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Deadly Zambian fever: deja vu all over again

7 October, 2008

The news media are presently fascinated by the appearance of what looks like a new and nasty virus from my old home country, Zambia: see a link to The Times article of 7th October for the official word.

Which is “Don’t Panic”, written in large, friendly letters across the face of the newspaper….

From The Times article by Sashni Pather:

“Disease transmitted via bodily fluids

THE deputy director of the National Institute for Communicable Diseases has assured the public that there is no need to panic, despite the fact that four people have been killed by an unknown, highly contagious virus.

Doctor Lucille Blumberg, who also heads up the NICD’s epidemiology unit and consults to its special pathogens unit, referred to the death of Cecilia van Deventer, 36, as an “isolated case” and said test results were not yet available.

…A paramedic, Hannes Els, 33, who treated the critically ill Van Deventer in Zambia, and brought her to the Morningside Medi-Clinic in Sandton on September 12, died last Thursday after being infected with the highly contagious disease.

On Sunday a nurse and a cleaner, who had possibly been exposed to the disease, died.

Blumberg said: “The cause of death of the cleaner is still being investigated. We are busy conducting tests on all four deceased. The cleaner might not have been killed as a result of the virus.

“This is an isolated case. There have been no other reported cases in Lusaka, Zambia. “”

OK, so no obvious panic there, then – but disturbing echoes of another incident from 1996, when a Gabonese doctor was medevacced in to South Africa, and passed on an Ebola virus infection to a theatre nurse, Marilyn Lahana.  He recovered, and she died – and there was close to panic in the land, as chronicled here.  And here we are again….  Incidentally, anyone who wants to see how the first Ebola outbreaks of the electronic age unfolded can see a day-by-day history here, on my original Ebola pages.  Still accessible, to my surprise!

That wonderful institution that is ProMED – who were the first people to break hard news of the Kikwit Ebola outbreak back in 1995, came to the attention of the serious medical reporting world as a result – has a slightly different view of the whole thing – and some interesting details not in the general news story.  In this morning’s digest:

UNDIAGNOSED FATALITIES – SOUTH AFRICA ex ZAMBIA (02)
***********************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the International Society for Infectious Diseases
<http://www.isid.org>

[1]
Date: Mon 6 Oct 2008
Source: South African Broadcasting Corporation News online [edited]
<http://www.sabcnews.com/south_africa/health/0,2172,177844,00.htm>

A 4th person with viral haemorragic fever (VHF) symptoms has died. The virus has already claimed the lives of a Zambian national and 2 other people at the Morningside Clinic in Johannesburg. The woman was a cleaner at the clinic.

The National Health Department has issued an alert in Gauteng following these deaths. Unconfirmed tests indicate they may have died of [a] fatal viral haemorragic fever. An Outbreak Response and Tracking Team has been set up to contain any further spread. The department’s Zanele Mngadi says investigations are still underway into the cause of the deaths.

Mngadi confirmed the death of the 4th person, who was admitted at the Leratong hospital last night [5 Oct 2008]. The patient, who showed symptoms of VHF, was transferred to the Charlotte Maxeke Johannesburg
Academic Hospital, where she died. The health department says there is no need for South Africans to panic. The department’s Frew Denson says the fever is highly contagious but is only transmitted through body fluids.

It is reported that the virus can kill a person within 72 hours. VHF is an extremely infectious and life-threatening disease caused by [several different] viruses, including Ebola virus. The death rate [in the case of Ebola virus] can be as high as 90 percent. Symptoms vary but include fever, vomiting, diarrhea and bleeding.

Communicated by:
Rabelani Daswa <rabedaswa@gmail.com>

******
[2]
Date: Mon 6 Oct 2008
From: Amy Cantlay <inka@iwayafrica.com>

I have just read the posting (Undiagnosed fatalities – South Africa ex Zambia: RFI 20081005.3139) on your site, and it appears to be rather misleading. The chronological order of events (as I can gather) is as follows (None of this information has yet been confirmed.):

4 Sep 2008 – Index Case – female South African, (living in Zambia for many years) begins to suffer from flu-like symptoms.

9 Sep 2008 – She is slowly deteriorating. She sees multiple doctors in Lusaka.

11 Sep 2008 – She is admitted to hospital and deteriorates over night.

12 Sep 2008 – Paramedic is called in to evacuate her to South Africa.  He does the transfer, along with another Dr assisting.

