Malaria: Africa's major parasitic disease 2001

Malaria is by far the world's most important tropical parasitic disease, and kills more people than any other communicable disease except tuberculosis

But since the advent of the HIV/AIDS pandemic, malaria has been relegated to the back pages, far from the minds of health planners. Over the years as AIDS has occupied an increasingly prominent place in the spotlight, almost perversely interest and awareness in malaria (like so many other pressing health problems) has declined in almost direct proportion to the attention devoted to AIDS.

Despite scientist’s best efforts an effective vaccine has yet to be developed, almost all the drugs used in treating malaria are now useless due to widespread resistance and the mosquito, vector of the malarial parasite is itself showing increasing resistance to many insecticides.

Instead we are forced to rely on an ancient toxic foul tasting drug, which by itself does not cure malaria– quinine, discovered over a century ago and still the last line of defence in treating the most severe cases of malaria. To make matters worse, there’s  evidence that the effects of global warming are aiding malaria to make a comeback in places from which it was thought to have been eliminated.

Malaria is a disease of the poor and the world’s poorest people living in rural communities are particularly affected. "Highly malarious countries are among the poorest in the world and typically have low rates of economic growth," WHO said in a report.

Magnitude of the problem

Malaria has gone on killing people year after year silently without much fanfair, noise or attention drawn to it, killing in numbers that rival those due to AIDS; up to 2.7 million people a year it is estimated.  Over 40 million people have died of malaria since the start of the AIDS epidemic 2 decades ago, most of them children under 5 years old.

And nowhere do more people die than in Africa where 90% of cases are found. Malaria accounts for over a quarter of child deaths every year.  

The figures are staggering:

Only a fraction of the amount needed to fight the disease is being spent on control and prevention measures. An annual investment of $1 billion is required to control the disease, today donor countries spend about $120 million per year to combat malaria.

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Economic effects

The socio-economic effects have been devastating. According to a recent study by Harvard University, malaria has the effect of slowing down economic growth by 1.3% a year. Over the last 30 years Africa as whole has lost at least $100 billion dollars due to malaria.

The morbidity and disability associated with malaria is huge. Rural and agricultural communities that comprise the majority of Africa’s population are often particularly hit hard by malaria. The intensity of malaria transmission often coincides with rainy season, a time when agricultural activity is most concentrated, and disease results in lost days of work, contributing to rural poverty.

The cost of malaria, in terms lost economic activity and output, as well as the strain on the health systems are estimated to be as high as 5% of GDP in affected countries. In 1997 estimates of the direct and indirect costs of malaria in Sub-Saharan Africa exceeded $2billion per year, this year the costs will exceed $2.5 billion dollars.

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Prevalence - the current picture

Malaria is found throughout tropical Africa.

In recent years the disease has undergone a dramatic resurgence. The reasons are many and varied. The resurgence is due to:

• The increasing resistance of the mosquito to insecticides
• The widespread resistance of the parasite to many anti-malarials
• The breakdown of malaria control programmes due to war and political instability
• Climate changes and natural disasters
   

The combination of the above factor has led to a dramatic increase in the number and severity of malaria outbreaks. Increasingly the disease is being found in areas it did not normally exist such as highland areas, or those that previously had low rainfall. The effect on populations that had not previously been exposed to the parasite has been devastating.

Already malaria outbreaks have been seen in Mozambique following the massive floods in February. The parasite is wreaking havoc among the 1.3 million people displaced by the war in the Democratic Republic of Congo.

Nearly 36,000 thousand people may have died from the malaria epidemic which hit Burundi since October 2000, according to health officials in Bujumbura. It is estimated that 300 people have been dying daily since October, while some three million cases of the mosquito-borne tropical disease were reported in the country in 2000 alone.

In January 2001, a malaria epidemic was confirmed in nine districts in southwestern Uganda, areas where it didn’t used to exist. In some places, reclamation of land projects may have led to an increase in temperatures and in one place, Kisoro, the irrigation project is blamed for the outbreak. Health officials are reported as saying that some 25,000 people in Mbarara district, southwestern Uganda, had suffered from malaria with at least 100 deaths in a month.

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Transmission

Malaria is caused by the plasmodium parasite single-celled parasites of which there are four species. P.falciparum, P.vivax, P.ovale and P.malariae. The P. ovale, P vivax and P. malariae parasites cause less severe disease, characterised by interment fever and chills, but they usually aren't debilitating or fatal.

