Singapore - Immunology: Bracing for a viral counterattack

Antibodies (green) isolated from patients with a secondary dengue infection can effectively label cultured infected cells, demonstrating their strong affinity for the viral particle.

Insights obtained by profiling the immune response to repeat viral infections could assist vaccine design efforts

Patients who successfully beat infection with dengue virus remain vulnerable to reinfection by other dengue variants, and these secondary infections tend to be more severe. The antibodies arising from the immune system’s first encounter with the virus can play a complicated role in how these secondary infections unfold.

“Antibodies made during dengue infection can be either protective or disease enhancing,” explains Katja Fink of the A*STAR Singapore Immunology Network. Fink and her team wanted to determine whether the antibodies produced very early after infection promote defense or vulnerability. To do this, her team isolated plasmablasts — immature precursors of antibody-secreting plasma cells — from two patients newly diagnosed with secondary infection1. After conducting assays to determine the extent to which these cells were targeting the various subtypes of dengue virus, the researchers learned that most patient plasmablasts were specifically generating antiviral antibodies (see image).

The secret of the immune system’s success is its diversity, but when the body finds a threat that resembles something it has previously encountered, it specifically stimulates proliferation of cells that secrete antibodies appropriate to that threat. Fink and co-workers characterized the extent to which antibodies produced by individual plasmablasts from such patients neutralized different dengue variants in a mouse model. They found that the antibodies were generally more effective at neutralizing strains from initial infections rather than those involved in secondary infections. This is in keeping with an immunological model called ‘antigenic original sin’, wherein an initial encounter with a pathogen determines antibody output generated in subsequent encounters.

Importantly, the researchers found that patients with acute secondary infections were also able to successfully mount a new wave of plasmablast-mediated immune defense against the secondary strain, manifested by the generation of a collection of antibodies that effectively recognized and neutralized all four viral subtypes. More than a few very potent antibodies dominate the protective effect, according to Fink. “The immune system responds to dengue with a very diverse repertoire,” she notes. Based on the timing with which the antibodies appeared, the researchers were also able to determine that they help rather than hinder the body’s antiviral effort.

The cross-protective antibodies generated in this acute plasmablast response preferentially recognized a particular viral coat protein as a target, or ‘epitope’. If validated in larger scale studies, these results could lead to better antiviral protection. “Knowledge about antibody epitopes on the virus that are naturally targeted by the human immune response could be translated into the design of vaccines,” says Fink.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network

References

1. Xu, M., Hadinoto, V., Appanna, R., Joensson, K., Toh, Y. X. et al. Plasmablasts generated during repeated dengue infection are virus glycoprotein–specific and bind to multiple virus serotypes. The Journal of Immunology 189, 5877–5885 (2012). | article

Singapore - Biomedical engineering: No batteries required

A handheld reader (top right) wirelessly powers and interrogates a tiny blood-pressure sensor embedded inside a prosthetic graft, inserted in this case as a conduit for haemodialysis in a patient with kidney failure.

Microscale medical sensors inserted under the skin can be powered wirelessly by an external handheld receiver

Implantable electronic devices potentially offer a rapid and accurate way for doctors to monitor patients with particular medical conditions. Yet powering such devices remains a fundamental challenge: batteries are bulky and eventually need recharging or replacing. Jia Hao Cheong at the A*STAR Institute for Microelectronics, Singapore, and his co-workers are developing an alternative approach that eliminates the need for a battery1. Their miniature devices are based on wireless power-transfer technology.

The research team has developed a microscale electronic sensor to monitor blood flow through artificial blood vessels. Surgeons use these prosthetic grafts to bypass diseased or clogged blood vessels in patients experiencing restricted blood supply, for example. Over time, however, the graft can also become blocked. To avoid complete failure, blood flow through the graft must be monitored regularly, but existing techniques are slow and costly.

These limitations prompted the researchers to develop a bench-top prototype of a device that could be incorporated inside a graft to monitor blood flow. The implant is powered by a handheld external reader, which uses inductive coupling to wirelessly transfer energy, a technology similar to that found in the latest wireless-charging mobile phones. The team developed an application-specific, integrated circuit for the implant designed for low power use (see image).

The incoming energy powers circuits in the device that control sensors based on silicon nanowires. This material is piezoresistive: as blood flows over the sensor the associated mechanical stresses induce a measurable increase in electrical resistance, proportional to the flow pressure.

Key to the success of the device is its ability to work with a very limited power supply. Most of the incoming energy is absorbed by skin and tissue before it can reach the implant, which may be inserted up to 50 millimeters deep.

“Our flow sensor system achieves an ultra-low power consumption of 12.6 microwatts,” Cheong says. For example, the sensor transmits its data to the handheld reader passively, by backscattering some of the incoming energy. “We have tested our system with 50-millimeter-thick tissue between the external coil and implantable coil, and it successfully extracted the pressure data from the implantable device,” he adds.

