Monitoring International Trends
posted February 2015
The NBA monitors international developments that may influence the management of blood
and blood products in Australia. Our focus is on:
 Potential new product developments and applications;
 Global regulatory and blood practice trends;
 Events that may have an impact on global supply, demand and pricing, such as
changes in company structure, capacity, organisation and ownership; and
 Other emerging risks that could potentially put financial or other pressures on the
Australian sector.
A selection of recent matters of interest appears below. Highlights include:
 At the Eighth European Association for Haemophilia and Allied Disorders
Conference, Swedish Orphan Biovitrum and Biogen Idec presented new data from
their haemophilia A and B clinical development programmes (Section 1).
 Baxter released new data from a phase III study of its investigational drug, BAX 855,
an extended half-life recombinant factor VIII (rFVIII) treatment for haemophilia A
(Section 1).
 Emmaus Life Sciences’ summary of Phase III results for its sickle cell treatment was
included in the American Society of Hematology's official 2015 Highlights of ASH, a
two-day seminar program held across North America (Section 1).
 The US Food and Drug Administration (FDA) accepted for review a Biologics License
Application from CSL Behring for its recombinant factor IX, rIX-FP, for patients with
haemophilia B. rIX-FP is engineered to extend the half-life of recombinant factor IX
through genetic fusion with recombinant albumin (Section 2).
 OPKO Health submitted an Investigational New Drug Application to the FDA to
conduct a Phase IIa study of its long-acting version of coagulation Factor VIIa (Factor
VIIa-CTP) for the treatment of bleeding episodes in haemophilia A or B patients with
inhibitors to Factor VIII or Factor IX (Section 2).
 The FDA expanded the administration options for CSL Behring’s Hizentra, Immune
Globulin Subcutaneous (Human), 20 per cent Liquid, to include the ability to
individualize therapy with flexible dosing (Section 2).
 The FDA received Sangamo BioSciences' Investigational New Drug Application for
its genome editing approach, a one-off therapy for beta-thalassemia (Section 2).
 CSL issued its half yearly profit report and downgraded financial guidance. CSL's net
profit was up 7.2 per cent in the six months to December 31 (Section 3).
 Baxter reported fourth quarter earnings for 2014. While revenue and earnings
estimates exceeded the company’s expectations, it did face adverse currency trends
which it expects to have a negative impact on overall 2015 results (Section 3).
 Baxter will split in mid-2015. Baxalta (the current biopharmaceuticals/ bioscience
division) will be headquartered in Bannockburn, Northern Illinois (Section 3).
 Biogen Idec will join with Italy’s Fondazione Telethon and Ospedale San Raffaele to
develop gene therapies for haemophilia A and B (Section 3).
 Sanofi added significantly to its shareholding in Alnylam Pharmaceuticals which is
developing therapeutics for bleeding disorders (Section 3).
 The Department of Health and Human Services announced $US 194.5 million in
funds to increase preparedness of the US health system for Ebola (Section 4).
 A multi-site study in patients with trauma and major bleeding has found that those
who were transfused with a balanced ratio of plasma, platelets, and red blood cells
were more likely to have their bleeding stopped and less likely to die due to loss of
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blood by 24 hours compared with patients who were transfused with a higher ratio of
red blood cells (Section 5).
Researchers reported that receiving a blood transfusion during coronary artery
bypass grafting surgery may raise a patient's risk of pneumonia (Section 5).
A study compared low dose iron supplementation with no supplementation in blood
donors, and found that supplementation significantly reduced the time to recovery of
post-donation lost iron and haemoglobin (Section 5).
In Australia, 18 cases of hepatitis A were blamed on imported frozen berries. Initially
the Red Cross Blood Service banned those who had eaten the berries from donating
blood for two months, but after further consideration of risk announced that “donors
who have eaten berries may donate, provided they remain well” (Section 5).
The US Centers for Disease Control and Prevention (CDC) awarded Georgia State
University a five-year, $US 2.7 million grant to investigate transfusion-related
complications in patients with haemoglobin disorders (Section 6).
In North America and Europe, the seasonal influenza vaccine has provided low
protection this winter against one particular subtype, A( H3N2). There has been a
mismatch between the A(H3N2) strain selected for the vaccine this year and the
main A(H3N2) strain that has been circulating (Section 7).
New cases of A( H7N9) avian flu in humans continue to be reported from mainland
China, which has also seen human cases of other avian influenzas, A(H5N6) and
A(H5N1). Some experts are concerned that the seasonal flu virus A(H3N2) which is
now circulating in China could mix with A(H7N9) and increase the latter’s potential for
human to human transmission (Section 7).
An international team of UN human and animal health experts visited Saudi Arabia to
investigate a recent surge in MERS cases (Section 7).
Contents
1.
Products .......................................................................................................................................... 3
Clotting factors ................................................................................................................................ 3
Market Size ..................................................................................................................................... 4
Other ............................................................................................................................................... 4
2.
Regulatory ....................................................................................................................................... 5
Plasma and recombinant products ................................................................................................. 5
Devices ............................................................................................................................................ 6
Other ............................................................................................................................................... 6
3.
Market structure and company news ............................................................................................. 7
4.
Country-specific events................................................................................................................... 9
5.
Safety and patient blood management ........................................................................................ 11
Appropriate transfusion ................................................................................................................ 11
Treating iron deficiency ................................................................................................................ 12
Other. ............................................................................................................................................ 12
6.
Research ........................................................................................................................................ 13
7.
Infectious diseases ........................................................................................................................ 14
2
Mosquito-borne diseases: dengue, chikungunya , malaria, Japanese encephalitis and Ross River
virus ............................................................................................................................................... 14
Influenza........................................................................................................................................ 15
Ebola.............................................................................................................................................. 16
MERS-CoV ..................................................................................................................................... 18
Other diseases: occurrence, prevention and treatment .............................................................. 18
1. Products
Here the NBA follows the progress in research and clinical trials that may within a
reasonable timeframe make new products available, or may lead to new uses or changes in
use for existing products.
Clotting factors
a) At the Eighth European Association for Haemophilia and Allied Disorders (EAHAD)1
Conference, Swedish Orphan Biovitrum (Sobi) and Biogen Idec presented new data
from their haemophilia A and B clinical development programmes. Six abstracts were
presented, including new, interim results from the ASPIRE long-term extension
study2 and results from the Kids A-LONG, A-LONG, and B-LONG Phase III studies.
i) The poster presentations concerning Elocta3, a long-acting recombinant factor
VIII, were:
(1) Long-term safety and efficacy of recombinant factor VIII Fc (rFVIIIFc) in adults
and adolescents with severe haemophilia A: an interim analysis of the
ASPIRE study4;
(2) Interim analysis of the ASPIRE study evaluating long-term safety and efficacy
of recombinant factor VIII Fc (rFVIIIFc) in children with severe haemophilia A;5
(3) Perioperative management of subjects with haemophilia A in the ASPIRE
study with long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc); 6
(4) Safety, efficacy, and pharmacokinetics of recombinant factor VIII Fc fusion
protein (rFVIIIFc) in previously treated paediatric subjects with severe
haemophilia A (Kids A-LONG);7 and
(5) Subject-reported changes in physical activity during the A-LONG study of
recombinant factor VIII Fc fusion protein (rFVIIIFc) for severe haemophilia A.8
1
in Helsinki, 11-13 February, 2015
Volck, Senior Vice President, Chief Medical Officer at Sobi said: “The new interim results
from the ASPIRE study discuss the longer term use of Elocta in people with severe haemophilia A,
followed in an open label extension from the pivotal A-LONG study, and further establishes the
efficacy and safety of Elocta”.
3
Elocta is the trade name in Europe for rFVIIIFc, but it is known as Eloctate in the US, Canada,
Australia, and Japan, where it is approved for the treatment of haemophilia A. A Marketing
Authorisation Application for Elocta is under review by the European Medicines Agency.
