Skip to main content
  • Loading metrics

Scale-up of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination Therapy: Challenges and Perspectives in Sub-Saharan Africa

  • Guido J. H. Bastiaens ,

    Affiliation Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands

  • Teun Bousema,

    Affiliations Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, United Kingdom

  • Toby Leslie

    Affiliation Department of Disease Control, London School of Hygiene & Tropical Medicine, London, United Kingdom

Summary Points

  • Scaling up and sustaining access to malaria diagnosis and treatment in all public sector, for-profit, and informal health facilities across sub-Saharan Africa is central to current global strategies for malaria control and elimination.
  • The use of malaria rapid diagnostic tests (RDTs) aims to eliminate reliance on signs and symptoms to diagnose and treat malaria but evidence shows health workers do not always test the right patients, nor provide treatment based on the results of the test.
  • Expanding access to malaria RDTs on the scale needed to achieve universal coverage requires retraining of public, private, and retail sector providers as well as sustained supplies and quality assurance.
  • Barriers to rational use of tests and drugs may be overcome through appropriate policy design for the local health service setting, which addresses health worker practice and patient perceptions.
  • Innovative methods have been used to increase access to the most effective antimalarial drugs in the last five years, but these efforts will be incomplete and unsustainable without similar efforts to incorporate RDTs into practice.


An estimated 627,000 malaria deaths occurred in 2012, mostly in African children and many of them preventable with prompt diagnosis and treatment [1]. Access to diagnosis remains poor—in half of endemic African countries, over 80% of malaria treatments are applied without diagnostic testing [2]. Improving diagnosis and treatment of malaria will improve treatment outcomes, rationalize health care costs by reducing drug consumption [3], minimize drug pressure that can contribute to resistance [4],[5], and assist in monitoring disease trends [2].

In April 2012, the World Health Organization's (WHO) Global Malaria Programme launched a highly ambitious new initiative: T3: Test. Treat. Track [1],[2]. T3 aims to address the widespread problem of poor access to diagnostic testing and antimalarial treatment, and to enhance case-reporting. It sets a target of universal access to diagnostic testing in the public and private health care sector by 2015 [1],[2]. Achieving this goal will centre on the use of malaria rapid diagnostic tests (RDTs).

In this Policy Forum article we examine the operational challenges to implementing the T3 strategy of scaling up and maintaining RDT coverage. We identify gaps in planning for at-scale implementation in policy design and implementation, the local health care setting, and the attitudes and demands of patients. While focussed on malaria diagnosis and treatment, the challenges illustrated here are not unique to malaria and may apply to health care provision across resource-poor settings.

Policy Design and Implementation

By 2012, 41 out of 44 endemic countries in the WHO African Region had adopted the policy of providing malaria diagnostic testing for all age groups before treatment [2]. RDT procurement increased worldwide from 45 million units in 2008 to 205 million in 2012 although supply remains far short of requirements [1],[2]. In theory, the availability of reliable easy-to-use tests should result in a switch from presumptive treatment based on signs and symptoms alone, to parasite-based diagnosis and treatment based on test results. Diagnostic processes and treatment decisions are, however, often irrational and health staff do not always test the right patients, nor provide treatment based on the results [6][8].

RDTs will be introduced in health facilities and among community health workers (CHWs) who work at local levels. To translate the change in policy to a change in routine practice where tests are appropriately used by providers, unambiguous messages and guidelines that are adapted to the local context are needed [6],[9],[10]. This targeted information must counter the widespread and long-held guidelines that promoted presumptive treatment of malaria in cases of fever [11]. Appropriate information and training will improve implementation at the community level [12]. Recent evidence shows that CHWs reliably provided Integrated Management of Childhood Illnesses to children after training and incorporation of RDTs into the algorithm [13],[14]. In one study, malaria and pneumonia were appropriately classified in 94%–100% of children, and supply management of medications and RDTs was excellent [13]. Replicating these effects outside the trial setting requires national level training to ensure safety and quality of services.

