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OPV strains circulation in HIV infected infants after National Immunisation Days in Bangui, Central African Republic

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  • Institut Pasteur of Bangui

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Humans are the only host of polioviruses, thus the prospects of global polio eradication look reasonable. However, individuals with immunodeficiencies were shown to excrete vaccine derived poliovirus for long periods of time which led to reluctance to prolong the vaccination campaign for fear of this end result. Therefore, we aimed to assess the duration of excretion of poliovirus after the 2001 National Immunization Days according to Human immunodeficiency virus status. Fifty three children were enrolled. Sequential stool samples were collected in between National Immunisation Days rounds and then every month during one year. Children were classified into 2 groups: no immunodepression (n = 38), immunodepression (n = 15) according to CD4+ lymphocytes cells count. Thirteen poliovirus strains were isolated from 11 children: 5 Human immunodeficiency virus positive and 6 Human immunodeficiency virus negative. None of the children excreted poliovirus for more than 4 weeks. The restriction fragment length polymorphism analysis showed that all strains were of Sabin origin including a unique Polio Sabine Vaccine types 2 and 3 (S2/S3) recombinant. From these findings we assume that Human immunodeficiency virus positive children are not a high risk population for long term poliovirus excretion. More powerful studies are needed to confirm our findings.
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Open Access
SHORT REPORT
BioMed Central
© 2010 Gouandjika-Vasilache et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of t he Cre-
ative Commons Attribution Licens e (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distri bution, and re-
production in any medium, provided the original work is properly cited.
Short Report
OPV strains circulation in HIV infected infants after
National Immunisation Days in Bangui, Central
African Republic
Alexandre Manirakiza
1
, Emmanuella Picard
2
, Richard Ngbale
2
, Didier Menard
3
and Ionela Gouandjika-Vasilache*
1
Abstract
Background: Humans are the only host of polioviruses, thus the prospects of global polio eradication look reasonable.
However, individuals with immunodeficiencies were shown to excrete vaccine derived poliovirus for long periods of
time which led to reluctance to prolong the vaccination campaign for fear of this end result. Therefore, we aimed to
assess the duration of excretion of poliovirus after the 2001 National Immunization Days according to Human
immunodeficiency virus status.
Findings: Fifty three children were enrolled. Sequential stool samples were collected in between National
Immunisation Days rounds and then every month during one year. Children were classified into 2 groups: no
immunodepression (n = 38), immunodepression (n = 15) according to CD4+ lymphocytes cells count. Thirteen
poliovirus strains were isolated from 11 children: 5 Human immunodeficiency virus positive and 6 Human
immunodeficiency virus negative. None of the children excreted poliovirus for more than 4 weeks. The restriction
fragment length polymorphism analysis showed that all strains were of Sabin origin including a unique Polio Sabine
Vaccine types 2 and 3 (S2/S3) recombinant.
Conclusions: From these findings we assume that Human immunodeficiency virus positive children are not a high risk
population for long term poliovirus excretion. More powerful studies are needed to confirm our findings.
Findings
Introduction
Humans are the only host of polioviruses, thus the pros-
pects of global polio eradication look reasonable [1,2].
However the discovery, after years of massive use of oral
polio vaccine (OPV), of individuals with immunodefi-
ciencies who were shown to excrete vaccine derived
poliovirus (VDPV) for long periods of time led to a reluc-
tance to prolong the vaccination campaign for fear of this
end result [3]. Considering the immunodeficiency that
prevails in Human immunodeficiency virus (HIV)
patients, long term poliovirus excretion would be likely
[4,5]. In Africa the OPV is used in mass vaccination cam-
paigns during National Immunization Days (NIDs) not-
withstanding HIV status of children. Two recent studies
showed that HIV-infected children have low persistence
of antibodies to vaccines used in the Expended Program
on Immunization (EPI) including OPV [6,7].
