SEARCH

SEARCH BY CITATION

Keywords:

  • malaria;
  • diagnosis;
  • rapid test;
  • Burkina Faso
  • malaria;
  • diagnostic;
  • test rapide;
  • Burkina-Faso
  • Malaria;
  • diagnostico;
  • prueba rápida;
  • Burkina Faso

Abstract

  1. Top of page
  2. References

Summary

Objective  To compare the performance of OptiMAL-IT®, a rapid diagnostic test for malaria, with that of microscopy in Burkina Faso.

Method  Finger-prick blood samples of 464 children attending hospital for suspected malaria were tested for malaria by microscopy and OptiMAL-IT®.

Results  The sensitivity and specificity of OptiMAL-IT® were 98.7% (CI 95% = 97.6–99.8) and 96.2% (CI 95% = 94.3–98.1) respectively, with a high positive likelihood ratio (25.97).

Conclusion  OptiMAL-IT® can be considered a good method to diagnose malaria in Burkina Faso, particularly in remote areas with little or no access to microscopy services.

Misdiagnosis of malaria cases is a major challenge for control programs, possibly resulting in delayed diagnosis and treatment followed by substantial mortality and morbidity in Sub-Saharan countries (Amexo et al. 2004). A rapid and accurate method for detecting malaria parasitaemia is essential to address this issue (WHO 2003). Microscopy is currently considered as the golden standard for malaria diagnosis but, despite its apparent simplicity, requires some conditions not always accessible for many peripheral health facilities in Africa (Haditsch 2004). In this context, the rapid diagnostic tests (RDTs) might be a possible alternative. National Malaria Control Programs are being encouraged to include RDTs in the algorithms designed for malaria case management. Nevertheless, choosing a particular RDT is not easy as several brands are available on the market. In addition, little information on the performance of RDTs in Africa is available (Vanderjagt et al. 2005). In this study, we evaluated the OptiMAL-IT® (DiaMed Basel, Switzerland), an RDT recently registered by Burkina Faso’s Drugs Authorities.

The study was conducted in 2005 in Nanoro, Burkina Faso, where malaria is hyperendemic and the entomological inoculation rate (EIR) is estimated at around 50–60 infecting bites/man/year (T. Baldet, personal communication). Children 6–59 months old attending the local hospital and with suspected malaria were recruited if a parent or guardian gave informed consent. For each patient, two drops of blood were collected by finger prick and used to determine the presence of peripheral parasitaemia (thick/thin blood film) and to perform the RDT. The parasite density was determined according to published methods (Warhurst & Williams 1996). The OptiMAL-IT® test was performed according to the manufacturer’s recommendations (Ratsimbasoa et al. 2007). The microscopic reader was blinded to the RDT’s results. Considering the results of the microscopy as the ‘golden standard’, we categorised each RDT result as a true-positive, true-negative, false-positive or false-negative. The test’s sensitivity, specificity, positive predictive value (PPV), negative predictive value (NNV) and likelihood ratio of a positive test (LR) were then calculated according to published methods (Mboera et al. 2006). For each value, the 95% confidence interval (95%CI) (α = 0.05) was calculated.

A total of 82.8% (384) of the 464 patients recruited had microscopically detectable peripheral parasitaemia with a geometric mean density of 5 237 parasites/μl (SD = 1 576, range = 40–234 280 parasites/μl), mostly P. falciparum (94.3%; 362/384). The percentage of children positive to the RDT was slightly lower (82.3%; 382/464) than the percentage detected by microscopy, also mostly P. falciparum (97.1%; 371/382) infections. The 379 true positive cases had a geometric mean-parasite density of 4 268 parasites/μl (SD = 740, range = 40–234 280). There were three false-positives and five false-negatives, the latter with a low parasite density (geometric mean = 225.3, SD = 112.8, range = 80–720 parasites/μl) (Table 1). The test’s sensitivity, specificity, PPV and NNV were, 98.70 [97.56–99.84], 96.25 [94.35–98.15], 99.21 [98.32–100.0] and 93.90 [69.96–96.29] respectively. OptiMAL-IT® performed very well with an LR of 25.97 [21.98–29.96]. However, its sensitivity falls with the level of parasite density (Table 2).

