Malaria Drug Binding Site

by

QUESTION

What is malaria, and drug binding site?

ANSWER

Malaria is caused by a single-celled protozoan parasite of the genus Plasmodium. Five kinds of Plasmodium are known to infect people: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

There is no one drug binding site with respect to malaria: different anti-malarial drugs have different modes of action, and not all are well described. I will briefly outline the proposed mechanism of action of two of the most common types of anti-malarials: artemisinin (and derivatives) and chloroquine (quinine is thought to act similarly to chloroquine).

Artemisinin is thought to have anti-malarial properties by virtue of possessing an endoperoxide moiety, or double oxygen bridge (-Carbon-Oxygen-Oxygen-Carbon). In the presence of intracellular free ion, this moiety is converted by a chemical reaction to “free radicals”, atoms with unpaired electrons which are highly reactive. The free radicals act as alkylating agents and induce cell death, but only those that are already pathologically crippled, for example due to malaria infection. Another hypothesis is that the free radicals directly damage the malaria parasite.

Chloroquine is thought to act by causing buildup of the toxic by-product of hemoglobin metabolism, heme – the malaria parasite usually converts heme to hemozoin, a non-toxic crystal, and stores it in the digestive vacuole. When chloroquine diffuses into an infected red blood cell, it reacts with heme to “cap” it, preventing further conversion into hemozoin. Moreover, chloroquine also converts hemozoin into a highly toxic substance called the FP-Chloroquine complex. This build-up of toxicity leads to breakdown of the cell membrane, and eventual cell death and autodigestion.

Celebral Malaria and Blindness

by

QUESTION

I live in Nigeria. Good friend of mine complained of headaches in Dec 2011. Did an MRI went to Germany had a general check up. Back in Nigeria in January, headaches increase, she gets blind in one eye, following day the other eye, now in Germany where they have induced her into a coma. They said that she got a brain Haemorrage from the malaria. Can malaria bring blindness. What are the chances of surviving and getting back eyesight.

ANSWER

Although rare, brain hemorrhage is sometimes associated with severe cerebral malaria (caused by infection with Plasmodium falciparum, the most deadly form of malaria). This bleeding in the brain could cause blindness—whether the visual impairment is permanent or not depends on the extent of the bleeding and how much damage it caused.

I have found one case in the literature where severe malaria caused a brain hemorrhage which resulted in permanent blindness, and the authors report their case is only the second they have heard of, so this is rare indeed. Similarly, her survival will depend on how well she responds to treatment, which will likely be intravenous quinine, at least at first. Given that she is in Germany, where health care is excellent, I would say her chances are as good as they would be anywhere else in the world. I hope she makes a full and swift recovery!

Malaria, Hepatitis and Cholera Deaths

by

QUESTION

Up to now how many people died of malaria?

Up to now how many people died of Hepatitis A?

Up to now how many people died of Cholera?

ANSWER

It is believed that malaria is singly responsible for the most deaths of humans in history. However, the exact number is impossible to know. Our modern concept of disease as caused by a particular organisms or pathogen is very new, having only really developed in the 19th century, though dating back to the work of Anton van Leeuwenhoek in the late 17th century (he has since been described as “the father of microbiology”).

As such, in the past, diseases were often mistaken for each other, and particularly since malaria has such general symptoms (fever, aches, chills—these are commonly seen in many other illnesses as well), it is hard to determine what people actually died from malaria and which died from other causes. Indeed, this difficulty remains today, making it hard to estimate accurately the number of people who die from malaria even now. The World Health Organisation currently estimates that approximately 700,000 people died last year of malaria, from close to 700 million cases – this actually represents a very low death rate, thanks is large part to global efforts to improve access to diagnosis and treatment.