13 Sep 2008 – Index Case dies.

14 Sep 2008 Paramedic starts to develop flu-like symptoms.

14-27 Sep 2008 – Paramedic slowly deteriorates.

27 Sep 2008 – Paramedic is diagnosed as very sick and medivaced [sic] to South Africa. Nurse who treated Index case begins to get flu-like symptoms.

30 Sep 2008 – Paramedic dies.

1 Oct 2008 – Nurse who treated Index Case is admitted to hospital.

5 Oct 2008 – Nurse who treated Index Case dies.

The information that I can gather is the following:

1. Incubation period is as little as 2 days (paramedic), but as long as 14 days (nurse).

2. Disease course is generally 4-7 days of flu-like illness with patient only becoming critically ill in 2nd week of disease.

3. Further information is that Index Case reportedly had an eschar on one of her feet, thought to be from a tick-bite. She had also been in contact with horses from Congo in the weeks preceding her illness. Transmission is hypothesized to be by 2 means: tick-borne 1st (which may have brought the disease into the human population from the animal population) followed by direct contact with bodily fluids (resulting in human to human transmission).

4. It appears further hospital staff are now critically ill in Zambia, though this has not been confirmed.

5. If the incubation period is as long as 2 weeks, then we should still be closely watching all “contact-cases” for any signs of the disease. Those in contact with the Index case should be in the clear by now, while those in contact with the paramedic and the nurse (as well as any hospital staff who are currently sick) are still at high risk. One should probably work on a 21-day incubation period/quarantine period to be safe.

6. Chances are this is a new virus (or new subtype of virus) in the [family _Filoviridae_]. The only 2 known viruses in this group are Ebola and Marburg. It looks as though [the infection] may have entered Zambia from the Democratic Republic of the Congo (DRC) through a tick (carried on a horse), but again this cannot be confirmed.

This comment assumes that labs in South Africa have already tested all known VHFs. It is unlikely to be pneumonic plague, as this would have been discovered in South Africa; however, it is still a possibility that this [putative] viral disease has been in the Southern Province of Zambia (and that the 4 reported cases seen there were not diagnosed or wrongly called pneumonic plague).

7. The important steps in control are 1. effective quarantine of sick patients, and 2. monitoring of all “in-contact” cases, with quarantine as soon as any signs of flu or fever are noted. The government should also ideally make a statement to calm the panic and prevent people from fleeing the capital (potentially carrying the disease countrywide). This disease only spreads to people who are in very close contact with sick individuals. Those family members who are potentially incubating the disease should be encouraged to stay
around Lusaka, so that signs can be picked up quickly and treatment issued rapidly….[section on use of ribavirin – effective only against Lassa fever – edited out].

Communicated by:
Dr Amy Cantlay BVSc.MRCVS <inka@iwayafrica.com>
Veterinarian
Mkushi, Zambia

[ProMED-mail thanks Dr. Cantlay for her commentary, which contributes some interesting detail. At this point, it would not be useful to speculate further on the identity of the infectious agent responsible for the deaths of the 4 Zambian patients. No doubt a firm diagnosis will be available shortly from a South African reference laboratory. Several different viruses cause viral hemorrhagic fever. Of these, Ebola, Marburg, Lassa or Crimean-Congo hemorrhagic fever viruses have not been recorded in Zambia up to the present. A comprehensive account of these and other viruses responsible for hemorrhagic fevers can be found at the US CDC website: <http://www.cdc.gov/ncidod/diseases/virlfvr/virlfvr.htm>.

So: an unknown fever-causing agent, possibly associated with a tick bite in the index case, but which seems definitely to be transmitted quite efficiently via exposure to (presumably) body fluids, in a hospital setting…which does not appear to be known strains / types of Marburg or Ebola viruses, or Crimean-Congo haemorrhagic fever virus.

Loose in Johannesburg…part of a greater conurbation housing some 9 million people….

Should we be worried??

And the answer would be – NO.

If Ebola didn’t spread out of Kikwit in 1995 – a city of 500 000+ with no decent infrastructure to speak of – even to get as far as Kinshasa, then why should it spread in Johannesburg, or even Lusaka, where the infrastructure is MUCH more sophisticated?

