Nine eleven and Malaria

Here I want to share another astonishing fact regarding Malaria. Do you know that malaria is responsible for 1 - 3 million deaths a year (mostly in sub-Saharan Africa), and this is equal to the death toll from the attacks of 9/11 every 8 to 24 hours. Think of it. More facts will follow.

Diagnosis of TB

Diagnosis of TB may be difficult due to the difficulty in culturing the slow growing organisms in Laboratory. So other methods besides culturing have to be employed. Medical history, chest X-ray & physical examinations are required for correct diagnosis. Currently two tests 1) The TB skin test & 2) QuantiFERON - TB Gold (QFT-G) test are employed to identify both Active & Latent form of the disease.

Testing for TB

As a precaution one should get tested for TB when one feels so. One should get tested if he/she has: -

Ø Spent time with a person having TB disease or suspected to have TB disease.

Ø HIV infection or any other immunosuppressed condition.

Ø Latent TB disease

Ø Gone to country/returned from a country with high active TB disease

Ø Gone to some areas where TB is common (homeless shelters, migrant camp, prison, hospitals etc.)

Ø Injected illegal drugs.

Mode of transmission of TB

Mode of transmission of TB is through air from infected to non-infected person when infected persons cough or sneezes. Each sneeze contains approximately 40,000 of infectious droplets (i.e. droplets containing TB bacteria) and when nearby person breath in these droplets they may become infected. The bacteria after entering a healthy individual settle in the lungs and grow and thus infection starts in the lungs of a new individual. From there they can be transmitted to other parts of the body (kidney, spine & brain) through blood and infect those organs.

One should keep in mind that though TB in lungs or throat is highly contagious that in other parts of the body are usually not. So people should be aware of the fact that person with Active lung TB (there is another Latent form of TB that I will discuss later) can spread the germ and hence family members, friends and co-workers of TB patients are the most susceptible persons to have TB.

Other strains of TB

There is not only one strain that can cause TB, instead there are many. The M. tuberculosis complex includes 3 other mycobacteria which can cause tuberculosis. They are M. bovis, M. africanum and M. microti. The first two types are very rare and cause TB usually to only immunocompromised people, and M. microti is not usually pathogenic. But in some cases it can cause minor infections.

Other names of TB

TB had many other names in the past and the most common was “Consumption”. This name came from the belief that TB consumes people from within with physical symptoms like bloodycough, fever, pallor (paleness) & relentless killing. There are many other names also arising mainly due to the fear in the past, as it was untreatable and extremely deadly. “Phthisis, phthisispulmonalis, scrofula, tabesmesenterica, lupusvulgaris, wastingdisease, white plague (due to paleness of the patient), king’s evil (it was believed that a King’s touch can heal the disease) and many more. This names originated in different communities and due to its ability to affect different parts of human body. Nowadays the term MiliaryTB is still occasionally used when the infection invades the circulatory system and the organism look like millet seeds when seen in x–ray plates although these form of TB is more commonly known as DisseminatedTB.

What is TB?

Tuberculosis (abbreviated as TB for Tubercle Bacillus) is a common and deadly infectious disease caused by the mycobacterium, Mycobacterium Tuberculosis or Mycobacterium bovis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system, lymphatic system, circulatory system, genitourinary system, bones, joints and even the skin. Over one-third of the world’s population now has the TB bacterium in their bodies & new infections are occurring at a rate of one per second. Not everyone who is infected develops the disease and asymptomatic latent TB infection is most common. However, one in ten latent infections will progress to active TB disease, which, if left untreated, will kill more than half of its victims. A rising number of people in developed world contract tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or due to HIV/AIDS. The rise in HIV infection levels and the neglect of TB control programs have caused a resurgence of tuberculosis.

My next focus

Hope you people have enjoyed my posts on Malaria. If you have any doubts or questions regarding Malaria, feel free to me. I will try my level best to solve your problem. Now after Malaria my focus will be Tuberculosis or TB, which, I think all know as a serious health problem especially in Third World Countries as well as in Developed Countries. So from my next posts I will try to give you an insight of TB. Happy blogging and Thank you for your support.

