scholarly journals Prevalence of Polymorphisms in Antifolate Drug Resistance Molecular Marker Genespvdhfrandpvdhpsin Clinical Isolates of Plasmodium vivax from Kolkata, India

2013 ◽  
Vol 58 (1) ◽  
pp. 196-200 ◽  
Author(s):  
Swagata Ganguly ◽  
Pabitra Saha ◽  
Moytrey Chatterjee ◽  
Ardhendu K. Maji
Keyword(s):  
Plasmodium Vivax ◽  
Therapeutic Efficacy ◽  
Point Mutations ◽  
Marker Genes ◽  
Clinical Trial Registry ◽  
Triple Mutant ◽  
Mutant Genotype ◽  
Content Type ◽  
Registration Number

ABSTRACTSulfadoxine-pyrimethamine has never been recommended for the treatment ofPlasmodium vivaxmalaria as the parasite is intrinsically resistant to pyrimethamine. The combination was introduced as a promising agent to treatPlasmodium falciparummalaria in many countries but was withdrawn after a few years due to development and spread of resistant strains. Presently, sulfadoxine-pyrimethamine is used as a partner drug of artemisinin-based combination therapy to treat uncomplicated falciparum malaria, and a combination of artesunate-sulfadoxine-pyrimethamine is currently in use in India. In countries like India, where bothP. vivaxandP. falciparumare equally prevalent, some proportion ofP. vivaxbacteria is exposed to sulfadoxine-pyrimethamine due to misdiagnosis and mixed infections. As reports on thein vivotherapeutic efficacy of sulfadoxine-pyrimethamine inP. vivaxare rare, the study of mutations in the marker genesP. vivaxdhfr(pvdhfr) andpvdhpsis important for predicting drug selection pressure and sulfadoxine-pyrimethamine resistance monitoring. We studied the prevalence of point mutations and haplotypes of both the genes in 80P. vivaxisolates collected from urban Kolkata, India, by the DNA sequencing method. Point mutation rates in both the genes were low. The double mutantpvdhfrA15N50R58N117I173(mutations are in boldface) and the single mutantpvdhpsgenotype S382G383K512A553V585were more prevalent, while 35% of the isolates harbored the wild-type genotype. The triple mutant ANRNI-SGKAV was found in 29.9% isolates. No quintuple mutant genotype was recorded. TheP. vivaxparasites in urban Kolkata may still be susceptible to sulfadoxine-pyrimethamine. Hence, a combination of antimalarial drugs like artesunate-sulfadoxine-pyrimethamine introduced forP. falciparuminfection might be effective inP. vivaxinfection also. Study of the therapeutic efficacy of this combination inP. vivaxis thus strongly suggested. (The study protocol was registered in the Clinical Trial Registry-India [CTRI] of the Indian Council of Medical Research under registration number CTRI/2011/09/002031.)

Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer

2021 ◽  
pp. ASN.2020091340
Author(s):  
Elizabeth R. Stremke ◽  
Gretchen N. Wiese ◽  
Sharon M. Moe ◽  
Meryl E. Wastney ◽  
Ranjani N. Moorthi ◽  
...  
Keyword(s):  
Healthy Adults ◽  
Clinical Trial Registry ◽  
Apparent Lack ◽  
Content Type ◽  
Dihydroxyvitamin D ◽  
Phosphorus Absorption ◽  
Dietary Phosphorus ◽  
Registration Number ◽  
Moderate Chronic Kidney Disease

BackgroundReducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method.MethodsPatients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP).ResultsIn total, n=8 patients with CKD (eGFR=29–55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant.ConclusionsIntestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined.Clinical Trial registry name and registration number:Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222

scholarly journals Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Anne C. G. Almeida ◽  
Maria C. B. Puça ◽  
Erick F. G. Figueiredo ◽  
Laila R. Barbosa ◽  
Yanka E. A. R. Salazar ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Ex Vivo ◽  
Plasma Concentrations ◽  
Similar Efficacy ◽  
Early Recurrence ◽  
Control Group ◽  
Recurrence Rates ◽  
Mutant Genotype ◽  
Content Type

ABSTRACT Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism.

scholarly journals Amplification ofpfmdr1,pfcrt,pvmdr1, and K13 Propeller Polymorphisms Associated with Plasmodium falciparum and Plasmodium vivax Isolates from the China-Myanmar Border

2015 ◽  
Vol 59 (5) ◽  
pp. 2554-2559 ◽  
Author(s):  
Jun Feng ◽  
Daili Zhou ◽  
Yingxue Lin ◽  
Huihui Xiao ◽  
He Yan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Yunnan Province ◽  
Point Mutations ◽  
Border Region ◽  
Molecular Surveillance ◽  
Content Type ◽  
Antimalarial Resistance ◽  
Local Transmission

