Article

Incidence of Haemophilus influenzae Type b Disease in The Gambia 14 Years after Introduction of Routine Haemophilus influenzae Type b Conjugate Vaccine Immunization

Child Survival Theme, Medical Research Council Unit, The Gambia.
The Journal of pediatrics (Impact Factor: 3.79). 07/2013; 163(1 Suppl):S4-7. DOI: 10.1016/j.jpeds.2013.03.023
Source: PubMed

ABSTRACT

Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine.
This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002.
The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100 000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months.
Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose.

Full-text

Available from: Claire Oluwalana, Feb 06, 2015
Incidence of
Haemophilus inuenzae
Type b Disease in The Gambia
14 Years after Introduction of Routine
Haemophilus inuenzae
Type b
Conjugate Vaccine Immunization
Claire Oluwalana, MBBS
1
, Stephen R. C. Howie, FRACP
1
, Ousman Secka, MSc
1
, Readon C. Ideh, FWACP
1
,
Bernard Ebruke, FMCPaed
1
, Sana Sambou, MSc
2
, James Erskine, MB, BS, MRCGP
3
, Yamundow Lowe, MPH
2
,
Tumani Corrah, FWACP
1
, and Richard A. Adegbola, PhD
1,4
Objective Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in
1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib
disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the
question of the need for a booster dose. The objective of this study was to determine the incidence of invasive
Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine.
Study design This hospital-based clinical and microbiolo gical Hib disease surveillance in 3 hospitals in the
western region of The Gambia was undertaken between October 2007 and December 2010 applying the same
methods used in a previous Hib vaccine effectiveness study in 1997-2002.
Results The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained
below 5 cases per 100 000 children during 2008-2010. The median age of patients with any invasive Hib disease
was 5 months.
Conclusion Hib conjugate vaccination as a primary 3-do se course in The Gambia remains highly effective in
controlling invasive Hib disease, and cur rent data do not support the introduction of a booster dose. (J Pediatr
2013;163:S4-7).
I
nvasive Haemophilus influenzae type b (Hib) disease, manifesting primarily as meningitis, pneumonia, and septicemia, re-
mains a major cause of childhood morbidity and mortality in unvaccinated populations, most of which reside in the devel-
oping world.
1
In 2005, we reported the disappearance of invasive Hib disease in The Gambia after the introduction of routine
immunization with the polyribosylribitol phosphate-tetanus toxoid Hib conjugate vaccine, despite irregular vaccine supplies
and suboptimal vaccine coverage.
2
The incidence of Hib meningitis, the most reliably detected form of invasive Hib disease,
dropped from >200 per 100 000 in 1990-1993 (before the advent of the vaccine) to 0 per 100 000 in 2002 in children aged <1
year, and from 60 cases per 100 000 to 0 cases per 100 000 in children aged <5 years. The prevalence of Hib carriage decrea sed
from 12% to 0.25% in children aged 1-2 years during this period, indicating the potential role of a herd immunity effect.
Systematic surveillance was stopped after 2002, but in 2005-2006, 5 cases of invas ive Hib disease (3 meningitis, 1 septicemia,
and 1 pneumonia ) came to light nonsystematically in an area with a population of children aged < 5 years of approximately
100 000 (2003 census data), for a minimum Hib meningitis incidence of 3 per 100 000 children aged <5 years.
3
The age distri -
bution of this small number of patients (median, 15 months; range, 0-36 months) was older than reported previously (where
80% of patients were aged <12 months), and there were examples of apparent vaccine failure, but nonetheless the cause of this
reemergence was not clear. No evidence of a hypervirulent strain was found.
The reemergence of Hib disease in The Gambia raised questions about the long-term effectiveness of Hib conjugate vaccine
in such settings, particularly when a booster dose is not given. Formal surveillance was reestablished in 2007 to address this
question, and the results of this surveillance are presented here.
Methods
Surveillance was carried out between October 22, 2007, and December 31, 2010, in
the same area and using the same methods as reported previously.
