Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study
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.
Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study. PLoS Med 10(12): e32767. doi:10.1371/journal.pmed.1001575
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001575
Souhrn
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.
Please see later in the article for the Editors' Summary
Zdroje
1. Roca-FeltrerA, CarneiroI, Armstrong SchellenbergJR (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.
2. 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.
3. MurphySC, BremanJG (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.
4. CalisJCJ, PhiriKS, FaragherEB, BrabinBJ, BatesI, et al. (2008) Severe anemia in Malawian children. N Engl J Med 358: 888–899.
5. MarshK, ForsterD, WaruiruC, MwangiI, WinstanleyP, et al. (1995) Indicators of life-threatening malaria in African children. N Engl J Med 332: 1399–1404.
6. ObonyoCO, VululeJ, AkhwaleWS, GrobbeeDE (2007) In-hospital morbidity and mortality due to severe malarial anemia in Western Kenya. Am J Trop Med Hyg 77: 23–28.
7. SlutskerL, TaylorTE, WirimaJJ, SteketeeRW (1994) In-hospital morbidity and mortality due to malaria-associated severe anaemia in two areas of Malawi with different patterns of malaria infection. Trans R Soc Trop Med Hyg 88: 548–551.
8. NevillCG, SomeES, Mung'alaVO, MutemiW, NewL, et al. (1996) Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Trop Med Int Health 1: 139–146.
9. AlonsoPL, LindsaySW, Armstrong SchellenbergJR, KeitaK, GomezP, et al. (1993) A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, West Africa. 6. The impact of the interventions on mortality and morbidity from malaria. Trans R Soc Trop Med Hyg 87: 37–44.
10. KorenrompEL, Armstrong-SchellenbergJRM, WilliamsBG, NahlenBL, SnowRW (2004) Impact of malaria control on childhood anaemia in Africa - a quantitative review. Trop Med Int Health 9: 1050–1065.
11. BrabinBJ, PremjiZ, VerhoeffF (2001) An analysis of anemia and child mortality. J Nutr 131: 636S–645S; discussion 646S–648S.
12. BuffetPA, SafeukuiI, DeplaineG, BrousseV, PrendkiV, et al. (2011) The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood 117: 381–392.
13. WickramasingheSN, AbdallaSH (2000) Blood and bone marrow changes in malaria. Baillieres Best Pract Res Clin Haematol 13: 277–299.
14. WoodruffAW, AnsdellVE, PettittLE (1979) Cause of anaemia in malaria. Lancet 1: 1055–1057.
15. DasBS, NandaNK (1999) Evidence for erythrocyte lipid peroxidation in acute falciparum malaria. Trans R Soc Trop Med Hyg 93: 58–62.
16. HaldarK, MohandasN (2009) Malaria, erythrocytic infection, and anemia. Hematology Am Soc Hematol Educ Program 87–93.
17. AbdallaS, WeatherallDJ, WickramasingheSN, HughesM (1980) The anaemia of P. falciparum malaria. Br J Haematol 46: 171–183.
18. NussenblattV, MukasaG, MetzgerA, NdeeziG, GarrettE, et al. (2001) Anemia and interleukin-10, tumor necrosis factor alpha, and erythropoietin levels among children with acute uncomplicated Plasmodium falciparum malaria. Clin Diagn Lab Immun 8: 1164–1170.
19. ChangK-H, StevensonMM (2004) Malarial anaemia: mechanisms and implications of insufficient erythropoiesis during blood-stage malaria. Int J Parasitol 34: 1501–1516.
20. BhattacharyaJ, Swarup-MitraS (1987) Reduction in erythrocytic GSH level and stability in Plasmodium vivax malaria. Trans R Soc Trop Med Hyg 81: 64–66.
21. SelvamR, BaskaranG (1996) Hematological impairments in recurrent Plasmodium vivax infected patients. Jpn J Med Sci Biol 49: 151–165.
22. WickramasingheSN, LooareesuwanS, NagachintaB, WhiteNJ (1989) Dyserythropoiesis and ineffective erythropoiesis in Plasmodium vivax malaria. Br J Haematol 72: 91–99.
23. HandayaniS, ChiuDT, TjitraE, KuoJS, LampahD, et al. (2009) High deformability of Plasmodium vivax-infected red blood cells under microfluidic conditions. J Infect Dis 199: 445–450.
24. DouglasNM, AnsteyNM, BuffetPA, PoespoprodjoJR, YeoTW, et al. (2012) The anaemia of Plasmodium vivax malaria. Malar J 11: 135.
