In vivo efficacy and safety of artemether-lumefantrine and amodiaquine-artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether-lumefantrine (AL) and amodiaquine-artesunate (AS-AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. METHODS: The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000-200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS-AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. RESULTS: Totals of 368 and 273 patients were enrolled in the AL and AS-AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS-AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS-AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3-89.2%) for AL and 98.8% (95% CI 96.7-99.8%) for AS-AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6-99.2%) for AL and 99.6% (95% CI 97.9-100%) for AS-AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS-AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. CONCLUSION: Both AL and AS-AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov: NCT04370977.

[Determination of impurity diketo aldehyde in bulk drug and preparations of dihydroartemisinin].

Diketo aldehyde (DKA),one of the most important impurities in dihydroartemisinin,was synthesized through reaction between dihydroartemisinin and anhydrous ferrous bromide under a N2 atmosphere, and an HPLC method was established for the determination of DKA in bulk drug and in DHA tablet. DKA was prepared from dihydroartemisinin in the presence of FeBr2.The chromatographic separation was achieved through an Agilent Eclise XDB-C18 column (4.6 mm×250 mm,5 µm), and the optimal mobile phase consisted of acetonitrile and water in the ratio of 37:63 at flow rate of 1.0 mL·min⁻¹.The detection was carried out at 216 nm, and column temperature was 15 °C.The injection volume was 40 µL.The method featured a good linearity (r=0.999 9),precision (1.0%),repeatability (1.3%),stability (DKA standards RSD=1.0% and in tablet form instability),recovery (92.88%),limits of detection (0.20 mg·L⁻¹) ,and limits of quantification (0.78 mg·L⁻¹). The result show that the content of DKA in bulk drug was 0.086 7%-2.622 9%, and the content of DKA in tablet was 0.068 3%-0.615 1%.

The role of antimalarial quality in the emergence and transmission of resistance.

The emergence and transmission of antimalarial resistance is hampering malaria eradication efforts and is shortening the useful therapeutic life of currently available antimalarials. Drug selection pressure has been identified as a contributing factor to the emergence and transmission of resistance, especially population treatment coverage and sub-therapeutic concentrations of active pharmaceutical ingredient (API) in the bloodstream. Medicine quality can be defined as good quality or poor quality. Poor quality antimalarials can be falsified, substandard or degraded and are estimated to make up between 10 and 50% of the antimalarial market in developing countries, and can be a source of sub-therapeutic doses of antimalarial API(s). The availability and use of poor quality antimalarials and the non-recommended use of quality assured monotherapies have historically been linked to treatment failure and in some cases, have coincided with the emergence and transmission of resistance in regions. We propose and outline the hypotheses that the use of poor quality antimalarial treatments and non-recommended quality assured monotherapies promote the (i) emergence and/or (ii) transmission of antimalarial resistance.

Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops: A cluster-randomised trial in Uganda.

BACKGROUND: Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. METHODS: Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever 'appropriately treated of malaria with ACT' was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors, community sensitisation, supervision and provision of mRDTs and ACTs to drug shops. Household costs of treatment-seeking were captured in a representative sample of drug shop customers. FINDINGS: The introduction of mRDTs in drug shops was associated with a large improvement of diagnosis and treatment of malaria, resulting in low incremental costs for the health sector at US$0.55 per patient appropriately treated of malaria. High expenditure on non-ACT drugs by households contributed to higher incremental societal costs of US$3.83. Sensitivity analysis showed that mRDTs would become less cost-effective compared to presumptive diagnosis with increasing malaria prevalence and lower adherence to negative mRDT results. CONCLUSION: mRDTs in drug shops improved the targeting of ACTs to malaria patients and are likely to be considered cost-effective compared to presumptive diagnosis, although the increased costs borne by households when the test result is negative are a concern.

Quality Testing of Artemisinin-Based Antimalarial Drugs in Myanmar.