2
Surveillance
was performed in the western region of The Gambia, which had a total population
of 836 000 according to the 2003 census (60% of the population of The Gambia)
and includes urban, periurban, and rural areas. In this region, the population of
From the
1
Child Survival Theme, Medical Research
Council Unit, The Gambia;
2
Ministry of Health and Social
Welfare, Banjul, The Gambia;
3
Worldwide Evangelisation
for Christ International (WEC) Hospital, Sibanor, The
Gambia; and
4
GlaxoSmithKline Vaccines, Wavre,
Belgium
Funded by the GAVI Hib Initiative and Medical Research
Council UK.
Please see the Author Disclosures at the end of this
article.
0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc.
All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.03.023
Hib Haemophilus influenzae type b
S4
Page 1
children aged <5 years was 100 000 in 2003, and the estimated
mean population of these children was 128 000 in 2008-2010.
Surveillance focused on the detection of meningitis and
was conducted at 3 hospitals in the western region: Royal
Victoria Teaching Hospital, The Gambia’s largest referral
hospital, located in the capital of Banjul (urban); Medical Re-
search Council Hospital, Fajara (urban); and Worldwide
Evangelisation for Christ International Mission Hospital, Si-
banor (rural). Surveillance data were gathered in children
aged <10 years who were investigated as possible cases of in-
vasive Hib disease, typically those presenting with signs of
meningitis, pneumonia, or septicemia. Patients were treated
at the health facilities to which they presented following stan-
dard practices based on national guidelines.
Definite bacterial meningitis was diagnosed when a sample
of cerebrospinal fluid had a leukocyte count of >10 cells/mL
and bacteria were isolated. Hib pneumonia was diagnosed
when there was clinical or radiologic evidence of pneumonia
and Hib was isolated from blood or lung aspirate or pleural
aspirate. Septicemia was diagnosed when bacteria were
isolated from blood in the absence of a clinical focus of
infection. The population denominator for incidence calcu-
lations was based on linear extrapolation from 1993 and
2003 census data. Pointwise 90% likelihood-based CI were
calculated for incidence estimates, as was done in our original
effectiveness study report.
2
Hib was isolated and identified following standard me th-
odology. In addition, Hib isolates were confirmed by stan-
dard slide agglutination with type-specific antisera (Mure x
Diagnostics, Dartford, United Kingdom). The study was ap-
proved by the Gambian Government–Medical Research
Council Joint Ethics Committee (SCC/EC 1090).
Results
A total of 122 “po ssible” cases of invasive Hib disease were
identified by initial screening during the surveillance period
(101 from Royal Victoria Teaching Hospital, 15 from Medical
Research Council Hospital, and 6 from Worldwide Evangel-
isation for Christ International Mission Hospital). Of these,
9 cases of invasive Hib disease (5 meningitis and 4 septicemia)
were confirmed (Table). The 9 affected patients included 7
boys and 2 girls, with a median a ge of 5 months (range, 3-
13 months). One of the patients was HIV-positive, 4 patients
were HIV-negative, and in 4 patients HIV serostatus was un-
known. Two of the 9 patients were fully vaccinated with 3
doses, and 1 patient received 2 doses. Two patients had defi-
nitely or probably spent time outside The Gambia; one had
presented at Roya l Victoria Teaching Hospital 1 month after
arriving from Mali, and the other came from a village on the
Senegalese border. Four of the 9 patients died, 2 at admission
and 2 with sequelae some months later, whereas 4 patients
survived intact, and the outcome of 1 patient was unknown.
The overall case fatality rate for bacterial meningitis was
30% during the surveillance period.
The incidence of Hib meningitis in the years 1990-2010 is
shown in the Figure. The annual incidence of Hib meningitis
remained well under 5/100 000 children aged <5 years
throughout the surveillance period. The incidences of Hib
meningitis and all invasive Hib disease in children aged <5
years were, respectively, 0.8 and 0.8/100 000 in 2008, 2.3
and 2.3/100 000 in 2009, and 0.7 and 3.7/100 000 in 2010.
