Continued Decline of Malaria in The Gambia with Implications for Elimination

BACKGROUND: A substantial decline in malaria was reported to have occurred over several years until 2007 in the western part of The Gambia, encouraging consideration of future elimination in this previously highly endemic region. Scale up of interventions has since increased with support from the Global Fund and other donors. METHODOLOGY/PRINCIPAL FINDINGS: We continued to examine laboratory records at four health facilities previously studied and investigated six additional facilities for a 7 year period, adding data from 243,707 slide examinations, to determine trends throughout the country until the end of 2009. We actively detected infections in a community cohort of 800 children living in rural villages throughout the 2008 malaria season, and assayed serological changes in another rural population between 2006 and 2009. Proportions of malaria positive slides declined significantly at all of the 10 health facilities between 2003 (annual mean across all sites, 38.7%) and 2009 (annual mean, 7.9%). Statistical modelling of trends confirmed significant seasonality and decline over time at each facility. Slide positivity was lowest in 2009 at all sites, except two where lowest levels were observed in 2006. Mapping households of cases presenting at the latter sites in 2007-2009 indicated that these were not restricted to a few residual foci. Only 2.8% (22/800) of a rural cohort of children had a malaria episode in the 2008 season, and there was substantial serological decline between 2006 and 2009 in a separate rural area. CONCLUSIONS: Malaria has continued to decline in The Gambia, as indicated by a downward trend in slide positivity at health facilities, and unprecedented low incidence and seroprevalence in community surveys. We recommend intensification of control interventions for several years to further reduce incidence, prior to considering an elimination programme

Computational investigation on structural and functional impact of oncogenes and tumor suppressor genes on cancer

Within the sequence of the whole genome, it is known that 99.9% of human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, human variation datasets for 5 oncogenes (ONGs)(AKT1, ALK, ERBB2, KRAS, BRAF) and 5 Tumor Suppressor Genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar to study the implications of nsSNPs. To this end, bioinformatics tools were used to differentiate deleterious variations from neutral and benign. The functional impact of the variations was also examined using available computational tools such as sequence-homology based, supervised learning methods, protein sequence and structure–based tools, consensusbased tools and methods using evolutionary conservation analysis. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.Tüm genom dizisi içinde, insan genomunun %99.9'unun benzer olduğu bilinirken, farklılıklarımız sadece kalan %0.1'den kaynaklanmaktadır. Bu küçük farklılıklar, bir protein dizisindeki nükleotid değişimi nedeniyle ortaya çıkan tek nükleotid polimorfizmi (SNP) sebebiyle proteinlerde stabilizasyon kaybına, dinamiklerinde değişikliklere ve diğer fizyo-kimyasal özelliklerde bozulmalara yol açan ve bir popülasyonda meydana gelen en yaygın genetik varyasyon türü’dür. Varyasyonlarçeşitli kanser türleri neden olurken, bir tedaviye veya bir hastalığa yanıt verme şeklimizdeki farklılığımızdan yüksek derecede sorumludurlar. İki tür SNP vardır; eşanlamlı tek nükleotid polimorfizmi (sSNP) ve eşanlamlı olmayan tek nükleotid polimorfizmi (nsSNP). sSNP, kodlanmış amino asitte bir değişikliğe neden olmadan gen kodlama bölgesinde meydana gelirken, nsSNP, gen kalıntısının içerisi bir nucleotid değişiklik nedeniyle başka amino asit ile sonuçlanan gen dizi olması nedeniyle zararlıdır. Kansere bağlı nsSNP'lerin protein stabilitesi, fonksiyonu ve dinamikleri üzerindeki etkilerini tahmin etmek, kanserin fenotip-genotip ilişkisinin önemi nedeniyle önemlidir. Bu çalışmada, 5 ONG (AKT1, ALK, ERBB2, KRAS, BRAF) ve 5 TSG (ESR1, CASP8, TET2, PALB2, PTEN) için varyasyon veri kümeleri, nsSNP'lerin etkilerini incelemek için ClinVar'dan elde edilmiştir. Zararlı varyasyonların nötr ve tehlikesiz olanlardan ayırt etmek için biyoinformatik araçlar kullanılmıştır.Varyasyonların işlevsel etkilerini incelemek için dizi-homoloji tabanlı yöntemler, denetimli öğrenme yöntemleri, protein dizilimi ve yapı tabanlı araçlar, ve evrimsel korunma analizi kullanan yöntemler gibi mevcut hesaplama araçları kullanılarak incelenmiştir. Elde edilen sonuçlar, kanser tedavilerinde yeni ufuklar açmak için gelecekteki araştırmalara ışık tutabilecektir

