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    Mean sequential organ failure assessment (SOFA) scores (A) and multiple organ dysfunction syndrome (MODS) risk (B) by parasitemia and hemoglobin concentrations on admission among patients admitted with malaria to Central Military Hospital, Bogotá between 2003 and 2012.

  • 1.

    Salord F, Allaouchiche B, Gaussorgues P, Boibieux A, Sirodot M, Gerard-Boncompain M, Biron F, Peyramond D, Robert D, 1991. Severe falciparum malaria (21 cases). Intensive Care Med 17: 449454.

    • Search Google Scholar
    • Export Citation
  • 2.

    Saissy JM, Rouvin B, Koulmann P, 2003. Severe malaria in intensive care units in 2003. Med Trop 63: 258266.

  • 3.

    Metha SR, Joshi V, Lazar AI, 1996. Unusual acute and chronic complications of malaria. J Assoc Physicians India 44: 451453.

  • 4.

    Krishnan A, Karnad DR, 2003. Severe falciparum malaria: an important cause of multiple organ failure in Indian intensive care unit patients. Crit Care Med 31: 22782284.

    • Search Google Scholar
    • Export Citation
  • 5.

    Manish R, Tripathy R, Das BK, 2003. Plasma glucose and tumor necrosis factor-alpha in adult patients with severe falciparum malaria. Trop Med Int Health 8: 125128.

    • Search Google Scholar
    • Export Citation
  • 6.

    Kochar DK, Kochar SK, Agrawal RP, Sabir M, Nayak KC, Agrawal TD, Purohit VP, Gupta RP, 2006. The changing spectrum of severe falciparum malaria: a clinical study from Bikaner (northwest India). J Vector Borne Dis 43: 104108.

    • Search Google Scholar
    • Export Citation
  • 7.

    Mohan A, Sharma SK, Bollineni S, 2008. Acute lung injury and acute respiratory distress syndrome in malaria. J Vector Borne Dis 45: 179193.

  • 8.

    Kanodia KV, Shah PR, Vanikar AV, Kasat P, Gumber M, Trivedi HL, 2010. Malaria induced acute renal failure: a single center experience. Saudi J Kidney Dis Transpl 21: 10881091.

    • Search Google Scholar
    • Export Citation
  • 9.

    Sarkar PK, Ahluwalia G, Vijayan VK, Talwar A, 2010. Critical care aspects of malaria. J Intensive Care Med 25: 93103.

  • 10.

    Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S, 1999. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med 25: 686696.

    • Search Google Scholar
    • Export Citation
  • 11.

    Jog S, Akole P, Pawar B, Gogate N, Gadgil S, Rajhans P, 2007. Sequential organ failure assessment score as an outcome predictor in malarial multiorgan dysfunction syndrome. Crit Care 11 (Suppl 2): 463.

    • Search Google Scholar
    • Export Citation
  • 12.

    Helbok R, Dent W, Nacher M, Lackner P, Treeprasertsuk S, Krudsood S, 2005. The use of the multi-organ-dysfunction score to discriminate different levels of severity in severe and complicated Plasmodium falciparum malaria. Am J Trop Med Hyg 72: 150154.

    • Search Google Scholar
    • Export Citation
  • 13.

    Fox L, Taylor T, Pensulo P, Liomba A, Mpakiza A, Varela A, Glover SJ, Reeves MJ, Seydel KB, 2013. HRP2 plasma levels predict progression to cerebral malaria in Malawian children with Plasmodium falciparum infection. J Infect Dis 208: 500503.

    • Search Google Scholar
    • Export Citation
  • 14.

    Hendriksen IC, Mwanga-Amumpaire J, von Seidlein L, Mtove G, White LJ, Olaosebikan R, Lee SJ, Tshefu AK, Woodrow C, Amos B, Karema C, Saiwaew S, Maitland K, Gomes E, Pan-Ngum W, Gesase S, Silamut K, Reyburn H, Joseph S, Chotivanich K, Fanello CI, Day NP, White NJ, Dondorp AM, 2012. Diagnosing severe falciparum malaria in parasitemic African children: a prospective evaluation of plasma PfHRP2 measurement. PLoS Med 9: e1001297.