In children aged <1 year, the incidences of Hib meningitis
and all invasive Hib disease were, respectively, 4.6 and
4.6/100 000 in 2008, 13.3 and 13.3/100 000 in 2009, and 4.2
and 17.0/100 000 in 2010.
There were 60 proven cases of bac terial meningitis out of
the 122 possible Hib cases identified during the surveillance
period, of which 5 (8%) were due to Hib, 28 (47%) were
due to S pneumoniae, and the remainder were due to various
organisms, including Staphylococcus aureus (n = 2; 3%),
Escherichia coli (n = 2; 3%), Salmonella spp (n = 2; 3%),
Neisseria menin gitidis serogroup B (n = 2; 3%), Neisseria
meningitidis serogroup A/Y (n = 2; 3%), group B streptococci
(n = 2; 3%), Haemophilus influenzae type a (n = 1; 1.7%),
Acinetobacter spp (n = 1; 1.7%), Pseudomonas spp (n = 1;
1.7%), and Haemophilus parainfluenzae (n = 1; 1.7%).
Discussion
This study has shown that the incidence of Hib meningitis in
children remained low, although not absent, in The Gambia
Table. Features of the 9 cases of invasive disease from Hib detected through systematic surveillance in the western region
of the Gambia between October 22, 2007, and December 31, 2010
Date
Age,
mo Sex Hospital
Disease site
(meningitis/septicemia)
Number of Hib
vaccine doses Outcome
April 11, 2008 7 Female RVTH Meningitis 2 Apparent full recovery; HIV-negative
April 21, 2009 3 Male MRC Meningitis 1 Apparent full recovery; HIV-negative
June 1, 2009 Female RVTH Meningitis 0 Survival with sequelae; died 5 months later (with severe malnutrition
and gastroenteritis); HIV-positive
June 7, 2009 9 Male RVTH Meningitis Unknown Death on day 1 of admission; HIV serostatus unknown
March 15, 2010 3 Male MRC Septicemia 1 Survival with neurologic sequelae and failure to thrive; died at home
several months after discharge; HIV-negative
May 28, 2010 5 Male RVTH Meningitis 0 Unknown (taken away against medical advice); HIV-negative
August 10, 2010 4 Male MRC Septicemia Unknown Death on day 1 of admission; HIV serostatus unknown
August 11, 2010 6 Male MRC Septicemia 3 Apparent full recovery; refused HIV screening
October 6, 2010 13 Male MRC Septicemia 3 Apparent full recovery; refused HIV screening
MRC, Medical Research Council Hospital, Fajara; RVTH, Royal Victoria Teaching Hospital, Banjul.
Vol. 163, No. 1, Suppl. 1 July 2013
Incidence of Haemophilus influenzae Type b Disease in The Gambia 14 Years after Introduction of Routine Haemophilus
influenzae Type b Conjugate Vaccine Immunization
S5
Page 2
14 years after the introduction of Hib conjugate vaccine into
its routine Expanded Programme of Immunization EPI
schedule. The concerns about the possible reemergence of
disease with a different epidemiology raised by our earlier re-
port,
3
which had too few patients to allow for firm conclu-
sions, have not been borne out. The age distribution of
patients in more than 3 years of reestablished systematic
surveillance of disease was the same as that seen in the past
(median, 5 months), in contrast to the older age (median,
15 months) seen in the nonsystematically detected cluster
of cases of 2005-2006. Around this time, routine Hib vaccina-
tion was introduced into Senegal (Figure), which surrounds
The Gambia, decreasing the risk of exposure to an
unvaccinated population.
In the present study, as in our previous study, there is evi-
dence of apparent vaccine failure, with 2 of 9 patients receiving
complete vaccinations and 1 patient receiving 2 doses. The role
of HIV infection in these patients is not clear, given that only 5
patients were tested. Of those not tested, 2 died at presentation,
and the mothers of 2 refused HIV screening. The community
prevalence of HIV infection remains low in The Gambia, at ap-
proximately 2%.