Hepatitis A is far less common than malaria; there are an estimated 1.4 million cases per year. Most of these are asymptomatic or mild, with a low fatality rate (4 deaths per 1000 people infected in people under 50; that rises to 17.5 per 1000 for people over 50, as older people tend to have more severe manifestations of the disease and a greater risk of subsequent liver complications – note that these data are from the CDC back in 1991). There is a very safe and effective vaccine available against hepatitis A virus (HAV)—almost 100% of people given the vaccine develop antibodies against infection.

Cholera is slightly more common than HAV (3-5 million estimated cases each year, according to the World Health Organisation) but similarly, most cases are of mild severity. Less than 20% of patients develop “typical” cholera with severe, life-threatening dehydration. 100,000-120,000 people are estimated to die from cholera each year.

Is it possible to inherit malaria?

by

QUESTION

I was wondering is it possible for a father who contracted malaria in the Korean War to pass it to his unborn child.

ANSWER

No. Malaria can only be transmitted by the bite of an infected mosquito, and in rare cases, through infected blood, for example from a blood transfusion or organ transplant. Mothers can transmit malaria to their unborn babies via the placenta or through blood during childbirth (this is called congenital malaria) but there is no way that a father could pass malaria on to his child.

Geographic Range of Malaria

by

QUESTION

Has the geographic range of malaria increased over the past 20 – 30 years? I have read that preventative measures have helped lower rates of infection, but I’m interested in the extension of the range itself.

ANSWER

That is a very interesting question, and one that garners quite a lot of debate. Preventative measures have actually also helped to limit the range of malaria globally. For example, malaria used to be relatively common in the Mediterranean basin and south-eastern United States, but control measures (mainly based around killing mosquitoes and removing suitable mosquito habitat) has largely eradicated malaria from these areas.

However, there is concern that on-going and future climate change has and will change the  distribution of malaria globally. For example, some predictions have suggested that malaria might be able to re-establish itself in the Mediterranean and Middle East, due to higher rainfall and higher winter minimums of temperature. Additionally, malaria may be able to spread to higher altitudes in areas where it is already present at low elevations. This is of huge concern in places like Kenya: Nairobi, the capital city (with around 5million people), sits at 1660 m altitude, and as such currently has generally negligible levels of malaria transmission. However, if climate change enables malaria to move up to this altitude, a huge number of people will be at additional risk of infection. Worryingly, there is some evidence from the Kenyan highlands that these changes are already underway.

Having said this, there are also parts of the world which might see malaria transmission ease as a result of climate change. This is particularly the case where rainfall is expected to decrease, or change significantly in relation to temperature. Moreover, some scientists think that on-going control efforts, particularly with respect to the distribution of bednets, vector control and greater coverage of diagnosis and treatment will continue to reduce the geographical spread of malaria over and beyond the changes associated with climate change. These scientists have compiled a map of Plasmodium falciparum transmission now as compared to data from before control interventions were rolled out—the reduction of transmission risk in many parts of the world, are clear to see (see below).

changing plasmodium falciparum map

Maps showing changes in transmission risk and endemicity of Plasmodium falciparum malaria between approximately 1900 (a) and now (b). (c) shows the balance of change in malaria transmission between the two time periods: the higher the negative number, the greater the reduction in malaria transmission. A positive number indicates increased malaria transmission. The different classes of malaria transmission risk are as follows: hypoendemic, prevalence < 10%; mesoendemic, PR ≥ 10% and < 50%; hyperendemic, prevalence ≥ 50% and < 75%; holoendemic, prevalence ≥ 75%. Image reproduced here from Gething et al., (2010), 'Climate change and the global malaria recession', in Nature, volume 465, pages 342-345.

Malaria in KwaZulu Natal

by

QUESTION

How many people are infected by malaria in KZN?

ANSWER

By “KNZ” I assume you mean KwaZulu Natal (for the benefit of other readers, this is a region of South Africa, in the north-eastern portion of the country). KZN is one of the few parts of South Africa that experiences malaria transmission, though effective control measures have reduced its impact as a public health threat.

