Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Dec;10(12):e1001575; discussion e1001575.
doi: 10.1371/journal.pmed.1001575. Epub 2013 Dec 17.

Major Burden of Severe Anemia From Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study

Affiliations
Free PMC article

Major Burden of Severe Anemia From Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study

Nicholas M Douglas et al. PLoS Med. .
Free PMC article

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow diagram of the merging process.
Figure 2
Figure 2. Age distribution of patient presentations to hospital by malaria status (top) and Plasmodium species (bottom).
Figure 3
Figure 3. Estimated mean hemoglobin concentration in hospital attendees by ethnicity from infancy to adulthood (A) and during the first 2 years of life (B).
Figures generated by multiple fractional polynomial regression analyses with the following covariables: ethnic group by age, Plasmodium species, sex, and year. Bands represent 95% CIs.
Figure 4
Figure 4. Estimated mean hemoglobin in hospital attendees by Plasmodium species from infancy to adulthood (A) and during the first 2 years of life (B) and the estimated probability of severe anemia (hemoglobin <5 g/dl) by Plasmodium species from infancy to adulthood (C) and during the first 2 years of life (D).
Figures generated by multiple fractional polynomial regression analyses with the following covariables: Plasmodium species by age, sex, ethnic group, and year. Bands represent 95% CIs.
Figure 5
Figure 5. Estimated mean hemoglobin in hospital attendees by number of malaria episodes in the last 63 days from infancy to adulthood (A) and during the first 2 years of life (B).
189,671 patients had no recent episodes of malaria, 30,174 had one episode, and 4,572 had two or more episodes. Figures were generated by multiple fractional polynomial regression analysis with the following covariables: number of previous malaria episodes by age, Plasmodium species, ethnic group, sex, and year. Bands represent 95% CIs.
Figure 6
Figure 6. Adjusted population attributable fractions of severe anemia (hemoglobin <5 g/dl) by Plasmodium species and age.
Figure generated by multiple logistic regression analyses with the following covariables for each age stratum: Plasmodium species, sex, ethnic group, and year. Bands represent 95% CIs.
Figure 7
Figure 7. Estimated probability of mortality by hemoglobin concentration overall (A) and by Plasmodium species (B).
Figures generated by multiple fractional polynomial regression analyses with the following covariables: Plasmodium species, hemoglobin, age, sex, ethnic group, and year. Bands represent 95% CIs. Risk of death in Figure 6A = 1/(1+exp(−(−1.44−0.4146 * hb+0.0006 * hb3))), where the other covariates in the model are set equal to their mean value (for continuous variables) or prevalence (for indicator variables).

Comment in

Similar articles

See all similar articles

Cited by 60 articles

See all "Cited by" articles

References

    1. Roca-Feltrer A, Carneiro I, Armstrong Schellenberg JR (2008) Estimates of the burden of malaria morbidity in Africa in children under the age of 5 years. Trop Med Int Health 13: 771–783. - PubMed
    1. Snow RW, Craig MH, Newton CRJC, Steketee RW (2003) The public health burden of Plasmodium falciparum malaria in Africa: deriving the numbers. BethesdaMaryland: Fogarty International Center, National Institutes of Health.
    1. Murphy SC, Breman JG (2001) Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 64: 57–67. - PubMed
    1. Calis JCJ, Phiri KS, Faragher EB, Brabin BJ, Bates I, et al. (2008) Severe anemia in Malawian children. N Engl J Med 358: 888–899. - PubMed
    1. Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley P, et al. (1995) Indicators of life-threatening malaria in African children. N Engl J Med 332: 1399–1404. - PubMed

Publication types

MeSH terms

Feedback