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Ensuring quality and access for malaria diagnosis: how can it be achieved?

Abstract

The replacement of conventional antimalarial drugs with high-cost, artemisinin-based alternatives has created a gap in the successful management of malaria. This gap reflects an increased need for accurate disease diagnosis that cannot be met by traditional microscopy techniques. The recent introduction of rapid diagnostic tests (RDTs) has the potential to meet this need, but successful RDT implementation has been curtailed by poor product performance, inadequate methods to determine the quality of products and a lack of emphasis and capacity to deal with these issues. Economics and a desire for improved case management will result in the rapid growth of RDT use in the coming years. However, for their potential to be realized, it is crucial that high-quality RDT products that perform reliably and accurately under field conditions are made available. In achieving this goal, the shift from symptom-based diagnosis to parasite-based management of malaria can bring significant improvements to tropical fever management, rather than represent a further burden on poor, malaria-endemic populations and their overstretched health services.

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Figure 1: Stages of development of Plasmodium falciparum at which antigens detected by malaria rapid diagnostic tests are produced.
Figure 2: Global distribution of malaria.
Figure 3: Hypothetical comparison between case cost of malaria diagnosis by microscopy and rapid diagnostic tests (RDTs).
Figure 4: The effect of adding parasite-based diagnosis to malaria case management based on symptoms and signs.
Figure 5: Outline of requirements for an adequate national quality assurance system for malaria rapid diagnostic tests (RDTs).
Figure 6: Mode of action of antigen-detecting malaria rapid diagnostic tests (RDTs).

References

  1. 1

    Font, F. et al. Diagnostic accuracy and case management of clinical malaria in the primary health services of a rural area in south-eastern Tanzania. Trop. Med. Int. Health 6, 423– 428 (2001).

    CAS  PubMed  Article  Google Scholar 

  2. 2

    Chandramohan, D. et al. A clinical algorithm for the diagnosis of malaria: results of an evaluation in an area of low endemicity. Trop. Med. Int. Health 6, 505– 510 (2001).

    CAS  PubMed  Article  Google Scholar 

  3. 3

    Luxemburger, C. et al. Clinical features cannot predict a diagnosis of malaria or differentiate the infecting species in children living in an area of low transmission. Trans. R. Soc. Trop. Med. Hyg. 92, 45– 49 (1998).

    CAS  PubMed  Article  Google Scholar 

  4. 4

    Armstrong-Schellenberg, J. R. M., Smith, T., Alonso, P. L. & Hayes, R. J. What is clinical malaria? Finding case definitions for field research in highly endemic areas. Parasitol. Today 10, 439– 442 (1994). Illustrates the poor specificity of symptom-based diagnosis of malaria in endemic countries.

    Article  Google Scholar 

  5. 5

    Smith, T., Hurt, N., Teuscher, T. & Tanner, M. Is fever a good sign for clinical malaria in surveys of endemic communities? Am. J. Trop. Med. Hyg. 52, 306– 310 (1995).

    CAS  PubMed  Article  Google Scholar 

  6. 6

    Chandramohan, D., Jaffar, S. & Greenwood, B. Use of clinical algorithms for diagnosing malaria. Trop. Med. Int. Health 7, 45– 52 (2002).

    PubMed  Article  Google Scholar 

  7. 7

    Reyburn, H. et al. Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. BMJ 329, 1212 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

  8. 8

    Bojang, K. A., Obaro, S., Morison, L. A. & Greenwood, B. M. A prospective evaluation of a clinical algorithm for the diagnosis of malaria in Gambian children. Trop. Med. Int. Health 5, 231– 236 (2000).

    CAS  PubMed  Article  Google Scholar 

  9. 9

    Kallander, K., Nsungwa-Sabiiti, J. & Peterson, S. Symptom overlap for malaria and pneumonia — policy implications for home management strategies. Acta Trop. 90, 211– 214 (2004).

    PubMed  Article  Google Scholar 

  10. 10

    Greenwood, B. M. et al. Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans. R. Soc. Trop. Med. Hyg. 81, 478– 486 (1987).

    CAS  PubMed  Article  Google Scholar 

  11. 11

    Berkley, J. A. et al. Use of clinical syndromes to target antibiotic prescribing in seriously ill children in malaria endemic area: observational study. BMJ 330, 995 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12

    Carcillo, J. A. Reducing the global burden of sepsis in infants and children: a clinical practice research agenda. Pediatr. Crit. Care Med. 6, S157– S164 (2005). Describes the burden of febrile disease, including non-malarial febrile infections, and the potential benefit of rapid diagnosis in their management.

    PubMed  Article  Google Scholar 

  13. 13

    Peters, R. P. et al. A prospective study of bloodstream infections as cause of fever in Malawi: clinical predictors and implications for management. Trop. Med. Int. Health 9, 928– 934 (2004).

    PubMed  Article  Google Scholar 

  14. 14

    WHO. World Malaria Report 2005 (WHO and UNICEF, Geneva, 2005). The most comprehensive data set on currently reported malaria and case management. Greatly under-estimates the burden, but generally reflects cases within the current reach of organized government health services that might be readily accessible to rapid diagnosis.

  15. 15

    Hay, S. I., Guerra, C. A., Tatem, A. J., Atkinson, P. M. & Snow, R. W. Urbanization, malaria transmission and disease burden in Africa. Nature Rev. Microbiol. 3, 81– 90 (2005).

    CAS  Article  Google Scholar 

  16. 16

    WHO. Strategic Orientation Paper on Prevention and Control of Malaria (WHO, Geneva, 2005).