    • Search Google Scholar
    • Export Citation
  • 15.

    Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG, 1996. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Working Group on Sepsis-Related Problems of the ESICM. Intensive Care Med 22: 707710.

    • Search Google Scholar
    • Export Citation
  • 16.

    Antelman G, Msamanga GI, Spiegelman D, Urassa EJ, Narh R, Hunter DJ, Fawzi WW, 2000. Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania. J Nutr 130: 19501957.

    • Search Google Scholar
    • Export Citation
  • 17.

    Finkelstein JL, Mehta S, Duggan CP, Spiegelman D, Aboud S, Kupka R, Msamanga GI, Fawzi WW, 2012. Predictors of anemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections. Public Health Nutr 15: 928937.

    • Search Google Scholar
    • Export Citation
  • 18.

    Ogawa E, Furusyo N, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Tanabe Y, Kotoh K, Shimoda S, Hayashi J, 2013. Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy. J Hepatol 59: 667674.

    • Search Google Scholar
    • Export Citation
  • 19.

    Mishra SK, Panigrahi P, Mishra R, Mohanty S, 2007. Prediction of outcome in adults with severe falciparum malaria: a new scoring system. Malar J 6: 24.

    • Search Google Scholar
    • Export Citation
  • 20.

    Tangpukdee N, Krudsood S, Thanachartwet V, Duangdee C, Paksala S, Chonsawat P, Srivilairit S, Looareesuwan S, Wilairatana P, 2007. Predictive score of uncomplicated falciparum malaria patients turning to severe malaria. Korean J Parasitol 45: 273282.

    • Search Google Scholar
    • Export Citation
  • 21.

    Koh KH, Chew PH, Kiyu A, 2004. A retrospective study of malaria infections in an intensive care unit of a general hospital in Malaysia. Singapore Med J 45: 2836.

    • Search Google Scholar
    • Export Citation
  • 22.

    Kochar D, Kumawat BL, Karan S, Kochar SK, Agarwal RP, 1997. Severe and complicated malaria in Bikaner (Rajasthan), western India. Southeast Asian J Trop Med Public Health 28: 259267.

    • Search Google Scholar
    • Export Citation
  • 23.

    Moudden MK, Boukhira A, Zyani M, Boughalem M, Hda A, 2006. Severe imported malaria. The experience of the military hospital of Marrakech. Ann Biol Clin (Paris) 64: 501505.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

Hemoglobin Concentration and Parasitemia on Hospital Admission Predict Risk of Multiple Organ Dysfunction Syndrome among Adults with Malaria

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  • University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, Michigan; Central Military Hospital, Department of Critical Medicine, Bogotá, Colombia; University of La Sabana, Faculty of Medicine, Chia, Colombia

Risk factors for progression from acute malaria to multiple organ dysfunction syndrome (MODS) are poorly understood. The MODS is commonly diagnosed with the sequential organ failure assessment (SOFA) scale, but this scale has been understudied in patients with severe malaria. We conducted a cohort study among 426 adult males admitted to hospital with malaria in Bogotá, Colombia. We estimated SOFA scores and relative risks (RRs) for MODS during hospitalization according to patients' characteristics on admission. Risk of MODS was 7.3% over a median 6.0 days in hospital. Baseline hemoglobin was strongly, inversely associated with MODS (adjusted RR for hemoglobin ≤ 8.5 g/dL versus hemoglobin > 11 g/dL = 9.5, 95% confidence interval [CI]: 3.6, 25.3). Plasmodium falciparum malaria and parasitemia were positively associated with MODS. There was a strong interaction between baseline parasitemia and hemoglobin on MODS risk. In conclusion, the use of parasitemia and hemoglobin on admission to identify high-risk patients deserves consideration.

