Use Of Artemisinin Combination Therapy Research Articles

PfHDAC1 is an essential regulator of P. falciparum asexual proliferation and host cell invasion genes with a dynamic genomic occupancy responsive to artemisinin stress.

Malaria is a major public health problem, with the parasite Plasmodium falciparum causing most of the malaria-associated mortality. It is spread by the bite of infected mosquitoes and results in symptoms such as cyclic fever, chills, and headache. However, if left untreated, it can quickly progress to a more severe and life-threatening form. The World Health Organization currently recommends the use of artemisinin combination therapy, and it has worked as a gold standard for many years. Unfortunately, certain countries in southeast Asia and Africa, burdened with a high prevalence of malaria, have reported cases of drug-resistant infections. One of the major problems in controlling malaria is the emergence of artemisinin resistance. Population genomic studies have identified mutations in the Kelch13 gene as a molecular marker for artemisinin resistance. However, several reports thereafter indicated that Kelch13 is not the main mediator but rather hinted at transcriptional deregulation as a major determinant of drug resistance. Earlier, we identified PfGCN5 as a global regulator of stress-responsive genes, which are known to play a central role in artemisinin resistance generation. In this study, we have identified PfHDAC1, a histone deacetylase as a cell cycle regulator, playing an important role in artemisinin resistance generation. Taken together, our study identified key transcriptional regulators that play an important role in artemisinin resistance generation.

The Role of Rural Health Centres in the Detection and Management of Malaria Outbreaks in a Low Transmission Setting of Choma District, Zambia

The Southern Province of Zambia has been afflicted with malaria for many years, but in recent times, with the success of the national malaria control programme, malaria transmission has declined significantly and is now at low ebb. This success has been attributed to the effective use of indoor residual spraying, proper use of insecticide-treated mosquito nets provided to the people, as well as the use of artemisinin combination therapies in all rural health centres (RHCs) to treat clinical malaria cases at health facilities as well as in the communities by trained community health workers (CHWs). Despite this success and in trying to understand the epidemiology and control of malaria in rural areas of sub-Saharan Africa, it has been clear that local elimination is most unlikely due many challenges such as lack of incentives for CHWs who are the first link of the community to the health care system, inability of the officially approved rapid diagnostic tests to detect low level parasitemia in asymptomatic individuals, and anti-malaria stock-outs in RHCs, especially during the rainy season when most areas are unreachable due to impassable roads. This paper discusses the role of RHCs in the detection and management of malaria outbreaks in low transmission settings and the challenges of achieving elimination in Choma District, Southern Province, Zambia. These challenges could adversely impact malaria elimination if they remain unanswered.

Detection of antimalarial drug resistance polymorphisms in Plasmodium falciparum chloroquine resistance transporter and Plasmodium falciparum multidrug resistance 1 genes of Plasmodium falciparum found in Kano State, Nigeria

Objectives: In 2018, malaria claimed an estimated 380,000 lives in African region, with Nigeria accounting for 24.0% (91,368) of malaria deaths from the region. Mutations in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr-1) genes had reduced the effective use of artemisinin combination therapy through the development of resistance to these antimalarial agents. Our study set out to determine the antimalarial drug resistance polymorphisms in Pfcrt and Pfmdr-1 genes of P. falciparum isolates among patients in Kano State, Nigeria. Material and Methods: Malaria positive samples were collected across the three senatorial districts of Kano State. The samples were amplified using nested polymerase chain reaction to detect the Pfcrt and Pfmdr-1 genes. The amplicons were sequenced and bioinformatic analysis was done using CLC Sequence viewer 8.0 and BioEdit sequence alignment editor to detect the single-nucleotide polymorphisms. Results: In the Pfcrt gene, CVIET haplotype was seen in 26.2% of the samples while only two samples showed the 86Y mutation in the Pfmdr-1 gene. All the 86Y mutations and majority of the CVIET haplotypes were detected in the patients from rural settings where some of them noted that they consumed modern and traditional (herbs) antimalarial agents. One sample was observed to have the CVIET haplotype and N86Y mutation while the other five CVIET haplotypes were seen in five separate samples. A new mutation V62A was found in the Pfmdr-1 gene as observed in one of the sample. Conclusion: It is imperative to ensure the rational use of the right antimalarial agents and employ continuous resistance surveillance/mapping to ensure synergy in malaria containment and elimination strategies.