Up until 1996, South African policy had been to use DDT (even though it was a banned substance) to control mosquito populations, and malaria levels had correspondingly been low. However, after cessation of spraying with DDT, the number of malaria cases increased, to a high of over 40,000 cases in the 1999/2000 malaria season (in KZN, malaria is most commonly transmitted during the wet summer months, from November to May). Since then, the use of DDT as an insecticide has been reintroduced (along with other public health measures, such as switching to artemisinin-based combination therapies for first-line malaria treatment), and the burden of malaria has plummeted.

The most recent data I could find reported less than 3500 cases for the 2001/2002 malaria season, and zero cases in 2002/2003 (though the data I found were only up to February 2003). Efforts to coordinate malaria control between South Africa, Mozambique and Swaziland have also contributed to the success of reducing malaria transmission in the region.

Why not create a vaccine for malaria?

by

QUESTION

Why not create a vaccine for malaria?

ANSWER

There are many teams of scientists working hard to try to produce a malaria vaccine. In fact, only last year, the preliminary results of a vaccine trial were published. The vaccine, called RTS,S, has been produced by GlaxoSmithKline and is in the midst of Phase III trials in Africa.

The preliminary results showed approximately a 50% reduction in malaria incidence, though it is not clear how much of that protection came from the vaccine and how much should be attributed to the vaccine adjunct (a compound given with the vaccine to boost immune responses). The preliminary results also did not include analysis of how much the vaccine prevented mortality due to malaria, and levels of protection against severe malaria appeared to be low.

However, we will have to wait until 2014 for the full and final results of the clinical trial to be made available. In the meantime, other vaccine candidates are being developed, but there are many challenges to overcome. For example, there are five different types of malaria that infect people: these differ significantly in the way they develop in the human host, and so a vaccine appropriate for one may not be effective against the others.

Most vaccine researchers are focusing on Plasmodium falciparum, the most deadly form of malaria, and a vaccine effective against this parasite would certainly do the most to reduce malaria-related mortality. However, Plasmodium vivax also causes high morbidity, particularly in Asia and the Pacific, and so should not be overlooked. Moreover, within each of these species exist different strains in different areas, each of which can be markedly different from a genetic perspective.

Finally, we do not yet fully understand the complex ways in which our immune system reacts to malaria. As such, this presents a challenge to developing an effective malaria vaccine, though many scientists are willing to address this challenge and have made big inroads in the search for a safe, effective vaccine.

Another stumbling block has been inadequate financial commitment; increased resources devoted towards vaccine development would help overcome the scientific and technical obstacles in our way. PATH, coordinating the Malaria Vaccine Initiative, mentions for example that it can cost up to half a billion dollars ($500,000,000!) to fund a vaccine through the full process of development, testing and clinical trials through to licensing.

Malaria Recurrence and Treatment

by

QUESTION

Since September 2011 I had malaria falciparum. The first medication I took was Coartem, after 2 weeks  I had the same symptoms then the test was +1.5 ,i took Coartem again. 2 weeks after the doctor gave me Malarone ,then 19 days it come back . the doc. gave me Quinine -tablets without doxycycline. but no thing change.

Until now each 14-25 days the malaria comes back, I ask my doctor to do any extra test or to do any thing else, but he told me that “I don’t have severe malaria.”  So why all this medication but i still sick??

On 10 feb 2012 I took Artequin. I feel better but after 15 days it came back , then I take Artequin again. I`m confused what to do?
PLEASE HELP!!!

ANSWER

I think I replied to the comment you made on the “Diagnostic Advice” Q&A post – I will copy the response I wrote there below:

It is certainly unusual to have such persistent malaria; usually Coartem cures it very quickly. Where are you obtaining your medication? It could be that the drugs you took were out of date (expired) or counterfeit; this can decrease efficacy and lead to a reduction of symptoms but not a complete cure. Also, what kind of test is your doctor using? If it is a blood smear, you might want to ask if another technician could read the slides, to double-check the diagnosis. I have seen cases elsewhere in Africa where doctors diagnose malaria by default without really examining the blood slide closely. You could try to get a malaria rapid diagnostic test; this looks for specific proteins associated with malaria infection in your blood, and can be more sensitive than blood slides. You can even perform these tests at home, so double check what the doctor tells you.

