Transmission and evolutionary dynamics of human coronavirus OC43 strains in coastal Kenya investigated by partial spike sequence analysis, 2015-2016

Human coronavirus OC43 (HCoV-OC43) is a major contributor to seasonal outbreaks of acute respiratory illness (ARI). The origins of locally circulating HCoV-OC43 strains and characteristics of their genetic diversity are unknown for most settings despite significance to effective HCoV control strategies. Between December 2015 and June 2016, we undertook ARI surveillance in coastal Kenya in nine outpatients and one inpatient health facility (HF). Ninety-two patient samples tested HCoV-OC43 positive and forty (43.5%) were successfully sequenced in spike (S) gene region (2,864 long, ∼70%). Phylogenetic analysis confirmed co-circulation of two distinct HCoV-OC43 clades that closely clustered with genotype G (n = 34, 85%) and genotype H (n = 6, 15%) reference strains. Local viruses within the same clade displayed low genetic diversity yielding identical sequences in multiple HF. Furthermore, the newly sequenced Kenyan viruses showed close phylogenetic relationship to other contemporaneous sampled strains (2015–16) including those originating from distant places (e.g. USA and China). Using a genetic similarity threshold of 99.1 per cent at nucleotide level, the HCoV-OC43 strains sampled globally between 1967 and 2019 fell into nine sequence clusters. Notably, some of these clusters appeared to have become extinct, or occurred only sporadically in a few geographical areas while others persisted globally for multiple years. In conclusion, we found that HCoV-OC43 strains spread rapidly both locally and across the globe with limited genetic evolution in the spike gene. Full-genome sequences that are spatio-temporally representative are required to advance understanding of the transmission pathways of this important human respiratory pathogen

Quantifying maternally derived respiratory syncytial virus specific neutralising antibodies in a birth cohort from coastal Kenya.

BACKGROUND: Severe respiratory syncytial virus (RSV) disease occurs predominantly in children under 6 months of age. There is no licensed RSV vaccine. Protection of young infants could be achieved by a maternal vaccine to boost titres of passively transferred protective antibodies. Data on the level and kinetics of functional RSV-specific antibody at birth and over the early infant period would inform vaccine product design. METHODS: From a birth cohort study (2002-2007) in Kilifi, Kenya, 100 participants were randomly selected for whom cord blood and 2 subsequent 3-monthly blood samples within the first year of life, were available. RSV antibodies against the A2 strain of RSV were assayed and recorded as the logarithm (base 2) plaque reduction neutralisation test (PRNT) titre. Analysis by linear regression accounted for within-person clustering. RESULTS: The geometric mean neutralisation antibody titre was 10.6 (SD: 1.13) at birth with a log-linear decay over the first 6 months of life. The estimated rate of decay was -0.58 (SD: 0.20) log2PRNT titre per month and a half-life of 36 days. There was no significant interaction between cord titre and rate of decay with age. Mean cord titres rose and fell in a pattern temporally tracking community virus transmission. CONCLUSIONS: In this study population, RSV neutralising antibody titres decay approximately two-fold every one month. The rate of decay varies widely by individual but is not related to titre at birth. RSV specific cord titres vary seasonally, presumably due to maternal boosting

Agreement between ELISA and plaque reduction neutralisation assay in Detection of respiratory syncytial virus specific antibodies in a birth Cohort from Kilifi, coastal Kenya.

Background: Severe disease associated with respiratory syncytial virus (RSV) infection occurs predominantly among infants under 6 months of age. Vaccines for prevention are in clinical development. Assessment of the vaccine effectiveness in large epidemiological studies requires serological assays which are rapid, economical and standardised between laboratories. The objective of this study was to assess the agreement between two enzyme linked immunosorbent assays (ELISA) and the plaque reduction neutralisation test (PRNT) in quantifying RSV specific antibodies. Methods: Archived sera from 99 participants of the Kilifi Birth Cohort (KBC) study (conducted 2002-2007) were screened for RSV antibodies using 3 methods: ELISA using crude RSV lysate as antigen, a commercial RSV immunoglobulin G (IgG) ELISA kit from IBL International GmbH, and PRNT. Pearson correlation, Bland-Altman plots and regression methods were used in analysis. Results: There was high positive correlation between the IBL RSV IgG ELISA and PRNT antibodies (Pearson r=0.75), and moderate positive correlation between the crude RSV lysate IgG ELISA and PRNT antibodies (r= 0.61). Crude RSV lysate IgG ELISA showed a wider 95% limit of agreement (-1.866, 6.157) with PRNT compared to the IBL RSV IgG ELISA (1.392, 7.595). Mean PRNT titres were estimated within a width of 4.8 log 2PRNT and 5.6 log 2PRNT at 95% prediction interval by IBL RSV IgG and crude RSV lysate IgG ELISA, respectively. Conclusion: Although, the IBL RSV IgG ELISA is observed to provide a reasonable correlate for PRNT assay in detecting RSV specific antibodies, it does not provide an accurate prediction for neutralizing antibody levels. An RSV neutralising antibody level is likely to fall within 2.4 fold higher and 2.4 fold lower than the true value if IBL RSV IgG ELISA is used to replace PRNT assay. The utility of an ELISA assay in vaccine studies should be assessed independent of the PRNT method