I will leave this with a couple of quotes from posts I compiled on Ebola back in August 1995 from the fondly-remembered virology group at bio.net:

“To: virology@net.bio.net
From: ED@molbiol.uct.ac.za (“Ed Rybicki”)
Subject: Re: The Ebola virus – the end of the civilized world
Date: 18 Aug 1995 05:53:07 -0700

I would say you – and many others – are being unnecessarily
frightened by a concerted media campaign designed at selling lurid
books and films.  Listen – for a change – to what experts tell you,
and react accordingly.

That is, RELAX!!!!!”

And:

“To: virology@net.bio.net
From: york@mbcrr.harvard.edu (Ian A. York)
Subject: Re: Ebola: the greatest threat, continued

In article <99792FA2E69@ida.ruc.dk>,  wrote:
>
>Ebola is another ballgame. There is no way to protect effectively
>against this disease, and we have seen at mutation of this virus, Ebola
>Reston, that evidently was airborn (luckily it only affects monkeys).

…
Ebola has killed less than 400 people in the past decade.  By contrast, typhoid fever kills over 600,000 people per year; measles kills 1,000,000 (one million) people per year.  If you think Ebola has the potential tokill anywhere near that many, you don’t understand the virus.  The Ebola outbreak in Kikwit *was* the worst-case scenario; *everything* went wrong.  300 deaths.  Not trivial.  But a tiny fraction of the real killers. 

Lobby and try to get measles vaccine in Africa, if you want to do some good.  So don’t waste your time worrying about Ebola.”

Amen to that!  Pity we have to keep revisiting The Threat From Darkest Africa – maybe we can sell the rest of the world some vaccines against them sometime soon…B-)

H5N1 flu: The End is still in sight

15 July, 2008

While the much-dreaded Big One – a major flu pandemic – still seems to be holding off, I am pleased to see that the latest edition of Nature has devoted an editorial and other commentary space to pandemic flu in general, and H5N1 flu in particular.

The Nature issue of 10th July 2008 – which has Ebola virus glycoprotein on the cover, about which, more later – has as its lead editorial title, “The long war against flu“.  The header goes on:

“That the H5N1 strain of bird flu has not yet caused a pandemic is no cause for complacency. Preparations for the inevitable must be redoubled to mitigate the potential devastation.”

My feelings entirely, and especially for the developing world – shared with you here and here, in MicrobiologyBytes, and here, in your own ViroBlogy.  It is all too easy to easy to fall into a state of complacency, or even H5N1 pandemic fatigue: however, this is really dangerous, especially for planners.  The editorial goes on:

“Five years after the deadly H5N1 avian influenza virus exploded into a global epidemic in birds, it has infected more than 300 people. Happily, it has not yet evolved into a strain that can transmit easily between humans — an event that would trigger a pandemic that could kill tens of millions. But as long as H5N1 continues to be present in animals, that risk persists. And with so many other flu strains out in the world, all constantly evolving, a flu pandemic is inevitable.”

 And:

“…improved control measures, especially for H5N1 itself, and public-health infrastructure are our frontline defences against a pandemic. Unfortunately, the overall control picture is bleak. Thailand, Vietnam and China have notched up successes in curbing outbreaks in birds, which is key to minimizing the chance that the virus can pass to humans. But South Korea had its worst outbreak ever in April, and the disease has become endemic in Indonesia, Bangladesh, Vietnam and Egypt. Eradication now seems impossible, and the task of containing the virus has become chronic and costly.”

Which sets the stage for Commentaries in the same issue: in “Ready for Avian Flu“, Tadataka Yamada et al. offer up “…a roadmap for heading off a global avian influenza catastrophe“.  They discuss how the WHO has made plans for stockpiling H5N1 vaccines, and that major vaccine manufacturers have offered to contribute – but also that the necessary allocation plan and ethics framework still need to be worked out.  They discuss how adjuvanting flu vaccines can reduce the dose by up to to four times, and how this together with dedicating the existing manufacturing framework – capable of some 500 million doses of trivalent vaccine a year  – to single-valency production, could allow some 6 billion doses a year to be produced.

Which, of course, would neatly cover the world’s population.  This sounds wonderful – but ignores the fact that H5N1 viruses are notoriously difficult to produce via conventional egg-based methods, which is what provides the bulk of the present manufacturing capacity….  Still, they also point out that adjuvanted, non-matched vaccines can still cross-protect against strains that have undergone seven or so years of genetic drift, meaning that stockpiled H5N1 vaccines could still be relevant in several years time.

