Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2; 1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

Association of ABO blood group and plasmodium falciparum malaria among children in the Federal Capital Territory, Nigeria

The ABO and Rhesus blood group systems are very important clinical tools that are commonly used in blood transfusion and their associations with various disease conditions have been widely reported. This study investigated the distribution of these blood group systems and assessed the association of malaria infection with the ABO blood groups among children in Federal Capital Territory; Abuja. Blood specimens from deep finger pricks of 730 children aged between 0-2 years were examined for malaria parasites using Field stains method. ABO and Rhesus blood group antigens tests were also performed using standard tile protocols. Of all the children admitted into the study; 445 were sick while 285 were apparently healthy. The prevalence of malaria parasites was significantly higher (P = 0.00047) among the sick children (69.8%) than the apparently healthy children (30.2%). The most prevalent blood group was O (55.7%) and the Rhesus D antigen was positive for 98.4% of all the children. The prevalence of blood group B among the sick children was significantly lower (P = 0.00373) than the other blood group types. There is no association between malaria infection and ABO blood groups but the prevalence of higher malaria parasite density was significantly greater (P = 0.0404) in children with blood group A (7.7%). In conclusion; blood group O was the most prevalent blood group in the study and children with blood group A appeared to be more susceptible to higher level of malaria parasitemia

Antibiotic resistance and virulence properities in escherichia coli stranins from cases of urinary tract infections

This study determined E. coli resistance to commonly used antibiotics together with their virulence properties in Ile-Ife; Nigeria. A total of 137 E. coli isolates from cases of urinary tract infection were tested for their sensitivity to commonly used antibiotics and possession of virulence factors using standard methods. Their ability to transfer resistance was also determined. The isolates demonstrated a high and widespread resistance (51.1 to 94.3) to all the antibiotics used except Nitrofurantoin (7.3). A total of 50 (36.5 ) of the isolates were resistant to 10 of the eleven antibiotics employed. Sixty three per cent (63) of the 107 trimethoprim resistant E. coli transferred their resistances while amoxicillin; gentamycin; augmentin; tetracycline and erythromycin were co-transferred with trimethoprim. Fifty one (37.2) of these multi-resistant isolates possessed one or more virulent factors. The study concluded that urinary tract infection due to E. coli in Ile-Ife may be difficult to treat empirically except with nitrofurantoin; due to high resistance to commonly used antibiotics. It is imperative that culture and susceptibility tests be carried out on infecting pathogen prior to treatment; in order to avoid treatment failure and reduce selective pressure that could result in the spread of uropathogenic E. coli in the environment

A study of the intestinal carriage of antibiotic resistant Staphylococcus aureus by Nigerian children.

BACKGROUND: The gastrointestinal tract has been recognized as a major ecological site for Staphylococcus aureus where it can reach neighboring sites and cause mild or serious infections. OBJECTIVES: To determine the prevalence of intestinal carriage of S. aureus in children aged 3 years and below in Ile-Ife, Nigeria and the antibiotic resistance characteristics of the organisms obtained. METHODS: The organisms isolated in the course of the study were identified by phenotypic and genotypic methods and screened against 13 antibiotics by conventional methods. A total of 293 subjects were sampled of which 130 were diagnosed with diarrheal at the time of the study while the rest were apparently healthy. RESULTS: 14.0% of the faecal samples yielded S. aureus with the carriage rate among the subjects being found to be highest at about 1 month approximately in subjected ages. Sixty-five percent of the isolates were found to be resistant to more than three different antibiotics with more than 50% being resistant to penicillin, erythromycin and trimethoprim. CONCLUSIONS: The results of the study indicated that a reservoir of multiply antibiotic resistant S. aureus exists in the gastrointestinal tracts of children living within the study environment.

A study of the In Vivo activity of the leaf extract of Alchornea cordifolia against multiply antibiotic resistant S. aureus isolate in mice.

