Am. J. Trop. Med. Hyg., 80(6), 2009, pp. 1033–1038
Copyright © 2009 by The American Society of Tropical Medicine and Hygiene
Haemophilus influenzae Type b Conjugate Vaccine Introduction in Mali:
Impact on Disease Burden and Serologic Correlate of Protection
Samba O. Sow,* Milagritos D. Tapia, Souleymane Diallo, Mamadou Marouf Keita, Mariam Sylla,
Uma Onwuchekwa, Marcela F. Pasetti, Karen L. Kotloff, and Myron M. Levine
Centre pour le Développement des Vaccins, Mali (CVD-Mali), Bamako, Mali; Center for Vaccine Development,
University of Maryland School of Medicine, Baltimore, Maryland; The Clinical Bacteriology
Laboratory and the Pediatric Service, Gabriel Touré Hospital, Bamako, Mali
Abstract. In Bamako, Mali, where surveillance revealed a high incidence of Haemophilus influenzae type b (Hib)
invasive disease, Hib conjugate vaccine was introduced into the Expanded Program on Immunization and the impact
assessed. Annual confirmed Hib hospitalizations for infants 0–11 months of age fell from 175/105 to 44/105 (P < 0.001);
among infants 6–7 months of age Hib hospitalizations fell from 377/105 to 69/105, (82% decrease, P < 0.001). Invasive
Streptococcus pneumoniae hospitalizations remained unchanged. In a baseline serosurvey, only 3/200 infants 6–7 months
of age (1.5%) had protective anti-polyribosylribitol phosphate (PRP) titers ≥ 0.15 μg/mL and 1(0.5%) had ≥ 1.0 μg/mL.
In serosurveys 18 and 30 months after vaccine introduction, 168/201 (84%) and 184/200 (92%) infants, respectively, had
titers ≥ 0.15 μg/mL and 141/201 (70%) and 163/200 (82%) had titers ≥ 1.0 μg/mL. Introduction of Hib vaccine led to rises
in anti-PRP seroprevalence, significant reductions in Hib disease, and all-cause hospitalizations, whereas S. pneumoniae
disease remained unchanged.
INTRODUCTION
MATERIALS AND METHODS
Mali, a land-locked Sahelian country in West Africa, falls
among the world’s six least developed nations.1 Approximately
10% of Malians reside in the capital region, Bamako, where
severely ill infants and young children requiring hospitalization are admitted to a government hospital, l’Hôpital Gabriel
Touré (HGT). A survey in 2000 revealed that 71% of admissions to HGT among children < 16 years of age were for presumed infectious diseases and 21% of all admitted children
died2; however, no clinical microbiology laboratory existed to
determine the agents causing these infections. In July 2002,
after a clinical bacteriology laboratory was established, systematic surveillance for invasive bacterial infections began. Within
24 months it became evident that invasive Haemophilus influenzae type b (Hib) infections constituted a major cause of hospitalizations.3 The Hib incidence was low in infants < 4 months
of age but rose precipitously to a peak of 370/105 among infants
6–7 months of age3; 18.2% of hospitalized infants 6–7 months
of age had invasive Hib disease.3 Revelation of this enormous
Hib disease burden led the Ministry of Health to apply to
the Global Alliance for Vaccines and Immunization (GAVI)
for support to introduce Hib vaccine into the Expanded
Program on Immunization (EPI). A three-step introduction
was planned, with Bamako (step 1, ~11% of the Malian infant
cohort) scheduled for July 2005, other urban centers (step 2)
for July 2006, and the remainder of the country (step 3) for July
2007. Ongoing systematic bacteriology laboratory-supported
clinical surveillance allowed us to measure the impact of vaccine introduction on the Hib disease burden. Because serum
IgG antibodies to Hib capsular polysaccharide, polyribosylribitol phosphate (PRP), constitute a correlate of protection
against invasive disease,4 in concert we monitored changes in
the seroprevalence of protective levels of anti-PRP in infants
6–7 months of age before and after Hib vaccine introduction
as an objective measure of vaccine coverage.
