Vol. XIII, No. 3 ~ EINet News Briefs ~ Feb 05, 2010

*****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
- 2010 Cumulative number of human cases of avian influenza A/H5N1
- WHO situation update on pandemic influenza H1N1
- Global: Surplus H1N1 vaccine not reaching countries that need it
- Egypt: Avian influenza H5N1 outbreaks reported in poultry
- UK: Pandemic hotline to end 11 February 2010
- ASEAN: Nations commit to quicker access to antiviral drugs, pandemic influenza vaccine
- Chinese Taipei: H1N1 pandemic influenza vaccine taken to airports, homes
- Indonesia: Scientist says avian influenza H5N1 may be outwitting poultry vaccines
- Indonesia (Lampung): H5N1 avian influenza kills more than thousand chickens
- Nepal: Avian influenza H5N1 outbreaks reported in poultry
- New Zealand: Influenza H1N1 vaccinations to begin
- Singapore: Purchase of one million H5N1 avian influenza vaccine doses
- Viet Nam, Cambodia: H5N1 avian influenza outbreaks in poultry
- USA: Pandemic H1N1 vaccine uptake estimated at 75 million

2. Infectious Disease News
- Global: Lancet retracts paper linking vaccines and autism
- Russia (Podmoskovye): Rabid dog bites 14 people
- Viet Nam (Quang Nam): Malaria outbreak
- USA: Salmonella outbreak prompts recall of more sausage products
- USA (New York): Rabies outbreak threat in New York City
- USA: Gates Foundation gives $10 billion for vaccines
- USA (Colorado): Hantavirus related death

3. Updates

4. Articles
- Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2
- Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency
- Targeted Antiviral Prophylaxis With Oseltamivir in a Summer Camp Setting
- Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1
- Protection of Mice against Lethal Challenge with 2009 H1N1 Influenza A Virus by 1918-Like and Classical Swine H1N1 Based Vaccines
- Effect of Rotavirus Vaccination on Death from Childhood Diarrhea in Mexico
- Effect of Human Rotavirus Vaccine on Severe Diarrhea in African Infants
- A broad-spectrum antiviral targeting entry of enveloped viruses

5. Notifications
- Emerging Infectious Diseases in Response to Climate Change
- 14th International Congress on Infectious Diseases (ICID)
- International Swine Flu Conference (ISFC)
- ISHEID Symposium on HIV and Emerging Infectious Diseases
- CDC 7th International Conference on Emerging Infectious Diseases
- Options for the Control of Influenza VII
- Updated influenza guidance and information from the US CDC

1. Influenza News

2010 Cumulative number of human cases of avian influenza A/H5N1
Economy / Cases (Deaths)
Egypt / 4 (0)
Total / 4(0)

***For data on human cases of avian influenza prior to 2010, go to: http://depts.washington.edu/einet/humanh5n1.html

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 471 (282)
(WHO 1/28/10 http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_01_28/ )

Avian influenza age distribution data from WHO/WPRO (last updated 12/30/09): http://www.wpro.who.int/sites/csr/data/data_Graphs.htm

WHO's map showing world's areas affected by H5N1 avian influenza (status as of 9/24/09): http://gamapserver.who.int/mapLibrary/Files/Maps/Global_H5N1Human_2009_FIMS_20090924.png.

WHO's timeline of important H5N1-related events (last updated 1/4/10): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html


WHO situation update on pandemic influenza H1N1
As of 31 January 2010, worldwide more than 209 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 15,174 deaths.

In the temperate zone of the northern hemisphere, overall pandemic influenza activity continues to decline or remain low in most regions since peaking during late October and November 2009. Several areas continue to have evidence of active but declining transmission, particularly in North Africa and in limited areas of Eastern Europe and East Asia.

In North Africa, pandemic influenza transmission remains active and geographically widespread but overall activity has been declining since peaking during late December 2009 and early January 2010. During January 2010, a substantial decline in the number of pandemic virus isolations and new cases was observed in Morocco and Egypt, respectively. In West Asia, pandemic influenza transmission remains geographically widespread to regional, but overall activity remained low.

In South and Southeast Asia, pandemic influenza transmission remains active but geographically localized to regional. The overall intensity of respiratory diseases activity was reported to be low to moderate in most places. In India, influenza activity continued to decline in all regions of the country, however, the most active areas of transmission currently are in the western states. An overall peak in the number of pandemic H1N1 cases was recorded in India during mid December 2009, and the majority of these cases were identified in the northern and western states of India. In Thailand, overall ILI activity remained low, however focal increase in activity were observed in several central and northern provinces.

