On gametocytes:

Now it is to these gametocytes that an extreme interest attaches, because it is to them, and to Manson’s study of them, that we owe the solution of the malaria problem.

- Ronald Ross, 1900 Malaria and mosquitoes Nature. Vol 61(1587) p:524

On the measurement of malaria

Note to begin with that we can never obtain any such estimates exactly; and also that the degree of approximation towards the truth must always depend on the amount of time and energy we have to spare for the task…

- Ronald Ross. 1910. The Prevention of Malaria

(image credit: gandhiserve.org)

What a stirring image! It’s one of my favorite photographs and depicts the potential of science to serve. The Mahatma Gandhi Institute of Medical Sciences a medical university in Maharashtra, India devoted to rural health aptly adopted the image in its logo. The image was taken in 1940 in front of the Sevagram ashram’s guest house, which Bapu later coverted into a 15 bed hospital, and is now part of the institute.

While many captions indicate Gandhiji was observing Mycobacterium leprae, the university suggests the slide contained Plasmodia:

There have been many conjectures about what Gandhiji was looking at in the microscope. Since his intrest in leprosy was well known, it was assumed that he was looking at Mycobacterium leprae. However, Dr KV Desikan, a leprologist of international standing, differs. He says that Shri Prabhakarji, a close associate of Mahatma Gandhi and Dr Sushila Nayar, had told him that Gandhiji was looking at malarial parasites. Prabhakarji has also told him that Gandhiji himself had malaria and had been treated by Dr BC Roy. What he did not know, however, was whether, in the picture, Gandhiji was examining a smear of his own blood. Dr Desikan feels that since Prabhakarji had lived and worked with the doctors during the very inception of the institute, his words would be authentic.

Images from malariastamps.com

Lucid writing, historical depth, and the framing of critical debates in malaria control make this book my favorite recounting of the last 130 years in the malaria world. Actually, this “history of the hostilities since 1880″ no longer covers the immediate events of the past 30 years but that does not matter. The beginning of the book, on the efforts and personality of Ronald Ross, dragged on a bit too long.  However, Harrison is easily forgiven after reading his description of the arguments cast by opposing schools of thought in Italy. On one side was Angelo Celli and the social reformers who advocated land reforms and higher wages to reduce transmission and quinine to control mortality. At the other end was Missiroli and the Rockefeller foundation led by Hackett who wished for nothing short of total war on the mosquito using the larvicide paris green and other new vector control tools. The fundamental question, “Can we control disease without addressing poverty?”, is one that remains controversial today and is not asked often enough.

From James | Parasitesinhumans.org:

A new study published in the Journal of the American Medical Association suggests that the famous pharaoh Tutankhamun was killed by malaria. According to their analysis, Tutankhamun was weakened by malaria and Köhler disease II. Tutankhamun ruled Egypt in 1334-1325 BC and he died at the early age of 19. His famous tomb, full of treasures, was found in 1922. Tutankhamun’s remains were studied from 2007-09 as part of the King Tutankhamun Family Project. In this study Tutankhamun was examined along with ten other royal mummies from 1410-1324 BC and five royal mummies from 1550-1479 BC.

The goal of the project was to introduce a new approach to medical and molecular Egyptology in order to determine familial relationships of eleven royal mummies and discover pathological features attributable to possible murder, inherited disorders, consanguinity, and infectious diseases. Radiological, anthropological, and genetic studies enabled the unraveling of the mystery behind Tutankhamon’s early death and his relationship with other royal mummies found in the same area. They found that Tutankhamun’s parents were siblings which is thought to have been common practice in the pharaoh family. This poor gene pool led Tutankhamun to have malformations, and he likely had severe impairments from birth.

Köhler disease II severely weakened Tutankhamun. Bone necrosis of the foot caused by Köhler forced him to use a walking stick. He had 130 of these canes in his tomb all showing signs of use and there was a fracture in his leg which was propably caused by a fall. Drawings of him sitting in various running activities such as hunting and of medicine for him to take to the afterlife further reference his medical condition. The scientists found a widening of the metatarsal-phalangeal joint space as well as secondary changes to the second and third metatarsal heads. This suggests that the Köhler disease II was still advancing when Tutankhamun died.