They state the following:

“In the next 18 months we [Bill & Melinda Gates Foundation, the Pasteur Institute and the Wellcome Trust] will develop, maintain and disseminate a central inventory of funded research activities that are relevant to human influenza to ensure that stakeholders are well-informed. We will also coordinate roadmapping exercises to identify knowledge gaps. These will assist funders and researchers in establishing research-funding priorities, with specific focus on vaccines, drug therapies and epidemiology/population science (for example, diagnostics, surveillance, transmission and modelling). The Bill & Melinda Gates Foundation and the Wellcome Trust will collaborate to fund these activities.”

And how much developing country input will there be into this?  Distressingly little, probably, given the propensity of these funds to at best give money to developed country groups to work with developing country folk, but at least the roadmap addresses issues that are relevant to the whole world community.  Like intellectual property concerns, coordination of stockpiling and distribution, fair distribution, funding…and surveillance, the forgotten and possibly most important factor in determining if a flu outbreak is getting out of hand.  

Apropos of which, another commentary in the same issue – “The contents of the syringe“, by Steven Salzberg – notes that the influenza vaccine failed this northern hemisphere winter, and that future success relies on sharing data more widely and making the virus strain selection process more transparent.  Salzburg says:

 
“The WHO met on 11–13 February this year to decide on the strains to be included in the vaccine for the 2008–09 season. As usual, the meeting was closed to all but invited participants, who this year included members of the WHO influenza surveillance network, representatives of national drug regulatory agencies, and influenza vaccine manufacturers. The experts involved chose to replace the H3N2 strain with a more recent isolate, from 2007, which should be a better match to the circulating viruses next season. Neither the WHO nor the CDC publishes the evidence used to support their decision [my emphasis]. That evidence includes hemagglutinin inhibition tests of hundreds of isolates, genome sequences of some isolates and data on the ease with which the isolates can be grown in eggs.”

“The process of choosing flu-vaccine strains needs to be much more open. Other scientists, such as those in evolutionary biology with expertise in sequence analysis, could meaningfully contribute to the selection. At present, external scientists cannot review the data that went into the decision, nor can they suggest other types of data that might improve it.”

Whoops…so those who would safeguard us, feel no need to tell us what is going on??  Salzburg has some suggestions:

“The leaders of the influenza community, especially the WHO and the CDC, should create policies — for sharing data and isolates — that are more open, and should insist that their own scientists follow those policies. When these leading organizations set an example, the rest of the community will follow.”

“Of course, preparing vaccine in cell culture could reduce some of the pressures put on that dark room of vaccine predictors. The current system, in which most of the world’s vaccine supply is grown in chicken eggs, is an antiquated, inefficient method requiring six months or more to ramp up production, which in turn means that the vaccine strains must be chosen far in advance of each flu season. More crucially it sometimes prevents the use of the optimal strain, as it did in 2007. And, if the next pandemic is an avian-influenza strain such as H5N1, then it could easily sweep through the chicken farms that we rely on to produce eggs for vaccines. [me again]”

 He goes on to extol the benefits of sharing sequence information in particular, so as to enable rational, evidence-based choice of flu strains for vaccines – and the use of non-egg-based cell culture methods for vaccine production, and how these should allow far quicker development of flu vaccines.

All of this is very cogent and timeous.  However, it begs the question, previously raised in ViroBlogy, as to how production will be increased to take care of everyone who may be affected.

I still think plants are the answer…!  I note the plant-based flu vaccine group paper that I blogged on previously in this forum has a sequel: this is a better paper all around, and points up the need to explore this sort of production system for this kind of virus.

But I digress – so let me do so thoroughly.  The Nature issue also has a news item on the Eppendorf Song, a new piece of viral advertising with a boy band extolling the virtues of a multipettor.  Not a patch on the Biorad PCR Song, guys – but nice to see some popular culture making its way into science equipment advertising!

What Rough Beast

19 May, 2008

I was surprised and rather gratified to see – via a suitably modest no-commentary post in MicrobiologyBytes – that ViroBlogy has been noticed by none other than the June editorial of Nature Reviews Microbiology.

Along with rather more material on MicrobiologyBytes and Small Things Considered.  But hey, a review’s a review…!

There are a number of useful comments and other links in the blog version of the post, on how to actually interact with such material, and the potential of “Web 2.0” applications.

So get busy, students…the wiki is coming – in fact, it was already established, but will be re-invented before the second semester – and your participation is vital.