In East Asia, pandemic influenza transmission remains active and geographically widespread across the region, however, overall activity continued to decline. In Japan, overall influenza activity continues to decline but transmission remains higher on the southern island of Okinawa than in other places. In the Republic of Korea (South Korea), rates of ILI continued to decline to near baseline after a substantial wave of activity which peaked during early to mid November 2009. In Mongolia, after a period of sustained elevated ILI activity since early November 2009, levels of ILI have recently fallen to the expected seasonal range. In northern and southern China, rates of ILI have returned to levels seen during recent seasons; however, approximately 30% of respiratory specimens tested were positive for influenza suggesting that active transmission of influenza viruses persists. Of note in China, in recent weeks the circulation of pandemic influenza H1N1 continued to decline with a concomitant increase in the circulation of seasonal influenza type B viruses (pandemic H1N1 and seasonal Type B viruses accounted for 34% and 66% of all influenza viruses detected, respectively). Active transmission of pandemic influenza virus also persists in Hong Kong SAR (China), although at significantly lower levels than an earlier peak of activity during September and October 2009.

In Europe, transmission of pandemic influenza virus remains active in a limited number of countries as overall activity remained low in most places. At least seven countries testing more than 20 sentinel respiratory samples reported that >20% of samples had tested positive for influenza (Albania, Bulgaria, the Czech Republic, Georgia, Greece, Luxembourg, and Romania); however, in all seven, rates of illness remained well below earlier peaks of activity. Small increases in ILI/ARI have been reported over the past two reporting weeks in Slovakia, Belarus, and the Russian Federation. The overall rate of sentinel respiratory samples testing positive for influenza fell to 14% after reaching a peak of 45% during early November 2009.

In the Americas, both in the tropical and northern temperate zones, overall pandemic influenza activity continued to decline or remain low in most places. In Central America and Caribbean, pandemic influenza virus transmission persists but overall activity remains low or unchanged in most places.

In temperate regions of the southern hemisphere, sporadic cases of pandemic influenza continued to be reported without evidence of sustained community transmission.

Pandemic influenza (H1N1) 2009 virus continues to be the predominant influenza virus circulating worldwide. In addition to the increasing proportion of seasonal influenza type B viruses recently detected in China, low levels of seasonal H3N2 and type B viruses are circulating in parts of Africa, East and Southeast Asia and are being detected only sporadically on other continents.
(WHO 02/05/2010)


Global: Surplus H1N1 vaccine not reaching countries that need it
There is now so much unused swine flu vaccine in the world that rich nations, including the United States, are trying to get rid of their surpluses. But the world's poorest countries - a few still facing the brunt of the pandemic - are receiving very little of it.

Of the 95 countries that told the WHO in 2009 that they had no means of getting flu vaccine, only two, Azerbaijan and Mongolia, have received any so far. Afghanistan is expected to be next. WHO officials previously said they hoped to have shipped vaccine to 14 countries by now, and even then it would have been only enough to protect two percent of the countries' populations.

While the flu has waned in North America, it is still affecting North Africa, Central Asia and parts of Eastern Europe. This imbalance between rich and poor countries, and the inefficiency of global vaccine transfers, frustrate many experts. "If we'd been confronted with H5N1, we'd be completely caught with our pants down," Dr. David S. Fedson, a former medical director for Aventis-Pasteur vaccines and an expert on pandemics, said, referring to the avian flu, which has a 60 percent mortality rate. "I don't think any nation got it right."

But the WHO is stuck with the world as it is: countries that can afford vaccines save themselves first and, when the worst has passed, transfer their leftovers to the poor, using the WHO as a clearinghouse. That transfer "turns out to be an incredibly difficult logistical action," said Dr. Keiji Fukuda, the WHO's chief of pandemic influenza. "It's a mammoth effort by an awful lot of people and organizations and countries but holy moly, it's a very complex operation."

Each country must submit a plan proving it can store refrigerated vaccine, give it to those who need it most, inject it safely and do medical follow-up. It must also sign letters exempting donors from legal liability, and the WHO has to certify the vaccine as safe if the country has no regulatory agency. Even shipping adds delays. By December, Dr. Fukuda said, only five countries had even received syringes.

