“Asymptomatic” Malaria: A Chronic and Debilitating Infection That Should Be Treated

PLoS Medicine

Volumn 13, Issue 1, 2016, Pages

  Chen, Ingrid ^a   Clarke, Siân E ^b   Gosling, Roly ^a   Hamainza, Busiku ^c   Killeen, Gerry ^d,e   Magill, Alan ^f   O’Meara, Wendy ^g   Price, Ric N ^h,i   Riley, Eleanor M ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^c MINISTRY OF HEALTH   (Zambia)

^d LIVERPOOL SCHOOL OF TROPICAL MEDICINE   (United Kingdom)

^e IFAKARA HEALTH INSTITUTE   (Tanzania)

^f BILL AND MELINDA GATES FOUNDATION   (United States)

^g DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h MENZIES SCHOOL OF HEALTH RESEARCH   (Australia)

ⁱ UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HEME OXYGENASE 1; REACTIVE OXYGEN METABOLITE;

ANEMIA; ARTICLE; BACTERIAL INFECTION; COGNITIVE DEFECT; COMORBIDITY; DISEASE CONTROL; DISEASE ELIMINATION; HEALTH PROGRAM; HUMAN; MALARIA; MALARIA FALCIPARUM; MORTALITY; PLASMODIUM VIVAX MALARIA; PREGNANCY; ASYMPTOMATIC DISEASES; CHRONIC DISEASE; COGNITION DISORDERS; TREATMENT OUTCOME;

ANEMIA; ASYMPTOMATIC DISEASES; CHRONIC DISEASE; COGNITION DISORDERS; HUMANS; MALARIA; TREATMENT OUTCOME;

EID: 84961328499     PISSN: 15491277     EISSN: 15491676     Source Type: Journal    
DOI: 10.1371/journal.pmed.1001942     Document Type: Article

References (73)

