Abudulai Adams Forgor

An Outbreak of Serotype 1 Streptococcus pneumoniae Meningitis in Northern Ghana with Features That Are Characteristic of Neisseria meningitidis Meningitis Epidemics

BACKGROUND The Kassena-Nankana District (KND) of northern Ghana lies in the African meningitis belt, where epidemics of bacterial meningitis have been reoccurring every 8-12 years. These epidemics are generally caused by Neisseria meningitidis, an organism that is considered to be uniquely capable of causing meningitis epidemics. METHODS We recruited all patients with suspected meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were collected and analyzed by standard microbiological techniques. Bacterial isolates were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic-resistance testing. RESULTS A continual increase in the incidence of pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited strong seasonality, a broad host age range, and clonal dominance, all of which are characteristic of meningococcal meningitis epidemics in the African meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%; the majority of pneumococcal isolates were antibiotic sensitive and expressed the serotype 1 capsule. MLST revealed that these isolates belonged to a clonal complex dominated by sequence type (ST) 217 and its 2 single-locus variants, ST303 and ST612. CONCLUSIONS The S. pneumoniae ST217 clonal complex represents a hypervirulent lineage with a high propensity to cause meningitis, and our results suggest that this lineage might have the potential to cause an epidemic. Serotype 1 is not included in the currently licensed pediatric heptavalent pneumococcal vaccine. Mass vaccination with a less complex conjugate vaccine that targets hypervirulent serotypes should, therefore, be considered.

Clonal Waves of Neisseria Colonisation and Disease in the African Meningitis Belt: Eight- Year Longitudinal Study in Northern Ghana

Background The Kassena-Nankana District of northern Ghana lies in the African “meningitis belt” where epidemics of meningococcal meningitis have been reoccurring every eight to 12 years for the last 100 years. The dynamics of meningococcal colonisation and disease are incompletely understood, and hence we embarked on a long-term study to determine how levels of colonisation with different bacterial serogroups change over time, and how the patterns of disease relate to such changes. Methods and Findings Between February 1998 and November 2005, pharyngeal carriage of Neisseria meningitidis in the Kassena-Nankana District was studied by twice-yearly colonisation surveys. Meningococcal disease was monitored throughout the eight-year study period, and patient isolates were compared to the colonisation isolates. The overall meningococcal colonisation rate of the study population was 6.0%. All culture-confirmed patient isolates and the majority of carriage isolates were associated with three sequential waves of colonisation with encapsulated (A ST5, X ST751, and A ST7) meningococci. Compared to industrialised countries, the colonising meningococcal population was less constant in genotype composition over time and was genetically less diverse during the peaks of the colonisation waves, and a smaller proportion of the isolates was nonserogroupable. We observed a broad age range in the healthy carriers, resembling that of meningitis patients during large disease epidemics. Conclusions The observed lack of a temporally stable and genetically diverse resident pharyngeal flora of meningococci might contribute to the susceptibility to meningococcal disease epidemics of residents in the African meningitis belt. Because capsular conjugate vaccines are known to impact meningococcal carriage, effects on herd immunity and potential serogroup replacement should be monitored following the introduction of such vaccines.

The Diversity of Meningococcal Carriage Across the African Meningitis Belt and the Impact of Vaccination With a Group A Meningococcal Conjugate Vaccine

Background. Study of meningococcal carriage is essential to understanding the epidemiology of Neisseria meningitidis infection. Methods. Twenty cross-sectional carriage surveys were conducted in 7 countries in the African meningitis belt; 5 surveys were conducted after introduction of a new serogroup A meningococcal conjugate vaccine (MenAfriVac). Pharyngeal swab specimens were collected, and Neisseria species were identified by microbiological and molecular techniques. Results. A total of 1687 of 48 490 participants (3.4%; 95% confidence interval [CI], 3.2%–3.6%) carried meningococci. Carriage was more frequent in individuals aged 5–14 years, relative to those aged 15–29 years (adjusted odds ratio [OR], 1.41; 95% CI, 1.25–1.60); in males, relative to females (adjusted OR, 1.17; 95% CI, 1.10–1.24); in individuals in rural areas, relative to those in urban areas (adjusted OR, 1.44; 95% CI, 1.28–1.63); and in the dry season, relative to the rainy season (adjusted OR, 1.54; 95% CI, 1.37–1.75). Forty-eight percent of isolates had genes encoding disease-associated polysaccharide capsules; genogroup W predominated, and genogroup A was rare. Strain diversity was lower in countries in the center of the meningitis belt than in Senegal or Ethiopia. The prevalence of genogroup A fell from 0.7% to 0.02% in Chad following mass vaccination with MenAfriVac. Conclusions. The prevalence of meningococcal carriage in the African meningitis belt is lower than in industrialized countries and is very diverse and dynamic, even in the absence of vaccination.

