Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana

Abuaku Benjamin, Duah Nancy, Quaye Lydia, Quashie Neils, Koram, Koram Kwadwo

Description

In 2008, artemether - lumefantrine (AL) and dihydroartemisinin - piperaquine (DHAP) were added to artesunate - amodiaquine (AS-AQ) as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. Methods The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. Results A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest zone and 93.8% (95% CI: 77.8, 98.9) in the coastal zone ( P = 0.017). Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. Conclusions The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences. The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite clearance observed in the zone.

Sujets

• Ghana

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 15
• Langue: English

Extrait

Abuaku et al. Malaria Journal 2012, 11:388
http://www.malariajournal.com/content/11/1/388
RESEARCH Open Access
Therapeutic efficacy of artemether-lumefantrine
combination in the treatment of uncomplicated
malaria among children under five years of age
in three ecological zones in Ghana
1* 1 1 1,2 1Benjamin Abuaku , Nancy Duah , Lydia Quaye , Neils Quashie and Kwadwo Koram
Abstract
Background: In 2008, artemether - lumefantrine (AL) and dihydroartemisinin - piperaquine (DHAP) were added to
artesunate - amodiaquine (AS-AQ) as first-line drugs for uncomplicated malaria in Ghana. The introduction of new
drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and
safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this
regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites
representing the three main ecological zones of the country.
Methods: The study was a one-arm prospective evaluation of clinical and parasitological responses to directly
observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009
WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based
20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any
time a study child was brought to the clinic with fever.
Results: A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41
in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28
were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively, with statistically significant differences
between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was
significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest zone and 93.8% (95% CI: 77.8, 98.9) in
the coastal zone (P=0.017). Fever and parasite clearance were slower among children enrolled in the savannah
zone. Gametocytaemia after day-3 post-treatment was rare in all the zones.
Conclusions: The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences.
The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite
clearance observed in the zone.
Keywords: Therapeutic efficacy, Artemether-lumefantrine, Uncomplicated malaria, Ecological zones, Ghana
* Correspondence: [e-mail]
1
Epidemiology Department, Noguchi Memorial Institute for Medical
Research, College of Health Sciences, University of Ghana, P. O. Box LG581,
Legon, Ghana
Full list of author information is available at the end of the article
© 2012 Abuaku et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.Abuaku et al. Malaria Journal 2012, 11:388 Page 2 of 8
http://www.malariajournal.com/content/11/1/388
Background The Navrongo War Memorial Hospital is located in
Malaria remains one of the major causes of morbidity the Kassena Nakana East district in the Upper East
reand mortality worldwide. It is estimated that in 2010 gion of Ghana. The Kassena Nankana East district has
there were approximately 216 million cases of malaria an estimated population of 109,944 with an annual
averworldwide, of which 81% were in Africa. In the same age rainfall of 950 mm. Malaria in the district is
perenyear, malaria accounted for approximately 655,000 nial with marked seasonal variation. The peak
deaths worldwide, of which 91% were in Africa [1]. In transmission season coincides with the major rains
be2010, malaria was estimated to account for 38.2% of all tween June and October. The Bekwai Municipal
Hosout patient attendance; 34.9% of all admissions; and pital is located in the Bekwai Municipality in the
33.7% of under-five mortality in Ghana [2]. Ashanti region of Ghana. The Bekwai Municipality has
The current control strategy in Ghana has case man- an estimated population of 118,024. Annual rainfall in
agement based on prompt recognition and adequate the municipality is 1,600 – 1,800 mm with double
maxtreatment as its main focus. Chloroquine had been the ima rainfall in May and October each year. Malaria
first-line drug for the treatment of uncomplicated mal- transmission in the Municipality is intense and