The effect of a 50% aqueous ethanol extract of Alchornea cordifolia (Schum and Thonn) Muell. Arg. leaf was investigated in mice which had been infected intraperitoneally with 5.0 x 10(9) cfu of Staphylococcus aureus. Dose-dependent antibacterial activity was demonstrated and the rate of survival of infected mice was improved significantly by doses between 25 and 200 mg/kg of injected extract when compared with untreated infected controls. The intraperitoneal median lethal dose of the extract was found to be 800 mg/kg.

Antimicrobial and Antioxidant Activities of Some Nigerian Medicinal Plants

Ten Nigerian plants suggested from their ethnomedical uses to possess antimicrobial and antioxidant activities were studied for their anti-microbial and anti-oxidant properties. Antimicrobial activity was tested against Escherichia coli NCTC 10418, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Candida pseudotropicalis and Trichophyton rubrum (clinical isolate). Trichilia heudelotti leaf extract showed both antibacterial and antifungal activities and was the most active against all the strains of bacteria tested. Boerhavia diffusa, Markhamia tomentosa and T. heudelotti leaf extracts inhibited the gram negative bacteria E.coli and P. aeruginosa strains whereas those of M. tomentosa, T. heudelotti and Sphenoceutrum jollyamum root inhibited at least one of the fungi tested. At a concentration of 312 µg/ml, hexane and chloroform fractions of T. heudelotti extract inhibited 6 and 14% of the fifty mult-idrug resistant bacteria isolates from clinical infectins, respectively. At ≤ 5mg/ml, the CHCl3 (64%) and aqueous (22%) fractions of T. heudelotti and those of CHCl3 (34%) and EtOAC (48%) of M. tomentosa gave the highest inhibition that was stronger than their corresponding methanol extracts. The corresponding EC50 of the extracts on M. acuminata, T. heudelotti, E. senegalensis and M. tomentosa were 4.00, 6.50, 13.33, and 16.50 ig/ml using the TLC staining and 1,1-dipheyl-2-picry-hydrazyl (DPPH) free radical scavenging assay. Therefore, leaf extracts of M. tomentosa and T. heudelotti, especially the latter, possess strong antimicrobial and antioxidant activities and should be further investigated. These activities justified the ethnomedical uses of these plants

Antibiotic resistance of helicobacter pylori from patients in Ile-Ife, South-west, Nigeria

Background: Helicobacter pylori has become recognized as a major cause of gastroduodenal diseases in man. Evidence indicates that once acquired; H. pylori persists; usually for life unless eradicated by antimicrobial therapy. Over the past few years; we have accumulated some knowledge of the epidemiology of H. pylori in Ile-Ife; South-West Nigeria. In one collaborative study; we detected H. pylori in 195 (73) patients referred for endoscopy at Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC). Furthermore we have observed a variegated gastric inflammatory response and atrophy including atrophic pangastritis but are yet to demonstrate MALToma in any of our patients. In addition we have demonstrated that dental plaque is a possible source of gastric H. pylori infection and such an endogenous source could account for difficulty in eradication leading to re-infection. Presently; infected patients are treated with standard combination therapy made up of amoxycilin and ciprofloxacin with a proton pump inhibitor /bismuth. Reports however have shown that the incidence of antimicrobial resistance in Helicobacter pylori is a growing problem and which has been linked with failures in treatment and eradication. Given this situation it has become necessary to have information about the susceptibility of isolates to particular antimicrobial agents before the selection of an appropriate treatment regimen. Objectives: More recently; we sought to study antimicrobial susceptibility of locally isolated H. pylori strains. Methods: We subjected 32 isolates to antimicrobial susceptibility testing against seven agents. Results: All the isolates showed multiple acquired antimicrobial resistance as they were all resistant to amoxicillin; clarithromycin; metronidazole; while 29/31; 27/31 showed resistance to rifampicin and tetracycline respectively. Five (15.6) of these isolates showed resistance to ciprofloxacin. Conclusions: Our findings suggest that H. pylori strains isolated within our study environment have acquired resistance to all the commonly pres-cribed antibiotics. On the basis of the findings it would be necessary to re-evaluate the eradication treatment regime in our setting

A study of the microbial quality and organoleptic properties of ophthalmic preparations obtained from traditional medical practitioners in South Western Nigeria.