Systematic surveillance at HGT. Since July 2002, clinical
staff of the Center pour le Développement des Vaccins du
Mali (CVD-Mali) and HGT have been conducting systematic surveillance to detect invasive bacterial disease among
hospitalized children < 16 years of age.3,5 Age-eligible children presenting to the emergency department with fever
(≥ 39°C) or focal clinical findings suggestive of invasive bacterial infection (meningitis, septic arthritis, etc.) and requiring
hospitalization are referred to CVD-Mali staff by the evaluating clinicians.3,5 For economic and logistical reasons, surveillance proceeded from 8 am until midnight (during which 90%
of pediatric patients are admitted). A CVD-Mali physician
obtains informed consent, records clinical and epidemiologic
data, and obtains blood (and other relevant fluids) for culture
in the HGT Clinical Bacteriology Laboratory.3 The child’s clinician is promptly notified when a culture yields a bacterial
pathogen. The surveillance protocol and consent form were
reviewed by the Ethics Committee of the Faculté de Medécine,
Pharmacie et Odonto-Stomatologie, University of Bamako,
and by the Institutional Review Board of the University of
Maryland, Baltimore.3 This impact study focuses on children
< 24 months of age.
Surveillance for hospitalized invasive Hib cases from July 1,
2002 through June 30, 2005, preceding the introduction of Hib
conjugate vaccine into the EPI in Bamako for infants 6, 10, and
14 weeks of age, constitutes the baseline period. The 12-month
transition period began when Hib vaccine was introduced into
the Bamako EPI on July 1, 2005 and extended through June
30, 2006. July 1, 2006 through June 30, 2008 represents the first
24 months of the intervention period. During all three periods,
parents of 94–97% of children gave permission for cultures
to be obtained. The Malian National Directorate of Statistics
and Informatics provided annual Bamako mid-year population data by age strata.
Serosurveys. Serosurveys were undertaken before the introduction of Hib vaccine (May 2005) and 18 and 30 months
thereafter to measure the prevalence of protective levels of
serum PRP antibody among random samples of 200 infants
6–7 months of age in three of the six communes of Bamako.
* Address correspondence to Samba O. Sow, Centre pour le
Développement des Vaccins – Mali, Ex-Institut Marchoux, Bamako,
Mali, BP251. E-mail: [email protected]
1033
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SOW AND OTHERS
and post-introduction serosurveys were compared by χ2 or,
for a numerator < 5, two-tailed Fisher exact test.8 Incidence by
6 monthly periods (July 1, 2002–June 30, 2008) was assessed by
linear regression of Poisson incidence rates on time.8
This age group was chosen because it represented when Hib
disease incidence peaked and maternal IgG antibodies had
for the most part disappeared. In each survey, sera were collected from 100 infants residing in Djikoroni and Sébéninkoro
quartiers (Commune IV), 50 in Banconi quartier (Commune
I), and 50 in Kalabankoro quartier (Commune VI). During the
initial serosurvey, standard immunization survey methods randomly identified the first household, after which a prescribed
route was followed to access additional households until the
required number of infants was attained. In the last two serosurveys, infants in Djikoroni and Banconi were selected using
a computer-generated random list of age-eligible children
compiled from the demographic surveillance database that
had been established in these quartiers since the initial survey;
infants in Sébéninkoro and Kalabankoro were identified as
during the initial survey. Informed parental consent was solicited to collect 2 mL of blood by venipuncture to measure IgG
anti-PRP by enzyme-linked immunosorbent assay (ELISA)
by a previously reported method, with slight modifications.6,7
Immulon II plates were coated with HbO-HA antigen (lot
#17) at 1 μg/mL. Samples were run in serial dilutions, in duplicate wells. The HRP-labeled goat anti-human IgG (Jackson
ImmunoResearch Laboratories, West Grove, PA) was used as
conjugate. Titers were calculated by interpolation of regression-corrected Absorbance values in the standard curve of the
Center for Biologics Evaluation and Research (CBER) Food
and Drug Administration (FDA) reference serum lot #1983
(70 μg/mL) and reported in μg/mL. During the two serosurveys conducted after the introduction of Hib vaccine, families
of enrolled infants were asked to present their infant’s immunization card. If a card was shown, the number of Hib vaccine
doses received was recorded.
