Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua

A Hospital-Based Surveillance Study

Nicholas (Nick) DOUGLAS, Daniel Lampah, Enny Kenangalem, Julie Simpson, Jeanne Rini Poespoprodjo, Paulus Sugiarto, Nicholas Anstey, Ric Price

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia.

Methods and Findings: 
Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present in 8,151 (3.7%) patients. Compared to patients without malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, p<0.001. Overall, 12.2% (95% CI 11.2%–13.3%) of severe anemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; p<0.001). Not all patients had a hemoglobin measurement, thus limitations of the study include the potential for selection bias, and possible residual confounding in multivariable analyses.

Conclusions: 
In Papua P. vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity.
Original languageEnglish
Article numbere1001575
Pages (from-to)1-17
Number of pages17
JournalPLoS Medicine
Volume10
Issue number12
DOIs
Publication statusPublished - 17 Dec 2013

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Malaria
Anemia
Hemoglobins
Plasmodium
Coinfection
Infection
Odds Ratio
Vivax Malaria
Indonesia
Selection Bias
Inpatients
Outpatients
Referral and Consultation
Public Health
Demography

Cite this

DOUGLAS, N. N., Lampah, D., Kenangalem, E., Simpson, J., Poespoprodjo, J. R., Sugiarto, P., ... Price, R. (2013). Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study. PLoS Medicine, 10(12), 1-17. [e1001575]. https://doi.org/10.1371/journal.pmed.1001575
DOUGLAS, Nicholas (Nick) ; Lampah, Daniel ; Kenangalem, Enny ; Simpson, Julie ; Poespoprodjo, Jeanne Rini ; Sugiarto, Paulus ; Anstey, Nicholas ; Price, Ric. / Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua : A Hospital-Based Surveillance Study. In: PLoS Medicine. 2013 ; Vol. 10, No. 12. pp. 1-17.
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abstract = "Background: The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia.Methods and Findings: Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8{\%}) were associated with a hemoglobin measurement, of whom 67,696 (30.8{\%}) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95{\%} CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95{\%} CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95{\%} CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95{\%} CI 9.49–9.57]); p-value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present in 8,151 (3.7{\%}) patients. Compared to patients without malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95{\%} CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95{\%} CI 2.00–2.23), 1.87 (95{\%} CI 1.74–2.01), and 2.18 (95{\%} CI 1.76–2.67), respectively, p<0.001. Overall, 12.2{\%} (95{\%} CI 11.2{\%}–13.3{\%}) of severe anemia was attributable to non-falciparum infections compared with 15.1{\%} (95{\%} CI 13.9{\%}–16.3{\%}) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95{\%} CI 5.17–6.50]; p<0.001). Not all patients had a hemoglobin measurement, thus limitations of the study include the potential for selection bias, and possible residual confounding in multivariable analyses.Conclusions: In Papua P. vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity.",
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Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua : A Hospital-Based Surveillance Study. / DOUGLAS, Nicholas (Nick); Lampah, Daniel; Kenangalem, Enny; Simpson, Julie; Poespoprodjo, Jeanne Rini; Sugiarto, Paulus; Anstey, Nicholas; Price, Ric.

In: PLoS Medicine, Vol. 10, No. 12, e1001575, 17.12.2013, p. 1-17.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua

T2 - A Hospital-Based Surveillance Study

AU - DOUGLAS, Nicholas (Nick)

AU - Lampah, Daniel

AU - Kenangalem, Enny

AU - Simpson, Julie

AU - Poespoprodjo, Jeanne Rini

AU - Sugiarto, Paulus

AU - Anstey, Nicholas

AU - Price, Ric

PY - 2013/12/17

Y1 - 2013/12/17

N2 - Background: The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia.Methods and Findings: Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present in 8,151 (3.7%) patients. Compared to patients without malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, p<0.001. Overall, 12.2% (95% CI 11.2%–13.3%) of severe anemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; p<0.001). Not all patients had a hemoglobin measurement, thus limitations of the study include the potential for selection bias, and possible residual confounding in multivariable analyses.Conclusions: In Papua P. vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity.

AB - Background: The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia.Methods and Findings: Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present in 8,151 (3.7%) patients. Compared to patients without malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, p<0.001. Overall, 12.2% (95% CI 11.2%–13.3%) of severe anemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; p<0.001). Not all patients had a hemoglobin measurement, thus limitations of the study include the potential for selection bias, and possible residual confounding in multivariable analyses.Conclusions: In Papua P. vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity.

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KW - Female

KW - Hemoglobins

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Malaria

KW - Male

KW - Middle Aged

KW - Risk Factors

KW - Young Adult

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DOUGLAS NN, Lampah D, Kenangalem E, Simpson J, Poespoprodjo JR, Sugiarto P et al. Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study. PLoS Medicine. 2013 Dec 17;10(12):1-17. e1001575. https://doi.org/10.1371/journal.pmed.1001575