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Neutralising Pathogens in Blood in Developing Countries – Thinking Outside the Screening Box
immunogenicity of these highly effective pathogen inactivation intake, retaining more at low intakes and absorbing less and excreting
compounds are both investigated further and resolved, their usage in more at higher intakes.
70
Sufferers of Wilson’s disease and Menkes
blood banking is uncertain. All of these methods require the introduction syndrome, two well-known diseases involving defective copper
of chemicals into the blood. Their toxicity or mutagenicity potential has metabolism, have mean levels of blood-copper concentrations of about
not been fully determined. In many cases the determination of the 525 and <70µg/dl, respectively. Normally, any excess copper absorbed by
dangers from the photodecomposition products of these chemicals has
not been evaluated. Additionally, the exposure of blood components to
UV or other radiation may also be harmful in ways not yet assessed.
56
All
of these pathogen-neutralisation technologies are expensive and cannot
Using human blood, especially
be easily and practically implemented in many developing countries.
in developing countries where
The development of safe, inexpensive and easy-to-implement approaches to
blood-borne pathogens are endemic,
inactivate or remove a broad spectrum of pathogens is highly desirable. One
poses significant safety concerns.
such approach may be the use of devices that filter out and/or deactivate
the pathogens in whole blood or blood products during their passage
through the device. One such device uses micro-porous filters capable of
removing large particles, such as viruses, in plasma and plasma products.
57,58
the body is readily secreted.
71
Due to its cost-effectiveness and speed of
This technology is based on filter pore size. Most viruses range in size from use, filtration with copper-based devices can be used as a back-up to,
approximately 20 to 200nm, and membranes used in these micro-porous and in conjunction with, nano-filters and any detection methods blood-
filters have a pore size of 15 to 40nm. Nano-filtration typically results in a supply managers may choose to employ.
four- to six-log removal of most viruses, with a 90–95% recovery rate of
protein activity.
27
Removal of small non-enveloped viruses by antibody- Conclusions
enhanced nano-filtration during the manufacture of plasma derivatives is Until alternative safe and effective solutions for the use of blood and
being explored.
59
Two significant problems with nano-filtration are the high blood components for medical treatment are developed, the use of
operating pressure (typically between 100 and 150 pounds per square inch allogeneic blood in numerous medical disorders and emergencies will
[psi]) and protein fouling, which can severely limit the membrane capacity continue. Using human blood, especially in developing countries where
and may even contribute to incomplete virus retention. blood-borne pathogens are endemic, poses significant safety concerns.
Ultra-filtration (UF) membranes, with a pore size of 1 to 100nm, are Implementation of safety measures, such as donor selection, staff
increasingly being used in the biopharmaceutical industry. These training and the use of sterile equipment, is highly desirable. The
commercial polymeric membranes are typically hydrophilic and can execution of careful screening of blood for the presence of pathogens
remove 99.9% of virus particles from the feed stream.
50,60
Despite an would significantly reduce the risk of TTIs in developing countries, as is
improved protein-fouling resistance, UF membrane technology requires the case in the developed countries. However, the incidence of infected
30–50psi of operating pressure, and the virus removal efficiency may be individuals is so high in many of these areas that little blood would be
insufficient for blood applications. available if all ‘marker-positive’ donors were excluded.
27
A durable platform technology was recently developed. It introduces New pathogens continue to emerge. A wide-spectrum technology, or a
copper oxide into polymeric materials, empowering them with potent combination of technologies, that can widely neutralise pathogens could
broad-spectrum antibacterial, antifungal and antiviral properties.
61,62
By confer the desired protection and may eliminate the need for blood
using this technology, copper-oxide-containing devices have been shown screening, which is too expensive to perform regularly. The
to drastically reduce infectious titres of a panel of viruses spiked into implementation of the current modalities of pathogen inactivation,
culture media, including enveloped, non-enveloped, RNA and DNA which further reduce the residual risk of TTI, is not practical and
viruses.
63,64
This suggests the possibility of using these devices to achievable in many of the developing countries. They significantly
deactivate a wide spectrum of infectious viruses found in filterable increase the cost of blood units and also require sophisticated equipment
suspensions. Copper neutralisation of infectious bronchitis virus, that needs infrastructure, constant maintenance and trained personnel.
poliovirus, HIV-1 and other enveloped or non-enveloped, single- or
double-stranded DNA or RNA viruses has previously been reported.
65
In many developing areas of the world, where infections are rampant and
Copper can inactivate viruses by damaging their genetic materials, blood transfusions are highly risky, cheap, one-time-usage, disposable
envelope and/or key proteins.
65
It has been demonstrated that the HIV-1 and wide-spectrum pathogen removal/inactivation devices would be
protease, essential for the replication of the virus, is inhibited by realistic. One such device could be a small filter containing a nano-
stoichiometric concentrations of copper ions.
66
membrane combined with a copper-oxide biocidal layer filter. These
devices may be attached to the blood transfusion containers, or to the
The biochemistry of copper in humans has long been studied and containers containing the blood fractions. The whole blood or blood
understood.
67
Excess copper in humans, at the levels ‘leached’ out into component would pass through it by simple gravitational force. The
the blood or plasma as it passes through such devices (less than 2µg/dl), safety of such devices has to be carefully studied and determined.
is not toxic. This represents only a minor perturbation to the normal
serum levels of copper in blood, which ranges from 80 to 160µg/dl.
68,69
While some damage may occur to key components of the blood, and
As a relatively benign trace element, humans adapt to changes in copper some of these simple devices may be used with some blood components
EUROPEAN HAEMATOLOGY 87
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