  17. 17

    Ridley, R. & Toure, Y. Winning the drugs war. Nature 430, 942– 943 (2004).

    CAS  PubMed  Article  Google Scholar 

  18. 18

    WHO. Guidelines for the Treatment of Malaria (WHO, Geneva, 2006). Recently published treatment guidelines, intended to guide movement to effective, higher cost antimalarial therapies.

  19. 19

    Kachur, S. P. et al. Prevalence of malaria parasitemia and accuracy of microscopic diagnosis in Haiti, October 1995. Rev. Panam. Salud Publica 3, 35– 39 (1998). An example of the evidence of the poor quality of much of the current field-based malaria microscopy.

    CAS  PubMed  Google Scholar 

  20. 20

    Durrheim, D. N., Becker, P. J. & Billinghurst, K. Diagnostic disagreement — the lessons learnt from malaria diagnosis in Mpumalanga. S. Afr. Med. J. 87, 1016 (1997).

    CAS  PubMed  Google Scholar 

  21. 21

    Kilian, A. H. et al. Reliability of malaria microscopy in epidemiological studies: results of quality control. Trop. Med. Int. Health 5, 3– 8 (2000). An example of the evidence of the poor quality of much of the current field-based malaria microscopy.

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Kain, K. C., Harrington, M. A., Tennyson, S. & Keystone, J. S. Imported malaria: prospective analysis of problems in diagnosis and management. Clin. Infect. Dis. 27, 142– 149 (1998).

    CAS  PubMed  Article  Google Scholar 

  23. 23

    Coleman, R. E. et al. Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand. Am. J. Trop. Med. Hyg. 67, 141– 144 (2002).

    PubMed  Article  Google Scholar 

  24. 24

    O'Meara, W. P. et al. Sources of variability in determining malaria parasite density by microscopy. Am. J. Trop. Med. Hyg. 73, 593– 598 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25

    Premji, Z., Minjas, J. N. & Shiff, C. J. Laboratory diagnosis of malaria by village health workers using the rapid manual ParaSight-F test. Trans. R. Soc. Trop. Med. Hyg. 88, 418 (1994).

    CAS  PubMed  Article  Google Scholar 

  26. 26

    Shiff, C. J., Minjas, J. & Premji, Z. The ParaSight(R)-F test: a simple rapid manual dipstick test to detect Plasmodium falciparum infection. Parasitol. Today 10, 494– 495 (1994).

    CAS  PubMed  Article  Google Scholar 

  27. 27

    Shiff, C. J., Premji, Z. & Minjas, J. N. The rapid manual ParaSight-F test. A new diagnostic tool for Plasmodium falciparum infection. Trans. R. Soc. Trop. Med. Hyg. 87, 646– 648 (1993).

    CAS  PubMed  Article  Google Scholar 

  28. 28

    Beadle, C. et al. Diagnosis of malaria by detection of Plasmodium falciparum HRP-2 antigen with a rapid dipstick antigen-capture assay. Lancet 343, 564– 568 (1994).

    CAS  PubMed  Article  Google Scholar 

  29. 29

    Whitty, C. J. M., Armstrong, M. & Behrens, R. H. Self-testing for falciparum malaria with antigen-capture cards by travelers with symptoms of malaria. Am. J. Trop. Med. Hyg. 63, 295– 297 (2000).

    PubMed  Article  Google Scholar 

  30. 30

    Hashizume, M. et al. Use of rapid diagnostic tests for malaria in an emergency situation after the flood disaster in Mozambique. Public Health 120, 444– 447 (2006).

    CAS  PubMed  Article  Google Scholar 

  31. 31

    WHO. The Use of Malaria Rapid Diagnostic Tests (WHO, Regional Office for the Western Pacific, Manila, 2004). Short guide on issues related to malaria RDT procurement and use.

  32. 32

    WHO. Malaria Management in Complex Emergencies: an Inter-agency Field Handbook (WHO, Geneva, 2005).

  33. 33

    D'Alessandro, U., Talisuna, A. & Boelaert, M. Editorial: should artemisinin-based combination treatment be used in the home-based management of malaria? Trop. Med. Int. Health 10, 1– 2 (2005). Discussion of community-based care for malaria, including a successful intervention programme based on low-cost drugs and symptom-based diagnosis.

    CAS  PubMed  Article  Google Scholar 

  34. 34

    Bell, D., Go, R., Miguel, C., Parks, W. & Bryan, J. Unequal treatment access and malaria risk in a community-based intervention program in the Philippines. Southeast Asian J. Trop. Med. Public Health 36, 578– 586 (2005).

    CAS  PubMed  Google Scholar 

  35. 35

    Konradsen, F., Amerasinghe, P. H., Perera, D., Van der Hoek, W. & Amerasinghe, F. P. A village treatment center for malaria: community response in Sri Lanka. Soc. Sci. Med. 50, 879– 889 (2000).

    CAS  PubMed  Article  Google Scholar 

  36. 36

    Sirima, S. B. et al. Early treatment of childhood fevers with pre-packaged antimalarial drugs in the home reduces severe malaria morbidity in Burkina Faso. Trop. Med. Int. Health 8, 133– 139 (2003).

    PubMed  Article  Google Scholar 

  37. 37

    Kallander, K. et al. Community referral in home management of malaria in western Uganda: a case series study. BMC Int. Health Hum. Rights 6, 2 (2006).

