Dataset Information

Clinical and molecular monitoring of Plasmodium falciparum resistance to antimalarial drug (artesunate+sulphadoxine-pyrimethamine) in two highly malarious district of Madhya Pradesh, Central India from 2012-2014.

ABSTRACT: The spread of P. falciparum resistant strain has led to a significant resurgence of malaria morbidity and mortality. The current cornerstone in malaria treatment in India is Artemisinin based Combination (Artesunate + Sulphadoxine-Pyrimethamine) Therapy (ACT) for treatment of uncomplicated P. falciparum malaria since 2010. In the present study we assessed the therapeutic efficacy of ACT and molecular monitoring of antimalarial resistance. Therapeutic efficacy was determined by in vivo method using 28 days follow-up. Molecular genotyping of dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps) and kelch13 genes were analyzed. msp-1 and msp-2 genotyping were used to differentiate recrudescence. Therapeutic efficacy of ACT was determined in 237 patients over the three year period. Most of the patients showed adequate clinical and parasitological response (99.6%). Molecular study revealed that 72% parasites were of mutant genotype (27.2% single mutants, 43.5% double mutants and 1.3% triple mutants) for pfdhfr while pfdhps showed 78.2% wild type alleles and 21.8% mutants (18.1% single mutants and 3.7% double mutants). Analysis of total 135 samples revealed mutation in k13 gene along with non-synonymous single mutation at codon M579T (1.5%) and double mutations at codon M579T & N657H in 37%. ACT remains effective for the treatment of uncomplicated P. falciparum malaria in Madhya Pradesh, Central India. However, increasing mutation in pfdhfr (particularly triple mutations) and pfdhps may reduce susceptibility to partner drug SP and mutation in k13 propeller gene, highlighting the need for continuous monitoring of the efficacy of ACT.

SUBMITTER: Mishra S

PROVIDER: S-EPMC5498763 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Clinical and molecular monitoring of Plasmodium falciparum resistance to antimalarial drug (artesunate+sulphadoxine-pyrimethamine) in two highly malarious district of Madhya Pradesh, Central India from 2012-2014.

Mishra Sweta S Bharti Praveen K PK Shukla Man M MM Ali Nazia A NA Kashyotia Sher S SS Kumar Avdhesh A Dhariwal Akshay C AC Singh Neeru N

Pathogens and global health 20170526 4

The spread of P. falciparum resistant strain has led to a significant resurgence of malaria morbidity and mortality. The current cornerstone in malaria treatment in India is Artemisinin based Combination (Artesunate + Sulphadoxine-Pyrimethamine) Therapy (ACT) for treatment of uncomplicated P. falciparum malaria since 2010. In the present study we assessed the therapeutic efficacy of ACT and molecular monitoring of antimalarial resistance. Therapeutic efficacy was determined by in vivo method usi ...[more]

PMID: 28549390

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Project description:BackgroundAn epidemiological and entomological study was carried out in Balaghat district, Madhya Pradesh, India to understand the dynamics of forest malaria transmission in a difficult and hard to reach area where indoor residual spray and insecticide treated nets were used for vector control.MethodsThis community based cross-sectional study was undertaken from January 2010 to December 2012 in Baihar and Birsa Community Health Centres of district Balaghat for screening malaria cases. Entomological surveillance included indoor resting collections, pyrethrum spray catches and light trap catches. Anophelines were assayed by ELISA for detection of Plasmodium circumsporozoite protein.FindingsPlasmodium falciparum infection accounted for >80% of all infections. P. vivax 16.5%, P. malariae 0.75% and remaining were mixed infections of P. falciparum, P. vivax and P. malariae. More than, 30% infections were found in infants under 6 months of age. Overall, an increasing trend in malaria positivity was observed from 2010 to 2012 (chi-square for trend = 663.55; P<0.0001). Twenty five Anopheles culicifacies (sibling species C, D and E) were positive for circumsporozoite protein of P. falciparum (44%) and P. vivax (56%). Additionally, 2 An. fluviatilis, were found positive for P. falciparum and 1 for P. vivax (sibling species S and T). An. fluviatilis sibling species T was found as vector in forest villages for the first time in India.ConclusionThese results showed that the study villages are experiencing almost perennial malaria transmission inspite of indoor residual spray and insecticide treated nets. Therefore, there is a need for new indoor residual insecticides which has longer residual life or complete coverage of population with long lasting insecticide treated nets or both indoor residual spray and long lasting bed nets for effective vector control. There is a need to undertake a well designed case control study to evaluate the efficacy of these interventions.