Artemisinin-based combination therapies are the frontline treatment of Plasmodium falciparum malaria. The circulation of falsified and substandard artemisinin-based antimalarials in Southeast Asia has been a major predicament for the malaria elimination campaign. To provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of Myanmar. The quality of these drugs in terms of their artemisinin derivative content was tested using specific dipsticks for these artemisinin derivatives, as point-of-care devices. A subset of these samples was further tested by high-performance liquid chromatography (HPLC). This survey identified that > 35% of the collected drugs were oral artesunate and artemether monotherapies. When tested with the dipsticks, all but one sample passed the assays, indicating that the detected artemisinin derivative content corresponded approximately to the labeled contents. However, one artesunate injection sample was found to contain no active ingredient at all by the dipstick assay and subsequent HPLC analysis. The continued circulation of oral monotherapies and the description, for the first time, of falsified parenteral artesunate provides a worrisome picture of the antimalarial drug quality in Myanmar during the malaria elimination phase, a situation that deserves more oversight from regulatory authorities.

Detection of Poor Quality Artemisinin-based Combination Therapy (ACT) Medicines Marketed in Benin Using Simple and Advanced Analytical Techniques.

BACKGROUND: Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa which bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality controls. METHODS: 12 samples of artemether/lumefantrine were collected from formal and informal drug sellers in Cotonou (Benin) as well as additional other similar samples from Rwanda (13 samples) and from D.R. Congo (9 samples). Thin Layer Chromatography (TLC) as classical and simple identification test was applied in Benin while an analytical chemistry laboratory in Belgium (ULg, Pharmacy Department) was asked for further analyses with HPLC and Raman spectroscopy using a developed and validated HPLC method for rapid analysis of artemether/lumefantrine. RESULTS: The results obtained in Belgium confirmed the lack of the two active ingredients in the suspected sample of ACT medicine from Benin whereas some samples from Rwanda and D.R. Congo were found to present risk of substandard drugs either for under-dosing or over-dosing. CONCLUSIONS: Counterfeit/falsified of artemisinin-based combination therapy (ACT) medicines are really scourge that needs to be fought through strong collaboration between public health authorities and appropriate quality control laboratories.

Quality of artemisinin-based antimalarial drugs marketed in Nigeria.

Background: Artemisinin combination therapy is first-line therapy for treatment of malaria, which is one of the most significant public health problems in Nigeria. With the increasing level of use of these drugs coupled with the emergence of resistance, there is a need for regular post-market surveillance. Method: Twenty different brands of artesunate-containing antimalarial drugs and 10 brands of artemether-lumefantrine were multi-sourced in the south western part of Nigeria and were subjected to identification, weight uniformity test, and assay using United State pharmacopoeia and International Pharmacopoeia monographs. In vitro-dissolution test of the artemether tablets was also investigated. Results: All 10 brands (100%) of the artemether-lumefantrine tablets met the assay requirement for artemether and 8 (80%) met the assay requirement for lumefantrine, but only 4 brands (40%) met the requirement for artemether dissolution. One of these brands failed the weight uniformity test. Of the 20 brands of artesunate-containing brands included in this study, 15 (75%) met the standard assay requirement for artesunate and two failed the weight uniformity test. Conclusions: There is evidence of the presence of substandard artemisinin products in the Nigerian market.

Do anti-malarials in Africa meet quality standards? The market penetration of non quality-assured artemisinin combination therapy in eight African countries.

BACKGROUND: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. RESULTS: In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. CONCLUSIONS: Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance.

Quality of Artemisinin-based Combination Therapy for malaria found in Ghanaian markets and public health implications of their use.

