China's best case scenario for an Ebola outbreak: 3000 deaths

by Michael Woodhead

With more than 600,000 annual passenger arrivals from Africa and a poor to non-existent public health infrastructure in most parts of the country, China faces  a very real risk of an Ebola outbreak. That the verdict of infectious disease specialists who have modelled what will happen if a person with Ebola lands in China and is not detected immediately.

Dr Chen Tianmu and colleagues from the Changsha Center for Disease Control and Prevention have used data from previous Ebola outbreaks overseas and also from outbreaks of dengue and HIV viruses in China to model the likely spread of the infection before it can be brought under control. They modelled several different scenarios based on different levels of infectivity of the virus and different levels of detection and containment.

They based their calculation on the fact that there were 524,900 African visitors and 112,966 Chinese returning from Africa each year in China. Based on current distribution of Ebola Virus Disease and the rates of carriage in Africa, they estimated that 0.04%–0.16% of these arriving passengers in China (255–1021 people) may carry Ebola. Even if an optimistic assumption is made that only 1% of them slip through the entry-exit inspection and only 1% of these are not picked up by further reporting and monitoring follow ups, this would still mean 3-10 Ebola virus carriers could be at large in China.

The researchers noted that China lacks a primary care system and most sick patients go direct to hospitals that are overcrowded and where Ebola patients might spread the virus to others. China also has limited public health reporting and surveillance systems for much of the country, and it would therefor be possible that cases of Ebola virus could be misdiagnosed and slip though the net until the patient became symptomatic and infectious.

The researchers then calculated that the likely impact of such 'index cases' spreading the Ebola infection to others would be outbreaks of Ebola in China affecting between 6000-10,000 people. With a likely fatality rate of around 50% this would mean a severe mortality burden for China, they wrote.

Writing in Travel Medicine and Infectious Diseases, they said the lack of Ebola testing facilities in China and poor infection control practices would further encourage the spread of the infection, they predicted. Other factors, such as the lack of quality control on blood transfusions (as seen with outbreaks of HIV and hepatitis) would also increase the risk of spreading Ebola in China, they warned.

"Even if a good surveillance and monitoring system is implemented at immigration, an effective and efficient local medical response system involving primary health care providers and awareness of the general public is necessary to minimise the risk of an Ebola Virus outbreak due to other unknown sources," they suggested.

Resisting the Japanese invader: the China success story against Japanese encephalitis

by Michael Woodhead
 As China cranks up its media hate campaign against its former enemy Japan, the country can actually celebrate victory in its war against another 'Japanese' invader from the 1940s: Japanese encephalitis. 

This mosquito borne viral disease used to cause about 200,000 cases of severe neurological illness in China every year at its peak in the 1960s and 70s - with about 30% patients dying and many of the survivors  left with lasting neurological disability as a result of the infection.

The name is misleading - the disease did not originate in Japan, but was first identified there in the 19th century. The infection was first recorded in China in the 1940s and became widespread in the 1960s - partly because of the breakdown in public health preventive activities during the chaos of Mao Zedong's Cultural Revolution.

A vaccine against the virus was developed in Japan in 1965, and China started manufacturing its own vaccine a few years later.  Writing in the journal PLOS Neglected Tropical Diseases, Dr Gao Xiaoyan and colleagues at the Chinese Centre for Disease Control and Prevention, Beijing, describe how Japanese encephalitis was brought under control in China.

The initial Chinese vaccine was only available in limited quantities and required many doses. It was expensive and was only available to privileged cadres and Party members, not to the peasants who were most at risk of the disease. With more than half the cases of Japanese encephalitis in the world, China continued to work on improving the vaccine and eventually developed one in 1988 that was more convenient and could be mass produced at relatively low cost, to make it affordable for public health use.

This vaccine was gradually made available at a cost of 1 yuan to rural residents, and was fully subsidised as a free vaccine after the year 2005. Since it was included in the "Expanded Program of Immunisation" this cheap and effective vaccine had reduced the incidence of Japanese encephalitis in China from 21/100,000 people to just a fraction of 1 per 100,000 - a remarkable achievement.

But the vaccine is not the only reason for the drastic reduction in Japanese encephalitis in China. Other public health measures were implemented by local health authorities to reduce mosquito breeding and transmission:  pig farms were moved away from villages,  sewage disposal was improved to reduce mosquito breeding, and mosquito breeding grounds in areas of static water were eliminated.

