Malaria (Bayoh, 2001). Consequently, temperatures below 180C inhibit

Malaria epidemiology

Malaria is a global health problem
where Sub-Saharan Africa being the worst hit (WHO, 2017). It is estimated that about
3.2 billion people were at risk of malaria with 216 million cases resulting in
445, 000 deaths globally (WHO, 2017).  Almost 91% of the total reported deaths
occurred in sub-Saharan Africa followed by South east Asia (6%) and lastly by
the Eastern Mediterranean region (2%)(WHO, 2016, 2017). However, recent analysis in
endemic Africa indicate that due to 
scale-up of vector control  and
use of artemisinin combination therapy, malaria prevalence and clinical
incidence have reduced by 50% and 40% respectively in the years 2000-2015 (Bhatt et al., 2015).
In Kenya, reports indicate that malaria is the leading cause of mortality in children
and pregnant women (Mohajan, 2014). Western Kenya which lies
along the lake region has been reported to bear the largest brunt of malaria
infection (MOH, 2014).

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2.2. Malaria transmission
pattern in Kenya

Due to difference in altitude,
temperature intensity and rainfall patterns within the Kenya, malaria
transmission pattern is diverse and is categorized into 4 major epidemiological
zones. They include: endemic regions (around the lake region of western Kenya
and Coastal region), highland epidemic prone zones (western highlands),
seasonal malaria transmission zones (arid and semi-arid areas) and low risk
transmission area such Nairobi and central part of Kenya (MOH, 2016b).

Temperature, rainfall and humidity
are important climatic factors that are capable of shifting malaria
transmission by influencing parasite development within the vector, vectors
survival and biting rate (Githeko et al., 2000; Gage et al.,
The aquatic stages of anopheline mosquito have been reported to ceases
development or breeding below 160C (Bayoh, 2001). Consequently, temperatures
below 180C inhibit the development of P. falciparum within the mosquito vector (Githeko et al., 2000; Aly et al., 2009; Bousema and Drakeley, 2011b).
Environmental factors such as land forms, water, topography and vegetation
cover have been shown to influence malaria transmission, species abundance and
distribution (Kelly-Hope et al., 2009; Cottrell et al., 2012; Githeko et al.,
Therefore changes in environmental factors can positively or negatively
influence establishment of breeding habitats for malaria vectors, thereby
affecting transmission rate.


Understanding the nature
and degree of malaria transmission is important when designing an effective
strategy to manage the disease (Hay and Snow, 2006). Diagnostic tools which can
detect both microscopic and submicroscopic infections remain a critical step
to minimizing global malaria burden (Rek et al., 2016). This is not
only applicable in low malaria transmission settings, but also in highly
endemic countries (Rek et al., 2016). Asymptomatic malaria in
endemic regions proves to be a challenge as concerted efforts are geared
towards eliminating the parasite (Trape et al., 1987; Bonnet et al.,
2002; Roucher et al., 2012). This is because reports
indicate that asymptomatic infections are likely to outnumber symptomatic
infections in endemic regions (Pinto et al., 2000; Alves et al.,
2002; Lindblade et al., 2013). Therefore, control
strategies that specifically aspire to scale down malaria transmission may be
required, and for such interventions to reach desired goal, identification of
the human reservoir of malaria is of utmost importance.

2.3. Life cycle of Plasmodium and gametocyte development

The life cycle of Plasmodium
species  is complicated due to the parasite’s
ability to switch its cellular and molecular composition and to develop both
within and outside the cell niches in the human host and mosquito vector (Aly et al., 2009). The life cycle of all species of human malaria parasites is
divided into both sexual in mosquito vector and asexual stages in human host
(Appendix I). The male and female gametocytes ingested during blood meal fuse
to form zygote which then develop into motile ookinete within the mosquito
midgut.  Ookinete develops to oocyst from
which numerous sporozoites emerge and migrate to salivary glands via
haemolymph. It’s during this point that the mosquito is able to transmit the
parasites to the new human host (Cator et al., 2013; Paaijmans et
al., 2013; Smallegange et al., 2013; Cator et al., 2014).


