Changing National Malaria Treatment Protocols in Africa

PRESS DOSSIER

Changing national malaria treatment protocols in Africa

Wednesday 13 February 2002

Nairobi, Kenya

Contents:

Page

Changing national malaria treatment protocols in Africa: What is the cost and who will pay?……2

Summary tables:

-Per patient costs – proposed mid-term versus optimal treatment prices……………………5

-Estimated supplementary cost of optimal treatment protocol at country level……………..5

Effectiveness of artemisinin derivatives in the treatment of uncomplicated malaria………………6

Country files:

-Burundi……………………………………………………………………………………...7

-Kenya…………………………………………………...…………………………………...9

-Rwanda……………………………………………………………………………………...10

-Tanzania……………………………………………………………………………………..11

-Uganda………………………………………………………………………………………12

Case studies:

-Burundi……………………………………………………………………………………...13

-Kenya………………………………………………………………………………………..15

Changing national malaria treatment protocols in Africa:

What is the cost and who will pay ?

(summary of a paper by Jean-Marie Kindermans)

“As doctors, we want to use effective treatments. We cannot continue prescribing a first-line malaria treatment – such as Fansidar® – which we know is not going to cure the patient.”

Christophe Fournier, Programme Director for Burundi, MSF Paris

Malaria: a few facts

Every year, there are an estimated 300 to 500 million cases of malaria in more than 90 countries worldwide. Ninety percent of cases occur in Africa.

Of the four species of malaria parasites, Plasmodium falciparum is responsible for most deaths – 1.5 to 2 million a year, ninety percent of which are African children.

Malaria remains the first cause of death for children under five in Africa – children are more vulnerable to the disease than adults because their immunity is less developed.

Malaria not only cuts lives short but has a huge socio-economic impact: patients are often bedridden and incapable of carrying out normal daily activities, therefore suffer considerable loss of income and place a heavy burden on their families, the health system and society as a whole.

Treatment

Malaria treatment protocols include both first-line and second-line treatment. Patients with uncomplicated malaria are treated with first-line drugs. Patients with severe malaria and those who don’t respond to first-line treatment are treated with second-line drugs.

Resistance to anti-malarial drugs

In Africa, national treatment protocols have traditionally mandated use of one anti-malarial drug, either chloroquine or Fansidar® as first-line treatment. But in recent years, resistance to these drugs has increased dramatically.

Experts now strongly recommend changing protocols to include a combination of drugs. By hitting different biochemical targets of the parasite, drug combinations are more effective and allow for shorter treatment courses. As importantly, they protect each individual drug from resistance.

It is widely agreed that the best current treatment solution is to use artemisinin-containing combinations. Artemisinin derivatives – which are extracted from a Chinese plant – have attributes that make them especially effective: they are fast-acting, highly potent and complementary to other classes of treatment. To date, no resistance to artemisinin-containing combinations has been reported.

National treatment protocols

Despite all the evidence in favour of artemisinin-containing combinations, many governments are changing their malaria treatment protocols from chloroquine to another drug used on its own (= in “monotherapy”), or to a combination of drugs that doesn’t include artemisinin derivatives.

For example, several countries in the East African Network for Monitoring Antimalarial Treatment (EANMAT) have recently switched from chloroquine to Fansidar® monotherapy for first-line treatment of malaria.

Considering the high levels of resistance to Fansidar® in East Africa (e.g. up to 60% or more in parts ofBurundi and Uganda), this short-sighted policy is likely to lead to continued increases in morbidity and mortality as well as a rapid rise in resistance to Fansidar®.

Effectiveness versus cost

Ministries of health are aware of the drawbacks of Fansidar® monotherapy and are planning to introduce combinations. But most are not planning to use the more effective artemisinin derivatives. It’s a question of cost: using a combination of amodiaquine and Fansidar® may be less effective and more likely to increase resistance rates, but treating one adult costs just US$0.25. Using the more effective combination of amodiaquine and artesunate (an artemisinin derivative) costs US$1.30. Coartem® (artemether/lumefantrine) has the further advantage of being easy to use, because the combination has been developed as a one-pill co-formulation – but it costs US$2.40 per adult dose.

