Two more show signs of fever (Unknow viral haemorrhagic fever spreads in South Africa)

A virus new to humanity, or an old acquaintance dressed up in slightly new clothes, the disease that so far appears to have achieved a 100% kill rate in Johannesburg, is now up against the full might of humanity's scientific detectives.

So far three people have died from the mysterious disease, which has retained its anonymity through an extensive first round of laboratory testing for viral haemorrhagic fevers. Based on the pattern of disease and a suspected tick bite on the first patient, the pathogen -- let us call it Virus X -- is suspected of being Crimean-Congo Haemorrhagic Fever (CCHF) or Lassa fever, or one of their close relatives. Such a diagnosis would be relatively good news if Virus X has infected other people, because these pathogens are estimated to kill about 30% of their victims.

The nastier haemorrhagic fevers such as Ebola and Marburg have achieved kill rates of up to 90% in some outbreaks. There is also one antiviral, ribavirin, which can be used against CCHF and Lassa. In the words of one World Health Organisation expert, haemorrhagic viruses kill by "melting the organs".

They disrupt the body's internal structure and damage the clotting mechanism. The patient effectively bleeds to death either internally, or with dramatic bleeding from all orifices detailed in several books and films. Blood pressure falls and the patient dies from multi-organ failure. Professor Guy Richards is an intensive care specialist at Charlotte Mxenge Johannesburg Hospital and one of the doctors who treated the outbreak of Ebola in Johannesburg in the late 1990s.

In that case the original patient, a man flown in from Congo, survived. Sadly the nurse treating him died. He says the haemorrhagic fevers typically attack the endothelial cells lining the blood vessels. The blood vessel system, with its myriad branching arteries, veins and capillaries, is the largest organ inside the body.

The membranes of these cells are damaged and fluids leak in and out of the holed cells which are no longer able to maintain their cohesion with their neighbours. Blood vessels collapse, blood pressure falls and the patient dies. Usually the best medical workers can do is try to keep the patient alive by giving fluids and keeping them cool, and hope that the individual's immune system will be able to fight off the pathogen.

Another infectious disease doctor says that the problem is that measures to help the patient, such as inserting drips or tubes to help them breathe, can then trigger further bleeding.

Samples of Virus X are undergoing further tests at the National Institute of Communicable Diseases in Johannesburg, which is one of the few laboratories in any developing country with the infrastructure and skills to test for such dangerous and rare pathogens.

The institute's Lucille Blumberg, who leads the laboratory investigations, says that it will probably take several days for Virus X to be identified -- and there is a chance it could be a new virus making its way on to the world stage.

Initial tests for the genetic material of these haemorrhagic viruses, and for the antibodies that victims make against the pathogens, all came back negative.

However, there are a range of reasons for this: the individual may have been too sick to produce sufficient antibodies; the levels of virus may have been too small when the samples were taken; the virus may have been a known pathogen which has mutated slightly and so not registered on the highly sensitive and targeted tests used; or it could be a previously unknown virus.

Samples have been flown to the Centers for Disease Control in the United States which collects pathogens from around the world and is probably the world's most important repository of information on infectious diseases. It will have a larger library of different types of viral haemorraghic fevers against which to compare the South African samples.

The first patient to die as a result of this virus, Cecilia van Deventer, was medi-evacuated from Zambia to Morningside Clinic on September 12 with suspected tick-bite fever. The critically ill woman died shortly after arriving at the hospital. One of the paramedics who had accompanied and helped treat her fell sick as well. He was also flown from Zambia to Johannesburg where he died on September 30.

The previous day doctors had linked the two patients, realising they had an outbreak of disease and alerted the national and provincial departments of health. An intensive care nurse who had treated the first patient also sickened and appears to have died from the virus.

An outbreak of dangerous infectious diseases such as haemorrhagic fevers triggers an automatic response: a higher level of infection control to prevent further infections of healthcare workers and tracing everyone who might have caught the virus. Mediclinic has identified 55 potential contacts, mainly healthcare workers and their families. The department of health has identified another 61.

Monitoring these individuals is simple: twice daily temperature checks for 21 days to detect the onset of a fever. The period is designed to cover the usual incubation period of haemorrhagic viral fevers.

Viral haemorrhagic fevers (VHFs) are diseases mainly caused by four families of viruses. They are virus zoonoses -- pathogens which depend on animals or insects for replication and survival. Zoonoses cause extreme reactions because the immune system sees them as entirely different from other intruders.

The most dangerous VHFs are classified as biosafety level 4, which should be studied only in specially equipped laboratories. Two other viruses, dengue haemorrhagic fever and yellow fever, can also causes haemorrhagic fevers, although neither is considered such a dangerous disease.

