More Than You Ever Wanted to Know About Malaria

As promised, here is another work-related blog. I have tried to keep the acronyms to a minimum but found it very difficult. The good news for me is that my work life is starting to get interesting. The bad news for all of you is that my upcoming blogs will invariably have a lot more to do with malaria (control) and a lot less to do with goats and beaches. But seriously, some of this stuff is really interesting (at least to me), and I will try my best to convey it in a way that you will also, hopefully, find it more than soporific. Now, the readership of this blog certainly has varying levels of knowledge about malaria. In an effort to get everyone on the same page, I will do a general overview of the disease and the main interventions currently in use to control it. Once that is taken care of, I can get into the interesting stuff in future entries and keep the explanations to a minimum. For those of you know all of this stuff, bear with me.

Malaria is an infectious parasitic disease endemic to most tropical and sub-tropical countries in the Americas, Asia and Africa. In humans, it is caused by 5 species of a parasite of the genus Plasmodium – falciparum, vivax, ovale, malariae and knowlesi – with falciparum by far the most deadly, as well as the predominant species in sub-Saharan Africa. The parasite is transmitted to humans via a mosquito bite, specifically the female Anopheles mosquito. Once inside humans, the parasites migrate to the liver and begin multiplying inside liver cells. After an incubation period, usually 6-15 days, these cells rupture and the parasites escape into the blood stream and infect red blood cells: killing those and infecting new ones. The most common clinical symptoms of malaria include sustained fever, shivering chills, joint and muscle pain, headache, vomiting, fatigue and dry cough. Severe malaria cases can lead to coma and death. Less common is a malarial infection of the brain, known as cerebral malaria, which can cause permanent cognitive impairments and brain damage, with children being much more vulnerable.

Annually, there are believed to be between 300-500 million cases of malaria each year, killing between 1 and 3 million people: 90% of these deaths occurring in sub-Saharan Africa and the vast majority killing children under 5. Adults die much less often from the disease, especially in endemic areas with "stable malaria" transmission, which I explained in a previous blog. (The large range of disease burden estimates is inherent in high-transmission, resource-poor countries with many constraints to adequate diagnosis. This will be discussed further in future entries, so stay tuned. I know you’re on the edge of your seat.) Malaria is the number one cause of death of children in Africa, and among adults, the lost productivity due to illness is estimated to be 1.3% of GDP. In some high-burden areas, it is estimated that malaria consumes up to ¼ of all household income.

Currently, there are 4 main interventions used to prevent and treat malaria in endemic areas. The first is using insecticide-treated bed nets (referred to as ITNs, LLINs, or other acronyms) to prevent the mosquitoes from biting humans, thereby preventing the transmission of the disease. The rationale behind this is that the Anopheles mosquito likes to bite at night. So, if people can cover their sleeping areas, this can prevent transmission. The current nets last 5 years; after that the insecticide wears off, and they become less effective. Many countries give nets out to pregnant women and children (the most vulnerable population) in the public sector hospitals and clinics for free. Prices vary greatly in the private sector, but in Ghana, you can pick one up in a pharmacy for about $7-$10. Bed nets have been shown to be an extremely cost-effective intervention, and they are now a major part of most national malaria control programs. There are also some NGOs and charities specializing in bed nets that you might have heard of across the pond, most notably Nothing But Nets, which partners with the NBA, and Malaria No More, which runs a very successful program with American Idol called "Idol Gives Back."

The second intervention is called Indoor Residual Spraying (IRS), and it involves going door to door to spray the inside walls of residences with insecticide (yes, sometimes even DDT). The rationale here is that the Anopheles mosquito, in addition to liking to bite at night, also prefers to hang out on the inside walls of homes. If we can make it so that they die every time they land on the wall, then that is one less malaria-carrying mosquito. The IRS only has a 6 month duration and can be fairly expensive, but it has still been shown to be another very cost-effective prevention intervention.

