| Literature DB >> 33919828 |
Marc Rondy1, Mamadou Tamboura2, Fati Sidikou3, Issaka Yameogo4, Kambire Dinanibe5, Guetwende Sawadogo6, Chantal Kambire7, Halima Mainassara3, Ali Elhaj Mahamane3, Baruani Bienvenu8, Haladou Moussa8, Rasmata Ouedraogo2, Katya Fernandez9, Muhamed-Kheir Taha10, Olivier Ronveaux11.
Abstract
New lateral flow tests for the diagnosis of Neisseria meningitidis (Nm) (serogroups A, C, W, X, and Y), MeningoSpeed, and Streptococcus pneumoniae (Sp), PneumoSpeed, developed to support rapid outbreak detection in Africa, have shown good performance under laboratory conditions. We conducted an independent evaluation of both tests under field conditions in Burkina Faso and Niger, in 2018-2019. The tests were performed in the cerebrospinal fluid of suspected meningitis cases from health centers in alert districts and compared to reverse transcription polymerase chain reaction tests performed at national reference laboratories (NRLs). Health staff were interviewed about feasibility. A total of 327 cases were tested at the NRLs, with 26% confirmed Nm (NmC 63% and NmX 37%) and 8% Sp. Sensitivity and specificity were, respectively, 95% (95% CI: 89-99) and 90% (95% CI: 86-94) for Nm and 92% (95% CI: 75-99) and 99% (95% CI: 97-100) for Sp. Positive and negative predictive values were, respectively, 77% (95% CI: 68-85) and 98% (95% CI: 95-100) for Nm and 86% (95% CI: 67-96) and 99% (95% CI: 98-100) for Sp. Concordance showed 82% agreement for Nm and 97% for Sp. Interviewed staff evaluated the tests as easy to use and to interpret and were confident in their readings. Results suggest overall good performance of both tests and potential usefulness in meningitis outbreak detection.Entities:
Keywords: Burkina Faso; Neisseria meningitidis; Niger; Streptococcus pneumoniae; cerebrospinal fluid; meningitis; national reference laboratory; rapid diagnostic test
Year: 2021 PMID: 33919828 PMCID: PMC8070799 DOI: 10.3390/microorganisms9040832
Source DB: PubMed Journal: Microorganisms ISSN: 2076-2607
Characteristics and distribution of symptoms among suspected cases (N = 327), Niger and Burkina Faso, 2018–2019.
| Characteristics | N | % | |
|---|---|---|---|
| Total patients | 327 | 100 | |
| Recruitment country | Burkina Faso | 81 | 25 |
| Niger | 246 | 75 | |
| Recruitment period | Epidemic | 198 | 61 |
| Non-epidemic | 129 | 39 | |
| Age—average (range) | 9 years (3 months—86 years) | ||
| Symptoms | Sudden onset of fever | 316 | 97 |
| Abdominal pain | 181 | 55 | |
| Confusion and disorientation | 180 | 55 | |
| Joint pain | 136 | 42 | |
| Stiff neck | 116 | 36 | |
| Bulging fontanelle | 10 | 3 | |
| Petechial rash | 1 | 0 | |
| other meningeal signs | 18 | 6 | |
| Nm RDT results | All serogroups | 106 | 32 |
| NmA | 9 | 3 | |
| NmC | 56 | 17 | |
| NmW | 2 | 1 | |
| NmX | 40 | 12 | |
| NmY | 1 | 0 | |
| Negative | 221 | 68 | |
| Sp RDT results | Positive | 28 | 9 |
| Negative | 295 | 91 | |
Concordance of results obtained by RDT in PHCs and NRLs with results obtained by PCR in NRLs, and serogroup-specific performances, Burkina Faso and Niger, 2018–2019.