Prevention of Malaria

There are many ways of preventing Malaria. You can also take medicine to cure Malaria. Besides indoor residual spraying for eliminating mosquitoes & use of mosquito nets coated with insecticides during night sleep and insecticide coated bed cloths give good results. Use of DDT in the endemic areas & DDT-spraying the interior walls of living spaces, where mosquitoes land, is an effective control. A new approach, announced in Science on June 10, 2005, uses spores of the fungus Beauveria bassiana, sprayed on walls and bed nets, to kill mosquitoes. While some mosquitoes have developed resistance to chemicals, they have not been found to develop a resistance to fungal infections. Use of prophylactic drugs can be another option: - Currently available anti-malarial drugs include:

· Artemether-lumefantrine (Therapy only, commercial names Coartem® and Riamet®)

· Artesunate-amodiaquine (Therapy only)

· Artesunate-mefloquine (Therapy only)

· Artesunate-Sulfadoxine/pyrimethamine (Therapy only)

· Atovaquone-proguanil, trade name Malarone (Therapy and prophylaxis)

· Quinine (Therapy only)

· Chloroquine (Therapy and prophylaxis; usefulness now reduced due to resistance)

· Cotrifazid (Therapy and prophylaxis)

· Doxycycline (Therapy and prophylaxis)

· Mefloquine, trade name Lariam (Therapy and prophylaxis)

· Primaquine (Therapy in P. vivax and P. ovale only; not for prophylaxis)

· Proguanil (Prophylaxis only)

· Sulfadoxine-pyrimethamine (Therapy; prophylaxis for semi-immune pregnant women in

endemic countries as "Intermittent Preventive Treatment" - IPT)

· Hydroxychloroquine, trade name Plaquenil (Therapy and prophylaxis)

Severity of Malaria

P. falciparum causes the most severe type of malaria. Consequence of severe malaria include coma & death if untreated (specially children & pregnant women). Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver) & hemoglobinuria with renal failure may occur. Renal failure may also cause black water fever, where hemoglobin from lysed RBC leaks into urine. This form cause death within hours or days in more than 20% cases even with intensive care & treatment. P. vivax & P. ovale produces chromic malaria, unlike P. falciparum. In this case the disease relapse months or years after exposure, due to presence of latent parasites in the liver. The largest incubation period reported for a P. vivax infection is 30 years. Malaria is often associated with hypoglycemia which has four causes – (i) High parasitemia (parasite’s inefficient use of glucose); (ii) you don’t as much because of loss of appetite; (iii) depletion of liver glucose & (iv) inhibition of gluconeogenesis.

More on symptoms of Malaria

The classical symptoms of malaria are cyclic occurrence of sudden coldness followed by rigor & then fever and sweating lasting 4 to 6 hr, occurring every two days. There may be a tingling in the skin as well. The symptoms vary with the species on plasmodium involved.

Symptoms of Malaria

As I have promised earlier, I am posting the symptoms of Malaria.

The following symptoms are common in malaria: -

· Fever

· Shivering

· Arthralgia (joint pain)

· Vomiting

· Anemia caused by hemolysis

· Hemoglobinuria

· Convalescence

The life cycle of Plasmodium

The life cycle of plasmodium has two stages. The asexual cycle takes place inside human body whereas the sexual cycle occurs within the body of the female Anopheles mosquitoes. Initially I thought of giving the life cycle in detail, but latter thought against it as it will be too complicated for common people without proper medical/biological back ground and hence may lose interest. So in my nest posts I will focus on symptoms, prevention & cure of malaria, which will be more useful to all.

Distribution and impact of Malaria on Human life

Malaria causes about 350 – 500 million infections in humans & approximately one to three million deaths annually – this represents at least one death every 30 seconds. Majority of the sufferers are children below 5 years. Pregnant women are also very vulnerable. Though many efforts have been made to reduce transmission & increase treatment there has been little change in the global scenario. Malaria is presently endemic in regions around equator, in areas of South America, South & South – East Asia, parts of Middle East and Oceania and much of Africa; however it is in Sub-Saharan Africa where Blue area shows the most Malaria-prone zones in 85%-90% of malaria fatalities occur. If the prevalence of
the world malaria stays on its present upwards rate, the death rate
could double in next twenty years.

More historical facts on Malaria

The protozoa were called Plasmodium by the Italian scientist Ettore Marchiafava and Angelo Celli. A Cuban doctor called Carlos Finlay, who was working in Havana, first proposed that the disease was transmitted by mosquitoes. But it was Sir Ronald Ross, a British doctor working in Kolkata, India proved that it was indeed transmitted by mosquitoes. He showed that mosquitoes are transmitting malaria to birds also isolated the protozoa from the salivary glands of mosquitoes that fed on infected birds. He received Nobel Prize for this in 1902.

