Antipneumococcal seroprevalence and pneumococcal carriage during a meningococcal epidemic in Burkina Faso, 2006.

BACKGROUND: To better understand the high incidence of pneumococcal meningitis in the African meningitis belt, we conducted a pneumococcal seroprevalence study during a meningococcal meningitis epidemic in Western Burkina Faso, March 2006. METHODS: In 3 villages experiencing epidemics, we included 624 healthy persons (1-39 years) by cluster sampling. We determined pneumococcal serum immunoglobulin G (IgG) antibody concentrations against 12 serotypes contained in 13-valent pneumococcal conjugate vaccine, and evaluated determinants for IgG ≥ 0.35 µg/mL by multivariate logistic regression. RESULTS: The percentage of subjects with serotype-specific IgG concentrations ≥0.35 µg/mL increased with age and was similar for the different serotypes: it was 20%-43% among 1-4-year-olds and 56%-90% among 20-39-year-olds. Prevalence of IgG ≥ 0.35 µg/mL against serotype 1 was up to 71% after age 10 years. During multivariate analyses, determinants of IgG concentrations ≥0.35 µg/mL varied by serotype; for 5 and 6 serotypes, respectively, female sex (around 2-fold increased odds) and cigarette smoking (about 5-fold reduced odds) predicted elevated titers. CONCLUSIONS: Despite a substantially higher historical pneumococcal meningitis incidence in Burkina Faso, the general population has an antibody seroprevalence against 12 pneumococcal serotypes similar to that reported from the United Kingdom. The role of putatively protective antibody seroprevalence in preventing pneumococcal meningitis in the meningitis belt requires more thorough evaluation.

Seroprevalence of bactericidal, specific IgG antibodies and incidence of meningitis due to group A Neisseria meningitidis by age in Burkina Faso 2008.

BACKGROUND: We investigated serological correlates of protection against Neisseria meningitidis serogroup A (NmA) in Burkina Faso before the introduction of NmA conjugate vaccine. METHODOLOGY/PRINCIPAL FINDINGS: We collected blood from a representative sample (N = 1022) of Bobo-Dioulasso residents. Sera were evaluated for serum bactericidal antibody (SBA) activity against NmA strains of immunotype L11 (F8238) and L10 (3125) and NmA-specific IgG. Seroprevalence was compared to the age-specific NmA meningitis incidence in Bobo-Dioulasso during March 2007-February 2008. Meningococcal carriage was evaluated in a subset (N = 538). Geometric mean titres (GMT)/concentrations (GMC) of SBA and NmA-specific IgG increased with age, peaking around age 20 years. Overall, 70% of our sample had NmA-specific IgG ≥2 ug/mL. Meningitis incidence was highest in those aged <6 months and 5-19 years. No NmA carriers were found. Compared to the reference strain SBA, GMTs were higher against a locally isolated strain and around 40-fold lower against Dutch strain 3125. CONCLUSIONS/SIGNIFICANCE: This study provides estimates of natural immunity to NmA, according to a variety of antibody measures, which will be helpful in ascertaining antibody persistence after MenAfriVac™ introduction. Age-specific seroprevalence of reference strain SBA titres most likely reflects exposure to meningococci and consecutive reactive immunity. We could not define any serological correlate of protection.

Pneumococcal serotype distribution among meningitis cases from Togo and Burkina Faso during 2007-2009.

We evaluated pneumococcal serotype/group distribution using polymerase chain reaction (PCR) testing on cerebrospinal fluid collected from patients from Burkina Faso and Togo who presented for care during 2007-2009. We identified 282 pneumococcal meningitis cases based on PCR, latex agglutination, or culture, of which 206 underwent serotyping. Serotype 1 was identified for 18% of serotyped cases from patients aged <5 years and 66% of those aged ≥5 years. The 13-valent and 10-valent pneumococcal conjugate vaccines (PCV-13 and PCV-10) contain 53% of serotypes identified among children age <5 years and 76-77% among persons aged ≥5 years. Pneumococcal meningitis was highly seasonal regardless of serotype. Data from this study emphasize the potential usefulness of PCVs among older children and adults.

Pneumococci in the African meningitis belt: meningitis incidence and carriage prevalence in children and adults.

