Re: Africa - Congo - 396 cases, 165 deaths in polio outbreak - at least one fatal case confirmed infected with novel enterovirus
Re: Africa - Congo - 396 cases, 165 deaths in polio outbreak - at least one fatal case confirmed infected with novel enterovirus
http://www.promedmail.org/pls/apex/..._BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86012
Archive Number 20101126.4272
Published Date 26-NOV-2010
Subject PRO/EDR> Poliomyelitis - worldwide (28): Rep of Congo, Asia, Russia
POLIOMYELITIS - WORLDWIDE (28): REPUBLIC OF CONGO, ASIA, RUSSIA
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In this update:
[1] Eurosurveillance: WPV1 and putative enterovirus 109
[2] Central Asia and North Caucasus Federal Region, Russian Federation
[3] Polio eradication initiative cumulative case count as of 25 Nov 2010
******
[1] Eurosurveillance: WPV1 and putative enterovirus 109
Date: Thu 25 Nov 2010
Source: Eurosurveillance edition 2010; 15(47)
<
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19723 >
Type 1 wild poliovirus and putative enterovirus 109 in an outbreak of acute
flaccid paralysis in Congo, Oct-Nov 2010
------------------------------------------------------------------
[Grard G, Drexler JF, Lekana-Douki S, Caron M, et al: Type 1 wild
poliovirus and putative enterovirus 109 in an outbreak of acute flaccid
paralysis in Congo, October-November 2010. Euro Surveill. 2010; 15(47):
pii=19723]
An outbreak of flaccid paralysis syndrome in adults is ongoing in Congo.
Molecular analysis of faecal, throat, and cerebrospinal samples identified
wild type 1 poliovirus and an additional enterovirus C strain related to
enterovirus 109 as the cause. As of [22 Nov 2010], the cumulative number of
cases was 409, of which 169 (41.3 per cent) were fatal. This is one of the
largest wild type 1 poliovirus (WPV1) outbreaks ever described associated
with an unusually high case fatality rate.
Background
----------
Following mass vaccination campaigns organised through the Global Polio
Eradication Initiative, the World Health Organization (WHO) declared that
poliomyelitis had been eradicated from many regions of the world. However,
although transmission of wild poliovirus type 2 (WPV2) has been
interrupted, isolated human cases and outbreaks of WPV1 and WPV3 are still
being reported in many countries (1). Epidemiological investigations showed
that all these clinical cases during the last decade were due to
importation of WPV from one of the 4 countries where indigenous WPV
transmission is still ongoing, namely Afghanistan, India, Nigeria, and
Pakistan (1).
In the past decade, several outbreaks and isolated clinical cases resulting
from WPV1 and/or WPV3 importation from Nigeria or India were reported in 15
polio-free countries in Africa. 2 small WPV1 outbreaks occurred recently,
in Namibia in 2006 and Angola in 2010, after importation of WPV1 of Indian
origin (2). In order to prevent these episodic cases of imported and
indigenous WPV transmission, polio immunisation campaigns were conducted
that targeted some 72 million children in 15 countries across western and
central Africa.
Outbreak description
--------------------
Congo had recorded its last official case of indigenous polio in 2000 (3).
On 5 Nov 2010 the Ministry of Health of Congo declared an outbreak of
poliovirus centred in the 2nd largest town, Pointe-Noire. The outbreak
presumably started in mid-October 2010, with an unusual accumulation of
cases of acute flaccid paralysis (AFP) syndrome in patients between 15 and
72 years old. Most cases occurred in Pointe-Noire and some in Cabinda
province. Cases exported from Pointe-Noire were then reported in several
towns and villages of Congo. As of [22 Nov 2010] the cumulative number of
cases was 409, of which 169 (41.3 per cent) were fatal. Direct contact
between cases was rare, and there was no apparent spatial pattern.
Likewise, there was no evidence of a common source such as food or water.
In most hospitalised patients the disease started with influenza-like
symptoms 4 to 7 days before the onset of AFP of the legs. AFP then ascended
rapidly (within a day), frequently leading to death from cardiac and/or
respiratory failure. The large number of severe cases and the high case
fatality rate contrast sharply with previous WPV outbreaks and point to a
role of unknown viral/host features or to the existence of massive numbers
of mild and therefore unreported additional cases.
