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SUPPLEMENT ARTICLE

Report on Invasive Disease and Meningitis due to Haemophilus influenzae and Streptococcus pneumonia from the Network for Surveillance of Pneumococcal Disease in the East African Region
Sandra Mudhune and Maranga Wamae, for the Network Surveillance for Pneumococcal Disease in the East African Region
Network for Surveillance of Pneumococcal Disease in the East African Region, Kenya Medical Research Institute/Wellcome Trust, Nairobi, Kenya

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Pneumococcal disease in young children has not been as well characterized in East Africa as it has been in industrialized countries. Although pneumococci are likely to cause substantial mortality and morbidity, universal diagnostic challenges plus the rudimentary nature of public health surveillance make the true epidemiological characteristics of these diseases difficult to ascertain with these methods alone. However, local data are critical to inform the debate on vaccine deployment and assess vaccine impact. The Network for Surveillance of Pneumococcal Disease in the East African Region has worked to expand the World Health Organization Paediatric Bacterial Meningitis Surveillance Network—initiated surveillance process aimed at Haemophilus influenza type b to perform surveillance on pneumococcal diseases. A total of 119 H. influenzae isolates from children aged 12 years but !5 years of age have been confirmed. Eighty-three isolates (69.75%) were serotype b, 19 belonged to other capsular antigen groups, and 17 were nontypable. For Streptococcus pneumoniae, a total of 442 isolates were confirmed to be pneumococci; 302 isolates were from blood cultures, and 140 were from cultures of cerebrospinal fluid. Most of the isolates were obtained from patients in the 6–29-month age group; in this age group, overall coverage by the heptavalent vaccine was 56% (increasing to 67% with the addition of cross-protection due to serotype 6A). S. pneumoniae isolates are susceptible to most commonly used antibiotics, with the exception of trimethoprim-sulfamethoxazole, and have exhibited no resistance to penicillin. A surveillance network is in place to provide local data on the importance of S. pneumoniae as a cause of both meningitis and bacteremia. Serotypes in the currently available heptavalent conjugate pneumococcal vaccine and related serotypes account for two-thirds of invasive pneumococcal disease among children aged 6–29 months. In sub-Saharan Africa, diseases caused by Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) are important causes of morbidity and mortality in children. Collectively, they cause up to 500,000 deaths per year [1]. In 2001, 2 East African countries, Kenya and Uganda, introduced the conjugate Hib vaccine into their routine immunization schedules with funding from the GAVI Alliance. The decision to introduce the vaccine was made in the absence of good epidemiological data on local disease. In 2001, recognizing this problem, the World Health Organization Africa Regional Office established the Paediatric Bacterial Meningitis Surveillance Network continent-wide [2] to help provide data that would inform vaccine introduction decisions. However, this network focused largely on Hib surveillance and initially included only 1 surveillance

This article is published with the permission of the Director of the Kenya Medical Research Institute. Reprints or correspondence: Sandra Mudhune, Network for Surveillance of Pneumococcal Disease in the East African Region, Kenya Medical Research Institute/Wellcome Trust, KNH Grounds, PO Box 43640-00100, GPO, Nairobi, Kenya (smudhune@nairobi.kemri-wellcome.org). Clinical Infectious Diseases 2009; 48:S147–52 2009 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2009/4805S2-0016$15.00 DOI: 10.1086/596494