    PubMed  PubMed Central  Article  Google Scholar 

  38. 38

    Kaseje, D. C., Spencer, H. C. & Sempebwa, E. K. Usage of community-based chloroquine treatment for malaria in Saradidi, Kenya. Ann. Trop. Med. Parasitol. 81 (Suppl. 1), 111– 115 (1987).

    PubMed  Article  Google Scholar 

  39. 39

    Ghebreyesus, T. A. et al. The community-based malaria control programme in Tigray, northern Ethiopia. A review of programme set-up, activities, outcomes and impact. Parassitologia 42, 255– 290 (2000). Describes a community-based programme for malaria care, including arguments for and against the introduction of ACT use at village level.

    CAS  PubMed  Google Scholar 

  40. 40

    Okanurak, K. & Ruebush, T. K. Village-based diagnosis and treatment of malaria. Acta Trop. 61, 157– 167 (1996).

    CAS  PubMed  Article  Google Scholar 

  41. 41

    Goodman, C. A., Coleman, P. G. & Mills, A. J. Cost-effectiveness of malaria control in sub-Saharan Africa. Lancet 354, 378– 385 (1999).

    CAS  PubMed  Article  Google Scholar 

  42. 42

    Roll Back Malaria (RBM) Partnership. Sources and Prices for Selected Products for the Prevention, Diagnosis and Treatment of Malaria (RBM Partnership, Geneva, 2004).

  43. 43

    Redd, S. C. et al. Usefulness of clinical case-definitions in guiding therapy for African children with malaria or pneumonia. Lancet 340, 1140– 1143 (1992).

    CAS  PubMed  Article  Google Scholar 

  44. 44

    Duong, S., Lim, P., Fandeur, T., Tsuyuoka, R. & Wongsrichanalai, C. Importance of protection of antimalarial combination therapies. Lancet 364, 1754– 1755 (2004).

    PubMed  Article  Google Scholar 

  45. 45

    Towie, N. Malaria breakthrough raises spectre of drug resistance. Nature 440, 852– 853 (2006).

    CAS  PubMed  Article  Google Scholar 

  46. 46

    Duffy, P. E. & Sibley, C. H. Are we losing artemisinin combination therapy already? Lancet 366, 1908– 1909 (2005).

    PubMed  Article  Google Scholar 

  47. 47

    Malaria R&D Alliance. Malaria Research & Development — An Assessment of Global Investment (PATH, Seattle, 2005).

  48. 48

    Roll Back Malaria (RBM) — A Global Partnership. Roll Back Malaria Partnership. http://www.rbm.who.int (2006).

  49. 49

    WHO. Stop TB Partnership, 2006. Stop TB Partnership. http://www.stoptb.org (2006).

  50. 50

    WHO. The 3 by 5 Initiative. http://www.who.int/3by5/en/ (2006).

  51. 51

    Rifkin, S. B. Paradigms lost: toward a new understanding of community participation in health programmes. Acta Trop. 61, 79– 92 (1996). Discusses community-based care for malaria, including a review of reasons for the failure and success of such programmes.

    CAS  PubMed  Article  Google Scholar 

  52. 52

    Tarimo, D. S., Minjas, J. N. & Bygbjerg, I. C. Malaria diagnosis and treatment under the strategy of the integrated management of childhood illness (IMCI): relevance of laboratory support from the rapid immunochromatographic tests of ICT Malaria P. f / P. v and OptiMal. Ann. Trop. Med. Parasitol. 95, 437– 444 (2001).

    CAS  PubMed  Article  Google Scholar 

  53. 53

    Gove, S. Integrated management of childhood illness by outpatient health workers: technical basis and overview. The WHO working group on guidelines for integrated management of the sick child. Bull. World Health Organ. 75, (Suppl. 1), 7– 24 (1997).

    PubMed  PubMed Central  Google Scholar 

  54. 54

    Cunha, M. L., Piovesan-Alves, F. & Pang, L. W. Community-based program for malaria case management in the Brazilian Amazon. Am. J. Trop. Med. Hyg. 65, 872– 876 (2001).

    CAS  PubMed  Article  Google Scholar 

  55. 55

    Banchongaksorn, T., Prajakwong, S., Rooney, W. & Vickers, P. Operational trial of ParaSight-F (dipstick) in the diagnosis of falciparum malaria at the primary health care level. Southeast Asian J. Trop. Med. Public Health 28, 243– 246 (1997).

    CAS  PubMed  Google Scholar 

  56. 56

    Mayxay, M. et al. Short communication: an assessment of the use of malaria rapid tests by village health volunteers in rural Laos. Trop. Med. Int. Health 9, 325– 329 (2004).

    PubMed  Article  Google Scholar 

  57. 57

    Tavrow, P., Knebel, E. & Cogswell, L. Using Quality Design to Improve Malaria Rapid Diagnostic Tests in Malawi (Quality Assurance Project (QAP) for the United States Agency for International Development, Bethesda USA, 2000).

    Google Scholar 

  58. 58

    Funk, M., Schlagenhauf, P., Tschopp, A. & Steffen, R. MalaQuick versus ParaSight-F as a diagnostic aid in travellers' malaria. Trans. R. Soc. Trop. Med. Hyg. 93, 268– 272 (1999).

    CAS  PubMed  Article  Google Scholar 

  59. 59

    Trachsler, M., Schlagenhauf, P. & Steffen, R. Feasibility of a rapid dipstick antigen-capture assay for self-testing of travellers' malaria. Trop. Med. Int. Health 4, 442– 447 (1999).