25. AnsteyNM, DouglasNM, PoespoprodjoJR, PriceRN (2012) Plasmodium vivax: clinical spectrum, risk factors and pathogenesis. Adv Parasitol 80: 151–201.
26. ManningL, LamanM, Rosanas-UrgellA, MichonP, AipitS, et al. (2012) Severe anemia in papua new guinean children from a malaria-endemic area: a case-control etiologic study. PloS Negl Trop Dis 6: e1972 doi:10.1371/journal.pntd.0001972
27. BlolandPB, BorigaDA, RuebushTK, McCormickJB, RobertsJM, et al. (1999) Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
28. MaitlandK, WilliamsTN, NewboldCI (1997) Plasmodium vivax and P. falciparum: biological interactions and the possibility of cross-species immunity. Parasitol Today 13: 227–231.
29. MaitlandK, WilliamsTN, BennettS, NewboldCI, PetoTEA, et al. (1996) The interaction between Plasmodium falciparum and P. vivax in children on Espiritu Santo Island, Vanuatu. Trans R Soc Trop Med Hyg 90: 614–620.
30. PriceRN, SimpsonJA, NostenF, LuxemburgerC, HkirijaroenL, et al. (2001) Factors contributing to anemia after uncomplicated falciparum malaria. Am J Trop Med Hyg 65: 614–622.
31. MayxayM, PukrittayakameeS, NewtonPN, WhiteNJ (2004) Mixed-species malaria infections in humans. Trends Parasitol 20: 233–240.
32. LancaEF, MagalhaesBM, Vitor-SilvaS, SiqueiraAM, BenzecrySG, et al. (2012) Risk factors and characterization of Plasmodium vivax-associated admissions to pediatric intensive care units in the Brazilian Amazon. PLoS ONE 7: e35406 doi:10.1371/journal.pone.0035406
33. TjitraE, AnsteyNM, SugiartoP, WarikarN, KenangalemE, et al. (2008) Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med 5: e128 doi:10.1371/journal.pmed.0050128
34. GentonB, D'AcremontV, RareL, BaeaK, ReederJC, et al. (2008) Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med 5: e127 doi:10.1371/journal.pmed.0050127
35. BarcusMJ, BasriH, PicarimaH, ManyakoriC, Sekartuti, et al. (2007) Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in Northeastern Indonesian Papua. Am J Trop Med Hyg 77: 984–991.
36. PoespoprodjoJR, FobiaW, KenangalemE, LampahDA, WarikarN, et al. (2008) Adverse pregnancy outcomes in an area where multidrug-resistant Plasmodium vivax and Plasmodium falciparum infections are endemic. Clin Infect Dis 46: 1374–1381.
37. KaryanaM, BurdarmL, YeungS, KenangalemE, WarikerN, et al. (2008) Epidemiology of multidrug resistant P. vivax and P. falciparum infection in Southern Papua, Indonesia. Malar J 7: 148.
38. RoystonP, AltmanD (1994) Regression using fractional polynomials of continuous covariates: parsimonious parametric modelling. Appl Statist 43: 429–467.
39. GreenlandS, DrescherK (1993) Maximum likelihood estimation of the attributable fraction from logistic models. Biometrics 49: 865–872.
40. World Health Organization, United Nations Children's Fund (2004) Focusing on anaemia: towards an integrated approach for effective anaemia control. Joint statement by the World Health Organization and the United Nations Children's Fund. Geneva: World Health Organization.
41. HemmerCJ, HolstFGE, KernP, ChiwakataCB, DietrichM, et al. (2006) Stronger host response per parasitized erythrocyte in Plasmodium vivax or ovale then in Plasmodium falciparum malaria. Trop Med Int Health 11: 817–823.
42. YeoTW, LampahDA, TjitraE, PieraK, GitawatiR, et al. (2010) Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax, compared with Plasmodium falciparum: a prospective study in Papua, Indonesia. J Infect Dis 202: 109–112.
43. KlingPJ, SchmidtRL, RobertsRA, WidnessJA (1996) Serum erythropoietin levels during infancy: associations with erythropoiesis. J Pediatr 128: 791–796.
44. SachsJ, MalaneyP (2002) The economic and social burden of malaria. Nature 415: 680–685.
45. McKenzieFE, JefferyGM, CollinsWE (2001) Plasmodium malariae blood-stage dynamics. J Parasitol 87: 626–637.
46. McQueenPG (2010) Population dynamics of a pathogen: the conundrum of vivax malaria. Biophys Rev 2: 111–120.
47. MuellerI, ZimmermanPA, ReederJC (2007) Plasmodium malariae and Plasmodium ovale–the “bashful” malaria parasites. Trends Parasitol 23: 278–283.