H. influenzae and S. pneumonia Invasive Disease and Meningitis • CID 2009:48 (Suppl 2) • S147

to introduce a coordinating laboratory for serotyping and species confirmation. mean months 14 27 30 14 (14) 26 16 29 21 (28) Country. . and 17 were nontypable (table 4). data to support decisions on their use at the country level would be required. Both blood isolates and CSF specimens were inoculated onto sheep blood agar and chocolate blood agar. Tanzania. Pneumococcal isolates were identified by colony morphologic analysis. Antibiotic susceptibility was determined using the Etest (AB Biodisk) to establish MICs. influenzae isolates were received.org/ by guest on September 27. Eighty-three isolates were serotype b. Uganda.000 Downloaded from http://cid. to improve completeness of the data by ensuring that sites had the technical ability to isolate and identify pneumococci. METHODS The initial scope of netSPEAR was limited to 4 countries: Kenya. Identification of Hib was accomplished by colony morphologic analysis and X and V factor requirements. and Ethiopia. The network used standard case definitions for children !5 years of age who should be considered for either lumbar puncture or blood culture. with antisera from the Statens Serum Institut in Denmark [3]. and to increase the use of local research data in informing policy. Kenya. Blood specimens were cultured in the BACTEC 9050 (Becton Dickinson) blood culture system at all but one of the sites. and Optochin susceptibility and were sent to the coordinating laboratory for serotyping using the Quellung technique. These case definitions were provided to each hospital. in line with international best S148 • CID 2009:48 (Suppl 2) • Mudhune and Wamae practice guidance.Table 1. but their use could not be enforced. well-performing sites to provide some data on the role of pneumococci and other pathogens in nonmeningitis invasive disease. in which a BacT/ALERT 3D (bioMerieux) system from a previous research project was ´ used. to improve the visibility of the data through better local dissemination and more-informed advocacy. 19 were other capsular antigens. by study site.000 8000 15. influenzae disease and 743 cases of disease caused by pneumococci were reported in netSPEAR (tables 1–3). particularly pneumonia. of pediatric admissions per year 5000 2000 5000 16. 289 cases of invasive H. Age of children with CSF samples collected (age of children with blood samples collected). a-hemolysis. RESULTS From August 2003 through February 2007.000 5000 5500 4600 4700 3800 5300 8000 20.oxfordjournals. of which 119 were viable for confirmation and antibiotic testing at the coordinating laboratory at the Kenya Medical Research Institute/Wellcome Trust Research Program in Kilifi. as part of good clinical practice and standard operating procedures for the laboratories. Number of pediatric admissions and patient age. 2012 14 21 (26) 28 16 (16) 18 17 (22) site from each country. A total of 153 H. With the prospect of effective but possibly more costly pneumococcal vaccines becoming available. The aims of netSPEAR were to increase the representativeness of the data collected by increasing the number of sites in each country. to introduce blood culture in selected. The Network for Surveillance of Pneumococcal Disease in the East African Region (netSPEAR) was therefore established in August 2003. Mary’s Hospital Lacor Mbarara University Teaching Hospital Mulago National Referral Hospital Mean no. which was usually the major teaching or national referral hospital. because the surveillance network was not research based. study site Ethiopia Black Lion Hospital Kenya Moi Teaching and Referral Hospital Embu Provincial General Hospital Kenyatta National Hospital Machakos District Hospital Nakuru Provincial General Hospital Nyeri Provincial General Hospital Kilifi District Hospital Tanzania Muhimbili National Hospital Hospitali Teule Uganda Mbale Regional Referral Hospital St.