    CAS  PubMed  Article  Google Scholar 

  60. 60

    Fryauff, D. J. et al. Performance of the OptiMAL assay for detection and identification of malaria infections in asymptomatic residents of Irian Jaya, Indonesia. Am. J. Trop. Med. Hyg. 63, 139– 145 (2000).

    CAS  PubMed  Article  Google Scholar 

  61. 61

    Jelinek, T., Grobusch, M. P. & Nothdurft, H. D. Use of dipstick tests for the rapid diagnosis of malaria in nonimmune travelers. J. Travel. Med. 7, 175– 179 (2000).

    CAS  PubMed  Article  Google Scholar 

  62. 62

    Kilian, A. H. et al. Application of the ParaSight-F dipstick test for malaria diagnosis in a district control program. Acta Trop. 72, 281– 293 (1999).

    CAS  PubMed  Article  Google Scholar 

  63. 63

    Mharakurwa, S., Manyame, B. & Shiff, C. J. Trial of the ParaSight-F test for malaria diagnosis in the primary health care system, Zimbabwe. Trop. Med. Int. Health 2, 544– 550 (1997).

    CAS  PubMed  Article  Google Scholar 

  64. 64

    Harvey, S. et al. Minimizing human error in malaria rapid diagnosis: clarity of written instructions and health worker performance. Trans. R.l Soc. Trop. Med. Hyg. (in the press).

  65. 65

    Njau, J. D. et al. Fever treatment and household wealth: the challenge posed for rolling out combination therapy for malaria. Trop. Med. Int. Health 11, 299– 313 (2006).

    CAS  PubMed  Article  Google Scholar 

  66. 66

    WHO. Malaria Rapid Diagnosis: Making it Work. Meeting report 20–23 January 2003 (WHO, Manila, 2003).

  67. 67

    Amexo, M., Tolhurst, R., Barnish, G. & Bates, I. Malaria misdiagnosis: effects on the poor and vulnerable. Lancet 364, 1896– 1898 (2004).

    PubMed  Article  Google Scholar 

  68. 68

    Wongsrichanalai, C. et al. Comparison of a rapid field immunochromatographic test to expert microscopy for the detection of Plasmodium falciparum asexual parasitemia in Thailand. Acta Trop. 73, 263– 273 (1999).

    CAS  PubMed  Article  Google Scholar 

  69. 69

    Gaye, O., Diouf, M., Dansokho, E. F., McLaughlin, G. & Diallo, S. Diagnosis of Plasmodium falciparum malaria using ParaSight-F, ICT malaria PF and malaria IgG CELISA assays. Parasite 5, 189– 192 (1998).

    CAS  PubMed  Article  Google Scholar 

  70. 70

    Quintana, M. et al. Malaria diagnosis by dipstick assay in a Honduran population with coendemic Plasmodium falciparum and Plasmodium vivax. Am. J. Trop. Med. Hyg. 59, 868– 871 (1998).

    CAS  PubMed  Article  Google Scholar 

  71. 71

    Forney, J. R. et al. Malaria rapid diagnostic devices: performance characteristics of the ParaSight-F device determined in a multisite field study. J. Clin. Microbiol. 39, 2884– 2890 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. 72

    Iqbal, J., Khalid, N. & Hira, P. R. Comparison of two commercial assays with expert microscopy for confirmation of symptomatically diagnosed malaria. J. Clin. Microbiol. 40, 4675– 4678 (2002).

    PubMed  PubMed Central  Article  Google Scholar 

  73. 73

    Wolday, D., Balcha, F., Fessehaye, G., Birku, Y. & Shepherd, A. Field trial of the RTM dipstick method for the rapid diagnosis of malaria based on the detection of Plasmodium falciparum HRP-2 antigen in whole blood. Trop. Doct. 31, 19– 21 (2001).

    CAS  PubMed  Article  Google Scholar 

  74. 74

    Happi, C. T. et al. Malaria diagnosis: false negative parasight-F tests in falciparum malaria patients in Nigeria. Afr. J. Med. Sci. 33, 15– 18 (2004).

    CAS  Google Scholar 

  75. 75

    Baker, J. et al. Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests. J. Infect. Dis. 192, 870– 877 (2005).

    CAS  PubMed  Article  Google Scholar 

  76. 76

    O'Dempsey, T. J. et al. Overlap in the clinical features of pneumonia and malaria in African children. Trans. R. Soc. Trop. Med. Hyg. 87, 662– 665 (1993).

    CAS  PubMed  Article  Google Scholar 

  77. 77

    WHO. Malaria Rapid Diagnostic Tests: Making Rapid Diagnosis Work. http://www.wpro.who.int/rdt (2005).

  78. 78

    WHO. Informal Consultation on Testing Methods for Malaria Rapid Diagnostic Tests, Geneva, Switzerland, 28 February–2 March, 2006 (WHO-Regional Office for the Western Pacific & Special Programme for Research and Training in Tropical Diseases (TDR), Manila, 2006). Outline of current plans by WHO and partners for malaria RDT product testing and laboratory-based quality control testing.

  79. 79

    Nsungwa-Sabiiti, J., Tomson, G., Pariyo, G., Ogwal-Okeng, J. & Peterson, S. Community effectiveness of malaria treatment in Uganda — a long way to Abuja targets. Ann. Trop. Paediatr. 25, 91– 100 (2005).

    PubMed  Article  Google Scholar 

  80. 80

    Unger, J. P., d'Alessandro, U., De Paepe, P. & Green, A. Can malaria be controlled where basic health services are not used? Trop. Med. Int. Health 11, 314– 322 (2006).