Mobilising sufficient resources for the training and monitoring required to sustain the new policy is the key to success. A reliable system for RDT delivery needs to include re-training of staff and consistent quality assurance at all levels. The quality of services is likely to wane over time and can be aggravated by high staff turnover, which occurs in many health service settings. Ensuring programme quality and sustainability therefore requires constant rolling interventions and local evidence for the best models of implementation.

The Local Health Care Setting

In the local health care setting, two problems persist: firstly, parasite-based testing is generally unavailable [1],[2] with treatment decisions based on clinical signs and symptoms that are neither sensitive nor specific [15]; and secondly, if tests are available, health workers often do not apply treatment according to the result of the test [10],[16][18]. Both situations result in extensive overuse of antimalarial drugs, especially in low transmission settings [19],[20].

When RDTs are introduced in presumptive treatment settings significant reductions in the overprescription of antimalarials have been seen in almost all studies published (Table S1). However, when they are introduced in settings that have used microscopic examination of blood smears, the advantages of RDTs are harder to define. Substantial numbers of patients may still be treated with an antimalarial drug despite a negative RDT or blood smear result, so the evidence of any clinical advantage of RDTs over microscopy is unclear in some settings (Table S2).

Often, the irrational use of tests and drugs is based on perceived shortcomings of the tests. A common concern amongst health staff is that negative tests do not definitively rule out malaria [21], but trials that withheld antimalarials in febrile children with negative test results have shown no additional malaria risk to patients in moderate-to-high transmission settings. In one trial in Uganda, 13/1,602 (0.8%) blood smear–negative patients who were not given antimalarial drugs developed clinical malaria over 7 days of follow-up and all 13 were detected by the health service and treated [22]. Similar findings were seen in Tanzania (3/603 [0.5%] of RDT-negative patients developed malaria within 7 days) [23]. These studies indicate that withholding antimalarial therapy in febrile children with negative test results is likely to be safe and results in a considerable reduction in antimalarial drug consumption.

Improvements in antimalarial prescription often coincide with increases in prescription of antibiotics amongst test-negative patients. All studies where antimalarial prescription rates were reduced in malaria-negative patients show an increase in antibiotic prescriptions (Tables S1 and S2) [16],[19],[24][26]. There is little data on the spectrum of infections in patients presenting with symptoms of suspected malaria but most of these are probably self-limiting [23],[27], and evidence that supports the prevailing practice of widespread antibiotic use in malaria negative patients is lacking.

Identifying patients at risk of progressing to severe disease in which antibiotic treatment and/or referral would have a clinical advantage, while withholding antibiotic treatment in other patients, is a considerable challenge. Affordable rapid diagnostics for bacterial infections or markers of severe infections would support the rational prescription of both antimalarials and antibiotics.

Patient load and malaria diagnosis

A high patient load in many clinics creates challenges in implementing new policies and motivating staff [28],[29]. In Tanzania, health workers identified high patient load and shortage of staff as key factors that hindered use of RDTs [28]. Most staff felt RDTs placed additional strain on normal operations and believed more staff were needed to conduct the tests [28]. Although these considerations apply to all diagnostic procedures and are not unique to RDTs, understanding the realities of routine practice is required because introducing extra staff into facilities will have an impact on cost.

Sustained supply of RDTs in public and private sectors

Sustaining the supply of RDTs is a substantial challenge. In rural areas, where access to services is often low but demand for services may be highest [1], drug stock-outs are common [30],[31] and supply is one of the biggest challenges facing the health system. The T3 recommendations imply that a constant supply of both artemisinin-based combination therapies (ACTs) and RDTs is needed. The shelf-life and performance of both diagnostics and drugs depends on their storage conditions; RDTs are degraded by high temperatures and humidity and the entire supply chain must ensure that RDTs remain within manufacturers' recommended limits. WHO testing of a range of commercially available RDTs demonstrated consistent detection of malaria at tropical temperatures [21], but actual field data on storage conditions affecting RDT stability are scarce.

