Pneumococcal disease burden,clinical presentations and vaccine coverage in the Jamaican population

Abstract

BACKGROUND:

Pneumococcal serotypes circulating in any population vary over time and between countries and impacts the effectiveness of pneumococcal vaccination.

OBJECTIVE:

This study investigated the epidemiology of pneumococcal disease in Jamaica.

METHODS:

Streptococcus pneumoniae isolates ( $n=$ 349) along with demographic and clinical information were collected from patients presenting at the 4 major hospitals in Jamaica over a 2-year period. Serotyping was done using latex agglutination tests and the Quellung reaction assay.

RESULTS:

Invasive pneumococcal disease (IPD) incidence was 45.4/100,000 in children under 5 yrs and 16.3/100,000 in adults over 65 yrs. Thirteen serogroups were identified among the 120 isolates subjected to grouping; the most common being serogroups: 19 (22/120,18.3%), 6 (20/120,16.7%), 14 (20/120,16.7%), 23 (18/120,15.0%), 3 (11/120,9.2%) and nontypeable (8/120,2.3%). The estimated vaccine coverage rates for the PCV7 and PCV13 vaccines in children less than 5 yrs were 82.5% and 88.7% respectively. The 23-valent PPV23 provided 100% coverage rate in adults over 65 yrs and 82.9% coverage rate for the entire population.

CONCLUSIONS:

Pneumococcal vaccine coverage rates in Jamaica are comparable to those reported in certain developed countries and higher than in other developing countries. The high incidence of IPD in the paediatric population indicates that routine vaccination would be beneficial.

Keywords

Streptococcus pneumoniae pneumococcus vaccine serotype Serogroup Jamaica Epidemiology

1. Introduction

Streptococcus pneumoniae (pneumococcus) is responsible for an estimated 7 million cases of otitis media, 500,000 cases of pneumonia, 50,000 cases of bacteraemia and 3000 cases of meningitis in the United States each year and an estimated 1.6 million deaths globally [1, 12]. Before widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7), the incidence of paediatric invasive pneumococcal disease (IPD) ranged from 3.1 to 110.2 per 100,000 in Europe and as high as 235 per 100,000 in the United States [5, 14]. Reported incidence rates of IPD in developing countries have typically been higher than those in Europe and the United States ranging from 60 to 797 per 100,000 children [22]. Notably a 5-year retrospective review of cases at one paediatric hospital in Jamaica reported an estimated IPD incidence at 21 cases/ 100,000 in children less than 10 years of age [4].

Serotyping of S. pneumoniae strains has identified more than 90 capsular types distributed in distinct geographical areas and epidemiologic groups. This led to the development of appropriate polyvalent pneumococcal vaccines to prevent IPD [11, 17]. In a global study comprising 13,616 pneumococcal isolates, the 10 most prevalent serotypes accounted for 61.7% of isolates and the 30 most prevalent accounted for 91.5% [10]. Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F accounted for approximately 80% of paediatric IPD cases in the United States prior to the widespread use of PCVs and accordingly were selected for inclusion in PCV7 [22]. The introduction of PCV7 in the USA in 2000 has resulted in decreased rates of colonization and IPD due to PCV7 serotypes; however, there was a concomitant increase in IPD caused by non-PCV7 serotypes [20, 22].

The proportion of IPD caused by PCV7 serotypes varies in other parts of the world. For example, in certain parts of Africa, Asia and Europe serotypes 1 and 5 which are non-PCV7 serotypes account for an important proportion of paediatric IPD; approximately 10–20% [22]. Furthermore the 9-valent pneumococcal conjugate vaccine (PCV9) formulation which adds serotypes 1 and 5 to those present in PCV7 has been shown to be effective in reducing the incidence of IPD in regions where these serotypes are prevalent [15]. In early 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) was licensed by the Food and Drug Administration (FDA) for prevention of IPD caused by the 13 pneumococcal serotypes covered by the vaccine. The World Health Organization (WHO) and the Advisory Committee on Immunization Practices (ACIP) recommend PCV13 for all children aged 2–59 months and for those children aged 60–71 months with underlying medical conditions that increase their risk for pneumococcal disease or complications [13, 22].

