Importancia de la acreditación internacional de facultades de medicina

A partir de 2024, egresados de facultades de medicina que deseen hacer estudios de postgrado en los EE.UU o el Canadá, deberán graduarse en escuelas de medicina con programas educativos de calidad avalados por agencias reconocidas capaces de otorgar una acreditación internacional. La World Federation for Medical Education (WFME) es una de estas agencias. La WFME aceptó la nueva política de acreditación del Educational Committee for Foreign Medical Education (ECFMG) por la que médicos que postulen para la certificación del ECFMG del 2024 en adelante, tendrán que haberse graduado en un centro universitario de medicina acreditado por una agencia de aseguramiento de calidad que se encuentre reconocida por la WFME. El COMAEM (Consejo Mexicano para la Acreditación de la Educación Médica) está avalado por la WFME y otros organismos internacionales que aseguran la calidad de la educación superior. La acreditación que concede el COMAEM es un reconocimiento que el programa de medicina cumple con los criterios, indicadores y parámetros de calidad establecidos por este organismo. A partir de 2024, los egresados de un programa acreditado podrán postular para la certificación del ECFMG a través del examen de licencia médica de los Estados Unidos o USMLE (United States Medical Licensing Examination) y así poder hacer una residencia de especialización o trabajar en EE. UU. En el Perú, solo la Facultad de Medicina Alberto Hurtado de la Universidad Peruana Cayetano Heredia ha completado el proceso de acreditación internacional a través de COMAEM y ha recibido dicha acreditación.

As of 2024, medical school graduates who wish to pursue graduate studies in the U.S. or in Canada, they must have graduated from medical schools with quality educational programs endorsed by recognized agencies, capable of granting international accreditation. The World Federation for Medical Education (WFME) is one of these agencies. The WFME accepted the new accreditation policy of the Educational Committee for Foreign Medical Education (ECFMG) whereby physicians applying for ECFMG certification from 2024 onwards, must have graduated from a university medical center accredited by a quality assurance agency that is recognized by the WFME. The COMAEM (Mexican Council for the Accreditation of Medical Education) is endorsed by the WFME and other international organizations that ensure the quality of higher education. The accreditation granted by COMAEM is a recognition that the medical program meets the criteria, indicators and quality parameters established by this organization. Starting in 2024, graduates of an accredited program will be able to apply for ECFMG certification through the United States Medical Licensing Examination (USMLE) and thus be able to do a specialty residency or work in the U.S. In Peru, only the Alberto Hurtado School of Medicine of the Cayetano Heredia Peruvian University has completed the international accreditation process through COMAEM and has received such accreditation.

El impacto de la pandemia del COVID-19 en la educación médica: adaptabilidad y experiencia con enseñanza a distancia de la Sociedad Médica Peruano Americana

La pandemia del COVID-19 tuvo un impacto significativo en el cuidado y la educación médicos en el Perú. En respuesta, la Sociedad Médica Peruano Americana (PAMS), una organización médica benéfica con sede en los EE.UU., adoptó sus misiones médicas y educativas en Perú usando estrategias virtuales. Desarrollamos colaboración con varias facultades de medicina y la Asociación Peruana de Facultades de Medicina (ASPEFAM) y ofrecimos un panel de veinte y cuatro miembros para brindar conferencias y seminarios multidisciplinarios en español. Hicimos 19 seminarios, incluyendo temas relacionados y no relacionados al COVID-19, que en los últimos dos años atrajo a 14 489 participantes de 23 países. Ellas fueron la base de 20 publicaciones en revistas médicas peruanas. Nuestro concurso de investigaciones clínicas y nuestro proyecto piloto de mentoría de investigación fueron recibidos positivamente. La pandemia del COVID-19 tuvo un efecto positivo en la misión educativa de PAMS en Perú.

The COVID-19 pandemic had a significant impact on medical care and medical education in Peru. In response, the Peruvian American Medical Society (PAMS), a charitable medical organization based in the USA, pursued its medical and educational missions in Peru by adopting virtual learning technology. We developed closer collaborative relationships with several medical schools and the Peruvian Association of Medical Schools (ASPEFAM) while offering a faculty panel of twenty-four members to provide lectures and multidisciplinary webinars in Spanish. We conducted 19 webinars including COVID -19 and non-COVID-19 related topics that over the last two years attracted 14,489 participants from 23 countries. They were the foundation for twenty publications in Peruvian medical journals. Our clinical investigations competition was positively received as was our pilot project on research mentorship. The COVID -19 pandemic had a positive effect on the educational mission of PAMS in Peru.