History of Malaria

Malaria has infected human for over 50,000 years & may have been a human pathogen for the entire history of human being. The references of malaria were found throughout the history of human life, beginning in 2700 BC in China during Xia Dynasty. Scientific studies on malaria made their first significance in 1880 when a French Army Doctor working in Algeria (Charles Louis Alphonse Laveran) observed parasite inside red blood cell of people suffering from malaria. He then proposed that the cause of the disease is protozoa, the first time protozoa were identified as causing disease. He got Nobel Prize for Physiology or Medicine in 1907.

Female Anopheles mosquitoes

Only female mosquitoes feed on blood, thus males do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. They usually start searching for a meal at dusk, and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by blood transfusions, although this is rare.

The mode of transmission of malarial parasite

Malaria parasites are transmitted to human via female Anopheles mosquito. The parasite's primary (definitive) hosts and transmission vectors are female mosquitoes of the Anopheles genus. Young mosquitoes first ingest the malaria parasite by feeding on an infected human carrier and the infected Anopheles mosquitoes carry Plasmodium sporozoites in their salivary glands.

Cause of malaria

Malaria is caused by protozoan parasite of the genus Plasmodium. The four major species involved (typically infect human) are P. falciperum, P. vivax, P. ovale, & P. malaria. Sometimes another form P. knowlesi is also found. Among them the 1st two cause the most serious forms of disease. These are collectively called malaria parasites.

Meaning of malaria

The term ‘Malaria’ derived from the Italian word “mala-aria” which means “Bad air”. Once it was thought that bad air is responsible for malaria, which off course is not true.

After the discovery of relation between human disease and bacteria, a new chapter of biological science has developed, "Medical Bacteriology". From now on my post will revolve around human disease and microbiology. Let us start with Malaria, one of the most deadliest disease in the world and in particular in India and Africa and the disease which kills around 2 to 8 million people every year. Malaria is a vector-borne infectious disease. It is one of the most common infectious diseases & is considered as an enormous public health problem in tropical & subtropical countries. Approximately 400 million people get affected each year and result in 1 to 3 million deaths annually (mostly among young children in Sub – Saharan Africa). Interestingly malaria is not considered as a disease caused by poverty but is a cause of poverty & hindrance in economic development.

Biological specificity of disease

Koch’s contribution to medical biology continues when he further established the fact of “Biological Specificity”. Now what actually Biological Specificity” means? It actually shows that a particular disease can be produced by a particular bacterium only. Other bacteria either do not produce any disease or may produce another form of disease following inoculation. He established this by trying to produce “Anthrax” disease from different types of spore forming bacillus like hay bacillus.
In the same time another interesting thing happened. J. Joubert, a person with profound medical knowledge collaborated with Pasteur and they together also started working with anthrax, a serious problem at that time. They were unaware of Koch’s advancement but the conclusions made by them were similar to that of Koch, further confirming Koch’s theory.

Koch’s postulate

Robert Koch thus has established the relationship between a specific microorganism and a specific disease. The criteria for this can be generalized as: -

1. The microorganism must be present in every case of the disease;
2. The microorganism must be isolated from the diseased host and grown in pure culture;
3. The specific disease must be reproduced when a pure culture of the microorganism and inoculated into a healthy susceptible host and
4. The microorganism must be recoverable once again from the experimentally infected host.

These criteria has been generalized as Koch’s postulate to show respect to Koch’s work.

Koch and Anthrax

After the discovery that anthrax can be transmitted from infected to healthy animal through inoculation of blood serum, Robert Koch started thinking about cultivating the causative agent of anthrax. To achieve this goal he performed a simple experiment. He took the spleen out from an infected animal and chopped it into fine particles & then dropped the particles in drops of sterile serum. He looked at it hour after hour and observed the tiny rods of bacterium forming long filaments. In between these filaments he also observed ovoid, refractive bodies somewhat different from the original bacteria (rod shaped). He mentioned that these are spores germinated from the original bacteria due to adverse environmental conditions. He was the first to isolate spores of bacteria. He eventually introduced the spores into fresh serum & again observed the formation of rods, filaments & spores. Likewise eight successive transfers of spores into fresh serum has been carried out and after that the spores were introduced in a healthy animal which rendered the animal ill. Finally the rod shaped organisms could again be isolated in culture.

