In medicine, mysteries lurk, waiting to be solved.
Why were hundreds of children dying every year of unexplained
encephalopathy every year in Muzafarpur? The question has haunted
physicians for two decades. Now the bits of evidence collected over
years have been pieced together to solve the puzzle. A large
case-control study published in the Lancet Global Health in
January 2017 examined various possible etiologies to explain the
recurrent epidemics, and confirmed that the real culprit is the litchi
fruit.
The epidemics happen every year between April and
July, affect hundreds of children with 40-60% mortality. Children who
had been perfectly normal till the previous day would usually present in
early morning with encephalopathy and seizures. Hypoglycemia had been
observed in many. Previous studies had ruled out Japnanese B
encephalitis. It was noticed that the cases occurred in areas where
litchi cultivation was rampant, and occurred mainly in the litchi
season. In 2014, Dr Jacob John from Vellore and Mukul Das from CSIR
hypothesized that hypoglycin A and methylene cyclopropyl glycine (MCPG)
contained in litchi induces hypoglycemia and also interferes with beta
oxidation of fats in the mitochondria resulting in encephalopathy and
seizures in malnourished and predisposed children.
In the present study, blood, urine and CSF samples of
children with unexplained acute encephalopathy in the epidemic season
were collected. Litchis from the particular area were also collected.
Biological samples were tested for various infectious etiologies and
litchis were tested for pesticides and MCPG. Urine organic acids and
plasma acyl carnitines were also tested to look for interference with
beta-oxidation of fats. There was no evidence of infectious etiology to
explain the epidemics. However, they found abnormal urine organic acids
in the form of elevated ethylmalonic, glutaric and adipic acids, which
suggest a block in fatty acid oxidation. Unripe litchis were found to
have higher concentrations of hypoglycin A and MCPG.
The final understanding is that during the litchi
season, children gorge on the fruit and go to bed without an adequate
meal. Both gluconeogenesis and fatty acid oxidation is affected by the
hypoglycin and MCPG. In children who are already malnourished, neither
the glycogen stores nor the fats can be metabolized leading to acute
encephalopathy. Children in Muzaffarpur are now being advised to take an
evening meal and avoid ingesting unripe litchi fruit. A beautiful piece
of investigative medicine indeed!
(The Lancet Global Health 31 January 2017)
US FDA Bans Antibiotics in Livestock
The US FDA has banned the use of ‘medically
important’ antibiotic use in livestock used for food. It has been a long
and arduous road to reach this point. In the 1940’s, it was discovered
that mixing sub-therapeutic doses of antibiotics in the feed of poultry
and cattle resulted in increased weight. In the 1950’s, FDA approved use
of penicillin and tetracyclines as feed additives for livestock as a
cost-effective strategy of increasing food production. Thereafter, the
Swan report from UK warned of increasing antibiotic resistance in humans
due to their overuse in livestock. Efforts by the FDA to ban use of
these antibiotics in livestock were vigorously resisted and finally
thwarted by the farmer and pharmaceutical lobbies.
For 34 years, the world slept as antibiotic
resistance mounted. Around 70% of all medically important antibiotics
were being used in the farming sector. In 2011, a group of consumer
protection activists sued the FDA for not taking any action in the face
of glaring evidence of the evils of antibiotics in the livestock
industry. The FDA finally woke up, and in 2013, recommended voluntary
reductions in antibiotic use. In 2016, the UN held an unprecedented
meeting declaring antibiotic use in livestock feed as a global health
emergency. In the wake of the ban by the FDA, now in the US, livestock
can receive antibiotics only after a prescription from a vet.
(Nature News January 2017)
The ‘Paperfuge – Frugal Medical Technology
Manu Prakash, an Assistant Professor of
Bioengineering in Stanford, went to a rural clinic in Uganda, and
noticed that an expensive centrifuge was being used as a doorstopper
because there was no electricity to use it. He began musing on ways to
develop a low cost centrifuge for the laboratory there with his
postdoctoral research fellow. They decided to use a common toy called a
whirligig. This is basically a wheel that is made to spin by both hands
pulling on a thread looped through the centre. He set up a high speed
camera, and was astonished to find that it was spinning at 10000–15000
rpm. Three undergraduate students from MIT were roped in to develop a
mathematical model.
The team created a computer simulation to capture
design variables like disc size, string elasticity and pulling force.
They then created a prototype that could spin at 125,000 rpm. They put
in a capillary of blood into it, and were able to separate the blood
into layers. From laboratory-based trials, they found that malarial
parasites could be separated from red blood cells in 15 minutes. And by
spinning the sample in a capillary precoated with acridine orange dye,
glowing malarial parasites could be identified by simply placing the
capillary under a microscope.
They call this paper centrifuge a ‘paperfuge.’ Field
trials to use it in diagnosis of malaria have just been completed in
Madagascar. Manu Prakash‘s laboratory believes in frugal design
philosophy. They dream of developing medical equipments, which do not
need a whole lot of money. By thinking, we can transform medicine. (Nature
News 10 January 2017).