Estimates of vaccine effectiveness. Vaccine effectiveness
(%VE) was estimated by the formula (1-RR [incidence rate
ratio]) × 100 for children older than 4 months (i.e., those old
enough to have received 2–3 doses of Hib vaccine). Incidence
rate ratios for infants 4–11 months and children 4–23 months
of age were calculated using the baseline period versus both
years and versus the second year of the intervention period.
Confidence interval (CI) estimation for %VE used a binomial transformation for the proportion of Hib cases occurring
during the intervention period.
Statistical analysis. Data captured using Microsoft Access
2000 were stored in Microsoft SQL Server 2000 (Microsoft,
Redwood, WA). Incidence rates during baseline and intervention periods were compared using a χ2 statistic for Poisson rates.
Proportions of seropositive 6–7 month olds during baseline
RESULTS
Incidence of invasive Hib. Table 1 shows the infant and toddler population of Bamako and the number of cases and incidence of confirmed, invasive Hib disease among hospitalized
children during the 36-month baseline, the 12-month transition, and the two individual years of the intervention period.
During baseline, the incidence of hospitalized cases of invasive
Hib disease was 5-fold higher in infants than toddlers (Table 1);
94% (251/267) of infant cases occurred in the age range 4–11
months and the peak annual incidence, 377 cases/105, was
observed in 6–7 month of age.
Among infants 0–11 months of age, the incidence of invasive Hib disease fell progressively during each ensuing semester of the transition and intervention periods (P < 0.001, linear
regression) (Figure 1). By the second year of the intervention period, the Hib incidence (30 cases/105) had decreased by
83% from the mean annual incidence of the baseline period
(175 cases/105) (P < 0.001) (Table 1). The incidence began to
fall during the second semester of the transition year (January
6–June 6, Figure 1) as vaccinated infants accumulated. By contrast, the incidence of invasive Hib disease among 12–23 month
olds did not decrease until the intervention period (Table 1). In
the high risk 6–7 month olds, the incidence dropped from 377
cases/105 during baseline to 53 cases/105 by the second year of
the intervention period, a decrease of 86% (P < 0.001).
During the three baseline years, the annual number of fatalities among confirmed Hib cases 0–11 months of age admitted to HGT was 10, 7, and 14 (mean 10.3). Infant Hib deaths
remained at 10 during the transition period but then dropped
to 3 and 4 deaths, respectively, during years 1 and 2 of the
intervention period.
Incidence of invasive pneumococcal infections. To verify
that the fall in incidence of invasive Hib disease was specific
to introduction of Hib conjugate vaccine and not to a secular trend or a broad change in pediatric ambulatory care,
we analyzed the hospitalized cases of invasive disease resulting from Streptococcus pneumoniae in the 0–11 month old age
group. Figure 1 compares the incidence of hospitalizations as a
result of invasive pneumococcal versus Hib disease in infants
0–11 months of age calculated in 6-month blocks. The annual
incidence of S. pneumoniae disease remained stable among
Table 1
Hospitalized cases of culture-confirmed invasive Haemophilus influenzae type b (Hib) disease, l’Hôpital Gabriel Touré, Bamako, Mali, July 1, 2002
through June 30, 2008
Baseline period
(July 1, 2002–June 30, 2005)
Age group
0–11
months
12–23
months
6–7
months
Transition period
(July 1, 2005–June 30, 2006)
Mean annual
Mean annual Mean annual Hib incid. per
pop’n, Bamako Hib cases
105 children
Annual pop’n, Annual
Bamako
Hib cases
Intervention period, year 1
(July 1, 2006–June 30, 2007)
Annual Hib
incid. per 105
children
Intervention period, year 2
(July 1, 2007–June 30, 2008)
Annual Hib
Annual Hib
Annual pop’n, Annual incid. per 105 Annual pop’n, Annual Hib
incid. per
Bamako
Hib cases
children
Bamako
cases
105 children
50,885
89
175
53,782
69
128
55,299
32
58
56,858
17
30
44,525
15
34
47,059
20
43
48,386
5
10
49,751
5
10
8,498
32
377
8,981
20
223
9,234
8
87
9,495
5
53
1035
IMPACT OF HIB VACCINE IN MALI
intervention (65/105) (Table 3), vaccine effectiveness (VE)
was 75% (95% CI, 66–82%); VE in year 2 of the intervention
period (incidence 44/105) was 83% (95% CI, 72–90%). Among
children 4–23 months of age, the Hib vaccine similarly showed
74% VE (95% CI, 66–81%) over both years of the intervention period and 81% VE (95% CI, 71–88%) in year 2.