Robert Koch

The proof of bacteria causing anthrax (etiology) was provided by a German country doctor Robert Koch in 1876. He was nowhere near a scientist and had no laboratory. He worked in his home with very primitive instruments and few small animals. He showed that mice cane be infected with by transferring materials (serum) from diseased animals and this he had done up-to a series of 20 mice by successive inoculation. Strikingly in every transfer the same symptoms were observed. He then performed an experiment to observe the bacterium or rather the causative agent as whether it was due to a bacterium was not clear till then.

Bacteria as causative agents of infectious disease

The fact that bacteria can be a potential agent for causing infectious disease came from the study on Anthrax, a serious disease of domestic as well as wild animals, which can be transmissible to humans. From 1850 - 1865 many researchers identified a rod shaped bacteria in enormous amount in the blood stream of infected animals i.e. animals suffering from anthrax. One of them was C. J. Davaine, who showed that the rods are invariably present in diseased animals but undetectable in healthy ones and also the disease can be transmitted to healthy animals by introducing the blood containing the rods shaped elements (bacteria).

Microorganisms as potential threat in surgery

After the invention of anesthesia, surgical treatment became an important part in medical science. Anesthesia gave the doctors the liberty to perform operations of longer duration and complexity. But this increase in time of operation leads to another problem. As time of operation increased the potential of microbes attack on exposed wounds also increased many folds. As a result many people suffered from post operative sepsis and even died. But the actual reason behind sepsis was not understood at first by the doctors. Pasteur by that time already showed the presence of microorganisms in air and developed many ways to prevent organic infusion from getting contaminated by air microbes during his study with “Spontaneous generation theory” (consult earlier posts). Joseph Lister, a young British surgeon was very much impressed by Pasteur’s work & thought that surgical sepsis might be the result of microbial infection of the tissue exposed during operation. He then continued developing many techniques to maintain aseptic condition during operation. Those include sterilization of the surgical instruments, aseptic dressings of the wounds and spraying of antiseptic agents in operation room to minimize air microorganism contamination. These methods gave instant success in reducing surgical sepsis many folds. People were not convinced about his theory but its striking success made every surgeon to follow the aseptic procedures just like canning process was successful in preserving food for long without knowing the reason behind it. This success is also an indirect proof of germ theory of disease.

Early evidence of microorganisms causing disease

As early as in 1813 there was evidence that specific fungi can cause diseases of wheat & rye, and in 1845 M. J. Berkley had proved that Potato Blight was also caused by a fungus. There was an incidence of “Great Potato Blight” in Ireland, which was a natural disaster that has immense effect on Irish history. So the importance of these diseases cannot be overlooked. Not only plants, fungal disease of animals were also in picture and in 1836 A. Bassi of Italy had shown the cause of certain silk worm disease was fungus. And few years later J. L. Schonlein showed that fungus can also cause skin disease to human. But unfortunately these discoveries fail to make medical science believe that microorganisms are responsible for major infectious diseases of humans. Actually they underestimated the capacity of microorganisms due to its small size. Everybody thought that an organism as small as bacteria cannot make much harm to a much bigger animal like human.

Microbes and disease

After observing few roles of microbes in fermentation process let us focus on its role in producing various diseases in human or other animal’s body. This is the most known fact about microbes by common people. Here also it was Pasteur who gave the insight. Pasteur was looking in to the spoilage of beer and wine by undesirable microorganisms & termed the fact as “disease” of beer and wine. He also added that many disease of human might also have similar origin i.e. produced by the growth of undesirable organisms in their bodies.

H. Buchner’s contribution in fermentation

After the discovery of fermentation by Pasteur who also showed that fermentation is far less energy yielding process than aerobic respiration, H. Buchner came out with a very important accidental discovery. Pasteur’s work had showed that fermentations are “vital processes” playing important role of basic physiological importance in the life of many cells. H. Buchner in order to prevent grounded yeast cells kept along with sand from decaying added sugar solutions to it. Astonishingly he found that CO2 formation was taking place, which suggest that grounded dead yeast cells can also ferment sugar solution i.e. the cell free extract of yeast can cause fermentation like the live cell. This is a revolution in Biochemistry & led to the belief that every biochemical process be made possible outside the cell. And thus the chemists came well at last. Their earlier theory that fermentation is a chemical process is actually true. The only difference is the presence of biological enzymes making the reaction possible at physiological temperature.