A review of severe acute respiratory syndrome - coronavirus 2

The pandemic caused by SARS-CoV-2 in 2020 and still raging in 2021 is a global emergency where no country was spared from its high morbidity and mortality. Life changed in innumerable ways, from lock downs to job losses, isolation and mental health crisis. All countries suffered. If it were not for the quick development of medications and vaccines, coupled with preventive measures like facial masks, social distancing and frequent washing of hands, we will be in a worse chaos. Some countries like India and many in Latin America have been devastated and its consequences will be long felt even after the pandemic is controlled. Understanding the cause, its epidemiology and controlled measures is important. Although it took 100 years to encounter a global pandemic of this magnitude, scientists warn of almost inevitable future global pandemics. This review will explore some salient aspects of SARS-CoV-2 impact and measures to control the infection. The world's death toll caused by SARS-CoV-2 exceeds 3 million and close to 200 million people have been infected. The available vaccines used in more than 400 million individuals, still fall short of producing herd immunity despite the high efficacy rate of most of them. There is a pressing need to immunize 80% or more. Some side effects to vaccine were reported, the majority of minor impact, although some rare ones are more serious such as thrombotic thrombocytopenia or myocarditis. Still the protection afforded from the vaccine vastly outweighs the risks and its wide use is encouraged.

La pandemia causada por el SARS-CoV-2 en 2020 y que aún continúa en 2021 es una emergencia mundial en la que ningún país se libró de su alta morbilidad y mortalidad. La vida cambió de innumerables formas, desde bloqueos hasta pérdida de empleo, aislamiento y crisis de salud mental. Todos los países sufrieron. Si no fuera por el rápido desarrollo de medicamentos y vacunas, sumado a medidas preventivas como mascarillas faciales, distanciamiento social y lavado frecuente de manos, estaríamos en un caos peor. Algunos países como India y muchos en América Latina han sido devastados y sus consecuencias se sentirán durante mucho tiempo incluso después de que se controle la pandemia. Es importante comprender la causa, su epidemiología y las medidas controladas. Aunque tomó 100 años encontrar una pandemia global de esta magnitud, los científicos advierten sobre pandemias globales futuras casi inevitables. Esta revisión explorará algunos aspectos destacados del impacto del SARS-CoV-2 y las medidas para controlar la infección. La cifra mundial de muertes causadas por el SARS-CoV-2 supera los 3 millones y se han infectado cerca de 200 millones de personas. Las vacunas disponibles que se utilizan en más de 400 millones de personas aún no logran producir inmunidad colectiva a pesar de la alta tasa de eficacia de la mayoría de ellas. Existe una necesidad imperiosa de inmunizar al 80% o más. Se informaron algunos efectos secundarios de la vacuna, la mayoría de impacto menor, aunque algunos raros son más graves, como trombocitopenia trombótica o miocarditis. Aún así, la protección que brinda la vacuna supera con creces los riesgos y se alienta su amplio uso.

Hepatitis C eradication with sofosbuvir leads to significant metabolic changes.

AIM: To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control. METHODS: This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study. Due to the known hemolytic effect of ribavirin, HbA1C was obtained a minimum of three months post-treatment for the patients treated with a ribavirin regimen. Medical history, demographics, HCV genotype, pre-therapy RNA, and liver biopsies were included in our analysis. The patients who started a new medication or had an adjustment of baseline medical management for hyperlipidemia or diabetes mellitus (DM) were excluded from our analysis. RESULTS: Two hundred and thirty-four patients were reviewed, of which 60 patients met inclusion criteria. Sixty-three point three percent were male, 26.7% were Caucasian, 41.7% were African American and 91.7% were infected with hepatitis C genotype 1. Mean age was 60.6 ± 6.7 years. Thirty-nine patients had HbA1C checked before and after treatment, of which 22 had the diagnosis of DM type 2. HbA1C significantly decreased with treatment of HCV (pretreatment 6.66% ± 0.95% vs post-treatment 6.14% ± 0.65%, P < 0.005). Those treated with SOF/LDV had a lower HbA1C response than those treated with other regimens (0.26% ± 0.53% vs 0.71% ± 0.83%, P = 0.070). Fifty-two patients had pre- and post-treatment lipid panels; there was a significant increase in low-density lipoprotein (LDL) and total cholesterol (TC) after treatment (LDL: 99.5 ± 28.9 mg/dL vs 128.3 ± 34.9 mg/dL, P < 0.001; TC: 171.6 ± 32.5 mg/dL vs 199.7 ± 40.0 mg/dL, P < 0.001). Pre-treatment body-mass index (BMI) did not differ from post-treatment BMI (P = 0.684). CONCLUSION: Eradication of HCV with a SOF regimen resulted in a significant drop in HbA1C and an increase in LDL and TC post therapy.

Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations.

BACKGROUND: Artemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population. METHODS: Genomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET™ Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B). RESULTS: CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. CONCLUSION: Prevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated.

The management of HCV-infected pregnant women.

Hepatitis C is, at present, a worldwide health problem and is the most common cause of liver transplantation. Its prevalence in pregnant women is similar to that of the general population. In the absence of cirrhosis and portal hypertension, most HCV-infected pregnant women do not have obstetric complications. Screening of pregnant women that are asymptomatic and do not have risk factors is not cost effective. A high hepatitis C viral load reportedly increases vertical transmission and is higher in women who are coinfected with HIV or who are intravenous drug users. Prolonged rupture of the membrane for more than 6 h, amniocentesis, and perineal lacerations increase the potential risk of perinatal transmission. Although the hepatitis C virus can be transmitted intrapartum, prevention by caesarean delivery is not generally indicated. The HCV virus can be found in maternal milk; however, breast feeding is not contraindicated. In conclusion, there are no antiviral treatment recommendations for HCV-infected women during pregnancy, or guidelines for the prevention of vertical transmission.

Enlarged lateral ventricles and aberrant behavior in mice overexpressing PDGF-B in embryonic neural stem cells.

Platelet-derived growth factor (PDGF) is important in central nervous system (CNS) development, and aberrant expression of PDGF and its receptors has been linked to developmental defects and brain tumorigenesis. We previously found that neural stem and progenitor cells in culture produce PDGF and respond to it by autocrine and/or paracrine signaling. We therefore aimed to examine CNS development after PDGF overexpression in neural stem cells in vivo. Transgenic mice were generated with PDGF-B under control of a minimal nestin enhancer element, which is specific for embryonic expression and will not drive adult expression in mice. The resulting mouse showed increased apoptosis in the developing striatum, which suggests a disturbed regulation of progenitor cells. Later in neurodevelopment, in early postnatal life, mice displayed enlarged lateral ventricles. This enlargement remained into adulthood and it was more pronounced in male mice than in transgenic female mice. Nevertheless, there was an overall normal composition of cell types and numbers in the brain and the transgenic mice were viable and fertile. Adult transgenic males, however, showed behavioral aberrations and locomotor dysfunction. Thus, a tightly regulated expression of PDGF during embryogenesis is required for normal brain development and function in mice.

Treatment options for HCV nonresponders and relapse patients.

The current standard-of-care treatment for chronic hepatitis C virus (HCV) infection, peginterferon plus ribavirin, results in a sustained virological response in 39-46% of genotype 1 patients, based on published reports and recently re-affirmed by findings in the IDEAL trial. While several directly targeted oral antiviral medications in development appear promising to decrease genotype 1 treatment failure, these agents are not yet approved for general clinical use, and their contribution to the management of relapsed or refractory HCV patients is uncertain. Other re-treatment approaches may include "watch and wait" or other strategies such as the use of consensus interferon plus ribavirin. Consensus interferon, a wholly synthetic interferon, was developed based on the most commonly represented amino acid sequence of the 14 different subtypes of interferon-alpha and has been shown in clinical trials to produce sustained virological responses in up to one-third of patients who do not respond to initial therapy and up to 50% of those that relapse after treatment with peginterferon plus ribavirin. In this monograph, the benefits and challenges of each of these available and future treatment options will be discussed with an eye toward optimizing therapy for an individual patient.

Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneurons caused by an unliganded thyroid hormone receptor alpha1.

Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor alpha1 (TR alpha1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TR alpha1 as the receptor isoform mediating these effects.

Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1.

