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Malaria transmission levels vary significantly between different geographic regions [75-77]. Grading of malaria transmission is important for targeting control interventions.

Malaria endemicity is typically classified into 4 levels, based on a variety of quantification methods [77, 78].

(a) Holoendemic, which is characterized by very intense, year-round transmission, resulting in severe anemia during early childhood but considerable degree of immunity outside early childhood.

(b) Hyperendemic, characterized by intense but seasonal transmission. Immunity is insufficient in all age groups, and cerebral malaria is common in older children.

(c) Mesoendemic, characterized by regular seasonal transmission under normal rainfall conditions. Transmission is low in dry seasons. Cerebral malaria is a common feature. Mesoendemicity is typical in communities in subtropical zones.

(d) Hypoendemic, where transmission is low and intermittent and the effect on the general population is unimportant. However, outbreaks of severe malaria and mortality are common in both children and adults.

Four main methods for grading the magnitude of malaria in the population are described in the literature, none of which appears completely satisfactory. They consist of (a) 2 host-based methods which involve estimating the prevalence of palpable splenomegaly (spleen rates) and/or parasitaemia (parasite rates) in the population [77-79], (b) a vector-based method which estimates malaria

prevalence in terms of transmission intensity [77, 79], and (c) a vector-based mathematical model which measures endemicity in terms of stability of transmission[77-79]. The descriptions and the relationship between these indices are shown in Table 3 below.

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Table 3: Criteria for classifying malaria endemicity

Criterion

Endemicity

Source

Hypoendemic Mesoendemic Hyperendemic Holoendemic

Description Low Moderate High High [77]

Spleen rate in children 2 – 9 years 0 – 10% 11 – 50% >51 – 75%

Also high in adults (> 25%) >75% Low in adults [77, 78]

Parasite rate in children 2 – 9 years 0 – 10% 11 – 50% >51 – 75% >75% (among infants aged 0 – 11 months)

[77, 78]

Annual Entomological Inoculation Rate (AEIR) <0.25 0.25 – 10 11 – 140 >140 [77]

Stability Unstable Intermediate Stable Stable [79]

28 a) Spleen rate

Spleen rate or spleen index is the method used in most malaria metric surveys to define malaria endemicity[77-79]. It is defined as the proportion of a selected age-group of the population with palpable enlargement of the spleen. It is measured per 100 individuals of similar ages; typically in children aged 2 to 5 years [77, 78]. This method was the first used to quantify malaria disease in the population, having been introduced in India in 1948 [79]. It is determined through a survey of a selected age-group of randomly sampled population. The quantity measured is a point prevalence of splenomegaly, although the term ―rate‖ is often used [79].

b) Parasite rate

Parasite rate is another method that has been used in malaria metric surveys because of its higher specifity than the spleen index [77]. It is defined as the proportion of the population of similar ages with parasitamia [77, 78]. It is also measured per 100 individuals of similar ages; typically in children aged 2 to 5 years [77, 78]. It is

determined through a survey of a selected age-group of randomly sampled population. It involves assessing the presence of asexual malaria parasite in peripheral blood by slide microscopy [79]. It represents the point prevalence of parasitaemia in the selected group of the population [78]. Its usefulness in malaria epidemiology remains questionable [79].

c) Transmission intensity

This measure depends on the capacity of the vector (Anopheles mosquito) to transmit malaria parasite during its life time. The measure of transmission intensity is

Entomological Inoculation Rate (EIR), which refers to the average number of infective bites by Anopheles mosquito per person per unit time, usually one year (i.e. Annual EIR = AEIR). EIR is normally measured through sentinel surveillance, using various methods [77, 79].

d) Stability of transmission

This is a mathematical model based on EIR. The classical mathematical model is the Ross-Macdonald model which can be used to predict the relationship between endemicity as measured by P falciparum parasite rate (PfPR) and transmission intensity measured by P falciparum EIR (PfEIR) [79]. The Ross-Macdonald model shows that PfPR is very sensitive to small changes in PfEIR at low transmission intensity, but it is

29 insensitive to small changes in PfEIR at high transmission intensity [79]. The Ross- Macdonald model classifies malaria endemicity into stable malaria and unstable malaria [79]. Stable malaria implies an overall balanced or constant presence of malaria, with persistently high prevalence of infection, which is insensitive to environmental changes. Transmission is year-round although there may be seasonal fluctuation. Unstable malaria implies irregular transmission of malaria in space and time. The background immunity in the population is low and therefore the risk of malaria epidemic is high [78].

Intermediate stability is designated between these two extremes. Thus unstable malaria settings consist of hypoendemic areas, intermediate stability corresponds to meso- endemic areas, while stable malaria settings comprise hyper and holoendemic areas. e) Classification method adopted in this thesis

In this thesis, malaria prevalence in Uganda is described as low, medium and high. This classification has been used in previous studies, including the trial analysed in chapter 4 [80, 81]. It is based on AEIR indices derived from a recent 1-year long entomological surveillance data obtained from 7 ecologically different sentinel sites throughout the country, including the study locations mentioned in this thesis [75]. The values of EIR and endemicity classification attributed to the locations studied as part of this thesis correspond to the grading presented in Table 3.

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