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MONITORING INTERNATIONAL TRENDS
Prepared August 2011
The NBA monitors international developments that may influence the management of blood and
blood products in Australia. Our focus is on:
 Information that may have an impact on global supply, demand and pricing, such as changes
in company structure, capacity, organisation and ownership
 Potential new product developments and applications
 Global regulatory and blood practice trends and
 Other emerging risks that could potentially put financial or other pressures on the Australian
sector.
A summary of current matters of interest appears below. Highlights include:
 The US Food and Drug Administration (FDA) has recommended more conservative dosing
of erythropoiesis – stimulating agents in patients with chronic kidney disease.
 CSL Behring has been granted Orphan Drug Designation by the
European Commission for the development of its recombinant fusion
protein linking coagulation factor VIIa with albumin (rVIIa-FP).
 CSL’s capacity to produce Hizentra has more than doubled.
 NovoNordisk is investing in a new manufacturing facility.
 CSL has removed Vivaglobin from the market.
 Baxter’s HyQ injectable immunoglobulin has performed satisfactorily in
a Phase III trial.
 An active pipeline in clotting factors has seen some progress.
 Serious doubts have been raised about whether chronic fatigue syndrome is linked to
xenotropic murine leukemia virus (XMRV).
 Two significant studies on red blood cell storage have been reported.
1. Regulatory Matters:
a. The US FDA publicised modified recommendations for more conservative dosing of
erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease (CKD).
ESA labels now warn: In controlled trials with CKD patients, patients experienced greater
risks for death, serious adverse cardiovascular reactions, and stroke when administered
ESAs to target a hemoglobin level of greater than 11 g/dL. No trial has identified a
hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
 ESA labels now recommend: For patients with CKD, consider starting ESA treatment
when the hemoglobin level is less than 10 g/dL. This advice does not define how far
below 10 g/dL is appropriate for an individual to initiate. This advice also does not
recommend that the goal is to achieve a hemoglobin of 10 g/dL or a hemoglobin
above 10 g/dL. Individualize dosing and use the lowest dose of ESA sufficient to
reduce the need for red blood cell transfusions. Adjust dosing as appropriate.
 The label previously recommended that ESAs should be dosed to achieve and
maintain haemoglobin levels within the range of 10 to 12 g/dL in CKD patients.
b. Baxter announced that the Committee for Medicinal Products for Human Use (CHMP) of
the European Medicines Agency (EMA) has issued a positive opinion for extension of the
therapeutic indications of KIOVIG to include a new indication for multifocal motor
neuropathy (MMN). With adoption by the European Commission, Baxter will receive
marketing authorization for KIOVIG MMN indication in all European Union (EU) Member
States. KIOVIG is marketed as GAMMAGARD LIQUID(TM) [Immune Globulin Intravenous
(Human)], in the US.
c. Shire announced that the Pulmonary-Allergy Drugs Advisory Committee to the FDA
recommended that the efficacy and safety data provides substantial evidence to support
approval of Firazyr (icatibant) for the treatment of acute attacks of hereditary angioedema
(HAE) in patients 18 years and older. In addition, the Committee recommended selfadministration of the drug by patients.
d. GTC Biotherapeutics, acquired by LFB Biotechnologies in 2010, has been granted a
patent covering any production of therapeutic protein in the milk of transgenic animals.
The patent, granted by the US Patent and Trademark Office, extends to 2027. GTC said
it has also received a new US patent for its lead product, ATryn, an anticoagulant and
anti-inflammatory product derived from the milk of genetically modified goats. The new
patent relates to a method of treatment of patients with a particular protein deficiency or
inflammation. ATryn is the only transgenically produced therapeutic protein that has
been approved by both the FDA and EMA.
e. CSL Behring has been granted Orphan Drug Designation by the European Commission
for the development of its recombinant fusion protein linking coagulation factor VIIa with
albumin (rVIIa-FP), a novel therapy to treat hemophilia A and hemophilia B patients with
inhibitors. The designation would entitle CSL Behring to exclusively market recombinant
factor VIIa fused with albumin in Europe for a period of 10 years if the product at the
stage of license application fulfills the orphan drug requirements. Based on the
submission of data from the company's Pediatric Investigation Plan, once available, the
10-year market exclusivity may be extended to 12 years. Under these designations EMA
will also provide CSL Behring with development assistance and reductions in regulatory
fees.
f. CSL Behring’s capacity to produce Hizentra®, its subcutaneous immunoglobulin, more
than doubled following FDA approval of the company’s high tech production facility in
Bern, Switzerland. Demand for Hizentra is growing rapidly in the US, and CSL Behring
anticipates regulatory approvals of Hizentra in Europe.
g. CSL Behring announced that the European Commission has granted marketing
authorization for Hizentra for treating patients diagnosed with primary
immunodeficiency (PI) as well as secondary immunodeficiencies. This is valid for all
29 European/European Economic Area member states.
h. At its August meeting, the FDA’s Transmissible Spongiform Encephalopathies
Advisory Committee will discuss donor deferral (for time spent in Saudi Arabia) to
reduce the risk of variant Creutzfeldt-Jakob disease (vCJD) by blood and blood
products and human cells, tissues and cellular and tissue-based products.
i. LFB was issued with a US Patent titled “Monoclonal Antibodies with Enhanced ADCC
Function”. LFB has developed in clinical trials two monoclonal antibodies with this new
technology: One is a monoclonal antibody targeting alloimmunization in expectant
mothers that are Rhesus negative with a baby that is Rhesus positive.
j. The FDA Blood Products Advisory Committeee at its August meeting will discuss a study
on the incidence of Trypanosoma cruzi infection in blood donors and its implications for
selective testing of blood donors. The Committee will also discuss measures to preserve
the blood supply during a severe emergency (Trypanosoma cruzi is the parasite which
causes Chagas disease).
k. The FDA is convening in September a public workshop entitled: “Quarantine Release
Errors in Blood Establishments.” The purpose of this public workshop is to provide a
forum for discussion of quarantine release errors (QREs) and provide FDA and industry
with information necessary to reduce the rates of QREs.
l. A number of Medicines Australia member companies are considering delaying bringing
new drugs into the country, following the Australian government's decision to defer listing
of new medicines on the Pharmaceutical Benefits Scheme (PBS), a Senate Committee
has been told as it investigates the new policy.
m. The FDA on 21 July issued draft guidance (for comment purposes only) on mobile
medical applications. This was to inform manufacturers, distributors, and other entities
about how the FDA intends to apply its regulatory authorities to select software
applications intended for use on mobile platforms (mobile applications or "mobile apps").
At this time, the FDA intends to apply its regulatory requirements solely to a subset of
mobile apps that it is calling mobile medical applications or "mobile medical apps."