Project description:Intermittent preventive treatment for malaria in children (IPTc) involves the administration of a full course of an anti-malarial treatment to children under 5 years old at specified time points regardless of whether or not they are known to be infected, in areas where malaria transmission is seasonal. It is important to determine the costs associated with IPTc delivery via community based volunteers and also the potential savings to health care providers and caretakers due to malaria episodes averted as a consequence of IPTc.Two thousand four hundred and fifty-one children aged 3-59 months were randomly allocated to four groups to receive: three days of artesunate plus amodiaquine (AS+AQ) monthly, three days of AS+AQ bimonthly, one dose of sulphadoxine-pyrimethamine (SP) bi-monthly or placebo. This paper focuses on incremental cost effectiveness ratios (ICERs) of the three IPTc drug regimens as delivered by community based volunteers (CBV) in Hohoe, Ghana compared to current practice, i.e. case management in the absence of IPTc. Financial and economic costs from the publicly funded health system perspective are presented. Treatment costs borne by patients and their caretakers are also estimated to present societal costs. The costs and effects of IPTc during the intervention period were considered with and without a one year follow up. Probabilistic sensitivity analysis was undertaken to account for uncertainty.Economic costs per child receiving at least the first dose of each course of IPTc show SP bimonthly, at US$8.19, is the cheapest to deliver, followed by AS+AQ bimonthly at US$10.67 and then by AS+AQ monthly at US$14.79. Training, drug delivery and supervision accounted for approximately 20-30% each of total unit costs. During the intervention period AS & AQ monthly was the most cost effective IPTc drug regimen at US$67.77 (61.71-74.75, CI 95%) per malaria case averted based on intervention costs only, US$64.93 (58.92-71.92, CI 95%) per malaria case averted once the provider cost savings are included and US$61.00 (54.98, 67.99, CI 95%) when direct household cost savings are also taken into account. SP bimonthly was US$105.35 (75.01-157.31, CI 95%) and AS & AQ bimonthly US$211.80 (127.05-399.14, CI 95%) per malaria case averted based on intervention costs only. The incidence of malaria in the post intervention period was higher in children who were <1 year old when they received AS+AQ monthly compared to the placebo group leading to higher cost effectiveness ratios when one year follow up is included. The cost per child enrolled fell considerably when modelled to district level as compared to those encountered under trial conditions.We demonstrate how cost-effective IPTc is using three different drug regimens and the possibilities for reducing costs further if the intervention was to be scaled up to the district level. The need for effective training, drug delivery channels and supervision to support a strong network of community based volunteers is emphasised.