The private for-profit sector plays an important role in delivering services across most of Africa and the majority of suspected malaria episodes are initially treated by private health workers [32],[33]. Data from a limited number of countries suggest neither microscopy nor RDTs have penetrated the private health care sector [1],[34] but more than 50% of patients purchase drugs from unregistered shops and peddlers [32],[33]. This occurs especially amongst lower income groups [35]. Improving diagnostic and treatment practices in the private sector could have a substantial impact on access to diagnosis before treatment but models of implementation have yet to be fully assessed in operational trials [35],[36].

Affordability and cost-effectiveness of RDT-based diagnosis

To improve access to drugs in sub-Saharan Africa, the Affordable Medicines Facility - malaria provided subsidised ACT drugs in a multi-country pilot [37]. This study demonstrated improved access and market share of ACTs in five out of seven pilot countries driven mainly by improvements in the private for-profit sector [38]. In 2012, 331 million courses of ACTs were procured by the public and private sectors in endemic countries, up from 182 million in 2010 [1]. Although the pilot rapidly improved availability, affordability, and market share of quality-assured ACTs at the point of use, no equivalent increase in RDTs has been observed [1],[38]. As diagnosis is seldom available and ACT orders are more than double that of RDTs, overtreatment is likely to be common in retail outlets. ACTs are approximately ten times more costly than previously used monotherapies [19],[31] so the use of RDTs prior to treatment may improve cost-effectiveness. Data from a willingness-to-pay study in private drug shops in Uganda indicated that there was a demand for RDTs in the private sector but this was far below the price of delivery [39]. Subsidised supply of RDTs, similar to the ACTs subsidy, should be assessed to examine the impact on the uptake of RDTs in the private retail sector.

In high and very high transmission areas, presumptive treatment has cost-effectiveness advantages given the imperfect sensitivity of tests under field conditions [3]. RDTs in settings with up to 62% Plasmodium falciparum prevalence were cost-effective compared to presumptive treatment, assuming that prescribers adhered fully to test results [31]. When treatment is consistent with the results of a test, cost savings of between 50% and 100% can be achieved compared with presumptive treatment [3]. Conversely, if treatment is inconsistent with the result of the test, cost-effectiveness is reduced, an association that varies with the malaria transmission setting [3],[31]. Other factors that can reduce cost-effectiveness are stock-outs, poor accuracy of RDTs, and poor quality assurance for drugs and diagnostics [31].

In low-endemic settings, RDTs and microscopy remain attractive compared to presumptive treatment even when there is poor adherence to negative test results [3]. RDTs can be more cost-effective than microscopy because they are more accurate under real-life conditions [31] and continuous (re-)training of microscopists is particularly important if fewer malaria positive slides with low parasite levels are encountered in low-endemic settings. Despite these advantages of RDTs over presumptive treatment, adherence to microscopy and RDT test results remains a key factor for cost-effective diagnosis and treatment [3],[40].

Malaria diagnosis in elimination programmes

Currently available RDTs will not detect all infections with low parasite loads. These submicroscopic infections frequently occur in low-endemic areas [41], are probably not associated with clinical risks [42], but do play a role in onward malaria transmission [43]. Diagnostics with a sensitivity that is higher than currently available RDTs will be needed to identify all malaria infections in elimination efforts [44]. Operational approaches may involve screening by RDT to identify geographic or demographic clusters of infections [45],[46] that can be targeted following molecular diagnosis of infection or by focal mass drug administration [47],[48].

Attitudes and Demands of Patients

Patients can influence the diagnostic and treatment practices of health workers [7],[8] and patient pressure on providers contributes to overtreatment [7]. There is a persistent perception that all fever episodes in malaria endemic areas are due to malaria [49] and, until recently, a global policy of presumptive treatment for malaria in cases of fever has been in place [2]. These factors have created entrenched demand for malaria treatment without first testing for malaria [29],[50],[51]. Efforts to change demands to promote malaria testing are particularly important in the private and informal sector, where few patients presently receive a diagnostic test. A change in public perceptions brought about by effective communication is needed to widen demand for testing before treatment.