2. Products
a. Immunetics received a grant to commercialize its BacTx® rapid test for detecting bacterial
b.
c.
d.
e.
f.
g.
h
i.
contamination in platelets. Immunetics has concluded clinical trials for BacTx® and is
submitting an application for approval to the FDA this year. Immunetics also received
grants from the National Heart, Lung, and Blood Institute (NHLBI), an agency of the
National Institutes of Health (NIH). The technology underlying the test is protected by
a recently issued US patent, and foreign patents with approved claims are in process of
issue.
Fenwal received CE Mark approval for a therapeutic plasma exchange (TPE) protocol for
the company’s Amicus® system. TPE removes substances from blood that can cause or
complicate disease and is used in the treatment of a wide range of haematologic,
neurologic, autoimmune, and kidney disorders. The Amicus® system is used globally to
collect platelets, platelets with concurrent plasma and red cells, and mononuclear cells
used for therapeutic applications and clinical research.
Affymax and Takeda announced the submission of a New Drug Application (NDA) to the
FDA for the investigational agent peginesatide (formerly known as Hematide™) for the
treatment of anemia associated with chronic renal failure in adult patients on dialysis.
Peginesatide is a synthetic PEGylated peptide compound that binds to and activates the
erythropoietin receptor, thus acting as an ESA.
A continuous spectrophotometric haemoglobin sensor may offer a new approach for
non–invasive blood haemoglobin monitoring during surgery, according to a study
published in the April issue of Anesthesia & Analgesia. Ronald D. Miller, from the
University of California in San Francisco, and his colleagues compared the accuracy of
SpHb and point-of-care HemoCue to that of the invasive laboratory Co-Oximetry (tHb)
method for monitoring blood haemoglobin during perioperative transfusions.
Medgenics announced an extension of its agreement with Baxter for the joint
development of the Factor VIII Biopump. Confirmatory studies will be conducted
implanting Factor VIII Biopumps in mice. During the extended agreement, which will
expire by 30 September 2011, Baxter has the opportunity, to exercise an exclusive
option for 6 months to negotiate with Medgenics an agreement for commercialization of
the Biopump Factor VIII technology. Medgenics’ Biopump is a proprietary tissue-based
platform technology for the sustained production and delivery of therapeutic proteins
using the patient's own skin biopsy for the treatment of a range of chronic diseases
including anaemia, hepatitis C and haemophilia. Medgenics has three long-acting protein
therapy products in development based on this technology. Hemodure is a sustained
Factor VIII therapy for the prophylactic treatment of haemophilia.
CSL Behring took its immune globulin subcutaneous (human) 6% liquid (Vivaglobin) off
the market on 4 April 2011. It was on the FDA watch list.
Inspiration Biopharmaceuticals reported on its clinical development program for OBI1, an intravenous (IV) recombinant porcine factor VIII product (rpFVIII), intended for
the treatment of bleeding in people with hemophilia A with inhibitors and in people
with acquired hemophilia. The data were presented at the 23rd Congress of the
International Society on Thrombosis and Haemostasis (ISTH) in Kyoto.
Nehora Photonics of Israel is developing optical technology for the non-invasive continuous
monitoring of hematocrit, the proportion of the blood, by volume, that contains red blood cells.
In July, Baxter presented preclinical data to the 23rd Congress of the ISTH on its
investigational compound BAX 499 for potential subcutaneous haemophilia therapy and
final Phase I data on recombinant von Willebrand Factor.
 BAX 499 is in early stage clinical development to treat blood clotting disorders
haemophilia A and B by targeting a novel pathway responsible for regulating the
clotting process. The studies presented at ISTH validate the pathway as a potentially
viable target for the treatment of haemophilia.
 Data were also presented on recombinant von Willebrand Factor (rVWF), the only
recombinant replacement protein currently in clinical development, to assess its
safety and efficacy for the treatment of von Willebrand disease (VWD). The data
indicated overall that the pharmacokinetics of rVWF and pdVWF were found to be
similar. A larger Phase III trial study is required to further assess the safety and
efficacy of rVWF. Baxter anticipates beginning recruitment later this year.
j. Biogen Idec's CEO, speaking on 26 July, said “we shared important data today at the
23rd Congress of the International Society on Thrombosis and Haemostasis in Kyoto,
Japan. Six out of our eight abstracts were platform presentations and focused on the
advancements of our hemophilia programs. One presentation that I'll highlight includes a
Phase I 2a study of our long-lasting fully recombinant Factor VIII Fc fusion protein, which
showed that the drug demonstrated on approximately 1.7 fold increase in half-life
compared with Advate, a commercially available Factor VIII product in 16 previously
treated patients with severe hemophilia A. Our long-lasting recombinant Factor VIII had
comparable -- in dose-dependent peak plasma concentration, comparable recovery but
reduced clearance relative to Advate. Importantly, no inhibitor formation was observed.
These data indicate that there would be 50 to 80 less injections per year for hemophilia A
patients”.
k. The FDA has approved the subcutaneous administration of Baxter’s Gammagard Liquid
10% [Immune Globulin Infusion (Human)] for patients with PI. Subcutaneous use of
GAMMAGARD LIQUID allows patients to self-administer their therapy at home on a
weekly basis.
3. Market structure and company news:
a. NovoNordisk plans to invest €134 million in a new biologics manufacturing facility at
its Kalundborg site, the largest in the group's production network. The new capacity
will be used to manufacture Factor VIIa, as well other biologic medicines. The
company says it needs to boost capacity for its existing products, but "also to be
ready to produce future haemophilia products that are in the pipeline". Nearest to the
market is Novo's recombinant factor XIII drug NN1841. The drug was filed for
approval in the US in February. An improved Factor VIII called N8 is in phase III trials
for haemophilia A, as is a long-acting formulation of Factor IX for haemophilia B. The
packaging facility is expected to be operational in 2013, while the other facilities are
expected to be up and running in 2015. A recent report in the Financial Times shows
Novo Nordisk is one of the world’s ten most valuable medical companies. It occupies
position 115 on the list of largest companies in the world.
b. Canadian company Compass Biotechnologies announced that the first product to be
sourced from its manufacturing partner (PanGen of South Korea) will be erythropoietins
(EPO).
c. OPK Biotech LLC has grown from eight employees to over 100 since its commencement
of operations in October 2009. The Massachusetts company manufactures two oxygen
therapeutics: Hemopure® [hemoglobin glutamer – 250 (bovine)], or HBOC-201, for
human use and Oxyglobin® [hemoglobin glutamer – 200 (bovine)], or HBOC-301, for
veterinary use. Hemopure has been approved for use the treatment of acute surgical
anaemia in South Africa since 2001 and recently won approval in Russia for acute
anaemia.
d. ProMetic Life Sciences has received a follow-on purchase order for its Mimetic Ligand
product, used for biomolecular purification manufacturing processes. The order stems
from a long-term supply agreement with Halozyme Therapeutics.
e. CSL Behring donated more than 1 million international units of von Willebrand factor
/Factor VIII replacement medication to patients through the World Federation of
Hemophilia (WFH). The donation supports WFH’s progress in improving the diagnosis
and treatment of bleeding disorders in developing countries through its Global Alliance
for Progress (GAP) program. It is part of the commitment CSL Behring has made to WFH
to donate two million IUs of FVIII each year for three years. The July donation is
commercially valued at $US 1.3 million.
