May 28, 2004 (CIDRAP News) – The National Institute of Allergy and Infectious Diseases (NIAID) said yesterday it has awarded contracts to two companies to develop vaccines based on the H5N1 avian influenza virus in an effort to limit the risk of a human influenza pandemic.Contracts were awarded to Aventis Pasteur Inc. of Swiftwater, Pa., and Chiron Corp., Emeryville, Calif., both of which make inactivated flu virus vaccines that are used each flu season. Each company will produce 8,000 to 10,000 doses of vaccine, which the NIAID will then test in clinical trials, the agency said.Each contract will be worth about $2 million and will cover about a 2-year period, according to an NIAID spokeswoman. She told CIDRAP News the amount and time frame for the contracts will be determined more precisely later this summer.Widespread outbreaks of H5N1 avian flu occurred in eight Asian countries beginning last December, triggering the loss of more than 100 million poultry from illness or culling. The outbreaks led to 34 documented human cases, including 23 deaths. Disease experts feared that the avian virus would combine with a human flu virus, possibly producing a new strain that could trigger a pandemic because people would have no immunity to it.In announcing the contracts, the NIAID said, “If a pandemic of H5N1 avian influenza were to occur in humans, production of such a vaccine on a commercial scale could be used to protect laboratory workers, public health personnel at risk and, if needed, the general public.”The two companies will use a strain of H5N1 avian flu virus taken from a Vietnamese patient last February, the NIAID said. With approval from the Food and Drug Administration, the NIAID will test the vaccines for safety and immunogenicity in phase 1 and phase 2 clinical trials. The vaccines will be tested in healthy adults first and later in children and elderly people.Avian flu had never been known to infect humans before 1997, when an H5N1 avian virus infected 18 people in Hong Kong, killing six of them, the NIAID noted. But the virus did not spread readily from person to person in that case or in this year’s outbreaks.In a statement from Chiron Corp., Chiron Vaccines President John Lambert said, “Chiron has produced vaccines designed to protect against other types of avian influenza, including the strain that resulted in several deaths in Hong Kong in 1997. Subsequent clinical testing demonstrated that it should be possible to protect against the lethal Hong Kong strain. Our current work with the NIAID builds on this experience.”David J. Williams, chairman and CEO of Aventis Pasteur, said in a statement, “As the world’s largest producer of influenza vaccine, it is important for us to partner with the government to expand our knowledge of how to prepare a safe and effective vaccine in as short a time frame as possible. This important project will help us gain that experience.”The NIAID said the companies would produce the vaccines by the established technique of growing the virus in eggs and then inactivating and purifying it before formulating it into vaccine. “The use of established techniques to develop the investigational vaccines will help to promote rapid licensing of commercial pandemic vaccines in the event of a pandemic outbreak,” the agency said.See also:May 27 NIAID news releasehttp://www.niaid.nih.gov/news/newsreleases/2004/Pages/flucontracts.aspx
Aug 31, 2004 (CIDRAP News) – Influenza viruses in 18% of a group of Japanese children who were treated with oseltamivir (Tamiflu) developed resistance to the antiviral drug, which is viewed as one of the key defenses against pandemic influenza, according to a new report in The Lancet.Oseltamivir and zanamivir block neuraminidase, an enzyme that enables the influenza virus to escape from an infected cell and spread to other cells. Previous clinical trials have shown low rates of viral resistance to the two drugs, called neuraminidase inhibitors. Because of this, and because they are effective against all strains of influenza, they are considered an important bulwark against new flu strains that could cause a pandemic. (Two older antiviral drugs used against influenza, amantadine and rimantadine, are effective only for influenza A and are associated with higher rates of viral resistance.)The new study suggests that viral resistance to oseltamivir may be a greater problem than previously believed. “In our study, about a fifth of children developed resistance by day 4 or later during treatment with oseltamivir,” says the report by Maki Kiso of the University of Tokyo and several Japanense and American colleagues. “Furthermore, just over a quarter of children who shed virus for 3 days or more had drug-resistant influenza viruses.”The researchers analyzed influenza A (H3N2) viruses collected from 50 children before and during treatment with oseltamivir in 2002 and 2003. The children ranged from 2 months to 15.8 years of age, but 80% were younger than 5 years; 29 of them were hospitalized for treatment.The authors extracted viral RNA from patient specimens, used polymerase chain reaction to amplify the hemagglutinin and neuraminidase genes, and then analyzed the gene sequences. To identify neuraminidase mutations, viruses from samples taken during patients’ first clinical visits were compared with those from samples obtained later. The investigators also isolated viruses from clinical samples, grew them in cell culture, and, after identifying those with particular mutations, tested them for sensitivity to oseltamivir.Neuraminidase mutations were found in viruses from 9 (18%) of the 50 children, the report says. In eight cases the mutation was known to confer resistance to neuraminidase inhibitors. The mutation in the ninth case had not previously been shown to cause resistance, but sensitivity testing by the authors showed that it did. The