Rwanda has 1.2 million cases of malaria every year and is about to change its national treatment protocol. It has been estimated that it would cost the country an extra US$945,000 per year to introduce artemisinin-containing combinations rather than a less effective combination. For Burundi, with 2 million cases of malaria a year, the switch would cost an extra US$1.6 million per year. For Burundi, Kenya, Rwanda, Tanzania and Uganda combined, the annual cost would be US$19 million.

Historical experience shows that the prices of artemisinin-containing combinations are likely to decrease over time as more producers are validated and competition is encouraged. We estimate that the price of the amodiaquine + artesunate combination will decrease from US$1.30 to US$0.60 by 2004. In this case, the supplementary cost of using the most effective treatment would come down to US$6.3 million per year for the five countries combined.

Longer term savings can be achieved by using artemisinin combinations

MSF believes that the only way to prevent the widespread use of sub-optimal, ineffective treatment and further malaria epidemics is to find resources to fund the use of more effective drugs.

The increase in cost today will be repaid many times over in years to come. Using effective treatment saves lives, reduces the number and length of medical consultations and hospital stays, and avoids the expense of ineffective treatment. People return more quickly to their families and workplace, thus reducing the enormous socio-economic burden of the disease.

International aid will be needed

Malaria is one of three priority diseases that the international community has committed to fight. UN secretary general Kofi Annan has estimated US$8 billion a year will be needed for the Global Fund, but so far only $1.9 billion has been pledged and even this amount is to be spread over a three year period.

Providing the cash to change national malaria treatment protocols in East Africa in a sustainable manner is a worthwhile investment and a pragmatic step in combating one of the leading killers in Africa today. Action must be taken now to avoid the needless deaths that will be caused by using treatment that no longer works.

Conclusions / recommendations:

1. When considering changing national treatment protocols, it is essential that financial considerations do not lead to sub-optimal medical choices. Effective drugs that can save lives are available and must be included in national protocols. Other “transition” strategies are short-sighted and merely postpone the necessary switch to more effective treatment. They will also lead to increased incidence of disease and drug resistance. The so-called “transition” strategy proposed by several countries may in fact remain in place for longer than expected, as protocol change is a difficult, expensive process which cannot be repeated every few years. It will also be more expensive in the long-term when it becomes essential to switch to more expensive drugs such as quinine, mefloquine or co-artemether.

1. Developing countries should not be forced to cope with the financial burden of improving malaria treatment on their own. Malaria is a growing worldwide crisis and international aid should be forthcoming to help implement practical solutions. International leaders must follow up on their political rhetoric and make available promised resources. There is great urgency in the case of malaria, and moderate investment can concretely improve treatment and save lives – it is a chance to transform words into actions. Furthermore, considering that international aid covers a significant proportion of the health budget of some developing countries, donors have an ethical responsibility to ensure that interventions are medically appropriate. WHO should work proactively to support the ministries of health in developing countries to adopt effective malaria protocols.

1. Antimalarials produced in Asia should be made available in Africa as soon as possible. UN organisations have a role to play: WHO should expand the existing AIDS drug pre-qualification system to malaria and UNICEF can directly support procurement and distribution.

1. In the long term, a considerable increase in research and development for malaria treatment is also necessary. Medicines for Malaria Venture (MMV) and other research initiatives should be actively supported.

1

Changing national malaria treatment protocols in Africa: what is the cost?

Table 1. Per patient costs – proposed mid-term versus optimal treatment prices.

AQ + SP*
(proposed mid-term solution) in US$ per adult treatment / AQ + AS**
(proposed optimal solution)
in US$ per adult treatment / Difference between mid-term and optimal solutions
Current cost (2002) / 0.25 / 1.30 / 1.05
Target cost (2004) / 0.25
(assumes no change) / 0.60 / 0.35

* amodiaquine + SP; ** amodiaquine + artesunate

Table 2. Estimated annual supplementary cost of optimal treatment protocol at country level.

