Effectiveness Of Artemisinin-based Combination Therapies Research Articles

Incomplete Plasmodium falciparum growth inhibition following piperaquine treatment translates into increased parasite viability in the in vitro parasite reduction ratio assay.

Antimalarial resistance to the first-line partner drug piperaquine (PPQ) threatens the effectiveness of artemisinin-based combination therapy. In vitro piperaquine resistance is characterized by incomplete growth inhibition, i.e. increased parasite growth at higher drug concentrations. However, the 50% inhibitory concentrations (IC50) remain relatively stable across parasite lines. Measuring parasite viability of a drug-resistant Cambodian Plasmodium falciparum isolate in a parasite reduction ratio (PRR) assay helped to better understand the resistance phenotype towards PPQ. In this parasite isolate, incomplete growth inhibition translated to only a 2.5-fold increase in IC50 but a dramatic decrease of parasite killing in the PRR assay. Hence, this pilot study reveals the potential of in vitro parasite viability assays as an important, additional tool when it comes to guiding decision-making in preclinical drug development and post approval. To the best of our knowledge, this is the first time that a compound was tested against a drug-resistant parasite in the in vitro PRR assay.

Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A case study of severe malaria from Mozambique

BackgroundThe effectiveness of artemisinin-based combination therapies (ACT) in treating Plasmodium falciparum, is vital for global malaria control efforts, particularly in sub-Saharan Africa. The examination of imported cases from endemic areas holds implications for malaria chemotherapy on a global scale. MethodA 45-year-old male presented with high fever, dry cough, diarrhoea and generalized muscle pain, following a two-week trip to Mozambique. P. falciparum infection with hiperparasitemia was confirmed and the patient was treated initially with quinine and doxycycline, then intravenous artesunate. To assess drug susceptibility, ex vivo half-maximal inhibitory concentration assays were conducted, and the isolated P. falciparum genome was deep sequenced. ResultsThe clinical isolate exhibited elevated ex vivo half-maximal inhibitory concentration values to dihydroartemisinin, lumefantrine, mefloquine and piperaquine. Genomic analysis identified a I416V mutation in the P. falciparum Kelch13 (PF3D7_1343700) gene, and several mutations at the Kelch13 interaction candidate genes, pfkics (PF3D7_0813000, PF3D7_1138700, PF3D7_1246300), including the ubiquitin carboxyl-terminal hydrolase 1, pfubp1 (PF3D7_0104300). Mutations at the drug transporters and genes linked to next-generation antimalarial drug resistance were also present. ConclusionsThis case highlights the emergence of P. falciparum strains carrying mutations in artemisinin resistance-associated genes in Mozambique, couple with a reduction in ex vivo susceptibility to ACT drugs. Continuous surveillance of mutations linked to drug resistance and regular monitoring of drug susceptibility are imperative to anticipate the spread of potential resistant strains emerging in Mozambique and to maintain effective malaria control strategies.

Plasmodium falciparum Multidrug Resistance-1 (pfmdr1) Gene Mutation in Adults Malaria Patients Attending Murtala Muhammad Specialist Hospital Kano, Northwest Nigeria

Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine in Kano state northwestern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) gene. Hundred adult patients comprising 43 males and 57 females were recruited for the study. The mean age of participants is 36.4 years, minimum and maximum ages were 16 and 60 years respectively, while 41% of them fall within the range of 16 to 30 years. Blood isolates were then analyzed for the presence of malaria parasite using microscopy, the results show a high prevalence of P. falciparum infection in the subject (30%). Pfmdr1 gene, a molecular marker of artemisinin resistance, was successfully sequenced in 21 out of 100 P. falciparum isolates collected from recruited participants. Pfmdr1 mutations were found in 19.5% (4/33) of the samples isolated. The prevalence of the Pfmdr1 N86Y allele was found in 4 samples whilst Y184F and D1246Y were not detected. A total of 4 non-synonymous mutations at codon N86Y were detected. The presence of these mutations highlights the challenges for malaria treatment in Kano state, northwestern Nigeria using antimalarials such as artemether lumefantrine, mefloquine, amodiaquine quinine and lumefantrine.

Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017

BackgroundMalaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur.MethodsHere, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach.ResultsAll samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively.ConclusionThe results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.

Prevalence of Mutations in the Pfdhfr, Pfdhps, and Pfmdr1 Genes of Malarial Parasites Isolated from Symptomatic Patients in Dogondoutchi, Niger.

The effectiveness of artemisinin-based combination therapies (ACTs) depends not only on that of artemisinin but also on that of partner molecules. This study aims to evaluate the prevalence of mutations in the Pfdhfr, Pfdhps, and Pfmdr1 genes from isolates collected during a clinical study. Plasmodium genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the Pfdhfr (codons 51, 59, 108, and 164), Pfdhps (codons 436, 437, 540, 581, and 613), and Pfmdr1 (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were sequenced for the Pfdhfr, Pfdhps, and Pfmdr1 genes. A high prevalence of mutations in the Pfdhfr gene was observed at the level of the N51I (84.97%), C59R (92.62%), and S108N (97.39%) codons. The key K540E mutation in the Pfdhps gene was not observed. Only one isolate was found to harbor a mutation at codon I431V. The most common mutation on the Pfmdr1 gene was Y184F in 71.43% of the mutations found, followed by N86Y in 10.20%. The triple-mutant haplotype N51I/C59R/S108N (IRN) was detected in 97% of the samples. Single-mutant (ICS and NCN) and double-mutant (IRS, NRN, and ICN) haplotypes were prevalent at 97% and 95%, respectively. Double-mutant haplotypes of the Pfdhps (581 and 613) and Pfmdr (86 and 184) were found in 3% and 25.45% of the isolates studied, respectively. The study focused on the molecular analysis of the sequencing of the Pfdhfr, Pfdhps, and Pfmdr1 genes. Although a high prevalence of mutations in the Pfdhfr gene have been observed, there is a lack of sulfadoxine pyrimethamine resistance. There is a high prevalence of mutation in the Pfmdr184 codon associated with resistance to amodiaquine. These data will be used by Niger’s National Malaria Control Program to better monitor the resistance of Plasmodium to partner molecules in artemisinin-based combination therapies.

The influence of biological, epidemiological, and treatment factors on the establishment and spread of drug-resistant Plasmodium falciparum.

The effectiveness of artemisinin-based combination therapies (ACTs) to treat Plasmodium falciparum malaria is threatened by resistance. The complex interplay between sources of selective pressure-treatment properties, biological factors, transmission intensity, and access to treatment-obscures understanding how, when, and why resistance establishes and spreads across different locations. We developed a disease modelling approach with emulator-based global sensitivity analysis to systematically quantify which of these factors drive establishment and spread of drug resistance. Drug resistance was more likely to evolve in low transmission settings due to the lower levels of (i) immunity and (ii) within-host competition between genotypes. Spread of parasites resistant to artemisinin partner drugs depended on the period of low drug concentration (known as the selection window). Spread of partial artemisinin resistance was slowed with prolonged parasite exposure to artemisinin derivatives and accelerated when the parasite was also resistant to the partner drug. Thus, to slow the spread of partial artemisinin resistance, molecular surveillance should be supported to detect resistance to partner drugs and to change ACTs accordingly. Furthermore, implementing more sustainable artemisinin-based therapies will require extending parasite exposure to artemisinin derivatives, and mitigating the selection windows of partner drugs, which could be achieved by including an additional long-acting drug.

Polymorphism Analysis of pfmdr1 and pfcrt from Plasmodium falciparum Isolates in Northwestern Nigeria Revealed the Major Markers Associated with Antimalarial Resistance.

Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine, across northern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) and chloroquine resistance transporter (pfcrt), in isolates from Kano, northwestern Nigeria. Out of the 88 samples genotyped for pfmdr1 N86Y mutation using PCR/restriction fragment length polymorphism, one sample contained the 86Y mutation (86Yfrequency = 1.14%). The analysis of 610 bp fragments of pfmdr1 from 16 isolates revealed two polymorphic sites and low haplotype diversity (Hd = 0.492), with only 86 Y mutations in one isolate, and 184 F replacements in five isolates (184Ffrequency = 31.25%). The analysis of 267 bp fragments of pfcrt isolates revealed high polymorphism (Hd = 0.719), with six haplotypes and seven non-synonymous polymorphic sites. Eleven isolates (61.11%) were chloroquine-resistant, CQR (C72V73I74E75T76 haplotype), two of which had an additional mutation, D57E. An additional sequence was CQR, but of the C72V73M74E75T76 haplotype, while the rest of the sequences (33.33%) were chloroquine susceptible (C72V73M74N75K76 haplotype). The findings of these well characterized resistance markers should be considered when designing resistance management strategies in the northwestern Nigeria.