4 PP066
5 PP076
6 PP116
7 PP032
8 PP035
2Birgitte
3
ii) The poster presentation concerning Alprolix9, a long-acting recombinant factor IX,
was: Subject-reported changes in physical activity during the B-LONG study of
recombinant factor IX Fc fusion protein (rFIXFc) for severe haemophilia B.10
b) Baxter released new data from a phase III study of its investigational drug, BAX 855,
an extended half-life recombinant factor VIII (rFVIII) treatment for haemophilia A11.
BAX 855 is based on Advate, and designed to extend the interval between infusions
while maintaining a similar efficacy profile to Advate. BAX 855 met the trial's primary
endpoint, with patients in the twice-weekly prophylaxis arm experiencing a 95 per
cent reduction in median annualized bleed rate compared with those in the ondemand arm. No trial participants developed inhibitors to BAX 855. The new findings
support Baxter's Biologics License Application for the approval of BAX 855,
submitted to the FDA in December 2014.
Market Size
c) The global albumin excipient market was valued at $US 704.9 million in 2013 and
has been estimated to grow at a compound annual growth rate (CAGR) of 2.3 per
cent from 2014 to 202012.
i) Applications of albumin include drug formulation and drug delivery, vaccines, and
component of media.
ii) Human serum albumin was the largest segment in 2013, valued at $US 476.7
million. The segment is expected to grow at a CAGR of 2.2 per cent between
2014 and 2020.
iii) Bovine serum albumin is used in the production of vaccines such as MMR II and
Zostavax.
iv) End-user preference has been transferring to recombinant human albumin
(rAlbumin) used in multiple applications, including nano-formulation. Advances in
yeast-based protein expression and in successful scale-up have permitted
development of industrial-scale manufacturing that can produce a highly pure,
animal-free rAlbumin suitable for use as an excipient in biotherapeutics.
v) Abraxis BioScience has applied nanotechnology to human serum albumin with its
nanoparticle albumin-bound, known as ‘NAB’ technology platform.
vi) The research community is focussing on using albumin as a carrier for micro-and
nano-particles for sustained-release injectable drugs.
Other
d) Emmaus Life Sciences announced that a summary of the results of the company's
Phase III clinical trial of its oral pharmaceutical grade L-glutamine treatment for sickle
cell anaemia and sickle beta-0 thalassemia was included in the American Society of
Hematology's official 2015 Highlights of ASH, a two-day seminar program held in six
cities across North America during January. The Phase III results were initially
presented in December 2014 at the ASH Annual Meeting. Dr Yutaka Niihara, CEO of
Emmaus said of inclusion in the Highlights tour: "We believe the results demonstrate
a well-tolerated safety profile that has the potential to help adult and pediatric
patients who are in need of new therapies to treat SCD." The therapy has orphan
drug designation in the US and Europe and fast track designation from the FDA.
9
Alprolix is approved for the treatment of haemophilia B in Australia, the US, Canada, and Japan.
PP028
11 Baxter presented data to the Eighth Annual Congress of the European Association for Haemophilia
and Allied Disorders (EAHAD) in Helsinki, Finland.
12 Transparency Market Research, Albumin (Excipient) Market-Global Industry Analysis, Size, Share,
Volume, Growth, Trends and Forecast, 2014-2020,
http://www.transparencymarketresearch.com/albumin-market.html
10
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e) Kamada reported additional data from the ongoing extension study of the company’s
open-label Phase I/II clinical trial of its intravenous Alpha1-Proteinase Inhibitor–
Human (AAT), to treat recently diagnosed type 1diabetes in paediatric patients. The
company says the treatment may slow the progression of the disease, improve
metabolic control, reduce daily insulin dose requirements, and reduce diabetes
complications. Twenty four subjects participated in the initial Phase I/II trial, but five
chose not to participate in the extension. David Tsur, Chief Executive Officer of
Kamada, said: “Despite the limitation of the small sample size, these results are
favorable. The scientific rationale for administering AAT to treat type 1 diabetes is
based on the anti-inflammatory and immune-modulatory activities of AAT …… This
mechanism of action supports beta-cells’ recovery processes from autoimmunemediated tissue injury……The preservation of beta cells is important as it may allow
patients to exhibit decreased diabetes complications such as cardiovascular disease,
kidney failure, eye disease, severe dermal wounds and more, thanks to the extended
time period by which they are able to produce insulin and better maintain their
glycemic control. These complications represent the real unmet need in this condition
as they are inadequately served by existing therapies, which include insulin, diet and
behavioral treatment. Moreover, these complications have direct correlation with the
extent of glycemic control the patient reaches during early disease phases. We
believe our intravenous AAT can be a ground-breaking treatment for newly
diagnosed type 1 diabetes patients, as it may demonstrate the ability to halt disease
progression and allow the pancreas to maintain secretions of self-insulin.”
f) Pluristem Therapeutics, a developer of placenta-based cell therapy products,
announced from Israel the positive results of a trial conducted by the US National
Institutes of Health (NIH) to evaluate PLX-R18 cells to treat bone marrow damaged
by exposure to high levels of radiation, such as might occur after a nuclear disaster.
Injection of PLX-R18 cells into muscle, as compared with a placebo, resulted in a
statistically significant improvement in the recovery of white blood cell, red blood cell,
and platelet levels in animals exposed to high levels of radiation. Findings also
suggested that the treatment may potentially be able to shorten time to recovery.
Pluristem is developing PLX-R18 cells for other potential indications including
enhancement of engraftment of transplanted hematopoietic stem cells for the
treatment of bone marrow deficiency. Trials for this indication are being conducted at
Case Western University and Hadassah Medical Center.
g) Sanofi announced that a trial treatment with its Cerdelga drug showed promise for
patients with the genetic disorder type 1 Gaucher disease. Nine months of treatment
with Cerdelga resulted in significant improvements in spleen volume, haemoglobin
level, liver volume and platelet count compared with a placebo drug13.
2. Regulatory
The NBA monitors overseas regulatory decisions on products, processes or procedures
which are or may be of relevance to its responsibilities.
Plasma and recombinant products
a) The FDA accepted for review a Biologics License Application from CSL Behring for
its recombinant factor IX, rIX-FP14, for patients with haemophilia B. rIX-FP is
engineered to extend the half-life of recombinant factor IX through genetic fusion with
recombinant albumin. The application was based on results from the Phase II/III
PROLONG-9FP study, an open-label, multi-centre, safety, pharmacokinetic and
efficacy study of rIX-FP in previously treated patients with severe haemophilia B
13
14
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The Journal of the American Medical Association, 17 February
Coagulation Factor IX [Recombinant], Albumin Fusion Protein
(factor IX ≤2%). The trial compared the change in frequency of spontaneous bleeding
events between on-demand treatment and weekly prophylaxis in patients previously
receiving only on-demand treatment; and the number of patients developing
inhibitors against factor IX. rIX-FP provides haemophilia B patients with dosing
intervals up to 14 days.
b) OPKO Health announced the submission of an Investigational New Drug Application
to theFDA to conduct a Phase IIa study of its long-acting version of coagulation
Factor VIIa (Factor VIIa-CTP) for the treatment of bleeding episodes in haemophilia
A or B patients with inhibitors to Factor VIII or Factor IX. OPKO’s proprietary
technology to extend the circulatory half-life of the factor is based on a naturally
occurring peptide, the C-terminal peptide (CTP) of the beta chain of human chorionic
gonadotropin15. Pre-clinical studies in animal models used both intravenous and
subcutaneous formulations. “We look forward to beginning clinical trials of Factor
VIIa-CTP,” said Phillip Frost, Chairman and CEO of OPKO Health. “A longer acting
Factor VII, administered either by IV or subcutaneous administration, could change
the Factor VIIa market by permitting children and adults to easily self-administer at
home on a prophylactic basis.” Factor VIIa-CTP has been granted orphan drug
designation in the US and Europe.
c) The FDA expanded the administration options for CSL Behring’s Hizentra, Immune
Globulin Subcutaneous (Human), 20 per cent Liquid, to include the ability to
individualize therapy with flexible dosing: treatment at regular intervals from daily to
once every two weeks, for people with primary immunodeficiency (PI). Hizentra, the
first and so far the only 20 per cent subcutaneous immunoglobulin, received FDA
approval in March 2010 as a once-weekly immunoglobulin replacement therapy to
help protect people with PI against infections, and was approved for biweekly (once
every two weeks) dosing in September 2013.
d) Raplixa (formerly Fibrocaps), was acquired by The Medicines Company from
Profibrix in June 2013. The FDA has accepted the filing of a Biologic License
Application for Raplixa, a fibrin sealant developed to aid topical haemostasis on mild
to moderate surgical bleeding sites. It contains human plasma-derived thrombin and
fibrinogen. Raplixa is in dry powder form. In this form, thrombin and fibrinogen are
stable when mixed and at room temperature. The dry powder form can be directly
sprinkled from vial to gelatin sponge or the bleeding sites, or sprayed by a device
developed by the same company. The spray is recommended for treating bleeding
sites with large surface areas, such as hepatic resection and soft tissue dissection, in
order to ensure a rapid and complete coverage.