Table 1.   Prevalences of malarial infection among the study population as determined by the OptiMAL-IT® and by microscopy
 Microscopy
Positive n (%)Negative n (%)Total n (%)
OptiMAL-IT Positive379 (81.68)3 (0.65)382 (82.33)
OptiMAL-IT Negative5 (1.08)77 (16.59)82 (17.67)
Total384 (82.76)80 (17.24)464
Table 2.   Sensitivity of OptiMAL-IT® at different levels of parasitemia
Microscopy parasitemia ranges n OptiMAL-IT® positiveSensitivity (%)
<500514792.2
501–1000242395.8
1001–50008585100
5001–100005959100
>10000157157100

OptiMAL-IT® RDT is based on the detection of a specific antigens produced by the malaria parasites, the plasmodium lactate dehydrogenase (pLDH) (Makler et al. 1998), present in the blood of currently or recently infected people. OptiMAL-IT® performs relatively well, with a false negative result only in children with a low-parasite density. Its sensitivity reported is higher than the 95% recommended by WHO (2003), but drops significantly when parasitaemia is less than 500 parasites/μl, a result consistent with earlier studies in Guyana and Thailand (Palmer et al. 1999).

False positives represented less than 1% of all positive by OptiMAL-IT®. This may be due to the cross-reactions with heterophile antibodies in patient’s plasma (Ghosh et al. 2001; Bell et al. 2005) or to parasite density below the microscopy threshold of detection (50–100 parasites/μl) (WHO 1998). Indeed, malaria infection can be detected by PCR in samples negative for microscopy but positive by RDT (Tham et al. 1999; Moody & Chiodini 2002).

The RDTs used in this study were permanently stored in individual packages at a temperature below 30 °C. These conditions may not be respected if the tests were stored and made available in peripheral health facilities and might result in a much higher percentage of false positive than described here. Stability is often mentioned when the percentage of false positive is higher than expected, for example in Thailand, where the percentage of false positives was 8% (Pattanasin et al. 2003).

In conclusion, in Burkina Faso, OptiMAL-IT® could be a useful alternative to microscopy, although the issue of conservation in peripheral health facilities should be carefully considered before their implementation. The high cost (2.5€) is another reason limiting their scaling up and use in most health facilities. Adequate diagnosis is considered an important component of malaria case management. However, in many African countries microscopy is not available in most peripheral health facilities, even after the change of antimalarial drug policy to artemisinin-based combination treatments. RDT could be a useful tool to overcome this limitation but need to be made more accessible in terms of cost and availability.

References

  1. Top of page
  2. References
  • Amexo M, Tolhurst R, Barnish G et al. (2004) Malaria misdiagnosis: effects on the poor and vulnerable. Lancet 364, 189698.
  • Bell DR, Wilson DW & Martin LB (2005) 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. American Journal of Tropical Medicine and Hygiene 73, 199203.
  • Ghosh K, Javeri KN, Mohanty D et al. (2001) False-positive serological tests in acute malaria. British Journal of Biomedical Science 58, 2023.
  • Haditsch M (2004) Quality and reliability of current malaria diagnostic methods. Travel Medicine Infectious Disease 2, 149160.
  • Makler MT, Piper RC & Milhous WK (1998) Lactate dehydrogenase and the diagnosis of malaria. Parasitology Today 14, 376377.
  • Mboera LE, Fanello CI, Malima RC et al. (2006) Comparison of the Paracheck-Pf test with microscopy, for the confirmation of Plasmodium falciparum malaria in Tanzania. Annals of Tropical Medicine and Parasitology 100, 115122.
  • Moody AH & Chiodini PL (2002) Non-microscopic method for malaria diagnosis using OptiMAL IT, a second-generation dipstick for malaria pLDH antigen detection. British Journal of Biomedical Science 59, 228231.
  • Palmer CJ, Validum L, Lindo J et al. (1999) Field evaluation of the OptiMAL rapid malaria diagnostic test during anti-malarial therapy in Guyana. Transactions of the Royal Society of Tropical Medicine and Hygiene 93, 517518.
  • Pattanasin S, Proux S, Chompasuk D et al. (2003) Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 97, 672674.
  • Ratsimbasoa A, Randriamanantena A, Raherinjafy R et al. (2007) Which malaria rapid test for Madagascar? Field and laboratory evaluation of three tests and expert microscopy of samples from suspected malaria patients in Madagascar American Journal of Tropical Medicine and Hygiene 76, 481485.
  • Tham JM, Lee SH, Tan TM et al. (1999) 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. Journal of Clinical Microbiology 37, 12691273.
  • Vanderjagt TA, Ikeh EI, Ujah IO et al. (2005) Comparison of the OptiMAL rapid test and microscopy for detection of malaria in pregnant women in Nigeria. Tropical Medicine and International Health 10, 3941.
  • Warhurst DC & Williams JE (1996) ACP Broadsheet no 148. July 1996. Laboratory diagnosis of malaria. Journal of Clinical Pathology 49, 533538.
  • WHO (1998) Malaria diagnosis: memorandum from a WHO meeting. Bulletin of the World Health Organization 66, 575594.
  • WHO (2003) Malaria Rapid Diagnosis: Making it Work. Meeting report January 20–23 Manila. World Health Organization, Geneva.