BACKGROUND: Ghana changed their antimalarial drug policy from monotherapies to Artemisinin-based Combination Therapies in 2004 in order to provide more efficacious medicines for treatment of malaria. The policy change can be eroded if poor quality Artemisinin-based Combination Therapies are allowed to remain on the Ghanaian market unchecked by regulatory bodies and law enforcement agencies. The presence and prevalence of substandard and counterfeit Artemisinin-based Combination Therapies need to be determined on open markets in Ghana; a review of the current policy; identifying any gaps and making recommendations on actions to be taken in addressing gaps identified are essential as the data provided and recommendations made will help in ensuring effective control of malaria in Ghana. METHODS: A field survey of antimalarial drugs was conducted in the central part of Ghana. The amount of active pharmaceutical ingredient in each Artemisinin-based Combination Therapy sample identified in the survey was measured using high performance liquid chromatographic analyses. Active pharmaceutical ingredient within the range of 85-115 % was considered as standard and active pharmaceutical ingredient results out of the range were considered as substandard. All samples were screened to confirm stated active pharmaceutical ingredient presence using mass spectrometry. RESULTS: A total of 256 Artemisinin-based Combination Therapies were purchased from known medicine outlets, including market stalls, hospitals/clinics, pharmacies, drug stores. Artemether lumefantrine (52.5 %) and artesunate amodiaquine (43.2 %) were the predominant Artemisinin-based Combination Therapies purchased. Of the 256 Artemisinin-based Combination Therapies purchased, 254 were tested, excluding two samples of Artesunate-SP. About 35 % of Artemisinin-based Combination Therapies were found to be substandard. Nine percent of Artemisinin-based Combination Therapies purchased were past their expiry date; no counterfeit (falsified) medicine samples were detected by either high performance liquid chromatographic or mass spectrometry. CONCLUSION: A high proportion of Artemisinin-based Combination Therapies sold in central Ghana were found to be substandard. Manufacturing of medicines that do not adhere to good manufacturing practices may have contributed to the poor quality of the Artemisinin-based Combination Therapies procured. A strict law enforcement and quality monitoring systems is recommended to ensure effective malaria case management as part of malaria control.

Fake anti-malarials: start with the facts.

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting.

Rapid and specific drug quality testing assay for artemisinin and its derivatives using a luminescent reaction and novel microfluidic technology.

Globally, it is estimated that about 10-30% of pharmaceuticals are of poor quality. Poor-quality drugs lead to long-term drug resistance, create morbidity, and strain the financial structure of the health system. The current technologies for substandard drug detection either are too expensive for low-resource regions or only provide qualitative results. To address the current limitations with point-of-care technologies, we have developed an affordable and robust assay to quantify the amount of active pharmaceutical ingredients (APIs) to test product quality. Our novel assay consists of two parts: detection reagent (probe) and a microfluidic testing platform. As antimalarials are of high importance in the global fight against malaria and are often substandard, they are chosen as the model to validate our assay. As a proof-of-concept, we have tested the assay with artesunate pure and substandard samples (Arsuamoon tablets) from Africa and compared with the conventional 96-well plate with spectrophotometer to demonstrate the quantitative efficacy and performance of our system.

Quality of Artemisinin-Containing Antimalarials in Tanzania's Private Sector--Results from a Nationally Representative Outlet Survey.

Ensuring that artemisinin-containing antimalarials (ACAs) are of good quality is a key component of effective malaria treatment. There are concerns that a high proportion of ACAs are falsified or substandard, though estimates are rarely based on representative data. During a nationally representative survey in Tanzania, ACAs were purchased from private retail drug outlets, and the active pharmaceutical ingredient (API) was measured. All 1,737 ACAs contained the labeled artemisinin derivative, with 4.1% being outside the 85-115% artemisinin API range defined as acceptable quality. World Health Organization (WHO) prequalified drugs had 0.1 times the odds of being poor quality compared with non-prequalified ACAs for the artemisinin component. When partner components of combination therapies were also considered, 12.1% were outside the acceptable API range, and WHO prequalified ACAs had 0.04 times the odds of being poor quality. Although the prevalence of poor quality ACAs was lower than reported elsewhere, the minority of samples found to be substandard is a cause for concern. Improvements in quality could be achieved by increasing the predominance of WHO prequalified products in the market. Continued monitoring of quality standards is essential.

Integration of novel low-cost colorimetric, laser photometric, and visual fluorescent techniques for rapid identification of falsified medicines in resource-poor areas: application to artemether-lumefantrine.

The availability of falsified antimalarial drugs can be reduced with effective drug regulatory agencies and proper enforcement. Fundamental to these agencies taking action, rapid identification must be made as soon as they appear in the market place. Since falsified antimalarials occur mostly in developing countries, performing drug analysis presents itself with unique challenges. A fundamental factor in choosing a useful technique is affordability and simplicity. Therefore, we suggest a three-tiered drug evaluation strategy for identifying a falsified drug in resource-poor areas. Tier I is a simple comparison of a tablet's weight and dimensions with official specifications. Tier II uses inexpensive photometric devices (laser and fluorescence) to evaluate a tablet. Suspicious samples from Tier I and II assessments are then subjected to a colorimetric assay for active ingredients identification and quantification. In this article, we evaluate a novel colorimetric assay for the simultaneous assessment of both lumefantrine and artemether in co-formulated Coartem™ tablets, and integrate the method with two novel, low-cost, fluorescence and laser photometric devices. Image analysis software is used for the assessments. Although artemether-lumefantrine is used as an example, the strategy may be adapted to other medicines.