BACKGROUND: The development of optimal vaccination strategies for pneumococcal conjugate vaccines requires serotype-specific data on disease incidence and carriage prevalence. This information is lacking for the African meningitis belt. METHODS: We conducted hospital-based surveillance of acute bacterial meningitis in an urban and rural population of Burkina Faso during 2007-09. Cerebrospinal fluid was evaluated by polymerase chain reaction for species and serotype. In 2008, nasopharyngeal swabs were obtained from a representative population sample (1 month to 39 years; N = 519) and additional oropharyngeal swabs from 145 participants. Swabs were evaluated by culture. RESULTS: Annual pneumococcal meningitis incidence rates were highest among <6-month-old (58/100,000) and 15- to 19-year-old persons (15/100,000). Annual serotype 1 incidence was around 5/100,000 in all age groups. Pneumococcal carriage prevalence in nasopharyngeal swabs was 63% among <5-year-old children and 22% among ≥5-year-old persons, but adding oropharyngeal to nasopharyngeal swabs increased the estimated carriage prevalence by 60%. Serotype 1 showed high propensity for invasive disease, particularly among persons aged ≥5 years. CONCLUSIONS: Serotype 1 causes the majority of cases with a relatively constant age-specific incidence. Pneumococcal carriage is common in all age groups including adults. Vaccination programs in this region may need to include older target age groups for optimal impact on disease burden.

Study of a localized meningococcal meningitis epidemic in Burkina Faso: incidence, carriage, and immunity.

BACKGROUND: To better understand localized meningococcal meningitis epidemics, we evaluated a serogroup A (NmA) epidemic in Burkina Faso by surveillance, carriage, and seroprevalence studies. METHODS: During March-April 2006, cerebrospinal fluid samples from patients suspected to have meningitis in 3 epidemic villages were analyzed by culture or polymerase chain reaction. We assessed meningococcal carriage and serogroup-specific serum bactericidal antibody titers with baby rabbit complement (rSBA) in a representative population sample (N = 624; age range, 1-39 years). A serogroup A/C polysaccharide vaccine campaign occurred in parallel. RESULTS: Cumulative incidence of Nm meningitis was 0.45% and varied among villages (0.08%-0.91%). NmA carriage prevalence was 16% without variation by vaccination status. NmA carriage and anti-NmA seroprevalence varied by village and incidence. In the 2 villages with highest incidence and seroprevalence, presence of rSBA titers ≥8 was associated with NmA carriage (odds ratio [OR], 9.33 [95% confidence interval {CI}, 1.90-45.91]) and vaccination ≤4 days earlier (OR, 0.10 [95% CI, .03-.32]). Visibly purulent or Nm meningitis was significantly associated with recent flulike symptoms and exposure to kitchen smoke (risk ratios >15). CONCLUSIONS: A surge of NmA carriage may be involved in the development of meningococcal epidemics and rapidly increase anti-NmA seroprevalence. Flulike infection and kitchen smoke may contribute to the strength of epidemics.

Short-term virological efficacy, immune reconstitution, tolerance, and adherence of once-daily dosing of didanosine, lamivudine, and efavirenz in HIV-1-infected African children: ANRS 12103 Burkiname.

Access to antiretroviral therapy (ART) and routine laboratory monitoring are limited for HIV-1-infected children from sub-Saharan Africa. This trial conducted in Bobo-Dioulasso, Burkina Faso, aimed to describe the biological efficacy, tolerance, and adherence of the combination of didanosine, lamivudine, efavirenz in once-daily administration among eligible HIV-1-infected children. From February 2006 to November 2007, 51 HIV-1-infected children aged from 30 months to 15 years and eligible for ART were enrolled in a phase II open clinical trial with follow-up visits every 3 months. HIV-1 genotype testing was performed in children with plasma viral load (PVL) >1000 copies per milliliter after ART initiation. Children were followed for a median of 13.4 months [interquartile range (IQR) 12.8-14.2]. At enrollment, median CD4 count was 8% (IQR = 4.5-12). PVL was 341,032 (IQR = 127,838-761,539) copies per milliliter. At 12 months, median CD4 increased significantly by +15% (P < 10(-3)), and median PVL decreases significantly by -290,500 copies per milliliter (P < 10(-4)). Hemoglobin and platelets counts increased significantly by +1.05 g/dL (P < 10(-5)) and 108,500 cells per milliliter (P < 10(-3)), respectively. Based on pill count, mean yearly adherence was 97.3%, and 48% of the children had an adherence rate ≥ 95% at the four quarterly visits. Adherence was better for girls than for boys independently of other sociodemographic variables or markers of HIV disease progression. Drug-resistant mutations were found in 11 children (21.6%). This once-daily drug combination is associated with excellent virological efficacy, immune reconstitution, and good adherence. However, the high prevalence of drug resistance mutations is a matter of concern.

Emergence of epidemic Neisseria meningitidis serogroup X meningitis in Togo and Burkina Faso.