The investigators examined the mummies for various diseases such as tuberculosis, pandemic plague, leprosy and leishmaniasis but none were found. They did however identify DNA of Plasmodium falciparum using PCR primers that amplified small subtelomeric variable open reading frame (STEVOR), merozoite surface protein 1 (MSP1), and the apical membrane antigen 1 (AMA1) gene. The evidence of P. falciparum that was present in four of the royal mummies is the oldest proof of malaria parasites in humans. This study is also a rare piece of evidence that malaria was present in ancient Egypt. Ancient texts do mention people used mosquito nets over their beds. It is not clear however how immune Tutankhamun and other people at that time were against malaria but it’s interesting that a modern scourge might have contributed to the death of the greatest pharaoh of all time.

Millions of people owe their lives to Fred Soper. Why isn’t he a hero?

Asks Malcolm Gladwell in his essay The Mosquito Killer. The article is an excellent look at the role played by an American physician in initiating the global malaria eradication efforts of the 50s and 60s.  Gladwell has a very accessible writing style, but sometimes his narrative seems too straightforward… His writing is generally suggestive of a purposeful, yet perhaps artificial, reduction of complexity. In this case the contributions of political climate, national priority, agricultural economics, Soviet and other scientists, and especially George MacDonald’s transmission models are made to pale in comparison to the force of a single, admittedly tenacious, personality.

I had heard of Soper from his role in leading the eradication of the deadly Anopheles gambiae from Brazil (through zealous anti-larval operations across 18,000 sq miles) in the 1930s. It appears, among other achievements, Soper also started PAHO – the Pan American Health Organization which is now the regional arm of WHO. Inspired to learn more, I’ve picked up Soper’s memoirs, Ventures in World Health, from our library and it’s proving to be a fun read.

DDT spraying to control malaria allegedly resulted in cats being poisoned in some areas, which led to increased rodent populations and, in turn, the parachuting of cats into the highlands of the island of Borneo to kill the rodents.

Of course, why not? Everyone knows the rationale response to a rodent menace must involve flying felines – and in large numbers! Another source suggests that in “Operation Cat Drop” some 14000 live cats were parachuted into Borneo. In any case I am indebted to Patrick O’Shaughnessy for his entertaining and meticulous research.

A malariologist troubles himself to understand all of the gathered science of malaria, without regard to what technology has been applied to gather it. This means reading the old literature, a lot. The more I read it and understand it, a clear and somewhat disturbing message sinks in. There are very few malariologists actively publishing today. And the malaria scientists of today do not read or understand malariology. We make fundamental errors of strategy and strategic thinking.

In my readings thus far, this rings true. What the old literature provides is a rare element of perspective – a vantage point of clarity in an increasingly complex landscape. And the lens of history need not restrict our ambitions but can inform and temper our methods. So, where to look? In addition to your standard archived articles at the BMJ, JAMA, and other journals, two fantastic resources are:

1) Google Books – many incredible texts such as The Prevention of Malaria by Ronald Ross (1910) and The Practical Study of Malaria and Other Blood Parasites by JWW Stephens and SR Christophers (1904)

2) The National Library of Scotland – an entire collection of rare public health reports on plague, cholera, kala-azar, and malaria from the British era of India including the classic data of devastating malaria epidemics in the Punjab

The close link between colonial industries and tropical diseases is apparent in this plaque dedicating research laboratories. The last scholarship for filariasis is even funded by a local Maharajah (king).

They have two dusty museums (I would not be surprised if I was the first visitor in months). One is maintained by the pathology department with a great set of clinical photographs, anatomical specimens ranging from enlarged spleens, amebic abscess ridden livers, and data on conditions from former times like black water fever (ie. intense hematuria precipitated by malaria infection in someone undertaking quinine prophylaxis).

The other museum in the department of helminthology is filled with jars of worms, flukes, and other parasites. Below is a photo of Dracunculus medinensis (better known as guinea worm) which has not plagued India since its elimination in 1996. It’s amazing how far we’ve come in just a generation given that my mother remembers hearing about guinea worm in her childhood.

The school is unfortunately a pale shadow of its former self. While it still has some great faculty who conduct tropical disease research when they can,  inclusion of the school into the general health services precipitated its decline. The pressing healthcare needs of the population the school serves and a large number of staff vacancies overwhelm the remaining staff with clinical duties. It is a story well-known in research institutions the world over.