Cheong and his co-workers’ tests showed that the prototype sensor was also highly pressure sensitive, providing pressure readings with a resolution of 0.17 pounds per square inch (1,172 pascals). “The next step of the project is to integrate the system and embed it inside a graft for [an experimental] animal,” Cheong says.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Microelectronics

References

1. Cheong, J. H., Ng, S. S. Y., Liu, X., Xue, R.-F., Lim, H. J. et al. An inductively powered implantable blood flow sensor microsystem for vascular grafts. IEEE Transactions on Biomedical Engineering 59, 2466–2475 (2012). |article

Vietnam - Rise in infertility in Vietnam

VietNamNet Bridge – A latest survey showed that the rate of childless couples in the country has gone up by 8 percent or a total of one million Vietnamese couples.

This upward trend is worrisome as even medical experts warn of more and more couples in the country facing infertility. 

The survey also pointed out that in some regions of the country the rate of childless couples was higher, such as in Hanoi with 13 percent and the central province of Khanh Hoa with 14 percent.

Infertility puts a lot of pressure on Vietnamese women and affects the quality of their marriage. X.Hoa, 35, a director of a private company in the northern province of Hai Phong, said although he married more than three years back, he is still issueless because both he and his wife suffer from a problem in the reproductive system.

The National Maternity Hospital in Hanoi used to receive only five such couples a week, which has now increased to 10 infertile couples a week for treatment.

Noticeably, the Hanoi-based Military Hospital's Embryo Technology Center treats around 10,000 childless couples annually. Doctor Quan Hoang Lam, the center's director, said the demand for infertility treatment is increasing and most infertile couples are between the ages of 25-32.

According to scientists, stress, improper diet, and consuming contaminated food are the main causes of infertility. Even living in a contaminated or unhealthy environment can cause infertility.

Infertility in men can be attributed to low sperm count, up to 90 percent, and the condition can be brought on by work pressure, alcohol and smoking.

More worrisome, infertility in women can be caused by unsafe sex resulting in infection in sexual organs, leading to miscarriages and abortions. Statistics show the rate of Vietnamese women undergoing abortion is around 32 percent or one million cases a year. This is the highest rate of abortion in women in the world.

Health Deputy Minister Nguyen Viet Tien said infertility is a grave challenge for the country.

Vietnam now has a total of 14 centers for infertility treatment. Skilled physicians in these centers are as good as their counterparts in the world with a higher rate of success of 35-40 percent or even 50 percent in Tu Du and the National Maternity Hospital, along with lower cost of VND60 million (US$2,867) while it is more than $15,000 in the US.

Source: SGGP

Vietnam - The border land of HIV

VietNamNet Bridge – The mountainous area of the central province of Thanh Hoa used to be called “the capital of opium.” Since then the storm of HIV has ravaged this region.

"HIV" is everywhere

According to the statistics of the Muong Lat district medical center, Thanh Hoa province, since 2001 the district has had 401 people living with HIV/AIDS, of which 181 people have developed to AIDS and 59 died. Currently, ARV treatment is provided for 155 people.

Just in 2012, the district has discovered 594 drug addicts, mainly in the communes of Pu Nhi, Tam Chung and Muong Chanh.

About 7 kilometers from Muong Lat town, Pu Nhi Commune was previously considered the valley for transit of drugs from Laos to Vietnam. Therefore, a lot of young people in the commune are drug addicted.

Mr. Luong Van Xich, Chairman of Pu Nhi Commune People's Committee, said in recent years, thanks to the implementation of the program calling for local people to eliminate poppy cultivation and detoxification, so far the commune has only 26 drug addicts.

However, this is only the statistic on paper, Xich said. The actual number of addicts in the area is difficult to define accurately. Therefore, the commune is still a “black spot” of Muong Lat district for drug addiction and HIV.

Na Tao village has more than 150 households, but this place is considered a hot spot of drug addiction and HIV.

The village’s chief told VietNamNet that according to official statistics, Na Tao has 157 households with 676 people, including 11 drug addicts, 40 HIV-infected people, including 26 who are on ART treatment.

But Tham admitted that the actual number is higher, because many people refuse to take HIV test or admit themselves as drug addicts. In the last 5 years, Na Tao had 8 people died of AIDS

Ms. Ngan Thi Long, 26, is an HIV carrier in Na Tao village. She married in 2009. Her family was very happy and they were waiting for the first baby when her husband was addicted to drugs.

Three years later, her husband's health went down seriously. He was very skinny. She urged her husband to go to hospital for examinations. She was numb because the HIV test was positive.

