Announcement

**Commonground** · July 14, 2008, 05:36 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Direct contact history referred to a patient who had direct
contact with sick or dead poultry. Indirect contact referred
to a patient who had contact with contaminated environments
including fertiliser or animal markets.

Fig. 3. Contact history of patients with laboratory confirmed H5N1 avian
influenza

Contact History
The largest number of cases (12 or 44.4%) had indirect
contact with poultry ? predominantly by visiting markets or
areas where outbreaks of poultry disease caused by H5N1
AI had been reported (Fig. 3). Unfortunately, for a significant
number of cases, the contact history could not be definitively
obtained partly because the disease was often rapidly fatal
by the time the patients presented to our hospital.

**Commonground** · July 14, 2008, 05:52 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Surprisingly, we found more patients with an indirect
contact history than with a direct contact history. This is
possibly because of transmission through fertilisers made
from chicken manure. Japanese researchers have reported
the detection of highly pathogenic H5N1 AI viruses in
blowflies near infected poultry farms. (5*) The role of the
contaminated environment in the transmission and
propagation of H5N1 in humans and animals needs to be
more clearly defined. It is also possible that some of the
patients or their relatives might not have been forthcoming
with their contact histories and this is borne out by the lack
of contact data in about a third of the cases ? one of the
limitations of this study.

* - 5. Sawabe K, Hoshino K, Isawa H, Sasaki T, Hayashi T, Tsuda Y, et al.
Detection and isolation of highly pathogenic H5N1 avian influenza A
viruses from blow flies collected in the vicinity of an infected poultry
farm in Kyoto, Japan, 2004. Am J Trop Med Hyg 2006;75:327-32.

**gsgs** · July 14, 2008, 05:58 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

now we need that history for average, normal, non-sick, people

or better : people with H3N2 or H1N1

**mixin** · July 14, 2008, 06:08 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Some interesting points from the article:
There were a total of 27 laboratory confirmed cases of
H5N1 AI in humans out of the 296 suspect cases managed
at Sulianti Saroso Infectious Diseases Hospital in Jakarta
between September 2005 and December 2007

The largest number of cases (12 or 44.4&#37

had indirect
contact with poultry – predominantly by visiting markets or
areas where outbreaks of poultry disease caused by H5N1
AI had been reported

AI in humans is predominantly a disease of young adults
and adolescents; the mean age among our patients was 16
years with the oldest patient being 40 years old. This is
probably due to a combination of factors including exposure
to sick or dead poultry or contaminated markets where
younger people are more likely to live and work.

As a result of the delay in reaching definitive care, the
majority of our patients were severely ill at presentation

**Oracle** · July 14, 2008, 09:15 PM

National Age Distribution graphic for Indonesia

http://www.nationmaster.com/country/id-indonesia/Age-_distribution

**Giuseppe** · July 17, 2008, 03:19 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Reports examine high H5N1 death rate in Indonesia
Robert Roos News Editor

Jul 17, 2008 (CIDRAP News) ?

Recent reports from Indonesian health officials tie the high fatality rate in human H5N1 influenza cases there to the difficulty of diagnosing the disease, late treatment with antiviral drugs, and a shortage of well-equipped hospitals.

The case-fatality rate (CFR) in Indonesia, which leads the world in H5N1 cases, climbed from 63% in 2005 to 80% in 2006 and 85.7% in 2007, according to a report in the journal Annals Academy of Medicine Singapore.

The CFR remains high so far this year, with 15 of 18 cases fatal, or 83.3%, according to World Health Organization (WHO) figures.

By comparison, the CFR for the global total of 385 cases with 243 deaths is 63.1%.

The fatality rate with Indonesian cases excluded is 53.2% (250 cases with 133 deaths, based on WHO figures).

Two reports in the Singapore journal discuss H5N1 cases in Indonesia.

One, written by Indonesian Ministry of Health (MOH) officials, looks at the 116 cases, including 94 fatal ones, the country recorded from 2005 through 2007 (the article also defends Indonesia's refusal to share H5N1 virus isolates with the WHO).