Pneumococcal vaccines are not a component of the routine childhood immunization schedule in Jamaica but the 23-valent pneumococcal polysaccharide vaccine (PPV23) is typically used in conjunction with penicillin to prevent IPD in patients with sickle cell disease (SCD). However, since 2005 the private sector usage of the PCV7 vaccine formulation for children less than 5 years has increased exponentially with a shift to PCV13 in 2011 [25]. Unfortunately, previous estimates of disease incidence and vaccine coverage in Jamaica applied only to respiratory isolates in both symptomatic and asymptomatic cases. The pneumococcal strains recovered from the respiratory tracts of a cohort of symptomatic and asymptomatic Jamaican children presenting at a pediatric hospital during 2003 revealed that PCV7 serotypes 6B, 19F and 14 accounted for over 40% of isolates [23]. This study estimated that the coverage of PCV7 in the cohort was 57% and that of PCV13 was 63%. There is an urgent need for accurate data on the burden of IPD and non-IPD in Jamaica and the serotypes causing disease. This study is the first of its kind for any single Caribbean country and is necessary to guide the implementation of appropriate pneumococcal vaccines and management strategies for various groups at risk for developing IPD in Jamaica.

2. Methods

2.1 Subjects and bacterial strains

The study was carried out between January 2008 and December 2009. Study patients were recruited from individuals presenting at 4 major health care facilities in Jamaica including the University Hospital of the West Indies (UHWI), a tertiary referral centre situated in the eastern region of the island; the National Public Health Laboratory (NPHL), the Bustamante Hospital for Children (BHC), both situated in the southeastern region of the island; and the Cornwall Regional Hospital (CRH), situated in the western region. The study population comprised both hospitalized patients who tend to have more severe disease and outpatients, whose pneumococcal infection did not require hospitalization. The pneumococcal isolates ( $n=$ 349) recovered from clinical specimens collected from patients for bacteriological investigations were collected consecutively over the study period and only one isolate per patient per infectious episode was included in the study. Ethical approval of the study was obtained from the relevant institutional oversight committees.

2.2 Demographic and clinical data

A standardized data abstraction form was used to collect demographic and clinical information from hospital records. The data collected pertained to age, gender, type of clinical specimen and date of collection, clinical presentation, and the presence of any co-morbid illnesses that increase risk for pneumococcal disease. Invasive disease was defined as cases in which pneumococci was isolated from a normally sterile body site such as the blood stream, central nervous system or synovial fluid [22]. The length of hospitalization was calculated in days from intake interview to discharge from the hospital and the length of hospitalization for patients who died was not included in statistical analyses. The development of complications was defined as the need for intensive cardiovascular or respiratory resuscitation measures. Population data were obtained from the Statistical Institute of Jamaica (STATIN).

2.3 Laboratory procedures

2.3.1 Isolation and Serotyping of S. pneumoniae isolates

Standard microbiological procedures were followed for the processing of each specimen type and bacterial isolates were identified as S. pneumoniae by microscopy, colony morphology, positive optochin sensitivity and bile solubility tests [2]. The pneumococcal strains were stored in tryptic soy broth containing 15% glycerol at $-$ 70 ${}^{\circ}$ C until required [3]. Pneumococcal strains were recovered from storage by thawing at room temperature followed by inoculation of horse blood agar plates, which were incubated at 37 ${}^{\circ}$ C for 24 hours to obtain a pure growth of S. pneumoniae. A single colony of this growth was used to prepare overnight cultures in 5 ml of Todd Hewitt Broth using standard procedures [8]. The serogroup/serotype of each S. pneumoniae strain was determined with 10 $\mu$ L aliquots of overnight broth culture using commercially prepared latex agglutination test kits (Pneumotest-Latex, Statens Serum Institut, Copenhagen) according to the manufacturer’s instructions. All pneumococcal strains that were untypeable and representative pneumococcal strains from each serogroup identified by the latex agglutination test were sent to the Statens Serum Institut, Copenhagen, for capsular typing (Neufeld) by the Quellung reaction test [18].

