Microbiological and epidemiological investigation of the Neisseria meningitidis serogroup A epidemic in Niger in 2009: last wave before the introduction of the serogroup A meningococcal conjugate vaccine?

The 2009 meningitis season in Niger was characterized by an early onset, beginning in the very first weeks of the year and peaking from the 12th to the 15th week with 5655 clinical cases over the 4 weeks. From 1 January 2009 to 28 June 2009 (week 26), a total of 13,733 clinical cases of meningitis were reported to the national epidemiological surveillance system with a case-fatality rate of 4·2%. During the season 25 of the 42 health districts reached the epidemic threshold and 11 the alert threshold. Reactive mass vaccination campaigns involving a total of 5 166,741 doses of the polysaccharide meningococcal bivalent (A+C) vaccine progressively controlled the outbreak in most parts of the country. A total of 3755 cerebrospinal fluid samples representing 28·1% of the suspected meningitis cases were analysed. Serogroup A meningococci were the causative agent in 97·5% of the meningococcal cases. Multi-locus sequence typing of 26 meningococal serogroup A strains showed 25 sequence type (ST)7 and one ST2859, both sequence types belonging to the ST5 clonal complex (CC5) of subgroup III. This is the largest epidemic observed in Niger since those of 1995-1996 (59,948 notified cases) and 2000 (14,633 notified cases).

Epidemiology of methicillin-resistant Staphylococcus aureus lineages in five major African towns: emergence and spread of atypical clones.

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Africa is poorly documented. From January 2007 to March 2008, we collected 86 MRSA isolates from five African towns, one each in Cameroon, Madagascar, Morocco, Niger and Senegal. Although one or two major clones, defined by the sequence type and staphylococcal cassette chromosome mec type, predominated at each site, genetic diversity (ten clones) was relatively limited in view of the large geographical area studied. Most of the isolates (n = 76, 88%) belonged to three major clones, namely ST239/241-III, a well-known pandemic clone (n = 34, 40%), ST88-IV (n = 24, 28%) and ST5-IV (n = 18, 21%). The latter two clones have only been sporadically described in other parts of the world. The spread of community-associated MRSA carrying the Panton-Valentine leukocidin genes is a cause for concern, especially in Dakar and possibly throughout Africa.

Epidemiology of methicillin-susceptible Staphylococcus aureus lineages in five major African towns: high prevalence of Panton-Valentine leukocidin genes.

The epidemiology of methicillin-susceptible Staphylococcus aureus (MSSA) in Africa is poorly documented. From January 2007 to March 2008, 555 S. aureus isolates were collected from five African towns in Cameroon, Madagascar, Morocco, Niger, and Senegal; among these, 456 unique isolates were susceptible to methicillin. Approximately 50% of the MSSA isolates from each different participating centre were randomly selected for further molecular analysis. Of the 228 isolates investigated, 132 (58%) belonged to five major multilocus sequence typing (MLST) clonal complexes (CCs) (CC1, CC15, CC30, CC121 and CC152) that were not related to any successful methicillin-resistant S. aureus (MRSA) clones previously identified in the same study population. The luk-PV genes encoding Panton-Valentine leukocidin (PVL), present in 130 isolates overall (57%), were highly prevalent in isolates from Cameroon, Niger, and Senegal (West and Central Africa). This finding is of major concern, with regard to both a source of severe infections and a potential reservoir for PVL genes. This overrepresentation of PVL in MSSA could lead to the emergence and spread of successful, highly virulent PVL-positive MRSA clones, a phenomenon that has already started in Africa.

Field evaluation of rapid diagnostic tests for meningococcal meningitis in Niger.

