Background
Despite international commitments that have led to the global malaria strategy from which the first results are expected within the Millennium Development Goals in 2015 [
1‐
4], the decline in malaria incidence in sub-Saharan African countries may be temporary. In 2013, it was estimated that 198 million malaria episodes occurred, of which 82 % (163 million) were in sub-Saharan African countries. Mortality remained at a high level with 584,000 deaths, of which 90 % were reported from sub-Saharan African countries [
5]. Using malaria control tools, mainly long-lasting insecticide-treated nets (ITN), intermittent preventive treatment during pregnancy, and artemisinin-based combination therapy (ACT), some sub-Saharan African countries have registered a substantial reduction in malaria burden in recent years. The quality of health systems has also contributed to this positive trend. In Central African countries, however, the complexity of the ecological context and poorly operating health system, including the lack of malaria surveillance system, limit the implementation of effective strategy to control malaria.
After several decades of intensive use of chloroquine and sulfadoxine-pyrimethamine (SP) to treat uncomplicated malaria, these two classical anti-malarial drugs had become less effective [
6‐
9], resulting in a high percentage of malaria cases seen in health centres [
10] and an increase in the number of severe malaria cases and malaria-associated mortality in hospitals [
11,
12]. As a consequence, in 2006, the Republic of Congo adopted ACT as the first-line treatment [
13]. Two forms of ACT, artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL), which have become first- and second-line anti-malarial treatment, respectively, have proven effective during the initial clinical assessment [
14‐
16].
To encourage the use of these new treatments by health personnel, the Congolese government decreed in 2008 free malaria treatment for all children less than 15 years old. ITNs have also been distributed free of charge to pregnant women and children under 5 years of age. This mass distribution was later extended to the entire population and performed regularly. Pregnant women also receive three doses of SP for intermittent preventive treatment of malaria. These measures have contributed to the reduction of malaria in pregnant women and children [
17]. However, the available data are still inadequate to reflect the evolution of malaria throughout the country since most previous studies had been conducted in southern Republic of Congo.
The present study was conducted to assess the therapeutic efficacy of ASAQ and AL from November 2012 to February 2013 in the city of Owando, located in equatorial flooded forest in northern Republic of Congo. All febrile children aged less than 12 years spontaneously consulting at one of two public health centres were screened for the presence of malaria parasites using rapid diagnostic test (RDT) and microscopy. The objectives of this study were to determine the burden of malaria among febrile children less than 12 years old consulting spontaneously at the health centres during the study period and to evaluate the tolerance and effectiveness of these two forms of ACT.
Discussion
In 2006, the Republic of Congo adopted a new drug policy for malaria, which includes the treatment of uncomplicated malaria with ASAQ and AL, treatment of severe and complicated malaria with parenteral quinine, and recommendations for collective and individual preventive measures [
13]. Long-lasting insecticide-treated nets (ITN) to protect pregnant women and children under 5 years old and intermittent preventive treatment during pregnancy (IPTp) with SP are the key measures of malaria prevention. The efficacy of ASAQ and AL had been assessed earlier in two sites, the rural Department of Pool and Brazzaville when the new anti-malarial drug policy was in preparation [
14‐
16]. A longitudinal survey in urban and suburban health facilities in Brazzaville, the capital city, from 2003 to 2007 showed high percentage of clinical malaria episodes [
10]. In 2011 and 2012, a study conducted among children under 5 years old and pregnant women in Brazzaville and Pointe-Noire (western Congo along the Atlantic coast) reported a reduction of malaria prevalence due to preventive measures [
16]. This reduction in malaria burden could have been even greater if treatment for malaria had been provided free of charge to all malaria-infected patients in public health facilities since 2007, as initially planned by the government. Unfortunately, the limited supply of ACT in health centres and the high price of these drugs in pharmacies have limited the success of the measures [
22].
RDTs are important tools that contribute to fight effectively against malaria. The ease of use of these devices allows untrained medical personnel to use them after a short training. Despite many advantages, the use of RDTs in Congolese health facilities is limited by its high cost and/or lack of adequate supply to meet the country’s demands. In public health centres with a microscope, the performance of microscopy to establish malaria diagnosis costs 500 FCFA (US $1.00). The local laboratory suppliers sell a box containing 25 RDTs for 25,000 FCFA, i.e. US $2.00 per RDT. At this price, RDT is not competitive in public health facilities.
In Uganda, the treatment of clinical malaria episodes was cost-effective when diagnosis was established with RDT, as compared to microscopic examination of thick blood films [
23], while in Tanzania the benefit of RDT was observed in moderate and low transmission areas [
24]. In Ghana, a reduction in treatment cost was obtained with RDT, as compared with presumptive treatment, but RDT was not advantageous when compared to microscopic diagnosis [
25]. Several studies have shown that anti-malarial treatment is more cost-effective when diagnosis is confirmed with RDT, as compared to treatment based on presumptive diagnosis [
26]. Although Global Fund provides funding to recipient countries to acquire RDT [
27], the impact of this programme is not yet known. In several research studies conducted in sub-Saharan Africa, RDTs have been acquired as part of research projects funded by donors or as a donation
[
23‐
25,
28‐
31]. In African private hospitals, several trademarks of RDT are used without taking into account the evaluation of RDT performed by the WHO [
32‐
34].