pneumoniae. Of the 93% of samples for which the age of the patient was reported.oxfordjournals. and profiled for antibiotic susceptibility (tables 2 and 3). a Site did not submit samples for species confirmation and antibiotic profiling. study site Ethiopia Black Lion Hospital Kenya Moi Teaching and Referral Hospital Embu Provincial General Hospital Kenyatta National Hospital Machakos District Hospital Nakuru Provincial General Hospital Nyeri Provincial General Hospital Kilifi District Hospital Tanzania Patient age. of blood samples collected Reported as Haemophilus influenzae !5 years Confirmed as Hib/ submitted as Hib !5 years Reported as Streptococcus pneumoniae !5 years 5 years 5 years 5 years 5 years 5 (6–13) 16 (5–37) 19 (11–32) 12 (8–21) 10 (1–30) 14 (5–33) 2447 18. pneumoniae/ submitted as S. Of the 442 isolates confirmed as pneumococci. Hib. H. pneumoniae !5 years Country. Number of blood samples and isolates retrieved for species confirmation from each site. site Kenya Kenyatta National Hospital Kilifi District Hospital Tanzania Hospitali Teule Uganda St. IQR. pneumonia Invasive Disease and Meningitis • CID 2009:48 (Suppl 2) • S149 . Of 522 blood and CSF isolates initially identified as S. of isolates. No.212 2 10 13 43 196 0 0 0 0 12 0/0 2/2 0/2 4/15 24/44 1/1 0/0 0/0 0/0 7/12 3 94 23 54 346 2 0 0 0 41 1/1 6/49 0/4 28/34 99/168 0/0 0/0 0/0 5/5 41/47 NOTE. Hib. Haemophilus influenzae type b. pneumoniae/ submitted as S. 10-. Mary’s Hospital Lacor Mbarara University Teaching Hospital Mulago National Referral Hospital All sites 10 (5–18) 18 (10–30) 749 641 8 37 0 8 … … 7 8 0 5 … … a 3/7 3/6 1/2 2/3 14 (8–36) 12 (6–24) 14 (5–29) 12 (4–24) 12 (5–26) 179 3983 919 3758 19. of CSF samples collected Reported as Haemophilus influenzae !5 years Confirmed as Hib/ submitted as Hib !5 years Reported as Streptococcus pneumoniae !5 years 5 years 5 years 5 years 5 years 8 (3–19) 453 36 0 … a … a 23 2 … a … a 22 (8–37) 17 (7–39) 8 (4–19) 22 (4–48) 7 (3–24) 24 (9–38) 11 (1–30) 467 569 2594 83 329 860 3628 0 2 20 1 5 3 16 0 0 0 0 0 1 3 0/0 0/0 0/0 … a 8 1/2 0/0 … a 1 4 0 0 1 5 21 3/7 7/7 13/13 … a 0/0 1/2 14/16 … a 7 62 0 10 13 37 2/2 0/0 13/16 a 0/0 0/0 2/3 a 4/6 1/6 35/39 a 2/2 0/0 17/19 Downloaded from http://cid. respectively) in this age group varied only slightly by country. IQR. of isolates. The percentage of cases of invasive pneumococcal disease that could be prevented through use of the 7-. 84% and 70% for Table 3. No.230 2375 2016 1214 26. and Tanzania. The other 80 isolates were either nonviable on receipt or were identified as another Streptococcus or other bacterial species. and PCV13. and 13-valent pneumococcal conjugate vaccines (PCV7. median years (IQR) No. influenzae and S.282 1 39 25 2 4 71 0 8 2 0 0 10 0/0 20/20 12/19 0/0 2/5 34/44 1/1 4/4 3/10 0/0 0/0 8/15 25 193 29 23 7 277 4 68 7 0 0 79 14/14 181/181 12/13 3/4 3/6 213/218 8/8 65/65 13/13 0/0 3/3 89/89 NOTE. interquartile range. coverage was 47% and 56% for PCV7 serotypes.org/ by guest on September 27. 314 were from children !5 years of age. Mary’s Hospital Lacor Mulago All sites Patient age. Number of CSF samples and isolates retrieved for species confirmation from each site.Table 2. a total of 442 isolates were confirmed as pneumococci. serotyped. Haemophilus influenzae type b. PCV10. Uganda. pneumoniae !5 years Country. For countries with a sufficient sample size to allow evaluation (Kenya and Uganda). 2012 Muhimbili National Hospital Hospitali Teule Uganda Mbale Regional Referral Hospital St. interquartile range. by patient age Confirmed as S. 302 were from blood samples and 140 were from CSF samples collected in Kenya. median years (IQR) No. by patient age Confirmed as S.