Not everyone says shifting swine flu vaccine to poor countries makes sense. Bill Gates, who just pledged $10 billion, the largest charitable donation in history, to getting other vaccines to the poor, dismissed flu vaccine shipments as "a pipe dream." "It's not practical; they have no infrastructure to deliver it," he said. "And you don't want to distract them away from measles vaccine, for example. That could cost lives."
(New York Times 2/1/2010)


Europe/Near East
Egypt: Avian influenza H5N1 outbreaks reported in poultry
Egyptian livestock officials said birds in several more locations have tested positive for the H5N1 virus. Details of 18 new outbreaks since 19 January 2010 or later appear on the Web site of Egypt-based Strengthening Avian Influenza Detection and Response (SAIDR). All except one occurred in household chickens and ducks. The lone farm outbreak occurred at a broiler breeding operation in Dakahliya governorate where the birds had been vaccinated. The outbreaks spanned seven different governorates, and six occurred in Dakahliya.
(CIDRAP 2/4/2010)


UK: Pandemic hotline to end 11 February 2010
Due to waning flu activity, Britain's hotline for pandemic flu diagnosis and antiviral prescriptions will be shut down on 11 Feb 2010, Chief Medical Officer Sir Liam Donaldson announced in a letter to physicians. Donaldson said the service eased pressure on primary care physicians at the height of the pandemic, but flu-like illnesses and confirmed H1N1 cases now are less than half what they were before the service was launched. The service can be restored in seven days if needed, he said.
(CIDRAP 2/2/2010)


ASEAN: Nations commit to quicker access to antiviral drugs, pandemic influenza vaccine
The region's Ministries of Health, and the Food and Drug agencies said recently that they will jointly formulate regional policies to facilitate domestic production, importation and registration of the antiviral drugs and pandemic influenza vaccines. Representatives of ASEAN Member States also said that they would explore the feasibility of joint procurement to reduce the costs and to secure the availability of supply," said Mr. Dhannan Sunoto, Director of the Cross-Sectoral Cooperation Directorate of the ASEAN Secretariat. During the ASEAN Meeting on Promoting Access to Antiviral Drugs and Pandemic Influenza Vaccines held in Singapore, the sharing of antiviral drugs, vaccines and other resources was also discussed by the representatives of the Member States.

Meanwhile, at the national level Member States have been encouraged to enhance partnerships with the pharmaceutical industry to promote transfer of technology and to seek the cooperation of local industries to produce the drugs and vaccines needed. With this in mind, consultations between Governments and several international and regional pharmaceutical companies were also convened. "We are looking for win-win schemes that would allow the ASEAN people to have better and quicker access to the antiviral drugs and vaccines for pandemic influenza," said Mr. Sunoto, who expressed optimism that practical public-private partnership schemes could be explored to make the drugs and vaccines easily available in the region. Such schemes may be also open to drugs and vaccines against other infectious diseases in general.
(ASEAN Secretariat Press Release 2/1/2010)


Chinese Taipei: H1N1 pandemic influenza vaccine taken to airports, homes
To boost pandemic vaccination rates, health officials in Chinese Taipei have unveiled two new tactics, immunization at airports and in homes. Four airports will offer the vaccines to citizens entering Chinese Taipei. Home-based vaccinations are available to groups of at least 10 people in communities, companies, or institutions who make a reservation with the local health department. Vaccine safety concerns have slowed vaccine uptake, though 24% have received it.
(CIDRAP 2/1/2010)


Indonesia: Scientist says avian influenza H5N1 may be outwitting poultry vaccines
An Indonesian virologist says the H5N1 avian influenza virus in Indonesia may have evolved so as to make the poultry vaccines used there less effective. The virologist, I Gusti Ngurah Mahardhika, said genetic differences of up to 8.7% were found when viral isolates collected at farms with vaccinated flocks in 2008 and 2009 were compared with a virus isolated from Legok, Banten, in 2003. The Legok virus is still being used by most vaccine producers in Indonesia. Mahardhika suggested that the viral mutations may explain a series of outbreaks in Indonesian flocks over the past two years. He also said he had "strong evidence" that vaccines based on the Legok virus are not effective against newer strains. Another scientist, Amin Soebandrio of the University of Indonesia, said he concurred with Mahardhika's findings and commented, "We need to see whether the changes increase the capacity of the virus to infect the human respiratory system."
(CIDRAP 2/3/2010)


Indonesia (Lampung): H5N1 avian influenza kills more than thousand chickens
The H5N1 virus has stricken three sub districts in East Lampung District, killing at least 1,176 chickens. Avian influenza H5N1 is endemic on Java, Sumatra, Sulawesi and probably Bali islands, with sporadic outbreaks reported elsewhere.
(ProMED 1/30/2010)


Nepal: Avian influenza H5N1 outbreaks reported in poultry
Veterinary officials in Nepal said tests have confirmed an H5N1 avian influenza outbreak in ducks and chickens in Pokhara, Nepal's third largest city. The samples were positive in preliminary tests conducted in Pokhara on 26 January 2010 and were sent to London for further testing. A response team has been sent to disinfect the outbreak vicinity, and officials have stopped the movement of birds in the area. The outbreak is Nepal's first since January 2009, according to the World Organization for Animal Health.
(CIDRAP 2/4/2010)