OBJECTIVE: To evaluate dipstick rapid diagnostic tests (RDTs) for meningococcal meningitis in basic health facilities. METHODS: Health facility staff received a one-day training. During the meningitis season, they performed RDTs on cerebrospinal fluid (CSF) specimens from suspected cases of meningitis. A frozen aliquot of CSF was later tested using polymerase chain reaction (PCR) to establish the reference diagnosis. RDTs used in health facilities were archived to allow checking the concordance between reported diagnosis and observed results. Reported diagnosis was also compared to PCR diagnosis. A second RDT was performed on each CSF specimen at the reference laboratory. RESULTS: Using RDTs, health facilities reported 382 negative results (73.9%), 114 NmA (22.1%), 12 NmW135 (2.3%) and nine uninterpretable results (1.7%), the latter corresponding to the misuse of a reagent by three agents. The agreement between reported diagnosis and archived dipsticks was excellent (kappa = 0.98). The agreement between PCR diagnosis and reported RDTs results was strong (kappa = 0.82). In health facilities, the sensitivity of RDTs for N. meningitidis A was Se = 0.91. The kappa coefficient measuring the agreement between RDTs operated in the reference laboratory and RDTs operated in health facilities was kappa = 0.78. CONCLUSION: We confirmed that dipstick RDTs to identify N. meningitidis serogroups A, C, W135 and Y can be reliably operated by non-specialized staff in basic health facilities. RDTs proved very useful to recommend vaccination in NmA epidemics, and also to avoid vaccination in epidemics due to serogroups not included in vaccines (NmX).

Evaluation of the Pastorex meningitis kit for the rapid identification of Neisseria meningitidis serogroups A and W135.

The recent emergence of Neisseria meningitidis W135 as a cause of epidemic bacterial meningitis and the availability of a trivalent ACW135 vaccine have created a need for accurate and timely meningococcal serogroup determination for organization of epidemic vaccine response. The sensitivity and specificity of the Pastorex meningitis kit (Bio-Rad) to identify serogroups A and W135 in the African meningitis belt was assessed using PCR testing as the gold standard. The sensitivity and specificity for serogroups A and W135 were 87 and 85%, respectively, while the specificities were 93 and 97%. The positive and negative likelihood ratios for A were 12 and 0.14 and for W135 were 33 and 0.16. The positive and negative predictive values, computed to simulate an epidemic of meningococcal meningitis with an estimated 70% prevalence of N. meningitidis among suspected cases, were 97% and 75% for A and 99% and 73% for W135. In remote locations of the African meningitis belt, latex agglutination is the only currently available test that can rapidly determine meningococcal serogroup. This study showed that latex agglutination performs well and could be used during the epidemic season to determine appropriate vaccine response.

Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.

BACKGROUND: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. METHODS: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. FINDINGS: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. INTERPRETATION: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.

Molecular epidemiology of meningococci isolated in Niger in 2003 shows serogroup A sequence type (ST)-7 and serogroup W135 ST-11 or ST-2881 strains.

In 2003, in the Zinder and Maradi regions (Niger), epidemics were due to serogroup A:4:P1.9 meningococci belonging to sequence type 7 (ST-7). In Niamey, only sporadic cases were reported: 55% of the meningococcus strains were in serogroup A, and 38% were in serogroup W135 and could be placed in ST-11, identical to the 2002 Burkina Faso epidemic clone, and in ST-2881, a new ST.

[Pharyngeal carriage of Neisseria meningitidis in a school of Niamey, Niger]. / Portage rhino-pharyngé de méningocoque X dans une école primaire de Niamey (Niger).

This study of pharyngeal carriage of Neisseria meningitidis in a school in Niamey, Nigeria was carried out to confirm the feasibility of evaluating the impact of conjugate vaccine on the meningococcal carriage. All 90 pupils attending the school were examined during the dry season in February 1998. All children had been vaccinated using polysaccharide A/C in 1996. Samples were collected from the soft palate and immediately seeded on selective medium. After incubation at 37 degrees C for 24 hours, suspicious colonies were re-seeded on Miller-Hinton medium. Identification of N. meningitidis was based on standard biochemical criteria, agglutination grouping and DNA fingerprinting. Seven carriers of N. meningitidis X:NT:P1.5 were found. One of these carriers also presented a strain of N. meningitis A:4:P1.9. The high prevalence of serogroup X strains coincided with an outbreak of meningitis involving the same sub-type and sequence-type in Niamey.

Immunogenicity, safety, and memory of different schedules of Neisseria meningitidis A/C-diphtheria toxoid conjugate vaccine in infants in Niger.

We studied one to four doses of meningococcal polysaccharides A and C conjugated to diphtheria toxoid (Men D) versus A/C polysaccharide (Men PS) vaccine in 618 infants in Niger. Men PS at 24 months permitted evaluating memory. Two Men D doses (at 3 and 9 months) induced higher serum bactericidal activity (SBA) than other regimens. SBA titers after Men PS at 24 months were higher in those given Men D in infancy versus Men PS. While responses were lower for serogroup C, hyporesponsiveness was not evident. Men D was well-tolerated. A single Men D dose in infancy appeared to induce memory.

