FEAR #7: Malaria

If you’re over the age of 10 then you may have noticed a trend in the way that infectious diseases are reported. When an outbreak occurs in a far-flung nation, TVs and computer screens across the world are lit up with close approximations of a zombie apocalypse.

ebola

While there have undoubtedly been some horrific outbreaks, most recently Zika and Ebola, by their very nature many of these diseases are unlikely to become a long-term scourge on humanity. Often an inaccurate picture of reality is conjured by vested interests to score political points or to maintain their position at the pinnacle of ignorant arseholery

We can only hope that the victims got some help during their disease’s fifteen minutes of fame because once the story has served its purpose and the disease fails to live up to the hype, we don’t hear about it again (Bird Flu? SARS? Swine Flu?). Unfortunately, some diseases won’t toe the editorial line, insisting on providing a constant flow of tragedy that numbs us to their awfulness. Malaria is one such disease.

The name “malaria” literally means “bad air” and the reality of transmission is almost as ethereal. Silent, minute creatures fly into your room while you sleep, inject you with an incurable disease and leave without waking you. It sounds like the nightmare of an anti-vax campaigner, but sadly for the 214 million annual victims the nightmare is all too real.

The Plasmodium parasites that cause malaria line the salivary glands of the Anopheles mosquito. When the mosquito takes a blood meal the parasites are injected into the bloodstream (normally around 10-100 of them) and immediately head for the liver where they enter the cells and replicate like mad. Normally, after one or two weeks the parasite leaves the liver and begins a cycle of infection, multiplication and reinfection of red blood cells.

SPOROZOITES

Mobile forms of the Plasmodium parasite, known as sporozoites, are present in the salivary glands of Anopheles mosquitoes. Credit.

The parasites break out of the red blood cells and into the bloodstream in a synchronised manner. The frequency of these breakouts is dependent upon the species of Plasmodium the patient is infected with, as shown in the table below:

Species % Cases Red Blood Cell Cycle Average No. Parasites per μL of Blood
P. falciparum 50 48 hours 20,000-500,000
P. vivax 43 48 hours 20,000
P. malariae 7 72 hours 6000
P. ovale Rare 50 9000
Data from http://www.mjhid.org/article/view/333/450

This synchronisation is a key factor in malaria’s success; a sudden onslaught of parasites producing toxins is far more difficult for the immune system to fight and is the cause of the spike in fever that is most closely associated with malaria.

If the disease is allowed to develop the situation can become grave, a quick search online offers up descriptions like:

“The pain was so intense; I actually believed I was dying”

Things can get especially bad if P.falciparum is involved. This species can cross into the brain and causes hundreds of thousands of cases of cerebral malaria annually. In endemic regions it is a leading cause of childhood neuro-disability and it can strike with devastating speed. In all, malaria causes approximately 400,000 deaths annually and in the 97 nations where it is endemic (see map below), it is often the primary cause of infant mortality.

malaria map

Always interesting to see how much it follows political boundaries.

In fact, the fight against malaria has gone on for so long that it has left its imprint on human genetics. For example, sickle cell anaemia – a genetic disorder which offers resistance to malaria – is thought to have evolved on several occasions. Unfortunately, people who inherit the gene from both parents tend to suffer from chronic pain and a massively reduced life expectancy. It’s the genetic version of out of the frying pan and into the fire and it kills hundreds of thousands per year.

Less terrifyingly, some West Africans have developed immunity to P.vivax and P.malariae by losing the red blood cell receptor (Duffy Blood Group) that these two species bind to. Furthermore, new-borns can gain resistance from their mother, but it wears off if they do not build up their own by contracting many strains of malaria in childhood. The same is true for adults; if they leave the malaria zone they may lose their resistance.

Thankfully, in the modern world humans are not entirely reliant on good genes and mother’s milk. Current malaria prevention techniques fit into 3 categories: stopping the parasite in humans, stopping the mosquitoes, and prevention of contact between the two.

Stopping the parasite in humans tends to mean drugs. The oldest example of effective chemotherapy is the use of artemisinin by, you guessed it, the Chinese around 2000 years ago. Europeans had to wait another 1700 years until they got their hands on quinine, and it wasn’t until 1934 that the German company Bayer invented chloroquine. Since then several chemically synthesised drugs have been mass produced.

The problem with relying on drugs against such a prolific and deadly parasite is that it encourages overuse and the development of resistant strains. For example, resistance to chloroquine first occurred in the early sixties in South America (it was mixed into salt and flour!) and South East Asia (potentially due to overuse by troops in Vietnam).

What is really required to stop the parasite in humans is a vaccine (because they work, despite what overzealous idiots on the internet say). Potential vaccines have three strategies, anti-infection (stop the parasites before they reproduce in the liver), anti-disease (stop the infection and re-infection of the red blood cells), and transmission blocking (stop the parasite getting back into a mosquito). Previously, promising vaccines have been shown to be ineffective, but the recent development of the RTS,S vaccine, which blocks the parasite before it reaches the liver offers hope. This vaccine has been approved by European regulators and is the first licensed vaccine against parasitic infection of any kind. While this is a massive positive step, RTS,S is only intended for use against P.falciparum – emphasising the problem with combating 4 species at once – and trials showed that it is only effective in infants 27% of the time.

The slow progress with vaccine development means that efforts must be made to reduce the mosquito population. One method is to reduce mosquito breeding sites. Mosquito larvae require standing water to develop so the elimination of open sewers and litter, such as plastic bottles where water can pool, is a must. This requires a concerted effort from individuals on a local scale and does little to help those who live near lakes or swamps.

Population control using insecticides has proven to be controversial; DDT was initially successful, but it persists in food chains and resistance has developed. Regardless of the insecticide, blanket spraying is too expensive for such a large problem and selective spraying is not 100% effective.  A less invasive option is biological control, such as the introduction of fish that prey on mosquito larvae.

The final technique, prevention of contact, has also run into some issues. In tropical climates thick clothing is not a realistic option, but bed nets have been provided by governments and NGOs for night-time protection. But, as anyone who’s slept under one knows, they can be stifling and any gap means mosquitoes can be trapped inside making things much worse. Misuse is also an issue.

Obviously more education on malaria prevention is required, but all is not lost. For those of us who can’t be trusted to look after our own welfare, scientists are working on introducing genetically modified mosquitoes that are resistant to the parasite. This may be a long way from realisation, but a trial using a similar technique is under way in the Florida Keys as part of an effort to limit the spread of dengue fever.

Despite all the flaws in the battle against malaria, using a variety of control methods in concert is beginning to pay off, and it does seem that humanity is finally starting to win. The Roll Back Malaria Campaign claims that from 2000 to 2015, an estimated 6.2 million lives were saved as a result of a scale-up of malaria interventions and around 5.9 million of these were children under the age of five. Furthermore, 19 countries are on the cusp of eliminating malaria. With this in mind, the campaign has set the ambitious target of reducing mortality rates by 90% and eradicating malaria in 35 more countries by 2030. To celebrate, here’s a photobombing mosquito.

JW

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