1. Doolan DL, Dobano C, Baird JK, Acquired immunity to malaria. Clin Microbiol Rev. 2009;22(1):13–36, Table of Contents. doi: 10.1128/CMR.00025-08 19136431; PubMed Central PMCID: PMC2620631.
2. Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect. 2013;11(6):623–39. doi: 10.1586/Eri.13.45 WOS:000320165400015.
3. Greenwood BM, Asymptomatic malaria infections—do they matter? Parasitol Today. 1987;3(7):206–13. 15462957
4. Bousema T, Okell L, Felger I, Drakeley C, Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nature reviews Microbiology. 2014;12(12):833–40. doi: 10.1038/nrmicro3364 25329408.
5. Hamainza B, Moonga H, Sikaala CH, Kamuliwo M, Bennett A, Eisele TP, et al. Monitoring, characterization and control of chronic, symptomatic malaria infections in rural Zambia through monthly household visits by paid community health workers. Malar J. 2014;13:128. doi: 10.1186/1475-2875-13-128 24678631
6. WHO. Test. Treat. Track. Scaling up diagnostic testing, treatment and surveillance for malaria 2012. http://www.who.int/malaria/publications/atoz/test_treat_track_brochure.pdf.
7. O'Meara WP, Bejon P, Mwangi TW, Okiro EA, Peshu N, Snow RW, et al. Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya. Lancet. 2008;372(9649):1555–62. doi: 10.1016/S0140-6736(08)61655-4 18984188
8. Scott JA, Berkley JA, Mwangi I, Ochola L, Uyoga S, Macharia A, et al. Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. Lancet. 2011;378(9799):1316–23. doi: 10.1016/S0140-6736(11)60888-X 21903251
9. Binka F, Kubaje A, Adjuik M, Williams LA, Lengeler C, Maude GH, et al. Impact of permethrin impregnated bed nets on child mortality in Kassena-Nankana District, Ghana: A randomised controlled trial Trop Med Int Health. 1996;1(2):147–54. 8665378
10. D'Alessandro U, Olaleye BO, McGuire W, Langerock P, Bennett S, Aikins MK, et al. Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme. Lancet. 1995;345(8948):479–83. 7861874.
11. Greenwood BM, Greenwood AM, Bradley AK, Snow RW, Byass P, Hayes RJ, et al. A Comparison of Two Strategies for Control of Malaria within a Primary Health Care Programme in The Gambia. Lancet. 1988;1(8595):1121–27. 2896957
12. Menon A, Snow RW, Byass P, Greenwood BM, Hayes RJ, N'Jie AB, Sustained protection against mortality and morbidity from malaria in rural Gambian children by chemoprophylaxis given by village health workers. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1990;84(6):768–72. 2096501.
13. Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte JJ, Font F, et al. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. Lancet. 1997;350(9081):844–50. 9310602
14. Otoo LN, Snow RW, Menon A, Byass P, Greenwood BM, Immunity to malaria in young Gambian children after a two-year period of chemoprophylaxis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1988;82(1):59–65. 3051550
15. Nevill CG, Ochen K, Munafu CG, Bekobita D, Sezi CL, Response of Plasmodium falciparum to chloroquine and Fansidar in vivo and chloroquine and amodiaquine in vitro in Uganda. East Afr Med J. 1995;72(6):349–54. 7498001
16. Mason DP, McKenzie FE, Blood-stage dynamics and clinical implications of mixed Plasmodium vivax-Plasmodium falciparum infections. Am J Trop Med Hyg. 1999;61(3):367–74. 10497972; PubMed Central PMCID: PMC2483693.
17. Douglas N, Lampah D, Kenangalem E, Simpson J, Poespoprodjo J, Sugiarto P, et al. Major burden of severe anemia from non-falciparum malaria species in southern papua: a hospital-based surveillance study. PLoS Med. 2013;10(12):e1001575. doi: 10.1371/journal.pmed.1001575 24358031
18. Price RN, Simpson JA, Nosten F, Luxemburger C, Hkirjaroen L, ter Kuile F, et al. Factors contributing to anemia after uncomplicated falciparum malaria. Am J Trop Med Hyg. 2001;65(5):614–22. 11716124; PubMed Central PMCID: PMC4337986.
19. Phillips RE, Pasvol G, Anaemia of Plasmodium falciparum malaria. Baillieres Clin Haematol. 1992;5(2):315–30. 1511178.
20. Looareesuwan S, Merry AH, Phillips RE, Pleehachinda R, Wattanagoon Y, Ho M, et al. Reduced erythrocyte survival following clearance of malarial parasitaemia in Thai patients. Br J Haematol. 1987;67(4):473–8. 3322362.