Portage rhino-pharenge de meningocoque X dans une ecole primaire de Niamey (Niger)

This study of pharyngeal carriage of Neisseria meningitidis in a school in Niamey; Nigeria was carried out to confirm the feasibility of evaluating the impact of conjugate vaccine on the meningococcal carriage. All 90 pupils attending the school we re examined during the dry season in Feb ru a ry 1998. All ch i l d ren had been va c c i n ated using poly s a c ch a ride A/C in 1996. Samples were collected from the soft palate and immediately seeded on selective medium. After incubation at 37oC for 24 hours; suspicious colonies we re re-seeded on Muller-Hinton medium. Identifi c ation of N. meningitidis was based on standard biochemical criteria; agglutination grouping and DNA fingerprinting. Seven carriers of N. meningitidis X:NT:P1.5 were fo u n d. One of these carriers also presented a strain of N. meningi t i s A:4:P1.9. The high prevalence of serogroup X strains coincided with an outbreak of meningitis involving the same sub-type and sequence-type in Niamey

Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000.

In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.

[Epidemiology and control of bacterial meningitis in children less than 1 year in Niamey (Niger)]. / Epidémiologie et contrôle des méningites bactériennes chez les enfants de moins d'un an à Niamey (Niger).

A bacteriological and epidemiological study of bacterial meningitis occurring in infants under one year of age was performed from September 1981 to June 1997 in Niamey, a city of 575,000 residents, located within the African meningitis belt. Cases of meningitis were defined either by culture of the cerebrospinal fluid (CSF), specific antigen agglutination, staining or cell counts of the CSF. Over the 16 years involving both epidemic and non epidemic periods, 1,481 infant's CSF were analysed, representing 20% out of the total CSF samples. The average of annual incidence rates was 511.4 cases per 100,000 infants under one year. Haemophilus influenzae b represented 35.1% of the cases, Streptococcus pneumoniae 26.3% and Neisseria meningitidis 17.6%. The other bacteria represented 5.5% and, for 15.5% out of the analysed CSF, the causative agent was not identified. The average annual mortality rate was 146.9 deaths for 100,000 infants under one year. The specific case fatality rates were 43% for H. influenzae b, 58.9% for S. pneumoniae and 17.8% for N. meningitidis. This study showed that in Niamey, as in the rest of the meningitis belt, S. pneumoniae and H. influenzae b were the main causes of bacterial meningitis occurring in infants under one year. However, the specific incidence of N1 meningitidis was identical for every age group between 0 and 20 years, and varied from 45 per 100,000 during non epidemic year to 550 per 100,000 during epidemic year. Immunisation with conjugate vaccines, particularly anti-Haemophilus vaccine appears to be the best preventive measure. The systematic use of ceftriaxone in infants, during meningococcal meningitis either epidemics or not, is highly recommended.

Epidemiology of bacterial meningitis in Niamey, Niger, 1981-96.

In the African meningitis belt the importance of endemic meningitis is not as well recognized as that of epidemics of meningococcal meningitis that occur from time to time. Using retrospective surveillance, we identified a total of 7078 cases of laboratory-diagnosed bacterial meningitis in Niamey, Niger, from 1981 to 1996. The majority (57.7%) were caused by Neisseria meningitidis, followed by Streptococcus pneumoniae (13.2%) and Haemophilus influenzae b (Hib) (9.5%). The mean annual incidence of bacterial meningitis was 101 per 100,000 population (70 per 100,000 during 11 non-epidemic years) and the average annual mortality rate was 17 deaths per 100,000. Over a 7-year period (including one major epidemic year) for which data were available, S. pneumoniae and Hib together caused more meningitis deaths than N. meningitidis. Meningitis cases were more common among males and occurred mostly during the dry season. Serogroup A caused 85.6% of meningococcal meningitis cases during the period investigated; three-quarters of these occurred among children aged < 15 years, and over 40% among under-5-year-olds. Both incidence and mortality rates were highest among infants aged < 1 year. In this age group, Hib was the leading cause of bacterial meningitis, followed by S. pneumoniae. The predominant cause of meningitis in persons aged 1-40 years was N. meningitidis. Use of the available vaccines against meningitis due to N. meningitidis, S. pneumoniae, and Hib could prevent substantial endemic illness and deaths in sub-Saharan Africa, and potentially prevent recurrent meningococcal epidemics.

