Tuesday, February 24, 2015

H1N1 Swine Flu - The Burden of Import Dependent Diagnosis

(Note: When this piece started out as a prospective op-ed article, the H1N1 death-count was around 650. Today - 18Mar15 -  it has crossed 1800)

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Your child has developed a fever. Could it be Swine Flu? Perhaps it is Bird Flu or Monkey Flu?  

It is difficult not to panic when you have been getting bombarded with daily reports on skyrocketing infections, a rising death toll, shortages of diagnostic kits and medicines.

Unfortunately, our nationwide response to the spread of H1N1 Swine Flu has been just that - reactive rather than proactive. There has been a sudden rush to procure diagnostic kits; an increase the number of ‘authorised outlets’ selling drugs; A DGCI letter to requesting states to ensure that  diagnostic kits and drugs are available at the “right price”, and an awareness campaign that leaves you with more questions than answers.

Meanwhile, the number of deaths has climbed to 1537, and the number of confirmed cases has shot up to over 27,000. The list now includes film stars, top bureaucrats, and senior politicians.

Accurate Diagnosis is the Key

Accurate diagnosis is the first and most critical step in disease control.

For many known diseases the diagnosis and treatment protocols are centred on something called Antigen-Antibody Reactions. Antigens and antibodies are molecules with unique shapes that tend to lock into one another. Antibodies act like policemen in our blood-stream, waiting to ‘handcuff’ any foreign antigens that slip in. Most vaccines contain antigens that provoke our immune systems to produce more antibodies, in case of a real attack. Diseases like measles, for instance, have only one antigenic-type, and this makes the vaccines relatively easy to make, and are therefore quite affordable.

Indian vaccine manufacturers are quite strong in this area. They supply 90 per cent of all measles vaccines worldwide, as well as half of WHO’s requirement for DPT and BCG vaccines against tuberculosis.

Influenza or Flu is caused a much smarter virus. It keeps changing its cell-surface proteins so frequently that detecting it accurately and then formulating drugs to counter them becomes rather difficult.  According to the US Centre for Disease Control there are now more than 800 different influenza viruses. This flu season, the annual influenza vaccine in USA proved only 23% effective. Last year, it was about 60% effective.

When it comes to diagnosis, the only reliable way identifying the flu virus comes from a method called Real Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).

Why is RT-PCR Test so Expensive?

RT-PCR is a technique that amplifies genetic material to get a detectable signal. Its accuracy and reliability has made it the cornerstone of modern molecular biology.

The starting point for this test is Deoxyribonucleic acid (DNA), a molecule that encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses.

Despite its unwieldy name, the RT-PCR machine is essentially a hi-tech heater. It ‘melts’ DNA strands at high temperatures and re-joins them again at lower temperatures using special enzymes called polymerases.

Every organism has certain nucleotide sequences which are unique to it. These ‘signature sequences’ are first carefully identified and recreated as “primers”. Detection of H1N1 Swine Flu usually begins with the DNA extracted from a sample of body fluids of an infected person.  It is mixed with H1N1 primers and probes are introduced into a RT-PCR machine.  If the primer finds a match, the machine creates multiple copies of it. Over time – usually 24 hours – there is enough of the genetic material that can be detected by running it through a device called gel chromatograph.

Most of the RT-PCR machines used in India are imported. Apart from the high cost of these machines, the cost of critical consumables - imported primers, probes, enzymes and assays - continue to drive the high cost of accurate diagnosis.  So even the minimum cost for a test comes to about Rs.4,500.

We also have home-grown pioneers like Molbio (Goa) and RAS LifeSciences (Hyderabd) who have developed indigenous, portable PCR kits that lower the cost of the tests to Rs. 800. Despite getting clearances from DCGI and ICMR, the state governments prefer to procure imported kits.

This state of affairs in not unique to diagnostic devices. According to a KPMG report (2011), even though there are about 700 medical device makers in the country, India imports approximately 75 percent of devices.

Is There a Better Way Forward?

Coming soon after the Ebola scare, our tardy response to the H1N1 influenza ought to set the alarm bells ringing.

As the number of nationwide flu-related deaths crosses 1600, we need to ask ourselves if we are sufficiently prepared to tackle the new cohorts of emerging drug-resistant diseases.

We already have world class facilities for manufacture of vaccines and pharmaceuticals. Will the ongoing Budget Session of Parliament introduce the much needed amendments to the Drugs and Cosmetics Act, 1940 – especially with respect to medical devices? Can the on-going ‘Make in India’ initiative pull together the key players in the Government and the private sector, to create the right policy environment for reducing our dependence on expensive, imported diagnostic kits?

Unless we get our act together, we are bound to lurch helplessly from one round of infections and pandemics, to another.
  
REFERENCES

·         DGCI Notice to states - H1N1 / SwineFlu Diagnostic Kits being sold at exhorbitant prices -- http://cdsco.nic.in/writereaddata/swine%20flue.pdf
·         National Centre for Disease Control (NCDC) -- http://www.ncdc.gov.in/
- Procurement of RT-PCR kits -- (11,12) -- http://www.ncdc.gov.in/writereaddata/tenders/160.pdf
·         Dr. Path Labs – List of Molecular Diagnostic Tests - http://www.lalpathlabs.com/genetics.aspx
·         (28Feb15) - http://indianexpress.com/article/india/india-others/swine-flu-deaths-breach-1000-mark-40-more-succumb-to-virus/
·         (9Mar15) - DRDO-RAS diagnostic for SwineFlu -- http://www.thenewsminute.com/news_sections/3181


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