In Central African Republic (CAR), it have been
assessed that the prevalence of HIV infection is 6% in
general population [8] thus it would be of interest to
study the impact of HIV infection on poliovirus excretion
in infants of 0 to 5 years of age receiving OPV during
NIDs in Bangui. Very few studies have been conducted
and no persistent excretion of poliovirus has been
reported among HIV infected people [9,10] except two
vaccine derived polioviruses isolated from 2 HIV-
infected children in South Africa [4,5]. Therefore we
studied the duration of excretion of poliovirus after the
2001 NIDs according to HIV status.
Materials and methods
Population
This survey was achieved within "Foyer de Charité" cen-
ter from October 2001 until June 2002. This health struc-
ture is set up by the Catholic Church and take health care
* Correspondence: ionela512@yahoo.fr
1 Virology Unit, Institut Pasteur de Bangui, Avenue Pasteur, BP 923, Bangui,
Central African Republic
Full list of author information is available at the end of the article
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of the children descended of the very poor families in
return for a weak financial involvement (2 US$ per child).
All children included in this study were under 5 years old.
The informed consent of parents or legal tutors was
obtained before inclusion in the study. One blood sample
(for confirmation of HIV status and CD4+ count) and
stool samples were collected before NIDs. All enrolled
infants received 3 doses of OPV during the 3 rounds of
NIDs. Sequential stool samples were collected in between
NIDs rounds and then every month for one year period
from the enrolled children. HIV+ positives infants were
identified and followed up for opportunistic diseases at
this health care structure. Children who did not present
at the scheduled day were followed up at home when pos-
sible. All samples were processed at Institut Pasteur de
Bangui. The date of the last OPV dose administrated was
noted.
Status of human immunodeficiency virus-infected children
According to their HIV status and CD4+ count, the chil-
dren were classified into 2 groups: i) group A no immu-
nodepression (n = 38; 5 HIV+ and 11 HIV-); ii) group I
immunodepression (n = 15; 11 HIV+ and 4 HIV-). Chil-
dren less than 12 months of age were considered as
immunodepressed if the CD4+ count was <500/mm3,
and children of more than 12 months of age were consid-
ered immunodepressed if the CD4+ was <750/mm3 [11].
Western blot tests (new Lav blot I©, BioRad, Marne la
Coquette, France) were carried out at Institut Pasteur de
Bangui to confirm the HIV status of children. Tests were
performed using the same sample to determine the CD4
count. Haematological analysis and CD4 T-cell counts
were carried out with a Coulter AcT Diff 2 Analyser and a
FACSCalibur Flow Cytometer (Becton Dickinson Immu-
nocytometry Systems, San Jose, CA, USA), as previously
described [12].
Virus isolation and identification
Viruses were isolated and identified according to World
Health Organization (WHO) Polio Laboratory Network
Standard Protocols [13]. Internal quality-control proce-
dures associated with these methods were implemented.
Briefly, stool extracts were inoculated on the following
cell lines: RD (human rhabdomyosarcoma derived cells),
Hep2 (human epidermoid cancer cells) and murine L20B
(a transgenic mouse L cells). The latter cell line was used
to distinguish polioviruses from non-polio enteroviruses
[14]. Positive RD and Hep2 cell cultures were passaged in
L20B to separate poliovirus and non polio enteroviruses.
Isolates of poliovirus were identified by neutralization
tests with standardized pools of hyperimmune equine
serum. Tissue culture infectious dose can be determined,
using the double or triple cell-line system. The cells were
discarded every 15 passages, as recommended by WHO,
in order to ensure high cell sensitivity to enteroviruses
and especially for poliovirus. Sensitivity tests were con-
ducted at passage 7 by titration of reference Sabine
strains. If the titre is within ±0.5log10 of the expected ref-
erence value, it is considered that there is no decline in
cell-line sensitivity.
Reverse Transcriptase- Polymerase chain reaction (RT-PCR)
and multiple restriction fragment length polymorphism
(RFLP) analysis
Viral ribonucleic acid (RNA) was extracted using the
Quiaquick kit (QIAGEN®). Three different genomic
regions of the poliovirus genome, namely, VP3-VP1
(nucleotides positions 1913 to 2881 according to Sabin 1
numbering), VP1-2A (nucleotides 2870 to 3648) and 3D-
3'UTR (nucleotides 6536 to 7441) were targeted. RT-
PCR was followed by a multiple RFLP analysis using four
restriction enzymes (DdeI, DpnII, RsaI and HinfI). These
regions were amplified using nucleotides primers UG24
and UC1, UG19 and UC13 and UG17 and UC10 respec-
tively [15,16].