    PubMed  Article  Google Scholar 

  81. 81

    Foster, S. Treatment of malaria outside the formal health services. J. Trop. Med. Hyg. 98, 29– 34 (1995).

    CAS  PubMed  Google Scholar 

  82. 82

    Hamel, M. J., Odhacha, A., Roberts, J. M. & Deming, M. S. Malaria control in Bungoma District, Kenya: a survey of home treatment of children with fever, bednet use and attendance at antenatal clinics. Bull. World Health Organ. 79, 1014– 1023 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Fawole, O. I. & Onadeko, M. O. Knowledge and home management of malaria fever by mothers and care givers of under five children. West Afr. J. Med. 20, 152– 157 (2001).

    CAS  PubMed  Google Scholar 

  84. 84

    Ibeh, C. C., Ekejindu, I. M., Ibeh, N. C., Shu, E. N. & Chukwuka, J. O. The pattern of home treatment of malaria in under-fives in south eastern Nigeria. Afr. J. Med. Sci. 34, 71– 75 (2005).

    CAS  Google Scholar 

  85. 85

    Mwenesi, H., Harpham, T. & Snow, R. W. Child malaria treatment practices among mothers in Kenya. Soc. Sci. Med. 40, 1271– 1277 (1995).

    CAS  PubMed  Article  Google Scholar 

  86. 86

    Snow, R. W., Peshu, N., Forster, D., Mwenesi, H. & Marsh, K. The role of shops in the treatment and prevention of childhood malaria on the coast of Kenya. Trans. R. Soc. Trop. Med. Hyg. 86, 237– 239 (1992).

    CAS  PubMed  Article  Google Scholar 

  87. 87

    Pagnoni, F. et al. Artemisinin-based combination treatment in home-based management of malaria. Trop. Med. Int. Health 10, 621– 622 (2005).

    PubMed  Article  Google Scholar 

  88. 88

    Dondorp, A. M. et al. Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials. Trop. Med. Int. Health 9, 1241– 1246 (2004).

    CAS  PubMed  Article  Google Scholar 

  89. 89

    Newton, P. et al. Fake artesunate in southeast Asia. Lancet 357, 1948– 1950 (2001).

    CAS  PubMed  Article  Google Scholar 

  90. 90

    Amin, A. A., Snow, R. W. & Kokwaro, G. O. The quality of sulphadoxine-pyrimethamine and amodiaquine products in the Kenyan retail sector. J. Clin. Pharm. Ther. 30, 559– 565 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. 91

    WHO. New Perspectives: Malaria Diagnosis. Report of a Joint WHO/USAID Informal Consultation 25–27 October 1999 (WHO, Geneva, 2000).

  92. 92

    Mankhambo, L., Kanjala, M., Rudman, S., Lema, V. M. & Rogerson, S. J. Evaluation of the OptiMAL rapid antigen test and species-specific PCR to detect placental Plasmodium falciparum infection at delivery. J. Clin. Microbiol. 40, 155– 158 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. 93

    Singh, N., Saxena, A., Awadhia, S. B., Shrivastava, R. & Singh, M. P. Evaluation of a rapid diagnostic test for assessing the burden of malaria at delivery in India. Am. J. Trop. Med. Hyg. 73, 855– 858 (2005).

    PubMed  Article  Google Scholar 

  94. 94

    Vanderjagt, T. A. et al. Short communication: comparison of the OptiMAL rapid test and microscopy for detection of malaria in pregnant women in Nigeria. Trop. Med. Int. Health 10, 39– 41 (2005).

    CAS  PubMed  Article  Google Scholar 

  95. 95

    Rogers, W. O., Atuguba, F., Oduro, A. R., Hodgson, A. & Koram, K. A. Clinical case definitions and malaria vaccine efficacy. J. Infect. Dis. 193, 467– 473 (2006).

    PubMed  Article  Google Scholar 

  96. 96

    Chirenda, J., Siziya, S. & Tshimanga, M. Association of HIV infection with the development of severe and complicated malaria cases at a rural hospital in Zimbabwe. Cent. Afr. J. Med. 46, 5– 9 (2000).

    CAS  PubMed  Google Scholar 

  97. 97

    Grimwade, K. et al. Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence. Pediatr. Infect. Dis. J. 22, 1057– 1063 (2003).

    PubMed  Article  Google Scholar 

  98. 98

    Cohen, C. et al. Increased prevalence of severe malaria in HIV-infected adults in South Africa. Clin. Infect. Dis. 41, 1631– 1637 (2005).

    PubMed  Article  Google Scholar 

  99. 99

    WHO. WHO Technical Consultation To Review The Role Of Parasitological Diagnosis To Support Malaria Disease Management: Focus On The Use Of RDTs In Areas Of High Transmission Deploying ACT Treatments (WHO, Geneva, 2005).

  100. 100

    Jorgensen, P., Chanthap, L., Rebueno, A., Tsuyuoka, R. & Bell, A. D. Malaria rapid diagnostic tests in tropical climates: the need for a cool chain. Am. J. Trop. Med. Hyg. 74, 750– 754 (2006).

    PubMed  Article  Google Scholar 

  101. 101

    WHO. Interim Notes on Selection of Type of Malaria Rapid Diagnostic Test in Relation to the Occurrence of Different Parasite Species: Guidance for National Malaria Control Programmes (Roll Back Malaria Department, WHO, Geneva, 2005).

  102. 102

    Fernando, S. D., Karunaweera, N. D. & Fernando, W. P. Evaluation of a rapid whole blood immunochromatographic assay for the diagnosis of Plasmodium falciparum and Plasmodium vivax malaria. Ceylon Med. J. 49, 7– 11 (2004).