Leaving Long’s house, we visited Mr. Ha Van Luong’s home. Luong told us why he caught HIV: "When I was young I was a playboy so I caught HIV. Since I got the disease, my physical and mental health has reduced. Sometimes I thought of suicide but people have encouraged and shared with me so I have been revived."

The hurts

Living in Pu Nhi, we continued our journey to Tam Chung commune, which is also considered a hot spot of HIV/AIDS.

According to the latest report of the Tam Chung authorities, in the past 7 years, about 80 people died of HIV/AIDS, including over 40 people in Poong village. The consequence of these dead is orphans.

We went to Poong village. The first impression we caught at the first look is that this is a very quiet village. Several soiled kids were playing on the soil ground under a house on stilts. Seeing strangers, they ran away.

Mrs. Ha Thi Pun, who has two sons with HIV, sat on the threshold of the house seeing the kids with sad eyes. "They are orphans. I am their grandmother but I cannot properly take care of them. I do not know how they will be when I die," she said.

Brushing tears on the face, she told us that her son-in-law used to be a good man. In 2003, during the leisure time after harvest he joined a group of young men in the village to drink and then use drugs. He became a drug addict and then an HIV carrier.

He transmitted the disease to his wife. Soon after the couple died, leaving her with two grandchildren. After the death of the couple, their 5-year-old son named Thuong was tested for HIV but the result has not been released yet, said Mrs. Pun.

Perhaps the most miserable case in Poong village is the family of Ha Thi C, 10. Her father died of HIV two years ago. Her mother, Ha Thi PH also contracted HIV from her husband. The woman left home and her four children aging between 2 to 10. The four children are living with Mr. Lo Van May, a distant relative who is very poor.

We left Poong village at the nightfall. The mountainous cold made this place more and more deserted. Children's sad eyes, the sigh of old are people covered by the darkness.

Le Anh - Duy Quang

Vietnam - One death from unidentified disease in Quang Ngai Province

VietNamNet Bridge – A young teenage boy from Reu Village in Son Ha District in the central province of Quang Ngai on March 11 succumbed to the bizarre disease that is plaguing the area. 

>> Bizarre skin disease outbreaks again in Quang Ngai

Dinh Van Thap, 17, suffered from thickening of the skin (keratosis) on palms and soles, stiffness in limbs and ulcers on hands and feet, before he finally succumbed to the disease.

Earlier he had been transferred to the Intensive Care Unit of the General Hospital in Quang Ngai Province, for treatment of liver failure but did not pull through.

By February, two more patients from Son Ha District including Dinh Van Hoan, 63, and his wife Dinh Thi Lo, 58, were hospitalized for thickening of the skin (keratosis) on palms and soles, stiffness in limbs and ulcers on hands and feet that looked like burns.

They have since left the hospital for their homes and have left their fate to God.

Son Ha District is the second district to report a death from the yet unidentified disease, after Ba To District. In 2012, Ba To District reported 23 deaths from the bizarre disease with 240 infected cases.

Since March, the district has reported 10 more cases, including two suffering from a relapse within a year of infection.

Health agencies have yet to find a cure or cause of the disease.

Source: SGGP

Vietnam - Bizarre skin disease outbreaks again in Quang Ngai

VietNamNet Bridge - People in the area of the strange skin disease are anxious with their fate while the Ministry of Health is struggling to "decode" the disease. The disease that has killed 23 people in Quang Ngai is raging violently.

>> Ministry issues new treatment plan for bizarre skin disease 

The "strange" disease, which is called by the Ministry of Health as dermatitis syndrome on hands and feet, in the central province of Quang Ngai has recently returned with new cases, while the specific cause of the disease is still vague.

Since late February 2013, the bizarre skin disease has come back in the mountainous districts of Quang Ngai.

On March 6, the total number of patients was 12. Of the 12 patients, there are 2 cases of recurrence.

The latest case is Mrs. Pham Thi Soi, 60 years old, in Reu village, Ba Dien commune. This is also a case of recurrence.

Last year, Soi had the disease and was well again after treatment. Two members of her family were dead by this disease, including her daughter, Pham Thi An, 26, who died in July 2012 and An’s son Pham Van Sam, 4.

The 2nd case of recurrence is Mrs. Pham Thi Ngap, 75, also a resident of Ba Dien commune.

Notably, the "strange" disease not only broke out in Ba To district, but also appears in the mountainous district of Son Ha.

The two patients here are Mr. Dinh Van Hoan, 63 years old and his wife Dinh Thi Lo, 57, in Ka Park Village, Son Ba commune.

The two patients were treated at the Dermatology Ward of the Quang Ngai Province Hospital on February 19. The couple has escaped the hospital to go home.

Mr. Le Han Phong, Chairman of Ba To district, says that the "strange" disease is developing complicatedly. He wishes health experts will soon clarify the cause to definitively treat people.

