Spatiotemporal Analysis of Serogroup C Meningococcal Meningitis Spread in Niger and Nigeria and Implications for Epidemic Response.

BACKGROUND: After the re-emergence of serogroup C meningococcal meningitis (MM) in Nigeria and Niger, we aimed to re-evaluate the vaccination policy used to respond to outbreaks of MM in the African meningitis belt by investigating alternative strategies using a lower incidence threshold and information about neighboring districts. METHODS: We used data on suspected and laboratory-confirmed cases in Niger and Nigeria from 2013 to 2017. We calculated global and local Moran's I-statistics to identify spatial clustering of districts with high MM incidence. We used a Pinner model to estimate the impact of vaccination campaigns occurring between 2015 and 2017 and to evaluate the impact of 3 alternative district-level vaccination strategies, compared with that currently used. RESULTS: We found significant clustering of high incidence districts in every year, with local clusters around Tambuwal, Nigeria in 2013 and 2014, Niamey, Niger in 2016, and in Sokoto and Zamfara States in Nigeria in 2017.We estimate that the vaccination campaigns implemented in 2015, 2016, and 2017 prevented 6% of MM cases. Using the current strategy but with high coverage (85%) and timely distribution (4 weeks), these campaigns could have prevented 10% of cases. This strategy required the fewest doses of vaccine to prevent a case. None of the alternative strategies we evaluated were more efficient, but they would have prevented the occurrence of more cases overall. CONCLUSIONS: Although we observed significant spatial clustering in MM in Nigeria and Niger between 2013 and 2017, there is no strong evidence to support a change in methods for epidemic response in terms of lowering the intervention threshold or targeting neighboring districts for reactive vaccination.

Invasive Meningococcal Disease in Africa's Meningitis Belt: More Than Just Meningitis?

Since the progressive introduction of the meningococcal serogroup A conjugate vaccine within Africa's meningitis belt beginning in 2010, the burden of meningitis due to Neisseria meningitidis serogroup A (NmA) has substantially decreased. Non-A serogroups C/W/X are now the most prevalent. Surveillance within the belt has historically focused on the clinical syndrome of meningitis, the classic presentation for NmA, and may not adequately capture other presentations of invasive meningococcal disease (IMD). The clinical presentation of infection due to serogroups C/W/X includes nonmeningeal IMD, and there is a higher case-fatality ratio associated with these non-A serogroups; however, data on the nonmeningeal IMD burden within the belt are scarce. Expanding surveillance to capture all cases of IMD, in accordance with the World Health Organization's updated vaccine-preventable disease surveillance standards and in preparation for the anticipated introduction of a multivalent meningococcal conjugate vaccine within Africa's meningitis belt, will enhance meningococcal disease prevention across the belt.

Meningococcal Meningitis Outbreaks in the African Meningitis Belt After Meningococcal Serogroup A Conjugate Vaccine Introduction, 2011-2017.

BACKGROUND: In 2010-2017, meningococcal serogroup A conjugate vaccine (MACV) was introduced in 21 African meningitis belt countries. Neisseria meningitidis A epidemics have been eliminated here; however, non-A serogroup epidemics continue. METHODS: We reviewed epidemiological and laboratory World Health Organization data after MACV introduction in 20 countries. Information from the International Coordinating Group documented reactive vaccination. RESULTS: In 2011-2017, 17 outbreaks were reported (31 786 suspected cases from 8 countries, 1-6 outbreaks/year). Outbreaks were of 18-14 542 cases in 113 districts (median 3 districts/outbreak). The most affected countries were Nigeria (17 375 cases) and Niger (9343 cases). Cumulative average attack rates per outbreak were 37-203 cases/100 000 population (median 112). Serogroup C accounted for 11 outbreaks and W for 6. The median proportion of laboratory confirmed cases was 20%. Reactive vaccination was conducted during 14 outbreaks (5.7 million people vaccinated, median response time 36 days). CONCLUSION: Outbreaks due to non-A serogroup meningococci continue to be a significant burden in this region. Until an affordable multivalent conjugate vaccine becomes available, the need for timely reactive vaccination and an emergency vaccine stockpile remains high. Countries must continue to strengthen detection, confirmation, and timeliness of outbreak control measures.

Status of the Rollout of the Meningococcal Serogroup A Conjugate Vaccine in African Meningitis Belt Countries in 2018.

