Dec 22, 2005 (CIDRAP News) – A new report says oseltamivir-resistant forms of H5N1 avian influenza virus were found in two Vietnamese girls who died of the infection, raising doubts about the antiviral drug that many countries are counting on to help protect them from a potential flu pandemic.One of the two girls died even though she started receiving oseltamivir (Tamiflu) within the first 2 days of her illness, the recommended window for effective treatment, according to the report in today’s New England Journal of Medicine. The other girl was not treated until the sixth day of her illness.The authors of the report say their findings suggest that a higher dosage, longer treatment course, or combination with other antiviral drugs may be necessary to ensure the effectiveness of oseltamivir.Roche, the manufacturer of oseltamivir, agrees with that assessment and says that studies of the safety of a higher dosage are about to get under way.Second study weighs in on stockpilingIn a separate article published today, a group of experts who have been monitoring resistance to oseltamivir and similar drugs says the evidence so far—including the New England Journal report—does not suggest that stockpiling of the drug is useless.”The available data do not indicate that potential oseltamivir resistance should be a deterrent to its stockpiling for pandemic response,” says the report by Frederick Hayden and other members of the Neuraminidase Inhibitor Susceptibility Network (NISN). It was published online today in Antiviral Therapy.The report on the Vietnamese patients was prepared by a team from the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, and Hong Kong University, with Menno D. de Jong of the Vietnamese hospital as first author.Their study focuses on eight patients who were treated for confirmed H5N1 infection at the Hospital for Tropical Diseases between February 2004 and January 2005. Throat samples were collected from the patients for analysis at admission and later in their illness. H5N1 infection was confirmed by polymerase chain reaction.All the patients were started on oseltamivir the day of admission to the hospital, which varied from 2 to 8 days after the onset of illness. They received the recommended regimen of 75 mg twice a day for 5 days. Four of the patients died.The researchers did a sequence analysis of the H5N1 virus’s neuraminidase gene to look for resistance, signaled by the substitution of tyrosine for histidine at amino acid position 274. This mutation was found in two patients, a 13-year-old girl and an 18-year-old girl.The 13-year-old was hospitalized the day after she fell ill with a fever and cough, which was also the day after her mother had died of H5N1 infection. Despite oseltamivir treatment, the girl’s condition worsened on her fourth day in the hospital, and she died of severe pneumonia on the seventh day.The viral load in her throat was higher by the time of her death than it had been earlier, which, along other laboratory evidence, suggests that “the development of drug resistance contributed to the failure of therapy and, ultimately, the death of this patient,” the report says.The 18-year-old was hospitalized and started on oseltamivir 6 days after she had fallen ill, but she died after 2 weeks in the hospital. Nonresistant H5N1 virus was found in a sample taken 2 days after she was hospitalized, but the resistant form was found 6 days later.Although the connection between viral resistance and the 18-year-old girl’s death was less clear than in the case of the 13-year-old, “The presence of replicating virus after 14 days of illness suggests an effect on the outcome,” the article says.It also says the viral load in throat specimens from the four patients who survived dropped quickly to undetectable levels during their treatment.”Our observations suggest that at least in some patients with influenza A (H5N1) virus infection, treatment with the recommended dose of oseltamivir incompletely suppresses viral replication,” the authors write. Consequently, “Strategies aimed at improving antiviral efficacy (e.g., the use of higher doses, longer durations of therapy, or combination therapy) may deserve further evaluation.”Tamiflu manufacturer, study authors commentRoche, Swiss-based maker of Tamiflu, released a statement today agreeing that such strategies deserve consideration. The company said some data already support the safety of using a higher dosage of the drug, and clinical trials assessing the efficacy of a higher dose are scheduled. Roche is collaborating with the National Institutes of Health and the World Health Organization (WHO) on that research, the statement said.Tran Tinh Hien of the Hospital for Infectious Diseases, one of the study’s authors, says Vietnamese health officials are already recommending increasing the dosage of oseltamivir for avian flu patients, according to a Reuters report published today.”We still recommend the use of Tamiflu for bird flu cases as soon as possible and at higher doses as there is no replacement yet,” he said. He added that the Vietnamese Ministry of Health has