Country

/ Population / Estimated number of malaria cases per year / Resistance to chloroquine / Resistance to SP / Estimated supplementary cost of optimal treatment*
(in US$ per year)
Burundi / 6.5 million / 2 million / 50-90% / 13-63% / 1,617,000
Kenya / 30 million / 8.2 million / 66-87% / 27-40% / 6,135,000
Rwanda / 7.2 million / 1.2 million / 40% / 16-45% / 945,000
Tanzania / 32.8 million / 8.6 million / 28% - 72% / 15-34% / 6,426,000
Uganda / 21.1 million / 5.3 million / 10-80% / 11-60% / 4,007,000

* Amodiaquine + artesunate

1

Effectiveness of artemisinin derivatives in the

treatment of uncomplicated malaria

 Proven safety and efficacy

• Artemisinin derivatives (artesunate or artemether) are fast-acting and five to ten times more effective than commonly used antimalarial drugs.
• They are quickly cleared from the body, which decreases the risk of emergence of resistance.
• They reduce the number of gametocytes (sexual form of the parasite responsible for transmission) and decrease parasite transmission which, in times of epidemic, could halt the spread of disease and reduce the transmission of resistance.
• In general, artemisinin derivatives do not cause significant side-effects. However, they are not prescribed to women in the first three months of pregnancy.

Prescribing habits must be adapted when using an artemisinin-containing combination: ideally, a diagnosis must first be established by microscopic blood examination or rapid test.

 Using combination treatment

The combination of an artemisinin derivative and a classical anti-malarial drug is currently considered the most effective malaria treatment.

While classical antimalarials can still be effective in some regions, combining them with an artemisinin derivative can help preserve their long-term effectiveness by delaying the emergence of resistant parasites.

The combination of a classical antimalarial that is still effective (such as Fansidar or amodiaquine, depending on existing resistance levels) and an artemisinin derivative has several advantages:

• The artemisinin derivative rapidly kills a large number of parasites, including resistant parasites; then the second anti-malarial, the effect of which is longer-lasting, kills the remaining parasites.
• Combining two drugs for which resistance mechanisms differ helps to reduce the risk of emergence of resistance.

NB: An artesunate treatment course is administered orally over a period of three days. An artemether treatment course is administered intramuscularly over three days.

Burundi

Malaria on the increase in Burundi

In Burundi, the number of cases of malaria has increased alarmingly in the last few years: two million cases were reported in 1999, compared to 200,000 ten years earlier. In October 2000, a malaria epidemic worse than any seen before swept through six of the country’s sixteen provinces. It lasted six months and more than three million cases were reported countrywide (for 6.5 million inhabitants).

For the first time, regions of low risk (high plateaus from 1400-1700 metres’ altitude) were also affected. In these regions, people have poor immune protection, which helped the spread of the epidemic and caused a high mortality rate. Several factors were involved in the emergence and lasting nature of this epidemic: growth of the mosquito population caused by farming in swamp areas, abandonment of the vector control programme due to the 1993 war, and the high levels of resistance to the drugs recommended by the national protocol (chloroquine and Fansidar®).

High levels of resistance to classical antimalarials

In early 2001, MSF, in collaboration with the MOH, carried out resistance studies in Burundi according to the WHO protocol (1996). The results of these studies showed very high levels of resistance to classical antimalarials chloroquine and Fansidar®.

- KayanzaProvince: 54.2% resistance to SP; 42% resistance to chloroquine + SP

- KaruziProvince:91.3% resistance to chloroquine and 66.7% resistance to SP

- CankuzoProvince:63.8% resistance to chloroquine and 32.7% resistance to SP

As a reminder, WHO considers that 25% resistance is the rate at which it becomes imperative to change the treatment protocol.

Unsuitable national treatment protocol

In 2000, Burundi’s national protocol recommends the use of chloroquine for first-line malaria treatment and Fansidar® as second-line.

In 2001, in response to the results of resistance studies carried out in six provinces, the government decides to adopt a “transition protocol” recommending the use of Fansidar® as first-line treatment and quinine as second-line. The use of Coartem (a fixed dose combination of artemether and lumefantrine) is reserved for epidemics only. This protocol therefore advocates a first-line treatment which has been proven ineffective, and a restrictive second-line treatment (5-7 day treatment) which may reduce compliance and increase the risk of resistance.