ABSTRACTMalaria in the China-Myanmar border region is still severe; local transmission of both falciparum and vivax malaria persists, and there is a risk of geographically expanding antimalarial resistance. In this research, thepfmdr1,pfcrt,pvmdr1, and K13-propeller genotypes were determined in 26Plasmodium falciparumand 64Plasmodium vivaxisolates from Yingjiang county of Yunnan province. Thepfmdr1(11.5%),pfcrt(34.6%), andpvmdr1(3.1%) mutations were prevalent at the China-Myanmar border. The indigenous samples exhibited prevalences of 14.3%, 28.6%, and 14.3% forpfmdr1N86Y,pfcrtK76T, andpfcrtM74I, respectively, whereas the samples from Myanmar showed prevalences of 10.5%, 21.1%, and 5.3%, respectively. The most prevalent genotypes ofpfmdr1andpfcrtwere Y86Y184and M74N75T76, respectively. Nopvmdr1mutation occurred in the indigenous samples but was observed in two cases coming from Myanmar. In addition, we are the first to report on 10 patients (38.5%) with five different K13 point mutations. The F446I allele is predominant (19.2%), and its prevalence was 28.6% in the indigenous samples of Yingjiang county and 15.8% in samples from Myanmar. The present data might be helpful for enrichment of the molecular surveillance of antimalarial resistance and useful for developing and updating guidance for the use of antimalarials in this region.

scholarly journals Cytoplasmic Copper Detoxification in Salmonella Can Contribute to SodC Metalation but Is Dispensable during Systemic Infection

2017 ◽  
Vol 199 (24) ◽  
Author(s):  
Luke A. Fenlon ◽  
James M. Slauch
Keyword(s):  
Superoxide Dismutase ◽  
Immune Cells ◽  
Gastrointestinal Disease ◽  
Systemic Infection ◽  
Copper Binding ◽  
Wild Type ◽  
Triple Mutant ◽  
Content Type

ABSTRACT Salmonella enterica serovar Typhimurium is a leading cause of foodborne disease worldwide. Severe infections result from the ability of S. Typhimurium to survive within host immune cells, despite being exposed to various host antimicrobial factors. SodCI, a copper-zinc-cofactored superoxide dismutase, is required to defend against phagocytic superoxide. SodCII, an additional periplasmic superoxide dismutase, although produced during infection, does not function in the host. Previous studies suggested that CueP, a periplasmic copper binding protein, facilitates acquisition of copper by SodCII. CopA and GolT, both inner membrane ATPases that pump copper from the cytoplasm to the periplasm, are a source of copper for CueP. Using in vitro SOD assays, we found that SodCI can also utilize CueP to acquire copper. However, both SodCI and SodCII have a significant fraction of activity independent of CueP and cytoplasmic copper export. We utilized a series of mouse competition assays to address the in vivo role of CueP-mediated SodC activation. A copA golT cueP triple mutant was equally as competitive as the wild type, suggesting that sufficient SodCI is active to defend against phagocytic superoxide independent of CueP and cytoplasmic copper export. We also confirmed that a strain containing a modified SodCII, which is capable of complementing a sodCI deletion, was fully virulent in a copA golT cueP background competed against the wild type. These competitions also address the potential impact of cytoplasmic copper toxicity within the phagosome. Our data suggest that Salmonella does not encounter inhibitory concentrations of copper during systemic infection. IMPORTANCE Salmonella is a leading cause of gastrointestinal disease worldwide. In severe cases, Salmonella can cause life-threatening systemic infections, particularly in very young children, the elderly, or people who are immunocompromised. To cause disease, Salmonella must survive the hostile environment inside host immune cells, a location in which most bacteria are killed. Our work examines how one particular metal, copper, is acquired by Salmonella to activate a protein important for survival within immune cells. At high levels, copper itself can inhibit Salmonella. Using a strain of Salmonella that cannot detoxify intracellular copper, we also addressed the in vivo role of copper as an antimicrobial agent.

scholarly journals Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

2012 ◽  
Vol 56 (11) ◽  
pp. 5764-5773 ◽  
Author(s):  
Joel Tarning ◽  
Palang Chotsiri ◽  
Vincent Jullien ◽  
Marcus J. Rijken ◽  
Martin Bergstrand ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Plasmodium Vivax ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTAmodiaquine is effective for the treatment ofPlasmodium vivaxmalaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women withP. vivaxinfection and again after delivery. Twenty-seven pregnant women infected withP. vivaxmalaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and withoutP. vivaxinfections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of completein vivoconversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.

scholarly journals Emergence of Plasmodium vivax Resistance to Chloroquine in French Guiana

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Lise Musset ◽  
Christophe Heugas ◽  
Richard Naldjinan ◽  
Denis Blanchet ◽  
Pascal Houze ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Therapeutic Efficacy ◽  
French Guiana ◽  
Gene Copy Number ◽  
Chloroquine Resistance ◽  
World Health ◽  
Gene Copy ◽  
Content Type ◽  
Gene Copy Number Variation ◽  
Health Organization