New Zealand: Influenza H1N1 vaccinations to begin
New Zealand, which saw some of the earliest deaths from H1N1 influenza during its 2009 winter flu season, has received its first doses of H1N1 vaccine and is scheduling a national immunization campaign. The first recipients of the one million doses will be health workers, pregnant women, young children, and the chronically ill. The Southern Hemisphere country is concerned that the virus may return from the Northern Hemisphere and trigger an earlier than usual flu season.
(CIDRAP 2/3/2010)


Singapore: Purchase of one million H5N1 avian influenza vaccine doses
As H1N1 pandemic flu subsides globally, Singapore is returning its attention to preparing for a possible outbreak of H5N1 avian flu. The country's Health Ministry announced 28 January 2010 that it will purchase and stockpile one million doses of avian flu vaccine. The announcement came as Singapore's media challenged the government about poor acceptance of H1N1 vaccine: Of 1.3 million doses bought, 425,000 were ordered by medical sites.
(CIDRAP 1/29/2010)


Viet Nam, Cambodia: H5N1 avian influenza outbreaks in poultry
More than 1,000 ducks were infected with avian flu on a farm in Viet Nam's central province of Quang Tri, leading to the culling of another 1,000 ducks, vaccination of 8,300, and other control measures. The province's animal health officer said the ducks' owner was slow to report the outbreak, which allowed the disease to spread. Meanwhile, Cambodian authorities began culling ducks 3 February 2010 to control an H5N1 avian flu outbreak that killed more than 15,000 ducks, during the week of 25 January 2010, in the southern province of Takeo. Samples tested positive for the virus 2 February 2010.
(CIDRAP 2/3/2010)


USA: Pandemic H1N1 vaccine uptake estimated at 75 million
A US CDC official estimated today that more than 75 million Americans, or close to 25% of the population, have been vaccinated against the pandemic H1N1 virus.
(CIDRAP 2/4/2010)


2. Infectious Disease News

Global: Lancet retracts paper linking vaccines and autism
In an unusual reversal, The Lancet has published a statement in which it "fully retracts" a 1998 paper that linked measles, mumps and rubella (MMR) vaccine with the development of autism in children. On 28 January 2010, the General Medical Council of the United Kingdom found that the paper's lead author, Dr. Andrew Wakefield, acted "dishonestly and irresponsibly" in arranging the research and taking advance payments from attorneys. The original paper, titled "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children," is widely held to be responsible for the now-widespread belief that vaccines cause autism, which has been disproved by multiple subsequent studies.
(CIDRAP 2/2/2010)


Russia (Podmoskovye): Rabid dog bites 14 people
A rabid dog bit at least 14 people in Podmoskovye. A quarantine is being imposed on the inhabitants of the village of Yadrominskoe. These people had been bitten by the dog between 18 and 21 January 2010. The sick dog had been roaming in the market area of the Kuskovo district of Istarinskoe region in Moscow oblast. Those attacked by the rabid dog have received post-exposure rabies vaccination in the regional hospital. The dog was euthanized by the local veterinary service. The population in the surrounding area is being asked for information about other victims.
(ProMED 1/27/2010)


Viet Nam (Quang Nam): Malaria outbreak
On 31 January 2010, the Nam Tra My General Hospital in the central province of Quang Nam reported admitting 25 people with malaria over the week of 25 January 2010. The local health agency found nearly 100 additional people affected with malaria that did not seek treatment at the hospital. This is the first report of a malaria outbreak in Viet Nam in 2010.
(ProMED 2/3/2010)


USA: Salmonella outbreak prompts recall of more sausage products
A Rhode Island sausage company at the center of a widespread Salmonella outbreak expanded its recall to include about 24,000 more pounds of salami products that include 3-oz packages of Daniele salami coated with coarse black pepper and 6-lb packages of Daniele salami coated with pork fat and pepper, according a statement 4 February 2010 from the US Department of Agriculture's Food Safety and Inspection Service (FSIS). On 3 February 2010 the US CDC said that it has received four more reports of illnesses linked to the outbreak, raising the total to 207. The number of affected states stayed the same, at 42.
(CIDRAP 2/4/2010)


USA (New York): Rabies outbreak threat in New York City
Authorities and medical experts warned 29 January 2010 that a rabies outbreak in Central Park could spread from raccoons to humans. Health investigators have confirmed reports of 28 rabid raccoons in or near Central Park during January 2010 and December 2009. There were only three cases from 2003 through November 2009.
(ProMED 2/3/2010)


