1921
Volume 103, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, , type b (Hib), and serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for , , and used in routine meningitis surveillance A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and . Overall, was the most prevalent (4.8%), followed by (3.5%) and (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.19-0566
2020-05-26
2020-09-28
Loading full text...

Full text loading...

/deliver/fulltext/14761645/103/2/tpmd190566.html?itemId=/content/journals/10.4269/ajtmh.19-0566&mimeType=html&fmt=ahah

References

  1. Brandtzaeg P, van Deuren M, 2012. Classification and pathogenesis of meningococcal infections. Methods Mol Biol 799: 2135.
    [Google Scholar]
  2. Collaborators GBDM, 2018. Global, regional, and national burden of meningitis, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 17: 10611082.
    [Google Scholar]
  3. Ramakrishnan M, Ulland AJ, Steinhardt LC, Moisi JC, Were F, Levine OS, 2009. Sequelae due to bacterial meningitis among African children: a systematic literature review. BMC Med 7: 47.
    [Google Scholar]
  4. Wahl B et al., 2018. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15. Lancet Glob Health 6: e744e757.
    [Google Scholar]
  5. Trotter CL, Lingani C, Fernandez K, Cooper LV, Bita A, Tevi-Benissan C, Ronveaux O, Préziosi MP, Stuart JM, 2017. Impact of MenAfriVac in nine countries of the African meningitis belt, 2010–15: an analysis of surveillance data. Lancet Infect Dis 17: 867872.
    [Google Scholar]
  6. Mwenda JM et al., 2019. Pediatric bacterial meningitis surveillance in the World Health Organization African region using the invasive bacterial vaccine-preventable disease surveillance network, 2011–2016. Clin Infect Dis 69 (Suppl 2): S49S57.
    [Google Scholar]
  7. WHO, 2018. Defeating Meningitis by 2030: First Meeting of the Technical Taskforce. Available at: https://www.who.int/immunization/research/Defeating_meningitis_2030_TTFJuly2018_report.pdf. Accessed July 1, 2019.
    [Google Scholar]
  8. Liu J et al., 2014. Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicentre study. Lancet Infect Dis 14: 716724.
    [Google Scholar]
  9. Sacchi CT et al., RT-PCR Surveillance Project Team, 2011. Incorporation of real-time PCR into routine public health surveillance of culture negative bacterial meningitis in Sao Paulo, Brazil. PLoS One 6: e20675.
    [Google Scholar]
  10. Heinsbroek E, Ladhani S, Gray S, Guiver M, Kaczmarski E, Borrow R, Ramsay M, 2013. Added value of PCR-testing for confirmation of invasive meningococcal disease in England. J Infect 67: 385390.
    [Google Scholar]
  11. Moore CC, Jacob ST, Banura P, Zhang J, Stroup S, Boulware DR, Michael Scheld W, Houpt ER, Liu J, 2019. Etiology of sepsis in Uganda using a quantitative polymerase chain reaction-based TaqMan array card. Clin Infect Dis 68: 266272.
    [Google Scholar]
  12. Abade A et al., 2018. Use of TaqMan array cards to screen outbreak specimens for causes of febrile illness in Tanzania. Am J Trop Med Hyg 98: 16401642.
    [Google Scholar]
  13. Velaphi SC et al., 2019. Surveillance for incidence and etiology of early-onset neonatal sepsis in Soweto, South Africa. PLoS One 14: e0214077.
    [Google Scholar]
  14. Saha SK et al., 2018. Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study. Lancet 392: 145159.
    [Google Scholar]
  15. Liu J et al., 2016. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet 388: 12911301.
    [Google Scholar]
  16. Sonko MA et al., 2019. Changes in the molecular epidemiology of pediatric bacterial meningitis in Senegal after pneumococcal conjugate vaccine introduction. Clin Infect Dis 69 (Suppl 2): S156S63.
    [Google Scholar]
  17. Renner LA et al., 2019. Hospital-based surveillance for pediatric bacterial meningitis in the era of the 13-valent pneumococcal conjugate vaccine in Ghana. Clin Infect Dis 69 (Suppl 2): S89S96.