Of these, P.falciparum accounts for the majority of infections and is the most lethal. It has systemic effects on the body affecting and damaging organs such as the brain, liver, kidney and lungs as well as destroying red blood cells and damaging vital organs. It is the most common type in Africa.

Malaria is transmitted by Anopheline mosquitoes, the number and type of which determine the extent of transmission in a given area. Transmission of malaria is affected by climate and geography, and often coincides with the rainy season. The mosquito spreads the disease by biting an infected individual, sucking up their infected blood and then passing it onto another person when it feeds off them.

N.B. THE HIV/AIDS VIRUS IS NOT SPREAD BY THE MOSQUITO!

Symptoms

Symptoms of malaria include fever, shivering, pain in the joints, headache, repeated vomiting, generalized convulsions and coma. Severe anaemia (exacerbated by malaria) is often the attributable cause of death in areas with intense malaria transmission. If not treated, the disease progresses to severe malaria. Severe malaria is associated with death. 

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The health burden

Malaria is the greatest single cause of mortality in Africa in 1999 according to the WHO. Malaria particularly affects children under 5 year of age causing over a quarter of all child deaths in Africa.  

Children under 5 years are chronic victims of the disease, because they have not yet had the chance to develop partial immunity to the parasite, suffering from 4 – 6 bouts of infection a year, often requiring hospitalization. Their small underdeveloped bodies are particularly sensitive to the effects of the parasite, afflicted children can die within 48-72 hours of developing symptoms.

In absolute numbers, malaria kills 3,000 children a day, a death toll that is far greater than HIV/AIDS mortality.  In children who survive the effect of repeat attacks result in impaired physical and intellectual development.

Another group who are particularly at risk from malaria are pregnant women. Pregnancy lowers the mothers immunity to malaria, making them more susceptible to infection. The malaria parasite kills red blood cells and causes severe anaemia. Malaria is a major factor contributing to maternal deaths in malaria endemic regions.

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Treatment and resistance

Malaria is a curable disease and there are a wide number of drugs of which perhaps the best known and most commonly used are choloroquine and quinine.  Many of the drugs used in the treatment of Malaria are also used in prevention from disease from non-immune persons a process that is called chemoprophylaxis.  

The fight against malaria is compounded by the ability of the parasite to develop resistance to anti-malarial drugs. Many of the key drugs currently in use suffer from severe build-up of resistance, which is approaching 60% in some areas, rendering them highly ineffective. Kenya and Malawi were forced to abandon Cholorquine, one traditional treatment, due to its failure to fight resistant forms of the parasite, and there is already evidence of resistance to mefloquine one of the newer drugs in SE Asia.

In spite of drug resistance, malaria is a curable disease, not an inevitable burden. Although there is only a limited number of drugs, if these are used properly and targeted to those at greatest risk, malaria disease and deaths can be reduced, as has been shown in many countries. 

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The Roll Back Malaria Initiative

The global initiative to Roll Back Malaria was launched in May 1998 in response to the worsening global malaria situation. It is envisioned as an opportunity for joint action to tackle the threat of malaria for human development. The aim is to halve the global malaria burden by the year 2010.

The WHO Director General and the Regional Directors of WHO’s African and Eastern Mediterranean regional offices have proposed the spearhead for efforts to Roll Back Malaria should be in Africa. Existing WHO initiatives for malaria control in Africa will be taken forward as Roll Back Malaria in Africa.

The need for affordable drugs

One strategy to improve the management of malaria in the home is to use prepackaged doses of antimalarials. TDR sponsored studies showed that prepackaging of anti-malarials significantly improves compliance with the full course of treatment.

This also resulted in improved drug and case management leading to reduced costs and reduced waiting times in dispensaries particularly when coupled with provision of better information to prescribers and dispensers of anti-malarials.

Now, a package of interventions including prepackaged ant-imalarials and appropriate information is under pilot study in populations of about 10 000 each in three districts in Ghana, Nigeria and Uganda

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Prevention and Control

Prevention by Chemoprophylaxis

Measures which protect against disease but not against infection. A person who has never been exposed to malaria will take preventive doses of anti-malarials that prevent the onset of symptoms despite being bitten and infected by the mosquito.

Prevention by effective disease management

Early diagnosis and prompt treatment is fundamental to malaria control. By reducing the number of infected in a population, the number of transmission sources of the parasite is reduced and so then is the transmission rate. It is a basic right of affected populations and needs to be available wherever malaria occurs. Children and pregnant women, on whom malaria has its greatest impact in most parts of the world, are especially important.