increased the treatment period to 7 days from 5 days.The article published today by NISN, the experts who have been monitoring resistance to the neuraminidase inhibitors, say the new findings do not contraindicate stockpiling of oseltamivir, but much more research is needed. The neuraminidase inhibitors include oseltamivir and zanamivir (Relenza).The group said no one knows how often resistance emerges in H5N1 patients being treated with oseltamivir, and the clinical consequences of such resistance are also unclear.Many H5N1 patients treated with oseltamivir have died, but in most cases treatment was started late, after pneumonia had already developed, the report says. Some evidence suggests that the emergence of oseltamivir resistance early in treatment may lead to treatment failure, but more studies are needed.The group also said there is no indication that H5N1 viruses now circulating in birds are resistant to neuraminidase inhibitors. Further, the likelihood that oseltamivir-resistant strains will spread in the community appears low, in contrast to the situation with two older antiviral drugs, amantadine and rimantadine, to which ordinary flu viruses are often resistant. In animal studies, the article says, the mutation that confers resistance in both H5N1 and H1N1 viruses reduces infectiousness 100-fold and reduces viral replication more than 10-fold.The NISN statement also says that all avian and human H5N1 isolates tested so far by the Centers for Disease Control and Prevention have been susceptible to zanamivir. However, zanamivir, which is inhaled, has not been tried in human H5N1 patients.Despite this, “Inhaled zanamivir would be a therapeutic consideration if oseltamivir resistance were likely to be present,” the NISN members write. They also say the drug would be “an appropriate choice for pandemic response stockpiles.”Other experts offer opinionsTo infectious disease expert Michael T. Osterholm, PhD, MPH, the report from Vietnam “reminds us again that none of us know how much drug [oseltamivir] we have in the stockpile.” If a longer, higher-dose regimen is needed, a stockpile now described as 3 million treatment courses is actually smaller, said Osterholm, director of CIDRAP, publisher of this Web site.Osterholm also said the report suggests oseltamivir resistance can have much graver consequences in H5N1 cases than in ordinary flu. In the latter, drug resistance has not been associated with treatment failure or a severe outcome, but “with H5N1 this may be a very different outcome,” he said.Osterholm called for clinical studies of the use of oseltamivir very early in the illness and at a much higher dosage than is used in ordinary seasonal flu. If that approach improves outcomes, it would have “tremendous implications for how we get Tamiflu to patients in a timely manner,” he said.A WHO official said the resistance findings are “not necessarily alarming” but do point up the need for more information, according to the Reuters report.”What really is critical is understanding whether the way we are using the drugs contributes” to resistance, said Keiji Fukuda of the WHO’s global influenza program.Some resistance is expected whenever antivirals and antibiotics are used, Fukuda said, adding that using too-small doses or too short a treatment regimen can promote resistance.De Jong MD, Thanh TT, Khanh TH, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005 Dec 22;353(25):2667-72 [Full text]Hayden F, Klimov A, Toshiro M, et al. Neuraminidase Inhibitor Susceptibility Network position statement: antiviral resistance in influenza A/H5N1 viruses. Antivir Ther 2005;10(8):873-7 [Abstract]See also:Dec 22 statement by Roche
Local renters have the opportunity to show their excellence in Europe by applying for the competition for the best family tourism accommodation Best European Holiday Home (BEHH) organized by the European Holiday Home Association (EHHA). Applications are open until September 30, and prizes for the best in eight categories of family accommodation will be awarded on November 8 in Barcelona. The title of the best beach holiday home (Best beach holiday home) went to Villa Palma from Naplovac on the island of Korcula, for the best eco holiday home (Best Green holiday home) was chosen Villa Milica from Sajini near Pula, and the award for best house for a holiday with pets (Best pet holiday home) went into the hands of Green Frame from Klarić near Vodnjan. We remind you that last year’s competition was held in 14 categories, and among the 112 finalists there were as many as 15 Croatian houses, three of which were awarded prizes for the best holiday homes. In the last two years, Croatian holiday homes have received as many as seven of these prestigious awards Martina Nimac-Kalcina, president of the Family Tourism Association of the Croatian Chamber of Commerce, invites local renters to re-apply in as many numbers as possible. You can sign up HERE. “Thanks to last year’s success at the BEHH Awards, Croatia has built a country brand with the most beautiful villas and holiday homes. In the fierce competition, we have once again