Serogroup X meningococci (NmX) historically have caused sporadic and clustered meningitis cases in sub-Saharan Africa. To study recent NmX epidemiology, we analyzed data from population-based, sentinel and passive surveillance, and outbreak investigations of bacterial meningitis in Togo and Burkina Faso during 2006-2010. Cerebrospinal fluid specimens were analyzed by PCR. In Togo during 2006-2009, NmX accounted for 16% of the 702 confirmed bacterial meningitis cases. Kozah district experienced an NmX outbreak in March 2007 with an NmX seasonal cumulative incidence of 33/100,000. In Burkina Faso during 2007-2010, NmX accounted for 7% of the 778 confirmed bacterial meningitis cases, with an increase from 2009 to 2010 (4% to 35% of all confirmed cases, respectively). In 2010, NmX epidemics occurred in northern and central regions of Burkina Faso; the highest district cumulative incidence of NmX was estimated as 130/100,000 during March-April. Although limited to a few districts, we have documented NmX meningitis epidemics occurring with a seasonal incidence previously only reported in the meningitis belt for NmW135 and NmA, which argues for development of an NmX vaccine.

Low prevalence rate of indeterminate serological human immunodeficiency virus results among pregnant women from Burkina Faso, West Africa.

Rapid human immunodeficiency virus (HIV) antibody tests have been adopted into national guidelines for HIV testing in many countries in sub-Saharan Africa. One goal of HIV rapid testing is to minimize the occurrence of indeterminate results. From January 2005 to December 2007, plasma (or serum) samples from pregnant women in Bobo-Dioulasso (Burkina Faso, West Africa) were screened for HIV by using two rapid tests (the Determine HIV1/2 test [Abbott] and Genie II HIV-1/HIV-2 [Bio-Rad]) through a sequential algorithm prior to enrollment of HIV-1-infected women in a prevention of mother-to-child transmission (PMTCT) trial (WHO/ANRS 1289 Kesho Bora trial). Samples exhibiting indeterminate results (Determine positive and Genie II negative) were further tested with a fourth-generation HIV enzyme immunoassay (EIA) (Murex HIV Ag/Ab combination in 2005 and 2006 and Vironostika HIV Uni-Form II Ag/Ab in 2007). If positive, they were finally assessed for HIV-1 RNA (Generic HIV-1 RNA viral load assay; Biocentric). From a total of 44,653 samples tested, 597 (1.3%) showed indeterminate results. Of these, 367 could be analyzed by EIA. Only 15 (15/367, 4.1%) samples were found EIA reactive. Of these, 11 could be tested for HIV-1 RNA. All were HIV-1 RNA negative. In our clinical practice, pregnant women with such indeterminate results are now reassured during posttest counseling that they are very unlikely to be infected with HIV-1. As a consequence, such women with indeterminate results can reliably be considered negative when urgent clinical decisions (such as providing PMTCT prophylaxis) need to be taken.

Incidence, seasonality, age distribution, and mortality of pneumococcal meningitis in Burkina Faso and Togo.

Streptococcus pneumoniae causes a substantial proportion of meningitis cases in the African meningitis belt; however, few reports exist to quantify its burden and characteristics. We conducted population-based and sentinel hospital surveillance of acute bacterial meningitis among persons of all ages in Burkina Faso and Togo in 2002-2006. S. pneumoniae and other organisms were identified by culture, polymerase chain reaction, or detection of antigen in cerebrospinal fluid (CSF). Information was collected on 2843 patients with suspected acute bacterial meningitis. CSF specimens were collected from 2689 (95%) of the patients; of these 2689, 463 (17%) had S. pneumoniae identified, 234 (9%) had Haemophilus influenzae type b identified, and 400 (15%) had Neisseria meningitidis identified. Of the 463 cases of S. pneumoniae meningitis, 99 (21%) were aged <1 year, 71 (15%) were aged 1-4 years, 95 (21%) were aged 5-14 years, and 189 (41%) were aged >or=15 years (age was unknown for 9 [2%]). In Burkina Faso, the annual incidence rate of pneumococcal meningitis was 14 cases per 100,000 persons, with annual incidence rates of 77, 33, 10, and 11 cases per 100,000 persons aged <1 year, <5 years, 5-14 years, and >or=15 years, respectively. The case-fatality ratio for S. pneumoniae meningitis was 47% (range for age groups, 44%-52%), and 53% of deaths occurred among those aged >5 years. S. pneumoniae meningitis had an epidemic pattern similar to that of N. meningitidis meningitis. Of 48 isolates tested for serotype, 18 were from children aged <5 years; of these 18, 3 isolates (17%) each were serotypes 1, 2, and 5, and 5 isolates (28%) were serotype 6A. The 7-, 10-, and 13-valent pneumococcal conjugate vaccines would cover 6%, 39%, and 67% of serotypes identified among children aged <5 years, respectively. Of the 30 serotypes identified for patients aged >or=5 years, 18 (60%) were serotype 1, whereas no other serotype constituted >10%. The 7-, 10-, and 13-valent vaccines would cover 7%, 70%, and 77% of serotypes. Epidemic pneumococcal meningitis in the African meningitis belt countries of Burkina Faso and Togo is common, affects all age groups, and is highly lethal. On the basis of a modest number of isolates from a limited area that includes only meningitis cases, 7-valent pneumococcal conjugate vaccine might have only a limited and short-term role. By contrast, the proposed 10- and 13-valent vaccines would cover most of the identified serotypes. To better inform vaccine policy, continued and expanded surveillance is essential to document serotypes associated with pneumonia, changes in serotype distribution across time, and the impact of vaccine after vaccine introduction.