Under these conditions, microscopy is expected to continue to occupy an important place in the diagnosis of malaria in the context of declining malaria prevalence, with a decrease in the number of clinical malaria cases, and for determining parasite density, when required, as long as RDT is not subsidized like drugs. Whether malaria diagnosis is confirmed by microscopy or RDT, a strong commitment of sub-Saharan African states would be essential to implement the national and regional anti-malarial treatment guidelines [
35].
This is the first epidemiological study conducted on malaria in the northern part of the country reporting malaria percentage in 0–11 years old febrile children attending health facilities spontaneously and drug efficacy. A reliable diagnosis was established in individual patients using both microscopy and RDT. Advantage Mal Card
® RDT is known for its good performance [
33,
34], and it is the second time that this device was used in an epidemiological study in the Republic of Congo [
17]. The combination of these two diagnostic methods ensures that these data can serve as a reference for future studies in the city of Owando.
The choice of age group 0–11 years constitutes one of the weaknesses of this study. An enrollment of all symptomatic malaria-infected patients (children and adults) would have generated more representative data in the health centres. The choice of 0–11 years old is justified by a limited quantity of available RDT. However, the 0–11 years age group is pertinent and of interest because it includes children under 5 years old who are considered as one of the target age groups, together with pregnant women, in the fight against malaria. The longitudinal study in Brazzaville from 2003 to 2007 (i.e. before the new anti-malarial drug policy based on ACT) had shown that in a suburban area of Brazzaville, 46.6 % of febrile children under 5 years old and 63.5 % of febrile patients aged between 5 and 10 years had clinical malaria [
10]. By contrast, in the urban area of Brazzaville, 24 % of febrile patients under 5 years old and 33.5 % of patients aged between 5 and 10 years had malaria [
10]. Studies conducted in Mayombe forest in southern Congo, where the annual entomological inoculation rate is high but variable (80–400 infective bites/man/year) [
36], showed the frequency of malaria-associated clinical episodes of 35.4, 32.1, and 33.3 % in febrile children aged between 0 to <2 years, 2 to <5 years and 6–15 years, respectively [
37]. This latter study also reported that malaria was the third cause of consultation in under 2 years old children and the fourth cause among children aged 2–15 years, after respiratory and gastro-intestinal diseases. With the low percentage of clinical malaria episodes among febrile children attending public health facilities in Owando city, it is likely that the majority of 0–11 years old patients consult for febrile diseases other than malaria as in Mayombe forest, including acute respiratory infections, upper respiratory tract infections, and gastro-intestinal infections.
Despite the unavailability of inoculation rate data, the city of Owando, located in a forest with shallows that are often flooded and scattered dwellings, may be considered as an area of high transmission encountered in Congolese forest regions. However, based on the results of the present study, the percentage of malaria-associated clinical episodes (i.e., 19.5 %) among patients 0–11 years attending Owando health centres appeared to be unusually low. Further studies at different times of the year are required to characterize malaria transmission in Owando.
In therapeutic efficacy studies, RDT which detects
P. falciparum lactate dehydrogenase (PfLDH) can be used for rapid screening of patients for inclusion, and parasite density can be determined by microscopy [
28]. In the present study, RDT was used to screen patients for inclusion in the study of ASAQ and AL efficacy. The PCR-corrected efficacy in Owando city was 100 % for ASAQ and 98.0 % for AL, which is in agreement with the results obtained in an earlier study conducted in a rural area in the Department of Pool, 200 km from Brazzaville, where the efficacy rate was 98.5 % for ASAQ (non-coformulated tablets) and 100 % for AL [
13]. These ASAQ and AL drug formulations had 94.4 and 97.1 % efficacy, respectively, in previous studies in Brazzaville [
15,
16]. Adverse events related to ASAQ intake and reported in studies in Congo [
14‐
16] may become one of the causes of non-compliance among patients or their parents for this drug provided free of charge in public health facilities. AL is generally better accepted by the population, which has led the Congolese health authorities to recommend this ACT as the first-line drug and ASAQ as the second-line drug since 2014 [
38]. However, AL requires six doses to cure malaria, and it is recommended to take AL with fatty food or drink. There are at present on the Congolese market more than a dozen AL specialties. Several dispersible formulations for children, with a fruity taste facilitating administration to children, are also available. The abundance of AL specialties available and freely prescribed in health facilities increases the risk of dissemination of poor quality drugs.
Authors’ contributions
MN coordinated the study, supervised enrolment and follow-up of patients, and analysed data. BPS, BDM, RDY, PNC and RM enrolled and followed up patients. HB, KYHN, BP, and LKB conducted PCR analysis. MN, LKB, and HB wrote the draft. All authors read and approved the final version.