This is one of the first studies into the clinical outcomes of ACT combination therapy in Sudan and provides useful information for decision-makers working to ensure effective antimalarial protocols in this part of the country.
Both of the artemisinin-based combination therapies tested here were found to be highly efficacious in the treatment of uncomplicated P. falciparum malaria in this area of the Sudan. AS+SP appears to be the better treatment option on the basis of non-PCR corrected responses, showing a lower percentage of patients returning with parasitaemia. The PCR analysis indicates the true efficacy is comparable between both treatments (near 99%), but is, however, limited by a high proportion of indeterminate cases. More realistically, an efficacy between 97–98% can be expected for AS+SP and 88–95% for AS+AQ, acceptable levels after the long follow-up of 42 days after treatment. A rapid parasite clearance and fever reduction was found following treatment with both ACTs. The rise in haemoglobin values and the reduction of the proportion of (moderately) anaemic children after treatment confirms that the malaria parasites were effectively removed from the blood and red blood cell levels rose after treatment.
The ACTs tested also had an effect on gametocytes. In general, the gametocidal action of AS appears to work through preventing the development of new gametocytes rather than clearance of existing ones . In our study, the 20% of gametocyte-carrying infections at enrolment cleared gradually by day 21. Newly detected gametocytes developed in 22% of cases after treatment, which is lower than after monotherapy, at least for SP. A previous study in Upper Nile  showed that 68% of patients (of all ages) treated with SP and 28% of those treated with AQ developed gametocytaemia during the 14 days after treatment, while gametocyte prevalence at admission was only 2%. Gametocidal effect is very important since the sexual stages of parasites are essential for person-to-person transmission of malaria via mosquito vectors.
The main limitations of the study were that the number of patient exclusions were higher than anticipated (15%) due to concomitant febrile illnesses and loss to follow-up, as well as the lack of results for PCR-analysis, caused by samples missing or an inability to provide sufficient DNA on amplification due to low densities in post-treatment samples. Increasing the number of inclusions compensated losses to follow-up. Repeated attempts at PCR-analysis for problematic samples were only partly successful and, therefore, lead to extrapolation about the findings for the missing samples.
At time of writing, a change of national protocols towards ACT in northern Sudan is in preparation – coordinated among health authorities, NGOs and other relevant actors. The first line treatment recommended country-wide is AS+SP, based on reported high efficacy of SP. Northern Sudan is the only country in Africa, which has chosen the option AS+SP . On the basis of the results of this study, this is justifiable. One other study in Sudan on AS+SP and AS+AQ efficacy was recently completed in the Nuba Mountains and also shows high efficacy of 91.2% and 92.7%, respectively, for these ACTs at 28 days after treatment . ACTs with SP or AQ as companion drugs have shown to be very effective in other areas of Africa, provided that the companion drug still maintained a good level of efficacy [19–22]. In the Upper Nile area both SP and AQ were still an effective treatment for P. falciparum and SP has shown high efficacy in various areas of northern Sudan [2, 4, 23]. It remains to be seen whether AS+SP will be equally efficacious in other, e.g. more northern areas of the Sudan. In Southern Sudan AS+AQ has recently been put forward as the therapy of choice . The use of two different therapies would seem a sensible option in a vast country with areas of different patterns of resistance.
An advantage of AS+SP over AS+AQ is that it is more convenient to administer, as SP is given as a single dose and can be administered under observation in a health facility, whereas AQ requires 3 days to complete a course. SP tablets are also easier to take (AQ has a bitter taste). Blister packs of AS+SP, which combine the two drugs and clearly indicate daily tablets to be taken, are currently available for different age categories in Sudan. AS+SP is cheaper than AS+AQ.
Implementation of the new national protocol with AS+SP will hopefully take place as quickly as possible to prevent rising morbidity and mortality. Vulnerable displaced populations in epidemic-prone areas and areas of high perennial malaria transmission should be prioritized. Introduction of ACT will have to go hand in hand with laboratory confirmed diagnosis (microscopy or rapid diagnostic tests) to prevent unnecessary use of valuable drugs (thus minimizing drug pressure) and ensure that non-malarial cases are appropriately treated. The change in guidelines should also filter through all health service providers, including the private sector and drug vendors to decrease the potential risk of SP monotherapy and incomplete dosages. The change will initially require more funds to be made available for malaria treatment. The international community – including many NGOs, the WHO, donors, and the Global Fund – has shown willingness to support countries to change antimalarial protocols [24, 25].
At present, MSF has already started to pilot AS+SP treatment in its project areas in Northern Sudan, i.e. Darfur, Upper Nile and Gedaref, on behalf of the Ministry of Health. The implementation of treatment as well as the future efficacy of AS+SP should be monitored carefully in a number of dispersed sentinel sites, as there is a possibility that SP resistance may further rise before the combination has been made available countrywide.