Thyroid hormone, via its nuclear receptors TRalpha and TRbeta, controls metabolism by acting locally in peripheral tissues and centrally by regulating sympathetic signaling. We have defined aporeceptor regulation of metabolism by using mice heterozygous for a mutant TRalpha1 with low affinity to T3. The animals were hypermetabolic, showing strongly reduced fat depots, hyperphagia and resistance to diet-induced obesity accompanied by induction of genes involved in glucose handling and fatty acid metabolism in liver and adipose tissues. Increased lipid mobilization and beta-oxidation occurred in adipose tissues, whereas blockade of sympathetic signaling to brown adipose tissue normalized the metabolic phenotype despite a continued perturbed hormone signaling in this cell type. The results define a novel and important role for the TRalpha1 aporeceptor in governing metabolic homeostasis. Furthermore, the data demonstrate that a nuclear hormone receptor affecting sympathetic signaling can override its autonomous effects in peripheral tissues.

Thymosin beta4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-beta receptor in human hepatic stellate cells.

Hepatic stellate cells (HSCs) are the main producers of type I collagen in the liver, and therefore are responsible, in part, for the fibrous scar observed in cirrhotic livers. Although there is no approved treatment for this deadly disease, drugs inducing HSC apoptosis in animals (gliotoxin) and hepatocyte regeneration in man (hepatocyte growth factor [HGF]), have been used successfully in ameliorating liver fibrosis. In this communication we investigated whether thymosin beta(4) (Tbeta(4)), an actin-sequestering peptide that prevents scarring of the heart after a myocardial infarction and that prevents kidney fibrosis in animals, has the potential to be used to treat liver fibrosis. To this end we studied whether the administration of Tbeta(4) to HSCs could alter the expression of genes encoding for extracellular matrix components, as well as those required for differentiation of HSCs. Our preliminary findings show that Tbeta(4) had no effect on the expression of alpha2 (I) collagen, tissue inhibitor of metalloproteinases-1, and matrix metalloproteinase-2 mRNAs. However, it upregulated the expression of HGF and downregulated the expression of platelet-derived growth factor-beta receptor mRNAs in these cells. Overall, these findings suggest that Tbeta(4) has antifibrogenic potential.

Antiviral response of HCV genotype 1 to consensus interferon and ribavirin versus pegylated interferon and ribavirin.

Achieving an antiviral response at a reasonable cost is a challenge in the treatment of patients with chronic hepatitis C. A previous study indicated that consensus interferon with ribavirin had promising activity against hepatitis C virus (HCV) genotype 1. The objective of this study was to determine the virologic response with consensus interferon or pegylated interferon alpha-2b plus weight-ribavirin in patients chronically infected with HCV genotype 1. Intention-to-treat analysis showed response in 37% and 41% of subjects treated with consensus interferon/ribavirin or pegylated interferon/ribavirin, respectively, with response rates of 42% and 44% observed in analysis of the per-protocol population, not a significant difference. Tolerability of the two treatment regimens was similar. In conclusion, both treatment regimens were safe and gave a similar antiviral response. It is possible that if consensus interferon is administered daily rather than three times weekly, eradication of HCV could be achieved in a larger proportion of patients infected with HCV genotype 1.

Prevention of hepatitis B in nonresponders to initial hepatitis B virus vaccination.

Although vaccination against hepatitis B virus (HBV) is highly successful, 5% to 10% of individuals do not experience a response with an adequate antibody level to hepatitis B surface antigen (anti-HBs). Contributing causes for nonresponse to the vaccine are genetic predisposition, immunosuppression, and certain chronic illnesses. The distinction between true nonresponse (after adequate immunization) and waning anti-HBs levels is important. The latter is not uncommon in populations in areas of the world with low endemicity for HBV infection. Data from subjects with waning anti-HBs levels show that immunologic memory may still protect these individuals against acute HBV infection or may prevent chronic infection with HBV for < or =10 years after immunization. Recent reports from Asia and Alaska describe cases of chronic HBV infection 15 years after immunization in subjects who have very low levels of anti-HBs. Thus, nonresponders or those with waning immunity who may be at risk of HBV infection in subsequent years may require a booster dose. Clinical algorithms to reimmunize nonresponders have been described and are discussed in this article. Experimental hepatitis B vaccines have shown some promise in nonresponders but are not commercially available in the United States.

Impaired Ca2+ handling and contraction in cardiomyocytes from mice with a dominant negative thyroid hormone receptor alpha1.