    CAS  PubMed  Article  Google Scholar 

  103. 103

    Kolaczinski, J. et al. Comparison of the OptiMAL rapid antigen test with field microscopy for the detection of Plasmodium vivax and P. falciparum: considerations for the application of the rapid test in Afghanistan. Ann. Trop. Med. Parasitol. 98, 15– 20 (2004).

    CAS  PubMed  Article  Google Scholar 

  104. 104

    Coleman, R. E. et al. Field evaluation of the ICT Malaria Pf/Pv immunochromatographic test for the detection of asymptomatic malaria in a Plasmodium falciparum/vivax endemic area in Thailand. Am. J. Trop. Med. Hyg. 66, 379– 383 (2002).

    PubMed  Article  Google Scholar 

  105. 105

    Richter, J., Gobels, K., Muller-Stover, I., Hoppenheit, B. & Haussinger, D. Co-reactivity of plasmodial histidine-rich protein 2 and aldolase on a combined immuno-chromographic-malaria dipstick (ICT) as a potential semi-quantitative marker of high Plasmodium falciparum parasitaemia. Parasitol. Res. 94, 384– 385 (2004).

    PubMed  Article  Google Scholar 

  106. 106

    Hernandez, E. et al. Evaluation of the OptiMal test in the diagnosis of imported malarial outbreak. Med. Trop. (Mars) 61, 153– 157 (2001).

    CAS  Google Scholar 

  107. 107

    Iqbal, J., Hira, P. R., Sher, A. & Al-Enezi, A. A. Diagnosis of imported malaria by Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein 2 (PfHRP-2)-based immunocapture assays. Am. J. Trop. Med. Hyg. 64, 20– 23 (2001).

    CAS  PubMed  Article  Google Scholar 

  108. 108

    Ricci, L. et al. Evaluation of OptiMAL Assay test to detect imported malaria in Italy. New Microbiol. 23, 391– 398 (2000).

    CAS  PubMed  Google Scholar 

  109. 109

    Huong, N. M. et al. Comparison of three antigen detection methods for diagnosis and therapeutic monitoring of malaria: a field study from southern Vietnam. Trop. Med. Int. Health 7, 304– 308 (2002).

    PubMed  Article  Google Scholar 

  110. 110

    Stow, N. W., Torrens, J. K. & Walker, J. An assessment of the accuracy of clinical diagnosis, local microscopy and a rapid immunochromatographic card test in comparison with expert microscopy in the diagnosis of malaria in rural Kenya. Trans. R. Soc. Trop. Med. Hyg. 93, 519– 520 (1999).

    CAS  PubMed  Article  Google Scholar 

  111. 111

    Mason, D. P., Kawamoto, F., Lin, K., Laoboonchai, A. & Wongsrichanalai, C. A comparison of two rapid field immunochromatographic tests to expert microscopy in the diagnosis of malaria. Acta Trop. 82, 51– 59 (2002).

    PubMed  Article  Google Scholar 

  112. 112

    Rubio, J. M. et al. Limited level of accuracy provided by available rapid diagnosis tests for malaria enhances the need for PCR-based reference laboratories. J. Clin. Microbiol. 39, 2736– 2737 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  113. 113

    Genton, B., Hii, J., Paget, S. & Alpers, M. P. Rapid manual diagnosis of Plasmodium falciparum malaria using parasight-F dipsticks applied to human blood and urine. J. Travel Med. 3, 172– 173 (1996).

    CAS  PubMed  Article  Google Scholar 

  114. 114

    Coleman, R. E. et al. Short report: failure of the OptiMAL rapid malaria test as a tool for the detection of asymptomatic malaria in an area of Thailand endemic for Plasmodium falciparum and P. vivax. Am. J. Trop. Med. Hyg. 67, 563– 565 (2002).

    PubMed  Article  Google Scholar 

  115. 115

    Pattanasin, S. et al. Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Trans. R. Soc. Trop. Med. Hyg. 97, 672– 674 (2003).

    CAS  PubMed  Article  Google Scholar 

  116. 116

    Bossuyt, P. M. et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 326, 41– 44 (2003). Outline of recommendations of STARD for diagnostic trials.

    PubMed  PubMed Central  Article  Google Scholar 

  117. 117

    Rapid-diagnostics.org. Rapid Tests for Malaria — Commercially available rapid tests for Malaria. http://www.rapid-diagnostics.org/rti-malaria-com.htm (2006).

  118. 118

    WHO. Informal Consultation On Laboratory Methods For Quality Assurance Of Malaria Rapid Diagnostic Tests; Manila, 20–22 July 2004 (WHO, Regional Office for the Western Pacific, Manila, 2004).

  119. 119

    Bigaillon, C., Fontan, E., Cavallo, J. D., Hernandez, E. & Spiegel, A. Ineffectiveness of the Binax NOW malaria test for diagnosis of Plasmodium ovale malaria. J. Clin. Microbiol. 43, 1011 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  120. 120

    Marx, A. et al. Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas. Ann. Intern. Med. 142, 836– 846 (2005).

    PubMed  Article  Google Scholar 

  121. 121

    Desakorn, V. et al. Stage-dependent production and release of histidine-rich protein 2 by Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 99, 517– 524 (2005).

    CAS  PubMed  Article  Google Scholar 

  122. 122

    Miller, R. S., McDaniel, P. & Wongsrichanalai, C. Following the course of malaria treatment by detecting parasite lactate dehydrogenase enzyme. Br. J. Haematol. 113, 558– 559 (2001).

