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Indian Pediatr 2015;52: 205 -211 |
|
Hospital-based Surveillance of Invasive
Pneumococcal Disease and Pneumonia in
South Bangalore, India
|
R Nisarga, *R Premalatha,
#Shivananda, KL Ravikumar, U Shivappa, A
Gopi, SB Chikkadasarahalli, ‡R
Batuwanthudawe, $PE
Kilgore, ‡SA Kim,
**I Balter, **S Jouve,
##J Ye and ##M
Moscariello
From Kempegowda Institute of Medical Sciences; *Vani
Vilas Hospital, Bangalore Medical College & Research Institute; #Indira
Gandhi Institute of Child Health, Bangalore, India; ‡International
Vaccine Institute, Seoul, Korea; $Wayne State
University, Detroit, MI, USA;**Pfizer Inc, Paris, France; and
##Pfizer Inc, Collegeville, PA, USA.
Correspondence to: Dr Ramalingowda Nisarga,
Kempegowda Institute of Medical Sciences,. 121/13, T. Mariyappa Road,
1st Block, Jayanagara, Bangalore 560011, India.
Email: [email protected]
Received: June 14, 2013;
Initial review: July 18, 2013;
Accepted: January 07, 2015.
|
Objective: To estimate the
incidence of invasive pneumococcal disease and pneumonia, distribution
of pneumococcal serotypes, and antibiotic susceptibility in children
aged 28 days to <60 months.
Design: Hospital-based surveillance.
Setting:; South Bangalore, India.
Participants: 9950 children aged 28 days to <60
months with clinical suspicion of invasive pneumococcal disease or
pneumonia.
Results: The estimated at-risk population
included 224,966 children <5 years of age. Forty cases of invasive
pneumococcal disease were identified. Estimated invasive pneumococcal
disease incidence was 17.8/100,000 with incidence being highest among
children aged 6 months to <12 months (49.9/100,000). Clinical pneumonia
syndrome was the most frequent diagnosis (12.5/100,000). Pneumococcal
serotypes included: 6A (n=6, 16.7%); 14 (n=5, 13.9%); 5 (n=4,
11.1%); 6B (n=4, 11.1%); 1, 18C, and 19A (n=3 each, 8.3%);
9V (n=2, 5.6%); and 3, 4, 10C, 18A, 18F, and 19F (n=1
each, 2.8%). Serotypes 6A, 14, 6B, 1, 18C, 19A, 9V, 4, 10C, and 18A
showed antibiotic resistance. Clinical pneumonia incidence was
2109/100,000, with incidence being highest among children aged 28 days
to <6 months (5033/100,000). Chest radiograph-confirmed pneumonia
incidence was 1114/100,000, with incidence being highest among children
aged 28 days to <6 months (2413/100,000).
Conclusion: Invasive pneumococcal disease and
pneumonia were found to be common causes of morbidity in young children
living in South Bangalore, India.
Keywords: Epidemiology, Streptococcus pneumoniae, Surveillance.
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Globally, approximately 541,000 children aged less
than 5 years die from pneumococcal disease annually with a
disproportionate number of deaths occurring in developing countries [1].
In India, recent data examining the overall incidence of invasive
pneumococcal disease and pneumococcal serotype distribution are scarce.
Pneumococcal conjugate vaccines are not currently
included in the national immunization program in India. To evaluate the
health impact of a national immunization program with pneumococcal
conjugate vaccine, it is crucial to assess disease burden and serotype
distribution before vaccine introduction [2]. Pneumonet (Pan Asia
Epidemiologic Surveillance Network) is a 2-year hospital-based
surveillance study that assessed the burden of invasive pneumococcal
disease in India, Thailand, Indonesia, and the Philippines. The primary
objective was to estimate incidence rates of invasive pneumococcal
disease and pneumococcal serotype distribution in children aged 28 days
to less than 60 months. For each area of surveillance, the secondary
objectives were to estimate incidence rates of clinical pneumonia and
chest radiograph-confirmed pneumonia; to estimate case fatality rates
for invasive pneumococcal disease and clinical and chest
radiograph-confirmed pneumonia; describe antibiotic resistance rates of
invasive pneumococcal isolates and serotype distribution of these
resistant isolates; assess neurological sequelae of pneumococcal
meningitis; and describe the risk factor distribution for invasive
pneumococcal disease.