testing showed that, depending on the particular mutation, mutant neuraminidase was anywhere from 300 to 100,000 times more resistant to oseltamivir than pretreatment neuraminidase was.Drug resistance was most frequent in viruses from 1-year-old children (4 of 12 patients) and was less common in those younger than 1 year (1 of 9) and from 2 to 6 years old (4 of 22). No resistance was found in the seven children aged 7 years or older.Resistance showed up in the viruses as early as 4 days after the beginning of treatment and persisted through day 7, according to the report. Children with resistant variants generally shed virus longer than the rest, but some of the patients with nonresistant virus were still infectious after 5 days of oseltamivir treatment. The study design did not allow the researchers to assess the relationship between drug resistance and the patients’ clinical course.The researchers write that the increased resistance they detected might be partly explained by their rigorous techniques. They also note that, depending on a patient’s weight, oseltamivir dosages used in Japan may be lower than in other countries and may be suboptimal, which could contribute to viral resistance.In an accompanying commentary, Dr. Anne Moscona of Mt. Sinai School of Medicine in New York City calls the study “a timely wake-up call.” She writes that neuraminidase inhibitors have been shown to be effective against neuraminidase from the virus that caused the 1918 flu pandemic, the avian flu viruses that infected some humans in Hong Kong in 1997 and 1999, and this year’s H5N1 avian flu strain.”Stockpiles of these drugs are a key piece of preparedness and would be critical to an effective response,” Moscona states.The question now, she says, is whether oseltamivir-resistant viruses are transmissible and pathogenic. “If we are very lucky, they may have a growth disadvantage, or, for other reasons, be less virulent or transmissible.” She adds that although there are no reports of transmission of oseltamivir-resistant viruses in humans, the Japanese findings suggest that it “is only a matter of time” until this happens.Moscona concludes that the findings should be taken as “an energizing mandate to learn more about the incidence and mechanisms of resistance to the neuraminidase inhibitors, so that appropriate strategies can be developed for their use during the next pandemic.”Kiso M, Mitamura K, Sakai-Tagawa Y, et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 2004;364(9436):759-65 [Abstract—access requires free registration]Moscana A. Oseltamivir-resistant influenza? (Commentary) Lancet 2004;364(9436):733-4 [Preview]See also:Aug 26 CIDRAP News story, “HHS releases plan for coping with pandemic flu”
Like boomtowns of the past, a city of 7,000 people mushroomed around the mine, which lies deep in the forest, an hour’s walk from the town of Zobia. Then the plague arrived, felling miners and mothers alike. The Ituri region is the most active focus of human plague in the world, he said. He worries that the next outbreak will find footing in a big city in the region. For example, the city of Bunia now has a refugee camp teeming with 12,000 people, many of them children. Some people worry that the developed world’s interest in bioterrorism dilutes attention to natural outbreaks. However, one expert says concerns about terrorist-caused outbreaks can lead to responses relevant to natural outbreaks as well. Perhaps because plague is so rare in the United States, there is a tendency to minimize its impact, according to Peters. “It’s important that people realize that plague is a worldwide problem,” he said. “There were many reasons for coughing,” Bertherat said. Without sufficient investigation, “It was difficult to say if it was the flu or the plague.” “People are working hard for rapid tests,” Peters said. Beyond the problem of developing them, diagnostic tests pose challenges in production, distribution, and user education. Investigators found myriad rodents near the mining camp, but no bubonic plague. “It was like a slum in the middle of the forest,” he said. People had to carry clothes, batteries, and other goods from Zobia. There was no clean drinking water. The plague spread beyond the mining camp, claiming the life of a young mother from Zobia. After a long scramble, doctors found a 4-month supply of milk for her 6-month-old baby and gave it to the father, Bertherat said. The pull of diamonds was so powerful that it was difficult to get miners to take preventive medication, and an isolation ward that was set up in the mine camp sat empty. No one wanted to stay there when they could be finding diamonds. “The index case was imported from somewhere else,” Bertherat said. The victim might have been a miner from a plague-prone part of the Ituri region. The samples were shipped to eight laboratories in several countries to bolster research on up to 15 different plague diagnostic tests, Bertherat said. The samples enable labs to compare testing techniques. Sensitive rapid field tests are the key to stopping outbreaks. Feb 18, 2004, CIDRAP News story “Pneumonic plague outbreak in Congo sparks WHO response”http://www.cidrap.umn.edu/cidrap/content/bt/plague/news/feb1805plague.html Panic had made the outbreak harder to control, he said. When miners fell sick, hundreds of people fled the site, which sparked fears that the outbreak might spread widely. Some died along forest trails. Initial reports suggested there might be hundreds of plague cases. That number dwindled to 124 confirmed, suspected, or probable cases, with 56 deaths. In addition, some people who felt sick and fled might have been suffering from something other than plague. Like a 19th-century American gold rush, news of the discovery of diamonds in a remote northeastern part of the Democratic Republic of the Congo (DRC) in November 2004 sparked an influx