Publications

Genuine hologram has the legend 'GUILIN PHARMA' here.Visible with the naked eye, as a thin strip below the waves.Letters are ~ 0.1mm high The photograph, left, is of the genuine hologram attached to the blister packs and packets of the genuine 'Guilin Pharma' artesunate.Below are pictures of 11 types of fake artesunate stickers & holograms with their distinguishing features.As hologram colour depends on the light, please do not use the colours printed here to judge whether artesunate is genuine or fake Guilin Pharmaceutical Co., Ltd.developed their hologram as a security device in response to the first type ('Type 1') of counterfeit artesunate circulated which had no hologram attached.As a result, any 'Guilin Pharma' artesunate now circulating without a blister pack hologram is almost certainly counterfeit or expired.Subsequently, at least 11 different types of counterfeit 'Guilin Pharma artesunate' have been found in Southeast Asia [Burma (Myanmar), Cambodia, China, Lao PDR, Thailand (only on the western border) and Vietnam] with counterfeit stickers or holograms, and there are probably more types circulating.Genuine and counterfeit holograms are ~ 13 mm in diameter.The genuine and 'Type 10' holograms have 'X-52' visible across the mountains when viewed under UV light.Other features of the counterfeit artesunate that differ from the genuine product include -poor printing of bar codes on packets,poor printing of codes on blister packs, codes on blister packs printed with the font made of numerous small dots, poor stamping of code 'AS' and score line on tablets, raised edges of tablets, very hard tablets, blisterpack abbreviations in capital letters ('MFG' and 'EXP') and unusually late expiry date in relation to date of manufacture (>3years).Counterfeits tend to be cheaper than the genuine product.This update has been issued following the discovery that counterfeit artesunate 'Types 4' and '9' contain small quantities of artesunate (~ 10mg) which will not be efficacious but may give misleading positive result on the Fast Red TR dye test and may facilitate the selection of artesunate-resistant malaria parasites.Although, regrettably, the counterfeiters have targeted the 'Guilin Pharma' product, it is possible that other fake artesunate products exist in Asia.Therefore, drug regulatory authorities should be vigilant and regularly monitor the quality of artesunate available on the market.If you are uncertain as the authenticity of any artesunate sample based on the characteristics of the packaging, please check by chemical analysis of the tablet Genuine hologram under UV light with 'X-52' at mountain base

Abstract Animal populations in arid environments, where extreme temperatures and erratic rainfall are normal, are particularly vulnerable to climate change. While numerous studies have examined the effects of temperature and rainfall on the breeding success and survival of arid‐zone species, the mechanistic pathways linking climate variation to demography remain poorly described for most species. Using long‐term data from meerkats ( Suricata suricatta ) in the Kalahari Desert, we show that increases in rainfall and primary productivity (as measured by normalized difference vegetation index) were associated with improved foraging success, daily body mass gain, and body condition, which in turn contributed to enhanced breeding success and survival. Conversely, high summer temperatures were associated with reduced foraging performance and body condition. Foraging efficiency declined when daily maximum summer temperatures exceeded 35°C, and at temperatures above 37°C, diurnal mass gains often failed to offset overnight mass losses. While high temperatures had short‐term detrimental effects, runs of hot days were relatively infrequent and often coincided with periods of high primary productivity. As a result, individuals were rarely in poor condition during the hottest periods of the year, suggesting that they could recover any mass lost on hot days during subsequent cooler periods. Only when high temperatures persisted alongside low primary productivity did body condition drop sharply. Although temperature variation has not yet affected the demography of our meerkat population as strongly as rainfall variation, further warming in the region and the potential for more frequent and severe hot droughts are likely to have major implications for the species' distribution and persistence. Our study emphasizes the need to consider both rainfall and temperature variations across seasons, as well as their interactions, to better understand and predict the impacts of climate change on arid‐zone animals. It also demonstrates the value of long‐term, high‐resolution behavioral and physiological data, including frequent, year‐round weighing of animals, in establishing causal links between climate and demography.

Introduction Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria. Methods In this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death. Results Patients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P <0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6–7.5, P =0.001), comparable to LA (OR 3.5, 95 % CI 1.5–7.8, P =0.003) (combined area under the receiver operating characteristic curve 0.81). Conclusions Newly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.

Artemether (AM) plus azithromycin (AZ) rectal co-formulations were studied to provide pre-referral treatment for children with severe febrile illnesses in malaria-endemic areas. The target profile required that such product should be cheap, easy to administer by non-medically qualified persons, rapidly effective against both malaria and bacterial infections. Analytical and pharmacotechnical development, followed by in vitro and in vivo evaluation, were conducted for various AMAZ coformulations. Of the formulations tested, stability was highest for dry solid forms and bioavailability for hard gelatin capsules; AM release from AMAZ rectodispersible tablet was suboptimal due to a modification of its micro-crystalline structure.

No abstract is provided for this article.

The amount and nature of dark energy (DE) can be tightly constrained by measuring the spatial correlation features and evolution of a sample of ~ 100,000 galaxy clusters over the redshift range 0

An open randomized comparison of 2 days (Ofx2) versus 3 days (Ofx3) of oral ofloxacin treatment (15 mg/kg/day) was conducted with Vietnamese children between 1 and 15 years of age with suspected typhoid fever. Of 108 children enrolled, 100 were blood culture positive for Salmonella typhi, and 86% of the isolates were multidrug resistant. There were no significant adverse effects. The therapeutic responses were similar in both groups, with mean (+/- standard deviation) fever clearances of 107 +/- 60 h in the Ofx3 group and 100 +/- 64 h in the Ofx2 group (P > 0.2). There were six "clinical" failures in the Ofx2 group and two clinical failures in the Ofx3 group (P > 0.2), in which fever and symptoms persisted for more than 1 week after the start of treatment, but only one of these was culture positive (Ofx3). There was one suspected relapse, and one carrier was identified. Short courses of ofloxacin are simple, inexpensive, safe, and effective for the treatment of uncomplicated multidrug-resistant typhoid fever.