Meeting the global target of universal coverage with parasite-based diagnosis by 2015 is a huge undertaking requiring sufficient resources. The cost-effectiveness of the intervention will hinge on the accurate use of RDTs in guiding treatment. Probably the biggest challenge in RDT implementation will be to provide adequate and sustained supplies of RDTs and appropriate training to all health workers in endemic areas. With increased access to malaria diagnosis, there will also be increased use of antibiotics, and interventions to guard against even greater overuse are needed to prevent worsening antimicrobial resistance. The Affordable Medicines Facility - malaria initiative demonstrated that large increases in access to ACTs were possible. Increasing access to RDTs is equally important. ACTs and RDTs should be seen as a package to improve management of febrile cases, and improving access to both of these in the public and private sectors has the potential to provide valuable returns.

Supporting Information

Table S1.

Patients treated with antimalarials and antibiotics in studies comparing clinical diagnosis with RDTs.


Table S2.

Patients treated with antimalarials and antibiotics in studies comparing microscopy with RDTs.



The authors would like to thank Seif Shekalaghe (Ifakara Health Institute, Bagamoyo, Tanzania), Alfred Tiono (Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso), Diadier Diallo (PATH Malaria Vaccine Initiative, Dakar, Senegal), and Robert Sauerwein (Radboud university medical center, Nijmegen, the Netherlands) for comments, suggestions, and critical reading of the article.

Author Contributions

Wrote the first draft of the manuscript: GJHB. Contributed to the writing of the manuscript: GJHB TB TL. ICMJE criteria for authorship read and met: GJHB TB TL. Agree with manuscript results and conclusions: GJHB TB TL.