4
Despite the instances reported herein, the
low overall incidence of disease suggests that the vaccine re-
mains highly effective. Based on these data, a booster dose of
Hib vaccine cannot be recommended in this setting.
This study has the limitation of all hospital-based surveil-
lance studies in that not all cases are likely to have been
ascertained. Nevertheless, meningitis is less subject to non-
ascertainment bias than other forms of the disease, which is
why we focused our surveillance on meningitis. As expected,
S pneumoniae was the predominant cause of meningitis
during this surveillance period, although only 1 case
was seen during the 15 months after introduction of the 7-
valent pneumococcal conjugate vaccine into routine use
in The Gambia in August 2009. This study has the great
strength of using the same sites, method s, and procedures
as in the previous surveillance, to which its results have
been compared.
Hib conjugate vaccination is known to be highly effective in
reducing the occurrence of invasive Hib disease in both indus-
trialized and developing country settings.
5
After a long delay,
there was a major push to get the vaccine introduced into de-
veloping countries, and in 2009 Hib conjugate vaccines were in
routine use in 83% of low-income countries eligible for vac-
cine support from the Global Alliance for Vaccines and Immu-
nisation.
6,7
Despite the vaccine’s success, however, there has
been evidence in some industrialized countries of resurgence
of disease, and in the United Kingdom an additional booster
dose at 12 months was added to the primary series at 2, 3,
and 4 months to counteract waning immunity.
8-10
In most
cases, it is too early to know whether a similar situation will oc-
cur in developing countries, and whether a booster dose will be
required in those settings; thus, a consistent global policy re-
mains elusive.
11,12
This is why the findings from 14 years of
routine use of Hib conjugate vaccine in The Gambia, the first
country in Africa to introduce the vaccine, are so important.
The application of these findings to similar settings in
Africa and elsewhere in the developing world requires cau-
tion, however. When they become available, local data on
vaccination delivery and cover age, the ages at which doses
are actually received, and levels of community carriage of
Hib and protective antibodies will allow a better understand-
ing of the dynamics of Hib protection in The Gambia. This in
turn will allow firmer judgments as to whether the long-term
success of the Gambian program, which includes no booster
dose, can be expected to apply more broadly in Africa and the
wider developing world. Collection and analysis of these data
are underway in The Gambia.
As the epidemiology of childhood disease changes in
developing countries, and as more vaccines are introduced,
continuing surveillance of Hib disease will be needed to
determine the continuing effectiveness of Hib conjugate
vaccine in the coming decades.
n
We thank the medical, nursing, and laboratory staff who cared for the
patients at the Royal Victoria Teaching Hospital, Medical Research
Figure. Incidence of Hib meningitis in children under age 5 years, cases per 100 000 population per year in the Gambia. The
dotted lines on either side of the measured incidence indicate 90% CI.
THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 163, No. 1, Suppl. 1
S6 Oluwalana et al
Page 3
Council Hospital, and Worldwide Evangelisation for Christ Interna-
tional Mission Hospital. We also thank Dr Momodou Jasseh (Medical
Research Council Gambian Unit demographer) for denominator data
for incidence calculations, Dr John Townend for statistical support,
Professor Kim Mulholland (Hib Initiative) for several review visits in
the course of the study, and Dr Karen Edmond (Hib Initiative) for ad-
vice and support.
Author Disclosures
R.A. is an employee of GlaxoSmithKline Vaccines (Belgium)
and has received grants for studies of bacterial diseases while
working as an employee of the Medical Research Council
Unit, The Gambia. The authors declare no conflicts of inter-
est, real or perceived.
Reprint requests: Stephen R. C. Howie, FRACP, Child Survival Theme,
Medical Research Council Unit, The Gambia, PO Box 273, Banjul, The
Gambia. E-mail: showie@mrc.gm.
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Incidence of Haemophilus influenzae Type b Disease in The Gambia 14 Years after Introduction of Routine Haemophilus
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