Methods
This was a hospital-based study with 3 participating
hospitals in South Bangalore, India: Kempegowda Institute of Medical
Sciences Hospital, Vanivilas Hospital, and Indira Gandhi Institute of
Child Health. These are the main hospitals catering to children from
South Bangalore, and were chosen based on their ability to conduct the
study assessed by a pre-determined set of criteria. The study was
approved by the institutional review board/independent ethics committee.
The parent(s) or legal guardian(s) of participants completed the
informed consent process.
Final case diagnoses were recorded either on Day 10
or the day of hospital discharge, whichever occurred first. Case
definitions were as follows:
• Sepsis: Presence of danger signs (unable to
drink, lethargy, hypothermia, severe malnutrition, convulsions) with
or without pneumonia clinical syndrome (meningitis excluded).
• Meningitis clinical syndrome: At least one of
the following usually with fever: stiff neck, altered or decreased
consciousness, bulging fontanelle, toxic appearance, lethargy, poor
sucking and irritability, petechial or purpural rash, convulsions
[3,4]
• Invasive pneumococcal disease (IPD) Isolation
of S. pneumoniae from a sterile body site
• Definite pneumococcal meningitis: Isolation of
S. pneumoniae by culture from the cerebrospinal fluid (CSF)
or a blood culture of a subject with >10 white blood cells per 1 µL
of CSF, and CSF protein >100 mg/dL or CSF glucose <40 mg/dL; or
glucose CSF-to-serum ratio <0.6; or a positive result from a
nonculture method for identification of S. pneumoniae in the
CSF [3,4].
• Probable pneumococcal meningitis: CSF with >10
white blood cells per 1 µl and other evidence suggestive of
pneumococcal infection; or isolation of S. pneumoniae in the
blood by culture or nonculture method in a subject admitted for
meningitis clinical syndrome, who lacked the CSF characteristics for
definite pneumococcal meningitis; or CSF not obtained [3,4].
• Clinical pneumonia syndrome: Tachypnea (>50
breaths/minute if subject was aged <12 months or >40 breaths/minute
if subject was aged 12 months to <60 months) and/or cough and/or
difficulty breathing.
• Chest radiograph (CXR)-confirmed pneumonia:
Lobar consolidation and/or pleural effusion [3].
• C-reactive protein (CRP) + CXR-confirmed
pneumonia: CXR-confirmed pneumonia, or clinical pneumonia with an
abnormal CXR result plus a CRP value
³40 mg/L [4].
• Bacteremia: Isolation of bacteria from the
blood; S. pneumoniae was isolated from the blood for
pneumococcal bacteremia.
The study enrolled a sample of convenience consisting
of all children aged 28 days to 36 months residing in the surveillance
area from February 27, 2009 to February 26, 2011, who presented to any
of the study hospital with a measured temperature or history of measured
temperature ³39.0°C
within 24 h prior to screening; or with clinical suspicion of pneumonia,
meningitis, sepsis, or other invasive pneumococcal disease (e.g.,
arthritis, osteomyelitis, peritonitis), regardless of temperature; and
children aged >36 months to <60 months with clinical suspicion of
pneumonia, meningitis, sepsis, or other invasive pneumococcal disease,
regardless of temperature. Signs and symptoms used to identify suspected
meningitis included fever, headache, stiff neck, nausea, vomiting,
seizures, and lethargy. Signs and symptoms of suspected pneumonia
included fever, cough, shortness of breath, rapid breathing, sputum
production, lack of appetite, and lethargy. Signs and symptoms of sepsis
included fever, lethargy, and lack of appetite. Children with suspected
or diagnosed dengue fever, malaria, or chronic or relapsing/recurring
febrile illness, with or without laboratory confirmation, were excluded.
For each subject, up to 3 study visits were planned.
