COVID-19 patients' sera induce epithelial mesenchymal transition in cancer cells.

Covid-19 Pneumonia of SARS-CoV-2 pandemic infection, persists to have high disease burden especially in cancer patients. Increased inflammation and thromboembolic processes are blamed to influence cancer patients more than the others but due to lack of knowledge regarding the pathophysiology of the both the virus itself and the response of the host, more basic and translational disease modeling research is needed to understand Cancer-Covid-19 interaction. In this study, serum samples from the patients, who were hospitalized due to Covid-19 pneumonia, applied to different cancer cells and cytotoxicity, motility, proliferation and gene expression analysis were performed. Serum samples derived from healthy volunteers and the fetal bovine serum that is used regularly in cell culture experiments used as controls. Hospitalized Covid-19 patients who had also cancer, were retrospectively screened, and their clinical course were recorded. Overall 12 Patient (PS) and 4 healthy serums (CS) were included in the experiments. PS applied cells showed increased motility in A549 cells as well as lost cell to cell connection in MCF7 and HCT116 cells, and induced expression of VIM, ZEB1 and SNAIL2 mRNA levels. Eight cancer diagnosed patients who were hospitalized due to Covid-19 between April and September 2020 were also reviewed retrospectively, which 5 of them were dead during SARS-CoV-2 infection. Thorax CT images of the 2 patients showed increased metastatic nodules in the lungs as of January 2021. The results of the study indicate that metastasis may be one of the prolonged consequences of COVID-19 pandemic in cancer sufferers.

Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19.

Passive immunotherapy with plasma derived from patients convalescent from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that Blood Establishments are prepared to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution and control of use of the product. This position paper is aimed to give recommendations on biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.

Safety and Varicella Outcomes in In Utero-Exposed Newborns and Preterm Infants Treated With Varicella Zoster Immune Globulin (VARIZIG): A Subgroup Analysis of an Expanded-Access Program.

BACKGROUND: Infants exposed to varicella zoster virus (VZV) in utero ≤5 days before or ≤48 hours after delivery and preterm infants are at high risk for varicella complications. An expanded-access program assessed varicella outcomes after administration of varicella zoster immune globulin (human) (VARIZIG) in a real-world setting. METHODS: In this open-label, expanded-access program, high-risk infants received ≤125 IU/10 kg of VARIZIG (NCT00338442). VZV outcomes and safety were assessed. RESULTS: There were 43 newborns exposed to VZV in utero and 80 preterm infants exposed to VZV; >80% received VARIZIG within 96 hours of reported exposure. When varicella outcomes were available, varicella occurred in 7 of 38 (18%) in utero-exposed newborns and zero of 65 preterm infants. Varicella-related complications were reported in 3 in utero-exposed newborns (3 with >100 lesions, 1 each with encephalitis and pneumonia). Adverse events were reported for 16% of in utero-exposed newborns and 25% of preterm infants, but few were considered related to VARIZIG. There were no deaths attributable to varicella or VARIZIG. CONCLUSIONS: Varicella incidence and morbidity were low in in utero-exposed infants and zero in preterm infants who received prophylactic VARIZIG. There were few VARIZIG-related safety concerns.

Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice.

Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection.IMPORTANCE Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations.

Varicella zoster immune globulin (VARIZIG) administration up to 10 days after varicella exposure in pregnant women, immunocompromised participants, and infants: Varicella outcomes and safety results from a large, open-label, expanded-access program.

