Journal Article > ReviewAbstract
Pathog Glob Health. 2014 January 1; Volume 108 (Issue 1); DOI:10.1179/2047773214Y.0000000126
Ali A, Jafri RZ, Messonnier N, Tevi-Benissan C, Durrheim DN, et al.
Pathog Glob Health. 2014 January 1; Volume 108 (Issue 1); DOI:10.1179/2047773214Y.0000000126
A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs.
Journal Article > ResearchFull Text
PLOS One. 2010 June 11; Volume 5 (Issue 6); DOI:10.1371/journal.pone.0011086
Rose AMC, Mueller JE, Gerstl S, Njanpop-Lafourcade BM, Page AL, et al.
PLOS One. 2010 June 11; Volume 5 (Issue 6); DOI:10.1371/journal.pone.0011086
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.
Journal Article > ResearchFull Text
Epidemiol Infect. 2011 October 5; Volume 140 (Issue 8); 1356-1365.; DOI:10.1017/S0950268811002032
Bharti N, Broutin H, Grais RF, Ferrari MJ, Djibo A, et al.
Epidemiol Infect. 2011 October 5; Volume 140 (Issue 8); 1356-1365.; DOI:10.1017/S0950268811002032
Throughout the African meningitis belt, meningococcal meningitis outbreaks occur only during the dry season. Measles in Niger exhibits similar seasonality, where increased population density during the dry season probably escalates measles transmission. Because meningococcal meningitis and measles are both directly transmitted, we propose that host aggregation also impacts the transmission of meningococcal meningitis. Although climate affects broad meningococcal meningitis seasonality, we focus on the less examined role of human density at a finer spatial scale. By analysing spatial patterns of suspected cases of meningococcal meningitis, we show fewer absences of suspected cases in districts along primary roads, similar to measles fadeouts in the same Nigerien metapopulation. We further show that, following periods during no suspected cases, districts with high reappearance rates of meningococcal meningitis also have high measles reintroduction rates. Despite many biological and epidemiological differences, similar seasonal and spatial patterns emerge from the dynamics of both diseases. This analysis enhances our understanding of spatial patterns and disease transmission and suggests hotspots for infection and potential target areas for meningococcal meningitis surveillance and intervention.
Journal Article > ResearchFull Text
Lancet Infect Dis. 2017 July 1; Volume 17 (Issue 7); 754-762.; DOI:10.1016/S1473-3099(17)30170-6
Parikh S, Newbold L, Slater S, Moschioni M, Lucidarme J, et al.
Lancet Infect Dis. 2017 July 1; Volume 17 (Issue 7); 754-762.; DOI:10.1016/S1473-3099(17)30170-6
BACKGROUND
The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes.
METHODS
Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases.
FINDINGS
In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease.
INTERPRETATION
In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes.
FUNDING
Public Health England, GlaxoSmithKline.
The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes.
METHODS
Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases.
FINDINGS
In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease.
INTERPRETATION
In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes.
FUNDING
Public Health England, GlaxoSmithKline.
Journal Article > ResearchFull Text
PLOS One. 2009 October 5; Volume 4 (Issue 10); DOI:10.1371/journal.pone.0007326
Rose AMC, Gerstl S, Mahamane AE, Sidikou F, Djibo S, et al.
PLOS One. 2009 October 5; Volume 4 (Issue 10); DOI:10.1371/journal.pone.0007326
The Pastorex((R)) (BioRad) rapid agglutination test is one of the main rapid diagnostic tests (RDTs) for meningococcal disease currently in use in the "meningitis belt". Earlier evaluations, performed after heating and centrifugation of cerebrospinal fluid (CSF) samples, under good laboratory conditions, showed high sensitivity and specificity. However, during an epidemic, the test may be used without prior sample preparation. Recently a new, easy-to-use dipstick RDT for meningococcal disease detection on CSF was developed by the Centre de Recherche Médicale et Sanitaire in Niger and the Pasteur Institute in France. We estimate diagnostic accuracy in the field during the 2006 outbreak of Neisseria meningitidis serogroup A in Maradi, Niger, for the dipstick RDT and Pastorex((R)) on unprepared CSF, (a) by comparing each test's sensitivity and specificity with previously reported values; and (b) by comparing results for each test on paired samples, using McNemar's test. We also (c) estimate diagnostic accuracy of the dipstick RDT on diluted whole blood. We tested unprepared CSF and diluted whole blood from 126 patients with suspected meningococcal disease presenting at four health posts. (a) Pastorex((R)) sensitivity (69%; 95%CI 57-79) was significantly lower than found previously for prepared CSF samples [87% (81-91); or 88% (85-91)], as was specificity [81% (95%CI 68-91) vs 93% (90-95); or 93% (87-96)]. Sensitivity of the dipstick RDT [89% (95%CI 80-95)] was similar to previously reported values for ideal laboratory conditions [89% (84-93) and 94% (90-96)]. Specificity, at 62% (95%CI 48-75), was significantly lower than found previously [94% (92-96) and 97% (94-99)]. (b) McNemar's test for the dipstick RDT vs Pastorex((R)) was statistically significant (p<0.001). (c) The dipstick RDT did not perform satisfactorily on diluted whole blood (sensitivity 73%; specificity 57%).Sensitivity and specificity of Pastorex((R)) without prior CSF preparation were poorer than previously reported results from prepared samples; therefore we caution against using this test during an epidemic if sample preparation is not possible. For the dipstick RDT, sensitivity was similar to, while specificity was not as high as previously reported during a more stable context. Further studies are needed to evaluate its field performance, especially for different populations and other serogroups.
Conference Material > Abstract
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/wg9g-dq47
INTRODUCTION
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
Conference Material > Poster
Yakum MN, Gignoux E
Epicentre Scientific Day 2024. 2024 May 23
Journal Article > CommentaryAbstract Only
Clin Infect Dis. 2022 August 29; Volume 76 (Issue 3); e773-e775.; DOI:10.1093/cid/ciac689
Burry J, Casas CP, Ford NP
Clin Infect Dis. 2022 August 29; Volume 76 (Issue 3); e773-e775.; DOI:10.1093/cid/ciac689
Cryptococcal meningitis accounts for 1 in 5 AIDS-related deaths globally. World Health Organization guidelines strongly recommend a single high dose of liposomal amphotericin B as part of preferred treatment, but this drug remains unaffordable in most low- and middle-income countries. A proactive approach is needed from manufacturers and other stakeholders to improve access.
Journal Article > Case Report/SeriesFull Text
J Med Case Rep. 2023 February 9; Volume 17 (Issue 1); 52.; DOI:10.1186/s13256-022-03704-0
Sood R, Walo C, Burton R, Khalife M, Dicko A, et al.
J Med Case Rep. 2023 February 9; Volume 17 (Issue 1); 52.; DOI:10.1186/s13256-022-03704-0
BACKGROUND
Gram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease.
CASE PRESENTATION
A 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis.
CONCLUSIONS
This case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.
Gram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease.
CASE PRESENTATION
A 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis.
CONCLUSIONS
This case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.
Journal Article > CommentaryFull Text
Lancet Infect Dis. 2018 October 18; Volume 19 (Issue 4); DOI:10.1016/S1473-3099(18)30493-6
Loyse A, Burry J, Cohn J, Ford NP, Chiller T, et al.
Lancet Infect Dis. 2018 October 18; Volume 19 (Issue 4); DOI:10.1016/S1473-3099(18)30493-6
In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.