc Trop Med Hyg 93: 283–286.
Were T, Davenport GC, Hittner JB, Ouma C, Vulule JM, Ong’echa JM, Perkins DJ, 2011. Bacteremia in Kenyan children presenting with malaria. J Clin Microbiol 49: 671–676.
Bronzan RN et al. 2007. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J Infect Dis 195: 895–904.
Prada J, Alabi SA, Bienzle U, 1993. Bacterial strains isolated from blood cultures of Nigerian children with cerebral malaria. Lancet 342: 1114.
Church J, Maitland K, 2014. Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review. BMC Med 12: 31.
Hogan B et al. Fever Without Source Study Group, 2018. Malaria coinfections in febrile pediatric inpatients: a hospital-based study from Ghana. Clin Infect Dis 66: 1838–1845.
Nadjm B et al. 2010. WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. BMJ 340: c1350.
World Health Organization, 2014. Severe malaria. Trop Med Int Health 19 (Suppl 1): 7–131.
Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, 2013. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther 11: 623–639.
Hendriksen IC et al. 2013. Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration. J Infect Dis 207: 351–361.
Nyein PP, Aung NM, Kyi TT, Htet ZW, Anstey NM, Kyi MM, Hanson J, 2016. High frequency of clinically significant bacteremia in adults hospitalized with falciparum malaria. Open Forum Infect Dis 3: ofw028.
Hanson J et al. 2010. A simple score to predict the outcome of severe malaria in adults. Clin Infect Dis 50: 679–685.
Mu TT, Sein AA, Kyi TT, Min M, Aung NM, Anstey NM, Kyaw MP, Soe C, Kyi MM, Hanson J, 2016. Malaria incidence in Myanmar 2005–2014: steady but fragile progress towards elimination. Malar J 15: 503.
Imwong M et al. 2017. The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study. Lancet Infect Dis 17: 491–497.
Imwong M, Hien TT, Thuy-Nhien NT, Dondorp AM, White NJ, 2017. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. Lancet Infect Dis 17: 1022–1023.
World Health Organization, 2012. Management of Severe Malaria: A Practical Handbook, 3rd edition. Geneva, Switzerland: World Health Organization.
Aung NM, Kaung M, Kyi TT, Kyaw MP, Min M, Htet ZW, Anstey NM, Kyi MM, Hanson J, 2015. The safety of a conservative fluid replacement strategy in adults hospitalised with malaria. PLoS One 10: e0143062.
Hanson J, Anstey NM, Bihari D, White NJ, Day NP, Dondorp AM, 2014. The fluid management of adults with severe malaria. Crit Care 18: 642.
Kaung M, Kyi TT, Aung NM, Kyaw MP, Min M, Htet ZW, Anstey NM, Kyi MM, Hanson J, 2015. The prognostic utility of bedside assessment of adults hospitalized with malaria in Myanmar: a retrospective analysis. Malar J 14: 63.
Hanson J et al. 2014. Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis. PLoS One 9: e87020.
World Health Organization, 2016. World Malaria Report. Geneva, Switzerland: World Health Organization.
Dondorp A, Nosten F, Stepniewska K, Day N, White N; South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) Group, 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717–725.
Hanson J et al. 2011. Laboratory prediction of the requirement for renal replacement in acute falciparum malaria. Malar J 10: 217.
Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB, 1975. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet 1: 1211–1213.
Davis JS, Cheng AC, McMillan M, Humphrey AB, Stephens DP, Anstey NM, 2011. Sepsis in the tropical top end of Australia’s northern territory: disease burden and impact on indigenous Australians. Med J Aust 194: 519–524.
White NJ, Turner GD, Day NP, Dondorp AM, 2013. Lethal malaria: Marchiafava and Bignami were right. J Infect Dis 208: 192–198.
Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, Kamiza S, Molyneux M, Taylor TE, 2011. The neuropathology of fatal cerebral malaria in Malawian children. Am J Pathol 178: 2146–2158.
MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA, 1985. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119: 385–401.
Yeo TW, Lampah DA, Kenangalem E, Tjitra E, Weinberg JB, Granger DL, Price RN, Anstey NM, 2014. Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria. J Infect Dis 210: 1627–1632.
Wilairatana P, Meddings JB, Ho M, Vannaphan S, Looareesuwan S, 1997. Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria. Clin Infect Dis 24: 430–435.
Takem EN, Roca A, Cunnington A, 2014. The association between malaria and non-typhoid Salmonella bacteraemia in children in sub-Saharan Africa: a literature review. Malar J 13: 400.
Church JA, Nyamako L, Olupot-Olupot P, Maitland K, Urban BC, 2016. Increased adhesion of Plasmodium falciparum infected erythrocytes to ICAM-1 in children with acute intestinal injury. Malar J 15: 54.
