Oral innate immunity in patients with type 2 diabetes mellitus in a tertiary hospital in Ibadan Nigeria: a cross-sectional study.

Introduction: diabetes mellitus is associated with a high prevalence of oral infections. However, it is unclear how diabetes impacts oral innate antimicrobial proteins. This study evaluated salivary lysozyme and histatins, two major innate antimicrobial proteins, in patients with diabetes and non-diabetic controls. Methods: a cross-sectional study where salivary lysozyme and histatins were measured alongside plasma glucose levels. Values of the salivary proteins were compared between the two groups; their association with glucose levels was also established using correlation and regression analysis. Results: one hundred and fifty-one participants were recruited for this study, 85 (56.3%) of them had type 2 diabetes mellitus with a median fasting plasma glucose of 108.8 mg/dl (IQR 91.2-134.8) while the remaining 66 (43.7%) healthy non-diabetic controls had a median random plasma glucose of 101 mg/dl (IQR 89-112). The median salivary lysozyme was 32.5 ng/ml (IQR 25.0-39.6) in the group with diabetes and 36.4 ng/ml (IQR 31.4-42.1; p=0.01) in the non-diabetic control group. The median salivary histatins was 9.2 ng/ml (IQR 7.6 -10.2) in the group with diabetes and 14.7 ng/ml (IQR12.8-16.5; p<0.001) in the non-diabetic control group. Salivary lysozyme (r = -0.127; p =0.163) and histatins (r = -0.025; p = 0.424) were both negatively correlated with plasma glucose levels, and logistic regression showed that patients with diabetes are more likely to have lower levels of salivary lysozyme (0.957; p=0.013) and histatins (0.527; p<0.001). Conclusion: patients with diabetes had reduced levels of salivary lysozyme and histatins, this could provide an insight into the associated high oral infection rates.

SARS-CoV-2 Seropositivity in Asymptomatic Frontline Health Workers in Ibadan, Nigeria.

Global health has been thrown into turmoil by the COVID-19 pandemic, which has caused devastating morbidity and unprecedented loss of life in almost all continents of the world. It was predicted that the magnitude of the pandemic in Africa will be high because of poor health structure and intensely poor living condition, but that has not happened, surprisingly. It was hypothesized that the youthful population and a vastly primed immune system were protective, and many people may have been exposed without coming down with the severe disease. Most of them would have presented in hospitals with other medical conditions and possibly transmit COVID-19 to health workers inadvertently. This study is designed to measure serum SARS-CoV-2 IgG levels in health workers as a marker of latent exposure. Asymptomatic frontline health workers were randomly selected from the University College Hospital Ibadan, Nigeria; venous blood samples were obtained from them, and the serum SARS-CoV-2 IgG level was determined using ELISA techniques. A proportion of participants with seropositivity were obtained, and factors associated with seropositivity were determined. A total of 133 participants were recruited for this study, and 60 (45.1%) of them were seropositive for SARS-CoV-2. Among the seropositive participants were doctors, nurses, health assistants, laboratory scientists and technicians, and nonmedical staff. Obstetrics, gynecology, and emergency departments had higher odds of seropositivity. Seroprevalence of SARS-CoV-2 is very high among frontline health workers, though asymptomatic. This calls for a more stringent precaution against further spread within the hospital environment.

A regimen containing bedaquiline and delamanid compared to bedaquiline in patients with drug-resistant tuberculosis.

There are limited data on combining delamanid and bedaquiline in drug-resistant tuberculosis (DR-TB) regimens. Prospective long-term outcome data, including in HIV-infected persons, are unavailable.We prospectively followed up 122 South African patients (52.5% HIV-infected) with DR-TB and poor prognostic features between 2014 and 2018. We examined outcomes and safety in those who received a bedaquiline-based regimen (n=82) compared to those who received a bedaquiline-delamanid combination regimen (n=40).There was no significant difference in 6-month culture conversion (92.5% versus 81.8%; p=0.26) and 18-month favourable outcome rate (63.4% versus 67.5%; p=0.66) in the bedaquiline versus the bedaquiline-delamanid combination group, despite the latter having more advanced drug resistance (3.7% versus 22.5% resistant to at least five drugs; p=0.001) and higher pre-treatment failure rates (12.2% versus 52.5% with pre-treatment multidrug-resistant TB therapy failure; p<0.001). Although the proportion of prolongation of the QT interval corrected using Fridericia's formula was higher in the combination group (>60 ms from baseline (p=0.001) or >450 ms during treatment (p=0.001)), there were no symptomatic cases or drug withdrawals in either group. Results were similar in HIV-infected patients.A bedaquiline-delamanid combination regimen showed comparable long-term safety compared to a bedaquiline-based regimen in patients with DR-TB, irrespective of HIV status. These data inform regimen selection in patients with DR-TB from TB-endemic settings.