Introduction

As many as 22% of patients admitted to hospital with malaria can develop multiple organ dysfunction syndrome (MODS).16 Among complications requiring intensive care unit (ICU) admission are acute lung injury and acute respiratory distress syndrome, pulmonary edema, bacterial sepsis,7 acute renal failure,8 severe anemia, cerebral malaria, and thrombocytopenia.9 The MODS is fatal in 10–49% of patients with malaria.2,4,10,11 Early identification of patients at the highest risk of MODS and related complications would provide treating clinicians with opportunities to target those who could benefit from intensive or special care. Some factors that predict multiple organ involvement include parasite virulence, host immune status, infection with Plasmodium falciparum, and plasma concentration of histidine-rich protein (HRP)-2 antigen.4,9,1214 Nevertheless, whether a combination of easy-to-obtain, inexpensive markers of risk could predict the outcome of patients admitted to hospital with malaria has not been determined. The aim of this study was to examine risk factors for multiple organ dysfunction in patients admitted to hospital with malaria.

Methods

Study population.

We conducted a longitudinal investigation of risk factors for MODS among all male patients 18 years of age or older who were admitted with malaria to the Central Military Hospital (CMH) in Bogotá, Colombia between January 2003 and December 2012. The CMH is a tertiary health care teaching hospital serving personnel in the Colombian armed forces and their families. During the study period, all affiliates receiving a thick blood film-confirmed malaria diagnosis at military health care centers around the country were referred to the CMH in Bogotá for treatment. Before 2010, treatment consisted of intravenous quinine with doxycycline or clindamycin for 7 days. Since 2010, standard treatment has consisted of 2 days of intravenous artesunate with doxycycline or clindamycin for 7 days. We identified all medical records of patients admitted to CMH with at least one of the following discharge diagnoses: malaria with cerebral complications, severe P. falciparum malaria, uncomplicated P. falciparum malaria, Plasmodium vivax malaria with splenic rupture, P. vivax malaria with other complications, uncomplicated P. vivax malaria, Plasmodium malariae malaria with nephropathy, complicated P. malariae malaria, uncomplicated P. malariae malaria, Plasmodium ovale malaria, other confirmed malaria, or malaria not otherwise specified. Patients did not meet MODS criteria at baseline.

Data collection.

Using a standardized data collection form, we extracted information on age, sex, and hemoglobin concentrations (g/dL) upon admission from each patient's medical record. In addition, we recorded the number of days from the onset of symptoms to consultation at CMH. We also registered the duration of hospital stay in days and history of previous malaria infection, current type of Plasmodium infection (falciparum, vivax, or falciparum and vivax), and parasitemia by thick blood smear. In cases of co-infection with more than one species, P. falciparum parasitemia was registered. We next extracted information on the outcomes of hospital stay including the highest recorded serum creatinine (mg/dL) and total bilirubin (mg/dL) concentrations, lowest recorded platelet count and Glasgow Coma Score, and systolic and diastolic blood pressure (mm of Hg). Lowest recorded PaO2/FIO2 (oxygen pressure/fraction inspired oxygen) was obtained when available; otherwise, the minimum Sat O2/FIO2 (oxygen saturation/fraction inspired oxygen) was extracted. The project was approved by the CMH's ethics committee. The Health Sciences and Behavioral Sciences Institutional Review Board at the University of Michigan exempted the project from review as non-human subjects research.

Data analysis.

The outcomes of interest were the maximum sequential organ failure assessment (SOFA) score, a continuous scale used to identify patients at risk of MODS, and the development of MODS during hospital stay. The SOFA scores were calculated for each of six criteria, including creatinine, bilirubin, Glasgow, PaO2/FIO2, mean arterial pressure (diastolic blood pressure + 1/3[systolic–diastolic blood pressure]), and platelet count using a conventional algorithm.15 The MODS was defined as a sum of all six SOFA score values ≥ 8. Of 431 records found, only five belonged to women. Thus, we decided to restrict the study to the 426 men admitted with malaria.