The threat from Japanese encephalitis has now been markedly reduced in the more prosperous eastern provinces of China but it remains a problem in the poorer parts of southwest China. Nevertheless, Chinese researchers say other developing countries can copy the Chinese model for eliminating Japanese encephalitis: low cost programs using inexpensive vaccine and anti-mosquito measures.

China's answer to Ebola: a lethal haemorrhagic fever that kills 20,000 people a year

by Michael Woodhead

Like many other countries, China has gone into a hysterical spin about the threat posed by Ebola virus disease.

Authorities have dusted off the useless thermal scanners last used in the avian flu outbreaks, and have started screening passengers arriving at from Africa at Chinese airports. And despite the World Health Organization saying that China does not need to be overly concerned about the disease, authorities have been issuing stern warnings to health workers about being vigilant for Ebola and also looking with suspicion on the African expats living in cities such as Guangzhou. The irony is that China has seen its own counterpart of Ebola virus disease, a killer disease that has been increasing dramatically in the last two years.

But first some background: Ebola is a haemorrhagic fever, caused by the Ebola virus, which belongs to the  Filoviridae family of RNA viruses. The virus comes from apes and bats and is only transmitted between humans by body fluids such as blood and saliva - in Africa it has been spread by hunters cutting up meat from infected animals, and spread to healthcare workers and close relatives to touch the dead bodies of Ebola victims at traditional African funerals. In the latest outbreak there have been 1323 confirmed and suspected cases of Ebola reported, and 729 deaths. That's a mortality rate of 55% according to my calculator.

What to make then of China's recent little remarked but lethal cases of haemorrhagic fever? In April, Dr Du Hong and colleagues from the Center for Infectious Diseases, Tangdu Hospital, Xian, described the horrific symptoms of some of the 356 patients who had been treated at their hospital for  "hemorrhagic fever with renal syndrome" (HFRS),  a disease caused by Hantavirus that is spread by rats (or more specifically in their droppings, which may become aerosolised and spread to anyone working near where rats have been active).

The symptoms are similar to Ebola: fever, circulatory collapse with hypotension, hemorrhage, but also with acute kidney failure (hence the name renal syndrome). The difference between Ebola and HFRS is that the Hantavirus disease has a death rate of 'only' 40%. For China, which has had about 50,000 cases of HFRS annually, that means about there have been, at a conservative estimate, 20,000 deaths from Hanta virus every year. Makes the 730 Ebola deaths in Africa look fairly insignificant doesn't it? And as with Ebola, there is no treatment or vaccine for Hantavirus, only supportive care.

And that's not all. China has other types of haemorrhagic fever. This month The Lancet carries a report of the emergence of one, known as "severe haemorrhagic fever with thrombocytopenia". This is a viral disease spread by ticks, caused by the SFTS phlebovirus in the Bunyaviridae family. According to Dr Liu Quan and colleagues from the State Key Laboratory of Veterinary Etiological Biology, Lanzhou, SFTS was first reported in 2010 and has since been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7%. That's about 175 deaths. As the study authors say with some understatement: "The disease has become a substantial risk to public health".

China is the epicentre for Hantavirus haemorrhagic fever in the world, but it is not the only country affected. The disease is also seen in Europe and the US - a Denver man died of the infection just this week. But with tens of thousands of Chinese people dying every year from this terrible haemorrhagic disease, perhaps China ought to worry more about curbing Hantavirus - and the rats that carry it - rather than panicking over the threat from an African outbreak of Ebola.

Antibody vaccine for H7N9 is more effective than Tamiflu, say Shanghai researchers