Statistical analysis
Data were managed using EpiInfo Software 3.3.2 version
(Centres for Disease Control and Prevention, USA).
Means of virus isolated were compared according to the
immune status of the patient using Mann-Whitney U
test.
Nucleotides sequencing analysis
Nucleotides sequencing of VP1-2A region PCR products
was performed with the same primers used for RT-PCR
and with internal primers UG1 and UC11. PCR products
were sequenced following purification with a Qiaquick
spin column purification kit (QIAGEN) immediately
after amplification. Sequencing reactions were performed
with a BigDye Terminator cycle sequencing ready kit
(version 1.1) according to the recommendations of
Applied Biosystems. Nucleotide sequences were aligned
and compared using Clustal W program [17].
Results
A total of 117 children were eligible before the first round
of the NIDs. Out of 117 children, 53 (45.3%) received the
all course of 3 OPV doses during of the NIDs (mean age,
56.3 months; male/female ratio, 0.8) and were enrolled in
the study.
HIV test was positive among 16 out of 53 (30.2%) chil-
dren and negative results were observed in 37 out of 53
(69.8%) children. From the 53 children who have received
3 doses of OPV, a total of 345 stools samples were col-
lected during the follow-up. The total number of stool
samples expected for each case was 10. But the number of
stools samples we collected significantly decreased dur-
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ing the follow up because of no compliance to indicated
visits schedules and lost of follow up at home (home
changes to addresses not easily accessible). The mean of
the stool sample collected from each case was of 7 and 6
for the HIV+ and HIV- groups respectively (Figure 1).
A proportion of 36.8% of them were positive for an
enterovirus (127 viruses isolated from 345 stools). Six
poliovirus were isolated on the 107 stools colleted from
HIV+ children (5.6%) while five poliovirus were isolated
on the 238 stools colleted from HIV- children (2.1%) (P
value = 0.185). Non Polio Enteroviruses (NPE) were
excreted in a proportion of 31.8% (34/107) from all HIV+
children and 34.4% (82/238) from all HIV- children (P
value = 0.626) (Table 1).
Only two HIV- children excreted poliovirus before the
NIDs as they received the routine vaccination during the
month preceding the first stool sample collection.
Figure 1 Sequential stools collection flow chart from the cohort study from Day 0 of follow up.
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All the 15 children with immunodeficiency (group I)
secreted an Enterovirus, and 11 of them secreted a virus
more than two times. Thirty four out 38 children with no
immunodeficiency (group A) secreted an Enterovirus,
and 13 of them secreted a virus more than two times.
None of the children excreted poliovirus for more than 4
weeks. Only two HIV- children excreted Poliovirus type 1
and 2 strains two times consecutively. There was no sta-
tistically significant difference of excretion of an Entero-
virus according to HIV serologic (Fisher exact test value =
0,069) and immune level status (U-test P values > 0,05 for
both HIV+ and HIV- groups) (Tables 1 and 22).
RFLP analysis showed that all strains were of Sabin ori-
gin, including a unique S3/S2 recombinant. Sequencing
of Poliovirus type 1 and Poliovirus type 3 strains, both
isolated from HIV+ infants, showed more than 99%
homology with homotypic Sabine strains.
Discussion
Literature reports that both cellular and humoral
immune responses are intact early in life in most children
infected with HIV [18,19]. Although HIV infected indi-
viduals may shed other enteric viruses for prolonged
periods, the lack of persistent poliovirus vaccine excre-
tion is consistent with their ability to develop immunity
after vaccination. Even after deterioration of CD4 cell
counts, these children retained sufficient immunologic
memory to prevent persistent infections from repeated
exposures to poliovirus [20,21].
The main aim of our study was to evaluate the risk of
prolonged OPV circulation in a population of children
receiving massive doses of OPV accordingly to their HIV
status. Our findings showed no trend of a prolonged
Poliovirus excretion in HIV+ and HIV- children groups.
The relatively small size of the cohort does not allow
exclusion of the possibility that a small proportion of HIV
infected children may develop prolonged excretion, espe-
cially since antiretroviral treatments were introduced in
CAR and prolonged the duration of life of these children.
Studies conducted on 28 HIV-infected adults popula-
tion exposed to vaccinated children in CAR and 419
adults in Cote d'Ivoire following anti-poliovirus vaccina-
tion campaigns showed no evidence of prolonged Entero-
virus excretion [9,10].
