Exogenous re-infection by a novel Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis in a child from The Gambia

We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae

Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine

BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. CONCLUSION: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum

As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis

The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction.

BACKGROUND: The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. METHODS: Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to 99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. CONCLUSIONS: Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries

Discovery and validation of biomarkers to guide clinical management of pneumonia in African children.

BACKGROUND: Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management. METHODS: We conducted a mass spectrometry-based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC). RESULTS: Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval, .64-.79]) and highly predictive of bacteremia (78% [64%-92%]), pneumococcal bacteremia (84% [71%-98%]), and "probable bacterial etiology" (91% [84%-98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%-100%]) and Kenyan children (82% [74%-91%]). CONCLUSIONS: Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study.

BACKGROUND: Routine immunisation of infants in The Gambia with a Haemophilus influenzae type b (Hib) polysaccharide-tetanus toxoid conjugate vaccine began in May, 1997. We investigated the effectiveness of the vaccine when delivered through the expanded programme on immunisation and the effect of national immunisation on incidence of Hib disease. METHODS: Surveillance for Hib disease was maintained in the western half of The Gambia using standard methods with an emphasis on meningitis. We estimated vaccine efficacy using the case control method, and vaccine coverage and population denominators for incidence rates using a cluster sample survey. Prevalence of Hib carriage in a sample of 1-2-year old children attending health centres for vaccination was ascertained with oropharyngeal swabs plated onto antiserum agar. FINDINGS: Between May, 1997, and April, 2002, a total of 5984 children were examined for possible Hib infections. 49 children had Hib disease, 36 of whom had meningitis. The annual incidence rates of Hib meningitis before any use of the vaccine (1990-93) dropped from over 200 per 100,000 children aged younger than 1 year to none per 100,000 in 2002, and from 60 to no cases per 100,000 in children younger than 5 years. The prevalence of Hib carriage decreased from 12% to 0.25% (p<0.0001). Two doses of vaccine were needed for direct protection from Hib disease (vaccine efficacy 94%, 95% CI 62-99). Since most children received a protective dose after the age of greatest disease risk, indirect effects were important in reducing disease incidence. INTERPRETATION: The Gambian Hib immunisation programme reduced the occurrence of Hib disease despite irregular vaccine supply. The effect of the programme in The Gambia has important implications for the introduction of the vaccine into routine immunisation programmes of other developing countries

Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial.

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia. METHODS AND FINDINGS: A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively). A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small. CONCLUSIONS: Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a "herd effect" in non-vaccinated older children and adults. No significant serotype replacement was detected. Please see later in the article for the Editors' Summary