of adventurers hoping to strike it rich. And despite the focus on plague as a potential bioterror weapon in the developed world, it remains to be seen how the recent attention will help address this age-old problem. “These rapid tests are frequently not economically viable,” he said. Bioterrorism preparedness efforts could bolster that process: if a good, reasonably priced rapid test for plague is created, it could be stockpiled, he added. In addition, experts hope to deepen the pool of existing antibiotics used to treat plague. Gentamicin works well, Peters said, but having other treatments is important to biodefense interests. A peculiar outbreakPlague is endemic in parts of the DRC’s Ituri region, but this outbreak was unusual, Bertherat said. The Zobia area is 400 kilometers from previous known plague-endemic areas, and all the cases were pneumonic. Overall, only about 2% of plague cases are pneumonic; most are bubonic, spread by rodents carrying infected fleas. People can contract pneumonic plague by inhaling the pathogen, Yersinia pestis, in aerosol form. Bertherat, who worked in the same DRC province in 1999 on a Marburg hemorrhagic fever outbreak, predicted the plague would recur there soon. The outbreak smoldered for 11 weeks. Healthcare workers at the scene knew that gentamicin works well and they used it quickly, helping limit the outbreak. The onset of the dry season also caused the mine camp population to dwindle to about 2,500 people, because water is necessary for diamond mining. What worries Eric Bertherat, MD, MPH, MSc, a World Health Organization (WHO) doctor whose team helped stop the outbreak, is history’s tendency to repeat itself. Bertherat said in a recent phone interview from Geneva that he is certain the conditions that led to 124 cases of pneumonic plague and 56 deaths earlier this year will resurface in the DRC—probably soon. CIDRAP overview of plaguehttp://www.cidrap.umn.edu/cidrap/content/bt/plague/biofacts/index.html May 27, 2005 (CIDRAP News) – The plot of the world’s latest pneumonic plague outbreak echoes with history. When it heard about a serious outbreak, the WHO sent a team to Zobia. Bertherat and his colleagues flew to the DRC on Feb 19, heading for the Ituri region, which has seen chronic and dramatic humanitarian crises since 1998. A United Nations helicopter ferried them partway; then the team hiked to the camp. “Sanitary conditions have decreased” in the region, he said. “We try to sound the alert, but in terms of plague . . . there is no interest by the donors,” meaning wealthy countries. Another area with potential for crossover is vaccines, Peters said. The US Army has produced a plague vaccine, although it hasn’t yet been tested. Despite the return of the rainy season in March, the DRC has not seen any new plague cases so far, he said. See also: Anticipating more episodesThe WHO team left Zobia March 12, nearly at the end of the outbreak. They took something valuable with them: about 120 blood and sputum samples from patients. Dual-purpose researchPlague is rare in the United States, with only 20 cases recorded between 1999 and 2003, according to the Centers for Disease Control and Prevention (CDC). Although the nation conducts some plague surveillance and research, the focus is chiefly on the potential for bioterrorism, C.J. Peters, MD, director of biodefense and professor of pathology, microbiology, and immunology at the University of Texas Medical Branch in Galveston, told CIDRAP News. Yet research on tests, vaccines, and treatments can serve both interests, in his view.
Sep 6, 2005 (CIDRAP News) – Japanese authorities have culled 500,000 birds and plan to cull about 1 million more to stop an outbreak of H5N2 avian influenza, a milder form than the deadly H5N1, which has infected a number of backyard poultry flocks in Thailand recently.Half a million birds have already been culled in two Japanese prefectures: Ibaraki, where the virus surfaced in late June, and Saitama, according to an International Herald Tribune/Asahi Shimbun online report that appeared on ProMED-mail. Another 1.02 million birds will be culled in the affected areas, which contain about 30 farms with 4.4 million chickens, the report said.Japan’s most recent report to the World Organization for Animal Health (OIE), dated Aug 23, said the outbreaks are in Ibaraki town and Mitsukaido city in Ibaraki prefecture and in Kounosu city in Saitama prefecture. Both areas are near Tokyo, Saitama to the northwest and Ibaraki to the northeast. The reports listed no poultry deaths attributed to the virus.H5N2 viruses have not been known to infect people. The concern is to stop the spread of the low-pathogenic virus before it can evolve into a highly pathogenic form.Officials in Japan’s Ministry of Agriculture, Forestry and Fisheries have raised the possibility that the infection was caused by use of an unauthorized, defective vaccine that contained an active virus, the report said.An analysis by Japan’s National Institute of Animal Health found that the virus is 94% to 97% genetically similar to a virus found in Central and South American countries such as Mexico and Guatemala, according to a Sep 4 story from the Japanese newspaper The Yomiuri Shimbun.Hiroshi Kida, a Hokkaido University professor and head of the agriculture ministry’s advisory panel, said a vaccine based on the Central and South American virus was brought into Japan and possibly used on poultry, the newspaper reported.The ministry has a vaccine stockpile, but approved vaccines have not been distributed. The virus detected on the farms differs from those in vaccines sold outside Japan, so ministry officials speculated that it was developed outside the formal process, the paper reported. Unauthorized use of vaccines is illegal.Although local authorities have checked to see if vaccines have been used, one official told the