Parasite prevalence rate
The parasite prevalence rate (PPR) is a measure of the prevalence of asexual peripheral blood-stage infection in a population (equation (6)) and has been the most evaluated metric of malaria endemicity (Guerra et al., 2007). It is actually a proportion as measurement is usually at one time point in the year (i.e. point prevalence), and so its value can be affected by within- and between year variations (like seasonality and sudden changes weather pattern respectively). Despite this PPR is a good metric to assess short- to medium term impact of scaling up of malaria control efforts, as it sensitive to changes in transmission intensity.
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Table 2: The pros and cons of using RDTs and microscopy to determine PPR during population-based surveys (Adapted from: Household Survey Indicators for Malaria Control (MEASURE Evaluation et al., 2013a))
Rapid Diagnostic Test Microscopy
Pros • Use requires less training than
microscopy
• Results are rapid (within 15
minutes), thus facilitating timely treatment.
• In survey settings, costs are lower
than microscopy
• Currently available RDTs have
sensitivity and specificity comparable to routine microscopy
• Historically, considered the gold
standard for malaria diagnosis
• Permits speciation and
quantification of parasites.
• Can detect low infection (<200
parasites/μl), assuming skilled microscopist
• Historical comparisons possible
assuming comparable skill of microscopists and consistency of methods of quantification over time.
• Slides can be stored and re-
examined, enabling retrospective quality control
Cons • Individuals may test positive by
Histidine Rich Protein 2 (HRP2)- based RDTs within 14 days after effective treatment for malaria, as antigens often persist after treatment
• Variation may exist between
brands and types of RDTs (including the antigens are detected) and this could affect the comparability of survey results.
• Tests that detect other species do
not identify which is present
• Quantification of parasites is not
possible
• Sensitivity is low for low parasite
densities
• Practical difficulties preparing
blood films in the field.
• Slides must be transported and
stored.
• Results take longer (more than 15
minutes)
• In survey settings, costs are
higher than RDTs
• Skilled microscopists are not
always available and this might affect the quality of speciation and quantification
• Intra-observer variation is likely
to occur between microscopists.
Since the majority of malaria infections and gametocyte carriage are asymptomatic regardless of transmission (Park et al., 2000; Pinto et al., 2000; Alves et al., 2002; Bousema et al., 2004; Macauley, 2005; Laishram et al., 2012), the parasite prevalence rate assessed through population-based cross-sectional surveys is a better measure of endemicity than the prevalence in clinical cases. Diagnostic confirmation of the presence of infection during this surveys is normally through microscopy or RDT (MEASURE Evaluation et al., 2013a). Though microscopy is
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historically considered as the “gold” standard for the diagnostic confirmation, RDTs are increasingly being view as a suitable objective particularly where P. falciparum accounts for more than 90% of all malaria infection and low level infections (<200 parasites/μl) are uncommon (MEASURE Evaluation et al., 2013a). The use of RDTs has some advantages over microscopy in survey settings as they provide timely results and have comparable sensitivity and specificity (Table 2). There is also a mechanism in place for the regular evaluation of the performance of RDTs through the WHO Product Testing Programme and this information is updated regularly with the most recent report being Round 3 (WHO, 2011a).
Polymerase chain reaction (PCR) has been reliably used as a complementary tool in malariometric surveys (Satoguina et al., 2009; Takem et al., 2013), but
because of cost and the requirement of advanced laboratory facilities, PCR has been more of a research tool for the quality control of speciation and quantification (Stich et al., 2006; Ebrahimzadeh et al., 2007; Schachterle et al., 2011; Asih et al., 2012; Fancony et al., 2013). Recent developments with molecular-based isothermal tests means that field deployment of PCR is now possible (Oriero et al., 2014), and this has promising prospects for malaria surveillance given the fact that plasmodium DNA can be recovered from alternative specimens like saliva (Nwakanma et al., 2009; Estevez et al., 2011). Polymerase chain reaction has great potential in the detection of sub-microscopic infection (Golassa et al., 2013; Mosha et al., 2013) which will be of increasing importance as transmission falls (Harris et al., 2010; Golassa et al., 2013).
