31 research outputs found

    Determinants of the Cost-Effectiveness of Intermittent Preventive Treatment for Malaria in Infants and Children

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    BACKGROUND: Trials of intermittent preventive treatment in infants (IPTi) and children (IPTc) have shown promising results in reducing malaria episodes but with varying efficacy and cost-effectiveness. The effects of different intervention and setting characteristics are not well known. We simulate the effects of the different target age groups and delivery channels, seasonal or year-round delivery, transmission intensity, seasonality, proportions of malaria fevers treated and drug characteristics. METHODS: We use a dynamic, individual-based simulation model of Plasmodium falciparum malaria epidemiology, antimalarial drug action and case management to simulate DALYs averted and the cost per DALY averted by IPTi and IPTc. IPT cost components were estimated from economic studies alongside trials. RESULTS: IPTi and IPTc were predicted to be cost-effective in most of the scenarios modelled. The cost-effectiveness is driven by the impact on DALYs, particularly for IPTc, and the low costs, particularly for IPTi which uses the existing delivery strategy, EPI. Cost-effectiveness was predicted to decrease with low transmission, badly timed seasonal delivery in a seasonal setting, short-acting and more expensive drugs, high frequencies of drug resistance and high levels of treatment of malaria fevers. Seasonal delivery was more cost-effective in seasonal settings, and year-round in constant transmission settings. The difference was more pronounced for IPTc than IPTi due to the different proportions of fixed costs and also different assumed drug spacing during the transmission season. The number of DALYs averted was predicted to decrease as a target five-year age-band for IPTc was shifted from children under 5 years into older ages, except at low transmission intensities. CONCLUSIONS: Modelling can extend the information available by predicting impact and cost-effectiveness for scenarios, for outcomes and for multiple strategies where, for practical reasons, trials cann be carried out. Both IPTi and IPTc are generally cost-effective but could be rendered cost-ineffective by characteristics of the setting, drug or implementatio

    Examining appropriate diagnosis and treatment of malaria: availability and use of rapid diagnostic tests and artemisinin-based combination therapy in public and private health facilities in south east Nigeria

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    <p>Abstract</p> <p>Background</p> <p>Rapid diagnostic tests (RDTs) and Artemisinin-based combination therapy (ACT) have been widely advocated by government and the international community as cost-effective tools for diagnosis and treatment of malaria. ACTs are now the first line treatment drug for malaria in Nigeria and RDTs have been introduced by the government to bridge the existing gaps in proper diagnosis. However, it is not known how readily available these RDTs and ACTs are in public and private health facilities and whether health workers are actually using them. Hence, this study investigated the levels of availability and use of RDTs and ACTs in these facilities.</p> <p>Methods</p> <p>The study was undertaken in Enugu state, southeast Nigeria in March 2009. Data was collected from heads of 74 public and private health facilities on the availability and use of RDTs and ACTs. Also, the availability of RDTs and the types of ACTs that were available in the facilities were documented.</p> <p>Results</p> <p>Only 31.1% of the health facilities used RDTs to diagnose malaria. The majority used the syndromic approach. However, 61.1% of healthcare providers were aware of RDTs. RDTs were available in 53.3% of the facilities. Public health facilities and health facilities in the urban areas were using RDTs more and these were mainly bought from pharmacy shops and supplied by NGOs. The main reasons given for non use are unreliability of RDTs, supply issues, costs, preference for other methods of diagnosis and providers' ignorance. ACTs were the drug of choice for most public health facilities and the drugs were readily available in these facilities.</p> <p>Conclusion</p> <p>Although many providers were knowledgeable about RDTs, not many facilities used it. ACTS were readily available and used in public but not private health facilities. However, the reported use of ACTs with limited proper diagnosis implies that there could be high incidence of inappropriate case management of malaria which can also increase the economic burden of illnesses. Government and donors should ensure constant availability of RDTs in both public and private facilities, so that every treatment with ACTs is accompanied with proper diagnosis.</p

    Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

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    BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites

    A qualitative study of the feasibility and community perception on the effectiveness of artemether-lumefantrine use in the context of home management of malaria in south-west Nigeria