confirmed that we are not only a destination of crystal clear sea and beaches, but also top accommodation “, said Nimac-Kalcina, adding that for each registered facility this competition is a form of self-promotion and presentation to potential partners. “In case of winning the award, it is also a confirmation of the specialization of the facility according to certain categories of guests”, Says Nimac-Kalcina. This year’s awards for the best family tourism accommodation will be given in the categories of Best Accessible Holiday Home (holiday home that provides high quality facilities and opportunities for people with disabilities), Best Family Friendly Holiday Home (holiday home especially suitable for families with children), Best Green Holiday Home (eco holiday homes), Best Health and Wellness Holiday Home (health and wellness tourism houses), Best Holiday Home Beach House (beach houses), Best Holiday Home in European Capital (holiday homes in big cities ), Best Pet Holiday Home (pet holiday homes) and Best Unique Spot Holiday Home (best original holiday home). Each landlord can apply in a maximum of three categories
The Ballon d’Or will not be awarded this year due to the extraordinary conditions created by the coronavirus pandemic, organizers France Football announced on Monday.It will be the first time the trophy given for the world’s best men’s footballer has not been awarded since Englishman Stanley Matthews won the inaugural edition in 1956.”There will be no edition in 2020, because it turns out, after thoughtful consideration, that all the conditions are not met,” said Pascal Ferre, the editor of the magazine. The COVID-19 outbreak saw all major football leagues shut down in March, with the German Bundesliga the first to resume behind closed doors in May.France Football said it would be unfair to vote on the world’s best player when some leagues, including the French Ligue 1, cancelled their seasons early.Ferre also suggested that it would not be right to judge players based on games played without spectators present.”We believe that such a singular year cannot… be treated as an ordinary year,” he added. “Two months [January and February], out of the eleven generally required to form an opinion and decide who should lift the trophies, represent far too little to gauge and judge, without forgetting that the other games were played –- or will be played –- in unusual conditions [behind closed doors, with five replacements, Champions League’s Final 8 played in a single game].”Lionel Messi won a record-breaking sixth Ballon d’Or last year.The women’s Ballon d’Or, which was first awarded in 2018, has also been cancelled.France Football added that it was looking forward to holding a ceremony in 2021, but that this year it would instead organize a vote for the all-time greatest men’s XI. Topics :
Moomba South appraisal program Phase 1 location map; Image courtesy of SantosAustralian LNG player Santos has confirmed significant gas resources following Phase 1 of the Moomba South Patchawarra Formation appraisal program in the Cooper Basin.Santos said that the program targeted two new plays in the Granite Wash and Fractured Granite which could have the potential to add significant new resources.The Patchawarra reservoir system on the deeper flanks of the Moomba South field was assessed to contain significant gas potential in thick, well-developed, gas-charged tight sandstone reservoirs.The company added that eight appraisal wells were drilled to total depths ranging from 3,034 to 3,303 meters and all intersected gas pay.Gas pay in the wells ranged from 16 to 64 meters, in line with assumptions underpinning pre-drill contingent resource estimates. The wells were stimulated with between four to six stages.Preliminary gas sample analysis indicates a higher natural gas liquids content and lower CO2 content compared to the adjacent and overlying Moomba field production areas. Additional analysis is underway to confirm the gas composition and associated gas liquids volumes.Santos stated that seven of the appraisal wells have now been tested and brought online with a stabilized single-well gas flow of 8.7 mmscf/d. One well was plugged and abandoned.In addition to the Patchawarra, significant upside in the Toolachee, Daralingie, and Epsilon reservoir complexes were also demonstrated with wells encountering near virgin pressures and better than expected porosity and permeability.“The results of the appraisal program will inform field development planning for the Moomba South project. Planning is underway to undertake further drilling on Moomba South towards the end of 2019. This further drilling may include horizontal wells to further appraise the field,” the LNG player said.Santos managing director and CEO Kevin Gallagher stated: “I am very pleased that the Moomba South Phase 1 appraisal program has confirmed a significant gas resource and resulted in seven new wells now producing in the Cooper.”It is worth noting that the Moomba South appraisal program is located in PPL 8 and PPL 9, operated by Santos 66.6% with Beach as a partner with a 33.4% stake.