ABSTRACT In South America, Plasmodium vivax resistance to chloroquine was recently reported in Brazil and Bolivia. The objective of this study was to collect data on chloroquine resistance in French Guiana by associating a retrospective evaluation of therapeutic efficacy with an analysis of recurrent parasitemia from any patients. Patients with P. vivax infection, confirmed by microscopy and a body temperature of ≥37.5°C, were retrospectively identified at Cayenne Hospital between 2009 and 2015. Follow-up and treatment responses were performed according to the World Health Organization protocol. Parasite resistance was confirmed after dosage of a plasma concentration of chloroquine and microsatellite characterization. The pvmdr1 and pvcrt-o genes were analyzed for sequence and gene copy number variation. Among the 172 patients followed for 28 days, 164 presented adequate clinical and parasitological responses. Eight cases of treatment failures were identified (4.7%; n = 8/172), all after 14 days. The therapeutic efficacy of chloroquine was estimated at 95.3% (95% confidence interval [CI], 92.5 to 98.1%; n = 164/172). Among the eight failures, five were characterized: two cases were true P. vivax chloroquine resistance (1.2%; 95% CI, 0 to 2.6%; n = 2/172), and three cases were found with subtherapeutic concentrations of chloroquine. No particular polymorphism in the Plasmodium vivax pvmdr1 and pvcrt-o genes was identified in the resistant parasites. This identified level of resistance of P. vivax to chloroquine in French Guiana does not require a change in therapeutic recommendations. However, primaquine should be administered more frequently to limit the spread of resistance, and there is still a need for a reliable molecular marker to facilitate the monitoring of P. vivax resistance to chloroquine.

scholarly journals Gene Models, Expression Repertoire, and Immune Response of Plasmodium vivax Reticulocyte Binding Proteins

2015 ◽  
Vol 84 (3) ◽  
pp. 677-685 ◽  
Author(s):  
Jenni Hietanen ◽  
Anongruk Chim-ong ◽  
Thanprakorn Chiramanewong ◽  
Jakub Gruszczyk ◽  
Wanlapa Roobsoong ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Significant Negative Correlation ◽  
Protein Coding ◽  
Content Type ◽  
Immune Pressure ◽  
The Family ◽  
Genes Encoding ◽  
Gene Models

Members of thePlasmodium vivaxreticulocyte binding protein (PvRBP) family are believed to mediate specific invasion of reticulocytes byP. vivax. In this study, we performed molecular characterization of genes encoding members of this protein family. Through cDNA sequencing, we constructed full-length gene models and verified genes that are protein coding and those that are pseudogenes. We also used quantitative PCR to measure theirin vivotranscript abundances in clinicalP. vivaxisolates. Like genes encoding related invasion ligands ofP. falciparum,Pvrbpexpression levels vary broadly across different parasite isolates. Through antibody measurements, we found that host immune pressure may be the driving force behind the distinctly high diversity of one of the family members, PvRBP2c. Mild yet significant negative correlation was found between parasitemia and the PvRBP2b antibody level, suggesting that antibodies to the protein may interfere with invasion.

scholarly journals Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin ResistanceIn Vivo

2011 ◽  
Vol 56 (1) ◽  
pp. 208-217 ◽  
Author(s):  
Keunsook K. Lee ◽  
Donna M. MacCallum ◽  
Mette D. Jacobsen ◽  
Louise A. Walker ◽  
Frank C. Odds ◽  
...  
Keyword(s):  
Weight Loss ◽  
Cell Wall ◽  
Candida Albicans ◽  
Point Mutations ◽  
Low Frequency ◽  
Normal Cells ◽  
Content Type ◽  
Echinocandin Resistance

ABSTRACTCandida albicanscells with increased cell wall chitin have reduced echinocandin susceptibilityin vitro. The aim of this study was to investigate whetherC. albicanscells with elevated chitin levels have reduced echinocandin susceptibilityin vivo. BALB/c mice were infected withC. albicanscells with normal chitin levels and compared to mice infected with high-chitin cells. Caspofungin therapy was initiated at 24 h postinfection. Mice infected with chitin-normal cells were successfully treated with caspofungin, as indicated by reduced kidney fungal burdens, reduced weight loss, and decreasedC. albicansdensity in kidney lesions. In contrast, mice infected with high-chitinC. albicanscells were less susceptible to caspofungin, as they had higher kidney fungal burdens and greater weight loss during early infection. Cells recovered from mouse kidneys at 24 h postinfection with high-chitin cells had 1.6-fold higher chitin levels than cells from mice infected with chitin-normal cells and maintained a significantly reduced susceptibility to caspofungin when testedin vitro. At 48 h postinfection, caspofungin treatment induced a further increase in chitin content ofC. albicanscells harvested from kidneys compared to saline treatment. Some of the recovered clones had acquired, at a low frequency, a point mutation inFKS1resulting in a S645Y amino acid substitution, a mutation known to confer echinocandin resistance. This occurred even in cells that had not been exposed to caspofungin. Our results suggest that the efficacy of caspofungin againstC. albicanswas reducedin vivodue to either elevation of chitin levels in the cell wall or acquisition ofFKS1point mutations.