INTRODUCTION: Despite vaccination, there were more than 100,000 annual cases of varicella in the United States in 2013-2014. Individuals at highest risk of developing severe or complicated varicella include immunocompromised people, preterm infants, and pregnant women. Varicella zoster immune globulin (human) (VARIZIG) is recommended by the CDC for postexposure prophylaxis to prevent or attenuate varicella-zoster virus infection in high-risk individuals. Contemporary information on administration of VARIZIG is limited. METHODS: This open-label, expanded-access program provided VARIZIG to physician-identified, high-risk participants exposed to varicella. Participants included immunocompromised children/adults, infants (preterm, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and those aged <1 year), and pregnant women. VARIZIG (125 IU/10 kg [up to 625 IU]) was administered intramuscularly, ideally within 96 hours, but up to 10 days, postexposure. Incidence of varicella rash and severity (>100 pox, pneumonia, or encephalitis) were assessed up to 42 days after administration. RESULTS: The varicella outcome population (n = 507) included 263 immunocompromised participants (32 adults, 231 children), 137 pregnant women, 105 infants, and 2 healthy adults with no history of varicella. Varicella incidence was 4.5% in immunocompromised participants, 7.3% in pregnant women, and 11.5% in infants. The incidence of varicella was similar when comparing VARIZIG administration ≤ 96 hours vs > 96 hours (up to 10 days) postexposure in the entire population (6.2% vs. 9.4%, respectively), and also in each subgroup. Of 34 participants with varicella, 5 developed > 100 pox and 1 developed pneumonia and encephalitis. There were no product-related deaths and only 1 serious adverse event (serum sickness) considered probably related to VARIZIG. CONCLUSION: Postexposure administration of VARIZIG was associated with low rates of varicella in high-risk participants, regardless of when administered within 10 days postexposure. VARIZIG was well-tolerated and safe in high-risk participants.

[Safety profile of heterologous serum produced by the Butantan Institute, in São Paulo-SP, Brazil, from 2012 to 2015]. / Perfil de segurança dos soros heterólogos produzidos pelo Instituto Butantan, São Paulo-SP, no período de 2012 a 2015.

OBJECTIVE: to describe the safety profile of the heterologous serum produced by the Butantan Institute (BI) of São Paulo-SP, Brazil. METHODS: a descriptive study of adverse events (AEs) post-exposure to serum produced by the BI, encoded in the medical terminology of the Medical Dictionary for Regulatory Activities (MedDRA), and spontaneously reported to BI from 2012 to 2015. RESULTS: 52 individuals reported AEs, mainly related to Bothrops antivenom (n=11), diphtheria antitoxin (n=9) and unspecified snakebite serum (n=9); a mean of 3.2 AEs per individual was observed; among the total of 173 AEs, 63.0% were expected considering that they were described in the package insert; most of them were classified as skin and subcutaneous tissue disorders (30.6%); there were six deaths temporally related to the use of serum, but this association was discarded. CONCLUSION: in the studied period, the serum produced by the BI had no changes in their safety profiles, considering that the AEs were expected, according to the information previously described in the package insert.

Perfil de segurança dos soros heterólogos produzidos pelo Instituto Butantan, São Paulo-SP, no período de 2012 a 2015 / Safety profile of heterologous serum produced by the Butantan Institute, in São Paulo-SP, Brazil, from 2012 to 2015 / Perfil de seguridad de los sueros heterólogos producidos por el Instituto Butantan, São Paulo-SP, Brasil, en el período de 2012 al 2015

Resumo OBJETIVO: descrever o perfil de segurança dos soros heterólogos produzidos pelo Instituto Butantan (IB) de São Paulo-SP, Brasil. MÉTODOS: estudo descritivo dos relatos de eventos adversos (EA) pós-exposição aos soros produzidos pelo IB, codificados pela terminologia do Dicionário Médico para Atividades Regulatórias (MedDRA), notificados espontaneamente ao IB entre 2012 e 2015. RESULTADOS: foram notificados 52 usuários com algum evento adverso relacionado, principalmente, aos soros antibotrópico (n=11), antidiftérico (n=9) e antiofídico não especificado (n=9); observaram-se, em média, 3,2 EA por indivíduo; dos 173 EA notificados, 63,0% eram esperados por serem eventos descritos em bula; os EA mais notificados foram categorizados como afecções dos tecidos cutâneos e subcutâneos (30,6%); houve seis óbitos temporalmente relacionados ao uso de soros, porém essa associação foi descartada. CONCLUSÃO: no período estudado, os soros produzidos pelo IB não apresentaram alteração em seu perfil de segurança, já que os EA relatados eram esperados conforme informação descrita em bula.