All-cause hospitalizations. Because multiple culture-negative
cases of invasive and pneumonic Hib disease are known to
occur for each culture-positive case, we analyzed the incidence
of all-cause hospitalizations before and after introduction of
Hib vaccine among infants 4–11 months of age. We focused
on this age group to assess direct protection (younger infants
would be only indirectly protected), and because this age group
contributed 80% of all cases among children < 24 months of
age during baseline. The incidence of all-cause hospitalizations
among infants 4–11 months of age dropped by 29.2% from the
baseline to the intervention periods (P < 0.001) (Table 3).
Figure 1. Incidence of invasive Haemophilus influenzae type b
(Hib) disease and invasive Streptococcus pneumoniae disease in
Malian infants 0–11 months of age by 6-month calendar periods, July
2002 through June 2008. Vertical lines indicate 95% confidence interval (CI). Whereas the incidence of S. pneumoniae disease remained
unchanged, a progressive fall in incidence of Hib disease occurred
after introduction of vaccine (P < 0.001, linear regression of incidence
rates on time).
DISCUSSION
0–23 month olds during baseline (83 /105) and intervention periods (77/105) (P = 0.5), whereas Hib incidence dropped by 74%
from baseline (110/105) to intervention (28/105) (P < 0.001).
Survey to estimate Hib immunization coverage and the
prevalence of serum anti-PRP antibody. The baseline serosurvey in 6–7 month olds before the introduction of Hib vaccine
revealed that only 1.5% of 200 infants had serum concentrations of PRP antibody ≥ 0.15 μg/mL and just one infant had
an antibody concentration ≥ 1.0 μg/mL (Table 2). By the third
serosurvey, over 80% of 6–7-month-old infants at this peak age
of susceptibility now had ≥ 1.0 μg/mL of serum PRP antibodies (P < 0.001) (Table 2). Moreover, the proportion of infants
with PRP antibody ≥ 0.15 μg/mL or ≥ 1.0 μg/mL detected on
the third serosurvey was slightly (~8–12%) but significantly
greater than observed during the second survey (Table 2).
The proportions of families that produced the infant’s
immunization record during the second and third serosurveys were 187 of 201 (93%) and 180 of 200 (90%). The percentage of infants with immunization records who received at
least one dose of Hib conjugate and the proportion who got
all three vaccine doses are summarized in Table 2. Prevalence
and geometric mean concentration of serum PRP antibody
rose progressively with the number of doses of Hib vaccine
received (Figure 2).
Estimates of vaccine effectiveness. Comparing the incidence of invasive Hib disease among infants 4–11 months of
age in the baseline period (259/105) versus both years of the
Five factors led the Malian government to introduce Hib
conjugate vaccine into the Malian EPI: 1) enormity of the Hib
invasive disease burden revealed by systematic, laboratorysupported surveillance; 2) existence of a well-tolerated conjugate vaccine with an excellent effectiveness track record
in industrialized and transitional countries9–11; 3) potential to
receive donated vaccine for the cohort of Malian infants for
5 years through the GAVI Fund; 4) advocacy and support for
the introduction of Hib vaccine from the highest levels of the
Malian government; and 5) availability of practical pentavalent vaccine formulations that allow Hib conjugate and hepatitis B vaccines to be given in combination with diphtheria,
tetanus, pertussis (DPT) vaccine via a single injection.12
The impact of Hib vaccine introduction on disease burden in
Bamako was monitored by continuing surveillance for cases of
invasive Hib disease admitted to HGT. An impressive decline
was observed, with cases among infants falling by more than
80% by the second year of the 24-month intervention period.