BACKGROUND: A novel meningococcal serogroup A conjugate vaccine (MACV [MenAfriVac]) was developed as part of efforts to prevent frequent meningitis outbreaks in the African meningitis belt. The MACV was first used widely and with great success, beginning in December 2010, during initial deployment in Burkina Faso, Mali, and Niger. Since then, MACV rollout has continued in other countries in the meningitis belt through mass preventive campaigns and, more recently, introduction into routine childhood immunization programs associated with extended catch-up vaccinations. METHODS: We reviewed country reports on MACV campaigns and routine immunization data reported to the World Health Organization (WHO) Regional Office for Africa from 2010 to 2018, as well as country plans for MACV introduction into routine immunization programs. RESULTS: By the end of 2018, 304 894 726 persons in 22 of 26 meningitis belt countries had received MACV through mass preventive campaigns targeting individuals aged 1-29 years. Eight of these countries have introduced MACV into their national routine immunization programs, including 7 with catch-up vaccinations for birth cohorts born after the initial rollout. The Central African Republic introduced MACV into its routine immunization program immediately after the mass 1- to 29-year-old vaccinations in 2017 so no catch-up was needed. CONCLUSIONS: From 2010 to 2018, successful rollout of MACV has been recorded in 22 countries through mass preventive campaigns followed by introduction into routine immunization programs in 8 of these countries. Efforts continue to complete MACV introduction in the remaining meningitis belt countries to ensure long-term herd protection.

Future Directions for Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Sub-Saharan Africa.

In sub-Saharan Africa, bacterial meningitis remains a significant public health problem, especially in the countries of the meningitis belt, where Neisseria meningitidis serogroup A historically caused large-scale epidemics. In 2014, MenAfriNet was established as a consortium of partners supporting strategic implementation of case-based meningitis surveillance to monitor meningitis epidemiology and impact of meningococcal serogroup A conjugate vaccine (MACV). MenAfriNet improved data quality through use of standardized tools, procedures, and laboratory diagnostics. MenAfriNet surveillance and study data provided evidence of ongoing MACV impact, characterized the burden of non-serogroup A meningococcal disease (including the emergence of a new epidemic clone of serogroup C), and documented the impact of pneumococcal conjugate vaccine. New vaccines and schedules have been proposed for future implementation to address the remaining burden of meningitis. To support the goals of "Defeating Meningitis by 2030," MenAfriNet will continue to strengthen surveillance and support research and modeling to monitor the impact of these programs on meningitis burden in sub-Saharan Africa.

Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo. We describe bacterial meningitis epidemiology in these 5 countries in 2015-2017. METHODS: Case-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae cases were confirmed and N. meningitidis/H. influenzae were serogrouped/serotyped by real-time polymerase chain reaction, culture, or latex agglutination. We calculated annual incidence in participating districts in each country in cases/100 000 population. RESULTS: From 2015-2017, 18 262 suspected meningitis cases were reported; 92% had a CSF specimen available, of which 26% were confirmed as N. meningitidis (n = 2433; 56%), S. pneumoniae (n = 1758; 40%), or H. influenzae (n = 180; 4%). Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3. N. meningitidis incidence was 1.5 in Burkina Faso, 2.7 in Chad, 0.4 in Mali, 14.7 in Niger, and 12.5 in Togo. Several outbreaks occurred: NmC in Niger in 2015-2017, NmC in Mali in 2016, and NmW in Togo in 2016-2017. Of N. meningitidis cases, 53% were NmC, 30% NmW, and 13% NmX. Five NmA cases were reported (Burkina Faso, 2015). NmX increased from 0.6% of N. meningitidis cases in 2015 to 27% in 2017. CONCLUSIONS: Although bacterial meningitis epidemiology varied widely by country, NmC and NmW caused several outbreaks, NmX increased although was not associated with outbreaks, and overall NmA incidence remained low. An effective low-cost multivalent meningococcal conjugate vaccine could help further control meningococcal meningitis in the region.