Abstract OBJECTIVE: to describe the safety profile of the heterologous serum produced by the Butantan Institute (BI) of São Paulo-SP, Brazil. METHODS: a descriptive study of adverse events (AEs) post-exposure to serum produced by the BI, encoded in the medical terminology of the Medical Dictionary for Regulatory Activities (MedDRA), and spontaneously reported to BI from 2012 to 2015. RESULTS: 52 individuals reported AEs, mainly related to Bothrops antivenom (n=11), diphtheria antitoxin (n=9) and unspecified snakebite serum (n=9); a mean of 3.2 AEs per individual was observed; among the total of 173 AEs, 63.0% were expected considering that they were described in the package insert; most of them were classified as skin and subcutaneous tissue disorders (30.6%); there were six deaths temporally related to the use of serum, but this association was discarded. CONCLUSION: in the studied period, the serum produced by the BI had no changes in their safety profiles, considering that the AEs were expected, according to the information previously described in the package insert.

Resumen OBJETIVO: describir el perfil de seguridad de los sueros heterólogos producidos por el Instituto Butantan (IB) de São Paulo-SP, Brasil. MÉTODOS: estudio descriptivo de los informes de eventos adversos (EAs) post-exposición a los sueros del IB y codificados según el Diccionario Médico para Actividades Regulatorias (MedDRA). RESULTADOS: 52 usuarios presentaron EAs relacionados con los sueros antibotrópico (n=11), antidiftérico (n=9) y antiofídico no especificado (n=9); se observó, en los EAs, 3,2 de media por persona; de los 173 EAs reportados, 63,0% fueron "esperados", ya que figuran descritos en la bula farmacológica; los EAs más reportados fueron los trastornos de piel y tejido subcutáneo (30,6%); hubo seis muertes, pero se descartó la asociación con el uso de suero. CONCLUSIÓN: durante el período de estudio, los sueros del IB no mostraron ningún cambio en su perfil de seguridad, ya que los EAs reportados eran esperados conforme información descrita en la bula.

The Spleen Plays No Role in Nephrotoxic Serum Nephritis, but Constitutes a Place of Compensatory Haematopoiesis.

BACKGROUND: The spleen has been implicated in the pathogenesis of immune-complex glomerulonephritis by initiating and resolving adaptive immune responses. Thus, we aimed to evaluate the role of the spleen in experimental nephrotoxic serum nephritis (NTS). METHODS: In order to accelerate the disease, animals were subjected to NTS by preimmunizing male C57BL/6J mice with rabbit IgG three days before injecting the rabbit anti-glomerular basement antiserum, or were immunized only. A group underwent splenectomy before NTS induction. RESULTS: We observed enlargement of the spleen with a maximum at 14 days after NTS induction or immunization only. Splenectomized mice were found to develop albuminuria and renal histological changes comparable to sham-operated controls. Nevertheless, anaemia was aggravated in mice after splenectomy. During the course of NTS, we detected CD41+ megakaryocytes and Ter119+ erythroid precursor cells in the spleen of mice with NTS and of immunized mice. Ter119+Cxcr4+ cells and the binding partner Cxcl12 increased in the spleen, and decreased in the bone marrow. This was accompanied by a significant systemic increase of interferon-gamma in the serum. CONCLUSIONS: In summary, splenectomy does not influence the course of NTS per se, but is involved in concomitant anaemia. Extramedullary haematopoiesis in the spleen is probably facilitated through the migration of Cxcr4+ erythroid precursor cells from the bone marrow to the spleen via a Cxcl12 gradient and likely arises from the suppressive capacity of chronic inflammation on the bone marrow.

Fingolimod prevents blood-brain barrier disruption induced by the sera from patients with multiple sclerosis.