A second article, written by hospital physicians, profiles the 27 cases, including 21 fatal ones, treated at Sulianti Saroso Infectious Diseases Hospital in Jakarta during that period.

Hospital deficit called major factor
According to the second report, Indonesia, like most developing countries, has few primary or secondary care hospitals with the protocols, isolation rooms, or cardio-respiratory support equipment to treat patients critically ill with H5N1 influenza.

"This is probably the largest single contributor to the high mortality recorded," says the report, written by Sardikin Giriputro, MD, and colleagues.

The MOH report cites the infection's nonspecific early clinical features, medical providers' unfamiliarity with the disease, and the late clinical stage of patients when hospitalized as potential causes of the high mortality.

But with the increasing CFR over time, it adds, "the probability of an increase in the virulence of H5N1 viruses should also be considered."

Without a fast, convenient test for H5N1 infection, the disease is difficult to diagnose, the hospital article says.

Because the early signs and symptoms are not specific, primary care physicians "would find it extremely hard to predict which of their dozens of patients with influenza-like illness is going to turn out to have highly pathogenic H5N1 influenza in a few days time," it states.

The MOH report says that 71% of H5N1 patients in Indonesia were treated with the antiviral drug oseltamivir (Tamiflu), but only two patients received it within the recommended time frame of 48 hours after the first symptoms.

Those two patients survived.

The survival rate decreased as the time to start treatment increased, the report says.

Because early recognition is critical, the hospital report says, "The only conceivable solution is the development of cheap, effective point-of-care tests for H5N1 influenza that are as easy to use as a pregnancy test for example. These could be used by a rural primary healthcare clinic or district hospital in any developing country. This is clearly a challenge for the global scientific community."

Most H5N1 patients were severely ill by the time they were brought to the hospital, the report says.

"The vast majority had evidence of the systemic inflammatory response syndrome (SIRS) with marked tachycardia and tachypnoea" (rapid heart and breathing rates).

Gender gap in fatality rate
In other observations, the MOH report says the CFR was significantly higher among females than males?89% versus 73%; it offers no explanation for the difference.

Adults had a higher CFR than children, 83% versus 76%, but the difference was not significant.

The median age for all case-patients was 20 years.

The MOH report also says that 24% of the 116 cases "occurred in 10 clusters of blood-related family members."

But the report offers no opinion on how many cases of person-to-person transmission occurred. As reported previously, person-to-person transmission was considered likely in a widely publicized cluster of eight cases (seven confirmed, one probable) in Sumatra in May 2006.

WHO reports on the Indonesian cases so far this year show only one family case cluster, involving a 38-year-old woman from West Jakarta, who fell ill in late January, and her 15-year-old daughter, who got sick in early February.

According to the MOH authors, less than half of all the Indonesian patients?46%?had an "unmistakable history of direct contact with sick or dead poultry."

Another 36% had been near sick or dead poultry without direct contact, and the possible sources for the other 18% were unclear, the report says.

Among the Sulianti Saroso patients, 12 of 27 (44%) had indirect contact with poultry, mainly from visiting markets or areas where poultry outbreaks had occurred, the hospital report says.

A smaller, unspecified number had direct contact with poultry, and the source was unclear for the rest.

The authors speculate that some of the patients who had no direct contact with poultry might have caught the virus from fertilizers made of chicken manure.

As for the epidemiologic curve, the MOH report says Indonesia averaged 5 cases per month from September 2005 through May 2007, but the rate dropped to 3 cases per month from June through December 2007.

The WHO records indicate a similar pace so far this year, with 18 confirmed cases through June, but two thirds of those were in January and February.

While 31 of 33 Indonesian provinces have had H5N1 outbreaks in birds, only 12 provinces have had human cases, the MOH report says.