The decline in Hib incidence in toddlers (age 12–23 months)
did not commence until 1 year later when the initial vaccinated infant cohort reached toddler age. By analogy, cultureconfirmed hospitalized cases of Hib disease represent only
the “eyes and ears of the hippopotamus,” as a much larger
“submerged” Hib disease burden remains largely undetected.
Indeed, vaccine probe studies have estimated that ~5 cases of
non-bacteremic Hib pneumonia,13–15 and ~3–8 cases of culturenegative invasive Hib focal infection (e.g., purulent meningitis)
Table 2
Serum IgG PRP antibody in infants 6–7 months of age in surveys performed before and at two time points after the introduction of Haemophilus
influenzae type b conjugate vaccine into the Expanded Program on Immunization in Bamako, Mali
Survey
Baseline
18 months after
initiation of the Hib
vaccine program
30 months after
initiation of the Hib
vaccine program
Total infants in random
sample
No. (%) with
immunization records
No. (%) who got at least
1 dose of Hib vaccine*
No. (%) who got 3 doses
of Hib vaccine*
No. (%) with PRP
antibody ≥ 0.15 μg/mL†
No. (%) with PRP
antibody ≥ 1.0 μg/mL†
200
–
–
–
3‡ (1.5)
201
187 (93.0)
167 (89.0)
138 (73.8)
168§ (83.6)
141** (70.1)
200
180 (90.0)
175 (97.2)
146 (81.1)
184¶ (92.0)
163†† (81.5)
* Of the infants whose parents showed an immunization record.
† Of all infants in the survey.
‡ vs. § or ¶, P < 0.001; ll vs. ** or ††, P < 0.001, compared by two-tailed Fisher exact test.
§ vs. ¶, P = 0.010 and ** vs. ††, P = 0.008, compared by χ2 test.
1|| (0.5)
1036
SOW AND OTHERS
Figure 2. The percentage of randomly selected 6 to 7 month olds
with serum IgG anticapsular polysaccharide (PRP) antibody concentrations consistent with short-term protection (≥ 0.15 μg/mL) or
long-term protection (≥ 1.0 μg/mL), in relation to the number of Hib
vaccine doses received (as recorded on infants’ vaccination cards).
Shown are the results of surveys conducted in (A) 2007 and (B) 2008.
The prevalence of antibody increased with the number of doses of Hib
vaccine received. The geometric mean concentration (GMC) of PRP
antibody also increased with the number of doses.
occur for every culture-confirmed Hib case.16 Partially treated,
culture-negative cases are anticipated in Bamako because
antibiotic usage is promiscuous in many venues, including
government health centers, pharmacies, and even traditional
Table 3
A comparison of the incidence of hospitalizations from all causes, confirmed invasive Hib disease and confirmed invasive pneumococcal
disease among infants 4–11 months of age before and after introduction of Hib conjugate vaccine into the Expanded Program on
Immunization
Incidence per 105
infants age 4–11 months
All-cause
hospitalizations
Confirmed Hib
disease
Confirmed
Streptpcoccus
pneumoniae disease
Baseline*
Intervention†
Percent
decrease (%)
P value‡
2041
1444
29.2
< 0.001
259
65
75.0
< 0.001
113
113
0.0
0.99
* Mean annual incidence in the period July 2002 to June 2005.
† Mean annual incidence in the period July 2006 to June 2008.
‡ Compared by χ2 statistic.
healers. Thus, in evaluating the impact of vaccine introduction,
one would expect that many additional cases of disease were
prevented beyond the enumerated culture-confirmed cases.