USA: Gates Foundation gives $10 billion for vaccines
Speaking at the World Economic Forum 29 January 2010, Bill and Melinda Gates announced that their foundation will create a $10 billion, 10-year program to push development of new or improved vaccines for AIDS, tuberculosis, rotavirus, and pneumonia. They said the goal will be to distribute such vaccines in the developing world, where they aim to increase vaccine uptake to 90% of children under 5. If they are successful, they said, the investment could save the lives of 7.6 million children over the 10 years of the program. And if a new malaria vaccine in which they have also invested, due to be deployed in 2014, is added into the calculation, the total number of lives saved could be 8.7 million.
(CIDRAP 1/29/2010)


USA (Colorado): Hantavirus related death
The Alamosa County Health Department says a hantavirus caused the death of a county resident. No details have been given about the victim or when the person died. Alamosa County's last hantavirus death was in the 2007, when a 28-year-old woman died.
(ProMED 1/29/2010)


3. Updates
Influenza A/H1N1: http://www.who.int/csr/disease/swineflu/en/index.html
Influenza A/H1N1 frequently asked questions: http://www.who.int/csr/disease/swineflu/frequently_asked_questions/en/index.html
Pandemic Influenza Preparedness and Response - A WHO Guidance Document
International Health Regulations (IHR) at http://www.who.int/ihr/en/index.html

- WHO regional offices
Africa: http://www.afro.who.int/
Americas: http://new.paho.org/hq/index.php?option=com_content&task=blogcategory&id=805&Itemid=569
Eastern Mediterranean: http://www.emro.who.int/csr/h1n1/
Europe: http://www.euro.who.int/influenza/ah1n1
South-East: http://www.searo.who.int/EN/Section10/Section2562.htm
Western Pacific: http://www.wpro.who.int/health_topics/h1n1/

- North America
US CDC: http://www.cdc.gov/flu/swine/investigation.htm
US pandemic emergency plan: http://www.flu.gov
MOH México: http://portal.salud.gob.mx/index_eng.html
PHA of Canada: http://fightflu.ca

- Other useful sources
CIDRAP: Influenza A/H1N1 page: http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/biofacts/swinefluoverview.html
ProMED: http://www.promedmail.org/


- UN: http://www.undp.org/mdtf/influenza/overview.shtml UNDP's web site for information on fund management and administrative services. This site also includes a list of useful links.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/
- UN FAO: http://www.fao.org/avianflu/en/index.html. View the latest avian influenza outbreak maps, upcoming events, and key documents on avian influenza H5N1.
- OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm. Link to the Communication Portal gives latest facts, updates, timeline, and more.
- US CDC: Visit "Pandemic Influenza Preparedness Tools for Professionals" at: http://www.cdc.gov/flu/pandemic/preparednesstools.htm. This site contains resources to help health officials prepare for an influenza pandemic.
- The US government's website for pandemic/avian flu: http://www.flu.gov/. "Flu Essentials" are available in multiple languages.
- CIDRAP: Avian Influenza page: http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm. Link to the Avian Influenza Portal at: http://influenza.bvsalud.org/php/index.php?lang=en. The Virtual Health Library's Portal is a developing project for the operation of product networks and information services related to avian influenza.
- US National Wildlife Health Center: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp Read about the latest news on avian influenza H5N1 in wild birds and poultry.


Indonesia (East Java, Malang)
At least 17 residents of Malang died of dengue fever in 2009, according to a local health official on 25 January 2010. A total of 1,073 people had been infected with dengue fever during 2009. The Health Ministry has reported that in the current rainy season, the dengue fever cases have increased in the provinces of Riau, Jakarta, West Java, West Kalimantan, Central Kalimantan, South Kalimantan, West Sulawesi, and North Maluku. Dengue cases have also been reported in Bangka Belitung, East Kalimantan, Gorontalo, and Palu.
(ProMED 2/1/2010)

Indonesia (East Java, Lumajang)
From the start of 2010 through 26 January 2010, 76 people have been stricken with dengue fever. Two of them, both children, have died from the illness.
(ProMED 2/1/2010)


Russia (Magadanskaya Oblast)
Over 200 children, most of them younger than three years, were hospitalized with acute intestinal infection. Health authorities are taking measures to contain the spread of the infection which has affected the entire Magadanskaya Oblast in the country's Far East, with children hit hardest. According to a 31 January 2010 Russian language report in TSN.ua, the source of the infection was rotavirus contamination of the skins of fruit -- apples, bananas, and citrus fruits -- imported from China.
(ProMED 2/3/2010)

Thailand (Pattani)
A surveillance rapid response team (SSRT) has been sent to investigate and control a cholera outbreak in Pattani. The ongoing outbreak has spread from riverbank fishing communities to other villages located further away from rivers and the coastal area. According to Dr Udomkirt Poolsawat, senior medical officer of the Pattani provincial health office, cholera bacteria have recently been found in village water system. Consumption of contaminated seafood is also thought to have contributed to the outbreak.
(ProMED 1/28/2010)