By Dave PanskeOSHKOSH, Wis. (July 17) – Marcus Yarie bested a field of 24 Automotive Supply Company IMCA Modifieds to take the Christmas in July night checkers Friday at Oshkosh SpeedZone Raceway.Yarie passed eventual runner-up Mike Wedelstadt on the 15th circuit. Tim Lemirande started 18th and finished third.Paul Holschuh, Dion Wahl and Justin Jacobsen took turns up front before Travis Van Straten drove to the lead in the Total Power Sales IMCA Stock Car main event.Despite heavy pressure over the final laps, Van Straten was able to hold off the challengers to win his fifth feature of the season. Jacobsen took the runner up spot with Jerry Winkle taking a strong third place finish.Once in front, Colten Van Hierden pulled away for another Karl Chevrolet Northern SportMod victory.The race for second was tight to the finish with Jeff Steenbergen able to sneak by on the final lap.
RelatedPosts Kwara Governor to immortalise Rashidi Yekini COVID-19: Plateau state tops, as NCDC announces new infections in Nigeria Ministry reads riot act to NFA, Clubs over resumption of league The Nigeria Football Federation has announced a N30,000 monthly stipend for the mothers of ex-internationals Sam Okwaraji and Rashidi Yekini.The NFF made the announcement via Twitter handle on Thursday. The federation admitted they were making the move following the recent initiative taken by the Minister of Youth and Sports, Sunday Dare, who approved a N10,000 monthly stipend for Yekini’s mother during the eighth year remembrance of the football legend.The NFF tweeted: “In furtherance to, and in appreciation of, the recent pronouncement of the HM Sports @SundayDareSD to put the mothers of late ex-internationals Sam Okwaraji and Rashidi Yekini on a monthly stipend, the NFF has decided to support this noble initiative with a further monthly stipend of N30k to each of the two matriarchs.”Aside the pilot beneficiaries, the NFF also promised it would be doing a broad-based review so that more surviving mothers of ex-internationals that died in active service for the country would be supported financially.“In addition, the NFF will henceforth review the situation of surviving mothers of our ex-internationals that died in active service for the country and resolve what to do for them on a monthly basis,” it said.Yekini died eight years ago in Ibadan, Oyo State after retiring from football. He had a professional career spanning more than two decades and was mainly associated with Vitória de Setúbal in Portugal, but also played in six other countries besides Nigeria.Yekini scored 37 goals as a Nigerian international from 58 games and represented the nation in five major tournaments, including two World Cups where he scored the country’s first-ever goal in the competition against Bulgaria in the USA 94 World Cup.He was also named the African Footballer of the Year in 1993.Okwaraji was a professional footballer who played internationally for Nigeria.He was also a qualified lawyer who had a masters in international law from the Pontifical Lateran University of Rome. He collapsed and died of heart failure in the 77th minute of a World Cup qualification match against Angola at the Lagos National Stadium on August 12, 1989.Tags: NFFRashidi YekiniSam OkwarajiTwitter
Midfielder Juan Mata accepts Manchester United must learn the harsh lessons of their horrible start in the 3-0 defeat at Arsenal, but also not forget what took them to the top of the Barclays Premier League table. Press Association After the international break, the Red Devils travel to Everton and then have an away Champions League fixture against CSKA Moscow before returning to the small matter of the Manchester derby at Old Trafford on October 25. Mata, who now jets off on international duty with Spain, feels the squad have what it takes to recover. “It is not easy to write today and to find words of encouragement after a game like this, but we have to carry on,” Mata wrote in his personal blog at www.kicca.com. “Before the game our goal was to keep the top spot of the Premiership, but it wasn’t our day as we saw from the kick-off. “Arsenal started with more intensity, they scored very quickly and with no time for our reaction they scored the second goal. Not even 10 minutes have passed and things were already looking