Estimated vaccine coverage for pneumococcal serotypes among children !5 years of age. DISCUSSION Despite challenges at multiple stages of development in establishing surveillance from August 2003 through February 2007.25 79. pneumoniae. 2012 Table 5. country. Because PCV7 has been shown to be effective against serotype 6A and because of the structural similarity between this serotype and serotype 6B. respectively.50 PCV7 and PCV6A 46. and 88% and 79% for PCV13 serotypes in Kenya and Uganda. Data for serotype 6A has been added to the data for PCV10. and Tanzania). 20 of these isolates were confirmed as pneumococci.31 PCV13 84. Number of Haemophilus influenzae isolates. and specimen type.14 77. pneumococcus conjugate vaccine. a total of 19.5% of both CSF and blood samples. In addition to the isolates obtained from blood and CSF specimens and confirmed as S.05 75. 57 isolates without an indication of source were received for confirmation of species and serotyping.15 67. if this crossprotection were included (table 5).Table 4. and therefore.97 100.26 84.51 46. erythromycin.44 88. of patients 90 163 61 258 13 43 213 101 Estimated vaccine coverage. and chloramphenicol resistance peaked at 9% of S.70 54.00 69. pneumoniae isolates are susceptible to most of the antibiotics that are commonly used in the East African region.15 55.00 58. 19 were initially identified and submitted as Hib. ranging from 0% to 1. Uganda. Thirty-eight isolates were initially identified and submitted as S.oxfordjournals.07 100.44 52.44 34.00 79.48 37. by age group. in 2006) [4]. and some sites experienced increases in the rate of sample collection of Downloaded from http://cid. with the exception of trimethoprim-sulfamethoxazole. The prevalence of resistance to cefotaxime.38 PCV10 72.85 77. Of these 57 isolates. all data were pooled.07 88.48 50.67 67. pneumoniae isolates in Kenya in 2004.11 56. resistance to which has been increasing steadily (from 19% of isolates obtained from CSF samples and 27% of isolates obtained from blood samples in 2003 to 69% and 60% of such samples. 10 of these isolates were confirmed as Hib. Source Blood CSF Unknown Total Serotype a 10 5 1 16 Serotype b 42 31 10 83 Serotype c 1 0 0 1 Serotype e 1 0 0 1 Serotype f 1 0 0 1 Nontypable 10 7 0 17 Total 65 43 11 119 PCV10 serotypes. PCV. The other isolates were either nonviable or were identified as belonging to another species. the prevalence of resistance has decreased to 2% of isolates. the coverage of PCV7 and PCV10 would increase to 67% and 86%. influenzae (tables 2 and 3). however.22 74. and amoxicillin was low. There was a worrying increase in chloramphenicol resistance among meningitis cases. Also worth noting is that serotypes 1 and 5 were isolated more often from blood specimens (accounting for 30% of cases) than from CSF specimens (18% of cases) (figure 1).43 46. by serotype. respectively.58 62. from ∼420 samples collected per month in 2003 to 590 samples collected per month in 2007. since that time.282 blood samples were collected by sites in netSPEAR. We found no resistance to penicillin among isolates obtained from CSF or blood samples (0% for both).16 Variable Patient age. S150 • CID 2009:48 (Suppl 2) • Mudhune and Wamae . S.96 85.212 CSF samples and 26. The 6–29-month age group contributed most of the isolates and had the highest coverage of vaccine serotypes.81 46. pneumoniae or H. This represents a 40% increase in CSF collection. % PCV7 41.org/ by guest on September 27. months 0–5 6–29 30–59 Country Kenya Tanzania Uganda Specimen type Blood CSF NOTE. respectively (table 5). with overall coverage of PCV7 of ∼56%. Antibiotic resistance profiles of pneumococci are generally similar in the 3 countries that submitted isolates for testing (Kenya.26 46. No.