The classification of malaria of endemicity based on PPR was a subject of much debate and consensus was only achieved recently as part of the development of the Malaria Atlas Project (Guerra et al., 2007; Hay et al., 2008; Gething et al., 2011; Gething et al., 2012) and efforts to guide malaria control and eradication strategy based on classification of malaria risk (Hay et al., 2008) (Table 3and Table 4). This represented a revision of the classification proposed earlier by Metselaar & Van
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Thiel (WHO, 1963) and an expansion to include classification of the endemicity of P. vivax (Gething et al., 2012). The recommendation of both systems of classification is that the endemicity be classified by the species specific PPR in population at risk. Gething et al 2011 went further to specify that the population at risk as children aged 2 to 10 years influenced by the earlier work of Smith et al, who tested
algorithms for the age-standardization of PfPR and concluded that that age group was the most appropriate the purposes of comparing studies and mapping malaria endemicity (Smith et al., 2007a). The age at risk for P. vivax infection was considered to be all individuals aged 1 to 99 years, and the all-age infection prevalence the appropriate measure to classify endemicity (Table 4) (Gething et al., 2012).
Table 3: Current classification of P. falciparum malaria endemicity by P. falciparum
Prevalence Rate (PfPR)
Endemicity PfPR (Hay et al.,
2008)
PfPR2-10(Gething et al., 2011)
Intense stable (hyper-holoendemic) >40% >40% Moderate stable (hypo-
mesoendemic)
5.1 – 39.99% 5.1 – 39.99%
Unstable endemic <5.0% <5.0%
Non-endemic * *
Malaria free * *
*At this point PfPR is not a reliable estimate of endemicity and P. falciparum annual parasite incidence (PfAPI) is preferred.
Despite the recent evidence, it is still the policy-recommended approach to assess national-level PPRs for P. falciparum in children aged 6-59 months during population-based surveys; and that the PPR in older age groups should only be measured when there is no clear age pattern in infection, prevalence is low, malaria transmission is unstable or information is required for the modelling of malaria incidence (MEASURE Evaluation et al., 2013a). However, the assessment of parasite prevalence in children aged 2 to 9 years old is recommended for the continuous
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facility-based surveillance of malaria cases at all stages of control (WHO, 2012a; WHO, 2012b).
Table 4: Current classification of P. vivax malaria endemicity by P. vivax Prevalence Rate (PvPR)
Endemicity PvPR1-99(Gething et al., 2012)
Stable >1.0%
Unstable <1.0%
Unstable and high Duffy antigen negativity (>90%) <1.0%
Risk free *
*At this point PvfPR is not a reliable estimate of endemicity and Plasmodium vivax annual parasite incidence (PvAPI) is preferred.
Anaemia prevalence rate (APR)
Although anaemia (Hb<8.0g/dl is not specific to malaria, the APR (equation (7)) has remained a policy-recommended measurement to assess the impact of malaria control efforts (RBM, 2003; Korenromp et al., 2004), due the 60% reduction in the risk of moderate-to-severe anaemia (Hb<8.0 g/dL) observed in a quantitative review of the impact of malaria control on haemoglobin distributions and anaemia prevalences in children under 5 in malaria-endemic Africa (Korenromp et al., 2004). This cut-off point appeared to be more specific for assessing the impact of malaria control measures than the lower cut-off point of Hb<7.0g/dl recommended for the classification of nutritional anaemia (WHO, 1968; DeMaeyer and Joint
WHO/UNICEF Nutrition Support Programme, 1989), and the higher cut-off point for any anaemia (Hb<11.0g/dl) (Korenromp et al., 2004). The development of the HemoCue® Hb Point-of-care test (HemoCue AB, Ängelholm, Sweden) greatly simplified the measurement of the haemoglobin distribution during large-scale household surveys by providing an accurate, portable, and relatively low cost solution to the assessment of haemoglobin in the field than previous methods like the direct and indirect measurement of cyanmethaemoglobin (Sari et al., 2001).
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5* = +,. ,1 ℎ 6 6 − 59 ,ℎ .ℎ 8 < 8 6/</, ,. ,1 ℎ 6 6 − 59 ,ℎ × 100 (7)
APR unlike PPR is not designed to measure or classify endemicity but to measure impact of malaria control interventions, which is no surprise based on the evidence for its validity as an indicator (Korenromp et al., 2004). This means that unlike PPR, APR cannot be used to guide strategy during the phases of control or elimination. Another potential shortcoming to the use of APR is the fact that normal
haemoglobin distributions vary with altitude and adjustment factors are required when at high altitude (CDC, 1998). APR is also affected by seasonal variation where transmission is seasonal and this makes the values sensitive to the timing of surveys in these regions. Caution is advised in the interpretation of APR given the problems with its specificity particularly in areas with low malaria transmission, given other anaemia determinants such as paediatric HIV/AIDS, malnutrition and helminth infections (MEASURE Evaluation et al., 2013a).