Predictors of interest were hemoglobin concentration on admission, Plasmodium species (vivax, falciparum, or both), parasitemia, age, days with symptoms, and history of malaria. Age was categorized into tertiles, and the days with symptoms before hospital admission and parasitemia into quartiles. Hemoglobin was categorized as < 11 g/dL (normal), > 8.5 and ≤ 11 g/dL (anemic), and ≤ 8.5 g/dL (severely anemic).1618 In bivariate analyses, we compared the distribution of the continuous SOFA score outcome between categories of each predictor using the Kruskall Wallis test. Adjusted mean differences and 95% confidence intervals (CIs) for the continuous SOFA score outcome were estimated from multivariable linear regression using empirical variances. Next, we estimated the risk of MODS by levels of predictors and computed relative risks with 95% CIs. Adjusted relative risks of MODS were estimated with the use of Poisson regression models. The adjusted multivariable models included Plasmodium species, parasitemia, and hemoglobin as predictors. Hemoglobin was excluded from the model to obtain adjusted estimates for parasitemia because this variable could be on the causal pathway. Tests for linear trend were carried out for ordinal predictors by introducing a variable representing ordinal categories as a continuous covariate in the models. Finally, we examined the associations of parasitemia with SOFA score or MODS risk stratified by hemoglobin levels. We tested the interactions with the use of likelihood ratio tests. All analyses were carried out with the use of Statistical Analysis Software version 9.2 (SAS Institute, Cary, NC).

Results

Mean ± SD age of the 426 adult males included in the study was 24.5 ± 5.3 years; 43% had a history of malaria infection. Mean ± SD hemoglobin and median parasitemia on admission were, respectively, 12.4 ± 2.4 g/dL and 2,965 parasites/μL. Fifty-one percent of participants were infected with P. vivax, 27% with P. falciparum, and 23% with both P. vivax and P. falciparum. Mean ± SD maximum SOFA score during hospitalization was 4.1 ± 2.6. The overall risk of MODS, was 7.3% (N = 31) over a median 6 days of hospital stay.

In bivariate analyses, the mean SOFA score was higher in patients 21–24 years of age compared with younger or older patients (Table 1). It was also higher in patients who had had symptoms for 5–7 days versus < 5 or > 7 days before admission and in those without a history of infection. Both mean SOFA score and risk of MODS were positively associated with parasitemia and infection with P. falciparum and inversely associated with hemoglobin on admission. After adjustment for parasitemia and type of Plasmodium, patients with hemoglobin ≤ 8.5 g/dL had a 3.2 (95% CI = 1.7, 4.6) significantly higher mean SOFA score (p, test for trend < 0.0001), and a 9.5 (95% CI = 3.6, 25.3) higher risk of MODS (p, test for trend < 0.0001), compared with non-anemic patients. Similarly, after adjustment for type of Plasmodium, parasitemia was positively linearly associated with both the mean SOFA score and risk of MODS. The adjusted mean difference in SOFA score between patients in the 4th versus 1st quartiles of parasitemia was 1.9 (95% CI = 1.1, 2.6; p, test for trend < 0.0001) and the adjusted relative risk for MODS was 12.5 (95% CI = 1.6, 95.5; p, test for trend = 0.002). Further adjustment for age and days with symptoms did not change these results.

Table 1

Multiple organ dysfunction syndrome (MODS) among patients admitted with malaria to the Central Military Hospital, Bogotá, between 2003 and 2012*