paper that no evidence had been found, and owners of several farms where the virus has been detected said they did not use any vaccines, the paper noted.Meanwhile, the H5N1 virus continues to spread among poultry in Thailand, with a spate of new outbreaks in villages in Kampaengphet and Ayudhaya provinces between Aug 23 and Sep 1, according to a Thai report to the OIE.More than 300 chickens died or were culled in four different villages, the report said. A ProMED-mail posting from China’s Xinhua news service cited Thai speculation that the transport of fighting cocks from one area to another might have triggered the outbreaks.The infected poultry were described as backyard or free-range birds living under minimal biosecurity conditions.In nationwide surveillance of outbreaks from Jul 1 to Sep 1, the Thai government found that 29 outbreaks occurred in four provinces (the two previously mentioned, plus Chainat and Suphanburi). All cases involved free-range poultry, poor sanitation, and “insufficient biosecurity,” the report to OIE said. Most of the outbreaks involved chickens, but a few involved quail, fighting cocks, and laying ducks.See also: Sep 5 ProMED-mail report on H5N2 outbreaks in JapanAug 23 OIE report on Japanhttp://web.oie.int/eng/info/hebdo/aIS_56.htm#Sec4Sep 1 OIE report on Thailandhttp://web.oie.int/eng/info/hebdo/aIS_55.htm#Sec3
Jun 2, 2006 (CIDRAP News) – Wild birds have played and will continue to play a role in carrying the H5N1 strain of avian influenza over long distances, but the virus spreads mainly through poultry trade, according to the United Nations Food and Agriculture Organization (FAO).This was one of the primary conclusions reached during the 2-day FAO/World Organization for Animal Health (OIE) International Scientific Conference on Avian Influenza and Wild Birds, the FAO said in a news release. The meeting adjourned May 31 in Rome.A concluding document stated, “Several presentations at the conference, some supported by recent publications in peer-reviewed scientific journals, implicated wild birds in the introduction of HPAI [highly pathogenic avian influenza] H5N1 virus at considerable geographical distance from known H5N1 outbreaks in poultry.”Scientists attending the conference, however, could not resolve exactly how H5N1 has spread to more than 50 countries on three continents, or whether wild birds constitute a permanent H5N1 reservoir, the FAO reported.”This was one of the main gaps identified in our present scientific knowledge,” FAO chief veterinary officer Joseph Domenech said in the press release. “We must therefore intensify our investigations.”The conference noted that the presence of avian flu in eight African countries appears to be poultry-related and mainly linked to poultry trade, the FAO said.Tracking wild birdsTo further define and help limit the spread of H5N1 in wild and domestic birds, the conference called for global tracking and monitoring that would involve multiple groups worldwide, including scientific centers, farming organizations, hunters, bird watchers, and conservation societies.Part of that comprehensive plan, the FAO announced in a separate news release, would be a system of computers, satellites, and bird-mounted devices to track the migrations of wild birds.The $6.8 million plan would involve capturing thousands of wild birds before they migrate, testing some for disease, and fitting some with tiny (less than 50-gram) backpacks, according to the FAO news release. Once the birds were released, telemetry equipment inside the backpacks would track the birds’ movement. Radio beacons and communication satellites would feed data from the birds into computers for analysis by scientists around the world.”All we have now is a snapshot,” Domenech said in the news release. “We need to see the whole film.”Some of the money for the project is on hand, according to the FAO, but the agency needs assistance from donors and governments to fully launch the project.See also:FAO news release on wild birds’ rolehttp://www.fao.org/newsroom/en/news/2006/1000312/index.htmlFAO news release on proposal to track wild birdshttp://www.fao.org/newsroom/en/news/2006/1000311/index.html
Apr 26, 2007 (CIDRAP News) – The World Health Organization (WHO) says nations and vaccine manufacturers agreed yesterday that it may be feasible to set up a world stockpile of H5N1 influenza vaccine and find a way to ensure that developing countries could access pandemic flu vaccine supplies.Government officials and vaccine producers who met at WHO headquarters in Geneva agreed that “creating a stockpile of H5N1 vaccine, and separately developing a mechanism to ensure broader access to pandemic influenza vaccine for developing countries in the advent of a pandemic, may be feasible,” the WHO said in a news release today.”We have taken another crucial step forward in ensuring that all countries have access to the benefits of international influenza virus sharing and pandemic vaccine production,” WHO Director-General Dr. Margaret Chan said.Developing countries’ access to pandemic flu vaccines emerged as a major international health issue in February, when Indonesia revealed it had stopped sending H5N1 virus samples to the WHO 2 months earlier. The government complained that drug companies would use its virus samples to make vaccines that Indonesia couldn’t afford to buy.After a Jakarta meeting in late March, Indonesia promised to resume sharing its virus samples immediately, in return for two WHO promises: not to turn viruses over to drug companies without the country’s permission, and to prepare new virus-sharing guidelines. But Indonesia has not yet provided any more samples, according to news reports today.The WHO said vaccine producers from developed and developing countries at yesterday’s meeting expressed willingness to work with the WHO to pursue the possibility of an H5N1 