2.4 Statistical analyses

Statistical analyses were performed using the Xlstat Software, Version 16.6 (Addinsoft, New York, NY, USA). Data were compared by chi-square or Fisher’s exact tests as appropriate and the strength of association was expressed as odds ratios with 95% confidence intervals (OR 95% CI). The significance of difference in means was determined by Student’s t-test. Disease incidence was calculated using population denominators obtained from STATIN.

Table 1
Clinical characteristics of patients presenting with pneumococcal disease

Clinical Characteristic	Frequency (%)
Age (mean $\pm$ SD years [Range])*	16.0 $\pm$ 24.1 [newborn to 86]
Age (median (IQR] years)*	2.0 [0.7–26.3]
Sex (Female)**	169 (48.4)
Invasive Disease ${}^{\text{a}}$	169 (48.4)
Sepsis ${}^{\text{b}}$	128 (36.7)
Otitis	82 (23.5)
Conjunctivitis/Periorbital Cellulitis ${}^{\text{c}}$	67 (19.2)
Pneumonia (LRTI)	66 (18.9)
Co-morbid illness	43 (12.3)
CNS Infections ${}^{\text{d}}$	19 (5.4)
SSI	17 (4.9)
URTI	17 (4.9)
GUI	7 (2.0)
Infective Endocarditis	1 (0.3)

*Age is described as mean $\pm$ standard deviation with age range as well as median with the corresponding interquartile range (IQR), while all other variables are described as frequency and the corresponding percentage. ${}^{\text{a}}$ Invasive disease was defined as cases in which pneumococci was isolated from a normally sterile body site such as the blood stream, or secondary to blood stream spread, eg. meningitis or septic arthritis. ${}^{\text{b}}$ Sepsis was defined as the positive identification of S. pneumoniae in blood culture with or without the presence of a known primary focus of infection. ${}^{\text{c}}$ All cases of periorbital cellulitis occurred in conjunction with conjunctivitis and so were not grouped with other skin and skin structure infections (SSIs). ${}^{\text{d}}$ Central nervous system (CNS) infections included cases of meningitis and intracerebral abscesses. GUI – genitourinary infection; URTI – upper respiratory tract infections. **Gender and age data were not available in 14 and 53 pneumococcal cases respectively.

Table 2

Estimates of coverage provided by various pneumococcal vaccine formulations*

Vaccine formulation	Estimated coverage (%)
	All isolates	Children $<$ 5 yrs	Adults $>$ 65 yrs
PCV7 (4, 6B, 9V, 14, 18C, 19F, 23F)	89/120 (74.2)	51/62 (82.2)	5/8 (62.5)
PCV9 (PCV7 and 1, 5)	89/120 (74.2)	51/62 (82.2)	5/8 (62.5)
PCV13 (PCV11 and 6A, 19A)	100/120 (83.3)	55/62 (88.7)	6/8 (75)
PPV23 (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F)	107/120 (89.2)	56/62 (90.3)	8/8 (100)

*Coverage rates estimated based on serogroups present in vaccine formulation.

3. Results

During the 2-year period of study, a total 349 cases of S. pneumoniae infection were identified. Co-infection with 2 morphologically distinct strains occurred in 1 case, therefore a total 350 S. pneumoniae isolates were obtained. The incidence of all pneumococcal disease was 20.6 cases per 100,000 persons in the entire population, 126.5 per 100,000 in children less than 5 years and 17.9 per 100,000 in adults greater than 65. The incidence of IPD in the entire population was 8.6 per 100,000 compared to 45.4 per 100,000 in children less than 5 years and 16.3 per 100,000 persons in adults greater than 65 years of age. The clinical characteristics of the patients are shown in Table 1. The majority of pneumococcal cases (181/349, 51.9%) occurred in children less than 5 years and only 6.6% (23/349) cases occurred in adults over 65 years of age. The frequency of non-IPD was higher than IPD in children less than 1 year old (OR 6.4, 95% CI 3.6–11.2, $p<$ 0.0001) and children less than 5 years old (OR 3.8, 95% CI 2.3–6.3, $p<$ 0.0001). Conversely the frequency of IPD was higher than non-IPD in adults over 20 years old (OR 9.2, 95% CI 4.8–17.6, $p<$ 0.0001), the ratio increasing in those over 65 years (OR 12.5, 95% CI 3.3–47.4, $p<$ 0.0001).