Devices
e) Fresenius Kabi received from the FDA an Investigational Device Exemption for the
trial use of the Fenwal Amicus Red Blood Cell Exchange system in treating patients
with sickle cell disease. Amicus is currently approved for the collection of apheresis
platelets, mononuclear cell collection, and therapeutic plasma exchange. The Amicus
Red Blood Cell Exchange clinical protocol includes options for RBC exchange and
RBC depletion/exchange in combination.
Other
f) The FDA has accepted Sangamo BioSciences' Investigational New Drug Application
for its SB-BCLmR-HSPC genome editing approach, aimed at providing one-off
therapy for beta-thalassemia. The company will conduct a Phase I/II clinical trial in
This is also used in OPKO’s hGH-CTP, its long-acting recombinant human growth hormone product
which is being evaluated in Phase III clinical trials for adults and Phase II trials for children with growth
hormone deficiencies. OPKO has a global agreement with Pfizer for the development and
commercialization of hGH-CTP.
15
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patients with beta-thalassemia major who are transfusion-dependent. Biogen is
collaborating on development of the therapeutic. The ZFN genome editing
technology allows multiple approaches to the correction of sickle cell disease and of
beta-thalassemia.
g) The FDA has granted ProMetic Life Sciences orphan drug status for PBI-4050, an
anti-fibrotic drug candidate for the treatment of idiopathic pulmonary fibrosis.
ProMetic completed its PBI-4050 Phase I clinical trial in 40 healthy volunteers, in
which the drug was found to be safe and well tolerated, with no serious adverse
events.
3. Market structure and company news
The NBA’s business intelligence follows company profitability, business forecasts, capital
raisings or returns, mergers and takeovers, arrangements for joint research and/or
development, contracts for supply of manufacturing inputs, and marketing agreements.
Companies considered include suppliers, potential suppliers and developers of products
which may be of interest.
a) CSL issued its half yearly profit report and downgraded financial guidance. CSL's net
profit was up 7.2 per cent in the six months to December 3116, aided by a strong rise
in sales of flu vaccines and albumin. The company reduced its full year net profit
growth forecast from 12 per cent to 10 per cent, at constant currency rates.
i.
Chief executive Paul Perreault said the revision was due to increased
competition and CSL would meet this by continuing to develop more
innovative, differentiated products.
ii.
Shares in CSL fell 7.8 per cent, to $A 82.95, after recently hitting record
highs.
iii.
In CSL’s financial first half, CSL Behring, which develops and markets
protein-based therapies, lifted sales 8 per cent in constant currency terms to
$US 2.5 billion.
iv.
Sales of immunoglobulin products rose 5 per cent to $US 1.12 billion,
although the sales volume growth was 11 per cent17. Average sales prices
were lower as more sales were in lower priced markets. Hospitals under
budget pressure are buying CSL's older immunoglobulin product, Carimune,
which is about 20 per cent cheaper than newer products.
v.
Sales of haemophilia products grew at the slowest rate of the company's
divisions, returning growth of 3 per cent to $US 558 million. The company
made a regulatory application in December for its recombinant factor IX
fusion protein.
vi.
CSL's bioCSL reported a 15 per cent rise in sales to $A 276 million. Influenza
vaccine sales at $A 116 million were driven by a severe flu northern
hemisphere season.
b) Baxter reported fourth quarter earnings for 2014 on January 29. While revenue and
earnings estimates exceeded the company’s expectations, it did face adverse
currency trends which it expects to have a negative impact on overall 2015 results.
The company noted that hospital spending trends were weak. The quarterly report
showed that Advate had retained market share against competitive long-acting
products but concern about potential competition from rival products persists18.
16
Net profit of $US 692.2 million ($A 891 million) was up from $US645.7 million a year earlier.
Revenue of $US 2.74 billion was up 6.6 per cent from $US 2.57 billion. Earnings before interest and
tax rose 7 per cent to $US 878 million.
17 Volume in the world market is growing at around 6 to 8 per cent.
18 Baxter announced fourth quarter 2014 adjusted earnings per share of $US 1.34, an increase of 2.3
per cent from the year-ago quarter and just beating the company's earnings estimate of $US 1.30 to
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c) Baxter will split in mid-2015. Baxalta will encompass the current biopharmaceuticals/
bioscience division, which includes recombinant and plasma-based proteins to treat
haemophilia and other bleeding disorders, plasma-based therapies to treat immune
deficiencies, and other chronic and acute blood-related conditions. This division
contributed less than half of overall Baxter revenues in 2013, but more than half its
profit.
d) Headquarters for Baxalta Incorporated will be in Northern Illinois at 1200 Lakeside
Drive, Bannockburn. The long-term lease agreement for the approximately 260,000
square foot facility extends for more than a decade.
e) Biogen Idec has joined with Italy’s Fondazione Telethon and Ospedale San Raffaele
to develop gene therapies for haemophilia A and B. The joint venture will be known
as the San Raffaele-Telethon Institute for Gene Therapy, or TIGET. Biogen Idec will
pay the research costs for two programs—one for haemophilia A, the other for
haemophilia B. Biogen Idec will have the option to exercise worldwide development
and commercialization rights for each program after initial clinical proof of concept
trials. TIGET director Luigi Naldini said: "We at TIGET have worked for several years
to develop a new vector design that upon administration into the blood stringently
targets expression of its genetic cargo to the hepatocytes, the main cell type of the
liver. This was crucial to establish long-term expression of the therapeutic gene and
obtain proof-of-principle of its therapeutic benefit in experimental models of
haemophilia B.”
f) Sanofi has appointed the head of Bayer’s healthcare operations, Olivier Brandicourt
as its new chief executive.
g) Green Cross of Korea won a contract for immunoglobulin worth $US 5.72 million
from the government of Brazil.
h) rEVO Biologics, a subsidiary of LFB Biotechnologies has provided a multi-year grant
of up to $US 1 million to Yale University to establish a centre to further research and
education in preeclampsia19, and to identify the best models of clinical care for the
condition. rEVO has initiated PRESERVE-1, a Phase III clinical trial for its ATryn
[antithrombin (Recombinant)] for the treatment of preeclampsia in pregnant women
during the 24th to 28th week of pregnancy.
i) Biotest expanded its plasma collection capability in the US, opening a second
collection centre in Jacksonville, North Carolina.
j) Cerus Corporation and the SunCoast Blood Bank in Florida announced that they had
signed a three-year purchase agreement for the Intercept Blood System for platelets
and plasma. SCBB collects more than 6,000 units of platelets and 5,500 plasma units
annually in support of twelve hospitals.
k) Alnylam Pharmaceuticals is developing therapeutics for genetic diseases, including
bleeding disorders. Its investigational candidates are based on a ribonucleic acid
interface (RNAi) and it has been presenting study results it regards as encouraging.
