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Vol. XII, No. 16 ~ EINet News Briefs ~ Aug 07, 2009
*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
1. Influenza News
- Weekly APEC update of pandemic influenza (H1N1) 2009
- Cumulative number of human cases of avian influenza A/(H5N1)
- Global: WHO says pandemic influenza 2009 H1N1 has reached 168 countries
- Global: WHO lists warning signs for severe pandemic influenza 2009 H1N1 disease
- Global: WHO believes 2 billion people could catch pandemic influenza 2009 H1N1
- Global: WHO says pandemic influenza H1N1 vaccine process won't sacrifice safety
- Global: Two health care workers die of pandemic influenza 2009 H1N1 infection
- Australia (New South Wales): Pandemic influenza 2009 H1N1 confirmed in swine
- Chinese Taipei, Hong Kong: Influenza H3N2 circulating with pandemic H1N1 2009 virus
- Indonesia: Girl hospitalized with suspected avian influenza H5N1
- Russia: Official warns against travel to the UK due to pandemic influenza 2009 H1N1 outbreaks
- Argentina: Pace of pandemic influenza 2009 H1N1 has slowed
- North America: PAHO rejects report of resistant pandemic H1N1 cases on US-Mexico border
- USA: Some experts call for more use of pneumococcal vaccine in pandemic influenza H1N1 battle
2. Infectious Disease News
- China (Qinghai): Outbreak of pneumonic plague kills three, thousands quarantined
- Russia (Chelyabinsk): Update of tick-borne encephalitis in 2009
- Singapore: 3 clusters of malaria under investigation, suspected local transmission
- USA: Salmonellosis outbreak prompts ground beef recall
- USA (Minnesota): Cases of serious tick-borne disease in 2008 and 2009
- USA (Utah): Rabid bats attack girls in Weber County
- INFLUENZA A/H1N1
- AVIAN INFLUENZA
- Public Health and Medical Responses to the 1957-58 Influenza Pandemic
- Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus--United States, 2009
- Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households
- Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza
- Supply and safety issues surrounding an H1N1 vaccine
- Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation
- Artemisinin Resistance in Plasmodium falciparum Malaria
- Laboratory-Acquired Vaccinia Virus Infection--Virginia, 2008
- US Centers for Disease Control and Prevention tools and resources updated
- Weekly Epidemiological Record Bulletin
- International Swine Flu Conference
1. Influenza News
Weekly APEC update of pandemic influenza (H1N1) 2009
Viet Nam reports its first pandemic H1N1 fatality. The US CDC's flu surveillance report for the week ending 25 Jul 2009 says that novel H1N1 activity continued to drop for the fifth consecutive week, with only four states and Puerto Rico reporting widespread activity, down from seven states the week before. CDC reported a total of 5514 hospitalizations due to novel H1N1 infection. China's health ministry is canceling summer camps in areas where novel H1N1 outbreaks are occurring. The action follows reports of more than 120 illnesses in summer camps in Beijing and in Guangzhou in southern China.
(ProMED 8/5/09; CIDRAP 8/4/09)
***For data on human cases of avian influenza prior to 2009, go to:
Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 436 (262).
Avian influenza age distribution data from WHO/WPRO:
WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 5/10/09): http://gamapserver.who.int/mapLibrary/
WHO’s timeline of important H5N1-related events (last updated 7/29/09):
Global: WHO says pandemic influenza 2009 H1N1 has reached 168 countries
Hong Kong led the list of countries reporting new detections with 1,788, followed by Australia with 834 and Italy with 600. The number of deaths among known H1N1 cases reached 1,154 as of 31 Jul 2009, up from 816 on Jul 27, the agency reported. While noting that the number of confirmed cases understates the real numbers, the agency said the confirmed case tally reached 162,380 as of 31 Jul 2009, compared with 134,503 on 27 Jul 2009.
Six oseltamivir-resistant H1N1 cases have been detected so far, including three in Japan and one each in Denmark, Hong Kong, and Canada, the WHO reported. All but one of the patients had been treated with the antiviral, and all have recovered. All the resistant viruses carried the characteristic resistance-linked mutation at position 274/275.
The statement lists "qualitative indicators" of the H1N1 situation for the week of 13-19 Jul 2009. It says that most countries in North and South America had widespread activity, whereas in Europe only the United Kingdom and Portugal had widespread activity. Several other European countries had localized or regional outbreaks. Most Asian countries reporting cases had only localized outbreaks, the agency said.