48. VeenemansJ, Andang'oPEA, MbugiEV, KraaijenhagenRJ, MwanikiDL, et al. (2008) Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya. J Infect Dis 198: 401–408.
49. DanquahI, MockenhauptFP (2008) Alpha+-thalassaemia and malarial anaemia. Trends Parasitol 24: 479–481.
50. FowkesFJI, AllenS, AllenA, AlpersMP, WeatherallDJ, et al. (2008) Increased microerythrocyte count in homozygous alpha+-thalassaemia contributes to protection against severe malarial anaemia. PLoS Med 5: e56 doi:10.1371/journal.pmed.0050056
51. WilliamsTN, MaitlandK, BennettS, GanczakowskiM, PetoTE, et al. (1996) High incidence of malaria in alpha-thalassaemic children. Nature 383: 522–525.
52. KruatrachueM, CharoenlarpP, ChongsuphajaisiddhiT, HarinasutaC (1962) Erythrocyte glucose-6-phosphate dehydrogenase and malaria in Thailand. Lancet 2: 1183–1186.
53. KimuraM, SoemantriA, IshidaT (2002) Malaria species and Southeast Asian ovalocytosis defined by a 27-bp deletion in the erythrocyte band 3 gene. Southeast Asian J Trop Med Public Health 33: 4–6.
54. FooLC, RekhrajV, ChiangGL, MakJW (1992) Ovalocytosis protects against severe malaria parasitemia in the Malayan aborigines. Am J Trop Med Hyg 47: 271–275.
55. ShimizuH, TamamM, SoemantriA, IshidaT (2005) Glucose-6-phosphate dehydrogenase deficiency and Southeast Asian ovalocytosis in asymptomatic Plasmodium carriers in Sumba Island, Indonesia. J Hum Genet 50: 420–424.
56. SerjeantsonS, BrysonK, AmatoD, BabonaD (1977) Malaria and hereditary ovalocytosis. Hum Genet 37: 161–167.
57. Kitchen SF (1939) Malariology. London: W.B. Saunders.
58. KabyemelaER, FriedM, KurtisJD, MutabingwaTK, DuffyPE (2008) Decreased susceptibility to Plasmodium falciparum infection in pregnant women with iron deficiency. J Infect Dis 198: 163–166.
59. BrookerS, AkhwaleW, PullanR, EstambaleB, ClarkeSE, et al. (2007) Epidemiology of Plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control. Am J Trop Med Hyg 77: 88–98.
60. NacherM, SinghasivanonP, YimsamranS, ManibunyongW, ThanyavanichN, et al. (2002) Intestinal helminth infections are associated with increased incidence of Plasmodium falciparum malaria in Thailand. J Parasitol 88: 55–58.
61. SpiegelA, TallA, RaphenonG, TrapeJF, DruilheP (2003) Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 97: 198–199.
62. BoelM, CarraraVI, RijkenM, ProuxS, NacherM, et al. (2010) Complex interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese border. PloS Negl Trop Dis 4: e887 doi:10.1371/journal.pntd.0000887
63. MeloGC, Reyes-LeccaRC, Vitor-SilvaS, MonteiroWM, MartinsM, et al. (2010) Concurrent helminthic infection protects schoolchildren with Plasmodium vivax from anemia. PLoS ONE 5: e11206 doi:10.1371/journal.pone.0011206
64. StoltzfusRJ, ChwayaHM, MontresorA, AlbonicoM, SavioliL, et al. (2000) Malaria, hookworms and recent fever are related to anemia and iron status indicators in 0- to 5-y old Zanzibari children and these relationships change with age. J Nutr 130: 1724–1733.
65. Brabin BJ (1991) The risks and severity of malaria in pregnant women. Geneva: World Health Organization.
66. NostenF, ter KuileF, MaelankirriL, DecludtB, WhiteNJ (1991) Malaria during pregnancy in an area of unstable endemicity. Trans R Soc Trop Med Hyg 85: 424–429.
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2013 Číslo 12
- Statinová intolerance
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Co dělat při intoleranci statinů?
- Pleiotropní účinky statinů na kardiovaskulární systém
- DESATORO PRE PRAX: Aktuálne odporúčanie ESPEN pre nutričný manažment u pacientov s COVID-19
Najčítanejšie v tomto čísle
- Artemisinin Combination Therapy: A Good Antimalarial, but Is the Dose Right?
- Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation
- Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals
- Malaria and Severe Anemia: Thinking beyond