The first visit was for screening and enrolment. The second visit was
for collection of data related to final diagnosis and outcome. This
visit was performed either on Day 10 after enrollment or on the day of
hospital discharge (whichever came first) in hospitalized subjects, all
subjects whose cultures yielded S. pneumoniae, and those
in whom there was clinical suspicion of meningitis. The third visit was
performed 3-4 months after enrollment in subjects with a final diagnosis
of probable or definite pneumococcal meningitis. At this follow-up
visit, a neurologic examination was conducted for evaluation of
neurologic sequelae.
Sample collection and laboratory testing: In all
subjects who met the inclusion criteria, a medical history was taken by
the treating physician, risk factors for invasive pneumococcal disease
were recorded by interviewing the parents, and a blood specimen was
collected. Risk factors recorded included residence (urban/not urban),
antibiotic use in the previous 7 days, use of herbal or traditional
medicine in the previous 7 days, attendance at daycare or kindergarten,
smokers in the household, exposure to cooking smoke, malnutrition,
number of individuals in the household, number of children <60 months,
number of sleeping rooms in the house, and presence of underlying
medical illnesses or chronic conditions known to increase the risk for
pneumococcal disease. CSF was collected for culture when meningitis was
suspected. Specimens from other sterile sites (e.g., pleural
fluid) were collected as per routine medical practice. Blood, CSF, and
pleural fluid cultures were performed at the Central Research
Laboratory, Kempegowda Institue of Medical Sciences by using BACTEC
9050 (Becton Dickinson, Gurgaon, Haryana, India).
S. pneumoniae isolates were subcultured and sent to a central
laboratory for confirmation of identification, and serotyping using
type-specific sera by Quellung reaction. Antibiotic susceptibility
testing was performed at a central laboratory for penicillin,
amoxicillin, ampicillin, erythromycin, trimethoprim- sulfamethoxazole,
ceftriaxone, levofloxacin and vancomycin was carried out using standard
methodology, including microbroth dilution and/or E-test. A chest
radiograph was obtained in children with clinically-suspected pneumonia.
In addition, blood specimens from children with clinically-suspected
pneumonia were tested for CRP.
All blood, CSF, and pleural fluid specimens were
stored and tested using polymerase chain reaction (PCR) for nonculture
identification of S. pneumoniae. Samples were stored at the local
laboratory at –80°C and were transferred to the testing laboratory by
packing on dry ice. Only those blood samples not exceeding 3 months of
storage since sample collection were shipped and tested. Whole blood and
CSF were tested from children with meningitis, and whole blood and
pleural fluid were tested from children with pneumonia. For PCR
analysis, purified DNA from each specimen was first tested with duplex
PCR to detect lytA and ply genes. Specimens with high
concentrations of these genes were tested using 13 serogroup/serotypes
real-time PCR assays. Samples were considered PCR positive for each
serotype based on qualitative results. If a specimen tested
positive in the lytA assay but negative in the 13 serogroup/serotype
specific assays, the specimen was assigned a non-13-valent pneumococcal
conjugate vaccine serotype. Each PCR assay contained PCR positive and
negative controls, extraction negative controls, and
extraction/detection positive controls (S. pneumoniae type 1).
Quality control and assurance checks included
periodic monitoring of surveillance activities. During these site
visits, information recorded in case report forms for individual
subjects was verified against source documents. In addition, trained
research staff conducted a daily review of screening logs to ensure
complete and accurate documentation of eligible subjects. Investigators
also reviewed computerized patient lists from outpatient clinics and
emergency department lists to identify patients who may be eligible for
study enrolment. Regular meetings were held with practitioners in the
study area to encourage referral of patients for evaluation and possible
study enrollment. An external surveillance system monitor visited the
study site each month to conduct a weeklong assessment of the quality of
patient capture among those patients with suspected meningitis,
pneumonia, and sepsis who were treated at each study hospital.