Since the start of the epidemic, MSF has been asking to use an artemisinin derivative in combination with an effective classical antimalarial. This combination, recommended by most experts because of its safety and efficacy, would have enabled MSF doctors to treat patients effectively and possibly halt the spread of the epidemic.

At the end of 2001, the Burundi government started effectiveness studies for artemisinin-containing combinations: artesunate + amodiaquine, and Coartem. While waiting for the results of these studies, which will not be available for several months, patients continue to be treated with ineffective drugs. Artemisinin derivatives are available in most private pharmacies in Burundi, but they are only prescribed to patients who can afford to pay for the treatment themselves.

MSF and malaria

MSF runs programmes in several provinces of Burundi (Kayanza, Ngozi, Karuzi and Cankuso), and gives support to health centres and public hospitals. MSF teams played a very active role diagnosing and treating malaria patients during the last epidemic (end of 2000, beginning of 2001).

Today, MSF is fighting for the right to treat patients with effective medicines. MSF anxiously awaits the results of the resistance study and consequent government decisions regarding change of national protocol. As it stands, the national protocol recommends giving patients drugs that simply don’t work – MSF considers this unacceptable.

Kenya

Malaria: facts and figures

An estimated 8.2 million cases of malaria are reported every year in Kenya, for a total population of 30 million.

• Malaria is responsible for the greatest number of consultations (30% of new cases in medical centres within the public health service) and is most common reason for hospital admission (22,000 cases per year in public hospitals).
• Every year, malaria kills 26,000 children younger than five – 72 children a day.

Resistance rates and treatment protocol

• Resistance to chloroquine: 66-87%
• Resistance to Fansidar®: 27-40% (resistance is present primarily in the West – in other regions, resistance to Fansidar® is lower or even non-existant).

Treatment protocol: Fansidar® for first-line treatment, quinine or amodiaquine for second-line.

MSF: Fighting the malaria epidemic in Kissi in 1999

Treating malaria is an integral part of MSF’s programmes throughout the country. From June to September 1999, responding to a sharp increase in cases of malaria, MSF worked in Kissi and several districts in Gucha, in the South-West of the country. MSF supported three overburdened health centres by taking care of the most severe malaria cases and setting up mobile clinics. The spread of the epidemic can be attributed to the ineffective use of chloroquine treatment as well as favourable climatic conditions (rains, temperature, etc.).

In collaboration with the Ministry of Health, MSF treated almost 3,000 severe malaria cases in three hospitals and over 30,000 uncomplicated cases. MSF teams used artemether for severe cases and a combination of artesunate and Fansidar® (SP) for uncomplicated cases (one day treatment).

At the start of 2000, MSF set up an epidemiological surveillance system in the Gucha district, which has a population of 100,000 people. The aim was to ensure early detection of another epidemic and implement an artemisinin-containing combination treatment (three day treatment of Artesunate and Fansidar®) in order to reduce mortality and halt the spread of the epidemic. To avoid the emergence of resistance and to keep costs to a minimum, only confirmed malaria cases were to be treated.

At the same time, the Kenyan Ministry of Health changed its first-line treatment protocol from chloroquine to Fansidar®, and mosquito control programmes were implemented nation-wide. Thanks to the combination of these strategies and favourable climatic conditions, there were no malaria epidemics in 2000 and 2001.

Rwanda

Rwanda: facts and figures

Rwanda’s 7.2 million people are still reeling from the effects of genocide, war and large-scale population displacements. 54% of the population is illiterate and 66% live below the poverty line.

1.2 million cases of malaria are reported every year. Malaria is the first cause of death, and mortality is particularly high among infants. The disease is endemic in many areas of the country, including Kicukiru (Kigali), Gikongoro, Mashesa (Cyangugu), Kivumu (Gisenyi), Rwaza (Ruhengeri), Nyarurema and Rulara.

Resistance to anti-malarials

Resistance problems were first identified in 1997. Studies carried out in 1999 confirmed that resistance to chloroquine was high: 33% in Rwaza and 44% in Nyarurema for example. Rates varied according to region and altitude.

Resistance to sulphadoxine-pyrimethamine (SP, also known by its brand name Fansidar®) was in general lower (e.g. 16% in Rwaza), except in Rukawara where resistance was 45%.