OBJECTIVE: Effect of fingolimod in multiple sclerosis (MS) is thought to involve the prevention of lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system across blood-brain barrier (BBB). However, brain microvascular endothelial cells (BMECs) represent a possible additional target for fingolimod in MS patients by directly repairing the function of BBB, as S1P receptors are also expressed by BMECs. In this study, we evaluated the effects of fingolimod on BMECs and clarified whether fingolimod-phosphate restores the BBB function after exposure to MS sera. METHODS: Changes in tight junction proteins, adhesion molecules and transendothelial electrical resistance (TEER) in BMECs were evaluated following incubation in conditioned medium with or without fingolimod/fingolimod-phosphate. In addition, the effects of sera derived from MS patients, including those in the relapse phase of relapse-remitting (RR) MS, stable phase of RRMS and secondary progressive MS (SPMS), on the function of BBB in the presence of fingolimod-phosphate were assessed. RESULTS: Incubation with fingolimod-phosphate increased the claudin-5 protein levels and TEER values in BMECs, although it did not change the amount of occludin, ICAM-1 or MelCAM proteins. Pretreatment with fingolimod-phosphate restored the changes in the claudin-5 and VCAM-1 protein/mRNA levels and TEER values in BMECs after exposure to MS sera. CONCLUSIONS: Pretreatment with fingolimod-phosphate prevents BBB disruption caused by both RRMS and SPMS sera via the upregulation of claudin-5 and downregulation of VCAM-1 in BMECs, suggesting that fingolimod-phosphate is capable of directly modifying the BBB. BMECs represent a possible therapeutic target for fingolimod in MS patients.

Treatment of diffuse systemic sclerosis with hyperimmune caprine serum (AIMSPRO): a phase II double-blind placebo-controlled trial.

OBJECTIVE: The primary objective of the study was to explore safety and tolerability of hyperimmune caprine serum (AIMSPRO) in established diffuse cutaneous systemic sclerosis (SSc). Secondary objectives included assessment of potential efficacy and biological activity and exploration of candidate biomarkers. METHODS: This was a double-blind parallel group randomised placebo-controlled clinical trial. After informed consent 20 patients with established diffuse cutaneous SSc of greater than 3 years duration not receiving immunosuppressive therapy were randomised to receive either active (n=10) or placebo formulation (n=10) by subcutaneous twice weekly injection over 26 weeks. Clinical assessments were evaluated over 26 weeks. RESULTS: There were no safety concerns during this study. Frequency of adverse events was not different between active and placebo groups. Mean modified Rodnan Skin Score (mRSS) fell by 1.4±4.7 units with active treatment but increased by 2.1±6.4 units on placebo when baseline values were compared with 26 weeks and responder analysis showed clinically meaningful improvement in mRSS at 26 weeks in 5 (50%) of actively treated patients compared with 1 (10%) in the control group (p=0.062). PIIINP (µg/L) showed a comparatively larger increase in the treatment group compared with the placebo group, (p=0.0118). CONCLUSIONS: These results confirm tolerability and safety of this novel biological agent in established diffuse SSc. The value of a placebo treated control group in small clinical trials evaluating skin disease in SSc is confirmed. Potential improvement in mRSS and changes in PIIINP in cases receiving active therapy suggest that this intervention may be of clinical benefit and warrants further evaluation.

Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina.

Host defense against opportunistic fungi requires coordination between innate and adaptive immunity for resolution of infection. Antibodies generated in mice vaccinated with the fungus Pneumocystis prevent growth of Pneumocystis organisms within the lungs, but the mechanisms whereby antibodies enhance antifungal host defense are poorly defined. Nearly all species of fungi contain the conserved carbohydrates ß-glucan and chitin within their cell walls, which may be targets of innate and adaptive immunity. In this study, we show that natural IgM antibodies targeting these fungal cell wall carbohydrates are conserved across many species, including fish and mammals. Natural antibodies bind fungal organisms and enhance host defense against Pneumocystis in early stages of infection. IgM antibodies influence recognition of fungal antigen by dendritic cells, increasing their migration to draining pulmonary lymph nodes. IgM antibodies are required for adaptive T helper type 2 (Th2) and Th17 cell differentiation and guide B cell isotype class-switch recombination during host defense against Pneumocystis. These experiments suggest a novel role for the IgM isotype in shaping the earliest steps in recognition and clearance of this fungus. We outline a mechanism whereby serum IgM, containing ancient specificities against conserved fungal antigens, bridges innate and adaptive immunity against fungal organisms.