| PCR Negative/RDT Negative | PCR Positive/RDT Positive | PCR Negative/RDT Positive | PCR Positive/RDT Negative | Total | Sensitivity (%) | 95% CI | Specificity (%) | 95% CI | PPV (%) | 95% CI | NPV (%) | 95% CI | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| All Nm | 217 | 82 | 24 | 4 | 327 | 95 | (89;99) | 90 | (86;94) | 77 | (68;85) | 98 | (95;100) |
| NmA | 318 | 0 | 9 | 0 | 327 | NA | 97 | (95;99) | NA | 100 | (99;100) | |||
| NmC | 266 | 50 | 6 | 4 | 326 | 93 | (82;98) | 98 | (95;99) | 89 | (78;96) | 99 | (96;100) | |
| NmW | 324 | 0 | 2 | 0 | 326 | NA | 99 | (98;100) | NA | 100 | (99;100) | |||
| NmX | 284 | 29 | 11 | 3 | 327 | 91 | (75;98) | 96 | (93;98) | 73 | (56;85) | 99 | (97;100) | |
| NmY | 324 | 0 | 1 | 0 | 325 | NA | 100 | (98;100) | NA | 100 | (99;100) | |||
| Sp | 293 | 24 | 4 | 2 | 323 | 92 | (75;99) | 99 | (97;100) | 86 | (67;96) | 99 | (98;100) | |
|
| All Nm | 108 | 28 | 6 | 2 | 144 | 93 | (78;99) | 95 | (89;98) | 82 | (66;93) | 98 | (94;100) |
| NmA | 141 | 0 | 6 | 0 | 147 | NA | 96 | (91;99) | NA | 100 | (97;100) | |||
| NmC | 127 | 16 | 2 | 1 | 146 | 94 | (71;100) | 98 | (95;100) | 89 | (65;99) | 99 | (96;100) | |
| NmW | 142 | 0 | 3 | 0 | 145 | NA | 98 | (94;100) | NA | 100 | (97;100) | |||
| NmX | 132 | 12 | 0 | 1 | 145 | 92 | (64;100) | 100 | (97;100) | 100 | (74;100) | 99 | (96;100) | |
| NmY | 144 | 0 | 2 | 0 | 146 | NA | 99 | (95;100) | NA | 100 | (98;100) | |||
| Sp | 138 | 8 | 0 | 1 | 147 | 89 | (52;100) | 100 | (97;100) | 100 | (63;100) | 99 | (96;100) | |
RDT: rapid diagnostic test; PHC: primary health care center; NRL: national reference laboratory; PCR: polymerase chain reaction, 95% CI: 95% confidence intervel; PPV: positive predictive value; NPV: negative predictive value; Nm: Neisseria meningitidis; Sp: Streptococcus pneumoniae.
Concordance of results obtained by RDT in PHCs with results obtained by PCR in NRLs, and serogroup specific performances, by year of lumbar puncture, Burkina Faso and Niger, 2018–2019.
| PCR Negative/RDT Negative | PCR Positive/RDT Positive | PCR Negative/RDT Positive | PCR Positive/RDT Negative | Total | Sensitivity (%) | 95% CI | Specificity (%) | 95% CI | PPV (%) | 95% CI | NPV (%) | 95% CI | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2018 | All Nm | 80 | 16 | 17 | 1 | 114 | 94 | (71;100) | 83 | (73;89) | 49 | (31;67) | 99 | (93;100) |
| NmA | 106 | NA | 8 | NA | 114 | NA | NA | 93 | (87;97) | NA | NA | 100 | (97;100) | |
| NmC | 110 | 4 | NA | NA | 114 | 100 | (40;100) | 100 | (97;100) | 100 | (40;100) | 100 | (97;100) | |
| NmW | 112 | NA | 1 | NA | 113 | NA | NA | 99 | (95;100) | NA | NA | 100 | (97;100) | |
| NmX | 93 | 12 | 8 | 1 | 114 | 92 | (64;100) | 92 | (85;97) | 60 | (36;81) | 99 | (94;100) | |
| NmY | 114 | NA | NA | NA | 114 | NA | NA | 100 | (97;100) | NA | NA | 100 | (97;100) | |
| Sp | 108 | 4 | 1 | 113 | 100 | (40;100) | 99 | (95;100) | 80 | (28;100) | 100 | (97;100) | ||
| 2019 | All Nm | 135 | 64 | 7 | 3 | 209 | 96 | (88;99) | 95 | (90;98) | 90 | (81;96) | 98 | (94;100) |
| NmA | 208 | NA | 1 | NA | 209 | NA | NA | 100 | (97;100) | NA | NA | 100 | (98;100) | |
| NmC | 154 | 45 | 5 | 4 | 208 | 92 | (80;98) | 97 | (93;99) | 90 | (78;97) | 98 | (94;99) | |
| NmW | 208 | NA | 1 | NA | 209 | NA | NA | 100 | (97;100) | NA | NA | 100 | (98;100) | |
| NmX | 188 | 17 | 3 | 1 | 209 | 94 | (73;100) | 98 | (96;100) | 85 | (62;97) | 100 | (97;100) | |
| NmY | 207 | NA | 1 | NA | 208 | NA | NA | 100 | (97;100) | NA | NA | 100 | (98;100) | |
| Sp | 182 | 20 | 3 | 2 | 207 | 91 | (71;99) | 98 | (95;100) | 87 | (66;97) | 99 | (96;100) | |
RDT: rapid diagnostic test; PHC: primary health care center; NRL: national reference laboratory; PCR: polymerase chain reaction; 95% CI: 95% confidence intervel; PPV: positive predictive value; NPV: negative predictive value; Nm: Neisseria meningitidis; Sp: Streptococcus pneumoniae.
