Saacou Djibo

Meningococcal Meningitis: Unprecedented Incidence of Serogroup X—Related Cases in 2006 in Niger

BACKGROUND In Niger, epidemic meningococcal meningitis is primarily caused by Neisseria meningitidis (Nm) serogroup A. However, since 2002, Nm serogroup W135 has been considered to be a major threat that has not yet been realized, and an unprecedented incidence of Nm serogroup X (NmX) meningitis was observed in 2006. METHODS Meningitis surveillance in Niger is performed on the basis of reporting of clinically suspected cases. Cerebrospinal fluid specimens are sent to the reference laboratory in Niamey, Niger. Culture, latex agglutination, and polymerase chain reaction are used whenever appropriate. Since 2004, after the addition of a polymerase chain reaction-based nonculture assay that was developed to genogroup isolates of NmX, polymerase chain reaction testing allows for the identification of Nm serogroup A, Nm serogroup B, Nm serogroup C, NmX, Nm serogroup Y, and Nm serogroup W135. RESULTS From January to June 2006, a total of 4185 cases of meningitis were reported, and 2905 cerebrospinal fluid specimens were laboratory tested. NmX meningitis represented 51% of 1139 confirmed cases of meningococcal meningitis, but in southwestern Niger, it represented 90%. In the agglomeration of Niamey, the reported cumulative incidence of meningitis was 73 cases per 100,000 population and the cumulative incidence of confirmed NmX meningitis was 27.5 cases per 100,000 population (74.6 cases per 100,000 population in children aged 5-9 years). NmX isolates had the same phenotype (X : NT : P1.5), and all belonged to the same sequence type (ST-181) as the NmX isolates that were circulating in Niamey in the 1990s. Nm serogroup W135 represented only 2.1% of identified meningococci. CONCLUSIONS This is, to our knowledge, the first report of such a high incidence of NmX meningitis, although an unusually high incidence of NmX meningitis was also observed in the 1990s in Niamey. The increasing incidence of NmX meningitis is worrisome, because no vaccine has been developed against this serogroup. Countries in the African meningitis belt must prepare to face this potential new challenge.

Neisseria meningitidis Serogroups W135 and A Were Equally Prevalent among Meningitis Cases Occurring at the End of the 2001 Epidemics in Burkina Faso and Niger

ABSTRACT Meningococcal infections occur as epidemics in the African meningitis belt. Neisseria meningitidis serogroup A is predominantly involved in these epidemics. We report here new data on the involvement of both serogroups A and W135 in meningitis cases in Burkina Faso and Niger at the end of the 2001 epidemic.

Molecular Epidemiology of Neisseria meningitidis Isolated in the African Meningitis Belt between 1988 and 2003 Shows Dominance of Sequence Type 5 (ST-5) and ST-11 Complexes

ABSTRACT At the two World Health Organization Collaborating Centers for Reference and Research on Meningococci in Marseilles, France, and Oslo, Norway, the multilocus sequence typing technique was used for the characterization of a total of 357 strains of meningococci isolated from meningitis cases in 13 African countries of the meningitis belt between 1988 and 2003. Among these strains, 278 of 357 (77.9%) belonged to the sequence type 5 (ST-5) complex; 23.2% were ST-5 and 53.5% were ST-7. ST-5 was probably introduced in Africa in 1987 and was responsible for most of the meningitis cases between 1988 and 2001. ST-7 emerged in the mid-1990s and has totally replaced ST-5 since 2002. These two STs characterized serogroup A strains and have been responsible for hundreds of thousands of cases. Fifty-two strains (14.3%) belonged to the ST-11 complex. The ST-11 complex was characterized by serogroup W135, which has been responsible for an increasing number of sporadic cases since 2000 and the first W135 epidemic ever seen in Africa (in Burkina Faso in 2002). Identification of W135 ST-11 strains in many countries is a great concern for the region. Apart from these two major clonal complexes, a few other clones, such as ST-2881, ST-181, and ST-751, were sporadically detected. Careful surveys for these clones need to be conducted, but at present they play only a minor role in the overall epidemiology of meningococcal meningitis.

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.

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.

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.

Polymerase Chain Reaction Assay and Bacterial Meningitis Surveillance in Remote Areas, Niger

To compensate for the lack of laboratories in remote areas, the national reference laboratory for meningitis in Niger used polymerase chain reaction (PCR) to enhance the surveillance of meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. PCR effectively documented the wide geographic spread of N. meningitidis serogroup W135.