Falsified antimalarials: a minireview.

Malaria is a curable disease, provided timely access to efficacious drugs is sought. Poor quality and, in particular, falsified antimalarial drugs harm the population of malaria endemic areas; they put lives in peril, cause economic losses to patients, families, industry, and generally undermine the trust in health systems. The extent of the problem is not easily assessed, and although a prevalence of up to 35% of poor-quality antimalarials has been reported, this number should be interpreted with caution given the heterogeneity of methods used to measure it. The trade in falsified antimalarials can be curtailed by putting in place drug quality surveillance, better legislation and improving the access and affordability of these essential drugs.

Quality of antimalarial drugs and antibiotics in Papua New Guinea: a survey of the health facility supply chain.

BACKGROUND: Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. METHODS AND FINDINGS: Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. CONCLUSIONS: This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing.

Substandard artemisinin-based antimalarial medicines in licensed retail pharmaceutical outlets in Ghana.

BACKGROUND & OBJECTIVES: The artemisinin-based antimalarial medicines are first line medicines in the treatment of severe and uncomplicated falciparum malaria. Numerous brands of these medicines manufactured in various countries are available in the Ghanaian market. The study was aimed at evaluating the authenticity and quality of selected brands of artemisinin-based antimalarial medicines marketed in Ghana. METHODS: In all, 14 artemisinin-based antimalarial medicines were purchased from pharmacies (P) and licensed chemical shops (LCSs) in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin layer chromatography were employed in determining the authenticity of the samples. Important quality assessment tests, namely uniformity of mass, crushing strength, disintegration time, and the percentage content of active pharmaceutical ingredients (APIs) were determined. RESULTS: All the brands tested contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of mass test while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 & AM6 failed the crushing strength test. All the six artemether-lumefantrine tablet brands passed the uniformity of mass, crushing strength and disintegration tests. Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the drugs. The other 13 artemisinin products contained either a lower (underdose) or higher (overdose) amount of the specified drug. Artesunate monotherapy tablets were readily available in pharmacies and licensed chemical shops. INTERPRETATION & CONCLUSION: All the artemisinin-based medicines tested (except AL1) were of substandard quality. The results demonstrate the need for continuous monitoring and evaluation of the quality of artemisininbased antimalarials in the Ghanaian market. Also, the practice of artemisinin antimalarial monotherapy is prevalent in Ghana. Determined efforts should, therefore, be made to eradicate the practice to prevent the development of resistance to the artemisinins.

Effect of the Affordable Medicines Facility--malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data.

BACKGROUND: Malaria is one of the greatest causes of mortality worldwide. Use of the most effective treatments for malaria remains inadequate for those in need, and there is concern over the emergence of resistance to these treatments. In 2010, the Global Fund launched the Affordable Medicines Facility--malaria (AMFm), a series of national-scale pilot programmes designed to increase the access and use of quality-assured artemisinin based combination therapies (QAACTs) and reduce that of artemisinin monotherapies for treatment of malaria. AMFm involves manufacturer price negotiations, subsidies on the manufacturer price of each treatment purchased, and supporting interventions such as communications campaigns. We present findings on the effect of AMFm on QAACT price, availability, and market share, 6-15 months after the delivery of subsidised ACTs in Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and Tanzania (including Zanzibar). METHODS: We did nationally representative baseline and endpoint surveys of public and private sector outlets that stock antimalarial treatments. QAACTs were identified on the basis of the Global Fund's quality assurance policy. Changes in availability, price, and market share were assessed against specified success benchmarks for 1 year of AMFm implementation. Key informant interviews and document reviews recorded contextual factors and the implementation process. FINDINGS: In all pilots except Niger and Madagascar, there were large increases in QAACT availability (25·8-51·9 percentage points), and market share (15·9-40·3 percentage points), driven mainly by changes in the private for-profit sector. Large falls in median price for QAACTs per adult equivalent dose were seen in the private for-profit sector in six pilots, ranging from US$1·28 to $4·82. The market share of oral artemisinin monotherapies decreased in Nigeria and Zanzibar, the two pilots where it was more than 5% at baseline. INTERPRETATION: Subsidies combined with supporting interventions can be effective in rapidly improving availability, price, and market share of QAACTs, particularly in the private for-profit sector. Decisions about the future of AMFm should also consider the effect on use in vulnerable populations, access to malaria diagnostics, and cost-effectiveness. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria, and the Bill & Melinda Gates Foundation.