Improving Case-Based Meningitis Surveillance in 5 Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet consortium was established in 2014 to support implementation of case-based meningitis surveillance in 5 countries in the meningitis belt of sub-Saharan Africa: Burkina Faso, Chad, Mali, Niger, and Togo. Assessing surveillance performance is critical for interpretation of the collected data and implementation of future surveillance-strengthening initiatives. METHODS: Detailed epidemiologic and laboratory data were collected on suspected meningitis cases through case-based meningitis surveillance in participating districts in 5 countries. Performance of case-based surveillance was evaluated through sensitivity of case ascertainment in case-based versus aggregate meningitis surveillance and an analysis of surveillance indicators. RESULTS: From 2015 to 2017, 18 262 suspected meningitis cases were identified through case-based surveillance and 16 262 were identified through aggregate surveillance, for a case ascertainment sensitivity of 112.3%. Among suspected cases, 16 885 (92.5%) had a cerebrospinal fluid (CSF) specimen collected, 13 625 (80.7%) of which were received at a national reference laboratory. Among these, 13 439 (98.6%) underwent confirmatory testing, and, of those tested, 4371 (32.5%) were confirmed for a bacterial pathogen. CONCLUSIONS: Overall strong performance for case ascertainment, CSF collection, and laboratory confirmation provide evidence for the quality of MenAfriNet case-based surveillance in evaluating epidemiologic trends and informing future vaccination strategies.

MenAfriNet: A Network Supporting Case-Based Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Africa.

Meningococcal meningitis remains a significant public health threat, especially in the African meningitis belt where Neisseria meningitidis serogroup A historically caused large-scale epidemics. With the rollout of a novel meningococcal serogroup A conjugate vaccine (MACV) in the belt, the World Health Organization recommended case-based meningitis surveillance to monitor MACV impact and meningitis epidemiology. In 2014, the MenAfriNet consortium was established to support strategic implementation of case-based meningitis surveillance in 5 key countries: Burkina Faso, Chad, Mali, Niger, and Togo. MenAfriNet aimed to develop a high-quality surveillance network using standardized laboratory and data collection protocols, develop sustainable systems for data management and analysis to monitor MACV impact, and leverage the surveillance platform to perform special studies. We describe the MenAfriNet consortium, its history, strategy, implementation, accomplishments, and challenges.

Sero-prevalence of yellow fever and related Flavi viruses in Ethiopia: a public health perspective.

BACKGROUND: Yellow fever (YF) is a viral hemorrhagic fever, endemic in the tropical forests of Africa and Central and South America. The disease is transmitted by mosquitoes infected with the yellow fever virus (YFV). Ethiopia was affected by the largest YF outbreak since the vaccination era during 1960-1962. The recent YF outbreak occurred in 2013 in Southern part of the country. The current survey of was carried out to determine the YF seroprevalence so as to make recommendations from YF prevention and control in Ethiopia. METHODOLOGY: A multistage cluster design was utilized. Consequently, the country was divided into 5 ecological zones and two sampling towns were picked per zone randomly. A total of 1643 serum samples were collected from human participants. The serum samples were tested for IgG antibody against YFV using ELISA. Any serum sample testing positive by ELISA was confirmed by plaque reduction neutralization test (PRNT). In addition, differential testing was performed for other flaviviruses, namely dengue, Zika and West Nile viruses. RESULT: Of the total samples tested, 10 (0.61%) were confirmed to be IgG positive against YFV and confirmed with PRNT. Nine (0.5%) samples were antibody positive for dengue virus, 15(0.9%) forWest Nile virus and 7 (0.4%) for Zika virus by PRNT. Three out of the five ecological zones namely zones 1, 3 and 5 showed low levels (< 2%) of IgG positivity against YFV. A total of 41(2.5%) cases were confirmed to be positive for one of flaviviruses tested. CONCLUSION: Based on the seroprevalence data, the level of YFV activity and the risk of a YF epidemic in Ethiopia are low. However additional factors that could impact the likelihood of such an epidemic occurring should be considered before making final recommendations for YF prevention and control in Ethiopia. Based on the results of the serosurvey and other YF epidemic risk factors considered, a preventive mass vaccination campaign is not recommended, however the introduction of YF vaccine in routine EPI is proposed nationwide, along with strong laboratory based YF surveillance.

Large Outbreak of Neisseria meningitidis Serogroup C - Nigeria, December 2016-June 2017.