perenaria in Ghana for decades until 2001, when results from nial. The Begoro Government Hospital is located in the
studies conducted in six sentinel sites (between 1998 Fanteakwa district in the Eastern region of Ghana. The
and 2001) showed treatment failure rates of between F has an estimated population of
8.6% and 26.8% [3]. At a consensus-building workshop 108,614. Annual rainfall in the district is 150 –
in August 2003, Ghana decided to change her anti- 2,000 mm with double maxima rainfall in June and
malarial drug policy based on the evidence provided by October each year. Malaria transmission in the district is
the 2001 studies, among others. The focus of treatment intense and perennial. The Ewim Health Centre is
options was the use of artemisinin-based combination located within the Cape-Coast Metropolis in the Central
therapy (ACT) to slow down the spread of drug resist- region of Ghana. The Cape-Coast metropolis has an
estiance. This was recommended because of the rapid effect mated population of 169,894. Annual rainfall in the
meon fever and parasite clearance as well as a reduction in tropolis is 750 – 1,000 mm with double maxima rainfall
gametocyte carriage rates [4,5]. In January 2005, Ghana in June and December each year. Malaria transmission
adopted the artesunate-amodiaquine (AS-AQ) combin- in the metropolis is perennial [9-13].
ation as the first-line drug for the treatment of
uncomplicated malaria [6]. Artemether-lumefantrine (AL) and Study population
dihydroartemisinin-piperaquine (DHAP) were added to The study population involved all children aged between
AS-AQ as first-line drugs for uncomplicated malaria in six and 59 months presenting at the Out-Patient
DepartGhana in 2008 [7]. ment (OPD) of a study site clinic with symptoms
sugThe introduction of new drugs calls for continuous gestive of malaria. Once a clinical diagnosis of malaria
monitoring of these drugs to provide timely information was made by the study Nurse, samples of blood were
on trends of their efficacy and safety to enhance timely obtained from a finger prick to prepare thick and thin
evidence-based decision making by the National Malaria smears for malaria microscopy and haemoglobin level
Control Programme (NMCP). In this regard, a surveil- determination. Children meeting the inclusion criteria
lance system, coordinated by the Noguchi Memorial In- were recruited into the study and followed up for a
stitute for Medical Research (NMIMR), was established minimum of 14 days and a maximum of 28 days. Briefly,
in 2005 to provide data on first-line anti-malarial drugs the inclusion criteria included axillary temperature≥
from 10 sentinel sites across the country. This paper 37.5°C or history of fever during the past 24 hrs;
monocovers the therapeutic efficacy of AL across three eco- infection with Plasmodium falciparum; parasite count
logical zones in Ghana during the period September ranging between 1,000 and 250,000 per μl; haemoglobin
2010 to April 2011 using the 2009 WHO protocol for level>5 g/dl; absence of signs/symptoms of severe
malsurveillance of anti-malarial drug efficacy [8]. aria; and parent’s willingness to give their consent.
Children recruited into the study received
weightWMethods based 20/120 mg AL (Coartem – batch number x1435
Study sites supplied by WHO, Geneva) at 0, 8, 24, 36, 48, and
The AL study was conducted in four of the 10 sentinel 60 hrs. All treatments were given under direct
observasites representing the three main ecological zones of tion by a study nurse and children were observed for
Ghana. These were Navrongo War Memorial Hospital in 30 minutes to ascertain retention of medicine. Children
the savannah zone; Bekwai Municipal Hospital and who vomited during the observation period were
reBegoro Government Hospital in the forest zone; and treated with the same dose of medicine and observed for
Ewim Health Centre in the coastal zone. an additional 30 minutes. Children with repeatedAbuaku et al. Malaria Journal 2012, 11:388 Page 3 of 8
http://www.malariajournal.com/content/11/1/388
vomiting were given parenteral therapy with quinine as 28 for the different ecological zones based on the WHO
per national standard treatment guidelines and excluded 2009 criteria: Early treatment failure (ETF), Late
Parafrom the study. All children were allowed use of anti- sitological Failure (LPF), Late Clinical Failure (LCF), and
pyretics. Children who showed signs/symptoms of severe Adequate Clinical and Parasitological Response (ACPR)
malaria, had serious adverse events or required blood [8]. Secondary outcomes were patterns of fever and
transfusion were withdrawn from the study. parasite cle