Merit and Demerit of Polyvalent Snake Antivenoms

Polyvalent antivenoms contain specific antibodies capable of neutralizing a number of homologous venoms from different species/genera. They can save lives of victims of snake envenomations, even when the culprit snake has not been identified (the usual case, about 80% of the time), and a monovalent antivenom ca not be chosen. They are useful in areas where there are too many poisonous species to produce monovalent antivenoms against all of them. It is now possible to prepare polyvalent antivenoms with high potencies comparable to those of the corresponding monovalent antivenoms. With good manufacturing processes, these antivenoms have been shown to cause few and minor adverse reactions. In addition, polyvalent antivenoms exhibit a wider range of paraspecific neutralization of venoms from different species/genera, even from distant geographic areas. Lastly, it is less expensive and easier to produce and handle a few polyvalent antivenoms than batteries of monovalent antivenoms.     

A decade of G3P[8] and G9P[8] rotaviruses in Brazil: Epidemiology and evolutionary analyses

This study aims to estimate the frequency of group A rotaviruses (RVA) infection with genotypes G3P[8] and G9P[8] in children that suffered from diarrheal disease (DD) between 2001 and 2011 in different Brazilian regions. In addition, the genetic diversity of G3P[8] and G9P[8] RVA strains recovered from vaccinated and non-vaccinated children was assessed. Laboratory-based RVA surveillance included 15,115 cases of DD, and RVA was detected by enzyme immune-assay and/or polyacrylamide gel electrophoresis in 3357 (22%) samples. RVA was genotyped by the semi-nested RT-PCR and among RVA-positive samples, 100 (2.9%) were G3 (63 G3P[8], 32 G3P not typed [NT], and 5 G3P[6]) and 378 (16.2%) were G9 (318 G9P[8], 59 G9P[NT], and 1 G9P[6]). From the G3 and G9 positive samples, 16 and 12, respectively, were obtained from children aged 4–48 months vaccinated with the monovalent vaccine (Rotarix®, RV1). Phylogenetic analyses of the VP7 and VP8¹ encoding genes were performed for 26 G3P[8] and 48 G9P[8] strains. VP8¹ phylogenetic analysis revealed that all strains analyzed belonged to P[8] lineage III, whereas RV1 belongs to P[8]-I lineage. VP7 analysis revealed that all G3 and G9 strains belonged to G3-lineage III and G9-lineage III. The comparison of the VP7 and VP8¹ antigenic epitopes regions of Brazilian strains with RV1 strain revealed several amino acid changes. However, no particular differences among Brazilian strains detected before and after vaccine introduction were observed, or among strains detected from vaccinated and non-vaccinated children. Complete genome characterization of four G3P[8] and seven G9P[8] strains revealed a typical conserved human Wa-like genomic constellation. Changes in the genetic diversity of G3P[8] and G9P[8] RVA detected from 2001 to 2011 in Brazil seemed not be related to RV1 introduction in Brazil.     

2009-2010 novel influenza A (H1N1) vaccination coverage in the Republic of Korea

This study aimed to assess vaccination coverage for novel influenza A (H1N1) in Korea using a immunization registry system as the data source. Vaccination coverage was found to be 26.1% for the total population and 54.4% for priority groups targeted by a national vaccination campaign between October 27, 2009, to March 31, 2010. The factors associated with increased coverage were rapid vaccination and free vaccination; these factors may need to be considered in future pandemics.     

Different time courses of GTP[γ-S]-induced exocytosis and current oscillations in isolated mouse pancreatic acinar cells

Exocytosis in isolated mouse pancreatic acinar cells was investigated using the dual-frequency method for measuring membrane capacitance and ionic conductances. Under control conditions, single exo- and endocytotic events could be resolved. The total cell capacitance slightly decreased to 98.7 ± 0.9% of the initial cell capacitance within 10 min after establishing the whole-cell configuration. When guanosine 5′-O-(3-thiophosphate) (GTP[γ-S] was added to the patch pipette, stepwise elevations in membrane capacitance occurred and the cell capacitance increased to 106.7 ± 1.6% within 10 min. Exocytosis was also stimulated by GTP[γ-S] when a Ca²⁺-free pipette solution supplemented with 1 to 10 mM ethylenebis(oxonitrilo) tetraacetate (EGTA) was used. Measurement of the DC current component in parallel with AC current analysis was used to isolate components of the Ca²⁺-dependent Cl⁻ and monovalent cation conductances from the whole-cell conductance. These experiments demonstrate that in GTP[γ-S]-stimulated pancreatic acinar cells: (1) activation of Cl⁻ currents precedes that of cation currents, and (2) fusion of the zymogen granule membrane with the plasma membrane does not lead to incorporation of active Cl⁻ or nonselective cation channels (≥ 10 pS). Received: 11 March 1996/Accepted: 3 May 1996     