What are the effects of artemisinin-based combination therapy for people with uncomplicated malaria?

What are the effects of artemisinin-based combination therapy for people with uncomplicated malaria?

Haematological and Histopathological Effects of Artemisinin-Based Combination Therapy in Healthy Mice

Artemisinin-based combination therapy had been recommended for the treatment of uncomplicated malaria in Africa. &#x0D; Aim: This study investigated the effects of artesunate/amodiaquine (A/A) and dihydroartemisinin/ piperaquine (D/P) on some blood parameters and histopathology of the liver and kidney of mice.&#x0D; Materials and Methods: A Complete randomized design was applied. Fifty mice were randomly assigned to five treatment groups of ten animals each. Therapeutic doses of the drugs were orally administered to the animals. Group A received normal saline (control), group B received 10/14mg/kg body weight of artesunate/amodiaquine for 3 days, group C received 10/18mg/kg of dihydroartemisinin/piperaquine for 3 days, group D received similar treatment with group B, but were followed up to 28 days, group E received similar treatment with group C but were also followed up to 28 days. After experimental period, blood samples were collected for determination of white blood cell count, white blood cell differential count, red blood cell count, packed cell volume and haemoglobin concentration. Liver and kidney were also harvested for histopathological analysis.&#x0D; Results: Result showed that therapeutic doses of artesunate/amodiaquine and dihydroaretmisinin/ piperaquine had no significant (P&gt;0.05) effects on heamatological parameters accessed. Mild inflammation and degeneration of hepatocyte were observed in the liver of the group treated with D/P while fatty change was found in the group treated with A/A. Venous congestion was observed in the kidney of the group treated with D/P. After 28 days, degeneration of hepatocyte and inflammatory cells were observed in the liver. Shrunken glomerulus was found in the kidney of the group treated with D/P.&#x0D; Conclusion: These drugs are detrimental to the liver and kidney even at therapeutic dose therefore, they should be used with caution.

Effect of Artemisinin-based Combination Therapies on Schistosomiasis on Malaria Co-infection

Effect of Artemisinin-based Combination Therapies on Schistosomiasis on Malaria Co-infection

The Effect of Artemisinin-based Combination Therapy (ACT) Antimalaria Drugs on Liver Enzymes in Pregnancy

Aims: Artemisinin-based Combination Therapies (ACTs) are employed as first-line agents in malaria chemotherapy. This study is aimed at assessing the effects of ACTs on renal function of pregnant women.&#x0D; Study Design: Comparative study.&#x0D; Place and Duration of Study: Pregnant women aged 18 to 50 years were recruited from antenatal clinic of Obstetrics and Gynecology Department of Ekiti State Hospital, Ado Ekiti, Nigeria between 2016 and 2018&#x0D; Methodology: One hundred and eighty pregnant women were grouped into three which include: Sixty pregnant women with malaria parasite on ACT drugs (Group A), sixty pregnant women with malaria parasite not on ACT drugs (Group B), sixty pregnant women without malaria parasite (Group C/control). Plasma Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Alanine Transaminase (ALT) and Lactate Dehydrogenase (LDH) activities were evaluated by standard methods. The data collected were analyzed using one-way analysis of variance (ANOVA) and Student’s t test to compare the data between the test groups and control.&#x0D; Results: Results showed there was a significant decrease (P=.05) in Body Mass Index in the pregnant women with malaria on ACT and those that were not on ACT when compared with control (24.1± 0.32 versus (25+ 2.30 vs 27± 1.62). A significant increase (P=.05) occurred in the levels of ALP,AST, ALT and LDH in pregnant women with malaria not on ACT drugs when compared the control (168.45±0.19, 10.0±0.27, 8.19±0.25, 4.5±0.21) versus (143.20±0.12, 8.71±0.30, 5.99±0.21, 2.08±0.19),while no significant difference occurred in the levels of ALP,AST, ALT and LDH in pregnant women with malaria on ACT when compared with control (141.60±0.78, 8.02±0.32, 6.10±0.30, 2.75+ 0.20) vs (143.20±0.12, 8.71±0.30, 5.99±0.21, 2.08±0.19).&#x0D; Conclusion: Normal therapeutic dose of ACT has no harmful effect on the liver in pregnancy.