Otherwise, if you are truly getting re-infected very rapidly, you should look into more effective preventive measures against getting bitten by mosquitoes. This includes sleeping under a long-lasting insecticide treated bednet, wearing long-sleeved clothing at night and in the evenings and applying insecticide to exposed skin.

Malaria and Ross River Fever

by

QUESTION

Is malaria similar to Ross river Fever which is common in Australia? If you have Ross River and get bitten by a mosquito can the mosquito pass it on to some one else.

ANSWER

Ross River fever is similar to malaria in that both are transmitted by mosquitoes. However, Ross River fever is caused by a virus, whereas malaria is caused by a protozoan (single-celled) parasite. Also, the type of mosquitoes they use are different. Malaria can only be transmitted by mosquitoes of the genus Anopheles, whereas the Ross River fever virus is usually transmitted by Aedes or Culex mosquitoes.

Another difference is that Ross River virus also infects lots of other mammals, with kangaroos and wallabies key reservoir species in the wild, whereas the species of malaria which infect humans are more or less limited to us (though there have been cases of human malaria infecting closely related animals, such as gorillas and chimpanzees).

As for your other question, as far as I know there is no reason why a mosquito infected with Ross River virus couldn’t bite multiple humans or other mammals, and thus transmit the disease to several new hosts.

Malaria In Africa

by

QUESTION

What factors cause Africans to get this disease?

ANSWER

The highest number of malaria cases every year occur in Africa, not because of anything specifically due to the people living there (in fact, they may be better protected against malaria than most—I will come onto this later) but because malaria transmission is very high in many parts of sub-Saharan Africa and sufficient preventative measures are still lacking in some places.

Malaria transmission requires specific environmental criteria, such as sufficient temperature and rainfall. These conditions are met in many countries in Africa, and unlike some other parts of the world, temperatures are suitable year-round for the development of the Anopheles mosquitoes that act as the vector for mosquito, meaning that in some places, transmission can occur throughout the year. In addition, many people do not take appropriate preventative measures against malaria; in some cases, this is due to a lack of means to buy items such as insecticide-treated bednets, and in other cases people have not been educated about the dangers of malaria or how to prevent it, so they do not know what preventative measures they should be undertaking.

Organisations such as the World Health Organisation, the US Agency for International Development, the Global Fund, the Roll Back Malaria consortium and Malaria No More are working to improve both access to preventative measures, such as bednets and indoor residual spraying, while also educating people about the need for prevention and also what to do if they suspect themselves or a family member has malaria. These efforts have already reduced the burden of malaria in Africa; the number of deaths is dropping every year, and they hope to have eliminated deaths from malaria altogether by the year 2015.

I mentioned that Africans may be better protected against malaria naturally—scientists have noted that populations living in areas with high levels of malaria have some genetic protection against infection. One example of this is the Duffy antigen. People who are negative for this gene seem to be protected against Plasmodium vivax and P. knowlesi malaria (it was originally thought they were resistant to infection, but more recent evidence from Kenya suggests in fact they still get infected, but do not get as sick). Another is the gene for sickle cell anaemia; despite causing highly debilitating and even lethal anaemia if both copies of the gene are inherited, a single copy of the gene confers strong resistance against malaria. Both of these genetic traits are highly prevalent in African populations.

In addition, early exposure to malaria results in the acquisition of immunity to infection. This, over time, Africans who survive childhood malaria go on to be less susceptible as adults. The exception to this are pregnant women; in order to support the growing foetus, a pregnant women’s immune system becomes much weaker (otherwise there is a risk of the immune system rejecting the foetus). As such, even if she had high levels of acquired immunity to malaria prior to her pregnancy, once pregnant she becomes much more susceptible. This is particularly true for a woman’s first pregnancy.