translated by Michael Woodhead
Shanghai researchers say traditional inactivated vaccines cannot be developed against H7N9 but they have developed a gene vaccine which is more efficacious than Tamiflu against the virus.
According to an article in the Workers Daily, an antibody therapeutic vaccine that is effective against the current strain of H7N9 has been developed by Shanghai researchers and is now about to start  clinical trials. Researchers at the Shanghai Public Health Clinical Centre Infectious Disease Research Institute said they had developed antibodies that were effective against H7N9 in vitro and they are now starting tests in humans.
Professor Xu Jianqing of the Infectious Disease Research Institute said that work on the vaccine began in April last year after the first major H7N9 influenza virus outbreaks.  He said the team had made a breakthrough with a gene vaccine in December when they injected the vaccine into 30 mice infected with H7N9. After 30 days none of the mice had died and none had signs of H7N9 infection, which represented the first real proof of efficacy.
Professor Xu said many other research groups in China were doing H7N9 vaccine research but using  traditional inactivated vaccines. However, he said experiments had shown time and again that compared to other influenza viruses, the H7 influenza virus was not amenable to being incorporated into an inactivated vaccine, as it was deformed by the chemicals used, rendering the immune response inadequate. Similar efforts by Dutch researchers to develop a vaccine against the H7N3 virus strain in 2003 were also a failure for a the same reason. This showed that inactivated vaccine technology was not going to catch on for the H7 virus, he said.
The Shanghai researchers had therefore taken the bold step of taking the most important genetic material from the H7N9 virus and implanting it into a mature vaccine carrier. This was the equivalent of putting it into a safe and inserting this into a cell, said Professor Xu. And because the virus structure was not destroyed by putting it into an egg albumen, it elicited a good immune response, he added.
Professor Xu said the new vaccine would be suitable for people at high risk of H7N9 such as those working in live poultry markets and household members.
Within Shanghai's R&D community the new H7N9 vaccine was seen as a breakthrough after an audacious attack. Xu Jianqing said the immune system of H7N9-infected people produced antibodies, and the sooner the body produced antibodies the better the prognosis. He added that Tamiflu was effective if given within the first few days of viral infection, as this was the 'empty' window before the body had started producing its own antibody.  But after more prolonged infection Tamiflu quickly became ineffective,  and drug resistance appeared quickly. Researchers were inspired to try using exogenous antibodies during this initial 'empty window' period when there was no natural H7N9 antibody being produced. The observed effects of the gene vaccine were clearly better than Tamiflu during this period, said Xu Jianqing. In fact, in 2003 during the SARS outbreak, there had also been small scale treatment models of experimental antibody treatment that were successful in curing a patient.
It is reported that at present the H7N9 antibody treatment has already successfully completed two phases of in-vitro testing and it is estimated that Phase 3 testing will be complete within one month. From among the 100+ types of antibody currently in testing the best will be selected for clinical use.

Enterovirus vaccine safe and effective against hand foot and mouth disease, Chinese trial shows

A trial conducted in Jiangsu has provided major step forward in the development of  a vaccine against enterovirus 71 - a member of the Picornaviridae family of viruses associated serious and fatal outbreaks of hand, foot, and mouth disease across Asia.
Published in The Lancet,  the results of a phase 2 trial of an enterovirus vaccine in more than 1100 infants and children in Jiangsu found that the vaccine had good immunogenicity and a low incidence of adverse effects.
The inactivated EV71 vaccine developed by Beijing Vigoo Biological used the EV71 strain was given in two doses a month apart, injected intramuscularly into the deltoid region in children aged 12—36 months and into the anterolateral side of thigh in infants aged 6—11 months.
The trial compared four different doses of vaccine, and all procuced  good antibody responses, with the best seen with an adjuvant 320 U formulation.
Antibody titres had significantly declined by eight months, suggesting a need for a booster shot. Generally, the vaccine had a good safety profile in all participants. Most reactions were mild or moderate and severe adverse reactions were uncommon.
Researchers say an enterovirus  vaccine is a public health priority because mortality rates with enterovirus 71 are as high as 82—94% in severe cases and the incidence of hand, foot, and mouth disease seems to be increasing across the Asia region
As a result of our findings, the adjuvant 320 U formulation has been selected for larger multicentre, randomised, double-blind, placebo-controlled trial in about 10 000 participants aged six—35 months.
Source: Lancet

Clinical news in brief

Malnutrition and anaemia are rife in Shaanxi infants

One in three infants in impoverished rural Shaanxi have anaemic and malnutrition, a study has found
Researchers from the Maternal and Child Health Centre of the First Affiliated Hospital of Medical
College in Xi’an sampled 336 infants in 28 rural villages from two counties of Shaanxi province. They found that 35% of infants in suffered from anemia, 32% had malnutrition, stunting or
wasting. Anemia was linked with malnutrition, while low birth weight, having more siblings, less maternal education, low family income, crowded living conditions, and inappropriate complementary food introduction significantly increased the risk for infant anemia. Serum concentrations of iron, zinc, and retinol (vitamin A) were significantly lower in anemic infants, they study showed.
"Health education focusing on feeding practices and nutrition education could be a practical strategy for preventing anemia and malnutrition in young children.," the researchers suggest.
Source: BMC Public Health