Figure 1.

Clinical presentation of pneumococcal infections among various age groups. CNS – meningitis and intracerebral abscess cases, Ear – otitis cases, Eye – conjunctivitis and/or priorbital cellulitis cases, GUI – genitourinary infections, IE – infective endocarditis cases, LRTI – pneumonia cases, SSI – skin and skin structure infections, URTI – upper respiratory tract infections. Cases in which age data were not available were necessarily excluded from this analysis.

Figure 2.

Prevalence of pneumococcal serogroups among invasive and non-invasive disease presentations. Of the 120 pneumococcal isolates available for grouping, 57 (47.5%) occurred in cases of invasive pneumococcal disease (IPD) and 63 (52.5%) in non-IPD cases. Percentages indicate the prevalence of each serogroup among the available isolates. Among IPD infections, serogroups 10, 11, 16, 17 and 35 each accounted for 2% while among non-IPD infections, serogroups 9 and 13 accounted for 2% cases.

Sepsis with or without a known primary focus of infection (128/349, 36.7%) was the most frequent clinical presentation. More than half of sepsis cases occurred without an identified primary focus of infection (73/128, 57.0%). In descending order, bacteremia was most prevalent in cases of infective endocarditis (100%), CNS infections (68.4%), pneumonia (48.5%), SSI (17.6%), URTI (5.9%), conjunctivitis (4.5%), otitis (2.4%) and GU infections (0.0%). Co-morbid illnesses that were risk factors for pneumococcal disease were present in 12.9% (45/349) cases. These included human immunodeficiency virus infection or acquired immune deficiency syndrome (HIV/AIDS) (11/349, 3.2%), sickle cell disease (10/349, 2.9%), diabetes mellitus (7/349, 2.0%), hematological malignancy (5/349, 1.4%), solid tumors (4/349, 1.1%), malnutrition (3/349,0.9%), chronic obstructive pulmonary disease (3/349, 0.9%), viral pneumonia (1/349, 0.3%) and extensive burns (1/349, 0.3%). As shown in Fig. 1, the majority of cases of sepsis (54.5%) occurred in the under 5 age group. However, most cases of pneumococcal pneumonia occurred in adults over 20 years of age (63.6%) (also shown in Fig. 1).

3.1 Pneumococcal serogroups

Serogrouping was performed on 120 S. pneumoniae isolates (120/350, 34.4%), which were available. As shown in Fig. 2, the majority of isolates (91/120, 75.8%) belonged to serogroup 19 (22/120, 18.3%), serogroup 6 (20/120, 16.7%), serogroup 14(20/120, 16.7%), serogroup 23 (18/120, 15.0%) or serogroup 3 (11/120, 9.2%). Non-typable strains, which accounted for 2.3% (8/120) of isolates, were significantly associated with non-invasive disease (OR 7.8, 95% CI 1.1–65.8, $p=$ 0.007) while serogroup 6 strains (OR 3.0, 95% CI 1.1–7.9, $p=$ 0.029) were associated with invasive disease. All (8/8, 100%) non-typeable strains were isolates from conjunctivitis cases.

The estimated coverage rates based on serogroup information for the various pneumococcal vaccine formulations are shown in Table 2. PCV7 provides an estimated overall coverage of 74.2% (89/120), including 82.2% (51/62) of isolates recovered from children less than 5 years old and 62.5% (5/8) of isolates from adults over 65 years. Serotypes 1 and 5 were not identified among the isolates tested ( $n=$ 120), therefore PCV9 provided no added coverage compared to PCV7. In contrast, PCV13 provided increased overall coverage, 83.3% (100/120), including 88.7% (55/62) in children younger than 5 years old and 75.0% (6/8) in adults older than 65 years. Similarly, the PPV23 formulation provides 89.2% (107/120) overall coverage including 90.3% (56/62) and 100% (8/8) coverage in children under 5 years and adults over 65 years of age respectively.

4. Discussion

In this study we report for the first time the epidemiology of pneumococcal disease in Jamaica and coverage estimates for available vaccine formulations. Pneumococcal disease disproportionately affected the paediatric population, which is unsurprising given that children less than 5 years are the major reservoir for S. pneumoniae transmission [12, 22].