The report lists the following case counts and deaths tolls for WHO regions as of 31 Jul 2009: the Americas, 98,242 cases and 1,008 deaths; the Western Pacific, 26,661 and 39; Europe, 26,089 and 41; Southeast Asia, 9,858 and 65; the Eastern Mediterranean, 1,301 and 1, and Arica, 229 cases with no deaths. The latest countries to report confirmed cases are Azerbaijan, Gabon, Grenada, Kazakhstan, Moldova, Monaco, Nauru, Swaziland, and Suriname, the WHO said.
Global: WHO lists warning signs for severe pandemic influenza 2009 H1N1 disease
Because a patient's condition can worsen very quickly, medical attention should be sought when any of the warning signs appear, the WHO advised. The agency noted that most patients continue to have mild symptoms and recover fully within a week, but a few people, usually younger than 50, rapidly progress to severe and sometimes fatal illness. "No factors that can predict this pattern of severe disease have yet been identified, though studies are under way," the statement said.
Regarding pregnant women, the WHO noted a US study published this week in The Lancet that showed an increased risk of severe or fatal H1N1 disease in this group. Several other countries also have noted an increased risk for pregnant women and a higher risk of fetal death or spontaneous abortion, the agency said. "WHO strongly recommends that, in areas where infection with the H1N1 virus is widespread, pregnant women, and the clinicians treating them, be alert to symptoms of influenza-like illness," the statement said. The agency said pregnant women should be treated with oseltamivir as soon as possible after symptom onset and should be a priority group for immunization.
The WHO said monitoring of viruses from multiple outbreaks has revealed no evidence of a change in the virus's ability to spread or cause severe illness.
Global: WHO believes 2 billion people could catch pandemic influenza 2009 H1N1
As the northern hemisphere autumn approaches, WHO is working with drug companies to ensure vaccines to cope both with pandemic H1N1 and seasonal flu will be available. Leading flu vaccine makers include Sanofi-Aventis, Novartis , Baxter, GlaxoSmithKline and Solvay.
Novartis has started human testing of pandemic H1N1 flu vaccine candidates while Sanofi-Aventis, the world leader in flu shots, will commence within days, company officials said on 4 Aug 2009. GlaxoSmithKline said it would initiate clinical studies later in August 2009. Healthcare officials are relying on a vaccine to contain the spread of disease, providing a potential sales windfall for those companies that are able to deliver quickly and in large volume.
Australia's CSL has so far been the fastest commercial operator, after starting its first clinical trials in Australia two weeks ago. Others are catching up. Benoit Rungeard, product communications director for Sanofi Pasteur, the vaccines division of the French drug maker, said his company would start "in the coming days or next week." Althoff said Novartis was conducting its clinical trials in a number of countries, including the US, Britain and Germany, and was testing both single and booster, or repeat, doses of vaccines. Novartis, in common with other manufacturers, will also compare vaccines with and without adjuvants--ingredients that boost the immune system response. AstraZeneca, whose MedImmune unit makes smaller amounts of a flu vaccine that is sprayed into the nose rather than injected, said it would start clinical trials in the US around 17 Aug 2009.
Meanwhile, a Taiwanese biotech company on 4 Aug 2009 started mass production of a pandemic H1N1 flu vaccine before even completing clinical trials, in a bid to get a jump before the start of the winter flu season. Adimmune Corp, the island's only human vaccine manufacturer, said it was starting production at its plant in central Taichung. The company is due to deliver 5 million doses of A(H1N1) influenza vaccine before the end of October 2009, according to the purchase contract it has signed with the government, said deputy CEO and president Ignatius Wei. The company says it has completed some animal trials of the vaccine, but will only begin human trials in Sep 2009--sparking criticism about the risks of manufacturing an as-yet unproven product. But Huang Li-min of the National Taiwan University Hospital who will oversee the human trials says Adimmune is taking a calculated risk. "They have to do so. . .they are racing against time," Huang said, referring to the upcoming start of flu season.
Global: WHO says pandemic influenza H1N1 vaccine process won't sacrifice safety
WHO's Dr. Marie-Paule Kieny said the first results of H1N1 vaccine clinical trials are expected in the first half of Sep 2009, and some countries may start using the vaccines the same month, if their regulatory agencies approve. Trials are under way in China, Australia, the United Kingdom, Germany, and the US, she said. The trials are mainly designed to determine whether one or two doses of vaccine will be needed to induce an immune response, while providing some safety data.