Bruneel F, Gachot B, Timsit JF, Wolff M, Bedos JP, Regnier B, Vachon F, 1997. Shock complicating severe falciparum malaria in European adults. Intensive Care Med 23: 698–701.
Cunnington AJ, Njie M, Correa S, Takem EN, Riley EM, Walther M, 2012. Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction. J Immunol 189: 5336–5346.
Dasari P, Reiss K, Lingelbach K, Baumeister S, Lucius R, Udomsangpetch R, Bhakdi SC, Bhakdi S, 2011. Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes. Blood 118: 4946–4956.
Mabey DC, Brown A, Greenwood BM, 1987. Plasmodium falciparum malaria and Salmonella infections in Gambian children. J Infect Dis 155: 1319–1321.
Cunnington AJ, Riley EM, 2010. Suppression of vaccine responses by malaria: insignificant or overlooked? Expert Rev Vaccines 9: 409–429.
Hanson JP et al. 2013. Fluid resuscitation of adults with severe falciparum malaria: effects on acid-base status, renal function, and extravascular lung water. Crit Care Med 41: 972–981.
Hanson J et al. 2012. Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria. J Infect Dis 206: 571–579.
Nguyen HP et al. 2011. A retrospective analysis of the haemodynamic and metabolic effects of fluid resuscitation in Vietnamese adults with severe falciparum malaria. PLoS One 6: e25523.
Warrell DA, Looareesuwan S, Warrell MJ, Kasemsarn P, Intaraprasert R, Bunnag D, Harinasuta T, 1982. Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients. N Engl J Med 306: 313–319.
Modiano D, Sirima BS, Konate A, Sanou I, Sawadogo A, 2001. Leucocytosis in severe malaria. Trans R Soc Trop Med Hyg 95: 175–176.
Fiori B et al. 2014. Performance of two resin-containing blood culture media in detection of bloodstream infections and in direct matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) broth assays for isolate identification: clinical comparison of the BacT/Alert Plus and Bactec Plus systems. J Clin Microbiol 52: 3558–3567.
McNerney R, 2015. Diagnostics for developing countries. Diagnostics (Basel) 5: 200–209.
Bruneel F et al. Severe Imported Malaria in Adults (SIMA) Study Group, 2010. Severe imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS One 5: e13236.
Myat TO, Prasad N, Thinn KK, Win KK, Htike WW, Zin KN, Murdoch DR, Crump JA, 2014. Bloodstream infections at a tertiary referral hospital in Yangon, Myanmar. Trans R Soc Trop Med Hyg 108: 692–698.
Dondorp AM, Limmathurotsakul D, Ashley EA, 2018. What’s wrong in the control of antimicrobial resistance in critically ill patients from low- and middle-income countries? Intensive Care Med 44: 79–82.
Freund Y et al. French Society of Emergency Medicine Collaborators Group, 2017. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA 317: 301–308.
Andriolo BN, Andriolo RB, Salomao R, Atallah AN, 2017. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev 1: CD010959.
Pierrakos C, Vincent JL, 2010. Sepsis biomarkers: a review. Crit Care 14: R15.
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Abstract Views | 2214 | 1533 | 33 |
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It has been believed that concomitant bacteremia is uncommon in adults hospitalized with falciparum malaria. Accordingly, the World Health Organization treatment guidelines presently only recommended additional antibacterial therapy in these patients if they have a clinical syndrome compatible with serious bacterial infection. Admission blood cultures were collected from 20 consecutive adults in Myanmar, hospitalized with a positive immunochromatographic test and blood film, suggesting a diagnosis of falciparum malaria; four (20%) had bacteremia with a clinically significant pathogen. These case series’ data were pooled with a previously published multicenter study from Myanmar which had also collected blood cultures in adults hospitalized with a diagnosis of falciparum malaria. Among 87 patients in the two studies, 13 (15%) had clinically significant bacteremia on admission, with Gram-negative organisms in 10 (77%) and Staphylococcus aureus in the remaining three (23%). Bacteremic patients had more severe disease than non-bacteremic patients (median [interquartile range] respiratory coma acidosis malaria score 2 [1–4] versus 1 [1–2], P = 0.02) and were more likely to die (2/13 [15%] versus 1/74 [1%], P = 0.01). However, bacterial coinfection was suspected clinically in a minority of bacteremic patients (5/13 [38%] compared with 13/70 [19%] of non-bacteremic patients, P = 0.11). Concomitant bacteremia in adults diagnosed with falciparum malaria may be more common than previously believed and is difficult to identify clinically in resource-poor settings. Death is more common in these patients, suggesting that clinicians should have a lower threshold for commencing empirical antibacterial therapy in adults diagnosed with falciparum malaria in these locations than is presently recommended.