PredictorN*SOFA scoreMODS (score ≥ 8)
Mean (SD)Adjusted difference (95% CI)% (n)Adjusted relative risk (95% CI)
Age (years)
 18–20783.9 (2.6) 6.4 (5) 
 21–241834.5 (2.8) 9.3 (17) 
 ≥ 251653.7 (2.4) 5.5 (9) 
p§ 0.02 0.37 
Previous malaria
 No2434.3 (2.6) 8.2 (20) 
 Yes1833.7 (2.7) 6.0 (11) 
p 0.007 0.38 
Days with symptoms before admission
 1–41203.5 (2.0) 4.2 (5) 
 5–71244.6 (3.1) 8.9 (11) 
 8–9674.7 (2.9) 13.4 (9) 
 ≥ 101123.7 (2.5) 5.4 (6) 
p 0.003 0.09 
Hemoglobin on admission (g/dL)
 ≤ 8.5326.8 (4.6)3.2 (1.7, 4.6)28.1 (9)9.5 (3.6, 25.3)
 8.6–11814.6 (3.2)1.1 (0.4, 1.8)17.3 (14)7.1 (2.9, 17.2)
 > 113123.7 (1.9)Reference2.6 (8)1.0
p 0.0002< 0.0001< 0.0001< 0.0001
Type of Plasmodium infection
Vivax2154.1 (2.2)Reference4.2 (9)1.0
Falciparum1144.2 (3.4)−0.6 (−1.2, −0.1)13.2 (15)1.5 (0.6, 3.7)
Vivax and falciparum963.8 (2.4)−0.6 (−1.2, 0.0)7.3 (7)1.3 (0.5, 3.5)
p 0.320.040.010.63
Parasitemia (parasites/μL)
 2–770933.5 (1.9)Reference1.1 (1)1.0
 771–2965923.9 (2.0)0.5 (−0.1, 1.1)5.4 (5)4.8 (0.6, 41.3)
 2966–7220934.3 (2.6)0.9 (0.3, 1.6)8.6 (8)7.2 (0.9, 57.9)
 > 7220925.2 (3.5)1.9 (1.1, 2.6)16.3 (15)12.5 (1.6, 95.5)
p 0.002< 0.00010.0010.002

Totals may be < 426 because of missing data.

From a multivariable linear regression model with sequential organ failure assessment (SOFA) as the continuous outcome and hemoglobin, type of infection, and parasitemia as predictors. Hemoglobin was excluded from the model to obtain adjusted estimates for parasitemia because this variable could be on the causal pathway. 95% confidence intervals (CIs) were estimated using empirical variances.

From a multivariable Poisson regression model with multiple organ dysfunction syndrome (MODS) as the dichotomous outcome and hemoglobin, type of infection, and parasitemia as predictors. Hemoglobin was excluded from the model to obtain adjusted estimates for parasitemia because this variable could be on the causal pathway.

Kruskall Wallis test for SOFA score; χ2 test for MODS.

For adjusted differences and relative risks, p is from a test for linear trend for a variable representing the categories of the ordinal predictor introduced into the model as continuous.

From thick blood film.

Finally, we investigated the association of parasitemia with the mean SOFA score stratified by hemoglobin concentrations (Figure 1). The positive, linear association between parasitemia and SOFA was much stronger in patients with hemoglobin < 8.5 g/dL compared with non-anemic patients (p, test for interaction = 0.02). A similar interaction was observed with risk of MODS; the risk difference between parasitemia quartiles 4th and 1st was 55.6% among patients with hemoglobin < 8.5 g/dL and only 5.9% in non-anemic patients (p, test for interaction = 0.05).

Figure 1.
Figure 1.

Mean sequential organ failure assessment (SOFA) scores (A) and multiple organ dysfunction syndrome (MODS) risk (B) by parasitemia and hemoglobin concentrations on admission among patients admitted with malaria to Central Military Hospital, Bogotá between 2003 and 2012.

Citation: The American Society of Tropical Medicine and Hygiene 91, 1; 10.4269/ajtmh.13-0640

Discussion

We found that infection with P. falciparum, higher parasitemia, and low hemoglobin on admission were associated with higher SOFA scores and incidence of MODS in patients admitted to the hospital with a malaria diagnosis. In addition, there was a strong interaction between low hemoglobin and high parasitemia on the maximum SOFA score and risk for MODS.