Vaccine against tooth decay

Wuhan researchers have developed a vaccine that could make tooth decay - and visits to the dentist - a thing of the past.
The researchers from Hubei have shown that an anti-caries DNA vaccine induced salivary secretory immunoglobulin A (S-IgA) antibodies to Streptococcus mutans (S. mutans) the main causative agent for dental caries.
By stimulating the production of the antibodies, the vaccine  was effective in preventing adhesion of the S. mutans bacteria to a tooth model.
"These results demonstrate that the anti-caries DNA vaccine induces the production of specific S-IgA antibodies that may prevent dental caries by inhibiting the initial adherence of S. mutans onto tooth surfaces, thereby reducing the accumulation of S. mutans on the acquired pellicles," they say.
Read more: Acta Pharmacologica Sinica.

Tamiflu resistance emerges in China

Two new mutant forms of influenza virus detected in China are resistant to neuraminidase inhibitors drugs such as Tamiflu that are the only option for treatment.
Researchers from the National Institute for Viral Disease Control and Prevention at the Chinese Centre for Disease Control and Prevention, Beijing, tested more than 600 influenza B virus samples collected in 2010 and 2011 for susceptibility to oseltamivir and zanamivir. They found four influenza B virus samples showed reduced susceptibilities to oseltamivir, but not zanamivir, while another showed resistance to both.They say that "[antiviral] drug resistance is a public health concern" and that "this report underlies the importance of continued influenza antiviral susceptibility surveillance globally, even in countries where the use of neuraminidase inhibitors  has been low or non-existent."
Read more: Antiviral Research

In China, influenza-like illness is caused by many different viruses

In the Chinese winter flu season, human coronavirus is a common cause of influenza-like illness

by Michael Woodhead
Influenza-like illness is a common cause of diseases and disability in China but little is known about the causative viruses in China.
Therefore Dr Huo Xiang and colleagues at the Jiangsu Provincial Center for Disease Control and Preventionin  Nanjing screened almost 500 patients with influenza-like illness over a one year period  in Nanjing.
In their study, viruses were detected in samples from half the patients with influenza-like illness, and the viruses detected most frequently were influenza A (23%), influenza B  (8%), influenza C 30 (6%) patients, and rhinovirus (6%).  All other viruses such as human coronaviruses and respiratory syncytial virus (RSV) were found in less than 5% of patients.
Interestingly, the predominant types of viruses seen in influenza varied by season. Rates of influenza A and human coronavirus illness were much higher during the  winter peak 'flu season' than during the summer and other months. Co-infections were seen in 12% of patients.
"This study confirmed that multiple respiratory viruses may circulate concurrently in the population and account for a large proportion of influenza-like illness.
And the proportion was much higher in January (67%) than in June–August (33%), which was consistent with other findings indicating that respiratory viruses are more likely to be associated with influenza-like illness peak in winter rather than peak in summer.
The influenza-like illness peak in summer may be due to other respiratory pathogens including bacteria, chlamydia, or mycoplasma, the researchers say.
Also of interest was the observation that RSV was rarely a cause of influenza-like illness in China, as it is the most common cause of lower respiratory tract disease and the leading cause of hospital admission among young children worldwide
 "In the present study on outpatients with influenza-like illness, RSV was common in children up to fifteen but was not detected in other age groups, which may be attributed to the developing immune state and vulnerability to infections," the researchers note.
"In conclusion, this study confirms that multiple respiratory viruses may circulate concurrently among the population and account for a large proportion of influenza-like illness. In addition to influenza A, human coronavirus may be associated with the influenza-like illness winter peak in Nanjing, China, 2011."
Source: Journal of Medical Virology

Human metapneumovirus a major cause of pneumonia in China

Human metapneumovirus (hMPV) plays a significant role in pediatric community-acquired pneumonia in China, new research shows
In a study published in the Journal of Medical Virology, researchers from the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing have shown that the detection rate of hMPV ranked third in patients with community-acquired pneumonia.
They also found that similar clinical manifestations were observed between hMPV-positive and RSV-positive patients.
Nasopharyngeal aspirates were collected  from 1,028 children who were diagnosed with community-acquired pneumonia in Beijing, China. hMPV was detected in 6.3% of the patients with community-acquired pneumonia. This detection rate is the third highest for a respiratory virus in children with community-acquired pneumonia, after that of rhinovirus (31%) and respiratory syncytial virus (31%). "These findings indicate that human metapneumovirus (hMPV) plays a significant role in pediatric community-acquired pneumonia in China," they conclude

Read more: Journal of Medical Virology