Emergence of W135 meningococcal meningitis in Ghana

Neisseria meningitidis serogroup W135, well known for a long time as a cause of isolated cases of meningococcal meningitis, has recently increasingly been associated with disease outbreaks of considerable magnitude. Burkina Faso was hit by W135 epidemics in the dry seasons of 2002–2004, but only four W135 meningitis cases were recorded between February 2003 and March 2004 in adjoining Ghana. This reconfirms previous findings that bottlenecks exist in the spreading of new epidemic N. meningitidis clones within the meningitis belt of sub‐Saharan Africa. Of the four Ghanaian W135 meningitis patients one died and three survived, of whom one had profound neurosensory hearing loss and speech impairment. All four disease isolates were sensitive to penicillin G, chloramphenicol, ciprofloxacin and cefotaxime and had the multi‐locus sequence type (ST) 11, which is the major ST of the ET‐37 clonal complex. Pulsed‐field gel electrophoresis (PFGE) profiles of the Ghanaian disease isolates and recent epidemic isolates from Burkina Faso were largely identical. We conducted meningococcal colonization surveys in the home communities of three of the patients and in the Kassena Nankana District located at the border to Burkina Faso. W135 carriage rates ranged between 0% and 17.5%. When three consecutive surveys were conducted in the patient community with the highest carrier rate, persistence of W135 colonization over a period of 1 year was observed. Differences in PFGE profiles of carrier isolates taken at different times in the same patient community were indicative of rapid microevolution of the W135 bacteria, emphasizing the need for innovative fine typing methods to reveal the relationship between W135 isolates.

A Phase II, Randomized Study on an Investigational DTPw-HBV/Hib-MenAC Conjugate Vaccine Administered to Infants in Northern Ghana

Background Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. Methods and Findings In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres ≥1∶8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres ≥ 1∶8 or SBA-MenC titres ≥1∶8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 μg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 μg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6–28.1] of doses vs 14.1%; 95% CI [10.9–17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study. Conclusions Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt. Trial Registration Controlled-Trials.com ISRCTN35754083

Methods for Identifying Neisseria meningitidis Carriers: A Multi-Center Study in the African Meningitis Belt.

Objective Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers. Methods We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U) to swabbing the posterior pharynx behind the uvula plus one tonsil (T). Swabs were cultured immediately and analyzed using molecular methods. Results One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6%) based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7%) versus 4.9% (95% CI: 3.6-6.4%) respectively (p=0.6)). The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73), indicating good agreement. Conclusions These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence.

Household transmission of Neisseria meningitidis in the African meningitis belt: a longitudinal cohort study

BACKGROUND Information on transmission of meningococcal infection in the African meningitis belt is scarce. We aimed to describe transmission patterns of Neisseria meningitidis (meningococcus) in households in the African meningitis belt. METHODS Cross-sectional carriage surveys were done in seven African meningitis belt countries (Chad, Ethiopia, Ghana, Mali, Niger, Nigeria, and Senegal) between Aug 1, 2010, and Oct 15, 2012. Meningococcal carriers identified in these surveys and all available people in their households were recruited into this longitudinal cohort study. We took pharyngeal swabs at first visit and took further swabs twice a month for 2 months and then monthly for a further 4 months. We used conventional bacteriological and molecular techniques to identify and characterise meningococci. We estimated the rates of carriage acquisition and recovery using a multi-state Markov model. FINDINGS Meningococci were isolated from 241 (25%) of 980 members of 133 households in which a carrier had been identified in the cross-sectional survey or at the first household visit. Carriage was detected subsequently in another household member who was not an index carrier in 75 households. Transmission within a household, suggested by detection of a further carrier with the same strain as the index carrier, was found in 52 of these 75 households. Children younger than 5 years were the group that most frequently acquired carriage from other household members. The overall individual acquisition rate was 2·4% (95% CI 1·6-4·0) per month, varying by age and household carriage status. The mean duration of carriage was 3·4 months (95% CI 2·7-4·4). INTERPRETATION In the African meningitis belt, transmission of meningococci within households is important, particularly for young children, and periods of carriage are usually of short duration. FUNDING Bill & Melinda Gates Foundation, Wellcome Trust.

Using Weather Forecasts to Help Manage Meningitis in the West African Sahel

AbstractUnderstanding and acting on the link between weather and meningitis in the Sahel could help improve vaccine distribution and save lives. People living there know that meningitis epidemics occur in the dry season and end after the start of the rainy season. Integrating and analyzing newly available epidemiological and meteorological data quantified this relationship, showing that that the risk of meningitis epidemics climbed from a background level of 2% to a maximum risk of 25% during the dry season. These data also suggested that, of all meteorological variables, relative humidity has the strongest correlation to cases of meningitis.Weather acts alongside a complex set of environmental, social, and economic drivers, and a complementary investigation of local and regional knowledge, attitudes, and practices suggested several additional interventions to manage meningitis. These include improved awareness of early meningitis symptoms and vaccinations for farmworkers who migrate seasonally. An econom...