Preventive Treatment and Anti-malarial Drug Resistance

In This Article

Abstract and Introduction

Abstract

Background The use of intermittent preventive treatment in pregnant women (IPTp), children (IPTc) and infant (IPTi) is an increasingly popular preventive strategy aimed at reducing malaria risk in these vulnerable groups. Studies to understand how this preventive intervention can affect the spread of anti-malarial drug resistance are important especially when there is human movement between neighbouring low and high transmission areas. Because the same drug is sometimes utilized for IPTi and for symptomatic malaria treatment, distinguishing their individual roles on accelerating the spread of drug resistant malaria, with or without human movement, may be difficult to isolate experimentally or by analysing data. A theoretical framework, as presented here, is thus relevant as the role of IPTi on accelerating the spread of drug resistance can be isolated in individual populations and when the populations are interconnected and interact.

Methods A previously published model is expanded to include human movement between neighbouring high and low transmission areas, with focus placed on the malaria parasites. Parasite fitness functions, determined by how many humans the parasites can infect, are used to investigate how fast resistance can spread within the neighbouring communities linked by movement, when the populations are at endemic equilibrium.

Results Model simulations indicate that population movement results in resistance spreading fastest in high transmission areas, and the more complete the anti-malarial resistance the faster the resistant parasite will tend to spread through a population. Moreover, the demography of infection in low transmission areas tends to change to reflect the demography of high transmission areas. Additionally, when regions are strongly connected the rate of spread of partially resistant parasites (R1) relative to drug sensitive parasites (RS), and fully resistant parasites (R2) relative to partially resistant parasites (R1) tend to behave the same in both populations, as should be expected.

Conclusions In fighting anti-malarial drug resistance, different drug resistance monitoring and management policies are needed when the area in question is an isolated high or low transmission area, or when it is close and interacting with a neighbouring high or low transmission area, with human movement between them.

Table 1. State variables and their description
State variables	Description of state variables
S	Susceptible Untreated Non-immunes
S _a	Susceptible Untreated Semi-immunes
D	Symptomatic Infected and Treated Non-immunes
D _a	Symptomatic Infected and Treated Semi-immunes
A	Infected Untreated Non-immunes
A _a	Infected Untreated Semi-immunes
P	Uninfected Non-immunes with Temporary Immunity
P _a	Uninfected Semi-immunes with Temporary Immunity
	Symptomatic Infected and Treated Non-immunes with Drug in bloodstream
	Symptomatic Infected and Treated Semi-immunes with Drug in bloodstream
	Susceptible IPT treated Non-immunes with Drug in bloodstream
	Infected and IPT Treated Non-immunes with Drug in bloodstream

Table 2. Equilibrium proportions of individuals in each state with and without movement between areas of low and high transmission
Description	State	Without movement		With movement
Description	State	Low	High	Low	High
Uninfected and untreated	S	34.269%	0.027%	1.265%	0.079%
	S _a	2.725%	0.234%	7.414%	0.363%
Infected but untreated	A	3.156%	0.111%	0.161%	0.307%
	A _a	0.310%	2.658%	1.439%	3.533%
Immune-protected but uninfected	P	7.949%	0.539%	0.973%	1.042%
	P _a	10.137%	86.450%	79.764%	82.184%
Infected and treated	D	0.824%	0.103%	0.054%	0.270%
	D _a	0.089%	0.765%	0.420%	1.011%
Infected prior to treatment	T ₁	8.550%	1.063%	1.279%	2.087%
with drug in bloodstream	T ₃	1.310%	0.092%	0.172%	0.216%
Uninfected prior to treatment	T _a	0.925%	7.936%	6.324%	8.528%
with drug in bloodstream	T ₂	28.450%	0.022%	0.735%	0.380%

All results are based on model parameters as summarized in Additional file 2: Table S3, with p ₂₁/p ₂₁ = 1 = m, p12 = 0.02. Note that the values for T ₁, T ₂, T ₃ and T _a represent the sum of respectively.