Malaria Knowledge and Treatment Practices in Enugu State, Nigeria: A Qualitative Study.

Background: Malaria accounts for 60% of outpatient visits in Nigeria. The aim of the study was to assess the knowledge of malaria and its treatment practices in Enugu state, Nigeria. Methods: Qualitative data was collected through the use of focus group discussions (FGDs), from six villages three each from urban and rural areas of Enugu state, Nigeria. A total of 18 FGDs involving 189 participants were conducted and data on place of treatment for malaria and drug of choice for malaria treatment were collected. Results: Most discussants had a good knowledge of the signs and symptoms of malaria. They reported late for treatment when they had symptoms suggestive of malaria. Treatment timing was affected by financial capability and perceived severity of disease. There was preference for patent medicine dealers (PMDs) and pharmacies for malaria treatment. The reasons included drug affordability, obtaining preferred drug, short waiting time and polite treatment from the providers. Treatment in most cases was without proper malaria diagnosis. Cost was an important factor in determining the drug of choice for malaria treatment. This could explain why people were not aware of the use of artemisininbased combination therapy while preferring mono-therapies and herbal drugs. Public hospitals were considered as good sources of treatment for malaria although they remain the last resort when treatment from these drug outlets failed. Conclusion: The community members preferred PMDs and pharmacies for malaria treatment. Unfortunately, these drug outlets do not encourage the use of artemisinin combination therapy (ACT). This makes it necessary that pharmacists and PMDs are trained on management of malaria. Also, improving the knowledge of the public on the need for malaria diagnosis before treatment and use of artemisinin-based combination therapy will improve the control of malaria. The populace should be instructed to seek treatment early while also discouraging the use of herbal drugs for malaria treatment. There is also the need to improve service delivery at public health facilities.

Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique.

BackgroundA major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy.MethodsThe overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms.This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming.DiscussionDespite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy.Trial registrationNCT01232530Electronic supplementary materialThe online version of this article (doi:10.1186/s12978-015-0101-0) contains supplementary material, which is available to authorized users.

Quality of care for the treatment for uncomplicated malaria in South-East Nigeria: how important is socioeconomic status?

IntroductionEnsuring equitable coverage of appropriate malaria treatment remains a high priority for the Nigerian government. This study examines the health seeking behaviour, patient-provider interaction and quality of care received by febrile patients of different socio-economic status (SES) groups.MethodsA total of 1642 febrile patients and caregivers exiting public health centres, pharmacies and patent medicine dealers were surveyed in Enugu state, South-East Nigeria to obtain information on treatment seeking behaviour, patient-provider interactions and treatment received. Socioeconomic status was estimated for each patient using exit survey data on household assets in combination with asset ownership data from the 2008 Nigeria Demographic and Health Survey.ResultsAmong the poorest SES group, 29% sought treatment at public health centres, 13% at pharmacies and 58% at patent medicine dealers (p < 0.01). Very few of those in the richest SES group used public health centres (4%) instead choosing to go to pharmacies (44%) and patent medicine dealers (52%, p < 0.001). During consultations with a healthcare provider, the poorest compared to the richest were significantly more likely to discuss symptoms with the provider, be physically examined and rely on providers for diagnosis and treatment rather than request a specific medicine. Those from the poorest SES group were however, least likely to request or to receive an antimalarial (p < 0.001). The use of artemisinin combination therapy (ACT), the recommended treatment for uncomplicated malaria, was low across all SES groups.ConclusionsThe quality of malaria treatment is sub-optimal for all febrile patients. Having greater interaction with the provider also did not translate to better quality care for the poor. The poor face a number of significant barriers to accessing quality treatment especially in relation to treatment seeking behaviour and type of treatment received. Strategies to address these inequities are fundamental to achieving universal coverage of effective malaria treatment and ensuring that the most vulnerable people are not left behind.

