Some good research has shown that if all children in a district are treated for malaria just after the beginning of the rainy season, including those who are not sick at all, then all cause mortality, which basically means deaths from diarrhoea and pneumonia, is reduced by up to 30%. However a Mzungu, or someone who lives in Blantyre / Lilongwe where malaria is unlikely, has no immunity. When he is bitten he gets sick after 7 days, becomes very ill over the next 2 or 3 days and is dead in a week. Clearly he needs more radical treatment than someone who is not sick at all.

So what is the best treatment?
Fortunately the wheel has been invented and there is no need for anyone to rush around looking for a new, better cure. The WHO has quiet rightly persuaded most governments in malaria areas that ACT’s are the preferred treatment. Unfortunately in most of Europe and America they still use the awful quinine. More about that later.

So what are ACT’s?
It stands for Arthemether combination therapy. There are many Arthemether derivatives with nothing much to choose between them. They are mostly tasteless, extremely well absorbed after an oral dose and start to work within 2 hours. They kill almost all parasites after about 4 hours, and they have a very short half life, with most of it excreted in 4 hours.

Magic! So what’s the problem?
The problem is the very short half life. Any remaining parasites, and any new ones coming out of the liver, are free to grow again, unimpeded, 8 hours after you swallowed the tablets. So you need to keep taking them daily for at least 7 days. The other problem is monotherapy. If you try and treat a parasite with just one drug, eventually there is a risk of resistance. Hence combination therapies are in. There are 3 common ACT’s. One of the many Arthemether derivatives mixed with lumafantrine, piperaquin or amodiaquin. There is little to choose between them, all have the same idea, the fast acting“kill’em quick” Arthemether with a long acting drug in combination to prevent relapse.

So why should anyone have any problem with malaria when we have the near perfect treatment? And why so many injection abscesses?

First of all as we have already seen in the previous articles, good research has shown that in some places in the world up to 9 out of 10 people diagnosed and treated for malaria do not have malaria. We see it over and over. A visitor up country gets acute fever, diarrhoea and vomiting. Any one with a titter of wit can see this is acute gastroenteritis, and it will either get better with plenty to drink, or it can be treated with an appropriate antibiotic. We recommend norfloxacin. But “malariaphobia” is a powerful force to reckon with. Off they go to a health worker, or they get advice from their friend the IT specialist!

They confidently diagnose malaria, perhaps after looking down a microscope in desperate need of a service, at a dirty, scratched slide stained with bacteria contaminated reagents, seeing something vaguely purple that is probably a squashed platelet and reporting it as “MP+”. They are then given the ACT and they don’t get better. Not surprising, as they don’t have malaria. Then they are told that ACT’s don’t work and they need quinine. As this is often given as a drip, at least the fluids are useful and they get better. The visitor is now convinced that diarrhea and vomiting is malaria, that the recommended treatments don’t work and that he needs a quinine drip every time. Bad news.

So what is the truth?
ACT’s work. There is no true resistance in Malawi, in fact none in Africa. They work extremely quickly. We have used nothing else for the last 10 years, except combi tabs were not available so we gave Artenam and doxycyclin as our combination and we have never had a single failure.

They work so fast that most of the parasites die in 4 hours. This results in a sudden exacerbation of symptoms. You see, the fever vomiting and other symptoms of malaria are due to the toxins released from the ruptured red cell, as described in the first article. So after treatment, the parasites die in about 3 to 4 hours and the red cell is ruptured, releasing all the toxins. So this causes a new wave of symptoms, and because there are more parasites than there were in the last wave, you actually feel a lot worse. Someone who is quite well with a headache and not much fever can become very ill indeed 4 hours after treatment. They may have a fever up to 40, vomit, hallucinate and even go unconscious. This is not because the treatment isn’t working, it is because it is! For that reason people with a lot of parasites in the blood we usually keep in for 4 hours to see how they are after that time and we warn everybody that if they really have malaria, they will get a lot worse 4 hours after the first dose.

Most of our patients say they do not like the new ACT’s. I agree!! The “other drug” often has a lot more side effects than the Arthemether alone and those used to Artenam and doxycyclin usually say they feel worse after ACT’s. Sorry! But they are extremely effective, so put up with it

There is however a more serious problem. Duration. In Falciparum malaria most of the parasites come out at the same time about 5 to 7 days after being bitten. This is why the first symptoms, corresponding with rupture of the first wave of parasitized red cells, are usually after 8 days. However a few may dribble out of the liver up to 14 days, maybe even longer, after being bitten. So a 5 day course of Artenam will result in a relapse in about 10 to 20% of cases. The combination drugs have longer half lives, Piperazine weeks, and lumafantrine a bit variable but around 3 days, so the standard 3 or 4 day course will give a therapeutic level up to maybe the 7th or 8th day after starting treatment. This will make 100% of patients better, but there is still the possibility of a clone coming out of the liver very late and starting a relapse a week later. (If you want to be pedantic, it is a recrudescence, not a relapse!) For almost this doesn’t matter, the packets come with a 4 or 5 day course and they will all be cured. Why? Because the immune system slows the progress down, they get symptoms later, the chances of a clone coming out of the liver after the packet is finished is remote and the immune system will probably polish it off anyway. However, I have seen research that in children, there is still some relapses after the standard dose, so maybe for children the duration of lumafantrine ACT’s should routinely be longer. I leave
that to the experts to decide!