scholarly journals Plasmodium vivax Chloroquine Resistance and Anemia in the Western Brazilian Amazon

2013 ◽  
Vol 58 (1) ◽  
pp. 342-347 ◽  
Author(s):  
Marly M. Marques ◽  
Monica R. F. Costa ◽  
Franklin S. Santana Filho ◽  
José L. F. Vieira ◽  
Margareth T. S. Nascimento ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Univariate Analysis ◽  
Control Program ◽  
Brazilian Amazon ◽  
Small Sample ◽  
Chloroquine Resistance ◽  
Public Health Issue ◽  
Content Type

ABSTRACTData on chloroquine (CQ)-resistantPlasmodium vivaxin Latin America is limited, even with the current research efforts to sustain an efficient malaria control program in all these countries whereP. vivaxis endemic and where malaria still is a major public health issue. This study estimatedin vivoCQ resistance in patients with uncomplicatedP. vivaxmalaria, with use of CQ and primaquine simultaneously, in the Brazilian Amazon. Of a total of 135 enrolled subjects who accomplished the 28-day follow-up, parasitological failure was observed in 7 (5.2%) patients, in whom plasma CQ and desethylchloroquine (DCQ) concentrations were above 100 ng/dl. Univariate analysis showed that previous exposure to malaria and a higher initial mean parasitemia were associated with resistance but not with age or gender. In the multivariate analysis, only high initial parasitemia remained significant. Hemoglobin levels were similar at the beginning of the follow-up and were not associated with parasitemia. However, at day 3 and day 7, hemoglobin levels were significantly lower in patients presenting CQ resistance. TheP. vivaxdhfr(pvdhfr),pvmrp1,pvmdr1, andpvdhpsgene mutations were not related to resistance in this small sample.P. vivaxCQ resistance is already a problem in the Brazilian Amazon, which could be to some extent associated with the simultaneous report of anemia triggered by this parasite, a common complication of the disease in most of the areas of endemicity.

scholarly journals Artemisinin Resistance at the China-Myanmar Border and Association with Mutations in the K13 Propeller Gene

2015 ◽  
Vol 59 (11) ◽  
pp. 6952-6959 ◽  
Author(s):  
Zenglei Wang ◽  
Yingna Wang ◽  
Mynthia Cabrera ◽  
Yanmei Zhang ◽  
Bhavna Gupta ◽  
...  
Keyword(s):  
Survival Rates ◽  
Point Mutations ◽  
Artemisinin Resistance ◽  
Ring Stage ◽  
Antimalarial Drug Resistance ◽  
Mutant Genotype ◽  
Content Type ◽  
Survival Assay ◽  
Using Data ◽  
Efficacy Studies

ABSTRACTArtemisinin resistance inPlasmodium falciparumparasites in Southeast Asia is a major concern for malaria control. Its emergence at the China-Myanmar border, where there have been more than 3 decades of artemisinin use, has yet to be investigated. Here, we comprehensively evaluated the potential emergence of artemisinin resistance and antimalarial drug resistance status inP. falciparumusing data and parasites from three previous efficacy studies in this region. These efficacy studies of dihydroartemisinin-piperaquine combination and artesunate monotherapy of uncomplicated falciparum malaria in 248P. falciparumpatients showed an overall 28-day adequate clinical and parasitological response of >95% and day 3 parasite-positive rates of 6.3 to 23.1%. Comparison of the 57 K13 sequences (24 and 33 from day 3 parasite-positive and -negative cases, respectively) identified nine point mutations in 38 (66.7%) samples, of which F446I (49.1%) and an N-terminal NN insertion (86.0%) were predominant. K13 propeller mutations collectively, the F446I mutation alone, and the NN insertion all were significantly associated with day 3 parasite positivity. Increased ring-stage survival determined using the ring-stage survival assay (RSA) was highly associated with the K13 mutant genotype. Day 3 parasite-positive isolates had ∼10 times higher ring survival rates than day 3 parasite-negative isolates. Divergent K13 mutations suggested independent evolution of artemisinin resistance. Taken together, this study confirmed multidrug resistance and emergence of artemisinin resistance inP. falciparumat the China-Myanmar border. RSA and K13 mutations are useful phenotypic and molecular markers for monitoring artemisinin resistance.

Sign in / Sign up

Export Citation Format

Share Document