Statistical analysis: Incidence rates with 95%
confidence intervals (CIs) were determined based on numbers of cases
identified by the current study and the at-risk population for the three
hospitals in the surveillance area. Cases were counted only once in the
numerator, unless there were separate episodes of occurrence. At-risk
populations (denominator for incidence rates calculations) consisted of
children aged 28 days to less than 60 months in the catchment areas of
the three study hospitals. The age group specific, at-risk populations
were calculated based on data from the National Polio Surveillance
Project, with age and gender breakdown based on the Demographic and
Health Survey (National Family Health Survey) for the state of
Karnataka, where the surveillance area was located [5]. We
assumed that some children in the target study population would seek
care at medium-sized hospitals (i.e., >100 beds) with the capacity to
care for severely ill children and therefore would not be identified in
our study hospitals. By counting these hospitals and the number of
patients they serve, we could better estimate the total number of
children <5 years of age who were at risk for hospitalization due to
severe diseases, such as meningitis, pneumonia and septicemia. Data on
key demographic, clinical, and laboratory characteristics were collected
at study enrollment. Additional data were collected as they became
available during hospitalization. Univariate analyses were the only
analyses performed on these data and determined percentages of subjects
within groups having a specific characteristic or risk factor.
Frequency distributions (numbers and percentages)
were generated for each risk factor. Descriptive statistics were
calculated for the following continuous variables: number of individuals
in the household, number of children aged <60 months, and number of
sleeping rooms. Descriptions of risk factor distributions were generated
for the full study population and for subjects with clinical pneumonia,
chest radiograph-confirmed pneumonia, or CRP+CXR-confirmed pneumonia.
Standard statistical methods for categorical
comparisons of distributed data were employed, including the chi square
test and the Fisher exact test, where applicable.
Results
A total of 9950 children (56% males), 5249 in year 1
and 4701 in year 2, were enrolled from the estimated at-risk population
of 224,966 children. The mean (SD) age of the children was 19.7 (13.8)
months and the majority (66.2%) were aged <24 months. The majority of
enrolled subjects (55.9%) were male. The gender and age distributions
among the enrolled patient population mirrored the distribution of
residents in communities of Karnataka as reported in the National Family
Health Survey [5]. Premature infants (gestation <37 weeks) represented
2.6% of enrolled subjects.
At the time of patient discharge, 1300 of 1802
patients had a final diagnosis consistent with one of the targeted
conditions, including pneumonia clinical syndrome (n=883, 49%),
bacteremia (n=216, 12.0%), sepsis (n=114, 6.3%), and
meningitis clinical syndrome (n=78, 4.3%). Four of the children
with a final diagnosis of meningitis clinical syndrome had definite
pneumococcal meningitis, three of whom had a follow-up neurological
assessment. At follow-up, two children had a normal neurological
assessment and one had an abnormal neurological assessment.
Hospitalization was required for 18.1% of the enrolled children; 75.6%
of those hospitalized were aged <24 months. Almost half (49%) of
hospitalized subjects had a final diagnosis of pneumonia clinical
syndrome.
Forty children met the case definition for invasive
pneumococcal disease; 22 in Year 1 and 18 in Year 2. The mean (SD) age
of those with invasive pneumococcal disease was 19.7 (15.5) months; 65%
were aged <24 months. Prior pneumococcal conjugate vaccination occurred
in 0.3% of all enrolled subjects, and in none of the invasive
pneumococcal disease cases. Thirty of the 40 children with invasive
pneumococcal disease were hospitalized.
The overall estimated incidence rate for invasive
pneumococcal disease was 17.8 per 100,000 children (95% CI 12.7, 24.2).
The highest estimated incidence rate was observed in children aged 6
months to <12 months, 49.9 per 100,000 children (95% CI 26.5, 85.2) (Table
I). The overall estimated incidence rates for pneumonia clinical
syndrome, bacteremia, and meningitis were 12.5, 3.6, and 1.8 per 100,000
children, respectively.