Impact of rotavirus vaccine on acute gastroenteritis in children under 5 years in Senegal: Experience of sentinel site of the Albert Royer Children's Hospital in Dakar

BackgroundAcute gastroenteritis (AGE) is a leading cause of morbidity and mortality among children <5 years of age in developing countries, with rotavirus being the most common infectious etiology. In November 2014, monovalent rotavirus vaccine was introduced in Senegal. We determined the impact of rotavirus vaccine on hospitalizations for all-cause and rotavirus related AGE in children <60 months of age.MethodsWe examined two data sources from the national referral hospital. Using sentinel surveillance data from March 2011 to February 2017, we examined the proportion of AGE hospitalizations among children <60 months of age attributable to rotavirus, stratified by age groups (0–11, 12–23 and 24–59 months). Using pediatric logbook data from March 2010 to February 2017, we examined the proportion of all childhood hospitalizations attributable to AGE, among the same age groups.ResultsIn sentinel surveillance, 673 patients <60 months were hospitalized for AGE, with 30% (203/673) due to rotavirus. In pre-vaccine years, the median proportion of rotavirus-positive hospitalizations was 42%; this proportion declined by 76% to 10% rotavirus positive in 2015–2016 (p < .001) and by 59% to 17% in 2016–2017 (p < .001). From the logbook data, among all children <60 months, a median of 11% of all hospitalizations in the pre-vaccine period were due to AGE, with 2015–2016 seeing a 16% decline (p < .001), to 9% of all hospitalizations, and 2016–2017 seeing a 39% decline (p < .001), to 7% of all hospitalizations. Declines in both rotavirus-associated and all-cause AGE hospitalizations were most marked among infants, with a suggestion of herd effect among older children seen in the surveillance data.ConclusionRotavirus vaccine demonstrated a significant impact on rotavirus-associated hospitalizations and all-cause AGE hospitalizations in the first two seasons after vaccine introduction in Senegal. Our data support the continued use of this vaccine in national immunization program.     

Effectiveness of meningococcal serogroup C vaccine programmes

Since the introduction of monovalent meningococcal serogroup C (MenC) glycoconjugate (MCC) vaccines and the implementation of national vaccination programmes, the incidence of MenC disease has declined markedly as a result of effective short-term vaccination and reduction in acquisition of MenC carriage leading to herd protection. Monovalent and quadrivalent conjugate vaccines are commonly used vaccines to provide protection against MenC disease worldwide. Studies have demonstrated that MCC vaccination confers protection in infancy (0–12 months) from the first dose but this is only short-term. NeisVac-C^® has the greatest longevity of the currently licensed MCC vaccines in terms of antibody persistence, however antibody levels have been found to fall rapidly after early infant vaccination with two doses of all MCC vaccines – necessitating a booster at ∼12 months. In toddlers, only one dose of the MCC vaccine is required for routine immunization. If herd protection wanes following catch-up campaigns, many children may become vulnerable to infection. This has led many to question whether an adolescent booster is also required.     

流行性感冒病毒裂解疫苗甲醛含量的探讨

为了探索流行性感冒 (流感 )病毒裂解疫苗中灭活剂甲醛的最适浓度 ,单价病毒液采用不同浓度的甲醛进行灭活后 ,分别跟踪测定单价病毒液和配制的疫苗液中血凝素 (HA)含量的变化。结果显示 :用 0 0 1%甲醛灭活的单价病毒液和配制的疫苗液 ,HA含量下降明显 ;用 0 0 0 4 %甲醛灭活的单价病毒液和配制的疫苗液 ,HA含量则较为稳定。提示流感疫苗宜采用较低浓度的甲醛进行灭活。     

Modulation of guanylate cyclase and phosphodiesterase by monovalent cations and nucleoside triphosphates in light-sensitive excised patches of rod outer segments