The impact of rapid malaria diagnostic tests upon anti-malarial sales in community pharmacies in Gwagwalada, Nigeria

BackgroundRapid diagnostics tests for malaria (RDT) have become established as a practical solution to the challenges of parasitological confirmation of malaria before treatment in the public sector. However, little is known of their impact in private health sector facilities, such as pharmacies and drug shops. This study aimed to assess the incidence of malaria among unwell patients seeking anti-malarial treatment in two community pharmacies in Nigeria and measure the impact RDTs have on anti-malarial sales.MethodsThis was a comparison study of two pharmacies located in the suburbs of Gwagwalada, in the Federal Capital Territory of Nigeria, between May and July 2012. In the intervention arm, patients seeking to purchase anti-malarials had an RDT performed before treatment while the control pharmacy continued normal routine practice.ResultsA total of 1,226 participants were enrolled into the study. The incidence of malaria in the intervention arm (n = 619) was 13.6% and adolescent participants had a statistically significant higher incidence (26.0%) compared to adults (11.9%) (P = 0.001). A history of fever in the last 48 hours was associated with a statistically significant higher incidence of malaria (28.3%) (P < 0.001). Having a RDT test reduced the chance of purchasing an anti-malarial by 42% (95% CI: 38%-46%) compared to not having a test. 51.6% (276) of the study participants with a RDT negative result still purchased anti-malarials, especially if anti-malarials had been recommended by a health professional (58.9%) compared to self-referral (44.2%) (P = 0.001). Patients with RDT negative results were also more likely to purchase an anti-malarial if there was a reported malaria positive laboratory test prior to presentation (66.2%; P = 0.007), a history of fever in the last 48 hours (60.5%; P = 0.027), and primary school education or less (69.4%; P = 0.009). After adjusting for age group and gender differences, having at least a secondary school education reduced the chance of buying an anti-malarial (OR 0.504 (95% CI: 0.256-0.993)) compared to having primary education or lower.ConclusionThe study highlights the enormous potential for improving appropriate prescription of anti-malarials in pharmacies and preventing unnecessary use of artemisinin combination therapy (ACT).

Access to subsidized ACT and malaria treatment--evidence from the first year of the AMFm program in six districts in Uganda

To determine the effect of the Affordable Medicines Facility for malaria (AMFm) launched in April 2011 in Uganda on the use of Artemisinin Combination Therapies (ACTs) for malaria treatment. 2398 households across six districts in Eastern Uganda were monitored through monthly survey visits from April 2011 to April 2012. During each visit, health seeking modules were completed for any morbidity episode reported by the household. Additional surveys were conducted with 114 licensed drug shops in the same districts in April 2011 and April 2012. Changes in drug shops' stocking and pricing of ACTs, as well as changes in households' treatment behaviour and drug usage were analysed. The fraction of licensed drug shops reporting that an ACT was one of their top five bestselling antimalarial drugs increased from 32% to 84% (Δ=0.517, 95% Confidence Intervals (CI) [0.407, 0.628], P<0.001). The fraction of children under the age of 5 with fevers getting an ACT increased from 37% to 47% (Δ=0.103, 95% CI [0.070, 0.136], P<0.001), and the fraction of ACT treatments among patients getting any antimalarial increased from 51% to 65% (Δ=0.145, 95% CI [0.121, 0.169], P<0.001). The observed changes were particularly large among poorer households, and were smallest for households from the highest wealth quintile. The study results suggest that, during its first year of implementation in Uganda, the AMFm achieved its main objective of increasing the availability and use of ACTs. Estimates of the impact of the AMFm on ACT use for children under 5 imply that the program should be considered highly cost-effective under current World Health Organization (WHO) guidelines. The overall results look promising, but larger and longer term studies will be needed to assess the health impact and cost-effectiveness of the program.