TABLE I Estimated Invasive Pneumococcal Disease Incidence Rates
|
No. |
At-risk |
Incidence rate |
|
of cases |
population |
(95% CI) per |
|
|
|
100,000 children |
Overall |
40 |
224,966 |
17.8 (12.7, 24.2) |
By gender |
Male |
26 |
117,388 |
22.2 (14.5, 32.5) |
Female |
14 |
107,578 |
13.0 (7.1, 21.8) |
By age group |
28 d to <6 mo |
6 |
16,372 |
36.7 (13.5, 79.8) |
6 to <12 mo |
13 |
26,080 |
49.9 (26.5, 85.2) |
12 to <24 mo |
7 |
45,554 |
15.4 (6.2, 31.7) |
24 to <36 mo |
7 |
44,940 |
15.6 (6.3, 32.1) |
36 to <60 mo |
7 |
92,020 |
7.6 (3.1, 15.7) |
There were no significant differences between the
total study population and those with invasive pneumococcal disease for
smokers in the household (28.6% vs 27.5%), breastfeeding <2
months (13.1% vs 15.0%). Exposure to smoke from cooking occurred in
27.5% of the total population in comparison to 37.5% of those with
invasive pneumococcal disease. Malnutrition diagnosed by a healthcare
provider was reported in 5.8% of the study population and 12.8% of those
with invasive pneumococcal disease. Antibiotics were used within 7 days
prior to study enrolment in 19.8% of the total population and in 23.1%
of those with invasive pneumococcal disease.
Laboratory Results
PCR results: Due to concerns about sample
storage, PCR analysis was only performed on samples that had been
stored for <3 months (358 out of 9950). Of all cultures analyzed using
PCR, 62 were positive for S. pneumoniae: 20 blood samples (13.8%,
20 of 145), 29 CSF samples (15.1%, 29 of 192), and 13 pleural fluid
samples (56.5%, 13 of 23). S. pneumoniae serotypes identified by
PCR were: 1 (n=2), 3 (n=1), 5 (n=6), 6A (n=2),
6B (n=1), 7 (n=1), and 19F (n=3). Four
non–13-valent pneumococcal conjugate vaccine serotypes were identified.
Of the 45 samples that were positive for S. pneumoniae from
routine culture, 11 were tested by PCR, and samples from 6 subjects were
positive by both methods. Of the samples from 9910 subjects that were
negative from routine culture, 347 were tested by PCR, and 56 were
positive for S. pneumonia.
Bacteriology and antibiotic resistance: A total
of 9894 subjects (99.4% of 9950 total enrolled subjects) had 10,149
samples cultured. Overall, positive bacterial cultures were obtained in
788 (7.8%) samples. The rate of positive growth in blood, CSF, and
pleural fluid was 7.3%, 20.1%, and 46.7%, respectively. The most
commonly isolated pathogens were Salmonella species (n=80,
10.2%), Staphylococcus aureus (n=48, 6.1%), and S. pneumoniae
(n=45, 5.7%). Serotype information of S. pneumonia was
obtained from 36 samples. Serotyping information was not performed at
the central laboratory for four cases. These four cases were
culture-positive for S. pneumoniae at the local laboratory, and
were therefore included in the IPD population. Serotypes 6A (16.7%, 6 of
36) and 14 (13.9%, 5 of 36) were seen most frequently (Table
II). Maximum resistance was seen to erythromycin (Table II).
TABLE II Serotype Distribution and Antibiotic Resistance of Invasive Pneumococcal Disease Cases in
Children Aged 28 days to <60 months (N=36)*
Serotype |
n(%) |
Antibiotic resistance (No. of isolates) |
6A |
6 (16.7) |
Erythromycin (4), Trimethoprim/sulfamethoxazole (1) |
14 |
5 (13.9) |
Trimethoprim-sulfamethoxazole (4) |
|
|
Erythromycin (2), Penicillin (1) |
5 |
4 (11.1) |
– |
6B |
4 (11.1) |
Erythromycin (2) Trimethoprim-sulfamethoxazole (2) |
1 |
3 (8.3) |
Trimethoprim-sulfamethoxazole (1) |
18C |
3 (8.3) |
Trimethoprim-sulfamethoxazole (2) |
19A |
3 (8.3) |
Erythromycin (2) Trimethoprim-sulfamethoxazole (2) |
9V |
2 (5.6) |
Levofloxacin (1) Trimethoprim-sulfamethoxazole (1) |
3 |
1 (2.8) |
– |
4 |
1 (2.8) |
Trimethoprim-sulfamethoxazole |
10C |
1 (2.8) |
Trimethoprim-sulfamethoxazole |
18A |
1 (2.8) |
Trimethoprim-sulfamethoxazole |
18F |
1 (2.8) |
– |
19F |
1 (2.8) |
– |
*4 invasive pneumococcal disease cases were confirmed by a
local laboratory only; thus serotyping was not performed.