 GAP partners include CSL Behring, Baxter, Bayer, Biotest, the Irish Hemophilia
Society, the Jan Willem Andre de la Porte Family Foundation, Pfizer, Talecris and the
World Health Organization (WHO). Sixteen countries have participated in GAP:
Armenia, Azerbaijan, Belarus, China, Ecuador, Egypt, Georgia, Jordan, Lebanon,
Mexico, Philippines, Russia, Syria, Thailand, and Tunisia. A GAP project in Peru has
just been launched.
Cerus Corporation in its second quarter 2011 results reported sales grew by 19%
compared with the same quarter in 2010; and that it had entered a distribution
agreement with Ilex Biotech Ltd. for Israel and South Africa, an agreement with Grifols
for Mexico, and an agreement with Comércio Exportação e Importação de Materiais
Médicos for Brazil.
g. Baxter established Baxter Ventures to invest up to $US200 million in equity in earlystage companies developing therapies complementing Baxter's existing portfolio.
 Baxter announced strong financial results for the second quarter of 2011, and raised
its financial outlook for full-year 2011. It reported an increase of 15% in net income
compared with the same period last year. Worldwide sales totaled $US3.5 billion.
Excluding the impact of foreign currency, worldwide sales increased 6%. BioScience
sales advanced 10% boosted by strong demand for immunoglobulin, certain
specialty plasma-based therapeutics, and vaccines.
h. Israeli manufacturer Kamada signed a strategic cooperation agreement granting
marketing rights of its human rabies immune globulin in the US to an un-named
international pharmaceuticals manufacturer that markets in 40 countries. KamRAB is
administered along with the rabies vaccine to prevent infection caused by the rabies
virus. The partner will supply Kamada with the necessary plasma. KamRAB sales in the
US should begin in about three years. KamRAB has been sold in Israel since 2003. It is
also sold in Mexico, South Korea, Thailand, India and Russia. In August 2010 Kamada
entered into a collaboration with Baxter, under which Baxter received exclusive
distribution rights to Glassia, an intravenously administered therapy for emphysema, in
the United States, Australia and New Zealand. Baxter also supplies Kamada with the raw
materials for the product.
4. Overseas events
a. In the US, an infection caused by tick bites has gained a foothold in the Lower Hudson
Valley and in coastal areas of the Northeast. Babesiosis is a malaria-like illness caused
by Babesia microti, a parasite that lives in red blood cells and is carried by deer ticks.
Though far less common than Lyme disease, babesiosis can be fatal, particularly in
people with compromised immune systems. Because there is no widely used screening
test for babesiosis, its spread poses a particular threat to the blood supply. Many people
who are infected with the parasite have no symptoms at all, or moderate symptoms.
Experts fear that undiagnosed patients may be donating blood. Babesiosis already is the
most frequently reported infection transmitted through transfusion in the United States,
responsible for at least 12 deaths. Between 1999 and 2007, several infants in Rhode
Island developed babesiosis following blood transfusions. The Rhode Island Blood
Center has become the first in the country to use an experimental new test to screen
blood for the parasite. Symptoms of babesiosis can occur up to nine weeks after a
transfusion.
b. A French woman suffered a severe infection with cowpox virus, a relative of the smallpox
virus, as a result of contact with infected pet rats1. Wild rodents, not cows, are now
considered the true reservoir for cowpox virus, and in recent years, several human cowpox
infections have resulted from contact with pet rats, though humans are more commonly
infected through contact with cats, which are incidental hosts. The authors say the
cessation of smallpox vaccination may partly explain the reemergence of cowpox in
humans, as the vaccine probably induced some immunity to other orthopoxviruses.
Cowpox virus is distributed widely in Europe, western parts of the former Soviet Union,
and adjacent areas of Northern and Central Asia.
c. In May 2011 in the US the FDA Center for Biologics Evaluation and Research (CBER)
distributed a summary of transfusion fatalities reported for the fiscal year 2010 (1
October 2009 to 30 September 2010). There were 76 fatality reports, 71 transfusion
recipient fatalities and 5 post-donation fatalities. CBER concluded that of the 71
transfusion recipient fatality reports: 40 were transfusion-related, 24 were cases where
transfusion could not be ruled out as the cause of the fatality, and seven of the fatalities
f.
were unrelated to the transfusion. TRALI remains a cause of death, and there were still
some fatal reactions to bacterial- contaminated platelet transfusion.
e. New Zealand's PHARMAC is moving to a more "permissive" system of assessing people
seeking medicines not funded on the Pharmaceutical Schedule, in a move which is
expected to double the scheme's spending in the first full year.
f. In Ireland the Health Information and Quality Authority (HIQA) has said a suggested
vCJD intervention is “not cost-effective” and has alerted the Government to a potential
bill of between €51.6 million and €55.9 million over five years, for red blood concentrate
filtration for vCJD. HIQA estimated that such a measure would, over a 10-year period,
potentially prevent two deaths from vCJD. The Committee said the level of undiagnosed
vCJD in Ireland is likely to be low and that the corresponding risk of transfusiontransmitted infection would be extremely low.
g. Tweets posted by Bayer Healthcare about two of its products have been found to have
breached the UK pharmaceutical industry Code of Conduct, including Clause 2, which
deals with promotional activities that bring discredit upon, or reduce confidence in, the
industry. The tweets also constituted the promotion of prescription-only medicines to the
public, the Prescription Medicines Code of Practice Authority (which administers the
Code), has ruled, in the first-ever cases of breaches of the Code involving social media.
The guidance states that social media, including twitter, could be used to provide
information to the public provided the material complied with the Code. "If a company
wanted to promote a medicine via twitter it would have to ensure that if the medicine was
“Severe Ear Chondritis due to Cowpox Virus Transmitted by a Pet Rat”. By Antoine Elsendoorna et al., Journal of
Infection online, 24 Jun 2011
1
prescription-only, the audience was restricted to health professionals and that the
message, in addition to any link to further information, complied with the Code. In
addition, companies would also have to ensure that recipients had agreed to receive the
information," it says.
h. In the UK, where NHS Blood and Transplant (NHSBT), was given permission to sell on
surplus blood products and plasma2, there has been public questioning of why the
identity of the buyer cannot be revealed.
i. The UK government has said its plans to introduce a value-based pricing (VBP) system
for medicines from 2014 will go ahead, but respondents to its consultation on the plan
have called for more details on how the system would operate in practice.