    CAS  PubMed  Article  Google Scholar 

  123. 123

    Moody, A., Hunt-Cooke, A., Gabbett, E. & Chiodini, P. Performance of the OptiMAL malaria antigen capture dipstick for malaria diagnosis and treatment monitoring at the Hospital for Tropical Diseases, London. Br. J. Haematol. 109, 891– 894 (2000).

    CAS  PubMed  Article  Google Scholar 

  124. 124

    Oduola, A. M. et al. Plasmodium falciparum: evaluation of lactate dehydrogenase in monitoring therapeutic responses to standard antimalarial drugs in Nigeria. Exp. Parasitol. 87, 283– 289 (1997).

    CAS  PubMed  Article  Google Scholar 

  125. 125

    Palmer, C. J. et al. Field evaluation of the OptiMAL rapid malaria diagnostic test during antimalarial therapy in Guyana. Trans. R. Soc. Trop. Med. Hyg. 93, 517– 518 (1999).

    CAS  PubMed  Article  Google Scholar 

  126. 126

    Eisen, D. P. & Saul, A. Disappearance of pan-malarial antigen reactivity using the ICT Malaria P.f/P.v kit parallels decline of patent parasitaemia as shown by microscopy. Trans. R. Soc. Trop. Med. Hyg. 94, 169– 170 (2000).

    CAS  PubMed  Article  Google Scholar 

  127. 127

    Mayxay, M., Pukrittayakamee, S., Chotivanich, K., Looareesuwan, S. & White, N. J. Persistence of Plasmodium falciparum HRP-2 in successfully treated acute falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 95, 179– 182 (2001).

    CAS  PubMed  Article  Google Scholar 

  128. 128

    Tjitra, E., Suprianto, S., McBroom, J., Currie, B. J. & Anstey, N. M. Persistent ICT malaria P.f/P.v panmalarial and HRP2 antigen reactivity after treatment of Plasmodium falciparum malaria is associated with gametocytemia and results in false-positive diagnoses of Plasmodium vivax in convalescence. J. Clin. Microbiol. 39, 1025– 1031 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  129. 129

    Humar, A., Ohrt, C., Harrington, M. A., Pillai, D. & Kain, K. C. Parasight F test compared with the polymerase chain reaction and microscopy for the diagnosis of Plasmodium falciparum malaria in travelers. Am. J. Trop. Med. Hyg. 56, 44– 48 (1997).

    CAS  PubMed  Article  Google Scholar 

  130. 130

    WHO. Rapid Diagnostic Tests for Malaria: Methods Manual for Laboratory Quality Control Testing. Version 3 (WHO, Regional Office for the Western Pacific, Manila, 2006).

  131. 131

    Lon, C. T., Alcantara, S., Luchavez, J., Tsuyuoka, R. & Bell, D. Positive control wells: a potential answer to remote-area quality assurance of malaria rapid diagnostic tests. Trans. R. Soc. Trop. Med. Hyg. 99, 493– 498 (2005).

    CAS  PubMed  Article  Google Scholar 

  132. 132

    Forney, J. R. et al. Devices for rapid diagnosis of Malaria: evaluation of prototype assays that detect Plasmodium falciparum histidine-rich protein 2 and a Plasmodium vivax-specific antigen. J. Clin. Microbiol. 41, 2358– 2366 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  133. 133

    Kilian, A. H., Mughusu, E. B., Kabagambe, G. & von Sonnenburg, F. Comparison of two rapid, HRP2-based diagnostic tests for Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 91, 666– 667 (1997).

    CAS  PubMed  Article  Google Scholar 

  134. 134

    Cho-Min-Naing & Gatton, M. L. Performance appraisal of rapid on-site malaria diagnosis (ICT malaria P.f/P.v test) in relation to human resources at village level in Myanmar. Acta Trop. 81, 13– 19 (2002).

    CAS  PubMed  Article  Google Scholar 

  135. 135

    Guthmann, J. P. et al. Validity, reliability and ease of use in the field of five rapid tests for the diagnosis of Plasmodium falciparum malaria in Uganda. Trans. R. Soc. Trop. Med Hyg. 96, 254– 257 (2002).

    CAS  PubMed  Article  Google Scholar 

  136. 136

    Cropley, I. M., Lockwood, D. N., Mack, D., Pasvol, G. & Davidson, R. N. Rapid diagnosis of falciparum malaria by using the ParaSight F test in travellers returning to the United Kingdom: prospective study. BMJ 321, 484– 485 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. 137

    Richardson, D. C., Ciach, M., Zhong, K. J., Crandall, I. & Kain, K. C. Evaluation of the Makromed dipstick assay versus PCR for diagnosis of Plasmodium falciparum malaria in returned travelers. J. Clin. Microbiol. 40, 4528– 4530 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  138. 138

    Leke, R. F. et al. Detection of the Plasmodium falciparum antigen histidine-rich protein 2 in blood of pregnant women: implications for diagnosing placental malaria. J. Clin. Microbiol. 37, 2992– 2996 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. 139

    Singer, L. M. et al. Evaluation of a malaria rapid diagnostic test for assessing the burden of malaria during pregnancy. Am. J. Trop. Med. Hyg. 70, 481– 485 (2004).

    PubMed  Article  Google Scholar 

  140. 140

    Bell, D. R., Wilson, D. W. & Martin, L. B. False-positive results of a Plasmodium falciparum histidine-rich protein 2 — detecting malaria rapid diagnostic test due to high sensitivity in a community with fluctuating low parasite density. Am. J. Trop. Med. Hyg. 73, 199– 203 (2005).