In Vitro Assessment of Antiplasmodial Activity and Cytotoxicity of Polyalthia longifolia Leaf Extracts on Plasmodium falciparum Strain NF54.

Background Malaria is one of the most important life-threatening infectious diseases in the tropics. In spite of the effectiveness of artemisinin-based combination therapy, reports on reduced sensitivity of the parasite to artemisinin in Cambodia and Thailand warrants screening for new potential antimalarial drugs for future use. Ghanaian herbalists claim that Polyalthia longifolia has antimalarial activity. Therefore, antiplasmodial activity, cytotoxic effects, and antioxidant and phytochemical properties of P. longifolia leaf extract were investigated in this study. Methodology/Principal Findings Aqueous, 70% hydroethanolic and ethyl acetate leaf extracts were prepared using standard procedures. Antiplasmodial activity was assessed in vitro by using chloroquine-sensitive malaria parasite strain NF54. The SYBR® Green and tetrazolium-based calorimetric assays were used to measure parasite growth inhibition and cytotoxicity, respectively, after extract treatment. Total antioxidant activity was evaluated using a free radical scavenging assay. Results obtained showed that extracts protected red blood cells against Plasmodium falciparum mediated damage. Fifty percent inhibitory concentration (IC50) values were 24.0±1.08 μg/ml, 22.5±0.12 μg/ml, and 9.5±0.69 μg/ml for aqueous, hydroethanolic, and ethyl acetate extracts, respectively. Flavonoids, tannins, and saponins were present in the hydroethanolic extract, whereas only the latter was observed in the aqueous extract. Aqueous and hydroethanolic extracts showed stronger antioxidant activities compared to the ethyl acetate extract. Conclusions/Significance The extracts of P. longifolia have antiplasmodial properties and low toxicities to human red blood cells. The extracts could be developed as useful alternatives to antimalarial drugs. These results support claims of the herbalists that decoctions of P. longifolia are useful antimalarial agents.

Characterization of Plasmodium falciparum structure in Nigeria with malaria SNPs barcode

BackgroundPlasmodium falciparum malaria remains a major health challenge in Nigeria despite the global decline of its incidence and mortality rates. Although significant progress has been made in preventing the transmission of P. falciparum and controlling the spread of the infection, there is much to be done in the area of proper monitoring, surveillance of the parasite, investigating the population dynamics and drug resistance profiling of the parasite as these are important to its eventual eradication. Polymorphic loci of msp1, msp2 and/or glurp genes or microsatellites have been traditionally used to characterize P. falciparum population structure in various parts of Nigeria. The lack of standardization in the interpretation of results, as well as the inability of these methods to distinguish closely related parasites, remains a limitation of these techniques. Conversely, the recently developed 24 single nucleotide polymorphism (SNP)-based molecular barcode assay has the possibility of differentiating between closely related parasites and offer additional information in determining the population diversity of P. falciparum within and between parasite populations. This study is therefore aimed at defining the population diversity of P. falciparum in and between two localities in Nigeria using the SNPs barcode technique.MethodsThe 24-SNP high-resolution melt (HRM) barcode assay and msp2 genotyping was used to investigate both intra and inter population diversity of the parasite population in two urban cities of Nigeria.ResultsBased on SNP barcode analysis, polygenomic malaria infections were observed in 17.9% and 13.5% of population from Enugu and Ibadan, respectively, while msp2 analyses showed 21% and 19.4% polygenomic infections in Enugu and Ibadan, respectively. Low levels of genetic diversity (π) of 0.328 and 0.318 were observed in Enugu and Ibadan parasite populations, respectively, while the FST value of 0.02 (p = 0.055) was obtained when the genetic divergence of both populations was considered.ConclusionsThe 24-SNP barcode assay was effective in analysing P. falciparum population diversity. This study also showed that P. falciparum populations in Enugu and Ibadan had a degree of intra-population diversity, but very low divergence between the population. A low degree of polygenomic infections were also observed in the two parasite populations unlike previous years. This maybe as a result of the effect of artemisinin-based combination therapy (ACT), long-lasting insecticide-treated nets (LLITNs) and intermittent preventive treatments in the study populations.