The association between price, competition, and demand factors on private sector anti-malarial stocking and sales in western Kenya: considerations for the AMFm subsidy

BackgroundHouseholds in sub-Saharan Africa are highly reliant on the retail sector for obtaining treatment for malaria fevers and other illnesses. As donors and governments seek to promote the use of artemisinin combination therapy in malaria-endemic areas through subsidized anti-malarials offered in the retail sector, understanding the stocking and pricing decisions of retail outlets is vital.MethodsA survey of all medicine retailers serving Bungoma East District in western Kenya was conducted three months after the launch of the AMFm subsidy in Kenya. The survey obtained information on each anti-malarial in stock: brand name, price, sales volume, outlet characteristics and GPS co-ordinates. These data were matched to household-level data from the Webuye Health and Demographic Surveillance System, from which population density and fever prevalence near each shop were determined. Regression analysis was used to identify the factors associated with retailers’ likelihood of stocking subsidized artemether lumefantrine (AL) and the association between price and sales for AL, quinine and sulphadoxine-pyrimethamine (SP).ResultsNinety-seven retail outlets in the study area were surveyed; 11% of outlets stocked subsidized AL. Size of the outlet and having a pharmacist on staff were associated with greater likelihood of stocking subsidized AL. In the multivariable model, total volume of anti-malarial sales was associated with greater likelihood of stocking subsidized AL and competition was important; likelihood of stocking subsidized AL was considerably higher if the nearest neighbour stocked subsidized AL. Price was a significant predictor of sales volume for all three types of anti-malarials but the relationship varied, with the largest price sensitivity found for SP drugs.ConclusionThe results suggest that helping small outlets overcome the constraints to stocking subsidized AL should be a priority. Competition between retailers and prices can play an important role in greater adoption of AL.

Perception and practices of Lagos state residents on the prevention and control of malaria in Lagos, Nigeria

Background: Malaria remains one of the major public health problems worldwide. It is an important cause of death and illness in children and adults in sub-Saharan Africa accounting for over a million deaths per year. The purpose of this study was to determine the perception and practices of the Lagos state residents on malaria. Materials and Methods: A descriptive cross-sectional study was conducted in five of the 20 local government areas (LGAs) in Lagos Nigeria. Using a multistaged sampling method, 5 LGAs and 12, 500 study participants were selected. The survey instrument was a structured, pretested, interviewer-administered questionnaire which sought for information on knowledge, attitude, and practices of the respondents on malaria. Data analysis was done using Epi-info V6.04d software. Results: The mean age was 35.5 ± 10.5 years. There were 8697 females (69.7%) and 3786 (30.3%) males. About 84% of the respondents correctly knew that malaria is transmitted by mosquitoes. Headache was the most recognized symptom (56.6%), while vomiting was the least (17.9%). About half of the participants recognized cleaning the environment as a primary preventive measure and the same number claimed to do so. Approximately, half of respondents claimed usage of insecticide-treated bed nets. Sulphadoxime-pyrimethamine (Fansidar) was the most frequently used (32.7%) antimalarial agent and the use of artemisinin combination therapy was low. Conclusion: Knowledge of malaria symptoms was average and the use of preventive measures was suboptimal. Increasing awareness of all stakeholders on traditional and contemporary preventive measures may enhance the control of this health condition.

Status of potential Pf ATP6 molecular markers for artemisinin resistance in Suriname

BackgroundPolymorphisms within the PfATP6 gene have been indicated as potential molecular markers for artemisinin efficacy. Since 2004, the use of artemisinin combination therapy (ACT) was introduced as first-line treatment of the uncomplicated malaria cases in Suriname. The aim of this research was to determine changes in Suriname in the status of the polymorphic markers in the PfATP6 gene before and after the adoption of the ACT-regimen, particularly of the S769N mutation, which was reported to be associated with in vitro Artemether resistance in the neighboring country French Guiana.MethodsThe PfATP6 gene from Plasmodium falciparum parasites in Suriname was investigated in 28 samples using PCR amplification and restriction enzyme analysis, to assess and determine the prevalence of potentially interesting single nucleotide polymorphisms. The polymorphisms [L263E; A623E; S769N], which may be associated with the artemisinin resistant phenotype were characterized in parasites from three endemic regions before and after the adoption of the ACT-regimen. In addition, the status of these molecular markers was compared in paired P. falciparum isolates from patients with recurring malaria after controlled ACT.ResultsAll the investigated samples exhibit the wild-type genotype at all three positions; L263, A623, S769.ConclusionAll investigated isolates before and after the adoption of the ACT-regimen and independent of endemic region harbored the wild-type genotype for the three investigated polymorphisms. The study revealed that decreased artemisinin susceptibility could occur independent from PfATP6 mutations, challenging the assumption that artemisinin resistance is associated with these mutations in the PfATP6 gene.