Giriputro S, Agus R, Sulastri S, et al. Clinical and epidemiological features of patients with confirmed avian influenza presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007. Ann Acad Med Singapore 2008 Jun;37(6):454-7 [Full text]

Sedyaningsih ER, Isfandari S, Soendoro T, et al. Towards mutual trust, transparency and equality in virus sharing mechanism: the avian influenza case of Indonesia. Ann Acad Med Singapore 2008 Jun;37(6):482-8 [Full text]
-

Reports examine high H5N1 death rate in Indonesia

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/jul1708cases-jw.html

------

**Commonground** · July 17, 2008, 06:08 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

The CFR remains high so far this year, with 15 of 18 cases fatal, or 83.3%, according to World Health Organization (WHO) figures.

The MOH report says that 71% of H5N1 patients in Indonesia were treated with the antiviral drug oseltamivir (Tamiflu), but only two patients received it within the recommended time frame of 48 hours after the first symptoms.

Those two patients survived.

Contradictory.
WHO stats have a total of 20 died; 3 Recovered.
My list has 20 died, 3 Recovered. It does not count Tini Suhartini.

WHO does not have Tini Suhartini, confirmed by Indo Lab (in my notes)
Tini was from Asem Vill., Ranjeng, Cisitu, Sumedang. Died on 5/9. Twice to clinic in Siturja for diarrhea. On 5/13, all the Dr's, nurses and all the people who were in contact with her had blood drawn. A 5/18 article mentioned that 4 chickens tested positive in Pajagen Village.

**HenryN** · July 17, 2008, 06:42 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Commentary

http://www.recombinomics.com/News/07180801/H5N1_Indo_H2H_50.html

**HenryN** · July 17, 2008, 08:07 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

>>While drug resistance to amantadine was common among H5N1
influenza A virus Indonesian strain (76&#37

[Sedyaningsih
et al., 2008, unpublished data], resistance to oseltamivir

has yet to be proven.<<

Tamiflu resistance was present in one of the brothers (32M) in the Karo cluster. The story is in the sequence (but you have to be able to read).

**HenryN** · July 17, 2008, 08:17 PM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Originally posted by niman View Post

>>While drug resistance to amantadine was common among H5N1

influenza A virus Indonesian strain (76%) [Sedyaningsih
et al., 2008, unpublished data], resistance to oseltamivir

has yet to be proven.<<

Tamiflu resistance was present in one of the brothers in the Karo cluster. The story is in the sequence (but you have to be able to read).