    [Google Scholar]
  18. Tsolenyanu E et al., 2019. Etiology of pediatric bacterial meningitis pre- and post-PCV13 introduction among children under 5 years old in lomé, Togo. Clin Infect Dis 69 (Suppl 2): S97S104.
    [Google Scholar]
  19. Tagbo BN et al., 2019. Pediatric bacterial meningitis surveillance in Nigeria from 2010 to 2016, prior to and during the phased introduction of the 10-valent pneumococcal conjugate vaccine. Clin Infect Dis 69 (Suppl 2): S81S8.
    [Google Scholar]
  20. Kourna Hama M et al., 2019. Pediatric bacterial meningitis surveillance in Niger: increased importance of Neisseria meningitidis serogroup C, and a decrease in Streptococcus pneumoniae following 13-valent pneumococcal conjugate vaccine introduction. Clin Infect Dis 69 (Suppl 2): S133S139.
    [Google Scholar]
  21. Marc LaForce F, Ravenscroft N, Djingarey M, Viviani S, 2009. Epidemic meningitis due to group A Neisseria meningitidis in the African meningitis belt: a persistent problem with an imminent solution. Vaccine 27 (Suppl 2): B13B19.
    [Google Scholar]
  22. World Health Organization, 2018. WHO position paper, meningococcal a conjugate vaccine: updated guidance, February 2015. Vaccine 36: 34213422.
    [Google Scholar]
  23. WHO, 2014. Meningitis Outbreak Response in Sub-Saharan Africa: WHO Guideline. Geneva, Switzerland: World Health Organization.
    [Google Scholar]
  24. Kwambana-Adams BA et al., 2016. An outbreak of pneumococcal meningitis among older children (≥5 years) and adults after the implementation of an infant vaccination programme with the 13-valent pneumococcal conjugate vaccine in Ghana. BMC Infect Dis 16: 575.
    [Google Scholar]
  25. Vuong J et al., 2016. Development of real-time PCR methods for the detection of bacterial meningitis pathogens without DNA extraction. PLoS One 11: e0147765.
    [Google Scholar]
  26. Wang X 2011. Detection of bacterial pathogens in Mongolia meningitis surveillance with a new real-time PCR assay to detect Haemophilus influenzae. Int J Med Microbiol 301: 303309.
    [Google Scholar]
  27. Collaborators GM, 2017. Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390: 10841150.
    [Google Scholar]
  28. Onyango CO et al., 2017. Evaluation of a TaqMan array card for detection of central nervous system infections. J Clin Microbiol 55: 20352044.
    [Google Scholar]
  29. Diaz MH et al., 2013. Optimization of multiple pathogen detection using the TaqMan array card: application for a population-based study of neonatal infection. PLoS One 8: e66183.
    [Google Scholar]
  30. Liu J et al., 2016. Optimization of quantitative PCR methods for enteropathogen detection. PLoS One 11: e0158199.
    [Google Scholar]
  31. Liu J et al., 2016. Development of a TaqMan array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including ebola virus. J Clin Microbiol 54: 4958.
    [Google Scholar]
  32. Centers for Disease Control and Prevention (CDC), 2009. Pediatric bacterial meningitis surveillance–African region, 2002–2008. MMWR Morb Mortal Wkly Rep 58: 493497.
    [Google Scholar]
  33. Pholwat S, Sakai F, Turner P, Vidal JE, Houpt ER, 2016. Development of a TaqMan array card for pneumococcal serotyping on isolates and nasopharyngeal samples. J Clin Microbiol 54: 18421850.
    [Google Scholar]
  34. Greenwood B, 2006. Editorial: 100 years of epidemic meningitis in West Africa–has anything changed? Trop Med Int Health 11: 773780.
    [Google Scholar]
  35. Kwambana-Adams BA et al., 2018. Meningococcus serogroup C clonal complex ST-10217 outbreak in Zamfara state, northern Nigeria. Sci Rep 8: 14194.
    [Google Scholar]
  36. Sidikou F et al., 2016. Emergence of epidemic Neisseria meningitidis serogroup C in Niger, 2015: an analysis of national surveillance data. Lancet Infect Diseases 16: 12881294.
    [Google Scholar]
  37. Retchless AC et al., 2018. Molecular characterization of invasive meningococcal isolates in Burkina Faso as the relative importance of serogroups X and W increases, 2008–2012. BMC Infect Dis 18: 337.