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    <p>Abstract</p> <p>Background</p> <p>In Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect. The treatment regimen of ACT is however more complicated than that of CQ. There is thus a need to determine the feasibility of using ACT at the home level and determine community perception on its use.</p> <p>Methods</p> <p>A before and after qualitative study using key informant interviews (KII) and focus group discussions (FGDs) was conducted in selected villages in Ona-Ara local government area. At baseline, 14 FGDs and 14 KIIs were conducted. Thereafter, community medicine distributors (CMDs) were trained in each village to dispense artemeter-lumenfantrine (AL) to febrile children aged 6–59 months presumed to have uncomplicated malaria. After one year of drug distribution, nine KIIs and 10 FGDs were conducted. Participants and key informants were mothers and fathers with children under five years, traditional heads of communities, opinion leaders and health workers.</p> <p>Results</p> <p>None of the participants have heard of AL prior to study. Participants were favourably disposed to introduction of AL into the community. Mothers/caregivers were said to have used AL in place of the orthodox drugs and herbs reported commonly used prior to study after commencement of AL distribution. The use of CMDs for drug distribution was acceptable to the participants and they were judged to be efficient as they were readily available, distributed correct dose of AL and mobilised the community effectively. AL was perceived to be very effective and no significant adverse event was reported. Major concerns to the sustainability of the program were the negative attitudes of health workers towards discharge of their duties, support to the CMDs and the need to provide CMDs incentives. In addition regular supply of drugs and adequate supervision of CMDs were advised.</p> <p>Conclusion</p> <p>Our findings showed that the use of AL at home and community level is feasible with adequate training of community medicine distributors and caregivers. Community members perceived AL to be effective thus fostering acceptability. The negative attitudes of the health workers and issue of incentives to CMDs need to be addressed for successful scaling-up of ACT use at community level.</p

    The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data

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    Background: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. Findings: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. Funding: Bill and Melinda Gates Foundation

    Evidence for perinatal and child health care guidelines in crisis settings: can Cochrane help?

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    <p>Abstract</p> <p>Background</p> <p>It is important that healthcare provided in crisis settings is based on the best available research evidence. We reviewed guidelines for child and perinatal health care in crisis situations to determine whether they were based on research evidence, whether Cochrane systematic reviews were available in the clinical areas addressed by these guidelines and whether summaries of these reviews were provided in Evidence Aid.</p> <p>Methods</p> <p>Broad internet searches were undertaken to identify relevant guidelines. Guidelines were appraised using AGREE and the clinical areas that were relevant to perinatal or child health were extracted. We searched The Cochrane Database of Systematic Reviews to identify potentially relevant reviews. For each review we determined how many trials were included, and how many were conducted in resource-limited settings.</p> <p>Results</p> <p>Six guidelines met selection criteria. None of the included guidelines were clearly based on research evidence. 198 Cochrane reviews were potentially relevant to the guidelines. These reviews predominantly addressed nutrient supplementation, breastfeeding, malaria, maternal hypertension, premature labour and prevention of HIV transmission. Most reviews included studies from developing settings. However for large portions of the guidelines, particularly health services delivery, there were no relevant reviews. Only 18 (9.1%) reviews have summaries in Evidence Aid.</p> <p>Conclusions</p> <p>We did not identify any evidence-based guidelines for perinatal and child health care in disaster settings. We found many Cochrane reviews that could contribute to the evidence-base supporting future guidelines. However there are important issues to be addressed in terms of the relevance of the available reviews and increasing the number of reviews addressing health care delivery.</p

    Why population-based data are crucial to achieving the Sustainable Development Goals.

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    Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data

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    BACKGROUND: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP). METHODS: Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data. RESULTS: The systematic review identified 169 published and 9 unpublished studies, 126 of which were shared with the WorldWide Antimalarial Resistance Network (WWARN) and 121 trials including 48,840 patients were included in the analysis. Prevalence of gametocytaemia by microscopy at enrolment was 12.1 % (5887/48,589), and increased with decreasing age, decreasing asexual parasite density and decreasing haemoglobin concentration, and was higher in patients without fever at presentation. After ACT treatment, gametocytaemia appeared in 1.9 % (95 % CI, 1.7–2.1) of patients. The appearance of gametocytaemia was lowest after AS-MQ and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24–3.12; P = 0.005 compared to AL) and AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 2.40–6.72; P < 0.001 compared to AL). Among individuals who had gametocytaemia before treatment, gametocytaemia clearance was significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00–1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63–0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio (AOR), 9.05; 95 % CI, 3.74–21.90; P < 0.001) and new (AOR, 3.03; 95 % CI, 1.66–5.54; P < 0.001) infections with asexual-stage parasites were strongly associated with development of gametocytaemia after day 7. CONCLUSIONS: AS-MQ and AL are more effective than DP and AS-AQ FDC in preventing gametocytaemia shortly after treatment, suggesting that the non-artemisinin partner drug or the timing of artemisinin dosing are important determinants of post-treatment gametocyte dynamics

    Management of severe paediatric malaria in resource-limited settings

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