LOCUS EU146786 1353 bp cRNA linear VRL 01-MAY-2008
DEFINITION Influenza A virus (A/Indonesia/560H/2006(H5N1)) segment 6
neuraminidase (NA) gene, partial cds.
ACCESSION EU146786
VERSION EU146786.1 GI:157955511
KEYWORDS .
SOURCE Influenza A virus (A/Indonesia/560H/2006(H5N1))
ORGANISM Influenza A virus (A/Indonesia/560H/2006(H5N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1353)
AUTHORS Smith,G., Guan,Y., Peiris,M., Kandun,I.N., Soendoro,T. and
Sedyaningsih,E.R.
TITLE Direct Submission
JOURNAL Submitted (10-SEP-2007) Department of Microbiology, The University
of Hong Kong, Hong Kong SAR, China
COMMENT Sequence entered by GenBank staff on behalf of submitter. Please
acknowledge the Indonesian Ministry of Health if used in a
publication. Contact person for futher information is Dr. Triono
Sundoro. GenBank Accession Numbers EU146785-EU146792 represent
sequences from the 8 segments of Influenza A virus
(A/Indonesia/560H/2006(H5N1)).
FEATURES Location/Qualifiers
source 1..1353
/organism="Influenza A virus
(A/Indonesia/560H/2006(H5N1))"
/mol_type="viral cRNA"
/strain="A/Indonesia/560H/2006"
/serotype="H5N1"
/specific_host="Homo sapiens"
/db_xref="taxon:468968"
/segment="6"
/country="Indonesia"
/collection_date="20-May-2006"
/note="throat swab from Indonesia Case 560 (32M)"
misc_feature 1..1353
/db_xref="BioHealthBase:EU146786"
gene 7..>1353
/gene="NA"
CDS 7..>1353
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id="ABW06159.1"
/db_xref="GI:157955512"
/translation="MNPNQKIITIGSICMAIGTVSLMLQIGNMISIWVSHS IQTGNQH
QAESISNTNPLTEKAVASVTLAGNSSLCPIRGWAVHSKDNSIRIGSKGDV FVIREPFI
SCSHSECRTFFLTQGALLNDKHSNETVKDRSPHRTLMSCPVGEAPSPYNS RFESVAWS
ASACHDGTSWLTIGISGPDNGAVAVLKYNGIITDTIKSWRNNILRTQESE CACVNGSC
FTVMTDGPSNGQASYKIFKMEKGKVVKSVELDAPNYYYEECSCYPDAGEITCVCRDNW
HGSNRPWVSFNQNLEYQIGYICSGVFGDNPRPNDGTGSCGPMSSNGAYGV KGFSFKYG
NGVWIGRTKSTNSRSGFEMIWDPNGWTGTDSSFSVKQDIVAITDWSGYSG SFVQHPEL
TGLDCIRPCFWVELIRGRPKESTIWTSGSSISFCGVNSDTVSWSWPDGAE LPFTIDK"
ORIGIN
1 attaaaatga atccaaatca gaagataata accattggat caatctgtat ggcaattgga
61 acagttagct taatgttaca aattgggaac atgatctcaa tatgggtcag ccattcaatt
121 cagacaggga accaacacca agctgaatca atcagcaata ctaaccctct tactgagaaa
181 gctgtggctt cagtaacatt ggcaggcaat tcgtctcttt gccccattag aggatgggct
241 gtacacagta aggacaacag tataaggatc ggttccaagg gggatgtgtt tgttattaga
301 gagccgttca tctcatgctc ccactcggaa tgcagaactt tctttttgac tcagggagcc
361 ttgctgaatg acaagcactc caacgagact gtcaaagaca gaagccctca cagaacattg
421 atgagttgtc ctgtgggtga ggctccctct ccatacaact caaggtttga gtctgttgct
481 tggtcagcaa gtgcttgcca tgatggcacc agttggttga caattggaat ttctggccca
541 gacaatgggg ctgtggctgt gttgaaatac aatggcataa taacagacac tatcaagagt
601 tggaggaaca acatactaag aactcaagag tctgaatgtg catgtgtaaa tggctcttgc
661 tttactgtaa tgactgatgg accaagtaat gggcaggcat catataagat cttcaaaatg
721 gaaaaaggga aagtggttaa atcagtcgaa ttggatgctc ccaattatta ctatgaggag
781 tgctcctgtt atcctgatgc tggcgaaatc acatgtgtgt gcagggataa ttggcatggc
841 tcaaacaggc catgggtatc cttcaatcaa aatttggagt atcaaatagg atatatatgc
901 agtggagttt ttggagacaa tccacgcccc aatgatggaa caggtagttg tggtccgatg
961 tcctctaacg gggcatatgg ggtaaagggg ttttcattta aatacggcaa tggtgtttgg
1021 atcgggagaa ccaaaagcac taattccaga agcggctttg aaatgatttg ggatccaaat
1081 gggtggactg gaacggacag tagcttttcg gtgaaacaag atatagtagc aataactgat
1141 tggtcaggat atagtgggag ttttgtccaa catccagaac tgacaggatt agattgcata
1201 agaccttgtt tctgggttga gttaatcaga gggcgaccca aagagagcac aatttggact
1261 agtgggagca gcatatcttt ttgtggtgta aatagtgaca ctgtgagttg gtcttggcca
1321 gacggtgctg agttgccatt caccattgac aag

**AlaskaDenise** · July 18, 2008, 01:37 AM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Originally posted by niman View Post

Commentary

http://www.recombinomics.com/News/07...do_H2H_50.html

Commentary

Frequent Human H5N1 Transmission in Indonesia
Recombinomics Commentary 00:30
July 18, 2008

The MOH report also says that 24% of the 116 cases "occurred in 10 clusters of blood-related family members."

