Can charcoal improve outcomes in COVID-19 infections?

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation.

Two-year antibody persistence in children vaccinated at 12-15 months with a measles-mumps-rubella virus vaccine without human serum albumin.

One combined measles-mumps-rubella (MMR) vaccine without Human Serum Albumin (HSA) is currently licensed in the USA (M-M-R II; Merck, USA) and another has been developed (Priorix™ [MMR-RIT, GSK, Belgium]). In this follow-up study, children from USA or Puerto Rico, who had received one dose of M-M-R II or MMR-RIT at 12-15 months of age in the primary study (NCT00861744), were followed-up for 2 y post-vaccination. Anti-measles and anti-rubella antibodies were measured using Enzyme-Linked Immunosorbent Assay (ELISA), and anti-mumps antibodies using ELISA and plaque reduction neutralization (PRN) assays. Serious adverse events (SAEs) were recorded during the entire follow-up. The according-to-protocol (ATP) persistence cohort included 752 children (M-M-R II = 186, MMR-RIT = 566), who received primary vaccination at a mean age of 12.3 ( ± 0.67) months. 104 children were revaccinated with MMR-containing vaccines; therefore, serology results for timepoints after revaccination were excluded from the analysis. Seropositivity for measles (Year 1≥ 98.3%; Year 2≥ 99.4%) and rubella (Year 1≥ 98.9%; Year 2 = 100%) remained as high at Year 2 as at Day 42. Similarly, seropositivity for mumps determined by ELISA (Year 1≥ 90.1%; Year 2≥ 94.1%) and PRN assays (Year 1≥ 87.5%; Year 2≥ 91.7%) persisted. Thirty-three SAEs were recorded in 23 children; 2 SAEs (inguinal adenitis and idiopathic thrombocytopenic purpura) and one SAE (febrile convulsion) were considered as potentially related to MMR-RIT and M-M-R II, respectively. This study showed that antibodies against measles, mumps and rubella persisted for up to 2 y post-vaccination with either MMR vaccine in children aged 12-15 months, and that both vaccines were well-tolerated during the follow-up period.

Three Decades of Follow-up of Adults After Recovery From Invasive Pneumococcal Pneumonia.

BACKGROUND: Streptococcus pneumoniae infection is the most common cause of community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD) carries a high case fatality rate. We investigated the lifespan of adults who recovered from IPD during a 32-year follow-up. MATERIALS AND METHODS: We determined whether adults discharged after an episode of IPD from hospitals affiliated with the Marshall University Joan C. Edwards School of Medicine in Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate analysis, life expectancy using life tables for West Virginia, years of potential life lost and serotype occurrence. RESULTS: The study group comprised 155 adults who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%) patients lived longer than their life expectancy. Of the 13 comorbid diseases analyzed, cancer and neurologic diseases and the number of comorbid diseases suffered by each patient were the significant variables associated with survival. The mean years of potential life lost was 9.936 years. Only serotype 12 of 31 serotypes recovered occurred more often in patients who survived for 11 or more years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95). CONCLUSIONS: The fact that most adult patients who recovered from IPD died before their documented life expectancy argues for the pernicious severity of IPD and the importance of immunization of adults with pneumococcal vaccines.

A 32-Year Study of the Effect of Pneumococcal Vaccines on Invasive Streptococcus pneumoniae Disease.

BACKGROUND: Worldwide, Streptococcus pneumoniae commonly causes community-acquired pneumonia, meningitis, septicemia and otitis media. Invasive pneumococcal infection (IPD) represents the most serious presentation, occurs in approximately 1 in 4 cases and engenders case fatality rates (CFR) in pneumonia of 20-25% and meningitis of 35-40%. We investigated IPD for 32 years in an American city to assess the effect of differing pneumococcal vaccines on serotype occurrence and CFR among children and adults. METHODS: In this retrospective study of IPD conducted from 1983-2014, consecutive pneumococcal strains were obtained from inpatients at 3 affiliated hospitals. Each hospital laboratory submitted to our research laboratory S pneumoniae strains recovered from blood and otherwise sterile sites for serotyping by Quellung and penicillin susceptibility tests by ETEST. Clinical data were abstracted from hospital medical records. RESULTS: IPD occurred among 193 children and 1,003 adults. The overall CFR among adults was 19.2%. Only 2 children died. From 1983-2004, PCV7 serotypes dominated, but after routine PCV7 immunization began in 2000, PCV7 serotypes decreased and nearly disappeared, including penicillin-resistant PCV7 serotypes, few IPD occurred among children and incidence rates declined markedly, which continued after PCV13 replaced PCV7 in 2010. The 11 additional serotypes in PPSV23 became dominant during the past 5 years. Nonvaccine serotypes emerged also. Only serotypes 6B, 15 and 35F showed a significant relative risk of death. CONCLUSIONS: Community-wide usage of PCV7, then PCV13, changed the predominant serotypes. PCV7 serotypes and IPD among children almost disappeared and PPSV23 and nonvaccine serotypes became more dominant.

Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12-15 Months.

BACKGROUND: M-M-R(TM)II (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (Priorix(TM), GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States. METHODS: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12-15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed. RESULTS: Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3-99.2% (measles), 89.7-90.7% (mumps), and 97.5-98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups. CONCLUSIONS: Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7. CLINICAL TRIALS REGISTRATION: NCT00861744; etrack; 111870.

Routine pneumococcal vaccination of children provokes new patterns of serotypes causing invasive pneumococcal disease in adults and children.

INTRODUCTION: Routine vaccination of infants with protein-conjugated 7-valent pneumococcal vaccine (PCV7) begun in 2000 initiated a sea change of prevalent serotypes (STs) in invasive pneumococcal disease (IPD). The authors investigated in 1 community all STs causing IPD during 5 years before (PRE) and 2, 5-year periods after (POST1 and POST2) its initiation and found that PCV7 adversely affected ST coverage of 23-valent pneumococcal polysaccharide vaccine (PPV23) among adults. METHODS: From 1996-2010, 620 consecutive Streptococcus pneumoniae IPD strains from adults (521) and children (99) hospitalized with IPD in Huntington, WV, were collected. Each strain was typed by Quellung reaction. The Marshall University Institutional Review Board approved this study. RESULTS: By 6 to 10 years after the initiation of PCV7, IPD in children decreased significantly, whereas IPD in adults increased significantly. In both adults and children, IPD due to PCV7 STs decreased significantly. In adults with IPD, PCV7 STs were replaced by several non-PCV7 STs including STs contained in PPV23 but not in PCV7 and STs not contained in either vaccine. IPD due to 4 nonsusceptible STs included in PCV7 decreased from PRE to POST1 and POST2. IPD due to nonsusceptible STs not included in PCV7 increased from PRE to POST1 and POST2. CONCLUSIONS: Routine PCV7 decreased IPD in children but not in adults. Predominant STs changed--children exhibited fewer PCV7 STs and adults exhibited fewer PCV7 and PPV23 STs--reducing vaccine coverage and increasing the risk of replacement STs causing IPD in adults.

Immunogenicity and safety of two tetravalent (measles, mumps, rubella, varicella) vaccines coadministered with hepatitis a and pneumococcal conjugate vaccines to children twelve to fourteen months of age.

BACKGROUND: This study compared single-dose tetravalent measles, mumps, rubella, varicella vaccine, Priorix-Tetra, stored refrigerated (GSK+4C) or frozen (GSK-20C), with ProQuad (Merck-20C), when coadministered with hepatitis A vaccine (HAV) and 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Multicenter, observer-blind phase 2 study in 1783 healthy 12-14 month olds randomized to: GSK+4C (n = 705), GSK-20C (n = 689) or Merck-20C (n = 389), administered concomitantly with HAV (Havrix) and PCV7 (Prevnar). Seroresponse rates and antibody geometric mean concentrations/titers were determined from enzyme-linked immunosorbent assay and neutralization assays. Reactogenicity and safety were assessed. RESULTS: Seroresponse rates (day 42) were >97% for measles and rubella viruses and >92% for mumps virus, in all groups. Noninferiority of both GSK+4C and GSK-20C vaccines versus Merck-20C was demonstrated for seroresponse rates to measles, mumps and rubella viruses (lower 97.5% confidence interval above -5%, -10% and -5%, respectively). For varicella-zoster virus, seroresponse rates were 57.1%, 69.8% and 86.7% in the GSK+4C, GSK-20C and Merck-20C groups, respectively. Noninferiority was not shown for either GSK vaccine (lower 97.5% confidence intervals <-15%). Geometric mean concentration ratios for anti-varicella-zoster virus demonstrated noninferiority (lower 97.5% confidence interval ≥ 0.5) versus Merck-20C for GSK-20C only. Geometric mean concentration ratios for antibodies to HAV and to PCV7 pneumococcal serotypes also met criteria for noninferiority for both GSK groups compared with Merck-20C. GSK vaccine safety was observed comparable to Merck-20C. Localized but not generalized measles/rubella-like rash and grade 3 fever was reported slightly more frequently with GSK vaccines, but antipyretic use was similar. The incidence of subjects experiencing at least 1 serious adverse event was 2.0%, 2.9% and 1.8% in the GSK+4C, GSK-20C and Merck-20C groups, respectively. CONCLUSIONS: Noninferiority of both GSK measles, mumps, rubella, varicella vaccines versus Merck-20C was demonstrated for responses to measles, mumps and rubella viruses but was not fully demonstrated for varicella-zoster virus. The vaccines showed acceptable reactogenicity/safety when coadministered with HAV and PCV7.