New Rapid Diagnostic Tests for Neisseria meningitidis Serogroups A, W135, C, and Y

Background Outbreaks of meningococcal meningitis (meningitis caused by Neisseria meningitidis) are a major public health concern in the African “meningitis belt,” which includes 21 countries from Senegal to Ethiopia. Of the several species that can cause meningitis, N. meningitidis is the most important cause of epidemics in this region. In choosing the appropriate vaccine, accurate N. meningitidis serogroup determination is key. To this end, we developed and evaluated two duplex rapid diagnostic tests (RDTs) for detecting N. meningitidis polysaccharide (PS) antigens of several important serogroups. Methods and Findings Mouse monoclonal IgG antibodies against N. meningitidis PS A, W135/Y, Y, and C were used to develop two immunochromatography duplex RDTs, RDT1 (to detect serogroups A and W135/Y) and RDT2 (to detect serogroups C and Y). Standards for Reporting of Diagnostic Accuracy criteria were used to determine diagnostic accuracy of RDTs on reference strains and cerebrospinal fluid (CSF) samples using culture and PCR, respectively, as reference tests. The cutoffs were 105 cfu/ml for reference strains and 1 ng/ml for PS. Sensitivities and specificities were 100% for reference strains, and 93.8%–100% for CSF serogroups A, W135, and Y in CSF. For CSF serogroup A, the positive and negative likelihood ratios (± 95% confidence intervals [CIs]) were 31.867 (16.1–63.1) and 0.065 (0.04–0.104), respectively, and the diagnostic odds ratio (± 95% CI) was 492.9 (207.2–1,172.5). For CSF serogroups W135 and Y, the positive likelihood ratio was 159.6 (51.7–493.3) Both RDTs were equally reliable at 25 °C and 45 °C. Conclusions These RDTs are important new bedside diagnostic tools for surveillance of meningococcus serogroups A and W135, the two serogroups that are responsible for major epidemics in Africa.