The asexual phase takes place both in the liver and
red blood cells of the human host. During blood meal, an infected
mosquito injects numerous sporozoites into the blood stream (Amino et al., 2006; Yamauchi et al.,
2007; Lindner et al., 2012). The released sporozoites
locomote, enter the liver cells and begin asexual multiplication (Antinori et al., 2012). Development period within the liver cells differs among the
malaria parasites. Plasmodium falciparum has shorter development duration within the liver and
merozoites are released into the bloodstream after about 6–8 days (Mazier et al., 2009). They then invade red blood
cells and initiate the asexual multiplication cycle.  For both P. vivax
and P. ovale, instead of developing
directly into schizonts, some of their sporozoites differentiate into
hypnozoites which remain dormant in the liver cells but when reactivated, they
multiply and cause clinical relapse some weeks, months or years after the
initial infection (Garnham, 1988; Galinski et al., 2013).


The release of P. falciparum merozoites
into the bloodstream may trigger rapid increase of parasite densities during the
48 hour erythro­cytic cycle thereby influencing severe disease (Bousema et al., 2014). A fraction of
merozoites released from infected red blood cells develop into male and female sexual gametocytes. These gametocytes mature within the
bone marrow for about 10-12 days (Eichner et al., 2001), appear in
peripheral blood and can be ingested by mosquitoes when they take a blood meal (Garnham, 1988; Bousema et al., 2014). Studies indicate that the
first produced gametocytes are likely to circulate at very low densities but
can sustain transmission (Bousema and Drakeley, 2011a). A low level of gametocyte
in blood was also theorized to be a designed strategy to evade immune response
against these sexual parasites (Taylor and Read, 1997; Piper et al., 1999; Saeed et al.,
2008). Therefore, to interrupt
transmission, accurate quantification and clearance of gametocytes within a
population is very important.


2.4. Malaria pathology

Malaria is acute febrile
illness whose manifestations are due to infection
of the red blood cells by the asexual blood stage parasites (Omer et al.,
2003; Greenwood et al., 2008). Both severe and uncomplicated malaria manifests with common clinical
symptoms such as chills, fever, headache, and vomiting, sweating and joint
pains. As the parasites develop and multiply within the red blood cells, they
rapture the infected erythrocytes and waste products and toxic factors are
released into the blood stream which consequently stimulates the action of
immune system. The systemic manifestations of malaria such as headache, fever
and rigors, have been adversely linked to action of cytokines against these
parasite and red cell membrane products (Clark et al.,
2006). While P.
falciparum infection has been vastly linked to majority of severe malaria
and related mortality, increasing body of evidence indicate that non-falciparum infections can lead to
complications.  Recent studies reported
cases of severe infection including death due to P. vivax and P. knowlesi
infections (Kochar et al.,
2005; Anstey et al., 2007; Anstey et al., 2009; Daneshvar et
al., 2009; Cox-Singh et al., 2010) .


Majority of fatal cases   caused by P. falciparum infections, are due to severe anaemia or cerebral
malaria. However variable  clinical
symptoms which differs  in severity and
outcome also exist depending on the organ involved and the health seeking
behavior (Autino et al., 2012). Parasite sequestration which
may lead to organ failure or malfunction has been linked to occurrence of
severe clinical symptoms and cerebral malaria (Grau and Craig, 2012).  In western Kenya, P. falciparum account for about 92% of total malaria
infections  (MOH, 2016b), hence it is important to
determine the spectrum of disease severity within the study site to design
appropriate interventions.