$US 1.33. The company's revenue increased 3.5 per cent from the year-ago quarter to $US 4.47
billion, exceeding their expected growth of 3 per cent. On a constant currency basis, net sales
increased 7 per cent from the year-ago quarter. Sales growth rested on the bioscience division where
sales increased 7.8 per cent from the year-ago quarter to $US 1.91 billion. Growth in the division was
driven by an 8.5 per cent growth for haemophilia products, as well as growth in biotherapeutics and
biosurgery products. BAX expects revenues to grow in the range of 2 percent to 3 percent in the first
quarter of 2015, excluding foreign currency effects. The company expects adjusted earnings per
share of US 85 cents to $US 90 cents for the first quarter 2015.
19 Preeclampsia is a life-threatening progressive condition which develops in up to eight per cent of
pregnancies, typically after the twentieth week. Early onset preeclampsia is a severe form that arises
between 24 and 28 weeks gestation. The cause is unknown, but incidence is growing. According to
the American Congress of Obstetricians and Gynecologists (ACOG), the incidence in the US has
increased by approximately 25 per cent between 1987 and 2004. At present, delivery of the baby is
the only known way to stop the progression of preeclampsia, which without intervention, can escalate
to multi-organ failure, seizures, coma or death for both mother and baby.
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m)
n)
o)
p)
Sanofi has been a major shareholder, and at the end of January it added significantly
to its shareholding20. The Sanofi move, coupled with share purchases by Alnylam
officers21, suggests there may be development announcements shortly.
Novartis held its biennial Gulf Iron Summit in February in Muscat, Oman. The
incidence of haemoglobin blood disorders such as thalassemia and sickle cell
disease, and increasing liver and endocrine complications, were key focus areas.
Iron overload is common among transfusion dependent patients, so the summit
explored novel approaches to chelation therapy, the role of the liver in iron overload
and its management, and patient transition from childhood to adulthood when
suffering from iron overload.
Ortho-Clinical Diagnostics has agreed to distribute and sell Quotient’s transfusion
diagnostics platform MosaiQ. MosaiQ is being designed to allow improved time-totest results and more comprehensive matching of donor and patient blood, over and
above what is available from current transfusion diagnostic instruments.
Adam Grossman, President and Chief Executive Officer of ADMA Biologics, provided
a corporate overview at the Cowen and Company 35th Annual Health Care
Conference on 2 March in Boston. ADMA's product candidate, RI-002 is a plasmaderived, polyclonal, intravenous immune globulin, derived from human plasma
containing naturally occurring polyclonal antibodies (e.g., Streptococcus
pneumoniae, H. influenza type B, Cytomegalovirus (CMV), measles, tetanus, etc.) as
well as standardized, high levels of antibodies to respiratory syncytial virus (RSV).
ADMA is pursuing an indication for the use of this product for treatment of patients
diagnosed with primary immune deficiency diseases. The company says preliminary
review indicates that the polyclonal antibodies that are present in RI-002 support the
ability of this product to prevent infections in immune-compromised patients. It said a
Phase III trial met the primary endpoint with no serious bacterial infections (SBI)
reported and that these results are below the requirement specified by FDA guidance
of ≤ 1 SBI per patient-year.
Contract research firm Ergomed has agreed to co-develop a sickle cell drug in a deal
that will give it a stake in its partner, Sweden’s Dilaforette. They will work on
sevuparin for patients experiencing a vaso-occlusive crisis. Ergomed will carry out a
multi-centre, multi-national, randomised phase II study of the treatment, beginning in
mid-2015.
Capnia, announced the first US commercial sales of its CoSense End-Tidal Carbon
Monoxide (ETCO) Monitors and single-use sampling sets. CoSense is a portable,
non-invasive device that rapidly measures carbon monoxide in exhaled breath. The
measurement of carbon monoxide is significant for measuring haemolysis, a
condition that, if left untreated, may lead to elevated levels of bilirubin in the blood
and a range of neurodevelopmental disorders in newborns.
4. Country-specific events
The NBA is interested in relevant safety issues which arise in particular countries, and also
instances of good practice. We monitor health issues in countries from which Australia’s
visitors and immigrants come.
20
On January 29th Sanofi through its wholly-owned subsidiary, Genzyme Corp, purchased 97,118
shares in Alnylam Pharmaceuticals at an average price of $US 95.00 per share. This followed the
purchase of a much larger parcel of 843,699 shares (total cost $US 1.89 billion) on January 22nd and
26th, and brought the beneficial holding of Sanofi/ Genzyme to 10,051,603 shares. In the US, large
shareholders (with more than 10 per cent of a company’s stock are required to disclose their sales
and purchases to the Securities and Exchange Commission. Sanofi already had a 12 per cent stake
in the company, bought for $US 700 million in 2014.
21
Alnylam CEO John Maraganore bought $US 950,000 worth of Alnylam shares on January 29, and
Director Steven M. Paul acquired 1,000 shares, valued at $US 95,000,round that time.
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a) In the US, the Department of Health and Human Services released a new funding
opportunity announcement: the Hospital Preparedness Program (HPP) Ebola
Preparedness and Response Activities. This will award a total of $US 194.5 million to
states and others for Ebola health care system preparedness and response and the
development of a regional Ebola treatment strategy. This funding, in addition to the
Ebola emergency funds to be awarded through the Public Health Emergency
Preparedness (PHEP) program, provides a total investment of $US 339.5 enhance
state, local and health care system preparedness for Ebola through the emergency
appropriations passed with bipartisan support in Congress in December 2014. The
national strategy provides for:
i) Up to ten regional Ebola and other special pathogen treatment centres, including
one hospital in each of the ten HHS regions from among those that have already
been designated by their state health officials to serve as Ebola Treatment
Centers and have been assessed by CDC-led Rapid Ebola Preparedness (REP)
teams. These facilities will have enhanced capabilities to receive a confirmed
Ebola patient.
ii) State or jurisdiction Ebola Treatment Centers that can safely care for patients
with Ebola as needed.
iii) Assessment hospitals that can safely receive and isolate a person under
investigation for Ebola and care for the person until an Ebola diagnosis can be
confirmed or ruled out and until discharge or transfer are completed.
iv) Frontline health care facilities that can rapidly identify and triage patients with
relevant exposure history and signs or symptoms compatible with Ebola and
coordinate patient transfer to an Ebola assessment hospital.
b) Students entering the University of California system in 2017 will have to show proof
of vaccination against measles chickenpox, whooping cough, meningitis and tetanus,
and screened for tuberculosis. UC currently requires students to be inoculated only
against hepatitis B, although some individual campuses have stricter immunization
rules. The new vaccination requirements were based on recommendations from the
California Department of Public Health. University officials said there will be
exemptions for medical or religious reasons.
c) FDA Commissioner Margaret Hamburg will leave in March after six years in the
position. The agency's chief scientist, Stephen Ostroff, will serve as acting
commissioner.
d) Octapharma USA announced the Octapharma Co-Pay Assistance Program is
available to von Willebrand’s Disease (VWD) patients who are currently receiving
wilate® [von Willebrand Factor/Coagulation Factor VIII Complex (Human)] or have a
prescription to begin therapy. Eligible patients are offered a maximum of $6,000
annually for co-pay, co-insurance and deductible expenses associated with their
treatment without regard for their ability to pay. Patients must have third-party
commercial insurance to participate in the program, and must be US residents. The
program is not available to patients who are covered under Medicaid, Medicare,
MediGap, VA, DOD, TRICARE or any other state or federal medical or
pharmaceutical benefit program or pharmaceutical assistance program.
e) In the UK, National Health Service cost regulators have approved funding for
Alexion’s Soliris (eculizumab) as a treatment for the rare blood disease Haemolytic
Uraemic Syndrome, at a probable cost per patient of £340,000 in the first year.
Assuming a patient cohort of 170, Soliris would cost the NHS £57.8 million in the first
year, rising to £82 million in year five. The National Institute for Health and Care
Excellence (NICE) says the budget impact would be less if the potential for adjusting
the dose of the drug and stopping treatment was explored. “This is reflected in the
guidance which recommends eculizumab should be funded only if important
conditions are met, including the development of rules for starting and stopping
treatment for clinical reasons,” noted chief executive Sir Andrew Dillon.
