The study was carried out between July and December, 2007 in Uyo, Southern Nigeria. Uyo is located on latitude 5⁰03' North and longitude 7⁰57' East. It is the capital city of Akwa Ibom State Nigeria. Akwa Ibom State is located within the lowland coastal plain region of Nigeria between latitude 4⁰32' and 5⁰53' North and longitude 7⁰25' and 8⁰25' East. The state lies on the Eastern Niger Delta and shares the hot humid tropical climate of the region marked by two distinct seasons – dry (November to March) and wet (April to October) seasons. As in the entire country malaria is endemic and the transmission is intense (stable) and peaks during the rainy season.

This study followed the World Health Organisation⁷ recommendation, for the in-vivo investigations of antimalarial drug efficacy, in terms of treatment, follow up and data analysis. The study was conducted in children with fever weighing 5-25kg, who were attending Nedeke Paediatrics Specialist Hospital, Uyo, using the WHO 28 day in-vivo protocol, patients, were enrolled in the study, if they satisfied the following inclusion criteria, weight between 5 and 15 kg, monoinfection with P. falciparum parasitaemia, with parasitaemia in the range of 1000 to 100,000 asexual parasites per l of blood, presence of auxiliary temperature  37.5⁰C and a history of fever in the preceding 24 hr, informed consent by parents and guardians, ability to come for the stipulated follow-up visits and easy access to health facility. Key exclusion criteria were presence of general danger signs such as inability to drink or breastfeed, vomiting everything, recent history of convulsion, lethargic or unconscious state, unable to sit or stand up and use of any drug known to influence cardiac function (e.g. Halofentrine) within 4 weeks before screening. Also excluded were those showing signs and severe and complicated falciparum malaria namely cerebral malarial. A detailed inclusion and exclusion criteria has been given elsewhere^8,9.

Since there was no existing medication approved for a direct comparison, an open label, non comparative trial of three day regimen of artermisinin based tablet coartem (co-artmethar) comprising artemether 120mg plus lumefantrine 20mg was used in this study. The enrolled children (5-25kg) were allocated to one of three body weight group, 5 – 10kg or 10-15kg each given six doses of one coartem tablet. 15-25kg, each given six doses of two coartem tablets. Doses were administered under doctor’s supervision at 0, 8, 24, 36, 48 and 60 hours. Tablets were given with food or drink whenever possible. In children who were unable to swallow tablets, the tablets were crushed and suspended in sterile water for dosing. Treatment began on the day of enrolment (day 0). After drug administration on day 0, the patients were asked to return on days 1 and 2 to complete the drug regimen and for clinical assessment. They were also given appointment papers for days 3, 7, 14 and 28 for clinical examination and blood smears. Patients were also asked to return to the clinic on days other than these if they developed any additional complaints or any change in their condition compared to pre-administration of the drug if a patient did not report at the hospital for the scheduled visit, every effort was made to trace them to their homes.

Adverse events, unsatisfactory therapeutic effects, loss of patient to follow up, patients non-compliance or consent withdrawal as a result of treatment failure were criteria for discontinuation. All discontinued patients were followed up for 28 days for safety assessment where possible.

This was determined based on parasitological cure rates on days 7, 14 and 28 by the times to parasite and fever clearance and from the proportions of patients without gametocytes. Recrudescence denoted clinical recurrence of malaria after the initial clearance of parasite from the circulation. Parasite reappearance was interpreted as either true recrudescence or a new infection. In this study treatment efficacy for cure rates was described as uncorrected since DNA polymerase chain reaction (PCR) analysis was not performed.

All adverse events were monitored and recorded on case report forms. Treatment emergent symptoms of malaria were defined as adverse events occurring anew or worsening from baseline but occurring before possible recurrence of parasitamia.

Assessment of possible treatment related adverse events during acute diseases is difficult, due to the background dominance of malaria related signs and symptoms. Malaria clinical features were therefore recorded at baseline, during treatment and during follow-up visits.

At screening prior to enrolment thick and thin blood films were examined. A second Geimsa stained thick film was examined with a binocular microscope with an oil immersion objective lens to quantify the parasitaemia, parasitaemia was measured counting the number of asexual parasites against a number of leukocytes in the thick blood film based on a putative count of 8000 leukocytes per microlitre of blood or an adequate mean WBC in the population under investigation. The number of asexual parasites was counted against 200 leukocytes using a hand tally counter. The parasite microlite of blood was calculated by using the formula.

Figure 1

Temperature = Auxiliary temperature was recorded using a digital electronic thermometer.

This study was approved by the ethical committee of St. Luke’s General Hospital, Anua, Uyo. The Study ensured adherence to good clinical practice and conformed to TDR standard operating procedure (SOP). Informed consent for the minors were obtained from their parents and guardians.

The result showed that both 7 and 14 days uncorrected cure rate was 100%. However, 3 of the 113 patients who completed the 28 days of follow up had low grade parasite density of 110 parasite and 340 parasite l^- blood respectively. We could not determine whether it was as a result of recrudescence or of new infection since no polymerase chain reaction technique was used (Table 2).

Figure 3

Table 2: Parasitological Cure rates

Time to parasite clearance in 113 children was determined from the spread sheet data WHO/MAL/82.988 parasitaemia cleared in 40 children within 24 hours and 73 children within 48 hours and the remaining 2 children within 72 hour.

Figure 4

Only a very low proportion of patients 15/113 had gametocyte on day 0 – 3, none of the children had gametocyte after 14 days. Symptoms of malaria disappeared in almost all patients during the first 3 days of the study.

The adverse events reported during the study were gastric disturbance (5 cases), excessive sleepiness (5 cases) and dizziness (one case) were all mild and self-limiting, none of the patients withdraw because of side effects.