The third tried and true intervention is called Intermittent Preventative Therapy (IPT) during pregnancy. This is where pregnant women are able to take a drug during pregnancy to protect themselves and prevent mother-to-child transmission of malaria. In Ghana, the drug used is called sulfadoxine-pyrimethamine (SP, for short), and is, ideally, given 3 times at different intervals during the 9 month gestation. As children and pregnant women are the most vulnerable populations for malaria infection, this makes inherent sense and has been shown to be very effective.

The final intervention, and the one that I am most involved with in my current capacity, is increasing access to the most effective drugs available: artemisinin-based combination therapies (ACTs). Artemisinin is a drug derived from the plant Artemisia annua, or Chinese wormwood, whose antimalarial properties have been known to Chinese traditional herbalists for centuries. In the last 5-10 years, using ACTs has become the WHO (World Health Organization)-recommended treatment for uncomplicated malaria in all endemic countries due to their high efficacy and tolerability. Unacceptable levels of drug resistance have developed to all of the previous first-line antimalarial treatments, including chloroquine, SP, and artemisinin monotherapy, but using artemisinin in combination (as with ACTs) helps prevent the emergence of resistance, since 2 different drugs with 2 different mechanisms of action are attacking the parasite at once. The challenge with increasing access to ACTs is two-fold: first, over half of all malaria cases are treated in the private sector (mostly in pharmacies and community drug seller shops), and second, the natural extraction of artemisinin is costly, which means that ACTs are quite a bit more expensive than the aforementioned alternatives and out of reach for most people. A lot of this taking place in the private sector means less government control, and in resource-poor developing countries, this means that even though effective treatments are on the shelves, much less effective ones are often given (or a fraction of a regimen of ACT is given), which continues to drive drug resistance.

(Worth mentioning here is an exciting donor-funded project being piloted in 9 countries (including Ghana) called the Affordable Medicines Facility – malaria (AMFm), which will highly subsidize the purchase price of ACTs, hopefully making them as cheap as, if not cheaper than, all other alternatives for the end-user. Much more on this to come in future blogs.)

These challenges are also compounded by the difficulties of adequately diagnosing malaria, where the vast majority of diagnoses (especially in the private sector) are presumptive and symptomatic (euphemistically called clinical diagnosis) rather than confirmed with laboratory tests. This practice is actually recommended by WHO in most high-burden countries, especially for children under 5. However, as the main symptom of malaria is fever, it has becoming common practice to equate all fevers with malaria and treat accordingly. And, not surprisingly, more and more studies have concluded that there is vast over-diagnosis of malaria and over-prescription of antimalarials happening. Combined with this growing evidence base of over-diagnosis, studies showing decreasing transmission rates in some countries (thanks to the interventions above), as well as the development of accurate rapid diagnostic tests (RDTs), have made it feasible to take action in some countries. And Ghana is one of those countries. The 2009 Strategic Plan from Ghana’s National Malaria Control Program (NMCP) calls for moving from clinical diagnosis to laboratory or RDT-confirmed diagnosis. While this is an exciting paradigm shift, indeed, it is one thing to have it on paper, and another thing entirely to roll it out in practice (especially in the private sector).

So there you have it: Malaria 101 brought to you by Scott(y). Don’t say I never gave you anything. As you can see, there are several cost-effective proven interventions in the arsenal, which makes malaria control a very dynamic field to be in. However, challenges remain, especially in relation to leveraging the full potential of the private sector (“leveraging” is business speak for “using to the fullest”), which is why working with pharmacists is an exciting place to be. There will be much more on malaria to come, and you have been adequately warned, so try to contain your enthusiasm. And, to answer your question: no, there is not a vaccine (yet). The farthest one along in the pipeline is British pharmaceutical giant GlaxoSmithKline’s (GSK) RTS,S candidate. It is in phase III clinical trials, but it is at least 3 years away and will most likely only be partially effective (30-60%).

I know that I used the word gestation is this post, so I hope it wasn't too much like a science lesson. And I apologize about the lack of pictures. I’m tired of acronyms, aren’t you?