21. Gwamaka M, Fried M, Domingo G, Duffy PE, Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia. Malar J. 2011;10:386. doi: 10.1186/1475-2875-10-386 22206234; PubMed Central PMCID: PMC3322349.
22. Douglas NM, Anstey NM, Buffet PA, Poespoprodjo JR, Yeo TW, White NJ, et al. The anaemia of Plasmodium vivax malaria. Malar J. 2012;11:135. doi: 10.1186/1475-2875-11-135 22540175; PubMed Central PMCID: PMC3438072.
23. Buffet PA, Safeukui I, Milon G, Mercereau-Puijalon O, David PH, Retention of erythrocytes in the spleen: a double-edged process in human malaria. Curr Opin Hematol. 2009;16(3):157–64. doi: 10.1097/MOH.0b013e32832a1d4b 19384231.
24. Leoni S, Buonfrate D, Angheben A, Gobbi F, Bisoffi Z, The hyper-reactive malarial splenomegaly: a systematic review of the literature. Malar J. 2015;14:185. doi: 10.1186/s12936-015-0694-3 25925423; PubMed Central PMCID: PMC4438638.
25. Newton CR, Warn PA, Winstanley PA, Peshu N, Snow RW, Pasvol G, et al. Severe anaemia in children living in a malaria endemic area of Kenya. Trop Med Int Health. 1997;2(2):165–78. 9472302.
26. Nacher M, Singhasivanon P, Silachamroon U, Treeprasertsuk S, Vannaphan S, Traore B, et al. Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand. Am J Trop Med Hyg. 2001;65(6):834–6. 11791982.
27. Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, et al. An immune basis for malaria protection by the sickle cell trait. PLoS Med. 2005;2(5):e128. doi: 10.1371/journal.pmed.0020128 15916466; PubMed Central PMCID: PMC1140945.
28. Mockenhaupt FP, Bedu-Addo G, Junge C, Hommerich L, Eggelte TA, Bienzle U, Markers of sulfadoxine-pyrimethamine-resistant Plasmodium falciparum in placenta and circulation of pregnant women. Antimicrob Agents Chemother. 2007;51(1):332–4. doi: 10.1128/AAC.00856-06 17088491; PubMed Central PMCID: PMC1797640.
29. Mayengue PI, Rieth H, Khattab A, Issifou S, Kremsner PG, Klinkert MQ, et al. Submicroscopic Plasmodium falciparum infections and multiplicity of infection in matched peripheral, placental and umbilical cord blood samples from Gabonese women. Trop Med Int Health. 2004;9(9):949–58. doi: 10.1111/j.1365-3156.2004.01294.x 15361107.
30. Cottrell G, Moussiliou A, Luty AJ, Cot M, Fievet N, Massougbodji A, et al. Submicroscopic Plasmodium falciparum Infections Are Associated With Maternal Anemia, Premature Births, and Low Birth Weight. Clin Infect Dis. 2015;60(10):1481–8. doi: 10.1093/cid/civ122 25694651.
31. Tagbor H, Bruce J, Browne E, Greenwood B, Chandramohan D, Malaria in pregnancy in an area of stable and intense transmission: is it asymptomatic? Trop Med Int Health. 2008;13(8):1016–21. doi: 10.1111/j.1365-3156.2008.02111.x 18631316
32. Langhorne J, Ndungu FM, Sponaas AM, Marsh K, Immunity to malaria: more questions than answers. Nature Immunology. 2008;9(7):725–32. doi: 10.1038/ni.f.205 WOS:000256904900009. 18563083
33. Scholzen A, Sauerwein RW, How malaria modulates memory: activation and dysregulation of B cells in Plasmodium infection. Trends in Parasitology. 2013;29(5):252–62. doi: 10.1016/j.pt.2013.03.002 WOS:000319092000006. 23562778
34. Riley EM, Stewart VA, Immune mechanisms in malaria: new insights in vaccine development. Nat Med. 2013;19(2):168–78. doi: 10.1038/nm.3083 23389617.
35. Mabey DC, Brown A, Greenwood BM, Plasmodium falciparum malaria and Salmonella infections in Gambian children. The Journal of infectious diseases. 1987;155(6):1319–21. 3553352.
36. Nadjm B, Amos B, Mtove G, Ostermann J, Chonya S, Wangai H, et al. WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. BMJ. 2010;340:c1350. doi: 10.1136/bmj.c1350 20354024
37. Biggs HM, Lester R, Nadjm B, Mtove G, Todd JE, Kinabo GD, et al. Invasive Salmonella infections in areas of high and low malaria transmission intensity in Tanzania. Clin Infect Dis. 2014;58(5):638–47. doi: 10.1093/cid/cit798 24336909; PubMed Central PMCID: PMC3922215.