–:No resistance to antibiotics tested. |
Children aged 28 days to <6 months had the highest
estimated incidence rates for clinical pneumonia, CXR-confirmed
pneumonia, and CRP+CXR-confirmed pneumonia (Table III).
Over the 2-year study period, ³1
positive blood culture was reported in 354 children with clinical
pneumonia, 202 with CXR-confirmed pneumonia, and 212 with
CRP+CXR-confirmed pneumonia.
TABLE III Estimated Incidence Rates (per 100,000 chilcren) of Clinical Pneumonia, Chest Radiograph
(CXR)-Confirmed Pneumonia, and C-Reactive Protein (CRP)+CXR-Confirmed
Pneumonia In The Study Area
Age (at risk population) |
Clinical pneumonia* |
CXR-confirmed pneumonia* |
CRP+CXR-confirmed pneumonia* |
|
Cases |
Incidence rate |
Cases |
Incidence rate |
Cases |
Incidence rate |
|
(n) |
(95% CI) |
(n) |
(95% CI) |
(n) |
(95% CI) |
28 d to <6 mo (16372) |
824 |
5033 (4695, 5389) |
395 |
2413 (2181, 2663) |
406 |
2480 (2244, 2733) |
6 to <12 mo (26080) |
986 |
3781 (3548, 4024) |
492 |
1887 (1723, 2061) |
501 |
1921 (1756, 2097) |
12 to <24 mo (45554) |
1230 |
2700 (2551, 2855) |
700 |
1537 (1425, 1655) |
721 |
1583 (1469, 1703) |
24 to <36 mo (44940) |
765 |
1703 (1584,1827) |
388 |
863 (780.59, 954) |
397 |
883 (799, 975) |
36 to <60 mo (92020) |
939 |
1020 (956, 1088) |
530 |
576 (528, 627) |
542 |
589 (540, 641) |
Overall (224966) |
4744 |
2109 (2049, 2170) |
2505 |
1114 (1070, 1158) |
2567 |
1141 (1097, 1186) |
*Some patients had more than one diagnosis. |
A total of 59 deaths were reported among study
participants. Death was reported in 28 of the sepsis cases and 6 of the
meningitis cases, with corresponding fatality rates of 24.6% and 7.7%,
respectively. There were 39 deaths among subjects with clinical
pneumonia, 14 in subjects with CXR-confirmed pneumonia, and 14 in those
with CRP+CXR-confirmed pneumonia (some children had >1 diagnosis); the
corresponding fatality rates were 0.82%, 0.56%, and 0.55%, respectively.
These deaths include 5 (12.5%) deaths among the 40 children with
invasive pneumococcal disease. The final diagnoses among those with
invasive pneumococcal disease who died were bacteremia and pneumonia
clinical syndrome; right-sided empyema and pneumothorax with necrotic
middle lobe and pneumonia clinical syndrome; bacteremia, definite
pneumococcal meningitis, and sepsis; bacteremia and pneumonia clinical
syndrome; and bacteremia, definite pneumococcal meningitis, and sepsis.
Discussion
This prospective study examined the burden of
invasive pneumococcal disease and S. pneumoniae serotype
distribution among young children in an urban area in Southern India.
Notably, this is the first prospective study to document the presence of
serotypes 3, 6A, and 19A in children with invasive pneumococcal disease
in India.