    CAS  PubMed  Article  Google Scholar 

  141. 141

    Mishra, B., Samantaray, J. C., Kumar, A. & Mirdha, B. R. Study of false positivity of two rapid antigen detection tests for diagnosis of Plasmodium falciparum malaria. J. Clin. Microbiol. 37, 1233 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142

    Moody, A. H. & Chiodini, P. L. Non-microscopic method for malaria diagnosis using OptiMAL IT, a second-generation dipstick for malaria pLDH antigen detection. Br. J. Biomed. Sci. 59, 228– 231 (2002).

    CAS  PubMed  Article  Google Scholar 

  143. 143

    McKenzie, F. E., Sirichaisinthop, J., Miller, R. S., Gasser, R. A., Jr. & Wongsrichanalai, C. Dependence of malaria detection and species diagnosis by microscopy on parasite density. Am. J. Trop. Med. Hyg. 69, 372– 376 (2003).

    PubMed  PubMed Central  Article  Google Scholar 

  144. 144

    Raghavan, K. Statistical considerations in the microscopical diagnosis of Malaria, with special reference to the role of cross-checking. Bull. World Health Organ. 34, 788– 791 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. 145

    Uguen, C. et al. ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection. Bull. World Health Organ. 73, 643– 649 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. 146

    Lema, O. E. et al. Comparison of five methods of malaria detection in the outpatient setting. Am. J. Trop. Med. Hyg. 60, 177– 182 (1999).

    CAS  PubMed  Article  Google Scholar 

  147. 147

    Craig, M. H. et al. Field and laboratory comparative evaluation of ten rapid malaria diagnostic tests. Trans. R. Soc. Trop. Med. Hyg. 96, 258– 265 (2002).

    CAS  PubMed  Article  Google Scholar 

  148. 148

    Tham, J. M., Lee, S. H., Tan, T. M., Ting, R. C. & Kara, U. A. Detection and species determination of malaria parasites by PCR: comparison with microscopy and with ParaSight-F and ICT malaria Pf tests in a clinical environment. J. Clin. Microbiol. 37, 1269– 1273 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149

    Bechem, N. N., Leke, R. F., Tietche, F. & Taylor, D. W. Evaluation of a rapid test for histidine rich protein 2 for diagnosis of Plasmodium falciparum infection in Cameroonian children. Trans. R. Soc. Trop. Med. Hyg. 93, 46 (1999).

    CAS  PubMed  Article  Google Scholar 

  150. 150

    Erhart, L. M. et al. Hematologic and clinical indices of malaria in a semi-immune population of western Thailand. Am. J. Trop. Med. Hyg. 70, 8– 14 (2004).

    PubMed  Article  Google Scholar 

  151. 151

    Whiting, P. et al. Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann. Intern. Med. 140, 189– 202 (2004).

    PubMed  Article  Google Scholar 

  152. 152

    Kooij, T. W. A., Janse, C. W. & Waters, A. P. Plasmodium post genomics: better the bug you know? Nature Rev. Microbiol. 4, 344– 357 (2006).

    CAS  Article  Google Scholar 

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Acknowledgements

The authors wish to thank L. Dini and R. Peeling for advice and for reviewing the manuscript.

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DATABASES

Entrez Genome Project

Plasmodium falciparum

Plasmodium vivax

FURTHER INFORMATION

Global Fund to Fight AIDS, Tuberculosis and Malaria

Roll Back Malaria partnership

Stop TB

HIV: the 3 by 5 initiative

Integrated Management of Childhood Illness

Malaria rapid diagnostic tests

Rapid tests for malaria

Kenya Medical Research Institute (KEMRI)

Centers for Disease Control and Prevention (CDC)

AusAID

The Special Programme for Research and Training in Tropical Diseases (TDR)

Glossary

Lateral flow immunochromatographic assay

A device that produces a visible mark to signal the presence or absence of a protein antigen, based on the accumulation of dye-labelled antibodies to form a visible line after binding directly, or through a common antigen, to a fixed line of unlabelled antibody.

Artemisinin-based combination therapies (ACT)

Drug therapy for malaria consisting of a combination of an artemisinin derivative (derived from the plant Artemisia, also known by the Chinese name Qing Hao), and another drug with anti-plasmodial activity. ACT is rapidly replacing cheaper conventional medicines, to which parasite resistance is now widespread.

Positive predictive value (PPV)

The probability that a positive result accurately indicates the presence of infection.

Negative predictive value (NPV)

The probability that a negative result accurately indicates the absence of infection.

Arrhenius equation

The Arrhenius equation describes the relationship between temperature and the rate at which a reaction proceeds.

Heterophile antibodies

IgM antibodies that can reach high levels in serum after febrile illnesses (for example, infectious mononucleosis), and can bind nonspecifically to other proteins. They can cause false-positive reactions in immunochromatographic assays.

Giemsa-stained light microscopy

Detection of malaria parasites in blood by drying a thin blood film on a glass slide, fixing with methanol and staining with a mixture of aninline dyes, designed to highlight Plasmodium parasites when examined under a high-powered light microscope. Sometimes other aniline dye-based stains are used (for example, JSB or Field's stain).

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Bell, D., Wongsrichanalai, C. & Barnwell, J. Ensuring quality and access for malaria diagnosis: how can it be achieved?. Nat Rev Microbiol 4, S7–S20 (2006). https://doi.org/10.1038/nrmicro1525

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