Some support for this contention comes from the analysis of
all-cause hospitalizations among infants 4–11 months of age,
which fell by 29.2% between the baseline and intervention
periods (Table 3). Before Hib vaccine introduction, 80% of
all cases in children < 24 months of age occurred in this age
range. Comparing the decrease in incidence of all-cause hospitalizations (596 fewer hospitalizations/105) with confirmed
Hib cases (195 fewer cases/105) from baseline to intervention
(Table 3), one estimates that approximately two culture-negative Hib cases (total 401 cases) were prevented for each culture-positive case (total 195 cases). Thus, the actual Hib disease
hospitalizations averted may have been ~596/105, not 194/105,
indicating that Hib vaccination in Mali had a broad impact.
Moreover, the impact at the population level is surely even
greater than assessed just by hospitalizations, because many
children treated in ambulatory health centers and by traditional healers have invasive Hib disease but are not cultured
and yet other children never access health care.
The incidence of invasive pneumococcal disease remained
virtually unchanged in the same age groups where Hib disease
plummeted (Table 3, Figure 2). Streptococcus pneumoniae is
also transmitted by the respiratory route and induces identical clinical syndromes (meningitis, sepsis, septic arthritis, etc.)
as Hib via a similar pathogenesis. Thus, the stable incidence of
invasive pneumococcal disease indicates the vaccine-related
specificity of the decline in invasive Hib disease and in allcause hospitalizations.
Serum PRP antibodies are widely accepted as a correlate of protection and protective thresholds are recognized.4
Therefore, we used this serologic marker as an objective measurement of Hib immunization coverage and capacity of the
Malian EPI to deliver the new vaccine. A PRP antibody level
≥ 0.15 μg/mL represents a protective level present when that
serum specimen was obtained, whereas ≥ 1.0 μg/mL suggests
long-term protection.4 In the baseline serosurvey before Hib
vaccine introduction, only 3 of 200 infants age 6–7 months had
protective levels of PRP antibody and only one had a titer
≥ 1.0 μg/mL. These serologic data document the immunologic
susceptibility of infants at this age and explain their extremely
high attack rates of invasive Hib disease. The seroprevalence
data in unvaccinated Malian 6–7 month olds resemble seroprevalence data from unimmunized infants 9 months of age
in neighboring Niger who served as controls in a Hib conjugate vaccine immunogenicity study in the 1990s; among these
infants only 1/39 (2.6%) had a serum PRP antibody concentration ≥ 1.0 μg/mL (measured by Farr type radioimmunoassay).17
The two subsequent serosurveys conducted in Bamako during
the intervention period (18 and 30 months after initiation of
the Hib vaccine program) showed that 70.1% and 81.5% of
infants 6–7 months of age now possessed serum PRP antibody
at a concentration of ≥ 1.0 μg/mL (P < 0.001 versus baseline).
These antibody prevalences correlate well with estimates of
the immunization coverage for three doses of Hib vaccine
(73.8% and 81.1%), as determined by inspection of infant
immunization records during the surveys (Table 2) and with
the reductions in disease incidence (Table 1). Higher immunization coverage for three Hib vaccine doses would likely have
been observed if we surveyed slightly older infants, because
many infants receive vaccinations several weeks later than
1037
IMPACT OF HIB VACCINE IN MALI
the target age. However, we deemed it important to ascertain
coverage at the peak age (6–7 months) of susceptibility.
Our favorable experience in Bamako leads us to propose
that this serosurvey method be explored further as a useful
means to document the susceptibility of infant populations
to Hib and to monitor objectively the effectiveness of EPI
services in delivering Hib vaccine to infants in different geographic areas and settings. This serosurvey tool nicely complements methods that measure Hib disease incidence before and
after introduction of Hib vaccine, such as we used in Bamako
and that have been previously used in The Gambia,18 South
Africa,19 Kenya,20 and Malawi.21 Concern has been raised that
administrative estimates of vaccine coverage (number of doses
putatively given divided by the target population), even if subjected to data quality audits, do not correlate well with vaccine
coverage estimates based on random sample-based immunization surveys.22 Accordingly, it has been proposed that serosurveys be performed in conjunction with immunization record
surveys to document in an objective manner immunization
coverage, population susceptibility, and quality of local immunization services.22,23 The impact of Hib vaccine introduction
may be considered a composite of VE and vaccine coverage
in the local population. The VE largely depends on the antiPRP responses elicited by the vaccine; the same Hib conjugate
can stimulate substantially different anti-PRP responses from
one population to another.24,25 The Hib VE among children
2–59 months of age in Malawi was estimated by a case-control
method to be 93% (95% CI, 67–98%) for recipients of three
doses of vaccine.21 The VE among children < 24 months of age
in Kilifi, Kenya by 1-incidence RR method was 87% (95% CI,
66–96%).20 Using the RR method in Bamako, we calculated a
VE of 81% among children 4–23 months of age during the second year of the intervention period.