Metronidazole with Lactacyd vaginal gel in bacterial vaginosis.

AIM: To assess the efficacy and tolerability of lactic acid (Lactacyd vaginal gel; LVG) when given as an adjunct to metronidazole in the treatment of bacterial vaginosis (BV) among Filipino patients. METHODS: A multicenter, open-labeled, controlled, randomized, three-arm comparative study on 90 women aged 18 years or over with clinically and microbiologically proven BV. RESULTS: The lactobacilli colony count significantly increased over time in all three arms. At day 14, growth of lactobacilli was significantly higher among patients in the lactic acid gel and combination treatment arms. Significant reduction of malodorous vaginal discharge (whiff test) and lowest recurrence of BV were noted in the metronidazole plus lactic acid gel arm. Regarding disappearance of signs of BV, there was significant decrease in the pH level and frequency of clue cell positive patients across time but was not significantly different across treatment groups. Only one patient (3%, 1/60) among those who received lactic acid gel complained of increased curd-like discharge. Six patients (10%, 6/60) who received metronidazole complained of epigastric pain/discomfort, dizziness and dyspnea. CONCLUSIONS: Lactic acid gel (LVG) is safe and as efficacious as metronidazole in the treatment of BV. There is evidence that LVG when combined with metronidazole is superior to metronidazole alone in promoting lactobacilli colonization. LVG as an adjunct to metronidazole, having the least number of recurrent BV, appears to result in better long-term treatment effect on bacterial vaginosis.

Pulmonary lymphoid lesions in an experimental model of collapsing glomerulopathy in rats.

UNLABELLED: The characterization of lung damage in an experimental model of collapsing glomerulopathy (CG) in rats is described. METHODS: 12 rats were divided into two groups and injected intravenously (iv) with 1 mg/saline in a final volume of 1 ml/ day in the tail vein for 5 days, with fractionated serum from control and CG subjects. Proteinuria was quantified, and the Glomerular filtration rate was calculated based on creatinine clearance (CC). Rats were sacrificed by perfusion fixation at day 5. RESULTS: Rats injected with serum from CG patients developed proteinuria (p<0.001). A decrease in CC (0.68+/-0.19) in these rats was also observed. Glomerular tuft retraction and mesangial proliferation was observed in all rats receiving serum from the CG patients. Peribronchiolar infiltrate integrated mainly by lymphocytes, was identified in all CG rats. In some areas this infiltration disrupted the basement membrane and damaged the epithelium. No histopathological abnormalities in the kidney or lungs were found in rats receiving control serum. CONCLUSION: Patchy pulmonary lymphoid infiltrates were found in the CG model. Up to now there was no information about pulmonary lymphoid infiltration in CG patients. Besides fluid overload due to renal insufficiency or a nephrotic syndrome, other causes of pulmonary involvement in CG patients should be explored.

A phase I study of the pharmacokinetics and safety of passive immunotherapy with caprine anti-HIV antibodies, (PE)HRG214, in HIV-1-infected individuals.

PURPOSE: To establish the pharmacokinetics and safety of single-dose polyclonal caprine anti-HIV antibodies ((PE)HRG214)in HIV-1-infected individuals. DESIGN: A phase 1, open-label, nonrandomized, dose-escalating study. METHOD: HIV-1-infected patients with CD4+ T-cell counts of < or =200 cells/microL and plasma HIV viral load (VL)of > or =5,000 copies/mL received a single intravenous dose of HRG. Dosing began at 6,000 U/kg HRG with proposed step-wise escalation to 96,000 U/kg. RESULTS: Eleven males were enrolled; median CD4+T-cell count and VL were 96 cells/microL and 126,200 copies/mL, respectively. HRG exhibited linear pharmacokinetics across the dosing range studied. The mean terminal elimination half-life (t(1/2)) was 136.6 +/- 44.6 hours (range, 52.6-198 h). Serum sickness occurred in one 48,000 U/kg HRG recipient. One 6,000 U/kg and two 24,000 U/kg HRG recipients developed a mild rash. Between baseline and day 60, VL remained unchanged (n = 6), increased by 0.67 log(10) copies/mL (n = 1), or declined by 0.34-1.55 log(10) copies/mL (n = 4). CONCLUSION: Single-dose HRG exhibited linear kinetics and a long half-life. Although numbers in each dosing group were very small (n = 3), HRG was generally well tolerated in doses below 48,000 U/kg. Multiple dosing with HRG in the HIV-salvage setting may be complicated by immune-complex formation.