Thai adult males (N = 85) with acute Plasmodium vivax malaria and normal glucose-6-phosphate dehydrogenase screening were randomized to receive 30 mg or 60 mg primaquine daily for 7 days (N = 43 and 42, respectively). The regimens were well tolerated and all patients recovered fully. Median fever clearance (47 hours; range 4 to 130 hours), mean + or - SD parasite clearance times (87.7 + or - 25.3 hours), gametocyte clearance, and adverse effects were similar in the 2 groups. Two patients, 1 from each group, had a 30% reduction in hematocrit. The cumulative 28 day relapse rate (95% confidence interval) by Kaplan Meier survival analysis was 29% (16-49%) in the 30 mg group compared with 7% (2-24%) in the 60 mg group; P = 0.027. Comparison with previous data obtained at this same site suggests that the recurrences comprised approximately 17% recrudescences and 12% relapses in the 30 mg/day group compared with 3% recrudescences and 4% relapses in the 60 mg/day group. These data suggest that the dose-response relationships for primaquine's asexual stage and hypnozoitocidal activities in-vivo are different. A 1 week course of primaquine 60 mg daily is an effective treatment of vivax malaria in this region.

A retrospective study of 261 Vietnamese adults with severe malaria was conducted to determine the relationship between cerebrospinal fluid (CSF) levels of metabolites of the kynurenine pathway, the incidence of neurologic complications, and the disease outcome. Three metabolites were measured: the excitotoxin quinolinic acid (QA); the protective receptor antagonist kynurenic acid (KA); and the proinflammatory mediator picolinic acid (PA). These measurements were related prospectively to CSF lactate levels. QA and PA levels were elevated, compared with those of controls. There was no difference in the levels of KA between these groups. Although >40% of malaria patients had QA CSF concentrations in the micromolar range, there was no association with convulsions or depth of coma. Levels of QA and PA were associated significantly with death, but a multivariate analysis suggested that these elevations were a consequence of impaired renal function. CSF lactate remained an independent and significant predictor of poor outcome.

Background Plasmodium vivax is the second most prevalent malaria parasite affecting more than 75 million people each year, mostly in South America and Asia. In addition to major morbidity this parasite is associated with relapses and a reduction in birthweight. The emergence and spread of drug resistance in Plasmodium falciparum is a major factor in the resurgence of this parasite. P. vivax resistance to drugs has more recently emerged and monitoring the situation would be helped, as for P. falciparum , by molecular methods that can be used to characterize parasites in field studies and drug efficacy trials. Methods Practical PCR genotyping protocols based on polymorphic loci present in two P. vivax genetic markers, Pvcs and Pvmsp1 , were developed. The methodology was evaluated using 100 P. vivax isolates collected in Thailand. Results and Discussion Analysis revealed that P. vivax populations in Thailand are highly diverse genetically, with mixed genotype infections found in 26 % of the samples (average multiplicity of infection = 1.29). A large number of distinguishable alleles were found for the two markers, 23 for Pvcs and 36 for Pvmsp1 . These were generally randomly distributed amongst the isolates. A total of 68 distinct genotypes could be enumerated in the 74 isolates with a multiplicity of infection of 1. Conclusion These results indicate that the genotyping protocols presented can be useful in the assessment of in vivo drug efficacy clinical trials conducted in endemic areas and for epidemiological studies of P. vivax infections.

Characterization of anti-malarial drug concentration profiles is necessary to optimize dosing, and thereby optimize cure rates and reduce both toxicity and the emergence of resistance. Population pharmacokinetic studies determine the drug concentration time profiles in the target patient populations, including children who have limited sampling options. Currently, population pharmacokinetic studies of anti-malarial drugs are designed based on logistical, financial and ethical constraints, and prior knowledge of the drug concentration time profile. Although these factors are important, the proposed design may be unable to determine the desired pharmacokinetic profile because there was no formal consideration of the complex statistical models used to analyse the drug concentration data. Optimal design methods incorporate prior knowledge of the pharmacokinetic profile of the drug, the statistical methods used to analyse data from population pharmacokinetic studies, and also the practical constraints of sampling the patient population. The methods determine the statistical efficiency of the design by evaluating the information of the candidate study design prior to the pharmacokinetic study being conducted. In a hypothetical population pharmacokinetic study of intravenous artesunate, where the number of patients and blood samples to be assayed was constrained to be 50 and 200 respectively, an evaluation of varying elementary designs using optimal design methods found that the designs with more patients and less samples per patient improved the precision of the pharmacokinetic parameters and inter-patient variability, and the overall statistical efficiency by at least 50%. Optimal design methods ensure that the proposed study designs for population pharmacokinetic studies are robust and efficient. It is unethical to continue conducting population pharmacokinetic studies when the sampling schedule may be insufficient to estimate precisely the pharmacokinetic profile.

A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin-piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan-Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0-37%), thus establishing non-inferiority of DHA-PPQ. Fever clearance time (median 24 versus 12 hours,P= 0.02), parasite clearance time (median 36 versus 18 hours,P< 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours,P< 0.001) were all significantly shorter in the DHA-PPQ arm. All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward, with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients. Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam, but DHA-PPQ provides more rapid symptomatic and parasitological recovery.