A lower proportion of invasive pneumococcal disease
was identified by routine culture techniques compared with PCR. However,
the PCR results were obtained on a small fraction of the total number of
subjects (those with samples stored for <3 months), and thus cannot be
considered representative of the total samples. In addition, because
samples were considered PCR- positive based on qualitative results,
there is an increased risk of false positives. However, it appears that
using traditional culture techniques to identify cases of invasive
pneumococcal disease may result in a considerable underestimation of the
true burden of disease. Furthermore, important limiting factors for the
blood culture technique include previous antibiotic use and inability to
identify serotypes.
There were several limitations of this study. First,
this was a hospital-based study which may underestimate the true number
of cases in the region. Hospitals other than those selected for this
study as well as private clinics in the catchment area may also treat
some inpatients. In addition, the data may not be representative of the
entire country. Furthermore, calculation of the denominator and age- and
gender-adjustment based on Karnataka state data might have led to an
over- or under-estimate of the incidence rates because the surveillance
area may have a different age- and gender-distribution. Finally,
although almost all enrolled subjects had a culture performed, positive
culture was observed in only 8% of subjects. Obtaining positive blood
cultures in the pediatric population is a challenge [6]. In addition,
many different factors, including prior antimicrobial use, may influence
the ability to isolate pathogens. Although the sample size was limited,
PCR results support the need for exploring the inclusion of non-culture
methods in clinical and epidemiologic surveillance.
In the Invasive Bacterial Infection Surveillance
study conducted almost 15 years ago, no serotype 3 isolates were
detected in children aged <5 years and serotyping was not provided for
the serogroup 6 and 19 isolates obtained [7]. In a retrospective
examination of serotypes and susceptibility in patients with invasive
and clinically significant S. pneumoniae infections in Puducherry
[8], one serotype 3 isolate was identified in a child aged <5 years and
serotyping was not performed for serogroup 6 and 19 isolates. Several
recent publications suggest that the incidence of antibiotic-resistant
strains of S. pneumoniae is increasing in India [9-11]. Southeast
Asian estimates of S. pneumoniae burden of disease in children
aged <5 years are 2991 per 100,000 children (95% CI 2329, 3717) for
invasive pneumococcal disease and 2911 per 100,000 children (95% CI
2265, 3622) for pneumonia [12]. Other studies, including the Million
Death Study [4] and the Child Health Epidemiology Reference Group
(CHERG) analysis [13], similarly confirmed a higher incidence of
pneumonia in younger children.
In summary, continuous larger-scale surveillance
throughout India is needed to better understand the burden of
pneumococcal disease. The variability of serotype epidemiology and
antibiotic resistance are crucial data for determining country-specific
pneumococcal vaccination needs.
Contributors: From the Kempegowda Institute of
Medical Sciences: AC Ramesh, Srinivasa S, Yashoda HT and Muruli BH; Vani
Vilas Hospital: Asha Benakappa and Ramana HC; Indira Gandhi Institute of
Child Health: Govindaraju M, Siddaraju ML, Prahalda Kumar A, Ramesh L,
and Rajeshhekara Murthy GR.
Competing interests: IB and SJ were employees of
Pfizer, Global Research and Development, Paris, France during conduct of
study. PEK was an employee and SAK is still an employee of The
International Vaccine Institute, Seoul, Republic of Korea, contracted to
Pfizer Inc, Collegeville, PA, USA at the time of this study and during
development of this manuscript. JY is a former employee of On Assignment
Inc, and was a paid contractor to Pfizer to assist with study design,
statistical planning, data analysis and manuscript development. MM is a
current employee of Pfizer Inc, Collegeville, PA, USA.
Funding: This study was sponsored by Wyeth
Pharmaceuticals, which was acquired by Pfizer Inc in October 2009.
Medical writing support was provided by Elaine Santiago, MS, PharmD at
Excerpta Medica, and was funded by Pfizer Inc.
What is Already Known?
•
Invasive pneumococcal disease
burden in children aged <5 years is significant in India and
data regarding overall invasive pneumococcal disease incidence
are scarce.
What This Study Adds?
•
The estimated incidence of pneumococcal disease among
children aged 28 days to <60 months in South Bangalore was
17.8/100,000. Frequently occurring serotypes are 6A, 14, 5, and
6B.
|
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