Community Health Workers Use Malaria Rapid Diagnostic Tests (RDTs) Safely and Accurately: Results of a Longitudinal Study in Zambia

Malaria rapid diagnostic tests (RDTs) could radically improve febrile illness management in remote and low-resource populations. However, reliance upon community health workers (CHWs) remains controversial because of concerns about blood safety and appropriate use of artemisinin combination therapy. This study assessed CHW ability to use RDTs safely and accurately up to 12 months post-training. We trained 65 Zambian CHWs, and then provided RDTs, job-aids, and other necessary supplies for village use. Observers assessed CHW performance at 3, 6, and 12 months post-training. Critical steps performed correctly increased from 87.5% at 3 months to 100% subsequently. However, a few CHWs incorrectly read faint positive or invalid results as negative. Although most indicators improved or remained stable over time, interpretation of faint positives fell to 76.7% correct at 12 months. We conclude that appropriately trained and supervised CHWs can use RDTs safely and accurately in community practice for up to 12 months post-training.

The pharmacokinetic evaluation of artemisinin drugs for the treatment of malaria in paediatric populations

Introduction: The use of artemisinin combination therapies to treat uncomplicated malaria is growing and, therefore, so is the number of children exposed to these agents. As a result, there is a huge drive to develop paediatric formulations. However, relatively limited data exist regarding the pharmacokinetic properties of these drugs in this vulnerable population.Areas covered: The article reviews the pharmacokinetic data for artemisinin drugs used for the treatment of malaria in paediatric populations. The authors discuss how developmental and environmental factors can produce significant variation in the pharmacokinetic properties of artemisinin drugs. The authors also discuss how this variation may lead to suboptimal therapeutic drug concentrations with implications on efficacy, safety and the development of parasite resistance to these drugs.Expert opinion: There is currently a lack of published studies on the pharmacokinetics of artemisinin drugs in children and this subject is complicated by several interdependent variables. Therefore, the construction of a systems-based model of this subject should be a priority area in order to identify gaps in current knowledge to ensure their continued effective and safe use.

Waking the Sleeping Beauty

Waking the Sleeping Beauty

Knowledge and Treatment Practices of Malaria among Mothers and Caregivers of Children in an Urban Slum in Jos, Nigeria

Malaria is a public health problem in more than 90 countries, inhabited by a total of 2.4 billion people, representing about 40% of the world's population. Major trends over the last few decades point to a worsening situation if effective action is not taken. Sadly, this is in spite of enormous efforts and resources that have been invested in its control. The objective of this study was to describe the level of knowledge of malaria as a disease and the practice of its treatment by mothers and caregivers of under five children in Gangare, an urban slum of Jos City, Nigeria. A cross-sectional descriptive study design, a cluster sampling technique and an interviewer administered questionnaire were used to collect information on socio demographic profiles as well as knowledge and treatment practices of malaria from mothers and caregivers of under five children in Gangare, Jos North Local Government Area of Plateau State, central Nigeria. The data was then analyzed using Epi info2002 epidemiological software. The study revealed a low level of knowledge of malaria with 248 (49.6%) being able to recognize the disease and only 124 (24.9%) attributing it to the mosquito bite. The attitude of most respondents towards malaria as an illness was however good as 275 (55%) viewed it as a very serious illness and most of them 328 (65.6%) would use hospitals/clinics for treatment. Majority of them; 462 (92.4%) have not heard of Artemisinin Combination Therapy (ACT) and only 19 (50%) of those who had heard of ACT had ever used it for the treatment of malaria. Generally their knowledge of malaria and treatment seeking practice are influenced by cost of treatment, perceived safety and level of their education. (p < 0.05). Among mothers and caregivers living in slums in Jos, their ability to recognize malaria is poor. So also is their awareness and use of Artemisinin Combination Therapy. An improvement in their level of education and their economic power could improve their knowledge and treatment practices.