Effects of artemisinin, with or without lumefantrine and amodiaquine on gastric ulcer healing in rat.

Abstract Background Antimalarial drugs have been shown to predispose the stomach to ulceration in rats. However, their role in the modulation of gastric ulcer healing is not known. The aim of the present study is to investigate the effect of artemisinin-based combination therapies on ulcer healing. Methods Gastric kissing ulcers were induced in 40 male albino rats (150–180 g) using 0.2 mL 50% acetic acid. One day after the ulcer induction, experimental rats were divided into four groups and treated once daily orally for 3 days as follows: (1) normal saline, (2) artemether-lumefantrine (2/12 mg/kg), (3) artesunate-amodiaquine (4/10 mg/kg), and (4) artesunate (2 mg/kg) only. A fifth group of 10 rats served as overall control with no ulcer induced and no treatment given. Ulcer healing was determined on days 4 and 7 post induction using ulcer score and planimetry. Results Artesunate decreased ulcer severity by 12.5% and 52.0% on days 4 and 7, respectively. Significant increases in severity were observed in rats treated with artemether-lumefantrine (25.0% and 40.0%) and artesunate-amodiaquine (50.0% and 95.0%). Lipid peroxidation was decreased by artesunate by day 7 (27%; p&lt;0.05) but increased in artemether-lumefantrine and artesunate-amodiaquine administered rats (63.6% and 55%; p&lt;0.05). The activity of superoxide dismutase was reduced by artesunate-amodiaquine on day 7 (22%; p&lt;0.05) but no effect in the artemether-lumefantrine treatment. Neutrophil infiltration, total leukocyte count, neutrophil-lymphocyte ratio, and C-reactive protein values were significantly increased in the artemether-lumefantrine and artesunate-amodiaquine treated groups when compared with the untreated ulcer control group (p&lt;0.05). These variables were all reduced by artesunate (p&lt;0.05). Conclusions This study revealed that although artesunate may be beneficial in gastric ulcer healing, its combination with either lumefantrine or amodiaquine may delay healing of gastric mucosal injury.

Household beliefs about malaria testing and treatment in Western Kenya: the role of health worker adherence to malaria test results

BackgroundAlthough use of malaria diagnostic tests has increased in recent years, health workers often prescribe anti-malarial drugs to individuals who test negative for malaria. This study investigates how health worker adherence to malaria case management guidelines influences individuals’ beliefs about whether their illness was malaria, and their confidence in the effectiveness of artemisinin-based combination therapy (ACT).MethodsA survey was conducted with 2065 households in Western Kenya about a household member’s treatment actions for a recent febrile illness. The survey also elicited the individual’s (or their caregiver’s) beliefs about the illness and about malaria testing and treatment. Logistic regressions were used to test the association between these beliefs and whether the health worker adhered to malaria testing and treatment guidelines.ResultsOf the 1070 individuals who visited a formal health facility during their illness, 82% were tested for malaria. ACT rates for malaria-positive and negative individuals were 89 and 49%, respectively. Overall, 65% of individuals/caregivers believed that the illness was “very likely” malaria. Individuals/caregivers had higher odds of saying that the illness was “very likely” malaria when the individual was treated with ACT, and this was the case both among individuals not tested for malaria [adjusted odds ratio (AOR) 3.42, 95% confidence interval (CI) [1.65 7.10], P = 0.001] and among individuals tested for malaria, regardless of their test result. In addition, 72% of ACT-takers said the drug was “very likely” effective in treating malaria. However, malaria-negative individuals who were treated with ACT had lower odds of saying that the drugs were “very likely” effective than ACT-takers who were not tested or who tested positive for malaria (AOR 0.29, 95% CI [0.13 0.63], P = 0.002).ConclusionIndividuals/caregivers were more likely to believe that the illness was malaria when the patient was treated with ACT, regardless of their test result. Moreover, malaria-negative individuals treated with ACT had lower confidence in the drug than other individuals who took ACT. These results suggest that ensuring health worker adherence to malaria case management guidelines will not only improve ACT targeting, but may also increase patient/caregivers’ confidence in malaria testing and treatment.