These findings are important because MODS is a strong predictor of adverse outcomes in patients with complicated malaria, including ICU admission and mortality.4,9,19 Thus, simple, inexpensive tests that allow identification of patients at the highest risk of developing MODS could represent powerful tools to improve clinical outcomes of complicated malaria. Prior studies had found that either severe anemia,6,9,12,2022 high parasitemia,12,21,23 or plasma HRP-2 antigen13,14 among malaria patients admitted to hospital were related to increased risk of ICU admission, MODS, and death. However, the strong interaction between anemia and parasitemia on SOFA scores and MODS had not been reported previously. Our results indicate that the risk of MODS associated with severe anemia can be as low as that of non-anemic patients provided that parasitemia is low. Because parasitemia and anemia were assessed at the same time point, the opposite may also be true; i.e., that the risk associated with high parasitemia can be minimized if hemoglobin levels are increased. Whether measures such as transfusion or intensive anti-malarial treatment of severely anemic malaria patients with high parasitemia on admission could improve their immediate clinical outcome requires further investigation. The use of parasitemia and hemoglobin to identify high-risk patients with malaria deserves consideration in clinical settings.

ACKNOWLEDGMENTS

We are grateful to the Central Military Hospital medical records staff for their collaboration in the data collection. We also thank the Scientific Research Department of the Central Military Hospital for their institutional support of the project.

  • 1.

    Salord F, Allaouchiche B, Gaussorgues P, Boibieux A, Sirodot M, Gerard-Boncompain M, Biron F, Peyramond D, Robert D, 1991. Severe falciparum malaria (21 cases). Intensive Care Med 17: 449454.

    • Search Google Scholar
    • Export Citation
  • 2.

    Saissy JM, Rouvin B, Koulmann P, 2003. Severe malaria in intensive care units in 2003. Med Trop 63: 258266.

  • 3.

    Metha SR, Joshi V, Lazar AI, 1996. Unusual acute and chronic complications of malaria. J Assoc Physicians India 44: 451453.

  • 4.

    Krishnan A, Karnad DR, 2003. Severe falciparum malaria: an important cause of multiple organ failure in Indian intensive care unit patients. Crit Care Med 31: 22782284.

    • Search Google Scholar
    • Export Citation
  • 5.

    Manish R, Tripathy R, Das BK, 2003. Plasma glucose and tumor necrosis factor-alpha in adult patients with severe falciparum malaria. Trop Med Int Health 8: 125128.

    • Search Google Scholar
    • Export Citation
  • 6.

    Kochar DK, Kochar SK, Agrawal RP, Sabir M, Nayak KC, Agrawal TD, Purohit VP, Gupta RP, 2006. The changing spectrum of severe falciparum malaria: a clinical study from Bikaner (northwest India). J Vector Borne Dis 43: 104108.

    • Search Google Scholar
    • Export Citation
  • 7.

    Mohan A, Sharma SK, Bollineni S, 2008. Acute lung injury and acute respiratory distress syndrome in malaria. J Vector Borne Dis 45: 179193.

  • 8.

    Kanodia KV, Shah PR, Vanikar AV, Kasat P, Gumber M, Trivedi HL, 2010. Malaria induced acute renal failure: a single center experience. Saudi J Kidney Dis Transpl 21: 10881091.

    • Search Google Scholar
    • Export Citation
  • 9.

    Sarkar PK, Ahluwalia G, Vijayan VK, Talwar A, 2010. Critical care aspects of malaria. J Intensive Care Med 25: 93103.

  • 10.

    Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S, 1999. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med 25: 686696.

    • Search Google Scholar
    • Export Citation
  • 11.

    Jog S, Akole P, Pawar B, Gogate N, Gadgil S, Rajhans P, 2007. Sequential organ failure assessment score as an outcome predictor in malarial multiorgan dysfunction syndrome. Crit Care 11 (Suppl 2): 463.

    • Search Google Scholar
    • Export Citation
  • 12.

    Helbok R, Dent W, Nacher M, Lackner P, Treeprasertsuk S, Krudsood S, 2005. The use of the multi-organ-dysfunction score to discriminate different levels of severity in severe and complicated Plasmodium falciparum malaria. Am J Trop Med Hyg 72: 150154.

    • Search Google Scholar
    • Export Citation
  • 13.