5. Safety Issues:
a. Two studies posted in Science online on May 31 raised serious doubts about earlier
reports that chronic fatigue syndrome (CFS) is linked to infection with XMRV. In October
2009 the journal had published the initial research linking XMRV to CFS. In an "editorial
expression of concern" accompanying the two new studies, Bruce Alberts, editor in chief
of the journal, declared that the earlier finding "is now seriously in question" and was
probably attributable to laboratory contamination. In one of the two new studies,
researchers found no trace of XMRV or related viruses in the blood of 43 patients who
had previously tested positive for XMRV. In the second study, scientists reported
evidence that XMRV was probably a recombination of two mouse leukemia viruses
created accidentally in laboratory experiments.
b. In July a Duke University Medical Center study reported a problem in red blood cells
stored for long periods. Under US federal law, whole blood can be stored for up to 42
days. Some studies have found though, that patients who receive blood stored even for a
couple of weeks, are more likely to suffer infections, cardiovascular problems and even
organ failure, particularly those who use several units of older blood. Previous studies of
older blood have mainly focused on outcomes for patients using it, rather than the
specific mechanisms that lead to the problems.
 This study, published in the journal Critical Care Medicine, found that stored red
blood cells begin to lose the ability to release a key molecule called adenosine-5’triphosphate (ATP), which helps prevent the cell from sticking to the walls of blood
vessels. The researchers think the stuck cells cause a number of problems, from
obstructing blood circulation in the lungs to hampering the bloodstream’s ability to
deliver oxygen around the body, said Dr Timothy J. McMahon, senior author of the
study. McMahon said he and other researchers are now studying methods of
boosting ATP in older blood.
c. Transfused blood may need to be stored in a different way to prevent the breakdown of
red blood cells that can lead to complications including infection, organ failure and death,
say researchers at the University of Pittsburgh School of Medicine and Wake Forest
University. In July, 2011, in the early online version of Circulation, the team reported the
latest findings from its ongoing exploration of the interaction between red blood cell
breakdown products and nitric oxide (NO), revealing new biological mechanisms that can
reduce blood flow and possibly damage vital tissues after administration of blood that
has been stored for longer than 39 days.
 In recent years, doctors have noted that transfusion of either many units of blood or
of blood stored a long time may be associated with a greater frequency of
complications, such as increased infection risk, kidney, lung or multi-organ failure
and death, particularly among medically vulnerable patients, explained senior
investigator Mark T. Gladwin, MD, Chief, Division of Pulmonary, Allergy and Critical
Care Medicine, Pitt School of Medicine, and director of Pitt's Vascular Medicine
Institute. "When blood sits for a while, some of the cells break down and release their
The sale of whole blood is not allowed. Neither is anything that ‘might be administered to a person’. The discard
plasma is expected to be used for research purposes, or for making diagnostic reagents.
2
contents, which include molecules of hemoglobin and red blood cell microparticles" he
said. "These accumulate in the stored bag of blood and are transfused into the patient
with the blood. In the bloodstream, the hemoglobin and microparticles bind to and
destroy NO, a very important molecule that is used by the body to keep blood vessels
dilated for normal blood flow. "The scavenging of NO causes blood vessel constriction
that can prevent tissues and organs from getting adequate oxygen and activate the
platelets and the coagulation system, as well as cause inflammation”
Dr Gladwin said.
 From their experiments, he and his Wake Forest collaborators found that human blood
stored under standard conditions accumulated "free" haemoglobin that was no longer
contained in a cell and microparticles of damaged cells. Those breakdown products
reacted with NO about 1,000 times more quickly than did intact red blood cells. Also,
transfusion of even very low concentrations of haemoglobin caused blood vessel
constriction and hypertension in a rat model.
 "Avoiding the storage lesion, as it is referred to in our field, could require a new
approach to how donor blood is stored prior to transfusion" said senior author Daniel
B. Kim-Shapiro, professor of physics and director of the Translational Science Center
at Wake Forest. "Transfusion of stored blood is one of the most common medical
therapies" he said. "By understanding the mechanism of the storage lesion, we can
design methods to make blood transfusion safer. For example, perhaps we can
restore nitric oxide activity that is lost upon transfusion, use preservation solutions
that better limit the degradation of blood cells, or develop agents that scavenge free
hemoglobin".
d. A structured literature review3 of treatments for reversing warfarin anticoagulation in
patients with acute intercranial haemorrhage concluded that prothrombin complex
concentrate is statistically significantly faster at correcting the INR4 compared with fresh
frozen plasma transfusions. Recombinant factor VIIa appears to rapidly reverse
warfarin's effect on INR; however, this treatment is not FDA-approved and is associated
with a 5% thromboembolic event rate.
6. Research:
a. HyQ, an injectable subcutaneous immunoglobulin for treating a lifelong immunodeficiency
condition (made by Halozyme Therapeutics and Baxter International5) exceeded
requirements for preventing infections in a phase III clinical trial. HyQ combines
Halozyme's drug absorption enzyme rHuPH20 and Baxter's immune globulin product.
Halozyme's enzyme boosts absorption by breaking down the gel-like substance that fills
open spaces in tissue and sometimes gets in the way of drug molecules
reaching their targets. That allows a single dose of HyQ to be administered by a patient
at home every three or four weeks.
 Baxter submitted a Biological License Application to the FDA on 30 June and expects
to file regulatory submissions in Europe and Canada in the coming months. It will
present results from the phase III study by the end of 2011.
b. Prolor Biotech of Israel plans to initiate a Phase II trial for its factor IX (F-IX-CTP), a long
lasting version of the clotting factor. In preclinical models, mice treated with Prolor's longlasting treatment lost half as much blood as the BeneFIX (current marketed drug) treated
mice did, and approximately one third as much as the untreated group. In second bleeding
events the BeneFIX- treated mice bleeding persisted over 3 times as long compared with
the Factor IX - CTP. Furthermore, the Factor IX - CTP group experienced
no spontaneous rebleeding events 12 hours post-second bleeding event, compared with
3
Brett Bechtel, Timothy Nunez, Jennifer Lyon, Bryan Cotton, Tyler Barrett. International Journal of Emergency
Medicine 2011, 4:40
4
International normalized ratio, a laboratory test measure of blood coagulation based on prothrombin time
5
HyQ is a subcutaneous immune globulin product, being developed by Baxter using a recombinant human
hyaluronidase technology platform licensed from Halozyme Therapeutics. Baxter will pursue an extension study to
evaluate HyQ administration to patients through to March 2012.
c.
d.
e.
f.
g.
50% for the BeneFIX group. Prolor intends to begin roughly a 70 patient Phase II trial
sometime in 2012.