Linezolid interruption in patients with fluoroquinolone-resistant tuberculosis receiving a bedaquiline-based treatment regimen.

BACKGROUND: Treatment outcomes of patients with extensively drug-resistant tuberculosis (XDR-TB) are suboptimal and treatment options remain limited. Linezolid is associated with improved outcomes but also substantial toxicity, and details about the relationship between these are lacking from resource-poor HIV-endemic settings. METHODS: This was a prospective follow-up study of 63 South African XDR-TB patients (58.7% HIV-infected; median CD4 131 cells/µl) between 2014 and 2018. The frequency and severity of linezolid-associated adverse events and the impact on treatment outcomes were compared between linezolid interrupters and non-interrupters. RESULTS: Twenty-two patients (34.9%) discontinued or underwent dose reduction due to presumed linezolid-associated toxicity. Anaemia (77.3% vs. 7.3%; p< 0.001), peripheral neuropathy (63.6% vs. 14.6%; p= 0.003), and optic neuritis (18.2% vs. 9.8%; p= 0.34) occurred more frequently in linezolid interrupters than in non-interrupters. Anaemia, peripheral neuropathy, and optic neuritis occurred at a median of 5, 18, and 23 weeks, respectively, after treatment initiation. Linezolid interruption was not associated with unfavourable outcomes but was strongly associated with HIV co-infection (adjusted hazard ratio 4.831, 95% confidence interval 1.526-15.297; p= 0.007) and bacterial load (culture days to positivity; adjusted hazard ratio 0.824, 95% confidence interval 0.732- 0.927; p= 0.001). CONCLUSIONS: Linezolid-related treatment interruption is common, is strongly associated with HIV co-infection, and system-specific toxicity occurs within predictable time frames. These data inform the clinical management of patients with drug-resistant TB.

Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa.

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL-1) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p<0.001) and default (1.5% versus 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

Salivary immunoglobulin classes in Nigerian smokers with periodontitis.

AIM: To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis. METHODS: Sixty-nine individuals were recruited into this study after obtaining informed consent. They were subdivided into three groups that consisted of 20 (aged 46 ± 11 years) cigarette smokers with periodontitis (S+P); 24 (40 ± 12 years) smokers without periodontitis (S-P); and 25 (53 ± 11 years) non-smokers with periodontitis (NS+P). An oral and maxillofacial surgeon used radiographs for periodontal probing for the diagnosis of periodontitis. The smokers included subjects who smoked at least six cigarettes per day and all the periodontitis patients were newly diagnosed. About 5 mL of unstimulated saliva was expectorated by each subject into plain sample bottles. Salivary immunoglobulin levels were estimated using enzyme linked immunosorbent assay. Student's t test was used to determine significant differences between the means. Values of P < 0.05 were regarded as significant. RESULTS: No significant differences were observed in the mean salivary levels of the immunoglobulin classes (IgG, IgA, IgM and IgE) when S+P was compared with S-P. Mean salivary levels of IgA (520.0 ± 155.1 ng/mL vs 670.0 ± 110 ng/mL, P = 0.000) and IgM (644.5 ± 160.0 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.000) were significantly lower in the S+P compared with NS+P group. Salivary IgA (570.4 ± 145.6 ng/mL vs 670.0 ± 110 ng/mL, P = 0.008) and IgM (703.1 ± 169.3 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.012) levels were significantly lower in the S-P compared with NS+P group. Only one (5%) periodontal patient had detectable levels of salivary IgE (0.20 IU/mL). Similarly, only one smoker (4.17%) had detectable levels of salivary IgE (0.04 IU/mL) and two non-smokers (9.52%) had detectable levels of IgE (0.24 IU/mL). CONCLUSION: Our study suggests that reduced salivary IgA and IgM levels in smokers with periodontitis could enhance increased susceptibility to periodontitis.