Malaria in pregnancy

Malaria remains one of the highest contributors to the precarious maternal mortality figures in sub-Saharan Africa. At least 6 million women worldwide are at risk of malaria infection in pregnancy. Malaria contributes to at least 10, 000 maternal deaths and to at least 200, 000 newborn deaths annually. Malaria is a contributor or aetiologic factor in pregnancy complications including anaemia, spontaneous abortion, prematurity and stillbirths. Pregnancy results in increased incidence and severity of malaria. Cerebral malaria, acute renal failure and severe anaemia, rare complications in adults living in malaria endemic areas, may complicate malaria in pregnancy. Research implicate reduced maternal immunity from increased steroid levels in pregnancy, increased attractiveness of pregnant women to mosquito bites and increased adherence of parasitized erythrocytes to Chondroitin sulphate A expressed in the placentae. This is worse in the first and second pregnancies. With infection with the Human Immunodeficiency Virus [HIV], the effects of malaria in pregnancy are even worse. Over the decades, there have been concerted worldwide collaborative efforts, spearheaded by the World Health Organization [WHO] and including governments and allied agencies to tackle the scourge of malaria in pregnancy. The main thrusts of such efforts have been: to increase the use of insecticide treated mosquito bed nets [ITN]; intermittent preventive treatment of malaria [IPT]; and adequate case treatment of acute malaria attacks in pregnancy. While for IPT, Sulfadoxine-Pyrimethamine [SP] combination has been proven to be of benefit in preventing acute and latent malaria in pregnancy and its associated complications, the WHO has introduced the use of Artemisinin-Combination Therapy [ACT] for the first-line treatment of uncomplicated malaria in pregnancy, the need to confirm malaria before treatment and the enforcement of completion of therapy once started. The Roll Back Malaria [RBM] campaign was launched as a strategy to curtail the incidence and scourge of malaria especially in the vulnerable groups including pregnant women. The Millennium Development Goals [MDGs] offer a new hope if adequately pursued to achieving eradication of malaria and its complications in pregnancy. There is need to support research into effectiveness and utilization of established and newer control measures.

Potential contribution of prescription practices to the emergence and spread of chloroquine resistance in south-west Nigeria: caution in the use of artemisinin combination therapy

BackgroundPrescription practices have been shown to influence the emergence of anti-malarial drug resistance. Thus efforts in this study were devoted to evaluating the prescribing practices prior to introduction of the artemisinin based combination therapy (ACT) in Nigeria and its potential contribution to emergence of chloroquine resistant malaria in south-west Nigeria, in order to forestall a similar situation with the ACT.MethodsA retrospective quantitative study was designed to examine case records of patients treated for malaria in either a government or a private hospital in Ibadan, south-west Nigeria, over a 20-year period, cutting across three phases of resistance to chloroquine in Nigeria: pre-resistance, emerging resistance and dissemination of resistance. Patient prescriptions were examined for use of anti-malarial drugs, sub-therapeutic doses of chloroquine, co-administration of anti-histamines with chloroquine. Descriptive statistics of frequency and percentage were used to describe trends in the parameters assessed using EPI-info.ResultsCase record files of 2,529 patients were examined. Chloroquine was the main drug used in treatment of malaria throughout the periods studied, with frequency of prescription at both sites ranging from 91.4% to 98.3% during the pre-resistance years. It was administered as standard doses during the pre resistance years. Anti-histamines, especially promethazine, were routinely co-administered with chloroquine at this period too. However, the practice of prescribing sub-therapeutic doses of chloroquine at the private health care facility coincided with the latter phase of emerging resistance and phase of dissemination of resistance. Frequency of prescription of sub-therapeutic doses increased from 6.7% in 1983 (pre-resistance years) to 43.6% in 1997 (dissemination of resistance phase) at the private health care facility. Frequency of co-administration of anti-histamines with chloroquine also reduced during the period of dissemination of resistance.ConclusionThe results from this study describe a lack of adherence to national treatment guidelines, especially in the private sector, and a relationship between prescription practices and dissemination of drug resistant falciparum malaria. As Nigeria adopts the use of ACT, there is an urgent need to improve malaria treatment practices in Nigeria in order to prolong the clinical shelf-life of the combination.