PIP: The study presented information on the epidemiology of bacterial meningitis in Niamey, Niger from 1981 to 1996 using retrospective surveillance. During the 15-year period, 7078 cases of laboratory-diagnosed bacterial meningitis were identified. 3 years (1984-85, 1985-86, and 1994-95) were considered to be epidemic years, and in these years incidence of bacterial meningitis exceeded 140 cases/100,000 population. The major pathogens were Neisseria meningitidis (57.7%), Streptococcus pneumoniae (13.2%), and Haemophilus influenzae (Hib) (9.5%). Mean annual incidence of bacterial meningitis was 101/100,000 population with an average annual mortality rate of 17 deaths/100,000. Both S. pneumoniae and Hib had caused more meningitis deaths than N. meningitidis, as observed over the 7-year period for which data were available. Meanwhile, N. meningitidis was the major cause of meningitis in persons aged 1-40 years. Meningitis was more common among males than females and was more prevalent during dry seasons. Incidence of meningococcal meningitis was higher (74.3%) in children under 15 years of age, and over 40% of these cases occurred in children below 5 years old. Infants aged less than 1 year had the highest incidence and mortality rates; neonatal (1 month of age) meningitis was identified in 101 cases. The high rate of endemic illness and deaths due to meningitis in sub-Saharan Africa could be prevented through the use of available vaccines such as meningococcal polysaccharide vaccines and Hib conjugate vaccines.

Preventive immunisation could reduce the risk of meningococcal epidemics in the African meningitis belt.

Control of meningitis epidemics is based on early case detection followed by mass campaigns of immunisation. However, this strategy showed severe inadequacies during recent outbreaks in Africa. In Niamey, Niger, meningococcal vaccinations began in 1978 and detailed bacteriological and epidemiological surveillance of meningitis started in 1981. When vaccine coverage rates were higher than 50%, the prevalences of Neisseria meningitidis A meningitis were low in Niamey, although there was a concurrent epidemic in rural Niger. A massive outbreak of meningitis in Niamey in 1994-1995 followed a 6-year period during which the mean rate of vaccine coverage remained < 25%. The data indicate that, in the meningitis belt, preventive immunization should avoid a great number of deaths and be less expensive than mass immunisation campaigns performed after epidemics have begun.

A predictable comeback: the second pandemic of infections caused by Neisseria meningitidis serogroup A subgroup III in Africa, 1995.

Between 14 January and 4 April 1995 we isolated and characterized 44 meningococcal strains in Cameroon, Chad, Niger, and Burkina Faso; among these was the strain A:4:P1.9/clone III-1, which was involved in the second meningitis pandemic. This isolate was found in the clonal form in Niger and strains of the ET-37 complex were also found in the other three study countries, but apparently did not cause epidemics. One strain (Y:2a:P1.2,5 (ET-37 complex)) was isolated in January 1995 and another (A:4:P1.9) in March 1995 in Garoua (Cameroon). Eight strains were isolated in Moundou (Chad) between January and April 1995: the A:4:P1.9/clone III-1 (1 strain); members of the ET-37 complex (Y:2a:P1.2,5 (4 strains), Y:NT:P1.2,5 (1 strain), and Y:2a:-(1 strain)); and serogroup X (1 strain). In Niger, 31 strains were isolated between February and April 1995 from different regions. All were A:4:P1.9/clone III-1; between November 1994 and April 1995 there were 23814 cases of meningitis reported of which 2227 resulted in death. Three strains were isolated in Burkina Faso in April 1995: two were Y:2a:P1.2,5 (ET-37 complex) and one was A:4:P1.9/clone III-1. Thus in 1995 the epidemic and invasive strain (A:4:P1.9/clone III-1) responsible for the second pandemic was present in the four countries (Cameroon, Chad, Niger and Burkino Faso) that make up the area frequently affected by such epidemics and where cases are generally reported during the dry season.

La meningite cerebro-spinale dans les Etats membres de l'OCCGE

Les auteurs presentent la situation epidemiologique actuelle de l'endemie meningococcique a Neisseria meningitis en Afrique inter tropicale; en particulier dans les pays de l'OCCGE. La diffusion de Neisseria meningitis A:4:1.9 clone III-1 correspond a une extension significative de la zone d'endemie et a une modification sensible des caracteres epidemiologiques. Les auteurs rappellent brievement la conduite a tenir en cas d'epidemie