Prescription practices and availability of artemisinin monotherapy in India: where do we stand?

<p>Abstract</p> <p>Background</p> <p>The World Health Organization has urged all member states to deploy artemisinin-based combination therapy and progressively withdraw oral artemisinin monotherapies from the market due to their high recrudescence rates and to reduce the risk of drug resistance. Prescription practices by physicians and the availability of oral artemisinin monotherapies with pharmacists directly affect the pattern of their use. Thus, treatment practices for malaria, with special reference to artemisinin monotherapy prescription, in selected states of India were evaluated.</p> <p>Methods</p> <p>Structured, tested questionnaires were used to conduct convenience surveys of physicians and pharmacists in eleven purposively selected districts across six states in 2008. In addition, exit interviews of patients with a diagnosis of uncomplicated malaria or a prescription for an anti-malarial drug were also performed. Logistic regression was used to determine patient clinical care, and institutional factors associated with artemisinin monotherapy prescription.</p> <p>Results</p> <p>Five hundred and eleven physicians from 196 health facilities, 530 pharmacists, and 1, 832 patients were interviewed. Artemisinin monotherapy was available in 72.6% of pharmacies and was prescribed by physicians for uncomplicated malaria in all study states. Exit interviews among patients confirmed the high rate of use of artemisinin monotherapy with 14.8% receiving such a prescription. Case management, i.e. method of diagnosis and overall treatment, varied by state and public or private sector. Treatment in the private sector (OR 8.0, 95%CI: 3.8, 17) was the strongest predictor of artemisinin monotherapy prescription when accounting for other factors. Use of the combination therapy recommended by the national drug policy, artesunate + sulphadoxine-pyrimethamine, was minimal (4.9%), with the exception of one state.</p> <p>Conclusions</p> <p>Artemisinin monotherapy use was widespread across India in 2008. The accessible sale of oral artemisinin monotherapy in retail market and an inadequate supply of recommended drugs in the public sector health facilities promoted its prescription. This study resulted in notifications to all state drug controllers in India to withdraw the oral artemisinin formulations from the market. In 2010, artesunate + sulphadoxine-pyrimethamine became the universal first-line treatment for confirmed <it>Plasmodium falciparum </it>malaria and was deployed at full scale.</p

Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL), a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h) was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required.</p> <p>Methods</p> <p>One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa) were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers <it>msp</it>-<it>1 </it>and <it>msp</it>-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in <it>pfmdr</it>1 was also carried out in the samples obtained from patients before and after the treatment.</p> <p>Results</p> <p>The PCR corrected cure rates were high at both the sites viz. 100% (n = 53) in Assam and 98.6% (n = 71) in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91) and 184 (91.3%, n = 91) of <it>pfmdr1 </it>gene.</p> <p>Conclusion</p> <p>AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria in India. The polymorphism in <it>pfmdr</it>1 gene is not co-related with clinical outcome. However, treatment failure can also occur due to incomplete absorption of the drug as is suspected in one case of failure at D7 in the study. AL can be a viable alternative of artesunate plus sulphadoxine/pyrimethamine (AS + SP), however, the drug should be used rationally and efficacy needs to be monitored periodically.</p

Malaria molecular epidemiology : lessons from the International Centers of Excellence for Malaria Research Network

Molecular epidemiology leverages genetic information to study the risk factors that affect the frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by the International Centers of Excellence for Malaria Research (ICEMR) network in a variety of malaria-endemic settings. First, we discuss various novel approaches to understand malaria incidence and gametocytemia, focusing on Plasmodium falciparum and Plasmodium vivax. Second, we describe and compare different parasite genotyping methods commonly used in malaria epidemiology and population genetics. Finally, we discuss potential applications of molecular epidemiological tools and methods toward malaria control and elimination efforts

Summary of 353 samples collected at three sites in India.

<p>Summary of 353 samples collected at three sites in India.</p

Comparison of individuals with symptomatic and asymptomatic malaria.

<p>A) Breadth of response to 265 <i>P</i>. <i>vivax</i> antigens, and 373 <i>P</i>. <i>falciparum</i> antigens in symptomatic (<i>P</i>. <i>vivax</i> = 58; <i>P</i>. <i>falciparum</i> = 38) and asymptomatic (<i>P</i>. <i>vivax</i> = 16; <i>P</i>. <i>falciparum</i> = 9) malaria-positive adults at three sites in India. The box indicates the first and third quartiles, the line side of the box indicates the median, and whiskers represent the minimum and maximum values. B) Average of mean intensity of antibody binding to 265 <i>P</i>. <i>vivax</i> and 373 <i>P</i>. <i>falciparum</i> antigens in symptomatic and asymptomatic malaria-positive adults, top of bars indicate the mean value and error bars represent 95% confidence interval of the mean. C) Average of <i>P</i>. <i>vivax</i> and <i>P</i>. <i>falciparum</i> asexual parasitemia (number of asexual parasites per microliter) in symptomatic and asymptomatic malaria-positive adults. Kruskal–Wallis/Dunn adjusted p-values for pairwise comparison of groups are shown as asterisks: 0.03 (*), 0.002 (**), 0.0002 (***), <0.0001 (****).</p

Age-dependent breadth and intensity of response to <i>P</i>. <i>vivax</i> and <i>P</i>. <i>falciparum</i>.

<p>Age-dependent A) breadth of response to 265 <i>P</i>. <i>vivax</i> and 373 <i>P</i>. <i>falciparum</i> antigens in children (n = 61) and adults (n = 129) from Raurkela and Nadiad. The box indicates the first and third quartiles, the line inside the box indicates the median, and whiskers represent the minimum and maximum values. B) Average of mean intensity of antibody binding to the same subset of <i>P</i>. <i>vivax</i> and <i>P</i>. <i>falciparum</i> antigens in children and adults, top of bars indicate the mean value and error bars represent 95% confidence interval of the mean. Kruskal–Wallis/Dunn adjusted p-values for pairwise comparison of groups are shown as asterisks: 0.03 (*), 0.002 (**), 0.0002 (***), <0.0001 (****).</p

Breadth of antibody response to <i>P</i>. <i>vivax</i> and <i>P</i>. <i>falciparum</i>.

<p>Breadth of response to A) 265 <i>P</i>. <i>vivax</i> and B) 373 <i>P</i>. <i>falciparum</i> antigens in samples collected from malaria-positive (Chennai = 45; Nadiad = 55; Raurkela = 74) and malaria-negative adults (Chennai = 25; Nadiad = 34; Raurkela = 32) at three sites in India. The box indicates the first and third quartiles, the line inside the box indicates the median, and whiskers represent the minimum and maximum values. Kruskal–Wallis/Dunn adjusted p-values for pairwise comparison of groups are shown as asterisks: 0.03 (*), 0.002 (**), 0.0002 (***), <0.0001 (****).</p

<i>Plasmodium falciparum</i> antigens recognized with greater intensity in asymptomatic individuals.

<p><i>Plasmodium falciparum</i> antigens recognized with greater intensity in asymptomatic individuals.</p

Serological profiles of malaria-positive and malaria-negative individuals from three sites in India.

<p>Heat map showing signal intensity of antibody binding to 265 <i>P</i>. <i>vivax</i> and 373 <i>P</i>. <i>falciparum</i> polypeptides in 236 malaria-positive and 117 malaria-negative samples collected from Raurkela, Nadiad and Chennai. Red indicates positive reactivity, white indicates no reactivity, and the gradient indicates intermediate reactivity. Samples for each site and <i>Plasmodium</i> antigens were ranked from left to right and top to bottom, respectively, by decreasing log₂(FOC).</p