402
Y. A. Abdulhameed et al.
26.1 Introduction
Malaria is a life-threatening mosquito-borne disease [41], involving changes in the
dynamical properties of blood flow. There are still more than 200 million cases of
malaria annually, resulting in about 600,000 deaths. The disease is treatable when
arrested soon enough, so early diagnosis is highly desirable. Despite the development
of non-invasive alternatives [22], the current gold standards in malaria diagnosis are
still antigen-based rapid diagnostic tests (RDTs) and the microscopic examination of
blood films by a trained microscopist. Results vary widely in diagnostic sensitivity
and specificity.
To our knowledge, malaria-related impairment of cardiovascular oscillation has
not been investigated. To try to understand such effects, and to assess their potential
for detecting malaria, the present study involves simultaneous monitoring of blood
flow, skin temperature, respiration and electrocardiography. The time series are analysed using wavelet-based methods to establish, not only the intensity of oscillatory
processes involved in cardiovascular regulation, but also their degree of coordination
which, as we will see, is adversely affected by malaria.
Physiological oscillations and their potential for characterising cardiovascular dynamics in malaria. Measurements of blood flow and oxygenation in human
subjects reveal several co-existing oscillatory processes, covering a very wide range
of frequencies. Use of the continuous wavelet transform reveals at least six such
processes [34, 36]; with the same oscillations being seen at different sites and for
different measured quantities, not only in blood flow and oxygenation. Their physiological attribution has been established. Briefly: hemodynamic oscillations near
1 Hz (frequency interval FI-I) and 0.25 Hz (FI-II) are due to cardiac and respiratory activity respectively; the oscillation near 0.1 Hz (FI-III) is attributable to the
natural properties of smooth muscle which oscillates at about 0.1 Hz even in vitro;
that near 0.03 Hz (FI-IV) is neurogenic, associated with autonomic nervous activity;
and those near 0.01 Hz (FI-V) and 0.007 Hz (FI-VI) arise [23] from NO-related and
NO-independent endothelial activities respectively. The underlying physiological
oscillatory processes suggested the introduction of a coupled-oscillator model of the
cardiovascular system [36, 37, 39]. Understanding the nature of these oscillations in
healthy subjects allows their sometimes distinctive differences in pathological states
to be identified. This approach has not yet been applied to malaria, however, even
though the disease may be expected to cause significant changes in microvascular
dynamics.
Possible effects of malaria on the oscillations in blood flow. The increased
stiffness of the membrane of an infected erythrocyte (red blood cell, or RBC) [19],
and its tendency to stick to the endothelial cells lining all the blood vessels, cause
infected cells to pass less easily through the capillaries. The cell also changes shape,
and its ability to transport/release oxygen is compromised. Consequently, the viscosity, flow properties, and oxygenation of blood are all changed by malaria in ways
that do not occur in other diseases. Hemodynamics is altered [18] on account of the
spatial distribution of erythrocytes [33] and merozoites, and it is reasonable to infer
Y. A. Abdulhameed et al.
26.1 Introduction
Malaria is a life-threatening mosquito-borne disease [41], involving changes in the
dynamical properties of blood flow. There are still more than 200 million cases of
malaria annually, resulting in about 600,000 deaths. The disease is treatable when
arrested soon enough, so early diagnosis is highly desirable. Despite the development
of non-invasive alternatives [22], the current gold standards in malaria diagnosis are
still antigen-based rapid diagnostic tests (RDTs) and the microscopic examination of
blood films by a trained microscopist. Results vary widely in diagnostic sensitivity
and specificity.
To our knowledge, malaria-related impairment of cardiovascular oscillation has
not been investigated. To try to understand such effects, and to assess their potential
for detecting malaria, the present study involves simultaneous monitoring of blood
flow, skin temperature, respiration and electrocardiography. The time series are analysed using wavelet-based methods to establish, not only the intensity of oscillatory
processes involved in cardiovascular regulation, but also their degree of coordination
which, as we will see, is adversely affected by malaria.
Physiological oscillations and their potential for characterising cardiovascular dynamics in malaria. Measurements of blood flow and oxygenation in human
subjects reveal several co-existing oscillatory processes, covering a very wide range
of frequencies. Use of the continuous wavelet transform reveals at least six such
processes [34, 36]; with the same oscillations being seen at different sites and for
different measured quantities, not only in blood flow and oxygenation. Their physiological attribution has been established. Briefly: hemodynamic oscillations near
1 Hz (frequency interval FI-I) and 0.25 Hz (FI-II) are due to cardiac and respiratory activity respectively; the oscillation near 0.1 Hz (FI-III) is attributable to the
natural properties of smooth muscle which oscillates at about 0.1 Hz even in vitro;
that near 0.03 Hz (FI-IV) is neurogenic, associated with autonomic nervous activity;
and those near 0.01 Hz (FI-V) and 0.007 Hz (FI-VI) arise [23] from NO-related and
NO-independent endothelial activities respectively. The underlying physiological
oscillatory processes suggested the introduction of a coupled-oscillator model of the
cardiovascular system [36, 37, 39]. Understanding the nature of these oscillations in
healthy subjects allows their sometimes distinctive differences in pathological states
to be identified. This approach has not yet been applied to malaria, however, even
though the disease may be expected to cause significant changes in microvascular
dynamics.
Possible effects of malaria on the oscillations in blood flow. The increased
stiffness of the membrane of an infected erythrocyte (red blood cell, or RBC) [19],
and its tendency to stick to the endothelial cells lining all the blood vessels, cause
infected cells to pass less easily through the capillaries. The cell also changes shape,
and its ability to transport/release oxygen is compromised. Consequently, the viscosity, flow properties, and oxygenation of blood are all changed by malaria in ways
that do not occur in other diseases. Hemodynamics is altered [18] on account of the
spatial distribution of erythrocytes [33] and merozoites, and it is reasonable to infer