10
Canadian Blood Services continues to progress its “national facility redevelopment
program” which began in 2009 when blood production in the Maritime provinces was
consolidated to a single centre in Halifax. Ontario then moved its production
operations to Brampton. The focus will now move to the provinces of Saskatchewan
and Alberta, with production and quality control centred in Calgary for Regina,
Saskatoon and Edmonton22. “We’re still going to have collection. We’re still going to
have a storage unit here in Saskatchewan,” said Patrick O’Byrne, executive director of
the Saskatchewan Disease Control Lab. Ian Mumford, chief supply chain officer, said
the consolidation plan on the Prairies won’t go into effect for at least four years.
g) A team from Johns Hopkins Medicine International (JHI) Sickle Cell Centre for Adults
visited Bahrain’s Hereditary Blood Disorder Centre and interviewed patients, medical
staff and volunteers prior to advising Bahrain’s government on how to improve care
for sickle cell anaemia patients.
h) The first outbreak of a notifiable sexually transmitted infection of significant public
health importance has been reported in Dublin. There were 35 notifications of
lymphogranuloma venereum (LGV) between May and December 2014. All of them
have been among men who have sex with men (MSM) and most cases (more than 90
per cent) are HIV-positive. Sexually transmitted infection clinics in Dublin are finding
and managing cases as well as following up sexual contacts through partner
notification. Cases range in age from 20 years to 55 years, with a median age of 35
years. All of the LGV cases in this outbreak were tested at the molecular virology
laboratory at St James's Hospital where the isolates are also being sequenced, so far
indicating that most of the cases may be very closely linked. LGV is endemic in
certain areas of Africa, Southeast Asia, India, the Caribbean, and South America. In
the last decade it has been increasingly recognized in North America, Europe, and the
UK. After a cluster of 92 cases was identified in the Netherlands between 2003 and
2004 (where fewer than 5 cases was the annual norm), a number of countries have
begun active surveillance for LGV.
f)
5. Safety and patient blood management
We follow current issues in patient safety and achieving favourable patient outcomes.
Appropriate transfusion
a) A study23 by John B. Holcomb, of the University of Texas Health Science Center at
Houston, and colleagues examined ratios of blood products transfused against
outcomes in patients with severe trauma and major bleeding. Those who were
transfused with a balanced ratio24 of plasma, platelets, and red blood cells were more
likely to have their bleeding stopped and less likely to die due to loss of blood by 24
hours compared with patients who were transfused with a higher ratio of red blood
cells. The researchers found no significant difference in overall mortality at 24 hours
or at 30 days between the two transfusion strategies. In the study 680 severely injured
patients who arrived at 1 of 12 level I trauma centres and were expected to require
massive transfusion were randomly assigned to receive blood product ratios of 1:1:1
for units of plasma to platelets to red blood cells (the closest approximation to
reconstituted whole blood), or 1:1:2, during active resuscitation as well as all local
standard-of-care interventions.
22
The consolidation program will cost around $C 138 million.
See the Journal of the American Medical Association, JAMA 3 February
24 The balanced ratio was developed by the US Defense Department (and known as damage control
resuscitation) on the battlefields of Iran and Afghanistan. Holcomb served as a colonel in the US
Army, where he was a senior trauma surgeon and the Army Surgeon General's trauma consultant.
on the battlefields of Iran and Afghanistan. Holcomb served as a colonel in the US Army, where he
was a senior trauma surgeon and the Army Surgeon General's trauma consultant.
23
11
b) At the annual meeting of the Society of Thoracic Surgeons25, researchers reported
that receiving a blood transfusion during coronary artery bypass grafting (CABG)
surgery may raise a patient's risk of pneumonia. They considered data on 16,182
patients at 33 US hospitals between 2011 and 2013. They found patients receiving
one or two units of red blood cells were twice as likely to develop pneumonia as those
not given blood transfusions. Those who received six units or more were 14 times
more likely to develop pneumonia. The study was led by Donald Likosky, of the
University of Michigan Health System in Ann Arbor.
c) A US study found that receiving a blood transfusion while being flown via helicopter to
a trauma centre raises a patient's chances of survival.26
Treating iron deficiency
d) A study supported financially by the US National Institutes of Health (through the
National Heart, Lung, and Blood Institute, NHLBI) compared low dose iron
supplementation to no supplementation in blood donors, and found that
supplementation significantly reduced the time to recovery of post-donation lost iron
and haemoglobin27.
e) While a number of factors lead to iron deficiency anaemia (including dietary
deficiencies and iron losses), human hookworm infection is one of the leading causes
in poor countries, especially in sub-Saharan Africa, Southeast Asia, and Oceania28.
The Sabin Vaccine Institute Product Development Partnership has developed a
hookworm vaccine, now being progressed through a European consortium of
partners, HOOKVAC29. The vaccine is being tested in Gabon30 where more than one
in four people are infected with hookworms.
Other.
f) By 26th February 18 cases of hepatitis A in Australia had been blamed on imported
frozen berries, which were identified as the only common exposure. Initially the Red
Cross Blood Service banned those who had eaten the berries from donating blood for
two months, but lifted the ban a few days later after judging the blood supply was not
at risk. The Red Cross statement said “The risk assessment uses mathematical
principles and modelling of factors which influence the chance of hepatitis A entering
the blood supply…... Donors who have eaten berries may donate, provided they
remain well.”
g) Bayer HealthCare and Janssen Research & Development are collaborating with the
Population Health Research Institute (PHRI) and the Canadian Stroke Prevention
Intervention Network (C-SPIN) to carry out a Phase III NAVIGATE ESUS study in
patients with a recent embolic stroke of undetermined source (ESUS). The
randomized double-blind, event-driven superiority trial is designed to examine the
benefits of the once-daily, oral Factor Xa Inhibitor, rivaroxaban in these patients.
Around 7,000 patients will be enrolled in the trial at 350 sites, across more than 25
countries worldwide.
25
held from Jan. 24 to 28 in San Diego
Online 11 February in the Journal of the American College of Surgeons
27 The results of the Hemoglobin and Iron Recovery Study (HEIRS) appeared 10 February in the
Journal of the American Medical Association.
28 Hookworms attach to the inside of the intestines of their hosts. They are long-lived parasites,
extracting blood every day.
29 The consortium us based at the Amsterdam Institute for Global Health and Development, and
funded by the European Union, in addition to the Dutch Ministry of Foreign Affairs, the Bill & Melinda
Gates Foundation, and the Michelson Medical Research Foundation.
30 in collaboration with the Lambarene Research Centre linked to the Albert Schweitzer Hospital
26
12
h) A Swedish study31 says that in the case of certain heart attacks 32 patients who
received fondaparinux 33had a lower risk of major bleeding and death compared with
patients who received heparin.
i) Researchers examined a cohort of 1,432,855 patients who underwent surgery at 315
US hospitals from 2005 to 2011, relating surgical duration incidences of venous
thromboembolism (VTE). They found that, compared with a procedure of average
duration, patients undergoing the longest procedures had a 1.27-fold increase in odds
of developing VTE, while the shortest procedures had an odds ratio of 0.8634.
6. Research
A wide range of scientific research has some potential to affect the use of blood and blood
products. However, research projects have time horizons which vary from “useful tomorrow”
to “at least ten years away”. Likelihood of success of particular projects varies, and even
research which achieves its desired scientific outcomes may not lead to scaled-up
production, clinical trials, regulatory approval and market development.
a) Jeffrey H. Lawson, Professor of Surgery and Pathology at Duke University Medical
Center, Director of the Vascular Research Laboratory, Director of Clinical Trials for
the Department of Surgery and clinical consultant to biotechnology company
Humacyte was the keynote speaker at the 27th International Symposium on
Endovascular Therapy35. Dr Lawson’s address was titled “Bioengineering and the
Potential to Create New Blood Vessels”. He discussed early stage development and
clinical testing of Humacyte’s off-the-shelf human bioengineered blood vessel
replacement that is being developed for key applications in regenerative medicine and
vascular surgery. He later presented a session on “Future Procedures in Vascular
Therapy”.36
b) A study37 by the Spanish National Cancer Research Centre's Cell Division & Cancer
Group in the journal Developmental Cell describes how the cells that give rise to
platelets, megakaryocytes, can be reprogrammed artificially into platelets to rebuild
their levels in the blood. As, the study's lead researcher, Marcos Malumbres, says,
"the results can not only help treatment of thrombocytopenia, but also encourage the
design of improved therapies to treat cancer."
c) The Bill & Melinda Gates Foundation awarded Stanford University $US 50 million over
10 years to accelerate vaccine development efforts for the world's most deadly
diseases, including AIDS and malaria. The grant will establish the Human Systems
Immunology Center.