A recent study in Tanzania underlines just how important early and effective treatment can be. The study in southern Tanzania, where about half of all malaria hospital admissions and deaths are in children under 12 months was conducted by an international team of scientists.

Working with the WHO's Expanded Program on Immunisation, researchers gave anti-malarial drugs and iron supplements to more than 700 babies as part of their routine vaccinations.  The number of children who suffered severe malaria fell by almost two thirds, and anaemia rates were halved.

Prevention by protecting against infection

Measures that protect against infection are directed against the mosquito vector. These can be personal (individual or household) protection measures and physical barriers e.g., protective clothing, bednets, or chemical such as repellents, or insecticides.  Community/population protection measures make use of insecticides or environmental management techniques to control transmission of the parasite.

Formerly malaria control depended on insecticide spraying, now the selective use of protection methods, including vector control, is proving cost-effective and more sustainable. So, whereas house-spraying is now restricted to specific high-risk and epidemic-prone areas, increasing use is being made of insecticide-treated bednets (ITNs).

The use of insecticide treated bednets (ITNs)

Many studies have shown the effectiveness of insecticide treated bednets ITNs in reducing the burden of malaria in communities. In May 2001,a  Tanzanian study at the KINET project promoting increased use of ITNs by social marketing recorded an increase survival rate of 27% in children aged 1 month to 4 years.

During the period of research ITN use increased from 10% to over 50% over 3 years. The researchers concluded the “ social marketing of insecticide treated nets has great potential for effective malarial control.”

The challenge will be whether ITN use, promoted by social marketing can be sustained in the long term.  Some studies have found the necessary rate of re-impregnation of bednets is not achieved following the initial success of such projects. Permanently impregnated bednets will increase the chances of success.

The cost of ITNs is also an important factor. The subsidized $5.00 price may be beyond impoverished rural families, driving it down in the list of priorities. Calculations of the cost effectiveness suggest that ITN’s and vaccines or of similar value about $20.00 in prevented DALYS (disability adjusted life year).

Vaccines are provided free, and a strong case can therefore be made for governments, international donors and NGOs to work to provide free or heavily subsidized ITN’s particularly for the most vulnerable group, pregnant women and children.

To view the article: http://www.thelancet.com/journal/vol357/iss9267/full/llan.357.9267.original_research.16231.1

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Vaccine Development

There is an increasing interest and level of resources being made available to develop a malaria vaccine, through new, innovative and highly appropriate initiatives.  Whilst the development of a vaccine may eventually provide a broad solution to malaria, the development of an effective vaccine is considered to be some years distant.

In April 2001 it was announced that the first of a series of three clinical trials of a vaccine against malaria, which has been planned through a partnership between a US-based non-profit organisation and one of the leading research-based pharmaceutical and healthcare companies, will begin early next month in The Gambia.

Currently, no vaccine is licensed to protect against malaria. Anti-malarial drugs are available, but the parasite has consistently developed resistance to them, leaving millions vulnerable to the disease

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Development of new drugs

In May 2001 it was announced chemists have finally made synthetic quinine after more than a century of trying, reopening its file as a potential source of new antimalarial drugs. Gilbert Stork and co-workers at Columbia University have made quinine from scratch — a process called 'total synthesis'.

Quinine does not by itself cure malaria, it simply interferes with the growth of the malaria parasite Plasmodium falciparum.

More effective antimalarial drugs such as chloroquine were developed in the 1940s, but by the 1960s, resistance to chloroquine had become widespread. Today even newer quinine based drugs, such as mefloquine have also become useless due to resistance. Most of Africa and Asia are afflicted with drug-resistant strains of the parasite.

“The ability to build the quinine molecule piece by piece could be useful in a search for new, more potent and less toxic variants of the molecule to create quinine analogues that do the same prophylactic job as other anti-malarials while foiling the strategies of parasites resistant to current quinine-based drugs.”  

And In March 2001 it was announced that the pharmaceutical manufacturer GlaxoSmithKline says it has signed an agreement with the World Health Organisation (WHO) to develop a new malaria treatment to be sold cheaply to public health programmes in Africa. The new treatment could be available by next year.

The treatment, LAPDAP, is being made from two existing anti-malaria drugs, chlorproguanil and dapsone and is entering its final development phase. LAPDAP could be effective in some cases where the malaria parasite is resistant to treatments such as chloroquine and sulphadoxine/pyrimethamine (SP).

LAPDAP would be offered at a preferential price for public health programmes, said Glaxo, the world's biggest drugs firm by sales. A joint team from the WHO and Glaxo is overseeing the project and both groups have contributed towards its costs.

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