Excised inside-out patches of vertebrate rod outer segment can support phototransduction. I have examined how ionic and metabolic conditions influence the functional properties of light-sensitive patches fromGekko gekko. I find that such patches retain a variable level of basal phosphodiesterase activity, which lowers the cyclic guanosine monophosphate (cGMP) concentration reaching the channels and reduces the dark current. The dose/response relationship for channel opening by cGMP varies among patches and this variability is only reduced by working in darkness with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX), suggesting that it is only partially due to phosphodiesterase activity. MgATP or MgGTP, but not Mg or ATP separately, increase this activity but a kinase does not appear to be involved. Intracellular monovalent cations also influence dark current intensity and light response kinetics. With 5 mM MgGTP, 1 mM IBMX, and 144 mM Li⁺, Na⁺, K⁺, or Rb⁺, dark current intensity and recovery time follow the respective sequences K⁺>Rb⁺>Na⁺>Li⁺ and K⁺<Rb⁺<Li⁺<Na⁺. Without IBMX, a dark current develops with K⁺ but not with Na⁺. These effects are not due to altered channel permeability (P) = 0.841.00 1.011.090.42], or differential Mg²⁺ block, but to modulation of guanylate cyclase, which overcomes phosphodiesterase when the major cation is K⁺ but not when it is Na⁺.     

Effects of monovalent cations on cardiac Na+, K+-ATPase activity and on contractile force

Summary The relationship between Na⁺, K⁺-ATPase inhibition by monovalent cations and their inotropic effect was studied in guinea pig hearts. The activity of partially purified cardiac enzyme was assayed in the presence of 5.8 mM KCl and either 20 or 150 mM NaCl. Rb⁺ and Tl⁺ inhibited Na⁺, K⁺-ATPase activity, the magnitude of the inhibition by these cations being greater in the assay media containing lower Na⁺ concentrations. Tl⁺ produced a dose-dependent inhibition of Na⁺, K⁺-ATPase activity in the presence of 20 mM Na⁺ and 75 mM K⁺, a cationic condition similar to that of intracellular fluid. Other monovalent cations such as K⁺, Cs⁺, NH₄ ⁺, Na⁺ or Li⁺ produced essentially no effect on the Na⁺, K⁺-ATPase activity or slightly stimulated it. In left atrial strips stimulated with field electrodes and bathed in Krebs-Henseleit solution (5.8 mM K⁺ and 145 mM Na⁺), addition of Cs⁺ failed to alter the isometric contractile force significantly. NH₄ ⁺ and K⁺ caused a transient positive inotropic effect which was partially blocked by propranolol. The positive inotropic response to K⁺ was followed by a negative inotropic response. Rb⁺ produced a sustained, dose-dependent inotropic response reaching a plateau at 1–2 min, whereas Tl⁺ produced a dose-dependent positive inotropic effect which developed slowly over a 30-min period. The positive inotropic effects produced by Rb⁺ and Tl⁺ were insensitive to propranolol pretreatment. Concentrations of Tl⁺ and cardiac glycosides which produce similar inotropic effects appear to cause the same degree of Na⁺-pump inhibition. The onset of the positive inotropic response to Rb⁺ or Tl⁺ was not dependent on the number of contractions which is in contrast to the cardiac glycoside-induced inotropic response. Substitution of 20 mM LiCl for an equimolar amount of NaCl in Krebs-Henseleit solution produced a significantly greater inotropic response than that observed when sucrose was substituted for NaCl. It appears that, among monovalent cations, only sodium pump inhibitors produce a sustained positive inotropic response.     

Immunogenicity and safety of a monovalent,multicomponent acellular pertussis vaccine in 15 month–6-year-old German children

Immunization against pertussis has been re-recommended for healthy children in Germany in 1991. In addition the former restriction of immunizing only in the first 2 years of life was abolished. In children born before 1991 immunization rates against pertussis were 15% or less. With the new recommendations physicians are now faced with an increasing demand of parents for catch-up vaccinations in these children. Since they were immunized against diphtheria and tetanus previously monovalent pertussis vaccines are needed for this indication. Therefore a monovalent, multicomponent acellular pertussis vaccine was studied in 249 German children 15 months to 6 years of age. Three doses were administered at 6–10 week intervals. Reactogenicity and antibody responses against the vaccine antigens pertussis toxin (PT), filamentous haemagglutinin (FHA), 69-kd antigen (pertactin) and fimbriae-2 (agglutinogen) were investigated. Local and systemic reactions were minimal in frequency and severity. Antibody responses against all vaccine antigens were pronounced with 93%–100% of vaccinees demonstrating at least four fold titre rises above pre-immunization after the third dose. These findings indicate that this monovalent, multicomponent acellular pertussis vaccine with excellent immunogenicity and low reactogenicity is an appropriate candidate for closing immunization gaps in older children in countries with previously low vaccination rates against pertussis. Based on the results of this study the monovalent acellular pertussis vaccine was licensed in Germany in January 1994.