31
17 February, Journal of the American Medical Association.
non-ST-segment elevation myocardial infarction (NSTEMI)
33 Fondaparinux is used to treat heart attacks in Sweden. In the US, the FDA has approved it for
treating blood clots deep in the veins of the legs (deep vein thrombosis) and in the lungs (pulmonary
embolism).
34 The study was reported in JAMA Surgery
35 Held 31 January to 4 February in Florida.
36 He said: “More than 400,000 hemodialysis patients with end-stage renal disease suffer from yearly
surgical procedures having to do with graft complications. Through advances in tissue engineering,
we can potentially access non-living, immunologically tolerated blood vessels for implantation that
might allow us to reduce the number of interventions. This prospective alternative to the current
standard of care has the potential to be a significant game-changer for patients.”
37 Marianna Trakala, Sara Rodríguez-Acebes, María Maroto, Catherine E. Symonds, David
Santamaría, Sagrario Ortega, Mariano Barbacid, Juan Méndez, Marcos Malumbres. “Functional
Reprogramming of Polyploidization in Megakaryocytes”, Developmental Cell (2015)
dx.doi.org/10.1016/j.devcel.2014.12.015
32
13
d) A new study in The Journal of the American Osteopathic Association (JAOA)38
suggests that injections of platelet rich plasma (PRP) into injured parts of the body
can reduce pain and improve function more than surgery or steroids.
e) Nicolas Leuenberger, Certifying Scientist at The Swiss Laboratory for Doping
Analyses, in Lausanne Switzerland, is currently undertaking a research study on
methods of identifying illicit use of autologous transfusions.
f) The US Centers for Disease Control and Prevention (CDC) awarded a five-year, $US
2.7 million grant to Georgia State University's Georgia Health Policy Center to look at
transfusion-related complications in patients with haemoglobin disorders and enable
researchers to improve detection and understanding of transfusion-related
complications and develop approaches for reducing them. Georgia has one of the
nation's highest rates of sickle cell disease.
7. Infectious diseases
The NBA takes an interest in infectious diseases because: the presence of disease in
individual donors (e.g. influenza), or potential disease resulting from travel (e.g. malaria)
means a donor must be deferred; temporary disease burden within a community (e.g.
dengue in North Queensland) may limit blood collection in the community for a time; and
some people may not be permitted to donate at all (e.g. people who lived in the UK for a
period critical in the history of vCJD). Blood donations are tested for a number of diseases
(e.g. HIV and Hepatitis B), but there are also emerging infectious diseases for which it may
become necessary to test in the future (e.g. Chagas disease, and the tick-borne babesiosis
and Lyme disease).
Mosquito-borne diseases: dengue, chikungunya , malaria, Japanese encephalitis and Ross
River virus
a) Cairns in far north Queensland has once again had an outbreak of locally-acquired
dengue fever.
b) Residents of the Northern Territory were warned about dengue fever after a peak in
cases amongst recent overseas travellers to Bali, other parts of Indonesia, Sri Lanka,
Myanmar, Malaysia and East Timor.
c) Public health officials in Los Angeles County alerted physicians to watch for
chikungunya. Travellers were returning from South America and the Caribbean with
the disease and the possibility of future local transmission could not be ruled out.
d) Maryland-based diagnostics firm Tetracore has a one-year grant from the US
National Institute of Allergy and Infectious Diseases (NIAID) to develop a point-ofcare, real-time assay that both detects and distinguishes dengue and chikungunya
viruses.
e) Researchers have identified a powerful antibody where a minute amount will
neutralise the dengue virus. "This kind of binding with the virus has never been
observed and it explains why the antibody itself is so highly potent," said Associate
Professor Shee Mei Lok from Duke-NUS Graduate Medical School Singapore. While
antibody 5J7 has been found to be effective against DENV-3, the remaining
serotypes of dengue virus have also to be considered, researchers said.
f) Researchers at Singapore’s A*STAR research agency have developed a field
detector that identifies the dengue virus from a drop of saliva. Inside the portable
microfluidic device are a series of channels that move the saliva sample and
reagents that prepare it for final mixing with antibody coupled nanoparticles.
Jamil Bashir, Alberto J.Panero and Andrew L Sherman, “The Emerging Use of Platelet-Rich
Plasma in Musculoskeletal Medicine”, doi: 10.7556/jaoa.2015.004 J Am Osteopath Assoc January 1,
2015 vol. 115 no. 1 24-31
38
14
g) Some Florida Keys residents are angry about proposals to introduce genetically
modified mosquitoes in an attempt to restrict transmission of dengue and
chikungunya39. However the Florida Keys Mosquito Control Board has finalized the
deal.
h) Chikungunya is now a notifiable condition in the US.
i) A Melbourne man visiting Bali returned home with Japanese encephalitis, the first
case ever recorded in Victoria40. The disease is mosquito-born, and usually occurs in
China, India, south-east Asia and Indonesia. It is fatal in up to 30 per cent of cases.
For those who survive there can be long-term neurological effects. Appropriate
vaccination before travel is available.
j) Ross River virus cases have, as is usual each summer, been recorded at a number
of locations across Australia, some of them possibly acquiring the infection through
interstate travel. By 25 February, Queensland had reached 1000 cases this year and
many more were expected over the next few weeks.
Influenza
a) Public Health England (PHE) announced41 that the seasonal influenza vaccine has
provided low protection this winter against one particular subtype, H3N2. There has
been a mismatch between the A(H3N2) strain selected for the vaccine this year and
the main A(H3N2) strain that has been circulating42. Recent publication of the US and
Canada’s mid-season vaccine effectiveness estimates similarly revealed the vaccine
had provided little protection against currently circulating A(H3N2) viruses, linked to
drift observed in H3N2 viruses.
b) New cases of H7N9 avian flu in humans continue to be reported from mainland
China43.
c) China has also reported human cases of H5N6 avian flu, including fatalities.
d) China in late January reported a human case of A (H5N1), its fifth in five years.
e) Some experts are concerned that the seasonal flu virus A(H3N2) which is now
circulating in China could mix with A(H7N9) and increase the latter’s potential for
human to human transmission.
f) Hong Kong on 31 December banned live poultry imports after a farm in Guangdong
tested positive for H7N9 which led to a cull of 19,000 birds at New Kowloon’s
wholesale market. By 10 February live chickens were again arriving at the markets in
time for Lunar New Year. Hong Kong had another A(H7N9) case. The patient had
travelled to mainland China.
39
UK company Oxitec plans to produce mosquitoes with modified genetic code containing DNA from
the herpes simplex virus, E. coli, coral, and cabbage plants. Females, which bite and drink blood,
would be removed from the population before release. If the FDA approves then only non-biting male
mosquitoes would be released in Florida. When these males mate with wild female mosquitoes, all
the offspring will die, thus reducing the population of mosquitoes by crowding out wild-type males that
can produce viable offspring. Importantly, the genetically-modified mosquitoes are self-limiting as the
males cannot reproduce and the females SHOULD NOT BE RELEASED. Oxitec conducted initial
tests in Brazil and the Cayman Islands, both of which were so successful that the countries are
planning further deployments of genetically modified mosquitoes.
40 Nine cases have been recorded in Australia. The first “outbreak” of Japanese encephalitis occurred
in1995 in the remote outer islands of the Torres Strait. Of three cases two were fatal.
