Suzanne Chanteau

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.

Origins of ciguatera fish poisoning: a new dinoflagellate, Gambierdiscus toxicus Adachi and Fukuyo, definitively involved as a causal agent

Abstract We consider the precise role, in the biogenesis of ciguatera, played by the dinoflagellate Gambierdiscus toxicus which had been previously isolated in the Gambier Islands (French Polynesia) from toxic biodetritus covering dead corals. We studied the characteristics of the toxicity and its quantitative correlation with dinoflagellate numbers, assaying various samples of non-fractionated biodetritus, a sample of biodetritus fractionated according to particles size, and samples of G. toxicus cultured cells. The toxic substances, isolated in vivo and in vitro , have almost the same biochemical and biological properties as the reference ciguateric toxins. The direct and reproducible relationship between the number of G. toxicus cells and the toxins concentration in the biodetritus, and the capacity of the monoalgal G. toxicus cultured cells to produce the ciguatera toxin complex, confirm the dinoflagellate as the responsible agent of the phenomenon in French Polynesia. The distribution of this dinoflagellate in other endemic areas of the Pacific and the West Indies, provides a presumptive argument for a common worldwide origin for ciguatera.

Identification of putative palytoxin as the cause of clupeotoxism

In 1994 in Madagascar a woman died after eating a sardine, Herklotsichthys quadrimaculatus. Two heads removed, respectively, from a toxic and a nontoxic fish before cooking were retrieved, kept frozen, and used for toxin analysis. The causative toxin was identified as palytoxin or its analogs based on its cytotoxicity, delayed hemolysis, neutralization with an anti-palytoxin antibody, chromatographic properties on different columns, and MS data. The gill and esophagus of the fish contained large amount of bottom sediments indicating that the fish had fed on the bottom and thus probably obtained the toxin from a benthic organism. The benthic dinoflagellate Ostreopsis siamensis that produces palytoxin and its analogs was inferred as the probable toxin source. This is the first study to shed light on clupeotoxism, a highly fatal form of human intoxication due to ingestion of clupeoid fish.

Development and testing of a rapid diagnostic test for bubonic and pneumonic plague

BACKGROUND Plague is often fatal without prompt and appropriate treatment. It affects mainly poor and remote populations. Late diagnosis is one of the major causes of human death and spread of the disease, since it limits the effectiveness of control measures. We aimed to develop and assess a rapid diagnostic test (RDT) for plague. METHODS We developed a test that used monoclonal antibodies to the F1 antigen of Yersinia pestis. Sensitivity and specificity were assessed with a range of bacterial cultures and clinical samples, and compared with findings from available ELISA and bacteriological tests for plague. Samples from patients thought to have plague were tested with the RDT in the laboratory and by health workers in 26 pilot sites in Madagascar. FINDINGS The RDT detected concentrations of F1 antigen as low as 0.5 ng/mL in up to 15 min, and had a shelf life of 21 days at 60 degrees C. Its sensitivity and specificity were both 100%. RDT detected 41.6% and 31% more positive clinical specimens than did bacteriological methods and ELISA, respectively. The agreement rate between tests done at remote centres and in the laboratory was 89.8%. With the combination of bacteriological methods and F1 ELISA as reference standard, the positive and negative predictive values of the RDT were 90.6% and 86.7%, respectively. INTERPRETATION Our RDT is a specific, sensitive, and reliable test that can easily be done by health workers at the patients bedside, for the rapid diagnosis of pneumonic and bubonic plague. This test will be of key importance for the control of plague in endemic countries.

Epidemiological and diagnostic aspects of the outbreak of pneumonic plague in Madagascar

BACKGROUND Plague is a re-emerging disease and pneumonic plague is the most feared clinical form. We describe a well-documented outbreak of pneumonic plague in Madagascar. METHODS Field epidemiological data were collected. Biological tests (microscopy, culture of Yersinia pestis, F1 antigen ELISA and dipstick assays, IgG anti-F1 ELISA) were done on sputum, serum, or necropsy samples. The infection rate among 154 contacts was assessed by anti-F1 serological techniques. FINDINGS The index case was a bubonic patient with a secondary lung infection, who contaminated a traditional healer and his family. Funeral ceremonies and attendance on patients contaminated other villagers. In total 18 cases were recorded, and eight died. F1 antigen could be detected in sputum by ELISA and dipstick tests as early as the second day after the onset of the symptoms and also 48 h after treatment. Among the contact population 13 of 154 (8.4%) have been exposed to the plague bacillus (symptomless or latent infections). INTERPRETATION The F1 dipstick assay on sputum is an invaluable diagnostic tool for pneumonic plague. Treatment of patients and chemoprophylaxis of contacts were efficient in stopping the epidemic.

Epidemiologic Features of Four Successive Annual Outbreaks of Bubonic Plague in Mahajanga, Madagascar

From 1995 to 1998, outbreaks of bubonic plague occurred annually in the coastal city of Mahajanga, Madagascar. A total of 1,702 clinically suspected cases of bubonic plague were reported, including 515 laboratory confirmed by Yersinia pestis isolation (297), enzyme-linked immunosorbent assay, or both. Incidence was higher in males and young persons. Most buboes were inguinal, but children had a higher frequency of cervical or axillary buboes. Among laboratory-confirmed hospitalized patients, the case-fatality rate was 7.9%, although all Y. pestis isolates were sensitive to streptomycin, the recommended antibiotic. In this tropical city, plague outbreaks occur during the dry and cool season. Most cases are concentrated in the same crowded and insanitary districts, a result of close contact among humans, rats, and shrews. Plague remains an important public health problem in Madagascar, and the potential is substantial for spread to other coastal cities and abroad.

Phylogeography and Molecular Epidemiology of Yersinia pestis in Madagascar

Background Plague was introduced to Madagascar in 1898 and continues to be a significant human health problem. It exists mainly in the central highlands, but in the 1990s was reintroduced to the port city of Mahajanga, where it caused extensive human outbreaks. Despite its prevalence, the phylogeography and molecular epidemiology of Y. pestis in Madagascar has been difficult to study due to the great genetic similarity among isolates. We examine island-wide geographic-genetic patterns based upon whole-genome discovery of SNPs, SNP genotyping and hypervariable variable-number tandem repeat (VNTR) loci to gain insight into the maintenance and spread of Y. pestis in Madagascar. Methodology/Principal Findings We analyzed a set of 262 Malagasy isolates using a set of 56 SNPs and a 43-locus multi-locus VNTR analysis (MLVA) system. We then analyzed the geographic distribution of the subclades and identified patterns related to the maintenance and spread of plague in Madagascar. We find relatively high levels of VNTR diversity in addition to several SNP differences. We identify two major groups, Groups I and II, which are subsequently divided into 11 and 4 subclades, respectively. Y. pestis appears to be maintained in several geographically separate subpopulations. There is also evidence for multiple long distance transfers of Y. pestis, likely human mediated. Such transfers have resulted in the reintroduction and establishment of plague in the port city of Mahajanga, where there is evidence for multiple transfers both from and to the central highlands. Conclusions/Significance The maintenance and spread of Y. pestis in Madagascar is a dynamic and highly active process that relies on the natural cycle between the primary host, the black rat, and its flea vectors as well as human activity.

Current epidemiology of human plague in Madagascar.

From 1996 to 1998, 5,965 patients with suspected plague were identified in 38 districts of Madagascar (40% of the total population are exposed). Using standard bacteriology, 917 of them were confirmed or presumptive (C + P) cases. However, more than 2,000 plague cases could be estimated using F1 antigen assay. Two out of the 711 Yersinia pestis isolates tested were resistant to chloramphenicol and to ampicillin (both isolates found in the harbour of Mahajanga). Urban plague (Mahajanga harbour and Antananarivo city) accounted for 37.4% of the C + P cases. Bubonic plague represented 97.2% of the cases, and the lethality rate was still high (20%). In comparing the exposed population, plague was more prevalent in males (M:F sex ratio 1.3:1) and patients under 20 years (2.7% babies under two years). Buboes were mainly localised in the inguinal/femoral regions (55.8%). The epidemiological risk factors are discussed.

Use of Dipsticks for Rapid Diagnosis of Cholera Caused by Vibrio cholerae O1 and O139 from Rectal Swabs

ABSTRACT We evaluated the recently developed dipsticks for the rapid detection of Vibrio cholerae serotypes O1 and O139 from rectal swabs of hospitalized diarrheal patients after enrichment for 4 h in alkaline peptone water. The sensitivity and specificity of the dipsticks were above 92 and 91%, respectively. The dipsticks represent the first rapid test which has been successfully used to diagnose cholera from rectal swabs, and this would immensely improve surveillance for cholera, especially in remote settings.

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.