Blocking VLA-4 prevents progression of experimental crescentic glomerulonephritis.

BACKGROUND/AIMS: Integrins are adhesion molecules of fundamental importance to the recruitment of leucocytes in inflammation. The alpha4beta1 integrin (VLA-4) is a leucocyte ligand for endothelial vascular cell adhesion molecule-1 (VCAM-1), fibronectin and osteopontin. We addressed the role of VLA-4 in mediating progressive renal injury in vivo using a blocking monoclonal antibody (mAb) in a rat model of crescentic glomerulonephritis. METHODS: WKY rats with nephrotoxic nephritis were given anti-VLA-4 or control mAb at 2.5 mg/kg by i.p. injection on alternate days. In separate experiments, antibodies were given from days 5-13, from days 13-21 or from days 14-28. RESULTS: Early treatment with anti-VLA-4 mAb from days 5-13 showed a significant effect on renal function, with a reduction in albuminuria (p < 0.01) and a higher creatinine clearance (p < 0.05). Delayed treatment from days 13-21 also showed a reduction in albuminuria (p < 0.05) and serum creatinine (p < 0.05). However, there was no significant effect on glomerular or interstitial scarring in these two experiments. In the late treatment study, in which anti-VLA-4 mAb was administered from days 14-28, serum creatinine was reduced (p < 0.05), creatinine clearance was improved (p < 0.05), and renal survival was significantly prolonged (p < 0.05). Interstitial scarring was significantly less in treated rats (p < 0.05). Glomerular macrophage and CD8+ cell counts were higher in anti-VLA-4 mAb treated rats (p < 0.05), possibly reflecting greater glomerular scarring in control animals. CONCLUSION: Leucocyte VLA-4 mediates pro-inflammatory and pro-fibrotic effects within the kidney, independent of any role in recruitment of leucocytes into the kidney. Blocking VLA-4 is a promising therapeutic approach in human glomerulonephritis.

Serum concentrations, efficacy, and safety of a new, intravenously administered varicella zoster immune globulin in pregnant women.

Chickenpox is teratogenic in humans, and varicella zoster immune globulin (VZIG) is given to pregnant women believed to be susceptible to the virus after contact with chickenpox. Available VZIG is given as intramuscular injections. The objective of this study was to evaluate the efficacy, safety, and serum concentrations of a new VZIG that can be given intravenously. The new VZIG (Cangene Pharm., Inc.) was compared to the standard VZIG (Massachusetts Public Health Biologic Laboratories) in a randomized protocol in 57 pregnant women seronegative to varicella zoster virus (VZV). Pregnant women received 125 units per 10 kg body weight to a maximal dose of 625 units. Women were evaluated on days 2, 7, 14, and 28 and at other times if symptoms developed into clinical varicella, which was scored by the Constitutional Illness Score. The new VZIG was comparable to the standard VZIG on all parameters of efficacy and safety. Levels of VZV antibodies at day 2 postinjection were significantly higher among those receiving the new preparation intravenously. The authors concluded that the new intravenous form of VZIG confers higher initial levels of VZV antibodies and is comparable in terms of its maternal efficacy and safety to the standard form of VZIG.

Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child.

The Food and Drug Administration licensed a live-virus varicella vaccine (Varivax; Merck & Co Inc, West Point, PA) in March 1995. Prelicensure adverse events were minimal; however, since licensure and increased vaccine use, rare previously undetected risks have arisen. Presented here is the clinical course of a previously undiagnosed, human immunodeficiency virus-infected boy who developed dissemination of the vaccine strain of varicella zoster after immunization. chickenpox, human immunodeficiency virus, pneumonia, encephalopathy, varicella vaccine, adverse events, dissemination.