41 In Eurosurveillance, 5 February.
42 In the UK, influenza A(H3N2) has been the main subtype circulating this season, and the current
vaccine protects against H3N2 viruses similar to A/Texas/50/2012. PHE found that a large proportion
of flu viruses circulating have shown evidence of either antigenic or genetic drift from
A/Texas/50/2012, and were similar to another H3N2 strain: A/Switzerland/9715293/2013. The
A/Switzerland/9715293/2013 strain has been recommended for inclusion in the southern hemisphere
influenza vaccine to be used in 2015.
43 83 cases of laboratory-confirmed H7N9 were recorded between 20 December and 27 January. 78
of those patients had been exposed to live poultry or live poultry markets.
15
g) Two tigers in a Chinese zoo have died of A(H5N1)44.
h) The US Centers for Disease Control (CDC) advised people traveling to China to
avoid contact with poultry (including poultry markets and farms), birds, and their
droppings.
i) Swine flu (type A influenza, H1N1) has been sweeping India. It is easily and rapidly
transmitted human-to-human.
j) Egypt continues to experience human cases of H5N1. Between 1 January and 22
February there were 69 cases with 19 deaths.45
k) Egypt also reported human A(H9N2) infection in Aswan, a child aged three who had
contact with poultry. While A(H9N2) positive poultry has been detected in Egypt since
2011, this is the first confirmed human case46.
l) A meta-analysis covering 4,300 patients from 1997 to 2001 reported that Tamiflu
reduces hospital admissions for flu by 63 per cent and shortens symptoms by a
day'47. The research by the University of Michigan, the London School of Hygiene
and Tropical Medicine and the University of Alabama found that Tamiflu (oseltamivir)
reduces by 44 per cent the respiratory infections that sometimes develop.
m) Scientists from NTU Singapore, led by Andrew Tan, have developed an antibody
which they expect to increase the survival chances for patients suffering from
influenza and pneumonia48.
n) Antibodies that protect against H7N9 have been isolated in people who received
seasonal flu vaccinations. These antibodies are a small part of the total immune
response, but they appear to broadly neutralize H7 viruses. Scientists from the
University of Chicago and Icahn School of Medicine at Mount Sinai reported49 that
they represent promising new targets for therapeutic development against a wide
range of influenza strains.
Ebola
a) In the week ended 1 February there were 124 new cases of Ebola identified, 39 in
Guinea, five in Liberia and 80 in Sierra Leone. While an increase on the 99 new
cases a week earlier, it was still a very welcome improvement after the hundreds of
new cases weekly in the later months of 201450. In the week ended 15 February new
confirmed cases totalled 128, 52 in Guinea two in Liberia and 74 in Sierra Leone.
b) WHO’s estimates of deaths up to the 2 February were 3,746 in Liberia, 3,286 in
Sierra Leone, 1947 in Guinea and 8 in Nigeria.
c) WHO’s estimate of total case numbers by 26 January was 22,101.
44
In October 2004, captive tigers fed on fresh chicken carcasses began dying of A(H5N1) at a zoo in
Thailand (147 tigers out of 441). Subsequent investigation determined that at least some tiger-to-tiger
transmission of the virus occurred.
45 From 2003 until October 2014, there were 686 cases testing positive for H5N1 globally, of which
393 people have died, according to a World Health Organization (WHO) report published in October.
46
H9N2 appears to have a central role in the evolution of H5N1, H7N9, H5N6, and H10N8. All four of
them appear to emanate from Mainland China, all appear to have come about through viral
reassortment in poultry, and all carry internal genes from the avian H9N2 virus.
47
Published in The Lancet
48 Lab tests in mice have been successful. The anibody blocks the protein ANGPTL4 which was found
to be in high concentration in the tissue samples taken from patients suffering from pneumonia. Assoc
Prof Tan said: "We know that ANGPTL4 usually helps to regulate blood vessel leakiness. But this is
the first time we have shown that by blocking this protein, we are able to control the natural response
of inflammation, which in turn reduces the damage that inflammation does to the lungs." Two biotech
multi-national corporations, Abcam based in the United Kingdom and Adipogen International based in
the United States, have won the rights to license the antibody.
49 In the Journal of Clinical Investigations, 17 February
50 Figures released by the World Health Organization (WHO) showed 9,936 reported cases of Ebola
and 4,877 deaths caused by the virus in 2014.
16
d) WHO’s estimate of health worker infections by mid-February was 833 cases with 488
reported deaths.
e) Dr Jimmy Whitworth, head of population health at the Wellcome Trust, said from
Sierra Leone that some people are still out in the community living with the virus. “It’s
not over at all. It’s very dangerous to say that it’s over.” Sophie-Jane Madden, a
spokesperson for Médecins Sans Frontières (MSF), said “Ebola has paralysed the
health systems ….it only takes one case to reignite the epidemic”.
f) Researchers at the Institut Pasteur in France, tracking the Ebola outbreak in Guinea,
say the virus has mutated51. They are also investigating whether it could have
become more contagious. The Institut is currently developing two vaccines which
scientists hope will be in human trials by the end of 2015. One is a modification of the
widely used measles vaccine, where people receive a weakened and harmless form
of the virus which then triggers an immune response. That response fights the
disease if people come into contact with it.
g) A team52 of biomedical scientists and engineers from Harvard Medical School and
MIT are designing a diagnostic to detect Ebola, and other viral haemorrhagic fevers
such as yellow fever and dengue, in just ten minutes.53 Their goal is a cheap, reliable
and rapid test made of paper. The new device relies on lateral flow technology, which
is used in pregnancy tests and has more recently been used for diagnosing strep
throat and other bacterial infections.
h) WHO has already approved the first quick test for Ebola, although it still required
FDA approval to be shipped from the US. The test gives results in about 15 minutes.
The new test, called ReEBOV Antigen Rapid Test, is a piece of paper and a test
tube. "It's very similar to a pregnancy test," says Doug Simpson of Corgenix Medical
Corporation, in Boulder, Colorado, which designed and produced the test. "A drop of
blood is placed on the paper, and if two lines appear, then it's positive for Ebola."
However, the rapid test still requires blood. So, like the standard test, it needs to be
run inside a biosafety cabinet to protect healthcare workers from exposure to the
virus. That means the test isn't very portable. It is also said to have a significant
false-positive rate, around 15 per cent. About 15 per cent of people who aren't
infected with Ebola will test positive. Around 8 per cent of infected people will be test
negative.
i) Trials of a Japanese anti-influenza drug (Avigan, or favipiravir)54 against Ebola began
at a treatment centre in Guinea in mid-December. French President Francois
Hollande's office reported in February: "The results are encouraging. They show a
fall in the number of deaths in adults and teenagers. The recovery process is
accelerated." The treatment was given to 80 patients, adults and children.
j) Scientists protected 75 per cent of rhesus monkeys infected with Ebola virus with a
compound targeting the expression of VP24, a single Ebola virus protein--suggesting
that VP24 may hold the key to developing effective therapies for the deadly disease.
The study55 was conducted by the US Army Medical Research Institute of Infectious
Diseases (USAMRIID) in collaboration with firm Sarepta Therapeutics.
k) Chimerix announced it would cease participation in clinical studies in Ebola of its
cytomegalovirus drug, brincidofovir, because of a significant decrease in the number
51
Ebola is an RNA virus-like HIV and influenza-which have a high rate of mutation.
The team is led by Lee Gehrke, Harvard Medical School professor of microbiology and
immunobiology and the Hermann von Helmholtz Professor of Health Sciences and Technology at
MIT.
53
The test is described in the journal Lab on a Chip
54 developed by Toyama Chemical, a subsidiary of Fujifilm,
55 which appeared in mBio, the online journal of the American Society for Microbiology
52
17
of new Ebola cases in Liberia56. Chimerix will continue to study of brincidofovir for
other indications.
l) Researchers57 who tested swabs and tissue samples from the bodies of deceased
Ebola-infected monkeys found the virus can stay alive for up to seven days after
death. They also found that non-infectious viral genetic material can remain for up to
70 days after death.
m) Sierra Leone's government has promised a full investigation after an internal audit
found that nearly one-third of the funds received to fight Ebola was spent without
invoices and receipts for acquittal58.