On February 16, 2017, the Ministry of Health in Zamfara State, in northwestern Nigeria, notified the Nigeria Centre for Disease Control (NCDC) of an increased number of suspected cerebrospinal meningitis (meningitis) cases reported from four local government areas (LGAs). Meningitis cases were subsequently also reported from Katsina, Kebbi, Niger, and Sokoto states, all of which share borders with Zamfara State, and from Yobe State in northeastern Nigeria. On April 3, 2017, NCDC activated an Emergency Operations Center (EOC) to coordinate rapid development and implementation of a national meningitis emergency outbreak response plan. After the outbreak was reported, surveillance activities for meningitis cases were enhanced, including retrospective searches for previously unreported cases, implementation of intensified new case finding, and strengthened laboratory confirmation. A total of 14,518 suspected meningitis cases were reported for the period December 13, 2016-June 15, 2017. Among 1,339 cases with laboratory testing, 433 (32%) were positive for bacterial pathogens, including 358 (82.7%) confirmed cases of Neisseria meningitidis serogroup C. In response, approximately 2.1 million persons aged 2-29 years were vaccinated with meningococcal serogroup C-containing vaccines in Katsina, Sokoto, Yobe, and Zamfara states during April-May 2017. The outbreak was declared over on June 15, 2017, after high-quality surveillance yielded no evidence of outbreak-linked cases for 2 consecutive weeks. Routine high-quality surveillance, including a strong laboratory system to test specimens from persons with suspected meningitis, is critical to rapidly detect and confirm future outbreaks and inform decisions regarding response vaccination.

Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015.

In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013-2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa.

Meningococcal Meningitis Surveillance in the African Meningitis Belt, 2004-2013.

BACKGROUND: An enhanced meningitis surveillance network was established across the meningitis belt of sub-Saharan Africa in 2003 to rapidly collect, disseminate, and use district weekly data on meningitis incidence. Following 10 years' experience with enhanced surveillance that included the introduction of a group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in 2010, we analyzed the data on meningitis incidence and case fatality from countries reporting to the network. METHODS: After de-duplication and reconciliation, data were extracted from the surveillance bulletins and the central database held by the World Health Organization Inter-country Support Team in Burkina Faso for countries reporting consistently from 2004 through 2013 (Benin, Burkina Faso, Chad, Democratic Republic of Congo, Ghana, Côte d'Ivoire, Mali, Niger, Nigeria, Togo). RESULTS: The 10 study countries reported 341 562 suspected and confirmed cases over the 10-year study period, with a marked peak in 2009 due to a large epidemic of group A Neisseria meningitidis (NmA) meningitis. Case fatality was lowest (5.9%) during this year. A mean of 71 and 67 districts annually crossed the alert and epidemic thresholds, respectively. The incidence rate of NmA meningitis fell >10-fold, from 0.27 per 100,000 in 2004-2010 to 0.02 per 100,000 in 2011-2013 (P < .0001). CONCLUSIONS: In addition to supporting timely outbreak response, the enhanced meningitis surveillance system provides a global overview of the epidemiology of meningitis in the region, despite limitations in data quality and completeness. This study confirms a dramatic fall in NmA incidence after the introduction of PsA-TT.

Yellow Fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data.

BACKGROUND: Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. METHODS AND FINDINGS: Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000-380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000-180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%-31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys. CONCLUSIONS: With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns.

Diversity of picornaviruses in rural Bolivia.

The family Picornaviridae is a large and diverse group of viruses that infect humans and animals. Picornaviruses are among the most common infections of humans and cause a wide spectrum of acute human disease. This study began as an investigation of acute flaccid paralysis (AFP) in a small area of eastern Bolivia, where surveillance had identified a persistently high AFP rate in children. Stools were collected and diagnostic studies ruled out poliovirus. We tested stool specimens from 51 AFP cases and 34 healthy household or community contacts collected during 2002-2003 using real-time and semi-nested reverse transcription polymerase chain reaction assays for enterovirus, parechovirus, cardiovirus, kobuvirus, salivirus and cosavirus. Anecdotal reports suggested a temporal association with neurological disease in domestic pigs, so six porcine stools were also collected and tested with the same set of assays, with the addition of an assay for porcine teschovirus. A total of 126 picornaviruses were detected in 73 of 85 human individuals, consisting of 53 different picornavirus types encompassing five genera (all except Kobuvirus). All six porcine stools contained porcine and/or human picornaviruses. No single virus, or combination of viruses, specifically correlated with AFP; however, the study revealed a surprising complexity of enteric picornaviruses in a single community.

Intervene before leaving: clustered lot quality assurance sampling to monitor vaccination coverage at health district level before the end of a yellow fever and measles vaccination campaign in Sierra Leone in 2009.

BACKGROUND: In November 2009, Sierra Leone conducted a preventive yellow fever (YF) vaccination campaign targeting individuals aged nine months and older in six health districts. The campaign was integrated with a measles follow-up campaign throughout the country targeting children aged 9-59 months. For both campaigns, the operational objective was to reach 95% of the target population. During the campaign, we used clustered lot quality assurance sampling (C-LQAS) to identify areas of low coverage to recommend timely mop-up actions. METHODS: We divided the country in 20 non-overlapping lots. Twelve lots were targeted by both vaccinations, while eight only by measles. In each lot, five clusters of ten eligible individuals were selected for each vaccine. The upper threshold (UT) was set at 90% and the lower threshold (LT) at 75%. A lot was rejected for low vaccination coverage if more than 7 unvaccinated individuals (not presenting vaccination card) were found. After the campaign, we plotted the C-LQAS results against the post-campaign coverage estimations to assess if early interventions were successful enough to increase coverage in the lots that were at the level of rejection before the end of the campaign. RESULTS: During the last two days of campaign, based on card-confirmed vaccination status, five lots out of 20 (25.0%) failed for having low measles vaccination coverage and three lots out of 12 (25.0%) for low YF coverage. In one district, estimated post-campaign vaccination coverage for both vaccines was still not significantly above the minimum acceptable level (LT = 75%) even after vaccination mop-up activities. CONCLUSION: C-LQAS during the vaccination campaign was informative to identify areas requiring mop-up activities to reach the coverage target prior to leaving the region. The only district where mop-up activities seemed to be unsuccessful might have had logistical difficulties that should be further investigated and resolved.

Putting safety first: ensuring safe vaccination practices during the 2006 rubella campaign in Bolivia.

Over 3 weeks in 2006, 3826083 persons were vaccinated against rubella during a national immunization campaign in Bolivia. This campaign was the largest mass immunization campaign ever conducted in the country. Therefore, in addition to strategic and micro-planning and financial and social mobilization, issues of safety (eg, safe injection practices and waste management) were at the forefront of campaign preparations. Waste management practices were promoted through guidelines, training, and implementation of locally appropriate solutions. These experiences show that, with detailed planning and preparation, in addition to collaboration among key partners, effective management of waste during campaigns in low-income countries is both feasible and beneficial. However, challenges remain in implementing environmentally appropriate solutions. This campaign served as the launching pad for a focus on ensuring that proper waste management practices are used both in the routine immunization program and in subsequent campaigns across Bolivia.

Field Evaluation of the Performance of Two Rapid Diagnostic Tests for Meningitis in Niger and Burkina Faso.

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.

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review.

Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use.

Clustered lot quality assurance sampling to assess immunisation coverage: increasing rapidity and maintaining precision.

OBJECTIVE: Vaccination programmes targeting disease elimination aim to achieve very high coverage levels (e.g. 95%). We calculated the precision of different clustered lot quality assurance sampling (LQAS) designs in computer-simulated surveys to provide local health officers in the field with preset LQAS plans to simply and rapidly assess programmes with high coverage targets. METHODS: We calculated sample size (N), decision value (d) and misclassification errors (alpha and beta) of several LQAS plans by running 10 000 simulations. We kept the upper coverage threshold (UT) at 90% or 95% and decreased the lower threshold (LT) progressively by 5%. We measured the proportion of simulations with < or =d individuals unvaccinated or lower if the coverage was set at the UT (pUT) to calculate beta (1-pUT) and the proportion of simulations with >d unvaccinated individuals if the coverage was LT% (pLT) to calculate alpha (1-pLT). We divided N in clusters (between 5 and 10) and recalculated the errors hypothesising that the coverage would vary in the clusters according to a binomial distribution with preset standard deviations of 0.05 and 0.1 from the mean lot coverage. We selected the plans fulfilling these criteria: alpha < or = 5% beta < or = 20% in the unclustered design; alpha < or = 10% beta < or = 25% when the lots were divided in five clusters. RESULT: When the interval between UT and LT was larger than 10% (e.g. 15%), we were able to select precise LQAS plans dividing the lot in five clusters with N = 50 (5 x 10) and d = 4 to evaluate programmes with 95% coverage target and d = 7 to evaluate programmes with 90% target. CONCLUSION: These plans will considerably increase the feasibility and the rapidity of conducting the LQAS in the field.

Next generation rapid diagnostic tests for meningitis diagnosis.

Rapid diagnostic tests (RDTs) are increasingly recognized as valuable, transformative tools for the diagnosis of infectious diseases. Although there are a variety of meningitis RDTs currently available, certain product features restrict their use to specific levels of care and settings. For this reason, the development of meningitis RDTs for use at all levels of care, including those in low-resource settings, was included in the "Defeating Meningitis by 2030" roadmap. Here we address the limitations of available meningitis RDTs and present test options and specifications to consider when developing the next generation of meningitis RDTs.