Thailand (Songkhla)
According to Dr Chalermpong Sukontapol, deputy director of Songkhla hospital, more than 100 students have been hospitalized in Songkhla hospital due to a typhoid outbreak. More than 40 of these students have tested positive for typhoid fever and others are waiting for test results.
(ProMED 1/27/2010)

Viet Nam (An Giang)
A total of 45 people have been hospitalized for acute diarrhea in the Mekong Delta province of An Giang. Seven of these patients have tested positive for Vibrio cholerae bacteria. The Ministry of Health said all the positive cases came from the Cambodian provinces of Takeo and Kandal to An Giang seeking treatment.

(ProMED 1/31/2010)


4. Articles
Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2
Celum C, Wald A, Lingappa JR, et al. N Engl J Med. 4 February 2010; 362(5):427-439.
Available at http://content.nejm.org/cgi/content/full/362/5/427.

Background. Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1.

Methods. We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, ?250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses.

Results. A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.

Conclusions. Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log10 copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2.

ClinicalTrials.gov number. NCT00194519 [ClinicalTrials.gov]


Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency
Gordon C, Johnson P, Permezel M, et al. Clin Infect Dis. 1 February 2010;doi: 10.1086/650462.
Available at http://www.journals.uchicago.edu/doi/abs/10.1086/650462.

Background. Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G2 (IgG2) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection.

Methods. Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women.

Results. Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P<.001), anemia (P<.001), and low levels of total IgG (P=.01), IgG1 (P=.022), and IgG2 (15 of 19 vs 5 of 20; P=.001; mean value ± standard deviation [SD], 1.8 ± 1.7 g/L vs 3.4 ± 1.4 g/L; P=.003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P=.02) and low mean IgG2 levels (P=.043 ) remained significant after multivariate analysis. Follow?up of 15 (79%) surviving IgG2?deficient patients at a mean (±SD) of 90 ± 23days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG2 deficient. Among 17 healthy pregnant control subjects, mildly low IgG1 and/or IgG2 levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG2 (P=.001).

Conclusions. Severe H1N1 infection is associated with IgG2 deficiency, which appears to persist in a majority of patients. Pregnancy?related reductions in IgG2 level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG2 deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.


Targeted Antiviral Prophylaxis With Oseltamivir in a Summer Camp Setting
Kimberlin D, Escude J, Gantner J, et al. Arch Pediatr Adolesc Med. 1 February 2010; doi:10.1001/archpediatr.2009.299.
Available at http://archpedi.ama-assn.org/cgi/content/short/2009.299.

Objective. To describe the effectiveness of containment of novel influenza A(H1N1) infection at a summer camp.

Design. Targeted use of oseltamivir phosphate by individuals in close contact with influenza-confirmed cases.

Setting. Boys' camp in Alabama in July 2009.

Participants. A total of 171 campers, 48 camp counselors, and 27 camp staff.

Interventions. Campers with confirmed influenza received oseltamivir and were immediately isolated and sent home. All boys and counselors in the infected child's adjoining cabins received prophylactic oseltamivir for 10 days, including 8 campers at higher risk for influenza infection (eg, those with asthma, seizure disorder, or diabetes). Alcohol-based hand sanitizer was provided at each of the daily activities, in the boys' cabins, and in the dining hall, and counselors were educated by the medical staff on the spread of influenza and its prevention through good hand hygiene. All cabins, bathrooms, and community sports equipment were sprayed or wiped down with disinfectant each day.

Main Outcome Measure. Virologic confirmation of influenza.

Results. Three of the 171 campers tested positive for influenza A during the course of the 2-week fourth session, for an attack rate of 1.8%. The probability of observing 3 or fewer infected campers if the attack rate was 12% is less than 1 in 10 000 000 (P < .0000001). An exact 95% confidence interval based on 3 events among 171 individuals estimates the attack rate to be between 0.3% and 5.0%. While 31% to 57% of campers, counselors, or staff experienced nausea with the treatment, this did not result in discontinuation of therapy. No campers tested positive for influenza A after returning home at the end of the camp session.

Conclusion. In conjunction with comprehensive hand sanitization and surface decontamination, a targeted approach to antiviral prophylaxis contained the spread of influenza in a summer camp setting.


Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1
Greatorex JS, Page RF, Curran MD, et al. PLoS ONE. 1 February 2010;5(2): e8987. doi:10.1371/journal.pone.0008987
Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008987.

