Abstract

Meningococcal meningitis outbreaks occur every year during the dry season in the “meningitis belt” of sub-Saharan Africa. Identification of the causative strain is crucial before launching mass vaccination campaigns, to assure use of the correct vaccine. Rapid agglutination (latex) tests are most commonly available in district-level laboratories at the beginning of the epidemic season; limitations include a short shelf-life and the need for refrigeration and good technical skills. Recently, a new dipstick rapid diagnostic test (RDT) was developed to identify and differentiate disease caused by meningococcal serogroups A, W135, C and Y. We evaluated the diagnostic performance of this dipstick RDT during an urban outbreak of meningitis caused by N. meningitidis serogroup A in Ouagadougou, Burkina Faso; first against an in-country reference standard of culture and/or multiplex PCR; and second against culture and/or a highly sensitive nested PCR technique performed in Oslo, Norway. We included 267 patients with suspected acute bacterial meningitis. Using the in-country reference standard, 50 samples (19%) were positive. Dipstick RDT sensitivity (N = 265) was 70% (95%CI 55–82) and specificity 97% (95%CI 93–99). Using culture and/or nested PCR, 126/259 (49%) samples were positive; dipstick RDT sensitivity (N = 257) was 32% (95%CI 24–41), and specificity was 99% (95%CI 95–100). We found dipstick RDT sensitivity lower than values reported from (i) assessments under ideal laboratory conditions (>90%), and (ii) a prior field evaluation in Niger [89% (95%CI 80–95)]. Specificity, however, was similar to (i), and higher than (ii) [62% (95%CI 48–75)]. At this stage in development, therefore, other tests (e.g., latex) might be preferred for use in peripheral health centres. We highlight the value of field evaluations for new diagnostic tests, and note relatively low sensitivity of a reference standard using multiplex vs. nested PCR. Although the former is the current standard for bacterial meningitis surveillance in the meningitis belt, nested PCR performed in a certified laboratory should be used as an absolute reference when evaluating new diagnostic tests.

Highlights

  • Most large meningitis epidemics in sub-Saharan Africa are still caused by Neisseria meningitidis serogroup A [1], recent meningococcal outbreaks caused by serogroups W135 [2,3] and X [4,5] underline the importance of serogroup-specific bacteriological surveillance and outbreak investigation

  • They necessitate a well-equipped laboratory with well-trained, specialised technicians, neither of which is often available close to the outbreak location, cerebrospinal fluid (CSF) samples can be tested by polymerase chain reaction (PCR) after transport at ambient temperature in simple dry tubes, which makes it useful for surveillance in remote areas of sub-Saharan Africa [7]

  • Using an in-country reference standard of culture and/or multiplex PCR, we show that dipstick rapid diagnostic test (RDT) sensitivity at 70% (95%CI 55–82) was lower and specificity at 97% (95%CI 93–99) was substantially higher than found in an earlier dipstick RDT field evaluation using the same reference standard [89% (95%CI 80–95) and 62% (95%CI 48–75) respectively] [11]

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Summary

Introduction

Most large meningitis epidemics in sub-Saharan Africa are still caused by Neisseria meningitidis serogroup A [1], recent meningococcal outbreaks caused by serogroups W135 [2,3] and X [4,5] underline the importance of serogroup-specific bacteriological surveillance and outbreak investigation. Culture isolation plus strain serogrouping and PCR-based methods are generally considered as the reference standard for identification of N. meningitidis serogroups, since they are highly specific. They necessitate a well-equipped laboratory with well-trained, specialised technicians, neither of which is often available close to the outbreak location, CSF samples can be tested by PCR after transport at ambient temperature in simple dry tubes, which makes it useful for surveillance in remote areas of sub-Saharan Africa [7]. Some highly sensitive methods, such as nested PCR, used in supranational reference laboratories, are less adapted to field conditions due to the high probability of contamination, but are helpful as a reference standard

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