Increase in Neisseria meningitidis Serogroup W135, Niger, 2010

To the Editor: Meningococcal epidemics in the African meningitis belt are generally caused by Neisseria meningitidis serogroup A strains, but they also can be caused by serogroup W135 or X strains. The largest reported outbreak caused by serogroup W135 occurred in Burkina Faso in 2002 with ≈13,000 suspected cases (1). Sporadic cases of meningitis caused by serogroup W135 have, however, been detected previously, notably in Niger since the early 1980s (2). This serogroup has also been associated with outbreaks in pilgrims to Mecca, Saudi Arabia, in 2000, and several clusters of cases occurred worldwide before 2002 (3). After 2003, no major outbreak caused by serogroup W135 was detected in sub-Saharan countries, only sporadic cases. Although Niger borders Burkina Faso, Niger has not experienced a large outbreak of meningitis caused by serogroup W135, with the exception of 7,906 suspected cases and 595 deaths declared in 2001; serogroup W135 represented 12 (38.7%) of the small number (n = 31) of confirmed cases (4). In 2010, serogroup W135 may have caused a major outbreak (a large proportion of this serogroup was detected during the first 12 weeks). Niger residents have not been in contact with this serogroup in recent years and have never been immunized with the trivalent polysaccharide vaccine (A/C/W135). From January 1 through March 28, 2010, the Ministry of Public Health of the Republic of Niger reported 1,188 suspected cases of meningococcal disease, including 103 deaths (case-fatality rate 8.7%). Suspected cases were reported from all 8 provinces but predominantly in the provinces of Maradi (40%) and Tillabery (24%). At week 12, the districts of Maradi Commune and neighboring Madarounfa crossed the alert, or epidemic, threshold with cumulated attack rates per 100,000 inhabitants of 57.0 and 48.5, respectively. Zinder City district also crossed the alert threshold. Laboratory confirmation and microbiologic surveillance of meningococcal meningitis is conducted by the Centre de Recherche Medicale et Sanitaire by using culture or PCR (5) techniques on cerebrospinal fluid (CSF) or CSF-inoculated trans-isolates. During the study period, the Centre received 816 CSF or trans-isolate specimens (from 69% of the notified cases). Culture (n = 23, 2.8%) and PCR (all specimens) identified N. meningitidis as the predominant pathogen (n = 248, 30.4%), followed by Streptococcus pneumoniae (n = 35, 4.3%) and Haemophilus influenzae (n = 13, 1.6%). Among the 248 cases with confirmed meningococcal etiology, the most frequent serogroup was W135 (n = 121, 48.8%), followed by A (n = 116, 46.8%) and X (n = 2), indicating that serogroup W135 had increased markedly compared with the past 2 years (Figure). Among the 816 CSF specimens, 454 (56%) remained negative when tested for the presence of N. meningitidis, S. pneumoniae, or H. influenzae by PCR. Eighty-four (69.4%) of the serogroup W135 strains originated from the province of Maradi (southern Niger) and, more specifically, 36%.4% (n = 44) and 19.8% (n = 24) originated from the Madarounfa and Maradi districts, respectively. In contrast, serogroup A was mainly present in Tillabery (western Niger) with 49.1% (n = 57) of the strains and, to a lesser extent, in the provinces of Maradi (16.4%, n = 19) and Dosso (13.8%, n = 16). All meningococcal strains (n = 9 for W135, n = 1 for A) recovered from trans-isolates and analyzed by Etest (AB bioMerieux, Marcy l’Etoile, France) were susceptible to beta-lactams (penicillin, amoxicillin, and ceftriaxone), chloramphenicol, and rifampin. This finding supports the appropriateness of World Health Organization recommendations for antimicrobial drug treatment. The A strain belonged to the sequence type (ST) 7 and the W135 strains to ST 11, the same ST of the strain associated with outbreaks in pilgrims in Saudi Arabia in 2000 (3) and the strain that caused the large epidemic in Burkina Faso in 2002 (1). Figure Epidemic curve of cumulative confirmed cases of Neisseria meninigitidis serogroup W135 infections, Niger, 2008, 2009, and 2010 (weeks 1–12). No cases were found in 2008. The mean ages of patients with confirmed cases of infection with serogroup W135 and serogroup A were 8.1 (SD 8.5) and 10.9 (SD 7.9) years, respectively. Although no significant difference was found in the mean ages, the age group was 1–4 years of age had more disease caused by serogroup W135, and children 5–14 years of age were most affected by serogroup A. Similarly, the attack rate during the outbreak of meningitis caused by serogroup W135 in Burkina Faso in 2002 was highest in patients <5 years of age, and the attack rate decreased as patients’ ages increased (6). Reactive vaccination campaigns in some communes of Madarounfa district that had reached the epidemic threshold were launched by the Ministry of Public Health with a remaining 2009 stockpile (16,527 doses, 35.7% coverage) of the quadrivalent polysaccharide vaccine (A/C/Y/W135) from Medecins sans Frontieres. The International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control has also recently approved the release of 381,526 doses of trivalent polysaccharide vaccine (A/C/W135) for vaccination campaigns in Maradi and Zinder districts. Future immunization campaigns will be implemented by Ministry of Public Health with the support of the World Health Organization and partners, including Medecins sans Frontieres and The United Nations Children’s Fund. Given the large population at risk, and the low availability and high cost of the trivalent vaccine, a sound vaccination strategy is of particular importance to mitigate the expansion of serogroup W135 in the country. Microbiologic surveillance is critical in the early and accurate detection of meningococcal serogroups for determining the appropriate vaccine.

Epidemiological patterns of meningococcal meningitis in Niger in 2003 and 2004: under the threat of N. meningitidis serogroup W135.

Since the Neisseria meningitidis serogroup W135 epidemic in Burkina Faso in 2002, the neighbouring countries dread undergoing outbreaks. Niger has strongly enhanced the microbiological surveillance, especially by adding the polymerase chain reaction (PCR) assay to the national framework of the surveillance system. During the 2003 epidemic season, 8113 clinically suspected cases of meningitis were notified and nine districts of the 42 crossed the epidemic threshold, while during the 2004 season, the number of cases was 3521 and four districts notified epidemics. In 2003 and 2004, serogroup A was identified in most N. meningitidis from cerebrospinal fluid (CSF) specimens (89.7% of 759 and 87.2% of 406, respectively). Although serogroup W135 represented only 8.3% of the meningococcal meningitis in 2003 and 7.9% in 2004, and was not involved in outbreaks, it was widespread in various areas of the country. In the regions that notified epidemics, the proportion of serogroup W135 was tiny while it exceeded 40% in several non‐epidemic regions. Despite the wide distribution of W135 serogroup in Niger and the fears expressed in 2001, the threat of a large epidemic caused by N. meningitidis W135 seems to have been averted in Niger so far. There is no clear indication whether this serogroup will play a lasting role in the epidemiology of meningococcal meningitis or not. As early as in the 1990s, a significant but transient increase in the incidence of N. meningitidis serogroup X was observed. Close microbiological surveillance is crucial for monitoring the threat and for identifying at the earliest the serogroups involved in epidemics.