38. Mtove G, Amos B, Nadjm B, Hendriksen ICE, Dondorp AM, Mwambuli A, et al. Decreasing incidence of severe malaria and community-acquired bacteraemia among hospitalized children in Muheza, north-eastern Tanzania, 2006–2010. Malar J. 2011;10. Artn 320 doi: 10.1186/1475-2875-10-320 WOS:000297107500001.
39. Mackenzie G, Ceesay SJ, Hill PC, Walther M, Bojang KA, Satoguina J, et al. A decline in the incidence of invasive non-typhoidal Salmonella infection in The Gambia temporally associated with a decline in malaria infection. PLoS ONE. 2010;5(5):e10568. doi: 10.1371/journal.pone.0010568 20485496; PubMed Central PMCID: PMC2867957.
40. Reddy EA, Shaw AV, Crump JA, Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(6):417–32. doi: 10.1016/S1473-3099(10)70072-4 20510282; PubMed Central PMCID: PMC3168734.
41. Cunnington AJ, de Souza JB, Walther M, Riley EM, Malaria impairs resistance to Salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization. Nat Med. 2011;18(1):120–7. doi: 10.1038/nm.2601 22179318
42. Cunnington AJ, Njie M, Correa S, Takem EN, Riley EM, Walther M, Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction. J Immunol. 2012;189(11):5336–46. doi: 10.4049/jimmunol.1201028 23100518
43. Lokken KL, Mooney JP, Butler BP, Xavier MN, Chau JY, Schaltenberg N, et al. Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function. PLoS Pathog. 2014;10(5):e1004049. doi: 10.1371/journal.ppat.1004049 24787713; PubMed Central PMCID: PMC4006898.
44. Mooney JP, Butler BP, Lokken KL, Xavier MN, Chau JY, Schaltenberg N, et al. The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection. Mucosal Immunol. 2014;7(6):1302–11. doi: 10.1038/mi.2014.18 24670425
45. Fernando SD, Rodrigo C, Rajpakse S, The ‘Hidden’ Burden of Malaria: Cognitive Impairment Following Infection. Malar J. 2010;9:366. doi: 10.1186/1475-2875-9-366 21171998
46. Lucas AM, Malaria Eradication and Educational Attainment: Evidence from Paraguay and Sri Lanka. Am Econ J Appl Econ. 2010;2(2):46–71. doi: 10.1257/app.2.2.46 23946866; PubMed Central PMCID: PMC3740749.
47. Bleakley H, Malaria eradication in the Americas: A retrospective analysis of childhood exposure. Am Econ J Appl Econ. 2010;2(2):1–45.
48. Barofsky J, Chase C, Anekwe T, Farzadfar F. The Economic Effects of Malaria Eradication: Evidence from an intervention in Uganda 2011. http://www.hsph.harvard.edu/program-on-the-global-demography-of-aging/WorkingPapers/2011/PGDA_WP_70.pdf.
49. Burlando A. The Impact of Malaria on Education: Evidence from Ethiopia 2012. http://pages.uoregon.edu/burlando/Current_Research_files/Ethiopia%207-28-12.pdf.
50. Percoco M, The Fight Against Disease: Malaria and Economic Development in Italian Regions. Econ Geogr. 2013;89(2):105–25. doi: 10.1111/ecge.12008 WOS:000317130600001.
51. Thuilliez J, Sissoko MS, Toure OB, Kamate P, Berthelemy JC, Doumbo OK, Malaria and primary education in Mali: a longitudinal study in the village of Doneguebougou. Soc Sci Med. 2010;71(2):324–34. doi: 10.1016/j.socscimed.2010.02.027 20413198; PubMed Central PMCID: PMC2923336.
52. Nankabirwa J, Wandera B, Kiwanuka N, Staedke SG, Kamya MR, Brooker SJ, Asymptomatic Plasmodium Infection and Cognition among Primary Schoolchildren in a High Malaria Transmission Setting in Uganda. Am J Trop Med Hyg. 2013;88(6):1102–8. doi: 10.4269/ajtmh.12-0633 WOS:000319957700015. 23589533
53. Fernando D, de Silva D, Wickremasinghe R, Short-term impact of an acute attack of malaria on the cognitive performance of schoolchildren living in a malaria-endemic area of Sri Lanka. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2003;97(6):633–9. 16117954.
54. Fernando SD, Gunawardena DM, Bandara MR, De Silva D, Carter R, Mendis KN, et al. The impact of repeated malaria attacks on the school performance of children. Am J Trop Med Hyg. 2003;69(6):582–8. 14740872.
55. Vitor-Silva S, Reyes-Lecca RC, Pinheiro TRA, Lacerda MVG, Malaria is associated with poor school performance in an endemic area of the Brazilian Amazon. Malar J. 2009;8. doi: 10.1186/1475-2875-8-230 WOS:000271601700001.