Symphogen announced preliminary data from a phase II clinical trial with rozrolimupab
(SYM001) in adult, RhD positive, non-splenectomized patients with immune
thrombocytopenia (ITP). The study showed rozrolimupab is well tolerated with no
unexpected toxicities and shows preliminary signs of clinical and biological activity by
decreasing haemoglobin values. Preliminary results of the anti-RhD antibody mixture
rozrolimupab in ITP were presented in a poster at the 16th Congress of the European
Haematology Association meeting in London.
 Rozrolimupab is a fully human anti-RhD monoclonal antibody (mAb) mixture,
comprising 25 mAbs that bind to RhD. Rozrolimupab is produced by a single-batch
manufacturing strategy, designed to capture the natural diversity of the human
antibody response to RhD as a modern counterpart to the plasma-derived anti-RhD
immunoglobulins currently used in the treatment of ITP. The beneficial effect of this
agent in patients with ITP is also being evaluated at doses beyond 200µg/kg.
Biogen Idec was given a positive opinion by European healthcare regulators on a
planned paediatric trial of its new haemophilia B treatment. In association with partner
Swedish Orphan Biovitrum, the company is planning to initiate a global investigational
plan of their new long-lasting, fully-recombinant Factor IX Fc fusion protein among
previously treated patients aged below 12 years of age. Having received approval from
the EMA’s Paediatric Committee, the companies will seek to begin the study when
sufficient data has been collated from a trial involving adult patients. Dr Glenn Pierce,
senior vice-president for haemophilia at Biogen Idec, said: "With this opinion and the
ongoing phase III trials of our long-lasting Factor IX and Factor VIII programmes, we
continue to make progress toward our goal of improving the way haemophilia is treated
worldwide."
 Biogen Idec in April entered a partnership with Amunix to develop recombinant blood
factors with improved therapeutic properties. Amunix has expertise in protein
pharmaceuticals and focuses on the discovery and development of novel therapeutics
with improved dosing frequency and administration. The company's
patented platform technology, XTEN, extends the half-life of protein.
In July it was confirmed that the first of Baxter's two phase III IVIg for Alzheimer's trials
has completed enrollment. 390 patients have been randomized to either (a) 400mg of
IVIG/kg of bodyweight every 2 weeks; (b) 200mg of IVIg/kg; or (c) placebo. Patients will
be dosed and followed for 18 months with the last patient now expected to reach followup in January 2013. Given time for data gathering and analysis, this might mean
headline data by mid-2013.
 A number of papers/posters at a global Alzheimer’s disease conference continued to
feed an expectation that the outcome of the Baxter trial will be positive. They also fed
a continuing concern that plasma collection and fractionation, at least in the short
term, would struggle to meet demand arising from a positive outcome, and that price
will be a rationing mechanism. Some research is being directed to identifying the
mechanism by which IVIg may have a favourable effect on Alzheimer’s, and
synthesizing a compound which can replicate it.
Amgen announced that interim results from an international, single-arm study evaluating
the safety and efficacy of Nplate® (romiplostim) in adults with primary ITP demonstrated
that Nplate induced a rapid platelet response with a good safety profile in adult ITP
patients with low platelet counts and bleeding symptoms. With 400 patients to be enrolled
this will be the largest study so far in adult ITP. The interim results covered the first 235
patients enrolled.
The US Defense Advanced Research Projects Agency (DARPA) recently announced its
budget estimates for fiscal year 2012 . They included $US 17 million for Tactical
Biomedical Technologies, including preventing battlefield fatalities due to uncontrolled
blood loss by creating technologies that enable unskilled personnel to locate and stop
deep bleeders. $US4.295 million was provided for Blood Pharming to produce a large
quantity of safe, transfusable blood to satisfy battlefield demand and reduce logistics of
sourcing donated blood. The goal is to produce 100 units of O-negative red blood cells
per week using renewable stem cells. Arteriocyte and Johns Hopkins University have
developed the NANEX Stem Cell Expansion technology, which allows for quick
reproduction of universal donor red blood units from umbilical cord blood – and more
research is needed.
 Arteriocyte signed a research and development deal with the Army to investigate new
therapies for orthopedic trauma and battlefield injuries. Arteriocyte is already working
with the US Army Institute of Surgical Research (USAISR) to develop stem cellbased, point-of-care therapies for amputation prevention, burn debridement and postsurgical wound infection prevention. Under terms of the new three-year deal,
Arteriocyte would work with USAISR to explore broader use of its technologies to
treat orthopaedic trauma, such as limb injuries that affect battlefield-wounded soldiers.
The work will involve two Arteriocyte technologies: Magellan and NANEX. Magellan
involves a bedside device that harvests and quickly concentrates stem cells and blood
platelets during surgeries. The concentrated cells can then be fed back to patients to
boost the body’s ability to repair itself. NANEX technology is described above. “These
technologies have significant potential to improve outcomes for our injured personnel
and assist in their healthy recovery to active duty” said Joseph Wenke, manager of
USAISR’s orthopaedic extremity trauma research program. Earlier this year,
Arteriocyte received FDA approval to begin a phase 1 clinical trial that uses the
Magellan technology for the treatment of critical limb ischemia.
7. On the horizon
a. Scientists have for the first time isolated single stem cells that give rise to many different
types of blood cell, from the white cells of the immune system and the platelets that help
to clot blood, to the red cells that carry oxygen around the body. The breakthrough holds
out the promise that it may be possible one day to use stem cells to regenerate the entire
blood system, or to isolate stem cells from individual patients in order to grow their own
personal supplies of blood cells or clotting factors. John Dick of the University Health
Network in Toronto led the study. The study, published in the journal Science6, was
carried out using genetically modified mice that did not have their own immune systems.
This allowed the scientists to grow human bone marrow cells within the animals in order
to target those that are the stem cells of the blood system.
 The team discovered that the single cell type has the CD49f protein on its surface,
which marks it out from the rest. When they transplanted bone marrow and blood
samples minus the CD49f-marked cells, the blood system failed to regenerate.
 The CD49f "biomarker" is vital for further research, because it will enable the genuine
hematopoietic stem cells (HSCs) to be extracted from all other blood stem cells,
some of which will be at more advanced stages of maturity, and so not capable of
turning into all blood types. Dick says doctors might be able to safely regenerate a
patient's entire blood system from scratch, using just a small population of the
CD49f-marked cell, offering new ways to treat people with leukaemia. At present,
such patients would receive new bone marrow from tissue-matched donors, if
available – only a third of patients find a donor. But now it might be possible to
reconstitute marrow from HSCs extracted before chemotherapy starts. Checks could
be done to make sure the HSCs chosen for regeneration are not cancerous.
 Researchers can now also experiment with the HSCs to work out the different stages
and steps by which they develop into all types of blood cells, potentially allowing
them to make specific blood cells by design. "This specific HSC marker, CD49f,
could not only help to identify which cells are capable of long-term engraftment in
patients, but also as a tool to help us generate these cells in the lab from pluripotent
6
Science, DOI: 10.1126/science.1206360
b.
c.
d.
e.
