Exogenous re-infection by a novel Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis in a child from The Gambia
© Antonio et al; licensee BioMed Central Ltd. 2009
Received: 28 September 2008
Accepted: 20 January 2009
Published: 20 January 2009
We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively.
Pneumococcal meningitis is common within the African meningitis belt and occurs in a seasonal pattern indistinguishable from that of meningococcal meningitis . Streptococcus pneumoniae can be subdivided by serological typing based on the capsular polysaccharide protein into at least 91 different serotypes  the majority of which rarely cause disease. S. pneumoniae serotype14 is a common cause of severe pneumococcal disease in The Gambia and ranks first among 127 pediatric invasive isolates recently tested during a 9-valent pneumococcal conjugate vaccine trial in The Gambia . S. pneumoniae serotype14 has also been associated with meningitis outbreaks in Ghana  and Niger . The World Health Organisation recommends the use of the 7-valent pneumococcal conjugate vaccine  which contains serotype 14, but this is not yet available for routine use in Africa including The Gambia. Multilocus sequence typing (MLST) is a well-established method that has been used to assess the population structure of S. pneumoniae during vaccine studies in The Gambia . This report describes the use of MLST to demonstrate exogenous re-infection as a cause of recurrent meningitis in a child from The Gambia.
A six months old female of the Manjago tribe, from a peri-urban coastal village in The Gambia was referred from a primary health care facility and admitted to the Royal Victoria Teaching Hospital, Banjul on 6th December 2007 with clinical signs suggestive of meningitis. This diagnosis was confirmed by microscopic examination of the cerebrospinal fluid (CSF), which revealed gram-positive cocci and leucocytosis. The child was clinically successfully treated with intravenous ceftriaxone (100 mg/kg body weight daily for 13 days), during which S. pneumoniae was isolated from the CSF, subsequently identified as serotype 14 using methods described previously . No neurological sequelae were evident after this episode. On 3rd January 2008, the same child was re-admitted to the Medical Research Council Laboratories Hospital, Fajara again with clinical signs suggestive of meningitis. Similarly, this diagnosis was confirmed by microscopic examination of the CSF, which revealed gram-positive cocci and leucocytosis. Both CSF and blood culture from the second episode grew S. pneumoniae later confirmed as serotype 14. The second episode was treated without recurrence using intravenous chloramphenicol (25 mg/kg/dose) and crystalline penicillin (100,000 i.u/kg/dose) both 6 hourly for 14 days. Sadly the child had obvious neurological sequelae from the second episode.
The MRC microbiology laboratory submits to the external quality assurance programme of the United Kingdom National External Quality Assessment Service .
Antibiotic susceptibility patterns of S. pneumoniae serotype 14 used in this study.
E-Test MIC μg/ml
Serotype 14 is covered by both the 7-valent and 9-valent pneumococcal conjugate vaccines (Wyeth). However, during the efficacy trial in The Gambia, three of the children who received three doses of the 9-valent pneumococcal conjugate vaccine were infected with serotype 14 of ST 63, ST 3320 and ST 3333 . In this study, the first episode of meningitis was caused by serotype 14 of ST915; a clone previously described in carriage from The Gambia and is a single-locus variant (SLV) to the ST3318 clonal complex which has so far only been reported from The Gambia . The second episode was due to a novel ST (unassigned), which is a SLV to the hypervirulent ST63. The ST63 clonal complex has caused cases of meningitis in Northern Ghana and Niger [4, 5]. However in The Gambia, ST63 is common in cases of pneumonia and bacteraemia . Furthermore, ST63 can also express serotypes 15A, 19A, 19F and 23F  indicating it propensity to switch serotypes. The two clones (ST915 and unassigned ST) recovered from both episodes of meningitis shared no alleles and BOX-PCR fingerprinting analysis revealed distinct profiles indicating that these are unrelated clones (figures 1 and 2).
Recurrent systemic pneumococcal infection is known to occur in immunocompromised patients and patients with underlying conditions such as sickle-cell disease, asplenia, HIV, intracranial structural abnormalities or immununological abnormalities [12–15]. Unfortunately, we were not able to investigate any underlying conditions in this child.