Polymorphism of PfATPase in Niger: detection of three new point mutations

BackgroundPlasmodium falciparum resistance to drugs remains a major public health issue in Niger. The therapeutic failure index for chloroquine and sulphadoxine-pyrimethamine are, respectively 20% and 21.9%. In December 2005, the National Malaria Control Programme promoted the use of artemisinin combination therapy (ACT) as first-line treatment of the uncomplicated malaria cases. Recently, studies have shown a relationship between the SERCA PfATPase6 gene and artemisinin efficacy, and pointed it out as a potential molecular marker for resistance. The goal of this work was to describe the baseline polymorphism of PfATPase6 gene in Niger, at a time when the national implementation of the ACT policy had just begun.Materials and methodsThe DNA polymorphism of the PfATPase6 gene of 87 P. falciparum samples from Niger was analysed by sequencing. The links between the mutation occurrence and environment and human host factors were tested by bivariate analysis.ResultsThe P. falciparum PfATPase6 gene presented polymorphisms at codons 537, 561, 569, 630, 639, 716 levels. All the mutations found were rare, except the PfATPaseN569K found in 17.2% of samples. No associated factor has been observed.ConclusionThe P. falciparum PfATPase gene is polymorphic at the 569 codon. As ACT is getting more and more used, the PfATPase6 gene polymorphism needs to be monitored in association with phenotypic – in vivo and/or in vitro – drug efficacy tests.

Pregnancy exposure registries for assessing antimalarial drug safety in pregnancy in malaria-endemic countries.

Because pregnant women are routinely excluded from pre-licensure clinical trials for fear of harming the mother or the developing foetus [1], most drugs are marketed with limited information on their safety during pregnancy and therefore are not recommended for use by pregnant women. Yet drugs are widely used by pregnant women, and medication often cannot be avoided in chronic diseases such as epilepsy and HIV or other acute illness that harm the mother and the unborn child if left untreated.

Efficacy of combination therapy with artesunate plus amodiaquine compared to monotherapy with chloroquine, amodiaquine or sulfadoxine–pyrimethamine for treatment of uncomplicated Plasmodium falciparum in Afghanistan

In South and Central Asia resistance to chloroquine (CQ) has reached unmanageable levels, and resistance to sulfadoxine-pyrimethamine (SP) is emerging. Amodiaquine (AQ) is widely used in the region, and elsewhere shows only partial resistance to CQ. In Afghanistan, one option for slowing the spread of resistance and improving treatment outcomes is the use of artemisinin combination therapy (ACT). The efficacy of CQ, AQ, SP and amodiaquine plus artesunate (AQ/AS) in the treatment of uncomplicated falciparum malaria was investigated using standard World Health Organization (WHO) procedures. Malaria patients were randomized to four treatment groups: 268 were enrolled and 240 completed the trial. There was a high level of cross-resistance between CQ and AQ resistance: adequate clinical and parasitological response by day 42 was 11% after CQ treatment and 9% after AQ treatment. The trend of treatment failure between AQ and CQ was almost identical. Cure rates were considerably improved by the addition of artesunate to AQ or by use of SP; adequate clinical and parasitological response being 72% for AQ/AS and 92% for SP. The combination of AS/AQ substantially reduced the odds of treatment failure relative to AQ monotherapy by day 42 [odds ratio (OR) = 0.03, 95% confidence interval (CI) 0.01-0.1] in addition to reducing the proportion of patients with gametocytes throughout the 42-day period. Gametocyte carriage rate was only marginally higher in the SP than in the CQ- and AQ-treated groups. The therapeutic and parasitological cure rates with AS/AQ were inadequate, and the criteria for deploying ACT - namely to prevent further selection of drug resistance from a position of low frequency - was not met in the region. An alternative drug combination to AQ/AS is required for Afghanistan.