vaccine stockpile and a mechanism to broaden access to pandemic vaccine.The International Federation of Pharmaceutical Manufacturers and Associations, an industry organization, said it expects increased production capacity for seasonal flu vaccines to grow in the next 3 to 5 years, the WHO reported.The WHO said it would now set up “expert groups to focus on the details of how to create, maintain, fund and use an H5N1 vaccine stockpile” and would continue to work with member states and other partners on the problem of access to pandemic vaccines.The WHO statement didn’t suggest how large a stockpile might be. But Dr. David Heymann, the WHO’s assistant director-general for communicable diseases, said officials in developing countries have said they want enough vaccine to protect 1% of their populations, according to a Canadian Press (CP) report today.”We have no idea what our official number will be. . . . But when asking what might be reasonable, one percent is what everybody is saying in the developing countries, that they would feel they need for essential populations,” Heymann told CP.As for where the vaccines for the stockpile would come from, Heymann said, “We believe that there will be a combination of donations from industry, possibly portions of national stockpiles would be made available from industrialized countries and funding.”Global flu vaccine production capacity remains very limited. Chan, in opening remarks prepared for yesterday’s meeting, estimated the annual capacity at 500 million doses of trivalent (three-strain) vaccine, but other recent estimates have typically been lower, about 350 million trivalent doses. World population is more than 6 billion.The WHO statement voiced optimism about the potential effectiveness of H5N1 vaccines now in development. The Strategic Advisory Group of Experts on Immunization concluded last week that recent studies of H5 vaccines showed them to be safe and immunogenic and that “it was realistic to expect that vaccines offering cross protection (against immunologically related but different viruses not contained in the vaccine) could be developed,” the statement said.Participants in the meeting agreed that all the efforts to provide pandemic flu vaccines must be based on the International Health Regulations as revised in 2005. The regulations, which take effect in June and have been adopted by most countries, are designed to prevent the international spread of diseases and limit the effects of other health emergencies, such as chemical spills.In opening remarks at the WHO meeting, Director-General Chan said the threat of a flu pandemic is universal and requires global solidarity. “Public health security is a collective undertaking, a shared responsibility,” she said, adding that all countries will be affected and all populations will be susceptible. Her speech was posted on the WHO Web site.Chan, who is from Hong Kong, said further, “I believe that developing countries are right to ask us to address the issue of more equitable access [to vaccines] now. To date, developing countries have suffered the most from this virus.”She also observed that the course of the H5N1 avian flu problem has not been what experts expected back in early 2004, when the virus began spreading widely in Southeast Asia.”Most experts expected one of two things to happen,” she said. “Either a pandemic would start fairly quickly, especially since the virus was so widespread in animals, or the virus would attenuate. It would mutate into a form less deadly for poultry, and it would lose its ability to infect and kill humans.”Neither has happened. Instead, this virus has given us a more protracted warning than anyone dared hope.”Meanwhile, Indonesia still has not resumed sending H5N1 virus samples to the WHO and has not offered a clear explanation for the delay, according to news reports today.Reuters reported that Triono Soendoro, head of research and development for the Indonesian health ministry, said, “Last month’s meeting resulted in a new mechanism and there are some administrative issues that need to be sorted out.”An Associated Press (AP) report said it was not clear what has caused the delay. It quoted Soendoro as saying Indonesia would resume sending samples when it has confidence that drug companies won’t obtain the samples without Indonesia’s approval.WHO officials revealed last week that China had not shared any human H5N1 virus samples in about a year, though the Chinese did send some poultry samples of the virus last fall. After that revelation, Chinese officials promised they would resume sending human samples soon.Scientists need samples of the virus to track its evolution and spread, look for signs of resistance to antiviral drugs, and develop vaccines.See also:Apr 26 WHO news releasehttp://www.who.int/mediacentre/news/releases/2007/pr21/en/index.htmlText of Dr. Margaret Chan’s opening speech at the WHO meetinghttp://www.who.int/dg/speeches/2007/250407/en/index.htmlWHO description of the International Health Regulationshttp://www.who.int/features/qa/39/en/index.html