In most industrialized countries, inactivated polio vac-
cine (IPV) is administrated to individuals with immuno-
deficiency disorders because the potential risk of vaccine
associated paralytic poliomyelitis (VAPP). Nevertheless,
the limited data available indicate a risk of VAPP in chil-
dren with HIV and OPV which is generally administrated
to all children regardless their HIV status in low income
countries [4,5]. In the past 40 years only 23 persons with
IgG deficiency disorders have been found with prolonged
poliovirus excretion. Active search for additional persons
with prolonged poliovirus excretion among persons with
known IgG deficiency disorders revealed no new cases
[3,22].
Conclusion
The small size of the cohort do not allow us to draw a
definitive conclusion, but indicates that excretion of
poliovirus among HIV infected children is present and
Table 1: Viruses isolated according to sample collection session and HIV status from the study cohort (53 children).
Non polio enteroviruses Poliovirus Negative
HIV+ HIV- HIV+ HIV- HIV+ HIV-
A81602819
B 3 14 1 2 12 21
C28201229
D2631619
E41200820
F61400615
G5400518
H030068
I 450031
J000011
Total34826 567151
A = sam ple col lec tio n b efo re N ID' s: D ay 0 , B= sa mpl e co lle cti on b etw ee n th e 1st and 2nd round of NID's (Day 15), C= sample collection between
the 2nd and 3rd round (Day 45), D, E, F, G, H, I, J = sequential sample collection after the 3rd round at one.
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such short term excretion is unlikely to be a source of
reintroduction of neurovirulent poliovirus following the
cessation of OPV use in Central African Republic. More
powerful studies are needed to confirm our findings.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
IGV conceived the study, did the data management and paper draft writing
with substantial contributions of DM. Field study monitoring, data analysis and
interpretation was achieved by AM. The medical and nutritional care of the
children was achieved by EP and RN. All authors read and approved the final
manuscript.
Acknowledgements
We thank Prof. Alain LeFaou and Francis Delpeyroux for useful discussions, Mrs
Denise Cook for English corrections, Arthur Mazitchi and Jean Fandema for
help with virus isolation and identification. This work was funded by a French
Ministry of Foreign Affaires project.
Author Details
1Virology Unit, Institut Pasteur de Bangui, Avenue Pasteur, BP 923, Bangui,
Central African Republic, 2Foyer de Charité, Bangui, Central African Republic
and 3Malaria Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar
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Received: 12 January 2010 Accepted: 18 May 2010
Published: 18 May 2010
This article is available from: http://www.biomedcentral.com/1756-0500/3/136© 2010 Gouandjika-Vasilache et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BMC Research Notes 2010, 3:136
Table 2: Number of virus isolated (polio and NPENT together) according to the immune status of the children at the time of
inclusion.
HIV-/A HIV+/A HIV-/I HIV+/I
A173 1 5
B131 3 3
C7113
D52 2 3
E102 2 2
F102 4 4
G31 14
H30 00
I3123
J0000
Total71131627
Patients have been classified according to the CD4 count: i) group A no immunodepression (n = 37); ii) group I immunodepression (n = 16).
Children under 12 month of age were considered as immunodepressed if the CD4+ count was <500/mm3, and children of more than 12
month of age were considered immunodepressed if the CD4+ was <750/mm3 [11].
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doi: 10.1186/1756-0500-3-136
Cite this article as: Manirakiza et al., OPV strains circulation in HIV infected
infants after National Immunisation Days in Bangui, Central African Republic
BMC Research Notes 2010, 3:136
... We conducted a prospective cross sectional study evaluating stool shedding of vaccine strains and polio seroconversion in Kenyan children who received OPV per the national immunization schedule. The highly desired incremental evidence [31][32][33] could additionally benefit the global and regional policy environment on shaping the discourse around public health implications of potential VDPV, inform the potential need for large scale rigorous studies and the contention on the risk of the VDPV persistence among HIV-infected persons [4,7,19,31]. ...