    Fox L, Taylor T, Pensulo P, Liomba A, Mpakiza A, Varela A, Glover SJ, Reeves MJ, Seydel KB, 2013. HRP2 plasma levels predict progression to cerebral malaria in Malawian children with Plasmodium falciparum infection. J Infect Dis 208: 500503.

    • Search Google Scholar
    • Export Citation
  • 14.

    Hendriksen IC, Mwanga-Amumpaire J, von Seidlein L, Mtove G, White LJ, Olaosebikan R, Lee SJ, Tshefu AK, Woodrow C, Amos B, Karema C, Saiwaew S, Maitland K, Gomes E, Pan-Ngum W, Gesase S, Silamut K, Reyburn H, Joseph S, Chotivanich K, Fanello CI, Day NP, White NJ, Dondorp AM, 2012. Diagnosing severe falciparum malaria in parasitemic African children: a prospective evaluation of plasma PfHRP2 measurement. PLoS Med 9: e1001297.

    • Search Google Scholar
    • Export Citation
  • 15.

    Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG, 1996. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Working Group on Sepsis-Related Problems of the ESICM. Intensive Care Med 22: 707710.

    • Search Google Scholar
    • Export Citation
  • 16.

    Antelman G, Msamanga GI, Spiegelman D, Urassa EJ, Narh R, Hunter DJ, Fawzi WW, 2000. Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania. J Nutr 130: 19501957.

    • Search Google Scholar
    • Export Citation
  • 17.

    Finkelstein JL, Mehta S, Duggan CP, Spiegelman D, Aboud S, Kupka R, Msamanga GI, Fawzi WW, 2012. Predictors of anemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections. Public Health Nutr 15: 928937.

    • Search Google Scholar
    • Export Citation
  • 18.

    Ogawa E, Furusyo N, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Tanabe Y, Kotoh K, Shimoda S, Hayashi J, 2013. Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy. J Hepatol 59: 667674.

    • Search Google Scholar
    • Export Citation
  • 19.

    Mishra SK, Panigrahi P, Mishra R, Mohanty S, 2007. Prediction of outcome in adults with severe falciparum malaria: a new scoring system. Malar J 6: 24.

    • Search Google Scholar
    • Export Citation
  • 20.

    Tangpukdee N, Krudsood S, Thanachartwet V, Duangdee C, Paksala S, Chonsawat P, Srivilairit S, Looareesuwan S, Wilairatana P, 2007. Predictive score of uncomplicated falciparum malaria patients turning to severe malaria. Korean J Parasitol 45: 273282.

    • Search Google Scholar
    • Export Citation
  • 21.

    Koh KH, Chew PH, Kiyu A, 2004. A retrospective study of malaria infections in an intensive care unit of a general hospital in Malaysia. Singapore Med J 45: 2836.

    • Search Google Scholar
    • Export Citation
  • 22.

    Kochar D, Kumawat BL, Karan S, Kochar SK, Agarwal RP, 1997. Severe and complicated malaria in Bikaner (Rajasthan), western India. Southeast Asian J Trop Med Public Health 28: 259267.

    • Search Google Scholar
    • Export Citation
  • 23.

    Moudden MK, Boukhira A, Zyani M, Boughalem M, Hda A, 2006. Severe imported malaria. The experience of the military hospital of Marrakech. Ann Biol Clin (Paris) 64: 501505.

    • Search Google Scholar
    • Export Citation

Author Notes

* Address correspondence to Eduardo Villamor, University of Michigan School of Public Health, Department of Epidemiology, 1415 Washington Heights, Ann Arbor, MI 48109. E-mail: villamor@umich.edu

Financial support: This project was funded by the University of Michigan, Department of Epidemiology.

Authors' addresses: Emily Walton and Eduardo Villamor, University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, MI, E-mails: ewalt@umich.edu and villamor@umich.edu. Henry Oliveros, Central Military Hospital, Department of Critical Medicine, Bogotá, Colombia, E-mail: henryor@unisabana.edu.co.

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