very bad. “A start like this from us is unacceptable; if we want to fight for big things we must learn the lesson as soon as possible. The only thing I can say is that we shouldn’t play a game like this again. “We tried to get back into the game, fighting until the end, but obviously we were penalised by our horrible start. “Unfortunately, that was the end of a good month of September. “Earlier in the week we had won against Wolfsburg in the Champions League, coming from one goal behind, and the team was feeling good before the international break, but then we had those horrible 20 minutes. “Now we must carry on, as I said before, and play like we were doing in previous weeks. “We must learn from this defeat. We have an important month of October ahead, with games that will demand our best level of performance, and we have to be ready for them.” Mata added: “We still are in the top spots of the table and this is a long-distance race, we are sure of that. All the teams are finding difficulties, but we remain hopeful that we can achieve something important this season, and that’s what we are working for every week.” Louis van Gaal was left stunned by the manner of the loss at the Emirates Stadium on Sunday, where the Gunners had put the contest beyond his side with three goals inside the opening 20 minutes – the first two coming within 74 seconds of each other. United had started the weekend top of the table but finished it down in third place below Arsenal on goal difference, with rivals Manchester City having also romped to a 6-1 victory over Newcastle on Saturday afternoon.
“OMG, big boi Mr. B is a CHONK.” the Morris Animal Refuge tweeted. “He’s a chonk of a chonk. He redefines the term. Can you guess how much he weighs? More importantly, can you give him a home? Adopt this jumbo-sized package of fluff & love.”The shelter also has several other animals who are also searching for forever homes, but none make a bigger statement then Mr. B! An animal refuge in Philadelphia is currently searching for a forever home for one of its largest animals, a 26 pound cat name Mr. B.The Morris Animal Refuge posted about the loving animal on their Twitter account Tuesday.OMG, big boi Mr. B is a CHONK. He’s a chonk of a chonk. He redefines the term. Can you guess how much he weighs? More importantly, can you give him a home? Adopt this jumbo-sized package of fluff & love: https://t.co/v8aB6PzBbL. Please RT to help this sad-eyed guy find happiness! pic.twitter.com/tquRuvRaws— Morris Animal Refuge (@MorrisAnimal) August 22, 2019
FOUR intense quarter-finals are set for Ministry of Education ground today as Smalta Girls Pee Wee football tournament continues.North Georgetown are the first team to be in action from 13:00hrs with Smith Memorial carded as their opponents.The second game at 13:00hrs will pit Tucville against South Ruimveldt in a mammoth clash. Many are expecting the former to win.Timehri and West Ruimveldt clash at 13:50hrs with keen attention paid to that match as it could determine the final.In the other match, Redeemer play St Stephen’s on pitch two for the last spot in the following week’s semi-final.The tournament, which is organised by the Petra Organisation, is sponsored by Ansa McAl under the Smalta brand.
Ghana’s Samuel Takyie booked his place in the Tokyo Olympic boxing event after won his 3rd place playoff against Isaac Masemse of Uganda in Dakar, Senegal on Saturday.The city of Dakar has been hosting the continent’s boxers who are seeking places in the 2020 Olympic Games.Takyie took on Masemse with hopes to make it to Japan later this year and he won the first round. Masemse got into his groove and won that round.In the third and decisive round, the two boxers went at each other but it was Takyie who came out on top and got his place in the Olympic Games and he was very excited especially with his achievement.“I think I told you I’m going to Tokyo. I have never come to Africa qualifiers before, my first. I told my coach I that would qualify for the Olympics.My family and boxing mates will be very happy, I hope this will inspire them(training mates). We have very good boxers in Ghana and they too can make it like I have.”Takyie will represent Ghana at the Olympic Games together with Sulemanu Tetteh, captain of the Black Bombers team.