This summer, two tourists from Taiwan set off alarm bells among global health authorities when they flew from Kaohsiung via Hong Kong to attend a relative's wedding in Nanjing.
The couple was infected with tuberculosis. The 55-year-old husband had multi-drug-resistant TB (MDR-TB), a less treatable strain of the disease.
Like common tuberculosis, the strain is spread through germs in the air. But it is resistant to at least two of the leading first-line drugs used to treat the disease, and its potential spread prompted warnings this month of a global tuberculosis crisis by lung disease experts.
The husband and wife were eventually traced in July by mainland authorities in Funing, and sent home. Although World Health Organisation guidelines suggest the risk of infection was minimal because the flight lasted less than eight hours, officials nevertheless tried to trace the passengers seated next to the infected couple.
The manhunt reflected a growing concern among global health bodies over the spread of the drug resistant strain of tuberculosis, a fear that multiplied last December, when research revealed cases of MDR-TB to be much more numerous than previously estimated.
It had been believed that 300,000 new cases of MDR-TB were appearing every year. Researchers from the WHO and the Centres for Disease Control and Prevention in the US revised the figure to 450,000.
According to the WHO, the highest rates of MDR-TB are now on the mainland and in countries of the former Soviet Union.
Pieter van Maaren, Western Pacific regional adviser for the WHO's Stop TB programme estimates there to be 140,000 to 150,000 drug resistant cases in China. 'Not all of them are seriously drug-resistant,' he said.
Of even greater concern, however, is the global prevalence of extensive drug-resistant TB, or XDR-TB, which Dr van Maaren describes as 'almost untreatable'. While one in three people globally is infected with the TB bacillus (and annually around 1.6 million people die from TB), medicine has been developed to cure the disease. Yet strains have emerged that are now resistant to more than one drug used to treat TB, for example isoniazid and rifampicin. The most extreme form is resistant to all major drugs.
MDR-TB can be treated with extensive chemotherapy and second-line drugs with potent side effects. But an outbreak earlier this year of XDR-TB in Africa killed 99 per cent of its victims.
A total of 41 countries have reported cases of XDR-TB, including Hong Kong, Australia, Korea, Thailand, Vietnam and Japan. In Hong Kong, XDR-TB cases accounted for about 0.1 per cent of the bacteriologically positive TB cases as of March, and the risk is regarded as relatively low.
This month, 3,000 health experts at a major lung disease conference in Cape Town were given a stern warning from Mario Raviglione, director of the WHO's Stop TB department. Growing resistance to TB drugs was a world threat, he said.
'Scenarios of an apocalyptic nature are not likely ... but not impossible,' he said.
He said the chances of a completely drug-resistant strain becoming dominant were less than 5 per cent, but that this figure could be reached as new drugs to treat large-scale resistance were lacking. Nor is there any imminent prospect of a vaccine. The last TB vaccine was developed more than 40 years ago.
The WHO launched its Stop TB programme last year to deal with drug-resistant strains, the key focus being emphasis on the Dots (directly observed treatment, short-course) strategy it launched in 1995. Dots involves registering every patient with TB and giving them a standardised, multi-drug treatment, followed by constant evaluation.
Margaret Ip of the Chinese University of Hong Kong's microbiology department said jurisdictions such as Hong Kong had had a good rate of success with the Dots programme.
'There's a very good surveillance system in Hong Kong. It's generally with TB not being controlled globally - especially in Southeast Asia [that] we have a greater chance of getting drug-resistant TB.'
A fundamental problem in controlling the spread is to make sure patients follow treatment through. It can be a rigorous process: for up to 12 months, patients must take three to four drugs. Some people suffer side-effects that mean they must suspend the drug use.
That leaves potential for the disease to spread. According to the Centres for Disease Control, TB germs are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks or sings. The germs can float in the air for several hours and people breathing them can become infected.
The emergence of drug-resistant strains is blamed on non-adherence to the treatment regimen: patients who either fail to finish the course or only partly complete the treatment relapse into a form of TB that is more resistant to drugs.
Effective implementation of the Dots programme is seen as key to containing the threat. It was, however, previously lacking in China, partly due to funding constraints but also due to the sheer size of the country and a yawning disparity between urban and rural health care.
Although Dots was implemented in China in 1992, only in the past five years has it more effectively been in place, according to Dr van Maaren.
As Biao Xu, director of the TB research centre at the school of public health at Shanghai's Fudan University explains, funding for the programme was initially scant and covered only a fraction of the country. 'I would say since 2002 the whole country has been covered by Dots,' she said. 'It's a very hot topic now. The government is paying a lot of attention to this.'
The emphasis, she said, was now on co-ordinating the programme nationally to make sure patients' treatment was regulated.
China also benefited from a US$2.15 billion global plan launched earlier this year by the WHO to fight the rise of drug-resistant cases, with the money to go towards creating and improving laboratories capable of detecting the more potent strains. There are nevertheless concerns over the true reach of the programme. As Professor Ip said: 'In China, in some cities it [Dots treatment] might be good, but because it's such a big place we don't know the consistency.'
Initially, the WHO plan will see two provinces receive funding to help laboratories and to treat patients free of charge.
Zhang Li-wei, associate secretary general of the non-profit Amity Foundation in China, has been seeking to bridge the gap between rural and urban health care on the mainland and is alert to difficulties on the ground. He said the main problem in rural areas was a lack of expertise and equipment.
'There's still a shortage of funding compared to urban areas - although the government has realised that, and more money is being put in to rural areas,' he said. 'But most rural villages have only barefoot doctors or village doctors. The training they have is not sufficient and the skills are very low. So there's a great need to upgrade their skills and improve knowledge.'
Many TB sufferers in rural areas may not know they have been infected. If they are, they may be unaware of the free treatment on offer or too far away from the nearest clinic to receive it.
There is also an unclear picture of the number of TB sufferers who are also infected with HIV on the mainland. TB is the leading cause of death among an estimated 40 million people infected with HIV across the globe. A third of those 40 million have tuberculosis.
It is feared that drug-resistant strains of TB could trigger a wave of infections among those with weak immune systems. On the mainland, an estimated 650,000 people are living with HIV, although it is believed the actual figure could be two to three times higher.
Professor Xu said: 'We don't have a lot of information about the co-infected population. Across China, HIV infection varies a lot depending on provinces.'
Dr van Maaren said: 'Of course, we are concerned about the situation of HIV/Aids in China ... at this moment in time there's no evidence it is affecting the TB programme very dramatically.'
Yet in South Africa 60 per cent are infected with both diseases and the death rate is five times that of people infected with TB alone.
That country represents a chilling reality check on the potential effects of drug-resistant TB. It has imposed enforced quarantine on XDR-TB patients, who are kept behind high fences in buildings that were once used for smallpox sufferers.
As South Africa's Aids epidemic escalated, there was a tandem surge in TB cases, including the most extreme drug-resistant strain, of which there have been 64 cases this year. Twenty of the patients died.