Twenty eight samples of traditional ophthalmic preparations were obtained from various traditional medical practitioners in the South Western states of Nigeria over a one-year period. They were examined for sterility, clarity, presence of particulate contamination and pH. All of them were found to be contaminated with bacteria to the order of 2.00 x 10(6) to 1.60 x 10(11) colony forming units/ml, with Pseudomonas species and other potential pathogens such as Staphylococcus aureus, Yersinia enterocolita, Micrococcus varians and others being isolated from these preparations. A rotifer Rotaria rotatoria, at the adult stage, was also isolated from one sample, this being an indication of gross faecal contamination. All the samples were also found to contain significant particulate contamination and pH values encountered varied over the range of 2.5-9.2. None of the samples was found to comply with official specifications and all of them may therefore be regarded as being potentially dangerous to the users.

Antimicrobial and antioxidant activities of some Nigerian medicinal plants.

Ten Nigerian plants suggested from their ethnomedical uses to possess antimicrobial and antioxidant activities were studied for their anti-microbial and anti-oxidant properties. Antimicrobial activity was tested against Escherichia coli NCTC 10418, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Candida pseudotropicalis and Trichophyton rubrum (clinical isolate). Trichilia heudelotti leaf extract showed both antibacterial and antifungal activities and was the most active against all the strains of bacteria tested. Boerhavia diffusa, Markhamia tomentosa and T. heudelotti leaf extracts inhibited the gram negative bacteria E. coli and P. aeruginosa strains whereas those of M. tomentosa, T. heudelotti and Sphenoceutrum jollyamum root inhibited at least one of the fungi tested. At a concentration of 312 microg/ml, hexane and chloroform fractions of T. heudelotti extract inhibited 6 and 14% of the fifty multi-drug resistant bacteria isolates from clinical infections, respectively. At < or = 5 mg/ml, the CHCl(3) (64%) and aqueous (22%) fractions of T. heudelotti and those of CHCl(3) (34%) and EtOAC (48%) of M. tomentosa gave the highest inhibition that was stronger than their corresponding methanol extracts. The corresponding EC(50) of the extracts on M. acuminata, T. heudelotti, E. senegalensis and M. tomentosa were 4.00, 6.50, 13.33, and 16.50 ig/ml using the TLC staining and 1,1-dipheyl-2-picry-hydrazyl (DPPH) free radical scavenging assay. Therefore, leaf extracts of M. tomentosa and T. heudelotti, especially the latter, possess strong antimicrobial and antioxidant activities and should be further investigated. These activities justified the ethnomedical uses of these plants.

Antimicrobial susceptibility of Helicobacter pylori isolates of dyspeptic Nigerian patients.

The resistance of Helicobacter pylori to antibiotic treatment is a growing global concern, but this has not been well studied in our environment. This study sought to determine: the susceptibility of the organism to common antimicrobial agents used in its eradication therapy. Twenty H. pylori isolates from dyspeptic patients were subjected to standard procedures for sensitivity testing and the determination of minimum inhibitory concentration against amoxycillin, ciprofloxacin, clarithromycin, erythromycin, metronidazole, rifampicin and tetracycline. The study showed marked in vitro multiple antimicrobial resistance to the commonly used eradication agents. All twenty isolates were however sensitive to ciprofloxacin. The findings of marked antimicrobial resistance may affect the effectiveness of currently recommended eradication regimes. In our environment, incorporating ciprofloxacin into the existing H. pylori antimicrobial therapy may improve the outcome of eradication.

In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies.