... We conducted a prospective cross sectional study evaluating stool shedding of vaccine strains and polio seroconversion in Kenyan children who received OPV per the national immunization schedule. The highly desired incremental evidence [31][32][33] could additionally benefit the global and regional policy environment on shaping the discourse around public health implications of potential VDPV, inform the potential need for large scale rigorous studies and the contention on the risk of the VDPV persistence among HIV-infected persons [4,7,19,31]. ...
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Background Poliomyelitis is an acute viral infection caused by poliovirus and transmitted via the fecal–oral route. The causative agent is one of the three serotypes of poliovirus (serotypes 1, 2, 3) that differ slightly in capsid protein. Prolonged vaccine-related poliovirus shedding in human immunodeficiency virus (HIV) positive individuals has been linked to possible reservoir for reintroduction of polioviruses after eradication. The study therefore aimed at estimating the duration for vaccine-related poliovirus shedding among potentially and HIV-infected persons. Methods Poliovirus excretion was studied following vaccination of children aged ≤ 59 month per human immunodeficiency virus status after national immunization days. Their medical records were reviewed to identify the child’s HIV status, demographic and immunization data. Sequential stool samples were collected at site 2nd, 4th and 8th week after trivalent oral poliovirus vaccine (tOPV) was administered. To isolate suspected polioviruses and non-polio enteroviruses, characterize poliovirus subtypes by intratypic differentiation and Sabin vaccine derived poliovirus, real time polymerase chain reaction was applied. Shedding for ≥ 24 weeks was defined as long-term persistence. ResultsThe mean age of the study population was 28.6 months, while the median age was 24 months. Of the children recruited, majority were in the 25–48 months (n = 12; 46.2%) age category. All the HIV-positive children (n = 10) had mild symptomatic HIV status and did shed vaccine-related polioviruses between weeks 2 and 4 respectively. No participant shed polioviruses for ≥ 6 weeks. Conclusions It was evident mildly symptomatic HIV+ children sustain the capacity to clear vaccine-related poliovirus. The oral poliovirus vaccine-2 (Sabin like) that was detected in one HIV-infected child’s stool 6 weeks after the national immunization days was predominantly non revertant. There was no evident prolonged poliovirus shedding among the participants enlisted in the present study. High powered studies are desired to further corroborate these findings.
... Although there are several studies in the literature exploring whether HIV-infected children shed vaccine poliovirus for prolonged periods after OPV administration, they do not adequately answer the question of whether HIV-infected children might be sources of iVDPV. Two prospective studies did not show vaccine poliovirus shedding beyond 6 months, but they were small, and 1 had very low retention rates [14,15]. Of 2 cross-sectional studies, 1 detected no poliovirus in stool samples from 94 HIV-infected Guatemalan children 6 months to ≥10 years after their last OPV dose, but the other did detect VDPV in the stools of hospitalized HIV-infected South African children [16][17][18]. ...
... However, serotype 1 vaccine poliovirus was detected in 3 serial samples from 1 child with moderately symptomatic AIDS up to 87 days after OPV administration, and the VP1 region of the viral genome acquired 0.99% nucleotide substitution by the final positive sample. A prospective study in the Central African Republic enrolled 16 HIV-infected and 37 HIV-uninfected children who were receiving 3 doses of OPV during national immunization days, but low retention rates resulted in samples from only 12 HIV-infected and 32 HIV-uninfected children 1 month after the last OPV dose, down to 1 HIV-infected and 1 HIV-uninfected child 6 months after the last OPV dose [14]. Vaccine poliovirus was detected in 5.6% versus 2.1% of the samples from HIV-infected versus -uninfected children, but no poliovirus shedding was seen beyond 4 weeks. ...
Article
Full-text available
Background: With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. Methods: We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. Results: We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0-2 OPV doses but significantly higher in the HIV-infected versus uninfected children after ≥ 3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. Conclusions: HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.
... Although there are several studies in the literature exploring whether HIV-infected children shed vaccine poliovirus for prolonged periods after OPV administration, they do not adequately answer the question of whether HIV-infected children might be sources of iVDPV. Two prospective studies did not show vaccine poliovirus shedding beyond 6 months, but they were small, and 1 had very low retention rates[14,15]. Of 2 cross-sectional studies, 1 detected no poliovirus in stool samples from 94 HIV-infected Guatemalan children 6 months to ≥10 years after their last OPV dose, but the other did detect VDPV in the stools of hospitalized HIV-infected South African chil- dren161718. ...