Background. In the event of an influenza pandemic, the majority of people infected will be nursed at home. It is therefore important to determine simple methods for limiting the spread of the virus within the home. The purpose of this work was to test a representative range of common household cleaning agents for their effectiveness at killing or reducing the viability of influenza A virus.

Methodology/Principal Findings. Plaque assays provided a robust and reproducible method for determining virus viability after disinfection, while a National Standard influenza virus RT-PCR assay (VSOP 25, www.hpa-standardmethods.org.uk) was adapted to detect viral genome, and a British Standard (BS:EN 14476:2005) was modified to determine virus killing.

Conclusions/Significance. Active ingredients in a number of the cleaning agents, wipes, and tissues tested were able to rapidly render influenza virus nonviable, as determined by plaque assay. Commercially available wipes with a claimed antiviral or antibacterial effect killed or reduced virus infectivity, while nonmicrobiocidal wipes and those containing only low concentrations (<5%) of surfactants showed lower anti-influenza activity. Importantly, however, our findings indicate that it is possible to use common, low-technology agents such as 1% bleach, 10% malt vinegar, or 0.01% washing-up liquid to rapidly and completely inactivate influenza virus. Thus, in the context of the ongoing pandemic, and especially in low-resource settings, the public does not need to source specialized cleaning products, but can rapidly disinfect potentially contaminated surfaces with agents readily available in most homes.


Protection of Mice against Lethal Challenge with 2009 H1N1 Influenza A Virus by 1918-Like and Classical Swine H1N1 Based Vaccines
Manicassamy B, Medina RA, Hai R, et al. (2010). PLoS Pathog. 29 January 2010;6(1): e1000745. doi:10.1371/journal.ppat.1000745.
Available at http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000745.

Abstract. The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5,000 deaths worldwide. Early epidemiological findings indicated a low level of infection in the older population (>65 years) with the pandemic virus, and a greater susceptibility in people younger than 35 years of age, a phenomenon correlated with the presence of cross-reactive immunity in the older population. It is unclear what virus(es) might be responsible for this apparent cross-protection against the 2009 pandemic H1N1 virus. We describe a mouse lethal challenge model for the 2009 pandemic H1N1 strain, used together with a panel of inactivated H1N1 virus vaccines and hemagglutinin (HA) monoclonal antibodies to dissect the possible humoral antigenic determinants of pre-existing immunity against this virus in the human population. By hemagglutinination inhibition (HI) assays and vaccination/challenge studies, we demonstrate that the 2009 pandemic H1N1 virus is antigenically similar to human H1N1 viruses that circulated from 1918-1943 and to classical swine H1N1 viruses. Antibodies elicited against 1918-like or classical swine H1N1 vaccines completely protect C57B/6 mice from lethal challenge with the influenza A/Netherlands/602/2009 virus isolate. In contrast, contemporary H1N1 vaccines afforded only partial protection. Passive immunization with cross-reactive monoclonal antibodies (mAbs) raised against either 1918 or A/California/04/2009 HA proteins offered full protection from death. Analysis of mAb antibody escape mutants, generated by selection of 2009 H1N1 virus with these mAbs, indicate that antigenic site Sa is one of the conserved cross-protective epitopes. Our findings in mice agree with serological data showing high prevalence of 2009 H1N1 cross-reactive antibodies only in the older population, indicating that prior infection with 1918-like viruses or vaccination against the 1976 swine H1N1 virus in the USA are likely to provide protection against the 2009 pandemic H1N1 virus. This data provides a mechanistic basis for the protection seen in the older population, and emphasizes a rationale for including vaccination of the younger, naïve population. Our results also support the notion that pigs can act as an animal reservoir where influenza virus HAs become antigenically frozen for long periods of time, facilitating the generation of human pandemic viruses.


Effect of Rotavirus Vaccination on Death from Childhood Diarrhea in Mexico
Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, et al. N Engl J Med. 28 January 2010;362(4):299-305.
Available at http://content.nejm.org/cgi/content/full/362/4/299.

Background. A phased introduction of a monovalent rotavirus vaccine occurred in Mexico from February 2006 through May 2007. We assessed the effect of vaccination on deaths from diarrhea in Mexican children in 2008 and 2009.

Methods. We obtained data on deaths from diarrhea, regardless of cause, from January 2003 through May 2009 in Mexican children under 5 years of age. We compared diarrhea-related mortality in 2008 and during the 2008 and 2009 rotavirus seasons with the mortality at baseline (2003-2006), before the introduction of the rotavirus vaccine. Vaccine coverage was estimated from administrative data.