Association of respiratory tract infection symptoms and air humidity with meningococcal carriage in Burkina Faso.

OBJECTIVES: To evaluate risk factors for meningococcal carriage and carriage acquisition in the African meningitis belt, comparing epidemic serogroup A (NmA) to non-epidemic serogroups. METHODS: During the non-epidemic meningitis season of 2003, pharyngeal swabs were taken at five monthly visits in a representative population sample (N = 488) of Bobo-Dioulasso, Burkina Faso (age 4-29 years) and analysed by culture. Standardized questionnaires were administered. In 2006, a similar study was performed in 624 individuals (age 1-39 years) during an NmA meningitis epidemic. We evaluated serogroup-specific risk factors for carriage, carriage acquisition and clearance using multivariate logistic and Poisson regression, and a Cox proportional hazard model. RESULTS: The prevalence of NmA carriage (current or recent pharyngitis or rhinitis) was 16% (31%) vs. 0% (9%) in the epidemic vs. the hyperendemic setting. During the epidemic situation, NmA carriage was significantly associated with recent sore throat (adjusted odds ratio (OR), 3.41) and current rhinitis (OR 2.65). During the non-epidemic meningitis season in 2003, air humidity (20-39% and >or=40%, compared to <20%) during the month before swabbing was significantly and positively associated with carriage acquisition of non-groupable meningococci (OR 2.18 and 1.55) and inversely with carriage clearance (hazard ratio 0.61 and 0.27, respectively). CONCLUSION: Respiratory tract infections may increase meningococcal carriage, and thus contribute to epidemic risk, in addition to seasonality in the meningitis belt. Humid climate may favour carriage of unencapsulated meningococci. These findings may help identifying interventions against epidemic and hyperendemic meningococcal meningitis due to non-vaccine serogroups.

Meningococcal carriage and immunity in western Burkina Faso, 2003.

A prospective carriage and serological study was conducted in Burkina Faso during the 2003 meningitis season, which was characterized by hyperendemic Neisseria meningitidis serogroup W135 (NmW135) and serogroup A (NmA) disease. Participants were evaluated five times at monthly intervals. In the presence of moderate NmW135 carriage, we found a low prevalence of putatively protective levels of specific immunoglobulin G (IgG) and serum bactericidal antibody (SBA) against NmW135. Specific IgG concentrations and SBA titers against NmA were relatively high in this recently vaccinated population, while no NmA carriage was detected. NmW135 carriage infrequently induced protective immunity against reference or homologous strains, while natural immunity against NmW135 was frequently lost. A vaccine that is effective against W135 will be beneficial for sub-Saharan Africa.

The rise and fall of epidemic Neisseria meningitidis serogroup W135 meningitis in Burkina Faso, 2002-2005.

BACKGROUND: During the period 2001-2002, Burkina Faso reported its first meningitis epidemic due to Neisseria meningitidis (Nm) serogroup W135, prompting concerns that this serogroup would persist as a cause of epidemic disease. METHODS: During the period 2002-2005, hospital- and population-based surveillances were conducted in 3 districts in Burkina Faso. Etiology was determined by culture, polymerase chain reaction (PCR), and latex agglutination. Reference laboratories determined phenotype and genotype. RESULTS: Of 2004 subjects who received a lumbar puncture, 265 were identified as having Nm, including 93 who had Nm serogroup A (NmA) and 146 who had Nm serogroup W135 (NmW135). Over the study period, the proportion of cases due to NmW135 decreased by >75%, primarily because of decreased occurrence among young children and in a single district. During peak epidemic months, the annualized incidence of NmW135 decreased from 146 cases to <1 case per 100,000 population. All but 2 NmW135 isolates were phenotype W135:2a:P1.5,2 (sequence type [ST]-11 clonal complex). All NmA isolates were phenotype A:4:P1-9 (ST-2859 of the ST-5 clonal complex). We identified 1 isolate from serogroup Y (ST-11 clonal complex), 1 isolate from serogroup X that was similar to strains previously associated with epidemic disease, and 1 isolate from serogroup W135 of the newly described ST-4375 complex. CONCLUSIONS: For unknown reasons, serogroup W135 achieved epidemic status, primarily among young children, and then largely disappeared over a short time period. The continued circulation of multiple strains with epidemic potential emphasizes the need for ongoing surveillance and the potential benefit of vaccines that are protective across serogroups.