Review of Literature
IV. Gametocytocides: These drugs act on the sexual stage of the parasite development which take place in the blood and thus inhibit the transmission of infection to the
1.3 Malaria diagnosis approaches
1.3.2 Rapid Diagnostic tests (RDTs)
assay. It was better in term of response time and sensitivity and the results show 95.49 % sensitivity and 99.53 % specificity compare to microscopy (Peng et al., 2012).
Although RDTs help a lot to curb malaria problem from malaria endemic region where basic medical healthcare facilities are weak, it suffers from various disadvantages. The variability in RDTs results with the variation of temperature, humidity, patient’s age, season of the year, and storage condition, along with its short shelf life are the major drawbacks of the RDTs (Abeku et al., 2008). The most common reason for the low performance of RDTs is exposure to high temperature and humidity which are the typical conditions in tropical or subtropical region of world where malaria is prominent (Jorgensen et al., 2006). The major causes of variation are loss of activity of antibody and damage of NC membrane. Chiodini and coworkers studied the temperature sensitivity of RDTs (or Antibody) and observed their efficiency were affected when temperature increased from 25 °C to 60 °C (Chiodini et al., 2007). Moreover, RDTs are not efficient to provide quantitative information on parasitic load, unable to differentiate among species and showing false positive results due to persistent PfHRP-II antigenmia (Mayxay et al., 2001; Kyabayinze et al., 2008) or false negative result due to deletion of HRP-II gene (Palmer et al., 1998; Iqbal et al., 2004; Lee et al., 2006a). There is a rising frequency of HRP II gene deletions primarily in Amazon regions and in many African and Asian countries that demand for a test with non-HRP II falciparum-specific targets (Bharti et al., 2016; Gamboa et al., 2010; Maltha et al., 2012; Bendezu et al., 2010). As most RDTs available in the market are HRP-II based for P. falciparum identification, they are prone to false positive and false negative results. In regard to this WHO has issued guidelines to take extra precautions while RDTs are used for malaria diagnosis and to search for suitable alternative biomarker for P. falciparum identification (World Malaria Report., 2016).
The genetic polymorphism in biomarkers (PfGDH, PfHRP-II, PLDH and aldolase) may produce false negative results as observed in global region wise assessment for polymorphism. The high level of polymorphism was reported for PfHRP-II, III genes envisaging that approximately 9 % isolates from Madagascar region were not able to detected parasitaemia at < 250 parasite µl-1 (Mariette et al., 2008). The genetic polymorphism was also reported within and across malaria endemic countries (Joshi, 2003). This has led to low efficiency of the test and only 84 % of P. falciparum infection in Asia-Pacific are possible to detect at parasitic load < 250 parasite µl-1 based on probable regression analysis. Moreover, PfHRP-III is also supposed to play a significant
contribution in the performance of PfHRP-II based detection system (Baker et al., 2005).
Which bring a major challenge to distinguish severe form of malaria from other normal febrile illness caused by P. falciparum infection based on immuno chromatographic test.
Besides of this deletion and polymorphism in PfHRP-II gene, the result produced by PfHRP-II based RDTs have to consider with precaution and further confirmation is require with other diagnostic methods (World Malaria report, 2016). The various scientific reports on performance analysis of different RDTs from different part of world have been published (Chansuda, 2001). In spite of this large number of reports their comparative exploration is, however tough due to variance in demographic, different trial guidelines, their clinical and epidemiological symptoms etc. (Wongsrichanalai et al., 2007). However, a comparative study has been performed for few prominent field trial diagnostic tests on the ground of sensitivity and specificity, as shown in table 1.5. It is clearly reveled from the table that the performances of RDTs significantly vary across different studies. Because of these variations there is a demand for more sensitive, selective, reliable and pragmatic detection method for malaria diagnosis.
Table 1.5: Comparative assessment on sensitive and selective of various prominent dipstick RDTs.
Dipstick Standard Region of study
Sensitivity (%)
Selectivity (%)
Reference
Carestart
AccessBio,(Princet- on, USA)
GTTS* South-western
Uganda
95.6 91.5 Fogg et al.,
(2008) Vistapan Mitra,
(New Delhi, India)
GTTS* South-western
Uganda
91.9 89.6 Fogg et al.,
(2008) Parabank
Orchid/Zephyr, (Goa, India)
GTTS* South-western
Uganda
84.7 94.3 Fogg et al.,
(2008) Paracheck Pf,
Orchid/Zephyr, (Goa, India)
GTTS* South-western
Uganda
94 87.3 Fogg et al.,
(2008) Optimal-IT,
DiaMed,(Cressier, Switzerland)
GTS Gabon
Children n
94 97 Mawili-
Mboumba et al., (2010) Acon, Acon Labs,
(San Diego, CA)
GTS Gabon
Children under 11 years
94 90 Mawili-
Mboumba et al., (2010) PALUTOP+4
ALL.DIAG,(France)
GTTS* and PCR
Madagascar 95.4 97.1 Rakotonirina
et al., (2008) Optimal-IT,
DiaMed,(Cressier, Switzerland)
GTTS* and PCR
Madagascar 75.8 99.0 Rakotonirina
et al., (2008)
ParaHIT Pf Test, Span Diagnostic Ltd., (Surat, India)
GTTS* and PCR
Tanzania 69.2 100 Nicastri et al.,
(2009) Malaria Pf™,
ICT Diagnostics, (South Africa)
GTTS* Uganda 98 72 Kyabayinze et
al., (2008) Paracheck Pf,
Orchid Biomedical Systems, ( Goa, India)
GTTS* Kenya 91.7 96.7 de Oliveira et
al., (2009)
Malaria Check_Pf
test, Cumberland Diagnostics, (USA)
GTS** Brazil 97.4 88.5 Avila et al.,
(2002)
Makromed Dipstick Assay, Makro medical, (South Africa)
PCR Cananda 97.0 96.0 Richardson et
al., (2002)
ParaSight®-F, Becton Dickinson, (USA)
Thin blood smears and QBC
France 94 99 Uguen et al.,
(1995) ParaSight®-F,
Becton Dickinson, (USA)
Microscopy Iquitos, Peru,and Maesod, Thailand
95 86 Forney et al.,
(2001)
Paracheck Pf, Orchid Biomedical Systems,(Goa, India)
Microscopy India 93 84 Singh et al.,
(2005)
ParaHIT-Pf, Span Diagnostics, (Surat, India)
GTS** Tanzania 90.7 73.5 McMorrow et
al., (2010) ParaHIT-Pf ,
Span Diagnostics, (Surat, India)
Microscopy India 87.5 97 Singh et al.,
(2005) GTTS*-Giemsa thick and thin smear, GTS**-Giemsa thick smear