But the report offers no opinion on how many cases of person-to-person transmission occurred. As reported previously, person-to-person transmission was considered likely in a widely publicized cluster of eight cases (seven confirmed, one probable) in Sumatra in May 2006.

WHO reports on the Indonesian cases so far this year show only one family case cluster, involving a 38-year-old woman from West Jakarta, who fell ill in late January, and her 15-year-old daughter, who got sick in early February.

The above comments on the Indonesian Ministry of Health report include a gross underestimate of the number of cases in family clusters as well as the frequency of human to human (H2H) transmission in Indonesia.

The evidence for the underestimate can be seen in the confirmed clusters reported this year. Most of the recent confirmed cases in Indonesia have been in family clusters, but the index case was misdiagnosed with lung inflammation, typhus, or dengue fever. As a result, the index case was not tested, but the infection of the relative led to bird flu symptoms and testing, leading to confirmed H5N1 cases, but not to confirmed H5N1 clusters.

These three clear clusters had the appropriate time gap between the index case and the family member signaling H2H. This type of cluster was clear for the first confirmed case in Indonesia in 2005. The index case was infected from an unknown source. She then infected her sister who died without being tested. The father of the two girls was subsequently infected, and he tested positive (and the H5N1 isolated from him was used to make clade 2.1 vaccines, which led to Indonesia?s withholding of samples). Eventually, the index case was confirmed because of elevated H5N1 antibodies.

The second confirmed case in Indonesia was also in 2005 and also a cluster. In this case the index case infected her nephew. Both cases were confirmed, but the source of the index case infection was said to be fertilizer, but a match between putative H5N1 in the fertilizer and the index case was never demonstrated. The nephew was tested because he was a contact, but he never developed pneumonia and quickly recovered.

Both of these clusters clear were H2H, but as noted above, only the Karo cluster was officially acknowledged as H2H. Similar clusters were seen in Garut, but samples were not collected from index cases, who died before contacts were confirmed, and additional contacts who subsequently developed symptoms were treated with Tamiflu and were not confirmed.

Thus, it is likely that the number of H5N1 cluster members is close to half of the confirmed cases in Indonesia rather than the reported quarter.

The news blackout that followed the three recent clusters this year was not a coincidence.

.

**Anne** · July 18, 2008, 02:01 AM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Page not found | Annals Singapore

http://www.annals.edu.sg/PDF/37VolNo6Jun2008/V37N6p454.pdf

There were 27 confirmed cases of AI managed at Sulianti
Saroso Infectious Diseases Hospital from September 2005
to December 2007. The positivity rate among suspect cases
is low (<10%). This may suggest the need to develop more
reliable criteria for suspect cases or to a certain extent
underdiagnosis, since some cases showed clinical features
highly suggestive of viral pneumonia were negative by
PCR. The timing of sampling at the later stage in the
clinical course of the disease will most likely decrease the
sensitivity of the test due to the lower viral load at that time.
---------------------------------------------------------------------
what do they mean exactly?
underestimation ?

**HenryN** · July 18, 2008, 04:35 AM

Re: _|Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza|_

Originally posted by Anne View Post

http://www.annals.edu.sg/PDF/37VolNo.../V37N6p454.pdf

There were 27 confirmed cases of AI managed at Sulianti
Saroso Infectious Diseases Hospital from September 2005
to December 2007. The positivity rate among suspect cases
is low (<10%). This may suggest the need to develop more
reliable criteria for suspect cases or to a certain extent
underdiagnosis, since some cases showed clinical features
highly suggestive of viral pneumonia were negative by
PCR. The timing of sampling at the later stage in the
clinical course of the disease will most likely decrease the
sensitivity of the test due to the lower viral load at that time.
---------------------------------------------------------------------
what do they mean exactly?
underestimation ?

They mean that the treatment of the patient with tamiflu lowers the viral load, making it hard to detect the virus, leading to false negatives in the later tests.
Consequently, only 10% of suspect cases test positive.