The totally non-immune expat is a different story. He gets the symptoms earlier, has more parasites, sometimes gets treatment very early on and the 5 days plus 3 is often over before the last clone has come out of the liver. So relapses are more common. For this reason we recommend either an extra 2 days of treatment or doxycyclin for 10 days starting on the last day of the course. That way we have seen no relapses since we started using ACT’s. This should not be a problem with Piperazine ACT’s, as the Piperazine component should carry on killing parasites for well over 10 days after the course is finished, but I don’t have enough experience with it yet to see if theory translates into practice.

Can everyone take ACT’s?
Probably. However they are not fully recommended for small babies and I would be hesitant to give all of them to pregnant women. Also children may find them pretty bitter. So for those who cannot tolerate ACT’s and for stubborn mnzungu who say they make them feel ill, Artenam is still an alternative.

Artenam alone can be given for 7 days to small children under 10kg, or to children who absolutely refuse to swallow the ACT. It is also a good alternative for pregnant women. But remember what we said about monotherapy? So I would still give pregnant women doxy afterwards for 10 days. (OK, so it stains the teeth.
Maybe after the 5th month, but is that really an issue if the first baby tooth has a minute invisible brown line on it?)

Are injections better?
Usually not. In fact they are slower to work! The oil based injections may not give you a therapeutic level for 4 hours, whereas after an oral dose they are busy killing parasites after one to 2 hours. In a totally collapsed patient absorption of drugs IM can be even slower. An injection of Artenam or Artesunate may be indicated if you can’t swallow, vomit, and they can’t get a line in. Even then we prefer to give drugs to stop vomiting and give the ACT by NG tube if necessary. We hardly ever give antimalarials by injection.
Are there any alternatives?
Here is a theoretical list

Homeopathic treatment. Only works if you don’t have malaria. We have a special name for those who treat real malaria with homeopathy, we call them corpses. Quinine. Drug of choice in UK, USA and maybe still some other countries, and in Africa is sometimes used as IV for patients who are unconscious.

It is very slow, often after 24 hours there is still the same number of parasites under the microscope (though they are probably dieing). It doesn’t stop sequestration so you can go into full blown multiorgan failure many hours after the first does of quinine. Most of the cases I know who got quinine in the UK last year finished up on intensive care and with renal dialysis. Not surprisingly I prefer Arthemether derivatives!! In fact I really don’t know why they still insist on using it.

Quinine given IV is at least safe, if slow, causes temporary deafness and makes you feel as sick as a dog. However IM it is truly horrible. It causes the most awful abscesses and really should never be given IM if there is any alternative. My advice, if someone comes near you with a syringe of Quinine and you are still conscious, say thank you very much but can I have artesunate please? Malarone. Licensed for treatment, but why bother? Takes longer to get better, has more side effects, expensive and ACT’s beat it in every department. At least for the next few years, leave it as prophylaxis for the rich.

Chloroquin and fansidar. Doesn’t work. May slow the parasites down in immunes long enough for the immune system to gobble them up, but still no longer recommended in most of Africa. Other fansidar lookalikes the same applies: if you get better it probably wasn’t malaria! Mephloquin. Great drug if you don’t mind being off your head for 10 days. Also sometimes used as the “other drug” for single dose ACT mass treatment in some countries, but why bother when other ACT’s are better? Leave it for prophylaxis.

Best advice for travelers?
Carry 5 malaria rapid test kits and a packet of ACT with doxycyclin. If the children find it too bitter, Artenam for 7 days is still OK. If you are going to Europe or America take it with you and insist that the doctors allow you to use it; they cannot legally refuse you to“treat yourself” and it could save you a week on renal dialysis!

Summary
Arthemether derivative combination therapies are the latest recommended treatment for malaria for almost everybody almost everywhere.

There are many different combinations on the market with little to choose between them, but some popular brands may need a longer duration of treatment then the packet suggests.

Monotherapy is frowned upon but may sometimes be best for babies and pregnant women.

A Quinine drip is an alternative for unconscious patients, but intramuscular Quinine is unnecessary and can cause huge destructive necrotic muscle damage.