Epidemiology of measles cases, vaccine effectiveness, and performance towards measles elimination in The Gambia

Introduction: In 2011, member states of the World Health Organization (WHO) Africa Regional Office (AFRO) resolved to eliminate Measles by 2020. Our study aims to assess The Gambia’s progress towards the set AFRO measles elimination target and highlight surveillance and immunisation gaps to better inform future measles prevention strategies. Material and methods: A retrospective review of measles surveillance data for the period 2011–2019, was extracted from The Gambia case-based measles surveillance database. WHO—UNICEF national coverage estimates were used for estimating national level MCV coverage. Measles post campaign coverage survey coverage estimates were used to estimate national measles campaign coverage. Results: One hundred and twenty-five of the 863 reported suspected cases were laboratory confirmed as measles cases. More than half (53.6%) of the confirmed cases have unknown vaccination status, 24% of cases were vaccinated, 52.8% of cases occurred among males, and 72.8% cases were among urban residents. The incidence of measles cases per million population was lowest (0) in 2011–2012 and highest in 2015 and 2016 (31 and 23 respectively). The indicator for surveillance sensitivity was met in all years except in 2016 and 2019. Children aged 5–9 years (Incidence Rate Ratio—IRR = 0.6) and residents of Central River region (IRR = 0.21) had lower measles risk whilst unvaccinated (Adjusted IRR = 5.95) and those with unknown vaccination status (IRR 2.21) had higher measles risk. Vaccine effectiveness was 89.5%. Conclusion: The Gambia’s quest to attain measles elimination status by 2020 has registered significant success but it is unlikely that all target indicators will be met. Vaccination has been very effective in preventing cases. There is variation in measles risk by health region, and it will be important to take it into account when designing prevention and control strategies. The quality of case investigations should be improved to enhance the quality of surveillance for decision making

Evaluation of Fecal Inflammatory Biomarkers to Identify Bacterial Diarrhea Episodes: Systematic Review and Protocol for the Enterics for Global Health <i>Shigella</i> Surveillance Study.

BackgroundThe measurement of fecal inflammatory biomarkers among individuals presenting to care with diarrhea could improve the identification of bacterial diarrheal episodes that would benefit from antibiotic therapy. We reviewed prior literature in this area and describe our proposed methods to evaluate 4 biomarkers in the Enterics for Global Health (EFGH) Shigella surveillance study.MethodsWe systematically reviewed studies since 1970 from PubMed and Embase that assessed the diagnostic characteristics of inflammatory biomarkers to identify bacterial diarrhea episodes. We extracted sensitivity and specificity and summarized the evidence by biomarker and diarrhea etiology. In EFGH, we propose using commercial enzyme-linked immunosorbent assays to test for myeloperoxidase, calprotectin, lipocalin-2, and hemoglobin in stored whole stool samples collected within 24 hours of enrollment from participants in the Bangladesh, Kenya, Malawi, Pakistan, Peru, and The Gambia sites. We will develop clinical prediction scores that incorporate the inflammatory biomarkers and evaluate their ability to identify Shigella and other bacterial etiologies of diarrhea as determined by quantitative polymerase chain reaction (qPCR).ResultsForty-nine studies that assessed fecal leukocytes (n = 39), red blood cells (n = 26), lactoferrin (n = 13), calprotectin (n = 8), and myeloperoxidase (n = 1) were included in the systematic review. Sensitivities were high for identifying Shigella, moderate for identifying any bacteria, and comparable across biomarkers. Specificities varied depending on the outcomes assessed. Prior studies were generally small, identified red and white blood cells by microscopy, and used insensitive gold standard diagnostics, such as conventional bacteriological culture for pathogen detection.ConclusionsOur evaluation of inflammatory biomarkers to distinguish diarrhea etiologies as determined by qPCR will provide an important addition to the prior literature, which was likely biased by the limited sensitivity of the gold standard diagnostics used. We will determine whether point-of-care biomarker tests could be a viable strategy to inform treatment decision making and increase appropriate targeting of antibiotic treatment to bacterial diarrhea episodes

Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study

Background Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30 μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. Methods In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8–10 weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30 μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2–3–4 months (3 + 0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2–4–9 months (2 + 1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5–9–12 months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. Results 1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60–67%) and non-10VT (55–61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3 + 0 schedule) was 1.1% (95% CI −21.5, 19.5) and 2.1% (−20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2 + 1 schedule) was 0.5% (−22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. Conclusions In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. Funding: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872