7
stem cell sources" says Robert Lanza, chief scientist at Advanced Cell Technology in
Worcester, Massachusetts. In 2008, the company developed red blood cells from
human embryonic stem cells, and hopes soon to begin testing them in patients.
Scientists at the Salk Institute for Biological Studies have developed an improved
technique for generating large numbers of blood cells from a patient's own cells. The new
technique will be immediately useful in further stem cell studies, and when perfected, could
be used in stem cell therapies for a wide variety of conditions including cancers
and immune ailments.
 "There are further improvements that we need to make, but this takes us a significant
step closer to the ultimate goal, which is to be able to take ordinary cells from a
patient, induce them to become stem cells, and then use those stem cells to rebuild
lost or diseased tissues, for example the patient's bone marrow" says Inder M. Verma,
Irwin and Joan Jacobs Chair in Exemplary Life Science and American
Cancer Society Professor of Molecular Biology at the Salk Institute Laboratory of
Genetics. Verma is senior author (July edition of Stem Cells).
In a report in Nature, a team led by Katherine High at the Children's Hospital of
Philadelphia describes how genome editing reversed haemophilia B in mice, restoring
blood clotting times to near-normal without any apparent side-effects.
San Diego’s Sangart announced in June that it has launched a second Phase II clinical
trial of an experimental drug for boosting the delivery of oxygen in trauma patients who
have suffered large losses of blood. The study of MP4OX will be conducted on about 360
patients recruited from 50 trial sites in 15 countries. All participants will receive standard
treatments such as red blood cell transfusions, fluids, kidney dialysis, surgery and
mechanical ventilation, a company spokeswoman said. Additionally, one group will receive
MP4OX while the other will receive saline.
 An earlier Phase II trial of the drug on 51 trauma patients showed that it quickly
lowered levels of lactic acid, which builds up in oxygen-depleted tissue and can be an
indicator of damage. More patients who received the drug also left hospitals alive
within 28 days. MP4OX helps to open capillaries and carry oxygen deeper into
tissue. The liquid therapy is given alongside blood transfusions and doesn't replace
blood. Karim Brohi, a professor of trauma sciences at the Royal London Hospital, is
the trial's principal investigator.
iBio of Delaware announced successful production of human plasma proteins. Human
alpha 1-antitrypsin7 and human C1 esterase inhibitor8 were successfully produced at
high yield in green plants via the Company's proprietary iBioLaunch technology9. "…
iBio's technology offers traditional plasma protein producers the opportunity to move
away from reliance on the human blood supply and introduce recombinant alternatives
free of any animal or human cell or tissue components" said Robert Kay, iBio's Chairman
and Chief Executive Officer.
Plasma-derived alpha 1-antitrypsin is supplied by several companies for treatment of emphysema due to deficiency
of this protein, and several preclinical and clinical research programs suggest it also may be useful in additional
applications such as the treatment of diabetes and certain types of asthma.
8
Plasma-derived C1esterase inhibitor is an Orphan Drug approved by the FDA to treat or prevent the symptoms of
hereditary angioedema (HAE). In addition, this protein has been used in Europe for more than thirty-five years to treat
acute symptoms of HAE, and is the subject of multiple research programs investigating its potential use in the
treatment of other inflammatory diseases.
9
The iBioLaunch platform is a proprietary technology for development and production of biologics using transient gene
expression in unmodified green plants. The company says advantages over other systems include: success with
proteins difficult or impossible to produce with other methods; broadly applicable to biologics, including monoclonal
antibodies, other therapeutic proteins and vaccines; enables rapid development and validation of modular, scalable,
and optionally robotic, multi-product manufacturing facilities; production time measured in weeks instead of months or
more. The company claims additional benefits include a practically unlimited surge capacity for remedial action
against bioterrorism and pandemic disease; product entry that is unconstrained by traditional process patents, and
significantly lower capital and operating costs for comparable production.
f.
People at risk for Alzheimer's are twice as likely to fall as healthy people, and the disease
may also be visible in scans of the eye, researchers reported at the Alzheimer's
Association International Conference in Paris in July. The studies are part of a widespread
search for ways to detect Alzheimer's before memory problems begin, when drugs and
treatments have a better chance of making a difference. Shaun Frost, of CSIRO, looked to
see whether changes in the retina at the back of the eye -- which is closely related to the
brain -- could be used to detect early Alzheimer's disease. Frost's team found the width of
certain blood vessels were significantly different in people with early signs of Alzheimer's
disease compared with healthy people. People in the small study who had abnormal blood
vessels in their eye also had plaque deposits of an Alzheimer's-related protein known as
beta amyloid on positron emission tomography, or PET brain scans.
g. Scientists have launched a clinical trial of an anti-HIV biotech medicine produced using
genetically modified tobacco. Molecular farming may offer a cheaper way of making
complex biotech drugs and vaccines than traditional factory systems. Project coordinator is Julian Ma, Professor of Molecular Immunology at St George's, University of
London.
8. Legal actions and enquiries
a. An Ontario Supreme Court justice found that victims of Canada’s worst public health
scandal to date were never formally informed that they were entitled to compensation.
The thousands of haemophiliacs and transfusion recipients who received diseased blood
transfusions in the late 1980s and early 1990s were not given notice about a $500,000
sum for victims who contracted blood-borne illnesses other than HIV, hepatitis C and
Creutzfeldt-Jakob disease (CJD). Justice D.M. Brown granted a one-year extension on
the Other Transfusion Claims Trust, after only two individuals made claims in the last 10
years. 20,000 people contracted hepatitis C, and 2,000 people contracted HIV/AIDS in
the tainted blood scandal.
9. Infectious diseases:
a. Mosquito- borne diseases
 Technology developed by Arbovax creates virus host-range mutations that will reproduce
in insect cells while being severely restricted in their ability to reproduce in mammalian
cells. Pre-clinical animal experiments have shown that this approach can be used to
create immunity to insect-borne viral diseases such as dengue fever. Modifications to the
virus are hidden from the immune system and so produce strong immunity in the
absence of disease. The virus can also be grown in a very cost-effective manner in an
insect cell reactor. Arbovax expects to initiate human clinical trials of its dengue vaccine
by the end of 2012.10
 On 9 July, the Sydney Morning Herald reported that increasing numbers of Australians
have been returning home with dengue; travellers appear unaware of the dangers of
becoming infected overseas, particularly in south-east Asia. In Australia, the number who
tested positive to dengue in the three months to March more than doubled from the same
period last year, figures from the World Health Organisation (WHO) show. There had been
354 cases of dengue fever so far this year, compared with 156 last year. Almost
half of them were reported in Western Australia (166 in the first quarter of this year, 85
published in the June edition of Virology Journal, ‘Structural mutants of Dengue Virus 2
transmembrane domains exhibit host-range phenotype.’
http://www.virologyj.com/content/8/1/289
10
last year). The WA Department of Health says no recent infections were contracted in the
state. Nearly all were acquired in south-east Asia, predominantly in Bali. A specialist in
infectious diseases at the James Cook University clinical school at Cairns Base Hospital,
Professor John McBride, says the jump in dengue cases in north Queensland
corresponds with an increase in the spread of dengue fever worldwide over the past
decade11.