Laboratory investigations
-------------------------
The Centre International de Recherches Medicales de Franceville (CIRMF),
Gabon, received 3 plasma samples for aetiologic investigation on [29 Oct
2010]. Real-time and conventional reverse transcription (RT)-PCR testing
was negative for neurologic, enteric, and respiratory viral pathogens,
namely the genera _Enterovirus_, _Flavivirus_, _Alphavirus_, _Phlebovirus_,
human mastadenoviruses, the family Paramyxoviridae (mumps virus, measles
virus, parainfluenza viruses 1-4, respiratory syncytial virus, human
metapneumovirus) and the subfamily _Coronavirinae_ (human coronavirus Nl63,
HKU1, OC43, and 229E.
Also negative were species-specific real-time RT-PCR tests for West Nile
virus, tick-borne encephalitis virus, cytomegalovirus, human herpesvirus
type 6, herpes simplex virus type 1, varicella zoster virus, rotavirus
serogroup A, norovirus genogroups 1 and 2, sapovirus, astrovirus, influenza
viruses A and B, and rhinovirus.
CIRMF then received 15 rectal swabs, 14 throat swabs, and 5 cerebrospinal
fluid (CSF) samples on [2 Nov 2010] of which 13 rectal swab specimens (86.7
per cent), 5 throat specimens (35.7 per cent) and one CSF specimen (20.0
per cent) were positive for enterovirus in a real-time RT-PCR targeting the
5'-noncoding region (4). The faecal and throat samples had threshold cycles
ranging from 24 to 38 in real-time RT-PCR, indicating medium to high virus
concentrations, while the concentration in the positive CSF sample was low
(cycle threshold (CT) 38). The genome was studied by the Institute of
Virology at the University of Bonn Medical Centre in Germany, based on
partial VP1 sequencing (5), 3D sequencing (unpublished in-house assay) and
5'-UTR sequencing (6).
Poliovirus type 1 was identified in one sample (100 per cent amino acid
identity to recent poliovirus strains of Indian genotype in 'typing' VP1
PCR). The amplified 327 nt sequence of this sample (corresponding to genome
positions 2631 to 2957 in WPV1 strain Brunhilde) shared 94.8-96.3 per cent
identity with poliovirus type 1 sampled in Africa (Angola and Democratic
Republic of the Congo) in 2006 and 2007 (isolates ANG-LUA-KIL-07-003 and
RDC-BCG-SEK-06-004) and 95.1 per cent identity with a strain recovered
during a polio outbreak in Tajikistan in 2010 (GenBank accession number
HQ317702).
A more sensitive strain-specific nested PCR assay amplifying a 201 bp VP1
fragment was developed from the initial sequencing data, and all but 2 of
the 19 samples positive in the enterovirus real-time RT-PCR were typed as
wild type 1 polio virus. Partial sequences of the 3D genomic region
encoding the viral polymerase (181 nt corresponding to genome positions
6869-7049 in WPV1 strain Brunhilde) were retrieved from 5 samples. The
maximum nucleotide identity of all these samples was 96.1 per cent with 2
poliovirus type 1 strains recovered in Russia and the Philippines after the
year 2000 (isolates P1W/Bar65, and Mindanao-01-1, respectively).
Partial 5'-UTR sequencing yielded positive results for all the specimens
tested. The 115 nt thus obtained (corresponding to genome positions 466 to
580 in WPV1 strain Brunhilde) were 96.5 per cent identical to recent WPV1
strains from China (isolate CHN-Hainan/93-2). Therefore, all analysed
genomic regions were identified as WPV1, indicating absence of putative
intra- or interspecies recombination.
An additional enterovirus C strain distantly related to enterovirus 109
(EV109) in the VP1 region was retrieved from a rectal swab of a deceased
patient. In the 322 nt VP1 sequence fragment that could be retrieved, the
virus showed 75 to 77 per cent nt sequence identity with the 5 EV109
sequences available in GenBank, and 90.5 per cent nt identity in the 3D
genome region with EV109 isolate NICA08-4327 recovered in Nicaragua in 2010
(7).