Kieny, director of the WHO Initiative for Vaccine Research, noted that the US may treat pandemic H1N1 vaccines the same way it handles the switching of viral strains in seasonal flu vaccines, which does not require clinical trial data for licensing. European regulators do require a clinical trial for a strain change in a seasonal vaccine, she said, but manufacturers that have previously filed data for a "mock-up" pandemic vaccine may get approval for an H1N1 vaccine before submitting clinical trial data.
WHO said some media reports have voiced concern about the safety of H1N1 vaccines. The agency said vaccines need to be made available quickly and in large quantities to fight the pandemic. That didn't happen in the 1957 and 1968 pandemics, when vaccines arrived too late to be of much help during the height of the outbreaks.
Better yields expected
She gave no details on where the improved strain was developed, but a Canadian Press report published 5 Aug 2009 said it was produced by Britain's National Institute for Biological Standards and Controls. Kieny declined to make any predictions about global H1N1 vaccine production capacity. She said an earlier projection of up to 94 million doses per week was a best-case scenario, and the WHO needs more data before making any new predictions.
Kieny noted that the US Food and Drug Administration expects to use this approach with H1N1 vaccines based on the same technology and processes as seasonal vaccines. However, that won't be the case with vaccines containing dose-sparing adjuvants, she noted. Because the US, unlike Europe, has never licensed an adjuvanted flu vaccine, US regulators "will request to review full clinical development," she said. The US government has ordered millions of doses of two different adjuvants, and officials have said that adjuvanted vaccines could be used under a special emergency authorization.
The European Union requires small clinical trials for strain changes in seasonal flu vaccines, Kieny said. But she noted that in view of the threat of H5N1 avian flu, the EU set up a process allowing manufacturers to develop prototype H5N1 vaccines and submit data, with the understanding that when a pandemic emerged, the pandemic strain could be substituted for the prototype strain. Manufacturers that filed mockup vaccine data "can present to the regulatory agency all the documentation for the H1N1 vaccine, and as previously agreed already in 2007, obtain a registration without clinical trials," she said. However, she added that all manufacturers will conduct clinical trials and submit the data as soon as possible, with the earliest expected in September 2009.
Safety issues inevitable
Kieny said WHO has no special concerns about the safety of adjuvanted H1N1 vaccines. "We've reviewed the safety of adjuvanted vaccines as they've been tested for H5N1, and more than 40 million doses of adjuvanted vaccine have been used in Europe already," she said. But she also said there has been no experience in the use of adjuvanted flu vaccines in pregnant women, who are a priority group for H1N1 vaccination. The WHO's Strategic Advisory Group of Experts (SAGE), she said, recommended in July 2009 that pregnant women should receive unadjuvanted vaccine where possible, but that an adjuvanted vaccine could be used if necessary.
Kieny also said the WHO is discussing with manufacturers how to provide enough free or reduced-price vaccine to cover healthcare workers in all developing countries. She noted that donations of 100 million and 50 million doses have been pledged so far.
Global: Two health care workers die of pandemic influenza 2009 H1N1 infection
Australia (New South Wales): Pandemic influenza 2009 H1N1 confirmed in swine
Tests have confirmed that pandemic influenza H1N1 has broken out at a piggery in the central west of New South Wales (NSW). It is the first case of the virus among pigs in Australia and the State Government believes the animals probably caught the disease from workers at the piggery. A total of 280 pigs have been placed in quarantine and strict biosecurity measures are in place to try to contain the spread of the virus. NSW Primary Industries Minister Ian Macdonald says the piggery's owner and staff have previously suffered flu-like symptoms and are being tested for pandemic influenza H1N1. Macdonald says the outbreak poses no threat to humans.
Chinese Taipei, Hong Kong: Influenza H3N2 circulating with pandemic H1N1 2009 virus
The deputy director-general of the center, Lin Ting, said that since most of the infected are men in their 30s, these men are being considered for receiving the vaccines as well. Head of the physical education department of the education ministry Wang Jun-chuan said on 31 Jul 2009 that schools have the right to decide whether to stop classes if cases were to appear in schools.
"We have been in touch with the Taipei Centers of Disease Control. If a school were to have one infected case, we have agreed that the school can discuss with the county government and the health department about whether to stop classes for up to seven days. But if the situation is serious, this can extended to 10 days. Secondly, if the county happens to have more than two cases in a school or a case of cluster infection, then the health department can decide for all schools in the district or nearby region to be shut down," said Wang.