 Professor Michael Good from Griffith University says research has shown that a small
number of malaria parasites "hide" in white blood cells and escape treatments targeting
red cells and the liver. He says researchers at the Queensland Institute of Glycomics on
the Gold Coast are developing a vaccine to eradicate the disease. "A different class of
immune cell is induced by our vaccine compared to other types of immunity that are
being developed and that type we believe will target inside the white blood cell as well as
inside the red blood cell" he said. "It will prevent the infection within a patient and
eradicate it as well. We believe this acts like a Trojan Horse where the parasite can
actually hide inside the white blood cell while all the immune response is going on
around it and while perhaps drugs are having an effect outside the white blood cell it is
hiding inside there and then later on the parasite comes out of the white blood cell and
gets into the red cells". (July 2011)
 The University of Glasgow has received a grant from the Bill & Melinda Gates Foundation
to help in the diagnosis of malaria. The $100,000 award goes towards developing a device
which uses mobile-phone derived technology to detect and separate red blood cells
infected with malaria parasites. The researchers hope, if successful, devices based on the
technology could be produced for the masses for rapid and accurate malaria diagnosis.
The study will exploit surface acoustic wave devices which are electronic components
commonly found in televisions, mobile phones and other electronic display devices. The
team proposes to use surface acoustic wave devices to exert selective forces on malaria
infected red blood cells to separate them from uninfected red cells. Different cells respond
to surface acoustic waves in different ways, depending on their physical properties,
including their elasticity and their shape. Since malaria parasites cause red cells to alter
their elasticity and their shape, they should respond differently to surface acoustic waves
at particular frequencies. The team hopes to produce a hand-held device that can identify
infected cells quickly.
 Mosquitoes die soon after a blood meal if certain protein components are experimentally
disrupted, a team of biochemists at the University of Arizona has discovered (reported
July). When the researchers blocked a cellular process known as vesicle transport, on
which the mosquitoes rely to release digestive enzymes into the gut among other
functions, it caused the affected animals to die within two days of blood feeding.
b. Influenza/Avian Influenza
 The Department of Health and Ageing reported on 24 June that flu activity in Australia
was increasing, with the biggest spikes in South Australia, Queensland, and New South
Wales. The 2009 H1N1 virus was the most frequently detected strain, circulating
alongside influenza B. Circulating flu strains are a close match with the ones included in
the seasonal flu vaccine. Queensland Health was reported on 9 July to have estimated a
sixfold increase in flu cases in Brisbane compared with the same time period last year.
Nationally, the number of diagnosed cases by mid-July was some four times the “usual
rate”.
 Preliminary studies in cell culture and mice conducted by researchers at Scripps
Research Institute and the Dutch company Crucell have identified an antibody effective
against a broad array of group 2 influenza A strains, including H3 and H7, both of which

11
Last year, more than 80,000 cases of dengue were reported in Indonesia, compared with 33,443 a decade
earlier. In south-east Asia as a whole, dengue cases numbered more than 210,000 last year, compared with
63,668 in 2000. Brazil confirmed almost 500,000 cases last year.
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
have been transmitted to humans. The group said in a press release on 7 July that the
findings, coupled with their 2009 identification of a similar antibody effective against
group 1 influenza A strains, may offer a combination therapy effective against a wide
range of strains. Group 1 strains include H1N1, which caused pandemics in 1918 and
2009, as well as H5, including H5N1 avian flu. The newly identified antibody, CR8020,
interferes with a binding site, or epitope, on the stalk of the flu virus's mushroom-shaped
hemagglutinin protein, a portion of the virus that varies little among strains (as opposed to
the head, which varies widely and is the target of current vaccines).
Canadian company Medicago reported positive final results from a Phase II human clinical
trial with its H5N1 avian Influenza vaccine candidate. The vaccine induced a solid immune
response and was found to be safe and well tolerated. Medicago's H5N1
vaccine as formulated to protect against the Indonesian influenza virus. It is
manufactured in Nicotiana benthamiana, a relative of the tobacco plant, using the
Company's proprietary VLP (virus-like particles) technology. VLPs may have several
advantages over traditional flu vaccines. They are made to look like a virus, allowing
them to be recognized readily by the body's immune system, however, they lack the core
genetic material, so they are non-infectious and unable to replicate. Medicago's
technology requires only the genetic sequence of a viral strain and not the live influenza
virus. This allows vaccines to be manufactured within four weeks of obtaining the genetic
sequence of a pandemic strain. Current manufacturing technologies which rely on strain
adaptation can deliver a vaccine only six to nine months after a pandemic is declared.
Medicago expects to produce vaccines commercially in North Carolina shortly. It will be
trialing a seasonal flu vaccine candidate in the US later this year.
In late June, Australian company Biota released preliminary data from a flu Phase III
prophylaxis study that showed the protective efficacies of a single, inhaled dose of CS8958 of 20 milligrams and 40 milligrams as measured by the Risk Reduction Rate (RRR)
were 43.7% and 43.2%, but were lower than the preset RRR endpoint of 70%. The trial
evaluated the prevention and safety of laninamivir octanoate in families of influenza A and
B sufferers. The study measured transmission to other household members. Biota said it
will conduct additional trials.
Australian scientist Barry Marshall is planning a drinkable flu vaccine to begin trials next
year. He and J. Robin Warren won the 2005 Nobel Prize in Medicine for their discovery
of the Helicobacter pylori bacterium and its role in gastritis and peptic-ulcer disease.
Marshall founded Ondek, which plans to modify the bacterium, which colonizes the
stomach and can lead to cancer. Researchers will replace cancer-causing genes with
influenza genes to stimulate an immune response. Marshall envisions a freeze-dried
powder or a capsule, which would avoid cold-chain requirements and injection side
effects. A trial of at least 30 people in the US is planned for next year, with results
expected by mid-2013.
The chief of the US National Institutes of Health predicts a universal flu vaccine that
protects against all strains may be within reach in the next five years, replacing annual
shots developed for specifics flu viruses.
Researchers from the University of Hong Kong said an osteoporosis drug called
pamidronate was able to increase a class of human immune cells called gamma-delta Tcells in mice. The cells were effective in fighting various flu viruses, including the H5N1
bird flu virus, according to the findings reported in the Journal of Experimental Medicine.