Results. By December 2007, an estimated 74% of children who were 11 months of age or younger had received one dose of rotavirus vaccine. In 2008, there were 1118 diarrhea-related deaths among children younger than 5 years of age, a reduction of 675 from the annual median of 1793 deaths during the 2003-2006 period. Diarrhea-related mortality fell from an annual median of 18.1 deaths per 100,000 children at baseline to 11.8 per 100,000 children in 2008 (rate reduction, 35%; 95% confidence interval [CI], 29 to 39; P<0.001). Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P<0.001). As compared with baseline, diarrhea-related mortality was 29% lower for children between the ages of 12 and 23 months, few of whom were age-eligible for vaccination. Mortality among unvaccinated children between the ages of 24 and 59 months was not significantly reduced. The reduction in the number of diarrhea-related deaths persisted through two full rotavirus seasons (2008 and 2009).

Conclusions. After the introduction of a rotavirus vaccine, a significant decline in diarrhea-related deaths among Mexican children was observed, suggesting a potential benefit from rotavirus vaccination.


Effect of Human Rotavirus Vaccine on Severe Diarrhea in African Infants
Madhi S, Cunliffe N, Steele D, et al. N Engl J Med. 28 January 2010;362(4):289-298.
Available at http://content.nejm.org/cgi/content/full/362/4/289.

Background. Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.

Methods. We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine - the pooled vaccine group - or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.

Results. A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.

Conclusions. Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life.

ClinicalTrials.gov number. NCT00241644 [ClinicalTrials.gov]


A broad-spectrum antiviral targeting entry of enveloped viruses
Wolf M, Freiberg A, Zhangc T, et al. PNAS. 28 January 2010; doi:10.1073/pnas.0909587107.

Available at http://www.pnas.org/content/early/2010/01/27/0909587107.

Abstract. We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus-cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure-activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus-cell but not cell-cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus-cell fusion.


5. Notifications
Emerging Infectious Diseases in Response to Climate Change
New York City, USA, 2 March 2010
This symposium examines the complex relationship between the climate, environment, and infectious diseases.
Additional information and registration available at http://www.nyas.org/Events/Detail.aspx?cid=aa4086a1-6917-4cd3-b14f-7317214ed96c.


14th International Congress on Infectious Diseases (ICID)
Miami, Florida, USA, 9-12 Mar 2010
Additional information and registration available at http://www.isid.org/14th_icid/.


International Swine Flu Conference (ISFC)
London, United Kingdom, 10-12 Mar 2010
Reflecting their strong agreement about the importance of the International Swine Flu Conference (ISFC), renowned medical experts have agreed to share end-to-end H1N1 prevention, preparedness, and response and recovery strategies at the event.
Additional information and registration available at http://www.new-fields.com/isfc_uk/.


ISHEID Symposium on HIV and Emerging Infectious Diseases
Marseille, France, 24-26 Mar 2010
Tackling each topic from basic science to clinical applications, this meeting will deal with issues of HIV/AIDS, Viral Hepatitis, Emerging Infectious Diseases, and welcome many key opinion leaders.
Additional information and registration available at http://www.isheid.com/.

The ISHEID 2010 congress organizing office...
E-mail: isheid@clq-group.com; Ph. : +33 1 44 64 15 15 - Fax : +33 1 44 64 15 16


CDC 7th International Conference on Emerging Infectious Diseases
Atlanta, Georgia, USA 11-14 Jul 2010
The 2010 International Conference on Emerging Infectious Diseases (ICEID) is the principal meeting for emerging infectious diseases organized by CDC. This conference includes plenary and panel sessions, as well as oral and poster presentations, and covers a broad spectrum of infectious diseases of public health relevance. ICEID 2010 will also focus on the impact of various intervention and preventive strategies that have been implemented to address emerging infectious disease threats.
Additional information is available at http://www.iceid.org/.


Options for the Control of Influenza VII
Hong Kong, 3-7 Sep 2010
Options for the Control of Influenza VII is the largest forum devoted to all aspects of the prevention, control, and treatment of influenza. As it has for over 20 years, Options VII will highlight the most recent advances in the science of influenza. The scientific program committee invites authors to submit original research in all areas related to influenza for abstract presentation. Accepted abstracts will be assigned for oral or poster presentation.
Additional information is available at http://www.controlinfluenza.com.


Updated influenza guidance and information from the US CDC
Shortened Expiration Period For Sanofi Pasteur 2009 H1N1 Vaccine In Pre-filled Syringes Questions & Answers
Released 3 February 2010
Available at http://www.cdc.gov/h1n1flu/vaccination/qa_expiration.htm.

Non-Safety-Related Voluntary Recall Of Sanofi Pasteur 2009 H1N1 Flu Vaccine In Pre-filled Syringes (February 2010)
Released 3 February 2010
Available at http://www.cdc.gov/H1N1flu/HAN/012910.htm.