Effect of Artemisinin-Based Combination Therapy on some Selected Liver Function Indices of Pregnant Wistar Albino Rats

Article history: Received on: 28/06/2013 Revised on: 19/08/2013 Accepted on: 08/09/2013 In the risk assessment of the effect of administration of artemisinin-based combination therapy on some selected liver function indices of pregnant wistar albino rats. Fifteen (15) pregnant wistar albino rats were divided into three groups and were allowed to acclimatize to laboratory condition for seven (7) days. Rats in group A served as the control and were administered with normal saline throughout the experimental period of seven (7) days, while rats in group B and C were administered intra-peritoneally with 3 and 6mg/kg body weight of artemisininbased combination therapy respectively throughout the experimental period. Twenty four (24) hours after the last administration, the pregnant wistar albino rats were sacrificed. Blood was obtained by cardiac puncture for analysis of serum ALP, AST, ALT and bilirubin using standard methods and enzyme kits. The result showed that the drug at both 3and 6mg/kg body weight produced a significant (P<0.05) dosage increase in serum AST, ALT and ALP. The ratio of AST: ALT and AST: ALP showed a significant (P<0.05) increase. Similar pattern was also displayed by serum bilirubin concentration. These results are clear manifestations that artemisinin-based combination therapy might pose hepatic injury, hepatobilliary toxicity or complete hepatic damage in pregnant wistar albino rats. Thus, it is suggested that special precaution needs to be exercised on the usage of artemetherlumefantrine in pregnancy.

Impact assessment of malaria vector control using routine surveillance data in Zambia: implications for monitoring and evaluation

BackgroundMalaria vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with pyrethroids and DDT, to reduce malaria transmission has been expansively implemented in Zambia. The impact of these interventions on malaria morbidity and mortality has not previously been formally assessed at the population level in Zambia.MethodsThe impact of IRS (15 urban districts) and LLINs (15 rural districts) implementation on severe malaria cases, deaths and case fatality rates in children below the age of five years were compared. Zambian national Health Management Information System data from 2007 to 2008 were retrospectively analysed to assess the epidemiological impact of the two interventions using odds ratios to compare the pre-scaling up year 2007 with the scaling-up year 2008.ResultsOverall there were marked reductions in morbidity and mortality, with cases, deaths and case fatality rates (CFR) of severe malaria decreasing by 31%, 63% and 62%, respectively between 2007 and 2008. In urban districts with IRS introduction there was a significant reduction in mortality (Odds Ratio [OR] = 0.37, 95% CI = 0.31-0.43, P = 0.015), while the reduction in mortality in rural districts with LLINs implementation was not significant (OR = 0.83, 95% CI = 0.67-1.04, P = 0.666). A similar pattern was observed for case fatality rates with a significant reduction in urban districts implementing IRS (OR = 0.34, 95% CI = 0.33-0.36, P = 0.005), but not in rural districts implementing LLINs (OR = 0.96, 95% CI = 0.91-1.00, P = 0.913). No substantial difference was detected in overall reduction of malaria cases between districts implementing IRS and LLINs (P = 0.933).ConclusionRoutine surveillance data proved valuable for determining the temporal effects of malaria control with two strategies, IRS and LLINs on severe malaria disease in different types of Zambian districts. However, this analysis did not take into account the effect of artemisinin-based combination therapy (ACT), which were being scaled up countrywide in both rural and urban districts.