Of note, the corresponding sample contained one of the highest enterovirus
RNA copy numbers (CT value 24). Polio virus was not detected in this sample
with the broad-range typing assays described above, nor with
strain-specific VP1 nested and 3D real-time PCR assays. No other sample was
positive for the EV109-related virus in a strain-specific 3D real-time PCR
assay.
The presence of other enteric viruses (adenovirus, astrovirus, enterovirus,
rotavirus A, sapovirus, and norovirus genogroups 1 and 2) was ruled out in
all the faecal samples except for one WPV-positive sample which also
contained norovirus RNA. Genome sequencing and further typing of samples
containing poliovirus and enterovirus, targeting the complete VP1 genomic
region, are ongoing. Additional samples have been sent to CIRMF for analysis.
Conclusions
-----------
The preliminary sequencing data and clinical picture are compatible with a
wild type poliovirus outbreak. Further epidemiological and serological
studies are required to explain the unusually high case fatality rate and
the patients' relatively advanced age. One possible explanation is that
only severe cases may be reported. Alternatively, the population may be
immunologically naive and highly susceptible, although this is unlikely
given the claimed success of vaccination campaigns. Epidemiological
investigations have just begun. At this time, no direct contact between
cases has been observed, and no apparent spatial pattern was identified,
with neither domestic dissemination nor within the same subdivisions.
Together, these observations suggest a diffuse source of contamination,
such as, from water drawn from wells in the poor neighbourhoods of the
city. Involvement of a more virulent virus, or potentially other viruses,
is another possibility. More information on non-hospitalised patients and
mild cases is needed. Information on predisposing conditions of the fatal
cases as well as full-length sequencing of VP1 and the full genome are
currently ongoing.
The WHO Country Office, Regional Office, and Headquarters are supporting
the Ministry of Health in Pointe-Noire, and the WHO Country Office is
supporting the operational costs of the investigation and response teams.
At least 1.1 million people are to be vaccinated in the epicentre of the
outbreak (Pointe-Noire region), and further 600 000 people will be
vaccinated simultaneously in the neighbouring regions of Congo near Angola,
where the last cases of WPV1 occurred in 2010.
Acknowledgements
----------------
We thank Global Viral Forecasting, and the USAID Emerging and Pandemic
Threats PREDICT Cooperative Agreement for financial support. We also thank
P Yaba, P Engandja, and G Maganga from Centre International de Recherches
de Franceville, Gabon, as well as S Bruenink and T Bleicker from the
Institute of Virology, University of Bonn Medical Center, for technical
assistance during this work. SeqLab GmbH, Goettingen, provided prompt
sequencing. The work in Bonn was funded by the European Union DG Research
(contract 223498, EMPERIE).
References
----------
1. Centers for Disease Control and prevention (CDC). Wild poliovirus type 1
and type 3 importations - 14 countries, Africa, 2008-2009. MMWR Morb Mortal
Wkly Rep. 2009; 58(14): 357-62 [available from
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5814a1.htm>].
2. Outbreak of type-1 wild poliovirus in adults, Namibia, 2006. Wkly
Epidemiol Rec. 2006; 81(45): 425-32 [available from
<http://www.who.int/wer/2006/wer8145/en/index.html>].
3. Polio in Congo - update. Geneva: World Health Organisation; 9 Nov 2010.
Available from <http://www.who.int/csr/don/2010_11_09/en/index.html>
4. Dierssen U, Rehren F, Henke-Gendo C, et al: Rapid routine detection of
enterovirus RNA in cerebrospinal fluid by a one-step real-time RT-PCR
assay. J Clin Virol. 2008; 42(1):58-64 [abstract available at
<http://www.ncbi.nlm.nih.gov/pubmed/18164234>].
5. Oberste MS, Nix WA, Maher K, Pallansch MA: Improved molecular
identification of enteroviruses by RT-PCR and amplicon sequencing. J Clin
Virol. 2003; 26(3): 375-7.
6. Nix WA, Berger MM, Oberste MS, et al: Failure to detect enterovirus in
the spinal cord of ALS patients using a sensitive RT-PCR method. Neurology.
2004; 62(8): 1250-1 [abstract available from
<http://www.neurology.org/content/62/8/1372.abstract>].