Humans become infected from contact with host animals -- such as a tick bite or contact with the body or fluids of an infected animal. Viruses can be transmitted from person to person through bodily fluids or needles contaminated by blood, faeces, urine, vomit or even semen. Ebola, Marburg, Lassa and Crimean-Congo haemorrhagic fever can be spread among humans. Small mammals, such as bats, are often the hosts for VHFs, but in Marburg and Ebola the host has not been conclusively identified.

Vaccines exist only against yellow fever and Argentine haemorrhagic fever, although research is under way into vaccines against other VHFs -- especially those which could be "weaponised" for biological warfare. Marburg virus affects humans and other primates.

It is closely related to the Ebola virus, the only other member of the filovirus family. These two are considered the deadliest viruses known to man. Marburg was first recognised in 1967 with simultaneous outbreaks in Germany and former Yugoslavia. Ebola, named after the river in the DRC where it was first recognised in 1976, is often fatal.

There are four known types of this virus. Lassa fever was discovered in Nigeria in 1969. It is endemic in parts of Africa where it causes significant levels of mortality and morbidity.

Crimean-Congo haemorrhagic fever is a tick-borne disease first described in Crimea in 1944 and then recognised in 1969 in Congo. Humans contract the disease from tick bites or through contact with the blood of infected animals, such as cattle or goats.

Two more show signs of fever

October 12 2008 at 10:39AM

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By Eleanor Momberg, Myrtle Ryan, Liz Clarke and Niyantha Singh

Two more people have been admitted to the Morningside Medi-Clinic for observation after they showed signs of viral haemorrhagic fever.

The hospital confirmed on Saturday that a man was admitted on Thursday night and a woman on Friday. The woman is the second nurse to show signs of the disease.

At the same time, two relatives of Gladys Mthembu, the nurse who died after being admitted to the Sir Albert Robinson Hospital in Randfontein, were discharged after being given a clean bill of health. They were Mthembu's 11-year-old son and his 23-year-old nanny.

A cleaning supervisor at Morningside, who was admitted to Chris Hani Baragwanath Hospital in Soweto on Monday with symptoms of viral haemorrhagic fever, has since been discharged.

A total of 154 people remain under out-of-hospital observation for the signs of the mystery disease.

The outbreak has claimed three lives in South Africa since September 14, when Cecilia "Silky" van Deventer, a safari operator, died two days after being flown to Morningside from Zambia, apparently with tick-bite fever.

Hannes Els, the paramedic who treated Van Deventer, was admitted to the hospital on September 27, but died on October 2.

Mthembu, who also treated Van Deventer, subsequently went on leave and became ill at home. She went to her personal doctor, who referred her to the Sir Albert Robinson hospital, where she was admitted on October 1. Morningside was notified of her death on October 5.

Melinda Pelser, a Morningside spokesperson, said Maria Mokubung, a cleaner at the hospital who died at Charlotte Maxeke Hospital in Johannesburg, had a chronic illness for which she had been receiving treatment at Chris Hani Baragwanath hospital.

All the people who have been placed under observation have had direct contact with the people who died at Morningside.

Pelser said that, as a safety precaution, people who may have had direct contact with the patients who died at the hospital were being monitored and would continue to be monitored for 21 days from the time of their last contact.

"This number was initially 55 and has now been extended to 67 people. The monitoring consists of regular temperature checks and a daily check in with the Morningside Medi-Clinic. These people are not in isolation or quarantine and can continue with their daily activities," she said.

In addition, the department of health said that it was monitoring 66 people who may have had direct contact with Mthembu.

The World Health Organisation (WHO) said on Saturday that 23 people known to have had contact with the patients who died were being monitored in Zambia. None were symptomatic.

Clinical features common to the three patients include fever, headache, diarrhoea and muscle pain, which then developed into rash and hepatic (liver) dysfunction, followed by rapid deterioration and death, the WHO said.

"There is no indication at this point of the need for any restriction of travel to or from Zambia or South Africa and no special measures are required for passengers arriving from these countries," a WHO statement said.

What virologists were still trying to determine was which of the haemorrhagic viruses was responsible for the outbreak.

There was still concern about the family of Mthembu, who died last week in a Randfontein hospital. Mthembu had been urged to return to Morningside for treatment, but had chosen to be admitted to a local hospital, close to her family. Little is known about follow-up steps by the hospital to isolate those who came into contact with her.

Zambian authorities said they were still trying to trace people who had had contact with Van Deventer. Blood samples from all three victims who died in South Africa have been sent by the National Institute for Communicable Diseases to the Centres for Disease Control in the United States. The results are expected before the end of the week. South African specialists are also continuing their tests.

Professor Alan Smith, an eminent virologist, said the reason why virologists at the Special Pathogens Unit in Johannesburg - the only Level 4 laboratory in Africa - were taking so long to come up with an answer was that it was probably an emergent disease.

If it were Congo fever, it would have been identified in a few days, he said. "Ebola was one such emergent disease and in 1975 another was Marburg disease.

"There is no need to panic. Humans can only be infected through direct contact with the blood, urine or faeces of an infected person," he said.

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