TDR Tuberculosis
Mumbai has been in the national and international
focus after 12 cases of totally drug resistant (TDR) tuberculosis were
reported from PD Hinduja Hospital. The TDR tuberculosis bacteria is
resistant to all 1st and 2nd line antimycobacterial therapy. In contrast
MDR TB is resistant to INH and rifampicin and XDR (extensively drug
resistant) mycobacteria are resistant also to fluoroquinolones and one
of the three injectable drugs (amikacin, capreomycin and kanamycin). The
Union Government has asked the Maharashtra Government to trace the 12
patients and curtail spread of infection. The BMC has decided to trace
all these patients, counsel them and provide treatment to their
relatives.
TDR TB was first reported from Italy in 2006 and then
Iran in 2009. India is the third country to have this dubious honor. The
gold standard for diagnosis of tuberculosis still remains the 100 year
old microscopy and culture which is prone to false negatives and a long
time lag before results are out. Till culture reports come the patient
is on inappropriate drugs and free to infect others. The fully automated
PCR based test which also assesses rifampicin resistance – Xpert Rif is
not widely available. Since no 1st line antitubercular drugs have been
developed for more than half a century means constant exposure to the
same drugs has increased chances of emergence of drug resistance (Nature
13 January 2012; Totally Drug Resistant tuberculosis in India. Clin
Infect Dis Feb 2012, Times of India 15 January 2012).
Curing Cystic Fibrosis
It has been more than 20 years since the CFTR (cystic
fibrosis transmembrane regulator) gene was discovered to be defective in
the transport of various ions such as chloride and water in this
recalcitrant disease. 90% of people with cystic fibrosis have a
mutation, called F508del, which results in proteins that do not fold
into their proper shape and so get targeted for degradation, reducing
the number of channels. The FDA has just approved a drug Kalydeco (Ivacaftor)
attempting to correct the basic problem in cystic fibrosis. But
Ivacaftor will work only in 4% patients who have the mutation G551D. It
is designed to act directly on the malfunctioning CFTR protein to help
restore the balance of salt and water. Drugs to correct the functioning
of a protein are a new concept while blocking protein functions is
standard in pharmacology.
Drugs in the pipeline for other cystic-fibrosis
mutations include VX-809. This compound seems to protect proteins
affected by the F508del mutation from degradation. Trials of this drug
in combination with Kalydeco are under way to see whether VX-809 will
get the protein to the cell membrane so that Kalydeco could then get it
working (Nature News 7 February 2012, www.fda.gov 31 Jan 2012).
Boycotting Elsevier
Thousands of researchers have joined hands to protest
against the highhanded ways of the Amsterdam based publishing giant
Elsevier. Researchers are miffed because of Elsevier’s high prices; the
practice of bundling journals, which some see as forcing libraries to
subscribe to journals they don’t want to get those that they do; and the
company’s support for US legislation such as the Research Works Act
(RWA), which would forbid government agencies from requiring that the
results of research they fund be placed in public repositories. Since
the beginning of the protest more than 4800 researchers have signed in
with about 200 signatories adding on each day. About 20% of them are
mathematicians but this may not have so great an impact as there aren’t
too many top mathematical journals with Elsevier. What would really
impact would be protests from researchers in biology since they have
many important journals in the field including The Lancet and
Cell. It will take some time to see how far and how powerful this
movement will grow (Nature 9 February 2012).
Newborn Screening
Until now samples of babies born in the state of
Minnesota, USA who had a screening blood test were preserved. Minnesota,
like several other US states, had not asked parents for permission to
store their children’s samples indefinitely and use them in research.
The Minnesota Department of Health holds at least one million such
samples, collected since 1997. Then nine families sued the State that it
must obtain written informed consent to collect, store or use infants’
blood samples. The Minnesota Supreme Court ruled on 16 November in
Bearder v. State of Minnesota that by storing the blood
spots, the MDH violates the state’s Genetic Privacy Act, a 2006 law that
requires informed, written consent for the collection, storage, use and
dissemination of any genetic information. From beginning February
2012,The Minnesota Department of Health (MDH) has started destroying the
stored samples and will now actively ask parents for consent to store
blood spots collected from infants who have been diagnosed with one of
the 53 diseases tested for, and automatically destroy samples from
children who have been given the all-clear. Scientists are enraged since
this was a valuable store of patient material which was being used to
validate many tests such as for congenital CMV, SCID, etc. (Nature 3
February 2012)