Concordance of results obtained by RDT in PHCs with results obtained by PCR in NRLs, and serogroup specific performances, by epidemic vs. non epidemic period, Burkina Faso and Niger, 2018–2019.
| PCR Negative/RDT Negative | PCR Positive/RDT Positive | PCR Negative/RDT Positive | PCR Positive/RDT Negative | Total | Sensitivity (%) | 95% CI | Specificity (%) | 95% CI | PPV (%) | 95% CI | NPV (%) | 95% CI | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Epidemic period | All Nm | 123 | 64 | 8 | 3 | 198 | 96 | (88;99) | 94 | (88;97) | 89 | (79;95) | 98 | (93;100) |
| NmA | 197 | NA | 1 | NA | 198 | NA | NA | 100 | (97;100) | NA | NA | 100 | (98;100) | |
| NmC | 143 | 45 | 5 | 4 | 197 | 92 | (80;98) | 97 | (92;99) | 90 | (78;97) | 97 | (93;99) | |
| NmW | 197 | NA | 1 | NA | 198 | NA | NA | 100 | (97;100) | NA | NA | 100 | (98;100) | |
| NmX | 176 | 17 | 4 | 1 | 198 | 94 | (73;100) | 98 | (94;99) | 81 | (58;95) | 99 | (97;100) | |
| NmY | 196 | NA | 1 | NA | 197 | NA | NA | 100 | (97;100) | NA | NA | 100 | (98;100) | |
| Sp | 174 | 17 | 3 | 2 | 196 | 90 | (67;99) | 98 | (95;100) | 85 | (62;97) | 99 | (96;100) | |
| Non epidemic period | All Nm | 94 | 18 | 16 | 1 | 129 | 95 | (74;100) | 86 | (78;92) | 53 | (35;70) | 99 | (94;100) |
| NmA | 121 | NA | 8 | NA | 129 | NA | NA | 94 | (88;97) | NA | NA | 100 | (97;100) | |
| NmC | 123 | 5 | 1 | NA | 129 | 100 | (48;100) | 99 | (96;100) | 83 | (36;100) | 100 | (97;100) | |
| NmW | 127 | NA | 1 | NA | 128 | NA | NA | 99 | (96;100) | NA | NA | 100 | (97;100) | |
| NmX | 108 | 12 | 7 | 2 | 129 | 86 | (57;98) | 94 | (88;98) | 63 | (38;84) | 98 | (94;100) | |
| NmY | 128 | NA | NA | NA | 128 | NA | NA | 100 | (97;100) | NA | NA | 100 | (97;100) | |
| Sp | 119 | 7 | 1 | NA | 127 | 100 | (59;100) | 99 | (95;100) | 88 | (47;100) | 100 | (97;100) | |
RDT: rapid diagnostic test; PHC: primary health care center; NRL: national reference laboratory; PCR: polymerase chain reaction; 95% CI: 95% confidence intervel; PPV: positive predictive value; NPV: negative predictive value; Nm: Neisseria meningitidis; Sp: Streptococcus pneumoniae.
Concordance of the results of RDTs as interpreted live in the PHCs and by independent reading of photographs, Burkina Faso and Niger, 2018–2019.
| Test | Photo Reading Negative/RDT Negative | Photo Reading Positive/RDT Positive | Photo Reading Negative/RDT Positive | Photo Reading Positive/RDT Negative | Total | Concordance (%) | Kappa Coefficient | |
|---|---|---|---|---|---|---|---|---|
| RDTs at health centers | All Nm | 36 | 17 | 11 | 1 | 65 | 82 | 61 |
| NmA | 64 | 2 | 6 | 1 | 73 | 90 | 32 | |
| NmC | 71 | 1 | 3 | 0 | 75 | 96 | 39 | |
| NmW | 68 | 1 | 0 | 4 | 73 | 95 | 32 | |
| NmX | 53 | 13 | 4 | 0 | 70 | 94 | 83 | |
| NmY | 71 | 0 | 0 | 0 | 71 | 100 | NA | |
| Sp | 66 | 5 | 1 | 1 | 73 | 97 | 82 |
RDT: rapid diagnostic test; PHC: primary health care center; Nm: Neisseria meningitidis; Sp: Streptococcus pneumoniae.
Figure 1Photographs of six false positive NmA RDTs by independent expert classification, Burkina Faso and Niger, 2018–2019.