    [Google Scholar]
  38. Brynildsrud OB, Eldholm V, Bohlin J, Uadiale K, Obaro S, Caugant DA, 2018. Acquisition of virulence genes by a carrier strain gave rise to the ongoing epidemics of meningococcal disease in West Africa. Proc Natl Acad Sci USA 115: 55105515.
    [Google Scholar]
  39. WHO, 2015. Preparedness for outbreaks of meningococcal meningitis due to Neisseria meningitidis serogroup C in Africa: recommendations from a WHO expert consultation. Wkly Epidemiol Rec 90: 633636.
    [Google Scholar]
  40. Furyk JS, Swann O, Molyneux E, 2011. Systematic review: neonatal meningitis in the developing world. Trop Med Int Health 16: 672679.
    [Google Scholar]
  41. Roine I, Weisstaub G, Peltola H; LatAm Bacterial Meningitis Study Group, 2010. Influence of malnutrition on the course of childhood bacterial meningitis. Pediatr Infect Dis J 29: 122125.
    [Google Scholar]
  42. Mulla MI, Moosajee I, Rubidge CJ, Moosa A, 1984. Nutritional status of children with pyogenic meningitis. J Trop Pediatr 30: 303306.
    [Google Scholar]
  43. Kuti BP, Bello EO, Jegede TO, Olubosede O, 2015. Epidemiological, clinical and prognostic profile of childhood acute bacterial meningitis in a resource poor setting. J Neurosci Rural Pract 6: 549557.
    [Google Scholar]
  44. Nwadioha SI, Nwokedi EO, Onwuezube I, Egesie JO, Kashibu E, 2013. Bacterial isolates from cerebrospinal fluid of children with suspected acute meningitis in a Nigerian tertiary hospital. Niger Postgrad Med J 20: 913.
    [Google Scholar]
  45. Owusu M, Nguah SB, Boaitey YA, Badu-Boateng E, Abubakr AR, Lartey RA, Adu-Sarkodie Y, 2012. Aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in Ghana. Ann Clin Microbiol Antimicrob 11: 28.
    [Google Scholar]
  46. Li G et al., 2020. Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network. Arch Dis Child 105: 2631.
    [Google Scholar]
  47. Medugu N, Iregbu K, Iroh Tam PY, Obaro S, 2018. Aetiology of neonatal sepsis in Nigeria, and relevance of Group b streptococcus: a systematic review. PLoS One 13: e0200350.
    [Google Scholar]
  48. Airede KI, Adeyemi O, Ibrahim T, 2008. Neonatal bacterial meningitis and dexamethasone adjunctive usage in Nigeria. Niger J Clin Pract 11: 235245.
    [Google Scholar]
  49. Page AL et al., 2017. Aetiology and outcomes of suspected infections of the central nervous system in children in Mbarara, Uganda. Sci Rep 7: 2728.
    [Google Scholar]
  50. Thakur KT, Vareta J, Carson KA, Kampondeni S, Potchen MJ, Birbeck GL, MacCormick I, Taylor T, Sullivan DJ, Seydel KB, 2018. Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria. Malar J 17: 125.
    [Google Scholar]
  51. Barah F, Vallely PJ, Chiswick ML, Cleator GM, Kerr JR, 2001. Association of human parvovirus B19 infection with acute meningoencephalitis. Lancet 358: 729730.
    [Google Scholar]
  52. Okomo U, Akpalu ENK, Le Doare K, Roca A, Cousens S, Jarde A, Sharland M, Kampmann B, Lawn JE, 2019. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect Dis 19: 12191234.
    [Google Scholar]
  53. Patel JC et al., 2019. MenAfriNet: a network supporting case-based meningitis surveillance and vaccine evaluation in the meningitis belt of Africa. J Infect Dis 220 (Suppl 4): S148S154.
    [Google Scholar]
  54. Kelly MJ et al., 2012. Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis. J Infect Dis 205: 106110.
    [Google Scholar]
  55. Leber AL et al., 2016. Multicenter evaluation of BioFire FilmArray meningitis/encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol 54: 22512261.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.19-0566
Loading
/content/journals/10.4269/ajtmh.19-0566
Loading

Data & Media loading...

Supplemental files

  • Received : 30 Jul 2019
  • Accepted : 30 Mar 2020
  • Published online : 26 May 2020
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error