Clinical features of patients with recurrent invasive Streptococcus pneumoniae disease.

INTRODUCTION: Invasive Streptococcus pneumoniae (pneumococcal) disease (IPD) carries a high risk of death, approximately 15% to 20% in pneumonia, 40% in meningitis and 10% to 15% in septicemia. The occurrence of 2 or more IPD (recurrent) in the same individual is uncommon. The authors investigated the clinical features of patients with recurrent IPD to assess whether they possessed risk factors that increased their likelihood of recurrent IPD. METHODS: Between 1983 and 2010, the authors identified 27 patients with recurrent IPD during inpatient surveillance of 889 patients with IPD in Huntington, WV, by recovery of pneumococci from otherwise sterile sites. Serotype/serogroup (ST/SG) was determined by capsular swelling and the penicillin MIC by E-strip. Clinical data were abstracted from hospital charts. RESULTS: Sixteen (59%) of 27 patients were 65 years and older at first IPD, males predominated (67%), two-thirds had pneumonia and 21 (78%) had the same clinical diagnosis at both IPD. Four (80%) of 5 patients with the same ST experienced their second IPD 1 to 6 months apart, unlike most patients with discordant ST/SGs (P = 0.047). Eighty-four percent of ST/SGs were included in the 23-valent pneumococcal vaccine and occurred as often during the first and second IPD. Twenty (77%) of 26 adults suffered from comorbid diseases placing them at high risk of IPD, including multiple myeloma, HIV/AIDS, neoplasia of hematological origin and sickle cell disease. CONCLUSIONS: Recurrent IPD occurred uncommonly. Comorbid conditions including multiple myeloma and immunosuppressive/immunodeficient conditions, chronic alcoholism and splenectomy represented unique risk factors for recurrent IPD but did not predict recurrences.

Barriers to vaccinating the elderly with H1N1 vaccine.

INTRODUCTION: The development of a monovalent 2009 H1N1 influenza (swine flu) vaccine for the 2009-2010 season prompted a nationwide campaign of vaccination. The authors assessed the frequency of influenza vaccine usage among 3858 elderly patients with their practice and the most common barriers to receiving vaccine. METHODS: The authors calculated the usage of seasonal and 2009 H1N1 vaccines among seniors with their university practice and surveyed a cohort of 64 patients to determine whether they had received the 2009 H1N1 vaccine and their reasons for not receiving it. RESULTS: Of the 555 elderly vaccinated with seasonal influenza vaccine, only 18% were vaccinated with 2009 H1N1 vaccine. Among the survey cohort, 72% had not received the 2009 H1N1 vaccine; 39% of them offered no reason for refusing and 22% stated they were unaware of the need for it. CONCLUSIONS: Acceptance rates of seasonal influenza vaccine among elderly were low, and a significant proportion did not receive the 2009 H1N1 vaccine because it was unclear that they should receive it. Unambiguous education of patients and physicians is needed to achieve high rates of influenza vaccination among the elderly.

Emergence of a unique penicillin-resistant Streptococcus pneumoniae serogroup 35 strain.

We analyzed seven Streptococcus pneumoniae serogroup 35 isolates by pulsed-field gel electrophoresis of the genome and pbp2b gene nucleotide sequences. Three penicillin-susceptible strains and one penicillin-intermediate-resistant strain exhibited 100% identity to prototype R6. Two resistant strains and one other intermediate strain differed from them and contained a unique sequence.

Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children.

A live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine was evaluated in healthy respiratory syncytial virus/parainfluenza virus type 3 seropositive children aged 1 to 9 years. Three cohorts of 40 children were randomized 1:1 to receive 10, 10, or 10 median tissue culture infectious dose50 MEDI-534 vaccine or placebo. The vaccine's safety profile was similar to placebo, no viral shedding was detected, and the vaccine was minimally immunogenic.

Penicillin resistance not a factor in outcome from invasive Streptococcus pneumoniae community-acquired pneumonia in adults when appropriate empiric therapy is started.