Lentiviral-based vectors hold great promise as gene delivery vehicles for the treatment of a wide variety of diseases. We have previously reported the development of a nonprimate lentiviral vector system based on the equine infectious anaemia virus (EIAV), which is able to efficiently transduce dividing and nondividing cells both in vitro and in vivo. Here, we report on the application of EIAV vectors for the systemic delivery of an antibody fusion protein designed for the treatment of cancer. The therapeutic potential of a single chain antibody against the tumour-associated antigen, 5T4, fused to immune enhancer moieties has been demonstrated in vitro and here we evaluate the genetic delivery of a 5T4 scFv fused to B7.1 (scFvB7) using an EIAV vector. The kinetics and concentration of protein produced following both intravenous (i.v.) and intramuscular (i.m.) administration was determined in immune competent adult mice. In addition, the immune response to the EIAV vector and the transgene were determined. Here, we show that a single injection of EIAV expressing scFv-B7 can give rise to concentrations of protein in the range of 1-5 microg/ml that persist in the sera for more than 50 days. After a second injection, concentrations of scFv-B7.1 rose as high as 20 microg/ml and levels greater than 2 microg/ml were present in the sera of all mice injected i.v. after 210 days despite the detection of antibodies against both the transgene and viral envelope for the duration of this study. These results demonstrate the potential of EIAV as a gene therapy vector for long-term production of therapeutic recombinant proteins.

Seminars on controversial issues. A review of the pharmacological approach to the management of dental anxiety in children.

This paper aims to review the existing literature on the pharmacology of a number of sedative drugs used in the management of dental anxiety in the conscious child patient. Pharmacological agents may be used as a complement to behavioural techniques to assist in the management of anxiety in some paediatric dental patients. Their use may also be especially indicated in children with disabilities. These agents are usually sedative in action and do not, in themselves, eliminate anxiety but merely enhance patient acceptance by reducing arousal and modifying anticipation of danger. The agents used are varied and diverse and include nitrous oxide, benzodiazepines and narcotics. Nitrous oxide has proved to be of particular value but carries a degree of risk for the operating staff. Amongst the benzodiazepines, Midazolam has been used more frequently in recent years. It may be given by a variety of routes, including intra-nasally. Dentists who employ sedative agents and techniques should be familiar with the pharmacology of the agents selected, be cognisant of the risks and benefits of the technique employed and be able to manage any adverse events that may arise through their use.

Helicobacter pylori in the dental plaque and gastric mucosa of dyspeptic Nigerian patients.

BACKGROUND: Presence of helicobacter pylori (H.Pylori) in the dental plaques may be associated with the presence of the same organism in gastric mucosa. OBJECTIVES: To assess and compare the prevalence of H. pylori in dental plaques and gastric mucosa of dyspeptic Nigerians. METHODS: Sixty-six consecutive patients undergoing endoscopy for investigation of dyspepsia were included in the study. A predesigned questionnaire was used to collect information on socio-demographic and other factors. Each patient also had clinical dental examination. Dental plaque scrapping was collected before endoscopy for helicobacter pylori culture, and at endoscopy, two gastric biopsy specimens were taken for culture and histology. RESULTS: The mean age (+/- SD) of the patients was 44.8 (+/- 17.4) years (range 5 to 80 years). The positivity rate of helicobacter pylori in gastric biopsy was 35 of 66 (53.0%) while the same for dental plaque was 46 of 66 (69.7%). The correlation (Spearman's) between gastric mucosa and dental plaque colonization with helicobactor pylori was significant (R = 0.30, P = 0.01). When concordant positivity of gastric biopsy culture and histology was taken as diagnostic, the sensitivity of dental plaque culture was found to be 82.9% and the specificity was 45.2%. CONCLUSIONS: This study revealed that helicobactor pylori has a high prevalence in the dental plaque of the population that we have studied and may therefore be of potential relevance in screening for such infection.

Bacteriological quality of skin-moisturizing creams and lotions distributed in a tropical developing country.