A new Omicron lineage with Spike Y451H mutation that dominated a new COVID-19 wave in Kilifi, Coastal Kenya : March-May 2023

Objective Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). Design Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. Methods Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. Results and Conclusions Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean −1.24%, −1.30%, −2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

The descriptive epidemiology of Streptococcus pneumoniae and Haemophilus influenzae nasopharyngeal carriage in children and adults in Kilifi district, Kenya.

BACKGROUND: Transmission and nasopharyngeal colonization are necessary steps en route to invasive pneumococcal or Haemophilus influenzae disease but their patterns vary geographically. In East Africa we do not know how these pathogens are transmitted between population subgroups nor which serotypes circulate commonly. METHODS: We did 2 cross-sectional nasopharyngeal swab surveys selecting subjects randomly from a population register to estimate prevalence and risk-factors for carriage in 2004. H. influenzae type b vaccine was introduced in 2001. RESULTS: Of 450 individuals sampled in the dry season, 414 were resampled during the rainy season. Among subjects 0-4, 5-9, and 10-85 years old pneumococcal carriage prevalence was 57%, 41%, and 6.4%, respectively. H. influenzae prevalence was 26%, 24%, and 3.0%, respectively. Prevalence of H. influenzae type b in children &lt;5 years was 1.7%. Significant risk factors for pneumococcal carriage were rainy season (odds ratio [OR]: 1.65), coryza (OR: 2.29), and coculture of noncapsulate H. influenzae (OR: 7.46). Coryza was also a risk factor for H. influenzae carriage (OR: 1.90). Of 128 H. influenzae isolates, 113 were noncapsulate. Among 279 isolates of Streptococcus pneumoniae, 40 serotypes were represented and the distribution of serotypes varied significantly with age; 7-valent vaccine-types, vaccine-related types, and nonvaccine types comprised 47%, 19%, and 34% of strains from children aged &lt;5 years. Among older persons they comprised 25%, 28%, and 47%, respectively (P = 0.005). CONCLUSIONS: The study shows that pneumococcal carriage is common up to 9 years of age and that the majority of serotypes carried at all ages are not covered specifically by the 7-valent pneumococcal conjugate vaccine

Agreement between ELISA and plaque reduction neutralisation assay in Detection of respiratory syncytial virus specific antibodies in a birth Cohort from Kilifi, coastal Kenya

Background: Severe disease associated with respiratory syncytial virus (RSV) infection occurs predominantly among infants under 6 months of age. Vaccines for prevention are in clinical development. Assessment of the vaccine effectiveness in large epidemiological studies requires serological assays which are rapid, economical and standardised between laboratories. The objective of this study was to assess the agreement between two enzyme linked immunosorbent assays (ELISA) and the plaque reduction neutralisation test (PRNT) in quantifying RSV specific antibodies. Methods: Archived sera from 99 participants of the Kilifi Birth Cohort (KBC) study (conducted 2002-2007) were screened for RSV antibodies using 3 methods: ELISA using crude RSV lysate as antigen, a commercial RSV immunoglobulin G (IgG) ELISA kit from IBL International GmbH, and PRNT. Pearson correlation, Bland-Altman plots and regression methods were used in analysis. Results: There was high positive correlation between the IBL RSV IgG ELISA and PRNT antibodies (Pearson r=0.75), and moderate positive correlation between the crude RSV lysate IgG ELISA and PRNT antibodies (r= 0.61). Crude RSV lysate IgG ELISA showed a wider 95% limit of agreement (-1.866, 6.157) with PRNT compared to the IBL RSV IgG ELISA (1.392, 7.595). Mean PRNT titres were estimated within a width of 4.8 log 2PRNT and 5.6 log 2PRNT at 95% prediction interval by IBL RSV IgG and crude RSV lysate IgG ELISA, respectively. Conclusion: Although, the IBL RSV IgG ELISA is observed to provide a reasonable correlate for PRNT assay in detecting RSV specific antibodies, it does not provide an accurate prediction for neutralizing antibody levels. An RSV neutralising antibody level is likely to fall within 2.4 fold higher and 2.4 fold lower than the true value if IBL RSV IgG ELISA is used to replace PRNT assay. The utility of an ELISA assay in vaccine studies should be assessed independent of the PRNT method