Abstract
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. 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. 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.
Highlights
Anemia is a common manifestation of Plasmodium infection and is responsible for substantial morbidity [1,2,3,4] as well as direct [5,6,7] and indirect mortality [8,9,10,11]
Some of these processes have been described in the non-falciparum human malarias [20,21,22,23], less is known about the epidemiology and pathogenesis of anemia due to these Plasmodium species [24,25,26]
Confirmed malaria was diagnosed in 18.3% (168,525) of patient presentations, with P. falciparum accounting for 53.3% of monoinfections, P. vivax for 32.3%, P. malariae 2.7%, and P. ovale 0.06%
Summary
Anemia is a common manifestation of Plasmodium infection and is responsible for substantial morbidity [1,2,3,4] as well as direct [5,6,7] and indirect mortality [8,9,10,11]. In more chronic infections, decreased marrow production of functional red blood cells due to the direct inhibitory effects of parasites [17] and cytokines [13,18] along with dysregulation of erythropoietin and iron metabolism [19] adds to the anemia of ongoing red blood cell loss [16] Some of these processes have been described in the non-falciparum human malarias [20,21,22,23], less is known about the epidemiology and pathogenesis of anemia due to these Plasmodium species [24,25,26]. Infections with P. falciparum in particular can cause anemia (a reduction in red blood cell numbers) and can damage the brain and other vital organs by blocking the capillaries that supply these organs with blood
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