Meanwhile, Hong Kong's health authorities announced 27 Jul 2009 that a new variant of the H3N2 seasonal influenza virus has been found. The Brisbane strain has been the prevalent circulator of H3N2 in the past year, and the new variant is its direct descendent, said Thomas Tsang, controller of Hong Kong's Center for Health Protection (CHP). "However, it has some genetic changes distinguishing it from the old Brisbane strain," he said. He said it is normal for viruses to go through changes, adding that overseas health authorities, including those in Canada, Britain and Australia, had also found the new variant.
Tsang said although vaccines provided for the northern hemisphere may not be a direct match for this new variant, they will still provide some protection. According to the CHP, H3N2 accounts for 43 percent of flu viruses circulating in Hong Kong, while A/H1N1 accounts for 49 percent. Officials from the two economies will meet to discuss response to the pandemic influenza H1N1 2009 in August 2009.
Indonesia: Girl hospitalized with suspected avian influenza H5N1
Russia: Official warns against travel to the UK due to pandemic influenza 2009 H1N1 outbreaks
Argentina: Pace of pandemic influenza 2009 H1N1 has slowed
Argentina's pandemic H1N1 cases have peaked, and so far the death rate from the disease seems to be less than for seasonal flu, said public health experts on 31 Jul 2009. However, one official said the disease has had its greatest impact on young people. Scientists report that viruses isolated in Argentina are nearly identical to those circulating in North America.
North America: PAHO rejects report of resistant pandemic H1N1 cases on US-Mexico border
But in an e-mail message, Cerqueira said she was misquoted. She sent the message to PAHO. Cerqueria wrote that she mentioned McAllen and El Paso as being among the border towns where novel flu virus has been detected. She said that in response to a question about resistant cases, she said she was concerned and that PAHO has recommended surveillance for such cases, especially since people go back and forth across the border for medical care and to buy medicine. Cerqueira said she repeated that she had no information on any antiviral-resistant cases in the border area. "It is an unfortunate misinterpretation that needs to be clarified," she wrote.
So far, oseltamivir-resistant novel flu cases have been confirmed in Denmark, Hong Kong, Japan, and Canada. All of the patients had a history of oseltamivir prophylaxis or treatment, except for the patient in Hong Kong, a girl who was visiting from the US, where officials believe she was exposed to the virus.
USA: Some experts call for more use of pneumococcal vaccine in pandemic influenza H1N1 battle
2. Infectious Disease News
China (Qinghai): Outbreak of pneumonic plague kills three, thousands quarantined
A dog is suspected to be the origin of an outbreak of pneumonic plague in northwest China that has killed three people and left 10,000 under strict quarantine. Ziketan, a remote town in a Tibetan area of Qinghai province, has been locked down since 1 Aug 2009 in an effort to contain the spread of the highly virulent disease. One patient was in critical condition and eight others were infected, most of them relatives of the first fatality, a 32-year-old herdsman, or local doctors, Xinhua news agency said.
Initial tests had shown that the herdsman's dead dog was the likely origin of the outbreak, stated professor Wang Hu, director of the Qinghai disease control bureau. Wang said it was likely that the dog died after eating a plague-infected marmot and that the man became infected when he was bitten by fleas while burying the dead dog. He died three days later."The first victim buried the dead dog without any protection. After he became infected, his relatives and neighbors were in close contact with him without taking any protective measures, leading to their infection," Wang said. At present, 218 people are quarantined in hospital, and 115 of them had been in close contact with those infected.
Russia (Chelyabinsk): Update of tick-borne encephalitis in 2009
The health care services of the Chelyabinsk Oblast are responsible for implementing an immunization program against TBE virus infection. Through August 2009, 165,000 people, including 101,636 children, have been immunized. Treatments against tick infestation have been applied over an area of 4000 hectares, including 598.8 hectares of recreational land. During July 2009 outdoor activities for children, such as hiking and excursions, have been restricted to these treated areas.
Singapore: 3 clusters of malaria under investigation, suspected local transmission
The first cluster involves five cases comprising male foreign workers aged between 25 to 37 years at Jurong Island. The cases had onset of illness 3 to 25 May 2009 with symptoms such as fever, headache and chills. Four of the cases stayed at a dormitory on Jurong Island and work at the same site on Jurong Island. The fifth case works on Jurong Island close to the dormitory and worksite of the other four cases. The second cluster involves nine cases aged between 20 and 40 years in the Sungei Kadut/Mandai area comprised of eight foreign workers and one full-time national serviceman. The cases had onset of illness between 16 and 30 May 2009 with symptoms such as fever, headache and chills.