2.5. Diagnosis of malaria

Malaria is febrile illness which requires accurate and timely diagnosis accompanied
by immediate treatment for proper management and control (Endeshaw et al., 2008). Accurate diagnosis is also
important when realistic estimates of malaria burden are needed to guide on
informed interventions (Wongsrichanalai et al., 2007; Fancony et al., 2013)  Parasite based diagnosis has been recommended
by World Health Organization as the best option towards malaria case management
(WHO, 2015b). This is to minimize indiscriminate administration of
antimalarials in unconfirmed cases which may contribute to increasing resistance of parasites to the existing
drugs. Various diagnostic tools have been in practise with microscopy being the
gold standard for laboratory diagnosis of malaria (Makler et al.,
1998; Ndao et al., 2004). In regions where laboratories lack required
facilities, Clinical
diagnosis has been widely used; however, this type of diagnosis is unreliable
due to the non-specific nature of signs and symptoms of malaria (Bardaji et al., 2008; Endeshaw et al.,
2008; Juma and
Zurovac, 2011). In recent years, other
affordable, fast and simple diagnostic techniques such as application of Rapid
Diagnostic Test kits (RDT) are being introduced in endemic settings especially
in regions with few experienced microscopists (Lubell et al., 2007). Unfortunately, the
inability of RDTs to quantify the parasite load and its tendency to detect
gametocytes especially in Parasite Lactate
Dehydrogenase (pLDH)-based RDTs may confound treatment outcomes (Mueller et al., 2007).


Other parasite-based diagnostic methods such as
Polimerase chain reaction (PCR), flow cytometry, ELISA and indirect
immunofluorescence antibody assay (IFA) have been developed to help in
reduction of morbidity and mortality associated with malaria. However, most of
them are not frequently used in diagnosis of malaria especially in Kenyan
hospitals. Unlike microscopy and RDTs, molecular detection techniques have a
greater sensitivity that can reveal widespread presence of infections with very
low parasite densities (Snounou, Viriyakosol, Zhu, et al., 1993). Due to high detection of
both parasites and gametocytes, they are being introduced in many laboratories
in endemic countries and are widely used in interventions and field surveys (Andrade et al., 2010; Kamau et al.,
2011). These molecular detection
techniques are valuable in areas experiencing perennial malaria transmission
because majority of infections may be submicroscopic rendering microscopy
inefficient. Therefore, to accurately determine the proportion of individuals harboring
gametocytes and to quantify the actual burden of submicroscopic infection,
molecular techniques will be of utmost importance.


2.6. Malaria control strategies


of concerted efforts to control malaria has greatly minimized malaria burden and
transmission most countries (Gething et al., 2010; Murray et al., 2012; Cotter et al.,
2013) Various strategies that  have been put in place for management and
control of malaria include; use of insecticide-treated bednets (ITNs),
widespread application of Indoor Residual Spray (IRS) and availability of
effective treatment of clinical malaria (Lindblade et al., 2013). Early treatment with effective antimalarial drugs has
remained main intervention but treatment is threatened by the growing
resistance of parasites to the existing drugs (Laxminarayan et al.,
2006). Currently, artemisinins are the most effective remaining
antimalarial. These drugs  can
effectively clear  asexual blood stages
and  P. falciparum gametocytes at manageable concentrations (Maude et al., 2010). Efficacy of chloroquine, Sulphadoxine-Pyrimethamine (SP),
amodiaquine and quinine diminished after reported cases of emerging drug
resistant parasites (Trampuz et al., 2003; Achan et al.,
2011; Shujatullah et al., 2012; Wongsrichanalai and Sibley, 2013).


Both ITNs an IRS remain the major control
interventions against the malaria vectors. For successful implementation, World
Health Organization has intensified campaign to cover all population at risk
with either ITNs or indoor residual spraying (IRS) (WHO, 2008). Study findings further indicate that both ITNs and
IRS are capable of cutting down malaria transmission when applied independently
(Lengeler, 2004; Pluess et al., 2010; Kim et al., 2012).
As a result, many countries have adopted both interventions (Raghavendra et al., 2011). In Africa, the ownership of
ITNs per household increased from 3% in 2000 to 54% in 2013 while the
proportion of the population protected by IRS increased from below 5% in 2005
to 8% in 2012 (WHO, 2013; West et al., 2014).
In western Kenya, malaria control activities have been intensified for more
than 10 years but parasite prevalence in children under the age of 5, only
reduced from 83% in 1999 to 41% in 2009 by microscopy (Hamel et al., 2011). To improve efficiency of
these intervention strategies, asymptomatic individuals should be targeted to
interrupt continuous transmission. This is possible with adoption of very
sensitive detection tools.

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