The profound effects of thyroid hormone (TH) on heart development and function are mediated by the thyroid hormone receptors (TR) alpha(1) and beta(1). While numerous patients with TRbeta(1) mutations have been identified, patients with similar mutations in TRalpha(1) are yet to be discovered. Recently generated heterozygous mice with a dominant negative mutation in TRalpha(1) (TRalpha(1)+/m mice) have normal TH levels, which may have hampered the discovery of patients with such mutations. We now measure intracellular Ca(2+) and contraction in cardiomyocytes isolated from TRalpha(1)+/m mice and wildtype littermates (WT). TRalpha(1)+/m cardiomyocytes showed a phenotype similar to that in hypothyroidism with significant slowing of voltage-activated Ca(2+) transients and contractions. Increased stimulation frequency (from 0.5 to 3 Hz) or beta-adrenergic stimulation reduced the differences between TRalpha(1)+/m and WT cardiomyocytes. However, in TRalpha(1)+/m cells stimulation at 3 Hz gave a marked increase in diastolic Ca(2+) and beta-adrenergic stimulation triggered spontaneous Ca(2+) release events during relaxation. Both TRalpha(1)+/m and WT cardiomyocytes responded to TH treatment by displaying a "hyperthyroid" phenotype with faster and larger Ca(2+) transients and contractions. Excised TRalpha(1)+/m hearts showed an increased expression of phospholamban (PLB). In conclusion, isolated TRalpha(1)+/m cardiomyocytes display major dysfunctions with marked slowing of the Ca(2+) transients and contractions.

Interferon alfacon-1 and ribavirin versus interferon alpha-2b and ribavirin in the treatment of chronic hepatitis C.

Despite advances in the therapy of chronic hepatitis C, a large number of patients do not respond to current therapies. The study objective was to assess whether a combination of interferon (IFN) alfacon-1 and ribavirin improves the response rate compared with a combination of INF alpha-2b and ribavirin in chronic hepatitis C subjects. The study was designed as an open-label, prospective, randomized, controlled study; 128 subjects with chronic hepatitis C were randomized to INF alfacon-1, 15 microg three times per week, plus ribavirin, 1 g/day, or IFN-alpha2b, 3 million units three times per week, plus ribavirin, 1 g/day for 48 weeks. The end point of the study was a sustained viral response, defined as undetectable HCV RNA at 24 weeks post 48 weeks of treatment. Overall, 57% of subjects in the INF alfacon-1/ribavirin group achieved a sustained antiviral response, compared with 40% of subjects in the IFN-alpha2b/ribavirin group (P = 0.052). In the subset of subjects with a high viral load, HCV RNA was successfully eradicated in more individuals who received INF alfacon-1/ribavirin than subjects who received IFN-alpha2b/ribavirin (57 versus 31%; P = 0.025). Among individuals with genotype 1 and a high viral load, the sustained antiviral response was significantly higher with INF alfacon-1/ribavirin than with IFN-alpha2b/ribavirin (46 versus 14%; P = 0.019). Adverse events were similar in both treatment groups. In conclusion, this study demonstrated that the combination of INF alfacon-1 and ribavirin provides a significantly better treatment response compared with the combination of IFN-alpha2b and ribavirin in chronic HCV subjects infected with genotype 1 and a high viral RNA load.

Thymalfasin: an immune system enhancer for the treatment of liver disease.

Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Th1 immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, depressed response to vaccination and cancer. The basis for effectiveness in these conditions is primarily through modulation of immunological responsiveness, as thymalfasin has been shown to have beneficial effects on numerous immune system parameters and to increase T-cell differentiation and maturation. Thymalfasin is responsible for reconstitution of immune function when thymic tissue is given back to thymectomized animals. In addition, thymalfasin has been shown to have efficacy in multiple experimental models of immune dysfunction, mainly, infectious diseases such as hepatitis (woodchuck) and influenza (mouse), and cancer such as melanoma (mouse) and colorectal carcinoma (rat) where thymalfasin has shown antitumor effects.

Thymalfasin: an immune system enhancer for the treatment of liver disease.

Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Thl immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, depressed response to vaccination and cancer. The basis for effectiveness in these conditions is primarily through modulation of immunological responsiveness, as thymalfasin has been shown to have beneficial effects on numerous immune system parameters and to increase T-cell differentiation and maturation. Thymalfasin is responsible for reconstitution of immune function when thymic tissue is given back to thymectomized animals. In addition, thymalfasin has been shown to have efficacy in multiple experimental models of immune dysfunction, mainly, infectious diseases such as hepatitis (woodchuck) and influenza (mouse), and cancer such as melanoma (mouse) and colorectal carcinoma (rat) where thymalfasin has shown antitumor effects.

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid.

We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml. Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent. While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations.