We describe the MalariaGEN Pf7 data resource, the seventh release of
genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, ...including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging
mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the
gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.
Summary Community engagement is increasingly promoted in developing countries, especially in international health research, but there is little published experience. The Shoklo Malaria Research Unit ...(SMRU) conducts research with refugees, migrant workers, displaced people, and day migrants on the Thai-Burmese border, and has recently facilitated the set up of the Tak Province Border Community Ethics Advisory Board (T-CAB). Valuable lessons have been learnt from consultation with the T-CAB especially in the area of participant recruitment and the informed consent process. A lot of new research questions have emerged from consultation with the T-CAB. This paper describes our experience, lessons learnt and the unique challenges faced working with the T-CAB from its initial conception to date. We conclude that consultation with the T-CAB has made improvements in our research in particular operational and ethical aspects of our studies.
In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, ...atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P <.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval CI, 1.1–8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14–30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P ⩽.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria.
BackgroundIncreased pfmdr1 copy number is associated with reduced susceptibility to structurally unrelated antimalarial drugs. We assessed how administration of different antimalarial drugs altered ...pfmdr1 polymorphism in parasites from patients who experienced treatment failure MethodsIn studies conducted on the northwestern border of Thailand, amplifications and single-nucleotide polymorphisms in pfmdr1 were compared before and after antimalarial drug treatment ResultsIntrahost changes in pfmdr1 copy number were observed in 20% (26/132) of patients with recurrent infections. Among infections that recrudesced after mefloquine-containing regimens, increases in pfmdr1 copy number occurred in 68% (95% confidence interval CI, 46%–85%), and decreases occurred in 2% (95% CI, 0.4%–11%) of isolates; corresponding proportions after artemether-lumefantrine were 25% (2/8) and 11% (2/19); after quinine, 50% (1/2) and 40% (4/10); and after artemisinins alone, 0% (0/10) and 19% (3/16) of isolates (overall P<.001) ConclusionsIntrahost selection based on pfmdr1 copy number occurs frequently in parasite populations within individual patients. Amplification confers multidrug resistance but probably imposes a significant fitness cost to the parasites
Malaria continues to cause devastation during pregnancy. Unfortunately, there is still no clear strategy to effectively protect pregnant women and countless mothers living in malaria endemic ...countries are dying every year. The effective prevention of malaria during pregnancy will take much more than the so-called "Global Call for Action" for an intervention (IPTp-SP) that cannot succeed. A new and truly "global" strategy is urgently needed.
Purpose
We compared the pharmacokinetics of chloroquine in pregnant and nonpregnant women treated for
Plasmodium vivax
malaria.
Methods
Twelve pregnant women and 15 nonpregnant women of child-bearing ...age with acute
P. vivax
malaria were treated with 25 mg chloroquine base/kg over 3 days on the northwestern border of Thailand. Blood concentrations of chloroquine and desethylchloroquine were measured using hydrophilic interaction liquid chromatography coupled with fluorescence detection. Twenty-five women completed the pharmacokinetic study.
Results
Although increasing gestational age was associated with reduced chloroquine
, there was no significant difference overall in the pharmacokinetics of chloroquine between pregnant and nonpregnant women. Fever was associated with lower chloroquine
values. Desethylchloroquine area under the curve (AUC) values were not significantly affected by pregnancy.
Conclusions
Pregnancy did not significantly affect blood concentrations of chloroquine or its metabolite, desethylchloroquine, in women with
P. vivax
malaria.
Malaria parasites (Plasmodium falciparum) provide an excellent system in which to study the genomic effects of strong selection in a recombining eukaryote because the rapid spread of resistance to ...multiple drugs during the last the past 50 years has been well documented, the full genome sequence and a microsatellite map are now available, and haplotype data can be easily generated. We examined microsatellite variation around the dihydrofolate reductase (dhfr) gene on chromosome 4 of P. falciparum. Point mutations in dhfr are known to be responsible for resistance to the antimalarial drug pyrimethamine, and resistance to this drug has spread rapidly in Southeast (SE) Asia after its introduction in 1970s. We genotyped 33 microsatellite markers distributed across chromosome 4 in 61 parasites from a location on the Thailand/Myanmar border. We observed minimal microsatellite length variation in a 12-kb (0.7-cM) region flanking the dhfr gene and diminished variation for approximately 100 kb (6 cM), indicative of a single origin of resistant alleles. Furthermore, we found the same or similar microsatellite haplotypes flanked resistant dhfr alleles sampled from 11 parasite populations in five SE Asian countries indicating recent invasion of a single lineage of resistant dhfr alleles in locations 2000 km apart. Three features of these data are of especially interest. (1). Pyrimethamine resistance is generally assumed to have evolved multiple times because the genetic basis is simple and resistance can be selected easily in the laboratory. Yet our data clearly indicate a single origin of resistant dhfr alleles sampled over a large region of SE Asia. (2). The wide valley ( approximately 6 cM) of reduced variation around dhfr provides "proof-of-principle" that genome-wide association may be an effective way to locate genes under strong recent selection. (3). The width of the selective valley is consistent with predictions based on independent measures of recombination, mutation, and selection intensity, suggesting that we have reasonable estimates of these parameters. We conclude that scanning the malaria parasite genome for evidence of recent selection may prove an extremely effective way to locate genes underlying recently evolved traits such as drug resistance, as well as providing an opportunity to study the dynamics of selective events that have occurred recently or are currently in progress.
Burkholderia pseudomallei is a soil-dwelling aerobic bacterium prevalent in tropical and subtropical regions, particularly in Southeast Asia and Northern Australia. It is the causal organism of ...melioidosis, a severe infection that can manifest as chronic debilitating pneumonia resembling pulmonary tuberculosis. Here, we report a case of melioidosis, pulmonary tuberculosis, covid-19, and paragonimus co-infection in a 50-year-old male with poorly controlled diabetes mellitus and β-thalassemia trait. The patient recovered with intravenous antibiotics and standard anti-tuberculosis treatment.
Rectal pH in Well and Unwell Infants TURNER, Claudia; NAW AYE MYA THEIN; TURNER, Paul ...
Journal of tropical pediatrics (1980),
08/2012, Letnik:
58, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Prompt antibiotic treatment for infants with sepsis has the potential to save lives. A rectal formulation of an antibiotic could be used at a village level before referral to hospital. The ...development of such a preparation needs to take into account the rectal pH of infants that will affect drug partitioning and absorption. Rectal pH measurements were taken in 100 well and 45 unwell infants. We also measured rectal pH in 14 infants sequentially over the course of their illness. The mean rectal pH was 6.75 with no significant difference in well or unwell infants. The mean (95% CI) rectal pH of well neonates was significantly lower than that of older infants (>28 days): 6.47 (6.29-6.65) vs. 6.90 (6.68 to 7.12) p = 0.003.
Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. Artemisinin derivatives are highly effective antimalarials with a favorable safety profile. Concerns ...remain over their potential neurotoxicity, although there has been no clinical evidence of this in humans. In animals (rats, dogs, and monkeys) artemether, a derivative of artemisinin is associated with an unusual toxicity pattern in specific brain nuclei involving the auditory and vestibular pathways. A recent report from Mozambique described a small but significant and irreversible hearing loss in patients exposed to artemether-lumefantrine. To explore this issue, we conducted a case-control study using tympanometry, audiometry and auditory brain-stem responses. We assessed 68 subjects who had been treated with artemether-lumefantrine within the previous five years and 68 age- and sex-matched controls living in the malarious region along the Thailand-Myanmar border. There were no differences in the test results between cases and controls. There was no neurophysiologic evidence of auditory brainstem toxicity that could be attributed to artemether-lumefantrine in this study population.
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