Africa is facing a public health disaster in the form of multi-drug resistant malaria. People infected with malaria in eastern, central and southern Africa are rapidly becoming resistant to one of the most affordable and commonly used anti-malaria drugs, sulphadoxine-pyrimethamine (SP). Previously, a number of safe and cheap drugs including SP have kept down the number of deaths and people suffering from severe ill health caused by malaria. But there are ominous predictions that disaster looms – unless governments are willing to reconsider their treatment regime.

Sub-Saharan Africa is the region most afflicted by malaria. The disease, along with HIV/AIDS, tuberculosis (TB) and measles are among the most infectious diseases in the world. The poorest people are hit the hardest by this disease, in particular children under five years old and pregnant women. To date malaria has been treatable in Africa with affordable drugs such as chloroquine (CQ), amodiaquine (AQ) and SP. Yet resistance to SP – after CQ, the next affordable anti-malaria drug – is growing rapidly in the eastern/Great Lakes, central and southern Africa. This raises concern about the wisdom of combining SP with another of the anti-malaria drugs.

A study examines the effectiveness of SP on its own as well as in combination with AQ and CQ when used on Ugandan children aged 6-59 months with uncomplicated falciparum malaria. The research was carried out in a rural area where malaria is hyper- (equally endemic, at a high level, in all age groups of a population) to holoendemic (over 75 % of the population have malaria parasites in their blood) and the parasite is carried by 71 % of residents and 91 % of all children aged 2-9 years old. The effects of AQ/SP, CQ/SP and SP treatments on almost 300 children were examined using a 28-day follow-up.

The following findings were made:

• At day 14, treatment failure (early and late) was recorded in none of the children on AQ/SP, in 8 % of those on CQ/SP and in 9 % of those on SP. Thus the clinical response was significantly better for those children on AQ/SP.
• Most of the treatment failure occurred in the first three days for those on SP alone, while for CQ/SP this was true for two out of the eight children.
• During the 28 days, parasitological failure was 4.6 times higher in the CQ/SP group than the AQ/SP group, and 7.4 times higher in the SP group than the AQ/SP group.
• At 14 days, the acceptable parasite clearance rate declined significantly for the CQ/SP and the SP groups but not for the AQ/SP group.
• AQ/SP treatment is significantly more effective than the CQ/SP or SP on its own. However, the relative effectiveness of AQ/SP therapy may be due to the general efficacy of AQ, rather than the AQ/SP combination.
• CQ/SP treatment offered no improvement on SP. CQ in combination with any other anti-malaria drug is likely to fail in this region as it is saturated with mutations linked to CQ resistance.

The report makes a number of recommendations, including:

• The AQ/SP combination treatment is an effective short-term policy option for uncomplicated malaria in countries that have a high CQ resistance and which require affordable treatment for malaria.
• The research data from this study could be used in countries requiring affordable anti-malaria treatment and where resistance to CQ and SP therapy is high, to take up an artemisinin combination regimen which may be more effective in the long term.
• Countries such as Uganda should re-evaluate its decision to use CQ/SP therapy as a first-line treatment replacing CQ. There is growing evidence that the policy of using CQ/SP is not a good one.
• A CQ/SP regimen is not suitable for areas where there is a high resistance to CQ and SP therapies. Areas showing a high resistance to CQ should avoid any therapy in combination with CQ.

While this study finds that the short-term efficacy of AQ/SP therapy is good, the long-term usefulness of this combination is as yet unknown. Thus it may be a good short-term policy but a better long-term approach – such as an artemisinin combination – may be the more prudent way forward.

Source(s):
‘Efficacy of sulphadoxine-pyrimethamine alone or combined with amodiaquine or chloroquine for the treatment of uncomplicated falciparum malaria in Ugandan children’, Tropical Medicine and International Health 9(2): 222-229, by A.O. Talisuna et al, 2004
HINARI subscribers can access the full-text article here. Full document.

Funded by: WHO; Multilateral Initiative for Malaria; Belgian Development Co-operation; Prince Leopold Institute of Tropical Medicine; Fonds voor Wetenschappeljk Onderzoek-Vlanderen

id21 Research Highlight: 23 July 2004

Further Information:
Ambrose O. Talisuna
Ministry of Health Uganda
PO Box 7272
Kampala
Uganda

Tel: +256 77 506 275
Fax: +256 41 345 887
Contact the contributor: atalisuna@kla1.afsat.com or atalisuna@yahoo.com

Other related links:
'Resisting the inevitable? Combining drugs to tackle malaria'

'Resisting change? Tackling drug-resistant malaria'

'All in the mix: combining malaria drugs to beat resistance in sub-Saharan Africa'

'Systematic review: Is Amodiaquine still an appropriate treatment for malaria?'

'Artemether-lumefantrine: is it effective for treating uncomplicated malaria?'

'Sticking with it: linking patient information and chloroquine adherence in rural Ghana'

'A winning alliance: researchers and policy-makers tackle malaria drug resistance'