  1. 1. World Health Organization (2013) World Malaria Report 2013. Geneva: WHO.
  2. 2. World Health Organization (2012) T3. Test. Treat. Track. brochure. Geneva: WHO
  3. 3. Lubell Y, Reyburn H, Mbakilwa H, Mwangi R, Chonya S, et al. (2008) The impact of response to the results of diagnostic tests for malaria: cost-benefit analysis. BMJ 336: 202–205.
  4. 4. Naidoo I, Roper C (2010) Following the path of most resistance: dhps K540E dispersal in African Plasmodium falciparum. Trends Parasitol 26: 447–456.
  5. 5. Dondorp AM, Yeung S, White L, Nguon C, Day NP, et al. (2010) Artemisinin resistance: current status and scenarios for containment. Nat Rev Microbiol 8: 272–280.
  6. 6. Hausmann Muela S, Muela Ribera J, Mushi AK, Tanner M (2002) Medical syncretism with reference to malaria in a Tanzanian community. Soc Sci Med 55: 403–413.
  7. 7. Ofori-Adjei D, Arhinful DK (1996) Effect of training on the clinical management of malaria by medical assistants in Ghana. Soc Sci Med 42: 1169–1176.
  8. 8. Paredes P, Pena de la M, Flores-Guerra E, Diaz J, Trostle J (1996) Factors influencing physicians prescribing behaviour in the treatment of childhood diarrhoea. Soc Sci Med 42: 1141–1153.
  9. 9. Rowe AK, de Savigny D, Lanata CF, Victora CG (2005) How can we achieve and maintain high-quality performance of health workers in low-resource settings? Lancet 366: 1026–1035.
  10. 10. Hamer DH, Ndhlovu M, Zurovac D, Fox M, Yeboah-Antwi K, et al. (2007) Improved diagnostic testing and malaria treatment practices in Zambia. JAMA 297: 2227–2231.
  11. 11. World Health Organization (2008) Integrated Management of Childhood Illness (IMCI). Geneva: WHO
  12. 12. Haines A, Sanders D, Lehmann U, Rowe AK, Lawn JE, et al. (2007) Achieving child survival goals: potential contribution of community health workers. Lancet 369: 2121–2131.
  13. 13. Hamer DH, Brooks ET, Semrau K, Pilingana P, MacLeod WB, et al. (2012) Quality and safety of integrated community case management of malaria using rapid diagnostic tests and pneumonia by community health workers. Pathog Glob Health 106: 32–39.
  14. 14. Yeboah-Antwi K, Pilingana P, Macleod WB, Semrau K, Siazeele K, et al. (2010) Community case management of fever due to malaria and pneumonia in children under five in Zambia: a cluster randomized controlled trial. PLoS Med 7: e1000340
  15. 15. Chandramohan D, Jaffar S, Greenwood B (2002) Use of clinical algorithms for diagnosing malaria. Trop Med Int Health 7: 45–52.
  16. 16. Ansah EK, Narh-Bana S, Epokor M, Akanpigbiam S, Quartey AA, et al. (2010) Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana. BMJ 340: c930.
  17. 17. Reyburn H, Mbakilwa H, Mwangi R, Mwerinde O, Olomi R, et al. (2007) Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial. BMJ 334: 403.
  18. 18. Bisoffi Z, Sirima BS, Angheben A, Lodesani C, Gobbi F, et al. (2009) Rapid malaria diagnostic tests vs. clinical management of malaria in rural Burkina Faso: safety and effect on clinical decisions. A randomized trial. Trop Med Int Health 14: 491–498.
  19. 19. Bastiaens GJ, Schaftenaar E, Ndaro A, Keuter M, Bousema T, et al. (2011) Malaria diagnostic testing and treatment practices in three different Plasmodium falciparum transmission settings in Tanzania: before and after a government policy change. Malar J 10: 76.
  20. 20. Mwanziva C, Shekalaghe S, Ndaro A, Mengerink B, Megiroo S, et al. (2008) Overuse of artemisinin-combination therapy in Mto wa Mbu (river of mosquitoes), an area misinterpreted as high endemic for malaria. Malar J 7: 232.
  21. 21. World Health Organization (2008–2012) RDT Evaluation Programme - Product Testing Round 1–4. Geneva: WHO.
  22. 22. Njama-Meya D, Clark TD, Nzarubara B, Staedke S, Kamya MR, et al. (2007) Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children. Malar J 6: 7.
  23. 23. D'Acremont V, Malila A, Swai N, Tillya R, Kahama-Maro J, et al. (2010) Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test. Clin Infect Dis 51: 506–511.
  24. 24. Msellem MI, Martensson A, Rotllant G, Bhattarai A, Stromberg J, et al. (2009) Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar: a crossover validation study. PLoS Med 6: e1000070
  25. 25. D'Acremont V, Kahama-Maro J, Swai N, Mtasiwa D, Genton B, et al. (2011) Reduction of anti-malarial consumption after rapid diagnostic tests implementation in Dar es Salaam: a before-after and cluster randomized controlled study. Malar J 10: 107.
  26. 26. Mukanga D, Tiono AB, Anyorigiya T, Kallander K, Konate AT, et al. (2012) Integrated community case management of fever in children under five using rapid diagnostic tests and respiratory rate counting: a multi-country cluster randomized trial. Am J Trop Med Hyg 87: 21–29.