Because PCV7 includes most of the strains that exhibit antibiotic resistance. Although netSPEAR has a wide geographic base and has tried to collect data that are representative of the region. and some sites did not begin to do so until 2005. including the occurrence and magnitude of possible replacement disease [8]. 2012 H.oxfordjournals. The final decision as to whether to perform a test was the responsibility of the attending clinician who performed the investigation and was based on whether he considered the performance of the test to be beneficial to the child. Thus. Because the data result from routine surveillance and not from research. This article was published as part of a supplement entitled “Coordinated Surveillance and Detection of Pneumococcal and Hib Disease in Developing Countries. This is also likely to facilitate integration of the data that is obtained into local decision making. serotyped. The results for pneumococcal serotype epidemiology are informative in several regards. and the netSPEAR team of Dr. The burden of pneumococcal disease is substantially greater among individuals with HIV infection. [5] that appears elsewhere in this issue of Clinical Infectious Diseases. Anthony Scott. Because of logistical challenges that are still to be overcome. these guidelines are nonbinding. for their unlimited support and guidance. up to 600%. One of these sites is a research center and acts as the network’s reference laboratory. for their tireless efforts in performing serotyping for the collected isolates and consolidating data. Wamae Maranga. the Ministries of Health. it is obvious that isolation of bacteria as a reflection of microbiological performance of laboratories was low at some sites.org/ by guest on September 27. Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) at Johns Hopkins University. without whose help the regional surveillance work would not be a success. GlaxoSmithKline also provided an unconditional grant for network conferences for 3 years. Proportion of cases of pneumococcal disease due to serotype 1. where antibiotic resistance levels are relatively low. Although an attempt was made to introduce evidence-based standard operating procedures in netSPEAR to standardize and improve the quality of surveillance in clinical practice.. Linda Omolo. The East African region can be considered an area of high endemicity and has a high prevalence of HIV infection. serotype 5. some sites still do not send samples for confirmation and typing. Dr. there is a discrepancy between number of isolates confirmed. Coverage improved to 180% for PCV10 serotypes in Kenya and Tanzania but not Uganda. and tested for antibiotic susceptibility and the total number of isolates reported. for their helpful guidance and comments on this article. As shown in tables 2 and 3. and Tanzania that have hopes of introducing the vaccine are encouraged to conduct appropriate surveillance to establish a baseline measure and monitor the impact of vaccination. it should increasingly be driven by the Ministries of Health in each country and perceived as a critical public health function worthy of specific support. the number of samples collected has increased from 0 to ∼750 samples per month in 2007. Mike English and Dr. this may reflect low selection pressure for these strains in this region. the National Public Health Laboratories. This has the potential to increase the frequency of misdiagnosis and is an issue that is further discussed in the article by Ben Amos et al. Angela Karani and Joyce Nyiro. in part. These data must be interpreted with caution. differences in clinical practice and considerable variability in the operational case definition in different hospitals may occur. and the World Health Organization Paediatric Bacterial Meningitis offices in each participating country. Coverage with the available PCV7 was ∼50% in our network countries. the laboratory staff at the Kenya Medical Research Institute/Wellcome Trust Research Program (Kilifi. Supplement sponsorship. or other serotypes. PneumoADIP is funded in full by the GAVI Alliance and The Vaccine Fund. The coverage of the currently or soon to be available pneumococcal conjugate vaccines was relatively high. there have been great challenges in sustaining and improving performance to obtain a high volume of quality data. largely related to human resource inadequacies in the public health systems. serotype coverage of PCV7 is also relatively low. and laboratory staff of the participating hospitals. pneumonia Invasive Disease and Meningitis • CID 2009:48 (Suppl 2) • S151 . influenzae and S. reflecting the known association between these serotypes and respiratory disease [6. Acknowledgments We thank all of the dedicated clinical. ∼70% of the data came from 4 sites located in Kenya and Uganda. for training of surveillance staff on good laboratory practice. the proportion of isolates obtained from blood samples that were serotypes 1 and 5 (30%) is higher than the proportion of isolates obtained from CSF samples that were serotypes 1 and 5 (18%). Expanded Programs of Immunization. Kenya). nursing. Joe Oundo.g. Uganda. attributable to differences between the participating sites (e. Among the other sites. Dr.Figure 1. In the case of blood samples that were not originally part of World Health Organization Paediatric Bacterial Meningitis activities. Coverage with PCV13 was high in all countries (at least 79%). Financial support. Sandra Mudhune. adherence to laboratory standard operating procedures is likely to vary. Not surprisingly. 7] (figure 1). younger age of patients contributing serotype data in Kenya and the predominance of blood samples over CSF samples in Tanzania). For surveillance to succeed. In sub-Saharan Africa. for the continued efforts in coordinating and providing services for the regional surveillance. Differences in the coverage of vaccine serotypes may be largely attributable to a low prevalence of disease due to serotype 1 in Uganda and. Countries such as Kenya. Similarly. and Caroline Mate.” sponsored by GAVI Alli- Downloaded from http://cid.

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