Aug 22, 2007 (CIDRAP News) – A 28-year-old woman on the Indonesian resort island of Bali died yesterday of H5N1 avian influenza, marking the second fatal case there this month, according to Indonesian health officials.Also today, the US Centers for Disease Control and Prevention (CDC) confirmed that it has received from Indonesia a sample from the woman who had the first reported H5N1 infection on Bali, a 29-year-old who died of the disease on Aug 12.Joko Suyono of the health ministry’s avian flu information center said the woman who died yesterday worked for a chicken trader, and authorities suspect she was exposed to infected poultry at work, the Associated Press (AP) reported. She had been hospitalized 4 days at the time of her death.Suyono said tests from two laboratories showed the woman had the virus, according to reports from the Associated Press (AP) and Agence France-Presse.The health ministry said it was determined yesterday that several chickens at the woman’s workplace were infected with H5N1, the AP reported. The ministry gave no information on whether infected poultry might have been sold before the tests.With the latest case, Indonesia has had 105 human H5N1 cases and 84 deaths. The World Health Organization has not yet recognized the case and lists Indonesia’s count as 104 cases with 83 deaths.No human H5N1 cases had been reported on Bali until the 29-year-old woman died of the disease there on Aug 12. She was from the Jembrana district, which officials said is far from the major tourist sites and has avian flu in poultry.Indonesia said last week it was sending a sample from the 29-year-old to the CDC, ending the country’s prolonged withholding of human H5N1 samples from the World Health Organization (WHO). The CDC is a WHO collaborating center.Curtis Allen, a CDC spokesman in Atlanta, confirmed today that the agency received two samples from Indonesia. He said the results of tests by the CDC would be announced by the Indonesian government.In an Aug 20 statement, Indonesia’s avian flu committee said it had sent the CDC samples from the 29-year-old Bali woman and a 2-year-old girl, also from Bali, who had a suspected case but had tested negative for H5N1. The statement said the CDC had already confirmed the findings from the Indonesian labs regarding the two patients.Allen told CIDRAP News today, “I can confirm that we did receive those two samples and those are the two samples we tested. Indonesia would be the ones who would release the information on the results.”Previous reports mentioned a 2-year-old girl with suspected avian flu who was a neighbor of the 29-year-old woman. The Indonesian statement did not make clear whether the girl survived. The woman also had a 5-year-old daughter who died of pneumonia on Aug 3, but she was not tested for H5N1, according to previous reports.Indonesia stopped sending H5N1 patient samples to the WHO last December as a protest against what it considered the unaffordable cost of commercial vaccines derived from the samples. The WHO is trying to hammer out guidelines for sharing of flu viruses that will satisfy the concerns of Indonesia and other developing countries.The Aug 20 statement from Indonesia said H5N1 virus from the samples submitted to the CDC would be genetically sequenced in the next 2 to 3 weeks. The statement predicted that the sampling would show that the virus has not mutated to a more dangerous form, thereby signaling that Bali is safe to visit.
Jan 22, 2008 (CIDRAP News) – Indonesia’s health ministry said today that a 30-year-old man from the outskirts of Jakarta has been hospitalized with an H5N1 avian influenza infection.The health ministry said the man was admitted to a hospital in Jakarta after he got sick with a fever, breathing difficulties, and pneumonia, according to a report today from Reuters. If confirmed by the World Health Organization (WHO), his illness will be listed as Indonesia’s 120th H5N1 case.The patient is from Tangerang, a suburb of Jakarta, according to a statement today from Indonesia’s National Committee for Avian Influenza Control and Pandemic Influenza Preparedness (KOMNAS FBPI). The H5N1 findings were confirmed at the health ministry’s Health Research and Development Center and the Eijkman Institute.The man fell ill on Jan 14 and was initially hospitalized in Tangerang 4 days later, according to KOMNAS FBPI. On Jan 20 he was transferred to Persahabatan Hospital in Jakarta. The source of his infection is under investigation, said the report, which did not list any possible exposure to sick or dead birds.Several of Indonesia’s recent H5N1 patients have hailed from Jakarta suburbs, including Tangerang. Indonesian officials banned backyard poultry in early 2007, but officials have had difficulties enforcing the ban, and local people continue to keep birds in their homes and neighborhoods, according to previous reports.In related developments, the WHO yesterday confirmed the previously reported H5N1 infection and death of an 8-year-old boy, also from Tangerang. His illness pushed Indonesia’s case count to 119, including 97 deaths.The boy got sick on Jan 7, was hospitalized Jan 16, and died at an avian influenza referral hospital 2 days later, according to a statement yesterday from the WHO. An investigation into the source of the boy’s infection was continuing, but the WHO said initial reports reveal that he lived near a chicken slaughterhouse.See also:Jan 21 WHO statement
Oct 29, 2009 (CIDRAP News) – Though only available for emergency use, intravenous (IV) antivirals peramivir and zanamivir have been lifesaving for some pandemic H1N1 patients, including two dramatic cases that doctors presented yesterday during a US Centers for Disease Control and Prevention (CDC) conference call for clinicians.With rising levels of widespread flu activity sweeping the nation, physicians will face greater numbers of critically ill patients, some of whom will require extreme measures, including investigational regimens. Yesterday’s CDC call was designed to get doctors quickly up to speed on the IV antiviral treatment options for the severest pandemic H1N1 infections.The CDC invited two well-known flu experts to discuss the cases and answer clinicians’ questions: Fred Hayden, MD, a virologist at the University of Virginia, and Andrew Pavia, MD, chief of pediatric infectious diseases at the University of Utah.On Oct 23 federal officials issued an emergency use authorization for IV peramivir, to make it easier for physicians to obtain for their severely ill.Though IV zanamivir hasn’t been studied as long as IV peramivir, physicians can request it through the emergency use provision and have used it during