Financial support: This study was funded by the National Health and Medical Research Council of Australia (Program Grant 1037304 and Fellowships to NMA (Menzies) [1042072] and JH [1054195]).
Authors’ addresses: Ne Myo Aung and Mar Mar Kyi, Insein General Hospital, Yangon, Myanmar, and University of Medicine 2, Yangon, Myanmar, E-mails: drnaymyoaung@gmail.com and drmmkyi@gmail.com. Phyo Pyae Nyein, Thu Ya Htut, and Zaw Win Htet, Insein General Hospital, Yangon, Myanmar, E-mails: phyopyaenyein@gmail.com, thuyahtut999@gmail.com, and zawwinhtet1991@gmail.com. Tint Tint Kyi, Department of Medical Care, Ministry of Health and Sports, Nay Pyi Taw, Myanmar, E-mail: tinttint.kyi@gmail.com. Nicholas M. Anstey, Menzies School of Health Research, Charles Darwin University, Darwin, Australia, E-mail: nicholas.anstey@menzies.edu.au. Josh Hanson, University of Medicine 2, Yangon, Myanmar, Menzies School of Health Research, Charles Darwin University, Darwin, Australia, and Kirby Institute, University of New South Wales, Sydney, Australia, E-mail: jhanson@kirby.unsw.edu.au.
Berkley J, Mwarumba S, Bramham K, Lowe B, Marsh K, 1999. Bacteraemia complicating severe malaria in children. Trans R Soc Trop Med Hyg 93: 283–286.
Were T, Davenport GC, Hittner JB, Ouma C, Vulule JM, Ong’echa JM, Perkins DJ, 2011. Bacteremia in Kenyan children presenting with malaria. J Clin Microbiol 49: 671–676.
Bronzan RN et al. 2007. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J Infect Dis 195: 895–904.
Prada J, Alabi SA, Bienzle U, 1993. Bacterial strains isolated from blood cultures of Nigerian children with cerebral malaria. Lancet 342: 1114.
Church J, Maitland K, 2014. Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review. BMC Med 12: 31.
Hogan B et al. Fever Without Source Study Group, 2018. Malaria coinfections in febrile pediatric inpatients: a hospital-based study from Ghana. Clin Infect Dis 66: 1838–1845.
Nadjm B et al. 2010. WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. BMJ 340: c1350.
World Health Organization, 2014. Severe malaria. Trop Med Int Health 19 (Suppl 1): 7–131.
Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, 2013. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther 11: 623–639.
Hendriksen IC et al. 2013. Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration. J Infect Dis 207: 351–361.
Nyein PP, Aung NM, Kyi TT, Htet ZW, Anstey NM, Kyi MM, Hanson J, 2016. High frequency of clinically significant bacteremia in adults hospitalized with falciparum malaria. Open Forum Infect Dis 3: ofw028.
Hanson J et al. 2010. A simple score to predict the outcome of severe malaria in adults. Clin Infect Dis 50: 679–685.
Mu TT, Sein AA, Kyi TT, Min M, Aung NM, Anstey NM, Kyaw MP, Soe C, Kyi MM, Hanson J, 2016. Malaria incidence in Myanmar 2005–2014: steady but fragile progress towards elimination. Malar J 15: 503.
Imwong M et al. 2017. The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study. Lancet Infect Dis 17: 491–497.
Imwong M, Hien TT, Thuy-Nhien NT, Dondorp AM, White NJ, 2017. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. Lancet Infect Dis 17: 1022–1023.
World Health Organization, 2012. Management of Severe Malaria: A Practical Handbook, 3rd edition. Geneva, Switzerland: World Health Organization.
Aung NM, Kaung M, Kyi TT, Kyaw MP, Min M, Htet ZW, Anstey NM, Kyi MM, Hanson J, 2015. The safety of a conservative fluid replacement strategy in adults hospitalised with malaria. PLoS One 10: e0143062.
Hanson J, Anstey NM, Bihari D, White NJ, Day NP, Dondorp AM, 2014. The fluid management of adults with severe malaria. Crit Care 18: 642.
Kaung M, Kyi TT, Aung NM, Kyaw MP, Min M, Htet ZW, Anstey NM, Kyi MM, Hanson J, 2015. The prognostic utility of bedside assessment of adults hospitalized with malaria in Myanmar: a retrospective analysis. Malar J 14: 63.
Hanson J et al. 2014. Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis. PLoS One 9: e87020.
World Health Organization, 2016. World Malaria Report. Geneva, Switzerland: World Health Organization.
Dondorp A, Nosten F, Stepniewska K, Day N, White N; South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) Group, 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717–725.
Hanson J et al. 2011. Laboratory prediction of the requirement for renal replacement in acute falciparum malaria. Malar J 10: 217.
Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB, 1975. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet 1: 1211–1213.
Davis JS, Cheng AC, McMillan M, Humphrey AB, Stephens DP, Anstey NM, 2011. Sepsis in the tropical top end of Australia’s northern territory: disease burden and impact on indigenous Australians. Med J Aust 194: 519–524.
White NJ, Turner GD, Day NP, Dondorp AM, 2013. Lethal malaria: Marchiafava and Bignami were right. J Infect Dis 208: 192–198.
Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, Kamiza S, Molyneux M, Taylor TE, 2011. The neuropathology of fatal cerebral malaria in Malawian children. Am J Pathol 178: 2146–2158.
MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA, 1985. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119: 385–401.
Yeo TW, Lampah DA, Kenangalem E, Tjitra E, Weinberg JB, Granger DL, Price RN, Anstey NM, 2014. Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria. J Infect Dis 210: 1627–1632.
Wilairatana P, Meddings JB, Ho M, Vannaphan S, Looareesuwan S, 1997. Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria. Clin Infect Dis 24: 430–435.
Takem EN, Roca A, Cunnington A, 2014. The association between malaria and non-typhoid Salmonella bacteraemia in children in sub-Saharan Africa: a literature review. Malar J 13: 400.
Church JA, Nyamako L, Olupot-Olupot P, Maitland K, Urban BC, 2016. Increased adhesion of Plasmodium falciparum infected erythrocytes to ICAM-1 in children with acute intestinal injury. Malar J 15: 54.
Bruneel F, Gachot B, Timsit JF, Wolff M, Bedos JP, Regnier B, Vachon F, 1997. Shock complicating severe falciparum malaria in European adults. Intensive Care Med 23: 698–701.
Cunnington AJ, Njie M, Correa S, Takem EN, Riley EM, Walther M, 2012. Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction. J Immunol 189: 5336–5346.
Dasari P, Reiss K, Lingelbach K, Baumeister S, Lucius R, Udomsangpetch R, Bhakdi SC, Bhakdi S, 2011. Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes. Blood 118: 4946–4956.
Mabey DC, Brown A, Greenwood BM, 1987. Plasmodium falciparum malaria and Salmonella infections in Gambian children. J Infect Dis 155: 1319–1321.
Cunnington AJ, Riley EM, 2010. Suppression of vaccine responses by malaria: insignificant or overlooked? Expert Rev Vaccines 9: 409–429.
Hanson JP et al. 2013. Fluid resuscitation of adults with severe falciparum malaria: effects on acid-base status, renal function, and extravascular lung water. Crit Care Med 41: 972–981.
Hanson J et al. 2012. Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria. J Infect Dis 206: 571–579.
Nguyen HP et al. 2011. A retrospective analysis of the haemodynamic and metabolic effects of fluid resuscitation in Vietnamese adults with severe falciparum malaria. PLoS One 6: e25523.
Warrell DA, Looareesuwan S, Warrell MJ, Kasemsarn P, Intaraprasert R, Bunnag D, Harinasuta T, 1982. Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients. N Engl J Med 306: 313–319.
Modiano D, Sirima BS, Konate A, Sanou I, Sawadogo A, 2001. Leucocytosis in severe malaria. Trans R Soc Trop Med Hyg 95: 175–176.
Fiori B et al. 2014. Performance of two resin-containing blood culture media in detection of bloodstream infections and in direct matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) broth assays for isolate identification: clinical comparison of the BacT/Alert Plus and Bactec Plus systems. J Clin Microbiol 52: 3558–3567.
McNerney R, 2015. Diagnostics for developing countries. Diagnostics (Basel) 5: 200–209.
Bruneel F et al. Severe Imported Malaria in Adults (SIMA) Study Group, 2010. Severe imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS One 5: e13236.
Myat TO, Prasad N, Thinn KK, Win KK, Htike WW, Zin KN, Murdoch DR, Crump JA, 2014. Bloodstream infections at a tertiary referral hospital in Yangon, Myanmar. Trans R Soc Trop Med Hyg 108: 692–698.
Dondorp AM, Limmathurotsakul D, Ashley EA, 2018. What’s wrong in the control of antimicrobial resistance in critically ill patients from low- and middle-income countries? Intensive Care Med 44: 79–82.
Freund Y et al. French Society of Emergency Medicine Collaborators Group, 2017. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA 317: 301–308.
Andriolo BN, Andriolo RB, Salomao R, Atallah AN, 2017. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev 1: CD010959.
Pierrakos C, Vincent JL, 2010. Sepsis biomarkers: a review. Crit Care 14: R15.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 2214 | 1533 | 33 |
Full Text Views | 1057 | 12 | 0 |
PDF Downloads | 172 | 12 | 0 |