Relative costs and effectiveness of treating uncomplicated malaria in two rural districts in Zambia: implications for nationwide scale-up of home-based management

BackgroundMalaria case management is one of the key strategies to control malaria. Various studies have demonstrated the feasibility of home management of malaria (HMM). However, data on the costs and effectiveness of artemisinin-based combination therapy (ACT) and rapid diagnostic tests via HMM is limited.MethodCost-effectiveness of home management versus health facility-based management of uncomplicated malaria in two rural districts in Zambia was analysed from a providers' perspective. The sample included 16 community health workers (CHWs) and 15 health facilities. The outcome measure was the cost per case appropriately diagnosed and treated. Costs of scaling-up HMM nationwide were estimated based on the CHW utilisation rates observed in the study.ResultsHMM was more cost effective than facility-based management of uncomplicated malaria. The cost per case correctly diagnosed and treated was USD 4.22 for HMM and USD 6.12 for facility level. Utilization and adherence to diagnostic and treatment guidelines was higher in HMM than at a health facility.ConclusionHMM using ACT and RDTs was more efficient at appropriately diagnosing and treating malaria than the health facility level. Scaling up this intervention requires significant investments.

Community Effectiveness of Artemisinin-Based Combination Therapy for Malaria in Rural Southwestern Nigeria

A descriptive cross sectional survey using an interviewer-administered questionnaire was carried out among 700 caregivers whose children had fever during the previous two weeks. The aim was to determine the community effectiveness of malaria treatment using arthemeter-lumefantrine (AL) among under-5-year-olds in a rural community in southwestern Nigeria. A total of 353 (50.9%) children received AL. About half of these children (49%) were said to have been treated within 24 hours of onset of symptoms; 44% took the drug for the stipulated period of time; 42% received the correct dosage; and only 4% received all the treatment steps. With a drug efficacy of 100%, AL achieved a community effectiveness of 4%. The greatest effort in the home management of malaria strategy should be in reducing delay in treatment and improving dosage and duration of treatment.

Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: A report from three study sites in sub-Saharan Africa

BackgroundThe use of artemisinin-based combination therapy (ACT) at the community level has been advocated as a means to increase access to effective antimalarial medicines by high risk groups living in underserved areas, mainly in sub-Saharan Africa. This strategy has been shown to be feasible and acceptable to the community. However, the parasitological effectiveness of ACT when dispensed by community medicine distributors (CMDs) within the context of home management of malaria (HMM) and used unsupervised by caregivers at home has not been evaluated.MethodsIn a sub-set of villages participating in a large-scale study on feasibility and acceptability of ACT use in areas of high malaria transmission in Ghana, Nigeria and Uganda, thick blood smears and blood spotted filter paper were prepared from finger prick blood samples collected from febrile children between six and 59 months of age reporting to trained CMDs for microscopy and PCR analysis. Presumptive antimalarial treatment with ACT (artesunate-amodiaquine in Ghana, artemether-lumefantrine in Nigeria and Uganda) was then initiated. Repeat finger prick blood samples were obtained 28 days later for children who were parasitaemic at baseline. For children who were parasitaemic at follow-up, PCR analyses were undertaken to distinguish recrudescence from re-infection. The extent to which ACTs had been correctly administered was assessed through separate household interviews with caregivers having had a child with fever in the previous two weeks.ResultsOver a period of 12 months, a total of 1,740 children presenting with fever were enrolled across the study sites. Patent parasitaemia at baseline was present in 1,189 children (68.3%) and varied from 60.1% in Uganda to 71.1% in Ghana. A total of 606 children (51% of infected children) reported for a repeat test 28 days after treatment. The crude parasitological failure rate varied from 3.7% in Uganda (C.I. 1.2%–6.2%) to 41.8% in Nigeria (C.I. 35%–49%). The PCR adjusted parasitological cure rate was greater than 90% in all sites, varying from 90.9% in Nigeria (C.I. 86%–95%) to 97.2% in Uganda (C.I. 95%–99%). Reported adherence to correct treatment in terms of dose and duration varied from 81% in Uganda (C.I. 67%–95%) to 97% in Ghana (C.I. 95%–99%) with an average of 94% (C.I. 91%–97%).ConclusionWhile follow-up rates were low, this study provides encouraging data on parasitological outcomes of children treated with ACT in the context of HMM and adds to the evidence base for HMM as a public health strategy as well as for scaling-up implementation of HMM with ACTs.