AIMS: To evaluate the bacteriological quality of skin moisturizing products in the South-west part of Nigeria and study factors predisposing their bacterial contamination under tropical conditions. METHODS AND RESULTS: Viable counts for bacteria exceeded 10(3) cfu ml(-1) or cfu g(-1) in 8 (16.3%) commercially available creams and lotions at time of purchase. Escherichia coli (8), Pseudomonas spp. (7), Staphylococcus spp. (9) and Bacillus spp. (6) were the most commonly recovered bacteria. Following use by volunteers, the proportion of E. coli and other Gram-negative organisms recovered increased. Organic matter, particularly in the absence of preservatives, enhanced survival and growth of bacteria in creams stored under ambient tropical conditions during challenge experiments. CONCLUSIONS: Contaminated products are relatively uncommon but some products present a potential health hazard because they are unable to suppress the growth of organisms of likely faecal origin during use. SIGNIFICANCE AND IMPACT OF THE STUDY: Quality assurance during manufacture, pack size, preservative evaluation, organic matter and water content were identified as factors to be considered during the development of creams and lotions for use in tropical developing countries.

Regression of established human papillomavirus type 16 (HPV-16) immortalized tumors in vivo by vaccinia viruses expressing different forms of HPV-16 E7 correlates with enhanced CD8(+) T-cell responses that home to the tumor site.

Using vaccinia virus as a live vector, we show that the expression of human papillomavirus type 16 (HPV-16) E7 fused to a nonhemolytic portion of the Listeria monocytogenes virulence factor, listeriolysin O (LLO), induces an immune response that causes the regression of established HPV-16 immortalized tumors in C57BL/6 mice. The vaccinia virus construct expressing LLO fused to E7 (VacLLOE7) was compared with two previously described vaccinia virus constructs: one that expresses unmodified E7 (VacE7) and another that expresses E7 in a form designed to direct it to intracellular lysosomal compartments and improve major histocompatibility complex class II-restricted responses (VacSigE7LAMP-1). C57BL/6 mice bearing established HPV-16 immortalized tumors of 5 or 8 mm were treated with each of these vaccines. Fifty percent of the mice treated with VacLLOE7 remained tumor free 2 months after tumor inoculation, whereas 12 to 25% of the mice were tumor free after treatment with VacSigE7LAMP-1 (depending on the size of the tumor). No mice were tumor free in the group given VacE7. Compared to VacE7, VacSigE7LAMP-1 and VacLLOE7 resulted in increased numbers of H2-D(b)-specific tetramer-positive CD8(+) T cells in mouse spleens that produced gamma interferon and tumor necrosis factor alpha upon stimulation with RAHYNIVTF peptide. In addition, the highest frequency of tetramer-positive T cells was seen in the tumor sites of mice treated with VacLLOE7. An increased efficiency of E7-specific lysis by splenocytes from mice immunized with VacLLOE7 was also observed. These results indicate that the fusion of E7 with LLO not only enhances antitumor therapy by improving the tumoricidal function of E7-specific CD8(+) T cells but may also increase the number of antigen-specific CD8(+) T cells in the tumor, the principle site of antigen expression.

Quality and bioavailability of ampicillin capsules dispensed in a Nigerian semi-urban community.

Five samples of ampicillin capsules with a label claim of 250 mg were purchased from different dispensing points in a small town in Nigeria. The pharmaceutical quality of the products and a sample from a batch produced by a local manufacturer was evaluated and five of the capsule samples were employed in an in vivo bioavailability study. Three of the five capsule samples from dispensing points were found to be of lower quality than the officially prescribed standards of pharmaceutical quality. The quality lapses observed were sufficient to bring about determinable differences in biological availability. The results demonstrate that ampicillin capsules of sub-standard chemical quality are being dispensed within the study sources from authorised and unauthorised sources and that this may have biological, clinical and epidemiological consequences.

Antibiotic resistance in Escherichia coli from Nigerian students, 1986 1998.

We tested 758 fecal Escherichia coli isolates, recovered from Nigerian students in 1986, 1988, 1990, 1994, and 1998, for susceptibility to seven antimicrobial drugs. The prevalences of strains resistant to tetracycline, ampicillin, chloramphenicol, and streptomycin were 9% to 35% in 1986 and 56% to 100% in 1998. These findings demonstrate that resistance gene reservoirs are increasing in healthy persons.