the H1N1 pandemic, especially when managing the few oseltamivir-resistant cases that have surfaced.Peramivir after failed oseltamivirIn discussing the first case, Stacene Maroushek, MD, a pediatric infectious disease specialist at Hennepin County Medical Center in Minneapolis, described a 17-year-old boy who was first brought to urgent care by his friends after he started experiencing shortness of breath. She said that about a week before his becoming ill he had attended the Minnesota State Fair in late August and had contact with other people who were sick.Upon hospitalization, he was intubated and placed on high-frequency oscillatory ventilation, and his chest x-ray showed patchy ground-glass opacities. The patient had grossly bloody diarrhea from what physicians discovered was bowel ischemia.Though he received oseltamivir suspension though his nasogastric tube, his medical team didn’t note any improvement in his condition and suspected that the drug wasn’t being absorbed properly because of his gastrointestinal condition.Doctors assessed that the boy was experiencing systemic inflammatory response along with hypotension, pancytopenia, myocarditis, coagulopathy, acute renal failure with oliguria, hepatitis, and pancreatitis.Maroushek said doctors contacted the Minnesota Department of Health and the CDC to discuss IV antiviral treatment options and received emergency authorization to give the boy 600-milligram (mg) doses of IV peramivir for 5 days. Other treatment measures included norepinephrine, blood transfusions, and antibiotics for pneumonia.The patient improved 2 days after doctors initiated peramivir treatment. The boy did not develop a secondary bacterial infection. Though he was weak with symptoms of mental slowing at hospital discharge, she said the boy is improving with therapy and rehabilitation. His 25-day hospitalization cost about $300,000, she said.Oseltamivir-resistant caseIn the second case, Aditya Gaur, MD, an infectious disease specialist at St Jude’s Children’s Research Hospital in Memphis, Tenn., described a severe pandemic H1N1 infection a 10-year-old girl who was immunocompromised because she was undergoing treatment for leukemia.The patient was initially admitted to the hospital for 5 days with flu symptoms such as cough, runny nose, and fever. During hospitalization she received 150 mg of oseltamivir daily.In the 12 days after leaving the hospital the patient had mild residual symptoms, but her symptoms got worse and she was hospitalized again, this time with right lower-lobe pneumonia. Gaur said her respiratory status deteriorated and she was intubated and given broad-spectrum antibiotics. She also received oseltamivir through her nasogastric tube.The girl’s tracheal aspirates were positive for influenza A, and about a week later tests showed she had the oseltamivir-resistant H275Y mutation.Her medical team obtained an emergency investigational new drug clearance to give her IV zanamivir, 600 mg every 12 hours. Over the next 2 weeks the patient tolerated the drug well and her symptoms improved, Gaur said.Tim Uyeki, MD, a medical epidemiologist in CDC’s Influenza Division who moderated the clinician’s conference, commented that the child’s case pointed to evidence of prolonged viral shedding, which experts have documented in immunocompromised patients.Indications for IV antiviralsHayden said the two cases show value of IV antiviral treatment options for severely ill pandemic H1N1 patients. “We’ve known for some time the need for parenteral, rapid, and reliable delivery of these drugs,” he told clinicians.He said IV zanamivir can be life saving for patients who have oseltamivir-resistant viruses, especially when poor lung function precludes use of the powder or nebulizer version.Ribavirin is an older drug that has sporadically been used intravenously for severe flu patients and can be obtained on an emergency basis, Hayden said. “There’s not enough data on it, but if a patient is not responding to other antivirals, it can be used as a salvage drug,” he added.Physicians who use IV antivirals for critically ill patients should make sure therapy duration is sufficiently long, Hayden said, “It makes sense to push to at least 10 days,” he said, adding that immunocompromised patients may need the drugs for even longer.Hayden urged physicians to move quickly to IV antivirals when they encounter patients who are as severely ill as the two case study patients.Pavia agreed that early treatment is crucial. “To make the greatest difference, you need to shut off viral replication early, but it’s never too late to intervene,” he said.Some clinicians have used antiviral combination treatments that incorporate ribavirin, he said. However, he said the lack of data makes the strategy not an attractive option. “We’re very early in using combination treatment,” Pavia said.New drug in clinical trialsPavia and Hayden both mentioned a new antiviral drug that is in clinical trials, T-705, which is being developed by Toyama Chemical, a Japanese company. The new drug is not available yet for emergency use, but they urged physicians to be alert for any clinical trials of it that might be taking place near them.Today Fujifilm Holdings Corp, Toyama’s parent company, announced the launch of phase 3 clinical trials in Japan of T-705, a viral RNA polymerase inhibitor. The company said in a press release that phase 2 studies showed promising results as a treatment for seasonal flu and that animal studies have shown efficacy against the pandemic H1N1 virus.The company says because the drug’s mechanism of action is different than existing antivirals, it might provide an alternative treatment, especially given concerns about viruses developing resistance to neuraminidase inhibitors like oseltamivir, zanamivir, and peramivir.See also:Oct 29 Fujifilm Holdings press releaseOct 26 CIDRAP News story “Emergency authorization for peramivir draws fast response”