MERS-CoV
a) At the end of January the US Centers for Disease Control (CDC) issued a travel
advisory for MERS.
b) In early February, the World Health Organization (WHO) said after a meeting of its
emergency committee on Middle East Respiratory Syndrome said more must be
done to track the virus, which was then known to have infected at least 965 people,
of whom some 357 had died. It stressed the need for “increased surveillance in many
countries …to better monitor trends related to the spread of this virus."
c) In Saudi Arabia, there were 10 new cases in the three days 22-24 February.
d) An international team of UN human and animal health experts visited Saudi Arabia to
investigate a recent surge in MERS cases.
e) Clinics and other health facilities in Saudi Arabia that do not report cases of MERS
will be shut down and have their licences revoked. Abdul Aziz Bin Saeed, the health
ministry’s undersecretary for general health also said: “Fines …will be imposed on
facilities and on health practitioners who conceal cases, do not report them or do not
take the necessary measures to prevent the spread of the disease.”
f) The warning came after a large private hospital in the capital Riyadh was closed for
not addressing the spread of MERS properly, failing to comply with infection control
guidelines.
g) Saudi authorities warned of a possible peak in MERS cases because of the risk
posed by newborn camels. Young camels are particularly susceptible to the disease.
h) Malaysia’s health ministry has urged all tourism agencies to stop providing camel
farm tours in Middle East countries, especially to tourists going on Umrah or haj
pilgrimage.
i) A Filipino nurse from Saudi Arabia has been the first confirmed MERS-CoV patient in
the Philippines.
Other diseases: occurrence, prevention and treatment
a) Harvard Medical School investigators from Massachusetts General Hospital, with
colleagues from the US National Institute of Allergy and Infectious Diseases (NIAID),
have found that blood vessels supplying pulmonary granulomas59 have similar
structural and functional abnormalities to solid tumours60. Treatment with the
antiangiogenesis61 drug bevacizumab (Avastin)62 significantly improved delivery of a
56
The first Ebola patient diagnosed in the US, Thomas Eric Duncan, was given brincidofovir before he
died.
57 from the US National Institute of Allergy and Infectious Diseases (NIAID), a part of the US National
Institutes of Health (NIH). They reported in the journal Emerging Infectious Diseases.
58 The audit report to Sierra Leone's parliament detailed how some $US 5.75 million in funds either
had no or insufficient documentation.
59 dense masses of immune cells that surround pockets of the tuberculosis bacteria in the lungs of
infected patients
60 See Proceedings of the National Academy of Sciences Early Edition
61 Angiogenesis inhibitors slow the growth of new blood vessels (angiogenesis). Some angiogenesis
inhibitors are a normal part of the body's control and others are obtained through drugs or diet.
18
b)
c)
d)
e)
f)
g)
h)
i)
62
small-molecule drug surrogate within granulomas in an animal model. The
researchers concluded that combining bevacizumab with anti-TB drugs may enhance
TB treatment and reduce the growing problem posed by antibiotic resistance.
By the end of January California was reporting 59 cases of measles, in an outbreak
centred on Disneyland.
A new study has updated global herpes simplex virus type 2 estimates63. Dr
Katharine Looker from the University of Bristol’s School of Social and Community
Medicine, said: “Approximately 19 million people are newly infected with the virus
each year.” More women are infected with the disease than men–in 2012, it was
estimated that 267 million women and 150 million men were living with the infection.
Prevalence was estimated to be highest in Africa (31.5 per cent) followed by the
Americas (14.4 per cent). Dr Lori Newman, WHO expert on sexually transmitted
infections, and senior author of the study, said: “Genital herpes can have a
devastating effect on the social and psychological wellbeing of people who are
infected.”
Chronic wasting disease (CWD) is an infectious disease caused by prions. It affects
North American elk and deer. Researchers at the University of California, San Diego
School of Medicine have determined that human proteins aren't corrupted when
exposed to the elk prions, because there is a small loop in the human prion protein
that confers resistance to chronic wasting disease64. Christina Sigurdson, senior
author of the study, said: "Since the loop has been found to be a key segment in
prion protein aggregation, this site could be targeted for the development of new
therapeutics designed to block prion conversion."
Norway has announced its first-ever case of bovine spongiform encephalopathy
(BSE). The disease was found in a 15-year-old cow; no portion of the cow reached
the consumer food system.
Canada said that the beef cow in Alberta confirmed to have BSE was born in March
2009, two years after the country enacted a ban on cattle feed containing animal
proteins, to prevent the spread of the disease. The Canadian Food Inspection
Agency said it has quarantined both the farm where the infected animal was found
and the birth farm. Canada’s chief veterinary officer said the investigation will track
down what the cow was fed.
Jacquie Thomas, of the School of Civil and Environmental Engineering at the
University of NSW, led an 18-month study into the growth of legionella inside garden
hoses. It found65 the bacteria thrive inside garden hoses lying in the summer heat,
multiplying within host cells called free-living amoebae that amplify their virulence.
The legionella grow within microbial slime on the inside of the hose called biofilm
which dislodges in fragments and spurts out with the water when the tap is turned on.
An aggressive new strain of HIV in Cuba (and in parts of Africa) has been found to
progress to AIDS in three years66.
An NIH-sponsored HIV vaccine trial has been launched in South Africa67.
Bevacizumab is an FDA-approved drug widely prescribed for cancer and eye disease , specifically
macular degeneration.
63 Herpes simplex virus type 2 is mainly sexually transmitted, and can cause genital ulcer disease.
Genital herpes can also cause neonatal herpes when the virus is transmitted by a mother to a
newborn baby during labour through shedding of the virus. Whilst this is a relatively rare disease, it is
often fatal for the baby. People infected with herpes simplex virus type 2 are approximately three
times more likely to become infected with HIV, and people with both HIV and herpes are more likely to
spread HIV to others. Infection with herpes simplex virus type 2 in people living with HIV can lead to
serious but rare complications such as brain, eye, or lung infections.
64 See the Journal of Clinical Investigation, 23 February
65 See Journal of Environmental Science and Technology
66 Vandamme AM, Kouri V, Khouri R, et al. “CRF19_cpx is an evolutionary fit HIV-1 variant strongly
associated with rapid progression to AIDS in Cuba” EBioMedicine. 2015.
19
j)
Scientists from the Jupiter, Florida campus of The Scripps Research Institute (TSRI)
have announced a potent and effective novel drug candidate against AIDS that might
work as part of an unconventional vaccine. The research involved scientists from
multiple research institutions68.
k) Patients at the University of California’s Ronald Reagan Medical Center may have
been exposed to a drug-resistant superbug spread by contaminated medical scopes.
Some may have died. “These outbreaks at UCLA and other hospitals69 could
collectively be the most significant instance of disease transmission ever linked to a
contaminated reusable medical instrument,” commented Lawrence Muscarella, a
hospital safety consultant from Alabama. The superbug is CRE, CarbapenemResistant Enterobacteriaceae, an antibiotic-resistant bacterium that infects patients in
hospitals, nursing homes and other health clinics. CRE-related illnesses include
gastrointestinal problems, pneumonia and bloodstream infections. Though all
superbugs are tough to treat, CRE is the toughest. The UCLA outbreak was caused
by a specialized duodenoscope inserted down a patient’s throat70. These instruments
are minimally invasive, but the design of some scopes causes them to grip onto
bacteria that can be difficult to disinfect through conventional cleaning.
l) In the US, 121 measles cases were reported between 1 Jan and 6 Feb 2015 across
17 states and Washington, DC. The majority of cases (103) are linked to Disneyland
in California, which they visited between 17 and 20 Dec 2014.
67
This experimental vaccine regimen is based on the one tested in the US Military HIV Research
Program-led RV144 clinical trial in Thailand—the first study to demonstrate that a vaccine can protect
from HIV.
68
Published online ahead of print in Nature, 18 February
69 the CDC issued warnings last year about CRE, saying the bacteria spread from one medical facility
in 2001 to numerous facilities in 46 states in 2013.
70 In a procedure known as ERCP, or endoscopic retrograde cholangiopancreatography.
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