Project description:BackgroundMalaria Elimination Demonstration Project (MEDP) was started as a Public-Private-Partnership between the Indian Council of Medical Research through National Institute of Research in Tribal Health, Govt. of Madhya Pradesh and Foundation of Disease Elimination and Control of India, which is a Corporate Social Responsibility (CSR) initiative of the Sun Pharmaceutical Industries Limited. The project's goal was to demonstrate that malaria can be eliminated from a high malaria endemic district along with prevention of re-establishment of malaria and to develop a model for malaria elimination using the lessons learned and knowledge acquired from the demonstration project.MethodsThe project employed tested protocols of robust surveillance, case management, vector control, and capacity building through continuous evaluation and training. The model was developed using the learnings from the operational plan, surveillance and case management, monitoring and feedback, entomological investigations and vector control, IEC and capacity building, supply chain management, mobile application (SOCH), and independent reviews of MEDP.ResultsThe MEDP has been operational since April 2017 with field operations from August 2017, and has observed: (1) reduction in indigenous cases of malaria by about 91 %; (2) need for training and capacity building of field staff for diagnosis and treatment of malaria; (3) need for improvement insecticide spraying and for distribution and usage of bed-nets; (4) need for robust surveillance system that captures and documents information on febrile cases, RDT positive individuals, and treatments provided; (5) need for effective supervision of field staff based on advance tour plan; (6) accountability and controls from the highest level to field workers; and (7) need for context-specific IEC.ConclusionsMalaria elimination is a high-priority public health goal of the Indian Government with a committed deadline of 2030. In order to achieve this goal, built-in systems of accountability, ownership, effective management, operational, technical, and financial controls will be crucial components for malaria elimination in India. This manuscript presents a model for malaria elimination with district as an operational unit, which may be considered for malaria elimination in India and other countries with similar geography, topography, climate, endemicity, health infrastructure, and socio-economic characteristics.

Project description:BackgroundFirst-line schizontocidal treatment for uncomplicated malaria in the Republic of the Sudan is artesunate (total dose 12 mg/kg) plus Sulphadoxine/pyrimethamine (25/1.25 mg/kg) (AS/SP). Patients with Plasmodium vivax are also treated with 14 days primaquine (total dose 3.5 mg/kg) (PQ). The aim of this study was to assess the efficacy of the national policy.MethodsPatients above 1 year, with microscopy-confirmed, Plasmodium falciparum and/or P. vivax malaria were treated with AS/SP. Patients with P. falciparum were randomized to no primaquine (Pf-noPQ) or a single 0.25 mg/kg dose of PQ (Pf-PQ1). Patients with P. vivax received 14 days unsupervised 3.5 mg/kg PQ (Pv-PQ14) on day 2 or at the end of follow up (Pv-noPQ). Primary endpoint was the risk of recurrent parasitaemia at day 42. G6PD activity was measured by spectrophotometry and the Accessbio Biosensor™.Results231 patients with P. falciparum (74.8%), 77 (24.9%) with P. vivax and 1 (0.3%) patient with mixed infection were enrolled. The PCR corrected cumulative risk of recurrent parasitaemia on day 42 was 3.8% (95% CI 1.2-11.2%) in the Pf-noPQ arm compared to 0.9% (95% CI 0.1-6.0%) in the Pf-PQ1 arm; (HR = 0.25 [95% CI 0.03-2.38], p = 0.189). The corresponding risks of recurrence were 13.4% (95% CI 5.2-31.9%) in the Pv-noPQ arm and 5.3% (95% CI 1.3-19.4%) in the Pv-PQ14 arm (HR 0.36 [95% CI 0.1-2.0], p = 0.212). Two (0.9%) patients had G6PD enzyme activity below 10%, 19 (8.9%) patients below 60% of the adjusted male median. Correlation between spectrophotometry and Biosensor™ was low (rs = 0.330, p < 0.001).ConclusionAS/SP remains effective for the treatment of P. falciparum and P. vivax. The addition of PQ reduced the risk of recurrent P. falciparum and P. vivax by day 42, although this did not reach statistical significance. The version of the Biosensor™ assessed is not suitable for routine use. Trial registration https://clinicaltrials.gov/ct2/show/NCT02592408.

Dataset Information

Clinical and molecular monitoring of Plasmodium falciparum resistance to antimalarial drug (artesunate+sulphadoxine-pyrimethamine) in two highly malarious district of Madhya Pradesh, Central India from 2012-2014.

Publications

Clinical and molecular monitoring of Plasmodium falciparum resistance to antimalarial drug (artesunate+sulphadoxine-pyrimethamine) in two highly malarious district of Madhya Pradesh, Central India from 2012-2014.

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