Following the events of the past months, it is hard not to get the impression that private renters have become a thorn in the side of the domestic tourist scene.Starting with the banalization of activities, especially the emphasis on profitability with humorous calculations that indicate lucrativeness and encourage further expansion. Apartments and holiday homes pop out of the country like mushrooms after the rain, ignoring the actual cost of entering the business, operating costs, the duration of the season of only a few hectic weeks, and especially the uncertainty of business. Tourist demand has never been more dynamic in its decisions, loyalty is almost non-existent, and an increasing number of new destinations from year to year increases the competition, more precisely, reduces the likelihood of choosing us as holiday destinations. In a given environment, a feeling of helplessness and devotion to the hope that there will be a tourist prevails. So there is no guarantee of business, the uncertainty is great, we can only fear that there will be an escalation as a problem with migrants, an environmental disaster, a natural disaster or simply rain that has recently shown the power to destroy that long-awaited season. Let’s imagine that one year our coastline is left without income from tourism, a frightening picture, not only for entrepreneurs but also for the government. The importance of tourism in our economy and the contribution to the state budget in which private renters participate with half of the realized overnight stays is well known. Tourism, specifically, renting private accommodation is not a machinery that guarantees, but anxiety and expectation without much possibility of influence. But since the drive is currently in overproduction, the government has decided to come for its share of the pie. New levies in the form of a sojourn tax increase and a tax lump sum await renters in the coming year. The position that landlords have so far been treated as a privileged species is emphasized. The pointing of the finger by other entrepreneurs inside and outside the business has started, on the principle of why it is good for them and bad for us, let it be bad for them as well. Shouldn’t the case, let’s call it, of an incentive approach to taxation of private renters, be an example of the desired state of the entire hospitality industry. The question is what the government is aiming at, only budget revenue or, as it is partially pointed out, a measure to raise the quality of accommodation in a private household, assuming that low-quality accommodation will not be able to meet its earnings and leave the business. Photo: Pexels.comWhy would levies force entrepreneurs to close, why not educate them, point out market needs, teach them how to specialize and target their facilities in niche markets and raise awareness of the importance of quality service in tourism for sustainable business. It seems that we forget that it was private renters who raised Croatian tourism. Current numbers the largest share of accommodation capacities and realized overnight stays. Many coastal places have only accommodation facilities in the household. Without the offer of accommodation, the tourist demand has no need or possibility of staying in a certain destination. In this way, private renters create the basis for the development of the destination, because tourists who use their accommodation spend in the destination for example on restaurant services, agency services, trade services, public services. Private renters are a generator of multiplier effects on the local community – Dr.sc. Goran Čorluka Landlords provide accommodation services in places where there are no hotels and where the hotel is very likely never to be. It is an abstract thesis which advocates the position of exclusivity in the circles of the tourist profession, ie that accommodation capacities in the household prevent the development or entry into the market of hotels. The question is, is the private landlord really a competitor to the hotel?The specificity of Croatian tourism in the international environment is precisely the large share of accommodation capacity in the household. They are a tribute to authenticity and autochthony that we must not lose. It is desirable to develop a strategy by which we will valorize this specificity on the market. But judging by current developments, private renters will be exposed to the challenge by the government. The expected recategorization is an additional blow, especially for those who will not be able to meet the new criteria, followed by renovation or closure of the facility. With an increasingly competitive environment and insane demand, the livelihoods of many are questionable. It is necessary to emphasize that the income from the dumping of private accommodation on our coast feeds families, educates children, pays bills, builds the future and creates perspective. State levies will act as a tribute and potentially depopulate the coastal area of the Republic of Croatia. If the coast is threatened by the scenario of Slavonia, because if not from renting, what will people live on? What are the employment opportunities? Is the coast becoming a new zone of demographic issues? I appeal to the analysis of the benefits and harms of the planned activities. Let us nurture and appreciate what we have, what keeps us on our feet. We think long-term and strategically, because it is not a situation and time for wrong moves. Author: dr. Sc. Goran Ćorluka, Head of the Department of Trade Business, Department of Professional Studies, University of SplitRELATED NEWS:RENTERS HAVE THE MOST BENEFITS FROM TOURISM?THE MUNICIPALITY OF TISNO WILL NOT INCREASE THE PRICE OF THE Lump sum FOR RENTERS, AND YOUR CITY OR MUNICIPALITY?VIENNA TERMINATES COOPERATION WITH AIRBNB