We found an incidence of paediatric IPD that is substantially higher than the incidence reported in a previous Jamaican study, which involved children in only one pediatric hospital [4]. The authors of that study cited that the selective screening of febrile patients as dictated by limited resources might have contributed to an underestimation of the true incidence of IPD in Jamaican children. The reported rates of paediatric IPD from Jamaica, including the present study, are not as high as those in other developing countries and are more comparable to estimates from developed countries prior to the introduction of pneumococcal conjugate vaccines. However, much lower rates were observed in developed countries following adoption of PCVs into national immunization schedules [13, 22].

Co-morbid illnesses in which a compromised immune system could increase the risk for pneumococcal disease were present in a substantial proportion of our patients and these included HIV infection, DM, SCD, malignancies, malnutrition and pulmonary diseases. Several of these conditions pose serious public heath concerns in our population. HIV/AIDS, for example, is a growing problem in the Caribbean, which is the second most affected area worldwide after Sub-Saharan Africa [7]. The finding of a substantial proportion of patients having co-morbid factors for pneumococcal disease underscores the need for PCV implementation in our patient population. Paediatric IPD in Jamaican SCD patients has been estimated at 480/100,000 individuals [19]. While substantially higher than the overall rate for paediatric IPD we report here, these rates are much lower than those reported in SCD patients in other developing countries with rates as high as 6900/100,000 [24]. Our relatively low IPD rates in SCD paediatric patients are due in large part to the success of the Jamaican newborn screening program for SCD begun in 1995 and automatic enrollment of SCD children in the Sickle Cell Unit (SCU) which provides free ambulatory health care for these patients [19].

While pneumococcal disease in our adult population was marked by a high proportion of invasive disease, the need for routine vaccine administration in elderly patients may not prove to be cost-effective given the relatively low IPD incidence. Furthermore, there have been reported herd-protection effects resulting in reduced IPD incidence in older adults following routine PCV administration in children in several studies [16].

Our study revealed that serogroups 3, 6, 19, 14 and 23 together account for more than 75% of all pneumococcal isolates in our population which is similar to rates in North America [14]. The results also confirm the findings of the previous study of Jamaican children that reported respiratory isolates were most commonly of serotypes 6B, 19F and 14 [23]. Serogroup 6 was associated with an increased risk for IPD in the present study and this has been reported in other populations, however, more detailed analysis in a larger cohort of patients is necessary to adequately evaluate the link of serotype to risk for IPD in Jamaica [9, 12]. The similarity of serotype distribution found in this study to that in the United States translates into a relatively broad coverage provided by not just the PCV13 but also the PCV7 formulation in our population [14]. Our findings suggest that inclusion of PCV13 in the national immunization programme in Jamaica would result in effective reduction of paediatric IPD. The availability of expertise in economic evaluation and the cost of the vaccine would be important considerations in this effort [21].

The limitations to the study include the fact that not all pneumococcal isolates were available for serotyping, as some were lost during storage as a result of inconsistent electricity supplies. This problem is a common one in many developing countries and remains an obstacle to meaningful pneumococcal research in our setting [6]. Also, the use of serogroup rather than serotype analysis of pneumococcal isolates allowed for only estimated values of pneumococcal vaccine coverage rates. In conclusion, the study highlighted risk groups for pneumocococcal disease in Jamaica and the high incidence of IPD in children less than 5 years of age indicates that routine childhood vaccination would be beneficial. In contrast, the low burden of disease in adults $>$ 65 years of age precludes the need for routine PPV23 vaccination in this age group but patients with certain underlying conditions which increase the risk of IPD may benefit. The study also provided evidence of adequate coverage rates for available pneumococcal vaccines in Jamaica. These results will prove instrumental in guiding vaccine implementation strategies in Jamaica and the Caribbean region.

Footnotes

Acknowledgments

The authors would like to thank the staff of the Microbiology Laboratories at the University Hospital of the West Indies, Bustamante Hospital for Children, National Public Health Laboratory and the Cornwall Regional Hospital for their generous assistance in facilitating collection of pneumococcal isolates across the country.

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