7. Yozwiak NL, Skewes-Cox P, Gordon A, et al: Human enterovirus 109: a
novel interspecies recombinant enterovirus isolated from a case of acute
pediatric respiratory illness in Nicaragua. J Virol. 2010; 84(18): 9047-58
[available from <http://jvi.asm.org/cgi/content/full/84/18/9047>].
--
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[The authors of this Rapid Communication report the detection of 2 viruses
in some clinical samples obtained from patients during an ongoing outbreak
of flaccid paralysis in the Republic of Congo. This outbreak has been
characterised by a higher than usual case fatality ratio for outbreaks of
poliomyelitis. Curiously, any direct contact between cases was rare and
there is no evidence of a common source of infection. Molecular analyses
identified the presence of 2 enteroviruses -- wild poliovirus type 1, and a
2nd enterovirus identified as human enterovirus 109. The wild poliovirus
type 1 exhibited 100 per cent amino acid identity with the wild poliovirus
type 1 currently prevalent in India.
The human enterovirus 109 isolate is closely related to the novel
recombinant enterovirus previously associated with a case of acute
pediatric respiratory illness in Nicaragua. Similar molecular analyses
(real-time and conventional reverse transcription (RT)-PCR testing) were
negative for an impressively wide range of potential human neurologic,
enteric and respiratory viral pathogens.
However, so far the analysis of
the outbreak lacks any element of quantitation that would allow assessment
of the relative roles of these 2 viruses in the causation of flaccid
paralysis. It is unclear whether enterovirus 109 alone or in combination
with wild poliovirus type 1 is a determining factor responsible for the
high case fatality ratio observed in this outbreak. This question must
await further analysis. - Mod.CP
In Table 5 of Nathanson N, Kew OM. From emergence to eradication: the
epidemiology of poliomyelitis deconstructed. Am J Epidemiol. 2010; 172(11):
1213-29 (available at
<
http://aje.oxfordjournals.org/content/early/2010/10/26/aje.kwq320.full >),
the authors present data from Olin G (The epidemiologic pattern of
poliomyelitis in Sweden from 1905 to 1950. In: Fishbein M, editor.
Poliomyelitis: papers and discussions presented at the second international
poliomyelitis conference. Philadelphia, PA: Lippincott; 1952. p. 367-75)
from a review of polio in Sweden 1925-1944 demonstrating an increasing case
fatality rate (CFR) by increasing age, going from 4.5 per cent in the
population under 3 years of age to 23.5 per cent for those over 25 years of
age. This same increase in CFR with increased age has been observed by
other descriptive epidemiologic presentations in earlier years. Nielsena
NM, Aabya P, Wohlfahrta J, et al. The polio model. Does it apply to polio?
Int J Epidemiol. 2002; 31(1): 181-6. (available at
<http://ije.oxfordjournals.org/content/31/1/181.long>, mentions that
Weinstein L (Influence of age and sex on susceptibility and clinical
manifestations in poliomyelitis. N Engl J Med. 1957; 257:47-52),
demonstrates that there is
an increase in respiratory paralysis with
increasing age, which by the nature of the involvement is more serious and
results in a higher CFR. Hence, the observation that the majority of the
reported cases have been in older age groups might well support the
observation of a higher CFR in the outbreak in the Congo than usually seen
in recent outbreaks of polio elsewhere in Africa and Asia, that have
predominantly involved unvaccinated younger age groups.
That being said, the reported CFR of 41.3 per cent in this current outbreak
in the Congo is much higher than usually reported and one can't help but
wonder if there isn't significant under reporting of milder cases to
explain this observation. One also questions whether there might not have
been a problem with vaccine potency in earlier years, leading to a larger
than expected susceptible population presently at older ages, having been
vaccinated in earlier years with non-potent vaccine, hence further
explaining the unusual epidemiology of this outbreak.
We await further information as results of active case finding and
additional laboratory studies become available.
For a map of the Republic of Congo showing Pointe-Noire, see
<http://www.ecoi.net/file_upload/dh935_01460con.gif>. For the interactive
HealthMap/ProMED map of the Republic of the Congo, see
<http://healthmap.org/r/0f0G>. - Mod.MPP]
A child receives polio vaccine
</OBJECT>