CHAPTER ONE
1.0 INTRODUCTION
Malaria is a life-threatening illness,
that has continued to pose public health challenges. It affects millions
of people all around the globe especially, in Africa, Asia and South
America. Malaria is currently endemic in over 100 countries with 3
billion people at risk of infection and around 225 million cases in
2009, leading to approximately 781,000 deaths (WHO, 2010). Malaria has
remained a major public health problem in Nigeria, and is responsible
for 30% childhood and 11% maternal mortality (FMoH, 2005). It accounts
for 300,000 deaths each year and about 60% of outpatient visits
(President’s Malaria Iniative, 2011). Together Nigeria, and the
Democratic Republic of Congo account for over 40% the estimated total
malaria burden and deaths globally (WHO, 2012). It is caused by the
asexual form of the parasitic protozoan know as Plasmodium. The species incriminated are Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale which is found humans and Plasmodium knowlesi which found in non-humans. Among these parasites, Plasmodium falciparum and Plasmodium vivax are
the most widespread and common causes of mixed-species malaria, which
is defined as co-infection with more than one species or genotype of Plasmodium (Mayxay et al., 2004).
Most cases of malaria are uncomplicated,
commonly presenting with fever and sometimes with other non-specific
symptoms including headache, and aches and pains elsewhere in the body
(Gilles, 1991; WHO, 2003). Mtoni and Senosi (2007) noted that early
diagnosis and treatment are key to addressing morbidity and mortality
due to malaria. Proper management of malaria cases within the first 24
hours of onset is considered to be the best way to reduce its morbidity
and mortality (Singh et al., 2013). This would be adequately achieved if most of the patients have access to laboratory facilities (Kamugisha et al., 2008). Most victims of malaria still die, because the disease is not diagnosed in time by health workers (Uzochukwu et al.,
2009). Microscopy is the gold standard for laboratory diagnosis of
malaria in many developing countries, though expertise may be lacking in
both endemic and non-endemic settings (Moody, 2002), especially in
Nigeria. However, in situations lacking reliable microscopic diagnosis,
rapid diagnostic tests (RDTs) may offer a useful alternative to
microscopy (Nour et al., 2009).
In general, RDTs are fast, easy to perform and relatively cheap (Lubell et al.,
2007). A lot of research and development has been going on to develop
alternative methods for laboratory diagnosis of malaria. Rapid
diagnostic tests have been developed, validated and field tested. It was
introduced in the nineties, but has now undergone many improvements
(Martha et al., 2010). Malaria rapid diagnostic test plays a
key role in malaria control and elimination programmes in order to avoid
unnecessary anti-malarial therapy, to prevent drug resistance and to
enhance case finding (Eibach et al., 2013). The RDTs are based
on the principle of immunochromatography, which require finger prick
blood and detect malaria specific antigen. There are three different
RDTs that are available commercially; one of them is specific for
detecting P. falcipraum antigens, while the other two detects
one or more of the three human malaria species. The RDTs provide quick
results, are reliable, and require less skilled persons as compared to
microscopic diagnosis. They do not require electricity or any equipment.
It promotes patient’s confidence as well as health services.
More than 60 RDT brands and over 200
different products have been developed. Of these, the WHO and Foundation
for Innovative New Diagnostics (FIND) evaluated 70 from 26
manufacturers (WHO, 2008; 2009). Of these products, 39 are three-band
tests that detect and differentiate P. falciparum from non falciparum species (Martha et al.,
2010). The CareStart™ Malaria HRP-2/ pLDH (Pf/pan) Combo Test and the
SD Bioline Ag pf/pan, HRP-2 and pan-pLDH are both a three-band RDT
detecting HRP-2 and pan-pLDH. This present study is focused on
evaluating the efficacy of two of the many RDTs; SD Bioline and
CareStart™ Malaria kits using it microscopy test as the gold standard
for the diagnosis of malaria.
SD Bioline (Ag pf/pan, Cassette, RDT, kit) is a one step differential diagnosis by detecting HRP-II antigen from Plasmodium falciparum and pLDH antigen from other species (P. vivax, P. malariae, P. ovale) in human whole blood. The CareStart (Combo, dev., RDT) is a test designed for the differential diagnosis between Plasmodium falciparum and other Plasmodium species such as Plasmodium vivax, Plasmodium ovale and Plasmodium
malariae. Though, the gold standard for malaria testing remains
microscopy, but the limitations associated with this technique could
affect the speed of delivery of quality services to the patients (Ameh et al., 2012).
1.1 Statement of the Problem
Microscopy has been in use for over 100
years and is inexpensive, rapid and relatively sensitive when used
appropriately (Laveran, 1891). Microscopy is regarded as the ‘gold
standard’ for malaria diagnosis (WHO, 1999). However, the lack of
skilled scientists in medical facilities in affected areas often leads
to poor interpretation of data. In addition, microscopy is time
consuming, labour intensive, and cannot detect sequestered P. falciparum parasites (Leke et al., 1999). It is less reliable at low-density parasitaemia that is, 50 parasites (ml blood) (Kilian et al., 2000; Bell et al.,
2005). Even though microscopy is cheap, reliable and available on an
instant base, it has limitations. For instance, in resource-limited
centres, there are problems of equipment, training manpower, and
workload, whereas in non-endemic countries, laboratory staff may lack
sufficient exposure to malaria positive samples resulting in low
expertise (Moody, 2002; Hanscheid, 2003).
In Nigeria, RDTs are still new to the
people, and they are unsure of the efficacy, accuracy and authenticity.
It has been 7 years since the launching of malaria RDTs in Nigeria but
the populace know little or nothing about Malaria RDTs due to poor
promoting from the part of manufacturers. In addition, the
implementation of RDTs also faces many difficulties such as logistics;
transport and continuous supply, limited shelf life and the need of
proper storage rooms. RDTs are quickly affected by humidity and extreme
temperatures (Wongsrichanalai et al., 2007). They are not able
to quantify parasitaemia and may give false positive results owing to
the persistence of antigens that can remain in the circulation of a
patient after treatment (Wongsrichanalai et al., 2007).
1.2 Significance of the Study
The essence of continuous
research and development is to find a way to improve the lives of people
around the globe. Thus, finding an alternatively cheap, fast,
convenient and effective way to diagnosis malaria is a key to control
malaria. This study is therefore significant in many ways:
- The finding of this study will be useful and helpful to the Federal
and State Government with regard to malaria eradication in making
decisions on implementation of RDTs for routine diagnosis in the
Nigeria, especially in rural areas.
- The findings of this study will provide an alternative, effective
and reliable diagnosis of malaria patients in both those that are
asymptomatic and symptomatic.
- RDTs are fast, easy to perform and relatively cheap and can easily be used by both the trained and untrained.
1.3 Research Questions
- What is the efficacy of SD Bioline and Carestart when compared to microscopy?
- Can RDTs such as SD Bioline and Carestart be alternative for the gold standard (microscopy) in the diagnosis of malaria.
1.4 Research Hypothesis
HA: RDTs are more efficient in the detecting of malaria cases than microscopy
HO: Microscopy is more efficient in defecting malaria than RDTs
- 1. Aims and Objectives of the Study
The aims and objectives of this study were to:
- Evaluate the efficacy of the Carestart Malaria HRP2 and pLDH/HRP2 Combo compared to microscopy in the diagnosis of malaria.
- Determine the sensitivity, specificity, positive and negative predictive values of the malaria RDTs to microscopy.
- Determine the relationship between malaria parasite density and results of malaria RDTs.
- Correlate results of negative malaria detection rate by microscopy to results of malaria RDTs.