... However, serotype 1 vaccine poliovirus was detected in 3 serial samples from 1 child with moderately symptomatic AIDS up to 87 days after OPV administration, and the VP1 region of the viral genome acquired 0.99% nucleotide substitution by the final positive sample. A prospective study in the Central African Republic enrolled 16 HIV-infected and 37 HIV-uninfected children who were receiving 3 doses of OPV during national immunization days, but low retention rates resulted in samples from only 12 HIV-infected and 32 HIV-uninfected children 1 month after the last OPV dose, down to 1 HIV-infected and 1 HIV-uninfected child 6 months after the last OPV dose[14]. Vaccine poliovirus was detected in 5.6% versus 2.1% of the samples from HIV-infected versus -uninfected children, but no poliovirus shedding was seen beyond 4 weeks. ...
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Poliovirus eradication is dependent on maintaining adequate community-wide levels of serologic protection. Many African countries with conditions that favor continued wild poliovirus propagation also have a high prevalence of pediatric human immunodeficiency virus (HIV) infection. Data are limited regarding the degree of serologic immunity conferred on HIV-infected children after immunization with oral polio vaccine (OPV). This was a cross-sectional study correlating HIV infection and neutralizing antibodies against poliovirus serotypes 1, 2, and 3 in 95 Zimbabwean children 2 months to 2 years of age, born to HIV-infected mothers, who received OPV according to the national schedule. HIV-infected children had significantly lower rates of seroconversion to all 3 poliovirus serotypes than HIV-uninfected children (60%, 67%, and 47% vs. 96%, 100%, and 82%, P = 0.001, 0.0003, and 0.015 for serotypes 1, 2, and 3 in HIV-infected and uninfected children, respectively, after ≥3 OPV doses). Among poliovirus seroconverters, HIV-infected children also had significantly lower geometric mean titers against serotypes 1 and 2 than HIV-uninfected children (geometric mean titers: 198 and 317 vs. 1193 and 1056, P = 0.032 and 0.050, for serotypes 1 and 2, respectively, after ≥3 OPV doses). In addition, HIV-infected children had significantly higher levels of total IgG and significantly lower CD4% and mean weight than HIV-uninfected children. Of note, none of the HIV-infected children were receiving antiretroviral therapy, and 71% had a CD4% indicating severe immunodeficiency. Pediatric HIV infection is associated with a poor serologic response to OPV, which could pose an obstacle to global polio eradication.
... 379 million doses of OPV were administered in Nigeria in 2013 during 22 SIAs and at least 200 million doses in 11 SIAs as at April 2014; this was necessary because OPV 3 coverage in 2012 was low at 59%. 5 Campaigns are usually conducted without screening for immunodeficient states like HIV, and although it has been proven that HIV positive children shed OPV virus for a longer time than immunocompetent children, studies suggest there is minimal risk of outbreaks of Vaccine derived polio viruses (VDPVs) and as such pose little threat post-elimination. 19,20 Another common cause of immunodeficiency in African and Nigerian children is malnutrition, and this has been shown not to affect the seropositivity for antibodies to polio viruses. ...
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To determine the safety and immunogenicity of childhood vaccines in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection. Nonrandomized, prospective cohort study; 12-month follow-up period. Obstetric wards and outpatient pediatric clinics at two large hospitals in Kinshasa, Zaire. A total of 8108 pregnant women were screened for HIV-1 antibodies. The 474 children born to 466 seropositive women identified during screening and the 616 children born to 606 seronegative, age- and parity-matched women were vaccinated. The following vaccines were administered at the stated ages: bacille Calmette-Guérin (BCG) vaccine (2 days); trivalent oral Sabin poliomyelitis vaccine (2 days and 6, 10, and 14 weeks); and adsorbed diphtheria-tetanus-pertussis (DTP) vaccine (6, 10, and 14 weeks). Protective antibody titers to tetanus and poliovirus types 1, 2, and 3 were achieved in 95% of all children. Among children with HIV-1 infection, 70.8% had protective antibody titers to diphtheria compared with 98.5% of uninfected children (p < 0.05). Geometric mean antibody titers to diphtheria and poliovirus types 1, 2, and 3 were significantly lower in children with HIV-1 infection than in uninfected children. Vaccine-associated side effects were similarly low in all children. The low incidence of side effects and the high proportion of children with HIV-1 infection who achieved protective postimmunization antibody titers support the continuing use of BCG, DTP, and oral polio vaccines in childhood immunization programs in HIV-1 endemic areas.