Vague reasons

While the Ministry of Health announced to "find the causes and successfully control the bizarre skin disease which appeared in Vietnam for the first time in Ba To district, Quang Ngai” and called this as one of the 10 achievements of the health sector in 2012, the disease has flared up again.

Chief of the Department of Preventive Medicine--Nguyen Van Binh says: "The test of rice used by farmers in the area of the strange disease (Ba Dien Commune, Ba To district) in a Hong Kong laboratory finds out some kind of poisonous fungus but it does not indicate the exact type of fungus which is the specific agent of the disease."

Many experts have come to survey and collect samples for testing but in the last two years they have yet to determine the cause.

The health sector has made a lot of speculation about the cause, such as dermatitis caused by infection, fever caused by Rickettsia, hepatitis E, malnutrition...

2012 was the peak of the "strange" disease. The Minister of Health--Nguyen Thi Kim Tien visited Quang Ngai to inspect the disease. After that health experts said that "eating moldy rice is one of the suspicious factors." However, the Ministry of Health has not confirmed that eating moldy rice as the cause of the disease.

Mr. Pham Van But, Chairman of Ba Dien Commune, says that he and the local people are very worried of this disease. He adds that the district authorities firstly provided the local people 15 kg of rice per person per month. In August 2012, it reduced to 4 kg and nothing. Since then the local people have eaten moldy rice again.

Le Ha

Vietnam - HIV/AIDS fight faces cash crunch

VietNamNet Bridge – Viet Nam faces two major hurdles in combating HIV/AIDS: namely unsustainable achievements and the reduction of international financial support, says Minister of Health Nguyen Thi Kim Tien.

At a nation-wide conference on HIV/AIDS, drug and prostitution control yesterday, March 5, Tien said that last year the country had more than 14,100 people living with HIV, a fall of 26 per cent compared with 2011.

More than 2,100 people died for AIDS last year which is half of the figure in 2011.

“However, the results are not sustainable and HIV/AIDS infection still faces a high risk of spreading further if we do not have effective control measures,” said Tien.

The number of people infected with HIV via sexual intercourse has increased compared with the those infected via blood contact, and it is forecast that unprotected sexual contact will be the main means of HIV transmission in coming years.

“But controlling transmission via sexual intercourse is much more difficult than with transmission via blood contact, as approaching and supervising prostitutes and men who have sex with men faces a lot of obstacles,” she said.

Nearly 46 per cent of people living with HIV were infected with the virus via sexual intercourse last year whereas only 42 per cent were infected via heroin injections. The rate in 2011 was 41.8 and 46.4 per cent respectively.

Besides, provinces with new outbreaks of infection, including Binh Duong, Vinh Phuc and Ha Nam, so far have not invested much in carrying out control measures.

Moreover, in the provinces bordering the metropolises Ha Noi and HCM City faces a greater risk of transmission, said Tien.

In the meantime, foreign financial support, which makes up 70 per cent of the total funds for epidemic control, is expected to decrease sharply by 2015 as Viet Nam becomes a middle-income nation.

“It is a big difficulty for the country as the number of people living with HIV is still high with 4,000-5,000 new cases per year,” said Tien.

It is forecast that the country will have about 300,000 people living with HIV by 2015, and 140,000 of them will need antiretroviral drugs for HIV treatment during their whole life.

“Thus if funds for control is not enough, the country will not reach expected targets and thus faces a high risk of transmission to the community,” said Tien.

The President’s Emergency Plan for AIDS Relief (PEPFAR), the organisation that offers the biggest fund for HIV/AIDS control, plans to cut its financial support by US$10 million a year.

PEPFAR supported the control with more than $82 million in 2011, but by 2015 the fund will be only $40 million.

To mobilise funds for HIV control, Deputy Minister of Finance Nguyen Thi Minh proposed to diversify organisations and individuals joining the programme.

Under the proposed project, enterprises and organisations supplying HIV/AIDS prevention and control services will enjoy preferential tax policies.

The Law on Health Insurance will be amended so people living with HIV and drug addicts will benefit from the fund.

The fund can pay 20 per cent of the total treatment expenses, thus people living with HIV should be encouraged to buy the insurance, said Minh.

Speaking at the conference, Deputy Prime Minister Nguyen Xuan Phuc asked the HIV/AIDS control steering committee at different levels to research and complete the law system on HIV/AIDS prevention and control, and strengthen information output on the subject to the whole people, especially the youth, about the disease and how to avoid it.

International co-operation should be improved and different sponsor sources should be mobilised and used effectively, he said.

“The country will try to diversify its funding sources by seeking support from public-private partnerships and health insurance, but it will still require financial assistance from international donors.”

Source: VNS