56. Al Serouri AW, Grantham-McGregor SM, Greenwood B, Costello A, Impact of asymptomatic malaria parasitaemia on cognitive function and school achievement of schoolchildren in the Yemen Republic. Parasitology. 2000;121(PT 4):337–45. 11072896.
57. Fink G, Olgiati A, Hawela M, Miller JM, Matafwali B, Association between Early Childhood Exposure to Malaria and Children’s Pre-School Development: Evidence from the Zambia Early Childhood Development Project. Malar J. 2013;12:12. doi: 10.1186/1475-2875-12-12 23297692
58. Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, Romero RA, et al. Severe Malarial Anemia is Associated With Long-term Neurocognitive Impairment. Clin Infect Dis. 2014;59(3):336–44. doi: 10.1093/cid/ciu293 WOS:000342919700003. 24771329
59. Boivin MJ, Sikorskii A, Familiar-Lopez I, Ruisenor-Escudero H, Bigira V, Kapisi J, et al. Bouts Of Malaria Illness As Mediated By Anemia Diminishes Cognitive Development In Very Young Ugandan Children. Am J Trop Med Hyg. 2014;91(5):Suppl 1. 7.
60. Fernando D, de Silva D, Carter R, Mendis KN, Wickremasinghe R, A randomized, double-blind, placebo-controlled, clinical trial of the impact of malaria prevention on the educational attainment of school children. Am J Trop Med Hyg. 2006;74(3):386–93. 16525095.
61. Clarke SE, Jukes MC, Njagi JK, Khasakhala L, Cundill B, Otido J, et al. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9633):127–38. doi: 10.1016/S0140-6736(08)61034-X 18620950; PubMed Central PMCID: PMC2495044.
62. Clarke S, Rouhani S, Diarra S, Bamadio M, Jones R, Traore D, et al. The impact of intermittent parasite clearance on malaria, anaemia, and cognition in schoolchildren: New evidence from an area of highly seasonal transmission. Trop Med Int Health. 2013;18(Suppl 1):64.
63. Jukes MC, Pinder M, Grigorenko EL, Smith HB, Walraven G, Bariau EM, et al. Long-term impact of malaria chemoprophylaxis on cognitive abilities and educational attainment: follow-up of a controlled trial. PLoS Clin Trials. 2006;1(4):e19. doi: 10.1371/journal.pctr.0010019 17013430; PubMed Central PMCID: PMC1851720.
64. Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ, Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nature communications. 2012;3:1237. doi: 10.1038/ncomms2241 23212366; PubMed Central PMCID: PMC3535331.
65. WHO. WHO Policy Recommendation: Seasonal Malaria Chemoprevention (SMC) for Plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in Africa 2012. http://www.who.int/malaria/publications/atoz/smc_policy_recommendation_en_032012.pdf?ua=1.
66. WHO. Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) 2012. http://www.who.int/malaria/iptp_sp_updated_policy_recommendation_en_102012.pdf.
67. WHO. WHO Policy recommendation on intermittent preventive treatment during infancy with sulphadoxine-pyrimethamine (IPTi-SP) for Plasmodium falciparum malaria control in Africa 2010. http://www.who.int/malaria/publications/atoz/policy_recommendation_IPTi_032010/en/.
68. Nankabirwa J, Brooker SJ, Clarke SE, Fernando D, Gitonga CW, Schellenberg D, et al. Malaria in school-age children in Africa: an increasingly important challenge. Trop Med Int Health. 2014;19(11):1294–309. doi: 10.1111/tmi.12374 25145389
69. MORU. Malaria Elimination [4 December 2015]. http://www.tropmedres.ac/malaria-elimination-2.
70. PATH. Malaria Control and Elimination Partnership in Africa [4 December 2015]. http://www.makingmalariahistory.org/about/about-macepa-malaria-control-and-evaluation-partnership-in-africa/.
71. Evaluation of Targeted Parasite Elimination in Swaziland (TPE) [Internet]. [cited 4 December 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT02315690.
72. Tiono AB, Ouédraogo A, Ogutu B, Diarra A, Coulibaly S, Gansané A, et al. A controlled, parallel, cluster-randomized trial of community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso. Malar J. 2013;12(79).
73. Newby G, Hwang J, Koita K, Chen I, Greenwood B, von Seidlein L, et al. Review of mass drug administration for malaria and its operational challenges. Am J Trop Med Hyg. 2015;93(1):125–34. doi: 10.4269/ajtmh.14-0254 26013371; PubMed Central PMCID: PMC4497884.