The Malian Hib vaccine experience adds further data to
the burgeoning evidence base confirming the public health
importance of this vaccine for infants in sub-Saharan Africa.
Introduction of Hib vaccine in nearby Gambia and demonstration of its impact followed a pioneering large-scale controlled
field trial that assessed the efficacy of Hib conjugate vaccine
against both invasive disease and pneumonia of likely bacterial etiology.13,18,26,27 Kenya was another early introducer of Hib
vaccine but did so without quantifying the Hib burden beforehand.20 Cowgill and others20 note that, as a consequence, “there
was little enthusiasm among Kenya’s public health community to maintain the program when GAVI support was due to
expire.” Fortunately, the availability of Hib burden data in Kilifi
District from ongoing hospital-based surveillance before and
after Hib vaccine introduction ultimately provided the Kenyan
health authorities with invaluable evidence of effectiveness. The
Ugandan experience after Hib vaccine introduction,28 although
confined to measurement of the impact on meningitis and with
only 1 year of baseline, nevertheless shares many similarities to
what was observed in Mali. Evidence of the impact of Hib vaccine introduction in Rwanda29 and Ghana,30 based mainly on
changes in the occurrence of clinical meningitis, is more tenuous. The Malian Hib vaccine experience, a public health success, reinforces the collective African evidence base.
Received December 18, 2008. Accepted for publication February 11,
2009.
Acknowledgments: We thank Patrick Murray for invaluable early
help in establishing the Clinical Bacteriology Laboratory at l’Hôpital
Gabriel Touré, James D. Campbell for assistance in clinical activities, William C. Blackwelder for biostatistical assistance, and Mardi
Reymann and Lilian Cuberos from the CVD Applied Immunology
Section for technical assistance measuring Hib antibodies. During
the period 2002–2008, the activities described in this report received
enthusiastic support from the incumbent Ministers of Health
(Fatoumata Nafo Traoré, Keita Rokiatou N’Diaye, Maiga Zeinab Mint
Yuba, and Oumar Ibrahim Touré) and their respective Vice Ministers
(Abdramane Tounkara, Mamadou Adama Kane, Daba Diawara, and
Lansseni Konaté). We also acknowledge the staunch support for Hib
vaccine introduction provided by His Excellency, Amadou Toumani
Touré, President of the Republic of Mali.
Financial support: Grants from the Bill and Melinda Gates Foundation
(#1187 and #32470) and a grant from the Rockefeller Foundation to
M. M. Levine.
Authors’ addresses: Samba O. Sow and Uma Onwuchekwa, Ministry
of Health, Centre pour le Développement des Vaccins – Mali,
Ex-Institut Marchoux, Bamako, Mali, BP251, Tel: 223-20-23-6031,
Fax: 223-20-22-2883, E-mails: [email protected] and
[email protected]. Milagritos D. Tapia, Marcela
F. Pasetti, Karen L. Kotloff, and Myron M. Levine, University of
Maryland School of Medicine, Center for Vaccine Development,
685 W. Baltimore St., Rm. 480, Baltimore, MD 21201, Tel: 410-7065328, Fax: 410-706-6205, E-mails: [email protected],
[email protected], [email protected].
edu, and [email protected]. Souleymane Diallo,
Mamadou Marouf Keita, and Mariam Sylla, The Clinical Bacteriology
Laboratory and the Pediatric Service, Gabriel Touré Hospital, Bamako,
Mali, E-mails: [email protected] and [email protected].
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