To our knowledge this is the first report describing the exogenous re-infection of serotype 14 pneumococcal disease as the cause of meningitis from The Gambia. The prominence of exogenous re-infection over relapse in this patient with meningitis shows that current therapy for meningitis in The Gambia is effective. However, this case re-emphasizes the need for prevention of invasive pneumococcal disease through routine conjugate pneumococcal vaccination, which has yet to be introduced anywhere in Africa. In addition, molecular genotyping of bacterial isolates is critical to understand recurrent infections in patients with meningitis.
Consent was obtained from the patient's parents to report the case, which was identified through meningitis surveillance approved by The Gambian Government/MRC ethics committee
- Greenwood B: 100 years of epidemic meningitis in West Africa – has anything changed?. Trop Med Int Health. 2006, 773-780.Google Scholar
- Park I, Pritchard D, Cartee R, Brandao A, Brandileone M, Nahm M: Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae. J Clin Microbiol. 2007, 45 (4): 1225-1233. 10.1128/JCM.02199-06PubMed CentralView ArticlePubMedGoogle Scholar
- Antonio M, Dada-Adegbola H, Biney E, Awine T, O'Callaghan J, Pfluger V, Enwere G, Okoko B, Oluwalana C, Vaughan A: Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine. BMC Infect Dis. 2008, 8 (1): 81 10.1186/1471-2334-8-81PubMed CentralView ArticlePubMedGoogle Scholar
- Leimkugel J, Adams Forgor A, Gagneux S, Pfluger V, Flierl C, Awine E, Naegeli M, Dangy J, Smith T, Hodgson A: An outbreak of serotype 1 Streptococcus pneumoniae meningitis in northern Ghana with features that are characteristic of Neisseria meningitidis meningitis epidemics. J Infect Dis. 2005, 192: 192-199. 10.1086/431151View ArticlePubMedGoogle Scholar
- Yaro S, Lourd M, Traore Y, Njanpop-Lafourcade B, Sawadogo A, Sangare L, Hien A, Ouedraogo M, Sanou O, Parent du Chatelet I: Epidemiological and molecular characteristics of a highly lethal pneumococcal meningitis epidemic in Burkina Faso. Clin Infect Dis. 2006, 43: 693-700. 10.1086/506940View ArticlePubMedGoogle Scholar
- WHO: Pneumococcal conjugate vaccine for childhood immunisation-WHO position paper. Wkly Epidemiol Rec. 2007, 82 (12): 93-104.Google Scholar
- Cutts F, Zaman S, Enwere G, Jaffar S, Levine O, Okoko J, Oluwalana C, Vaughan A, Obaro S, Leach A: Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet. 2005, 365: 1139-1146. 10.1016/S0140-6736(05)71876-6View ArticlePubMedGoogle Scholar
- United Kingdom National External Quality Assessment Service . http://www.ukneqas.org.uk
- Hill P, Akisanya A, Sankareh K, Cheung Y, Saaka M, Lahai G, Greenwood B, Adegbola R: Nasopharyngeal Carriage of Streptococcus pneumoniae in Gambian Villagers. Clin Infect Dis. 2006, 43: 673-679. 10.1086/506941View ArticlePubMedGoogle Scholar
- eBURST V3 .http://eburst.mlst.net
- Multi Locus Sequence Typing. http://spneumoniae.mlst.net/
- Mason EJ, Wald E, Tan T, Schutze G, Bradley J, Barson W, Givner L, Hoffman J, Kaplan S: Recurrent systemic pneumococcal disease in children. Pediatr Infect Dis J. 2007, 6: 480-484.View ArticleGoogle Scholar
- Reinert R, Büssing A, Kierdorf H, Kühnemund O, Kaufhold A: Recurrent systemic pneumococcal infection in an immunocompromised patient. Eur J Clin Microbiol Infect Dis. 1994, 13: 304-307. 10.1007/BF01974605View ArticlePubMedGoogle Scholar
- Szabó J, Dobay O, Erdos M, Borbély A, Rozgonyi F, L M: Recurrent infection with genetically identical pneumococcal isolates in a patient with interleukin-1 receptor-associated kinase-4 deficiency. J Med Microbiol. 2007, 56: 863-865. 10.1099/jmm.0.47046-0View ArticlePubMedGoogle Scholar
- Turvey S, Speert D: Recurrent systemic pneumococcal disease and IRAK4 deficiency. Pediatr Infect Dis J. 2007, 11: 1074View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.