The third cluster consists of four cases near a row of shop houses located at the junction of Sembawang Road and Admiralty Road East. The first case is a 24-year-old Singaporean woman who works in the area. Her illness started on 30 Jun 2009 and she was admitted to hospital on 20 Jul 2009. She does not have any recent travel history or past history of malaria.
The second and third cases involve colleagues -- a 49-year-old Singaporean man and a 40-year-old Singaporean woman. They frequented a coffee shop at the row of shop houses. The male patient fell sick on 11 Jul 2009 and was admitted to hospital four days later. His colleague fell ill on 12 Jul 2009 and was hospitalized on 17 Jul 2009. The fourth case is a 24-year-old male foreign worker who was picked up during MOH's active case finding in the vicinity. He stayed at a nursery beside the row of shop houses and first had symptoms on 12 Jun 2009. He was admitted to hospital on 28 Jul 2009.
The third cluster is not related to the previous two clusters as none of the four cases had visited Jurong Island or Mandai/Sungei Kadut prior to their illness.
USA: Salmonellosis outbreak prompts ground beef recall
Beef Packers, Inc., a Fresno, California, establishment, is recalling approximately 825,769 pounds (375 tons) of ground beef products that may be linked to an outbreak of salmonellosis, the US Department of Agriculture's Food Safety and Inspection Service (FSIS) announced 6 Aug 2009. Details on the recall are available at http://www.fsis.usda.gov/News_&_Events/Recall_041_2009_Release/index.asp. This particular strain of S. Newport is resistant to many commonly prescribed drugs, which can increase the risk of hospitalization or possible treatment failure in infected individuals.
USA (Minnesota): Cases of serious tick-borne disease in 2008 and 2009
This type of encephalitis, also known as Powassa (POW) disease, struck a child in Cass County in 2008 and an adult in the same county in 2009. Both patients were hospitalized with severe neurological symptoms and require ongoing care, according to the department. Since this encephalitis virus was first identified in 1958 in Powassan, Ontario, about 50 cases have been reported in the US and Canada. The patients in Minnesota represent the western-most human cases identified in North America, state health officials said. Signs and symptoms of Powassa disease appear within two weeks of an infectious tick bite. Many patients never see the tick that bit them. People with POW encephalitis or meningitis may have fever, headache, vomiting, weakness, confusion, loss of coordination, speech difficulties, and memory loss. Long-term problems are common, and about 10 percent of reported cases result in death.
USA (Utah): Rabid bats attack girls in Weber County
The following websites provide the most current information, surveillance, and guidance.
- WHO regional offices
- North America
- Other useful sources
According to a department report, 36,046 dengue cases were reported nation-wide up to 19 Jul 2009, a 11.7 percent increase over the same period in 2008. Cases were mostly in the southern region. Nam explained that since most water in the southern region is brackish, residents use containers to store water, which act as reservoirs for mosquitoes.
Public Health and Medical Responses to the 1957-58 Influenza Pandemic
Henderson DA et al. Biosecurity & Bioterrorism: Biodefense Strategy, Practice, and Science. 2009; 7(3). Available at http://www.liebertonline.com/doi/pdfplus/10.1089/bsp.2009.0729?cookieSet=1.
As the U.S. prepares to respond this fall and winter to pandemic (H1N1) 2009, a review of the 1957-58 pandemic of Asian influenza (H2N2) could be useful for planning purposes because of the many similarities between the 2 pandemics. Using historical surveillance reports, published literature, and media coverage, this article provides an overview of the epidemiology of and response to the 1957-58 influenza pandemic in the U.S., during which an estimated 25% of the population became infected with the new pandemic virus strain. While it cannot be predicted with absolute certainty how the H1N1 pandemic might play out in the U.S. this fall, lessons from the 1957-58 influenza pandemic provide useful and practical insights for current planning and response efforts.
Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus--United States, 2009
The recent appearance and worldwide spread of novel influenza A (H1N1) virus has highlighted the need to evaluate commercially available, widely used, rapid influenza diagnostic tests (RIDTs) for their ability to detect these viral antigens in respiratory clinical specimens. As an initial assessment, CDC conducted an evaluation of multiple RIDTs. Sixty-five clinical respiratory specimens collected during April--May 2009* that had previously tested positive either for novel influenza A (H1N1) or for seasonal influenza A (H1N1) or A (H3N2) viruses by real-time reverse transcription--polymerase chain reaction (rRT-PCR) assay were used in the evaluation. The results showed that, although the RIDTs were capable of detecting novel A (H1N1) virus from respiratory specimens containing high levels of virus (as indicated by low cycle threshold [Ct] values), the overall sensitivity was low (40%--69%) among all specimens tested and declined substantially as virus levels decreased (and Ct values increased). These findings indicate that, although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus. Patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness, and risk for complications. If a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed. Additional evaluations of the accuracy of RIDTs in detecting novel influenza A (H1N1) virus should be conducted. (Excerpt with references removed.)
Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households
Background: Few data are available about the effectiveness of nonpharmaceutical interventions, such as hand hygiene and facemasks, for preventing influenza virus transmission.
Objective: To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza.
Design: Cluster randomized controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment.
Setting: Households in Hong Kong. Patients: 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.
Intervention: Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.
Measurements: Influenza virus infection in household contacts, as confirmed by reverse transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.
Results: Sixty (8%) household contacts in the 259 households had RT-PCR–confirmed influenza virus infection in the 7 days after intervention. Hand hygiene without or with facemasks seemed to reduce influenza transmission, but the differences in transmission compared with the control group were not statistically significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR–confirmed infection seemed to be reduced, an effect attributable to reductions in infection among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions was variable. Limitation: The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.
Conclusion: Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.
Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza
Background: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.
Purpose: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.
Data Sources: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries. Study Selection: Randomized, placebo-controlled, double-blinded human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.
Data Extraction: 2 reviewers independently assessed study quality and abstracted information from eligible studies.
Data Synthesis: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. NAI chemoprophylaxis decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], –3.9 percentage points [CI, –5.8 to –1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, –0.4 percentage point [CI, –1.6 to 0.9 percentage point). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, –0.2 to 0.4 percentage point), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.
Limitations: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.
Conclusion: Extended-duration zanamivir and oseltamivir chemoprophylaxis appears to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.
Supply and safety issues surrounding an H1N1 vaccine
Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation
The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza, and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir resistant seasonal A(H1N1) viruses in Europe, USA, Oceania and South Africa, to date there have been no reports of significant zanamivir resistance among A(H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal A(H1N1) influenza viruses in Australasia and South East Asia. Analysis of 391 A(H1N1) influenza viruses isolated between 2006 and early 2008 from Australasia and South East Asia revealed nine viruses (2.3%) which demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility, but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible A(H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wildtype virus in MDCK cells, but equivalent infectivity and transmissibility in a ferret model.
Artemisinin Resistance in Plasmodium falciparum Malaria
Methods In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance.
Results We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate–mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco–endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups.
Conclusions P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed.
Laboratory-Acquired Vaccinia Virus Infection--Virginia, 2008
Vaccinia virus (VACV) is the live viral component of smallpox vaccine. Inadvertent exposure to VACV can result in infection, and severe complications can occur in persons with underlying risk factors (e.g., pregnancy, immunodeficiencies, or dermatologic conditions). The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for laboratory workers who handle nonhighly attenuated VACV strains or other orthopoxviruses (e.g., monkeypox, cowpox, or variola). On July 8, 2008, CDC was notified by a Virginia physician of a suspected case of inadvertent autoinoculation and VACV infection in an unvaccinated laboratory worker. This report describes the subsequent investigations conducted by the Virginia Department of Health and CDC to identify the source of infection and any cases of contact transmission. Of the patient's 102 possible contacts, seven had underlying risk factors for developing serious vaccinia infection. Investigators found no evidence of contact transmission and, based on the results of molecular typing, further concluded that the patient had been exposed to a VACV strain that had contaminated the seed stock from the laboratory where the patient worked. This case underscores the importance of adherence to ACIP vaccination recommendations for laboratory workers and use of safety precautions when working with nonhighly attenuated VACV. (Excerpt with references removed.)
US Centers for Disease Control and Prevention tools and resources updated
Novel H1N1 Vaccination Recommendations: http://www.cdc.gov/h1n1flu/vaccination/acip.htm
Managing Calls and Call Centers during a Large-Scale Influenza Outbreak: Implementation Tool: http://www.cdc.gov/h1n1flu/callcenters.htm
Preparing for Vaccination with Novel H1N1 Vaccine: http://www.cdc.gov/h1n1flu/vaccination/provider/preparing.htm
School Dismissal Monitoring System: http://www.cdc.gov/h1n1flu/schools/dismissal_form/index.htm/?scan.
Weekly Epidemiological Record Bulletin
Learning objectives for the conference:
Additional information available at http://new-fields.us/em/link.php?M=9950864&N=90&L=187&F=T.