The drug is set to be tested for this indication in human trials.
Inovio Pharmaceuticals announced that significant T cell and antibody responses were
generated in its Phase I clinical study of VGX-3400X, a SynCon DNA vaccine for the
prevention of avian H5N1 influenza delivered using intramuscular electroporation.
The WHO says the world is better prepared for the next influenza pandemic than it was
in the past. WHO Assistant Director-General on Innovation, Information, Evidence and
Research Marie-Paule Kieny says there have been a number of successes. They
include new developments in production methods, new rules governing vaccine delivery
and progress toward, what she calls the holy grail of influenza vaccination, the
development of a universal vaccine. She notes pandemic vaccine production has
increased markedly from 350 million doses in 2006 to more than 800 million doses now.
She says a Global Action Plan is helping manufacturers in 11 developing countries
produce or increase production of influenza vaccines through financial and technology
transfers. New production of pandemic vaccines has been established in Brazil, Korea,
India and Romania; and the establishment of new manufacturing capacity for influenza
vaccine is ongoing in Egypt, Indonesia, Iran, Mexico, Serbia, Thailand, and Vietnam.
 A preliminary study suggests a breath test measuring the immune response to the H1N1
flu virus could help doctors avoid unnecessary vaccinations for people already infected
with the virus, and prioritize those most in need of them. The study was conducted by the
Cleveland Clinic in Ohio and New Zealand-based Syft Technologies, and published in
the Journal of Breath Research.
 In an effort to overcome the difficult problem of predicting which influenza B strain will
circulate in any given season, MedImmune has filed for US approval of a quadrivalent
(four-strain) flu vaccine containing two influenza B strains.
 10 regions of South Sulawesi in Indonesia are dealing with an unusually large die off of
poultry, even by Indonesian standards. More than 100,000 birds died in two weeks amid
reports of vaccine and disinfectant shortages.
c. vCJD
 The European Parliament decided in early July to support the EU Commission’s proposals
to relax the rules that control the use of animal protein in animal feed. This will permit pig
and poultry protein to be used in animal feed, while maintaining the ban on cattle and
sheep protein thus hoping to prevent another outbreak of bovine spongiform
encephalopathy (BSE) – or “Mad Cow Disease”. Meat and bone meal can be fed from one
species to another – pigs to poultry, and vice versa. The EU is only 40% self- sufficient in
protein animal feed and commodity prices remain very high, so the move will reduce
Europe’s spending and reliance on imported soy bean meal. The European Parliament
decided that the ban would be gradually lifted as further safeguards are put in place.
d. Other
 An immunodeficient woman receiving regular IVIg treatment became paralyzed and died
12 years after her child received the oral polio vaccine. "This patient had the first
nonimported case of paralytic poliomyelitis and the second case of [vaccine-derived
poliovirus] infection reported in the United States since the discontinuation in 2000 of oral
poliovirus vaccinations" wrote Aaron S. DeVries, MD, of the Minnesota Department of
Health in St. Paul, and colleagues. The case offers a caution for patients with primary Bcell deficiency, who may remain at risk for viral shedding and paralytic disease if they were
exposed to someone who had received the oral vaccine before 2000, the
investigators warned in the 16 June issue of the New England Journal of Medicine12.
Poliovirus is known to evolve at a rate of approximately 1% each year, and the
investigators were therefore able to date the patient's exposure to 11.9 years earlier
which was shortly after her child received the oral vaccine. As to why the patient was not
protected by the administration of immune globulin -- which is required to contain at least
minimal titres of antibodies against poliovirus -- the investigators noted that the titre
needed to be protective in immunodeficient patients is unknown. They also noted that
she had received a different immunoglobulin preparation 60 days before she became ill
and speculated that the lot may have contained lower titres of antibody against type 2
12
DeVries A, et al "Vaccine-derived poliomyelitis 12 years after infection in Minnesota" N Engl J Med 2011; 364:
2316-2323.
poliovirus. They concluded that the case underscores the importance of ongoing
surveillance, particularly among patients with B-cell immunodeficiency who could
become a persistent disease reservoir hindering public health efforts to eradicate polio.
 A study in Mekeo in Papua New Guinea has found over 70% of people either have, or
have had, the mosquito borne disease Japanese encephalitis (JE). The disease was
mistaken for malaria or dengue fever by the sufferers, said the study by Dr Takatua
Taufa. JE is caused by a flavivirus that affects the membranes around the brain.
 Researchers have discovered a new strain of gonorrhoea that is resistant to all currently
available antibiotics. Details of the discovery were presented at the International Society
for Sexually Transmitted Disease Research conference in Quebec. This new strain,
called H041, was discovered in Japan and "is likely to transform a common and once
easily treatable infection into a global threat to public health", the researchers claim.
 Two African studies report that taking one or two HIV pills daily can cut down on the
transmission of the disease by almost three quarters. One study found those who took
either the antiretroviral medication tenofovir or tenofovir in combination with emtricitabine
experienced significantly fewer HIV infections than those who received a placebo.
 Vical of San Diego signed a licensing deal with Japan's Astellas Pharma to develop and
sell its TransVax vaccine. TransVax prevents the activation of cytomegalovirus, a
common herpesvirus that is dormant in most people but can cause illness and even
death in those with compromised immune systems. Vical has tested the vaccine mainly
in people who have undergone bone marrow transplants.
 In June 2011, China had 9,773 reported cases of scarlet fever. The year-to-date total
was 30,999. By 13 July, Hong Kong had 874 reported cases year to date, with more than
200 of these in the previous two weeks.
 Horses have died in Queensland and New South Wales from Hendra virus. Human
contacts are being monitored. Of 7 people known to have contracted Hendra virus in the
past, four have died of the disease. Flying foxes are considered the most likely source of
infection. A dog was euthanized after it was thought to have tested positive. A crossborder taskforce including the chief vets of New South Wales and Queensland,
scientists, health officers and the CSIRO is co-ordinating the response.
 In July, South Australian health authorities issued a public alert after a man returned to
Adelaide from overseas infected with measles.
 The WHO set 28 July 2011 as the first World Hepatitis Day, to raise awareness of the
current epidemic.
 The outbreak of E. coli infections that began in Germany sickened more than 4,000
people in 16 countries and caused an unusually high number of cases of haemolyticuremic syndrome, which destroys red blood cells and damages the kidney. An
international team hoping to understand the genetic makeup of the bacteria responsible
has compared its genome to the genomes of 11 related strains of E. coli from around the
world. Their analyses show that the deadly strain likely emerged when a less pathogenic
E. coli picked up a critical set of virulence genes that made it more lethal in humans.
This horizontal gene transfer is common among bacteria. The team, led by Howard
Hughes Medical Institute investigator Matthew Waldor, published its findings in an online
article in the New England Journal of Medicine on July 27, 2011.