  27. 27. Punjabi NH, Taylor WR, Murphy GS, Purwaningsih S, Picarima H, et al. (2012) Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia. Am J Trop Med Hyg 86: 46–51.
  28. 28. Williams HA, Causer L, Metta E, Malila A, O'Reilly T, et al. (2008) Dispensary level pilot implementation of rapid diagnostic tests: an evaluation of RDT acceptance and usage by providers and patients–Tanzania, 2005. Malar J 7: 239.
  29. 29. Chandler CI, Jones C, Boniface G, Juma K, Reyburn H, et al. (2008) Guidelines and mindlines: why do clinical staff over-diagnose malaria in Tanzania? A qualitative study. Malar J 7: 53.
  30. 30. Proietti C, Pettinato DD, Kanoi BN, Ntege E, Crisanti A, et al. (2011) Continuing intense malaria transmission in northern Uganda. Am J Trop Med Hyg 84: 830–837.
  31. 31. Shillcutt S, Morel C, Goodman C, Coleman P, Bell D, et al. (2008) Cost-effectiveness of malaria diagnostic methods in sub-Saharan Africa in an era of combination therapy. Bull World Health Organ 86: 101–110.
  32. 32. Chuma J, Okungu V, Molyneux C (2010) Barriers to prompt and effective malaria treatment among the poorest population in Kenya. Malar J 9: 144.
  33. 33. Hetzel MW, Obrist B, Lengeler C, Msechu JJ, Nathan R, et al. (2008) Obstacles to prompt and effective malaria treatment lead to low community-coverage in two rural districts of Tanzania. BMC Public Health 8: 317.
  34. 34. Albertini A, Djalle D, Faye B, Gamboa D, Luchavez J, et al. (2012) Preliminary enquiry into the availability, price and quality of malaria rapid diagnostic tests in the private health sector of six malaria-endemic countries. Trop Med Int Health 17: 147–152.
  35. 35. Mills A, Brugha R, Hanson K, McPake B (2002) What can be done about the private health sector in low-income countries? Bull World Health Organ 80: 325–330.
  36. 36. Ikwuobe JO, Faragher BE, Alawode G, Lalloo DG (2013) The impact of rapid malaria diagnostic tests upon anti-malarial sales in community pharmacies in Gwagwalada, Nigeria. Malar J 12: 380.
  37. 37. The Global Fund (2013) Available: Accessed 31 March 2013.
  38. 38. Tougher S, Group AC, Ye Y, Amuasi JH, Kourgueni IA, et al. (2012) Effect of the Affordable Medicines Facility–malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data. Lancet 380: 1916–1926.
  39. 39. Hansen KS, Pedrazzoli D, Mbonye A, Clarke S, Cundill B, et al. (2013) Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono district, Uganda. Health Policy Plan 28: 185–196.
  40. 40. Ansah E, Epokor M, Whitty CJ, Yeung S, Hansen KS (2013) Cost-effectiveness analysis of introducing RDTs for malaria diagnosis as compared to microscopy and presumptive diagnosis in central and peripheral public health facilities in Ghana. Am J Trop Med Hyg 89: 724–736.
  41. 41. Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, et al. (2012) Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun 3: 1237.
  42. 42. Nsobya SL, Parikh S, Kironde F, Lubega G, Kamya MR, et al. (2004) Molecular evaluation of the natural history of asymptomatic parasitemia in Ugandan children. J Infect Dis 189: 2220–2226.
  43. 43. Churcher TS, Bousema T, Walker M, Drakeley C, Schneider P, et al. (2013) Predicting mosquito infection from Plasmodium falciparum gametocyte density and estimating the reservoir of infection. Elife 2: e00626.
  44. 44. The malERA Consultative Group on Diagnoses and Diagnostics (2011) A research agenda for malaria eradication: diagnoses and diagnostics. PLoS Med 8: e1000396
  45. 45. Littrell M, Sow GD, Ngom A, Ba M, Mboup BM, et al. (2013) Case investigation and reactive case detection for malaria elimination in northern Senegal. Malar J 12: 331.
  46. 46. Stresman GH, Kamanga A, Moono P, Hamapumbu H, Mharakurwa S, et al. (2010) A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia. Malar J 9: 265.
  47. 47. Bousema T, Stevenson J, Baidjoe A, Stresman G, Griffin JT, et al. (2013) The impact of hotspot-targeted interventions on malaria transmission: study protocol for a cluster-randomized controlled trial. Trials 14: 36.
  48. 48. Sturrock HJ, Hsiang MS, Cohen JM, Smith DL, Greenhouse B, et al. (2013) Targeting asymptomatic malaria infections: active surveillance in control and elimination. PLoS Med 10: e1001467
  49. 49. Amexo M, Tolhurst R, Barnish G, Bates I (2004) Malaria misdiagnosis: effects on the poor and vulnerable. Lancet 364: 1896–1898.
  50. 50. Font F, Alonso Gonzalez M, Nathan R, Kimario J, Lwilla F, et al. (2001) 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.
  51. 51. Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, et al. (2004) Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. BMJ 329: 1212.