Relationship between treatment-seeking behaviour and artemisinin drug quality in Ghana.

BACKGROUND: Artemisinin-based combination therapy (ACT) is currently the recommended first-line treatment for uncomplicated malaria infections. However, a significant proportion of ACT is assumed to be of poor quality, particularly in Africa. In addition, little is known about how treatment-seeking behaviour of individuals or drug price is associated with drug quality. METHODS: Caregivers of children less than 5 years of age were interviewed on their knowledge of malaria and their choices for treatment. Artemisinin drugs were then purchased from sellers that caregivers preferred or had previously patronized. The active ingredients were quantified by nuclear magnetic resonance spectroscopy. RESULTS: A negative relationship was anticipated between the education level of caregivers and the quality of anti-malarial drugs purchased. However, of the 33 drugs collected from 16 different shops, only one contained less than 80% of its purported active ingredient, and most drugs were within 90% of their listed amounts. No link was found between drug quality and price. Nonetheless, while ACT is the recommended first-line treatment in Ghana, 21% of the drugs collected were artemisinin monotherapy, and 27% of the ACT was not co-formulated. Among caregivers, higher education was found to be associated with both an increased likelihood of seeking treatment in a clinic first, as opposed to visiting drug shops or using herbal remedies, and with purchasing drugs from licensed sellers. CONCLUSION: Surprisingly, drug quality was found to be uniformly high and thus no significant relationship between price, treatment-seeking behaviour and the content of the active ingredients was observed. However, artemisinin monotherapy, which the WHO considers inappropriate therapy, was still widely available in Ghana in 2010. Monotherapy was more likely to be available in unlicensed vendors where less-educated caregivers generally shopped. This linkage between education, treatment-seeking behaviour and drug availability suggests that the global subsidy to reduce the cost of co-formulated ACT can play a significant role in increasing its availability.

Rectal artesunates, their utilization, and parental perception in the management of malaria in children from Abeokuta, southwestern Nigeria.

Utilization, efficacy, perception, and acceptability of rectal artesunates for treatment of malaria were assessed in 264 children below 5 years attending two tertiary health facilities in Abeokuta, Nigeria. The children systematically selected were 136 from State Hospital Ijaye and 128 from Federal Medical Centre (FMC), Idi-Aba. Body weights and vital statistics of the children were measured; and blood samples were collected before and 24 h after administration of the rectal artesunates (Plasmotrim-50/200 mg Artesunate) to evaluate the efficacy of the suppository. The first dose of rectal artesunate suppository was administered at a dose of 5-10 mg/kg of body weight per rectum. Giemsa thin and thick films were employed to determine parasite species, malaria parasite count/µL (MPC/µL), and percentage of parasitized red blood cells (PPRBCs). Data were analyzed using SPSS version 16.0. Plasmodium falciparum was the malaria parasite identified by blood examination, with a pretreatment prevalence of 98.9%. Male children had higher infection rate (55%) than females (45%), and infection among age groups and weight groups varied. Chi-square analysis revealed a significant difference between weight and malaria parasite count (p<0.05). Post-treatment analysis after 24 h showed that prevalence dropped by 73%, with females having higher crash rate (77%) than males (69%) but with no statistical difference (p>0.05) among the sexes. Chi-square analysis of pre- and post-treatment revealed a significant difference between MPC/µL and PPRBC at p<0.05. This confirmed the efficacy of rectal artesunate in reducing the parasite density (parasitaemia) within 24 h of treatment. On acceptability, 99.60% of parents accepted to use the suppository. However, 87.1% of parents preferred its usage, as it is easy to administer with no adverse effects when administered on their children. If health officials increase more public knowledge on the use of rectal artesunates, the high mortality now experienced in children under 5 years due to malaria disease would be greatly reduced.