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A prospective study of antibody production by adults infected with human immunodeficiency virus (HIV) after vaccination with T lymphocyte-dependent diphtheria toxoid, tetanus toxoid, and inactivated trivalent poliovirus vaccine was conducted. Individuals were divided into three groups according to CD4+ T-lymphocyte count: group 1 had a count of ⩽100 × 106/L; group 2, 101–300 × 106/L; and group 3, >300 × 106/L. After vaccination, 61%, 70%, and 73% of the individuals in groups 1, 2, and 3, respectively, developed protective titers of antibody to diphtheria toxin; the mean postvaccination antibody titer of HIV-infected individuals was significantly lower than that of healthy controls not infected with HIV. Furthermore, the mean titers of antibodies to tetanus toxin and poliovirus were significantly lower in HIV-infected individuals with CD4+ lymphocyte counts of <300 × 106/L than in controls. Of the HIV-infected vaccinees, 83%–100% were protected against tetanus and 78%–100% against polio. We conclude that HIV-infected individuals with CD4+ lymphocyte counts of <300 × 106/L have an impaired (secondary) antibody response after receipt of T lymphocyte-dependent vaccines.
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The biologic principles for the global eradication of poliomyelitis are as follows: Poliovirus causes acute, nonpersistent infections, virus is transmitted by infectious humans or their waste, survival of virus in the environment is finite, humans are the only reservoir, and immunization with polio vaccine interrupts virus transmission. These principles appear to be sound. The potential for prolonged virus excretion by immunocompromised patients requires further definition, although there is no epidemiologic evidence of a threat to eradication. Survival of poliovirus in the environment is highly variable, but viral inactivation is usually complete within months. Higher primates may be infected with poliovirus, but they are unlikely reservoirs in nature. The only poliovirus reservoir remaining after eradication will be laboratory stocks. Serious attention must be given to reducing this potential source of infection. Polio eradication through immunization is evidenced by the documented absence of poliomyelitis in an increasing number of countries and the progressive disappearance of poliovirus genotypes.
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Culture of polioviruses from clinical samples is the gold-standard method for virological surveillance in the world-wide initiative to eradicate wild-type polioviruses. Two poliovirus-sensitive cell lines of human origin were used originally by the laboratories of the World Health Organisation (WHO) global poliovirus network. However, the cell lines used, Hep2 and RD, also support cytopathic growth of a variety of non-poliovirus enteroviruses. This can make detection of polioviruses in samples with mixtures of viruses difficult and time consuming. The development of mouse cell lines that express the gene for the human cellular receptor for polioviruses allows selective poliovirus culture, because very few non-poliovirus enteroviruses grow in these murine cells. A WHO Collaborative Study was initiated to test one such cell line, L20B, and to compare under routine conditions the sensitivity and selectivity of L20B cells against RD and Hep2 cells. Five laboratories in countries endemic or recently endemic for wild polioviruses participated. A total of 425 samples were tested prospectively in all three cell lines and there was a clear and consistent trend for greater sensitivity for polioviruses in L20B cells. Overall, 148/160 polioviruses were detected in L20B cells compared with 89/160 in RD and 98/ 160 in Hep2. In part, this finding was due to detection in L20B cells of polioviruses from samples that also contained non-poliovirus enteroviruses in which the poliovirus was masked in RD or Hep2 cells. However, L20B cells were also significantly more sensitive for poliovirus than either RD or Hep2 cells in three of the five study laboratories. The L20B cells were completely selective for polioviruses, as 0/89 wild type non-poliovirus enteroviruses produced cytopathic effect in L20B cells. Finally, L20B cells provided a diagnosis of poliovirus infection in the same time as RD and Hep2 cells from samples that contained poliovirus only, but substantially more quickly for samples that contained another enterovirus. Taken together, these data indicate that L20B cells simplify primary diagnosis of poliovirus from clinical samples and as a result they have been introduced for routine use by laboratories of the WHO global poliovirus network.