BACKGROUND: Invasive Streptococcus pneumoniae pneumonia among adults due to penicillin-resistant or intermediate resistant strains was investigated to determine whether these patients responded poorly to common antibiotic regimens compared to pneumonia due to susceptible strains. METHODS: During a 21-year period (1983-2003), clinical outcome was analyzed among 3 groups of adults, 19 with resistant, 33 with intermediate, and 133 with susceptible invasive S pneumoniae pneumonia admitted to hospitals in Huntington, West Virginia. Adults with resistant and intermediate infections were matched by age and month of admission to a group of 133 adults with penicillin-susceptible infections. All isolates of resistant and intermediate infections were capsular serotypes/serogroups 6, 9, 14, 19, and 23, and isolates of susceptible infections included 24 different serotypes/serogroups. Case fatality rates were calculated for deaths that occurred during the first 7, first 14, and first 21 days of hospitalization. Minimal inhibitory concentration (MIC) was determined by E-test and capsular serotype by Quellung procedures. RESULTS: The resistant and susceptible groups did not differ in several measures of severity of illness, including admission vital signs, duration of fever, mean total leukocyte count, number of lobes involved, preexisting underlying diseases, and antibiotic treatment regimens. There were no significant differences in case fatality rates between the 3 groups of pneumonia by days in hospital, age, severity of illness, and empiric antibiotic treatment regimen with a cephalosporin and a macrolide, the most common antibiotic regimen. CONCLUSIONS: These findings provide evidence that combination antibiotic regimens effective in the treatment of invasive susceptible S pneumoniae pneumonia are equally effective in the treatment of invasive resistant (MIC = 2-4 microg/mL) and of intermediate (MIC = 0.1-1 microg/mL) S pneumoniae pneumonia.

Influenza season triggers pneumococcal vaccination.

OBJECTIVES: To investigate the frequency with which influenza and pneumococcal vaccines are administered alone and together. DESIGN: Retrospective review. SETTING: Marshall University internal medicine practice, Huntington, West Virginia. PARTICIPANTS: All patients aged 65 and older seen in the practice from 1999 through 2005 who received pneumococcal or influenza vaccine. MEASUREMENTS: Billing records were reviewed for administration of pneumococcal and influenza vaccines to Medicare beneficiaries, and rates of administration of these vaccines given alone and together were calculated. RESULTS: Nine hundred sixty-nine doses of pneumococcal vaccine were administered. Of these, 796 (82%) were administered during the fall and winter. Three hundred fifty-six (45%) pneumococcal vaccinees received it together with influenza vaccine. During 2001 and 2005, when influenza vaccine supply was limited, the rate of pneumococcal vaccine administered together with influenza vaccine declined sharply. Nonetheless, the rate of pneumococcal vaccination remained relatively stable because of an increase in the rate of vaccine administered alone. CONCLUSION: Four-fifths of pneumococcal vaccine was administered in the fall and winter, and approximately half was given together with influenza vaccine. When influenza vaccine was in limited supply, physicians continued to vaccinate with pneumococcal vaccine alone. These findings suggest that the imminent influenza season provides the trigger for physicians to prescribe pneumococcal vaccine. Physicians should be reminded that pneumococcal vaccine can be administered any time of year.

Standing orders in an ambulatory setting increases influenza vaccine usage in older people.

OBJECTIVES: To determine whether standing orders for influenza vaccine increase its usage in an ambulatory setting in elderly patients. DESIGN: Retrospective analysis of influenza vaccine usage over 4 years (1999-2002). SETTING: University ambulatory setting. PARTICIPANTS: Overall, 912 elderly patients of two physicians who issued standing orders and 884 elderly patients of two physicians who did not do so constituted the study group. MEASUREMENTS: Physicians were categorized as to whether they issued a verbal or written standing order to their nurses to administer the influenza vaccine to patients aged 65 and older. Rates of influenza vaccination of patients whose physicians used standing orders were compared with those of physicians who did not use standing orders. RESULTS: Five hundred seventy-six (63%) patients of physicians who used standing orders received influenza vaccine, compared with 332 (38%) patients of physicians who did not use them (P<.001). Standing orders accounted for a significantly higher rate of influenza vaccination in each study year. Moreover, in 2001, when influenza vaccine delivery was delayed, physicians who used standing orders maintained their same rate of usage, but physicians who did not had rates of about one-half their usage of the other 3 years. CONCLUSION: More Medicare recipients received influenza vaccine when their physicians used standing orders for its administration than when their physicians did not. Influenza vaccine represents an important prevention modality that demands widespread implementation, and standing orders can increase its usage.

Epidemiology of invasive Streptococcus pneumoniae infections and vaccine implications among children in a West Virginia community, 1978-2003.

From 1978 to 2003, in Huntington, WV, we investigated Streptococcus pneumoniae invasive disease and the effect of conjugated pneumococcal vaccine among 161 children 14 years of age and younger admitted to the hospital. During 2002 and 2003, the number and proportion of invasive disease caused by vaccine strains declined; and in 2003, no invasive disease occurred in young children, suggesting a vaccine effect.

Lack of synergy of erythromycin combined with penicillin or cefotaxime against Streptococcus pneumoniae in vitro.

We investigated a possible synergistic effect of a macrolide and beta-lactams against Streptococcus pneumoniae strains with different resistance profiles. Checkerboard and time-kill assays of erythromycin combined with penicillin or cefotaxime essentially showed indifference, suggesting that these antibiotics in combinations in vitro act substantially as individuals in their activity against S. pneumoniae.