Changes in the AIDS epidemiologic situation in Puerto Rico following health care reform and the introduction of HAART / Cambios en la situación epidemiológica del sida en Puerto Rico tras la reforma sanitaria y la introducción de la TARGA

Objetivos. Comparar la frecuencia de casos de sida, así como las características sociodemográficas y clínicas de los pacientes de sida en Puerto Rico, antes y después de la introducción de la terapia antirretrovírica de gran actividad (TARGA) y la privatización del sistema de salud de la isla. Métodos. Comparamos los nuevos casos de sida durante dos períodos de tres años, 1992­1994 y 1998­2000, en cuatro poblaciones: 1) todos los Estados Unidos, 2) Puerto Rico, 3) la Región de Salud de Bayamón (que se sitúa en la parte norte del centro de Puerto Rico y contiene 11 de las 78 municipalidades de la isla) y una cohorte de pacientes infectados por el VIH y atendidos en la Escuela de Medicina de la Universidad Central del Caribe (UCC). La UCC está en Bayamón, Puerto Rico, dentro de un complejo médico universitario donde se encuentran el hospital escuela (Hospital Universitario Ramón Ruíz Arnaú), las clínicas ambulatorias (Clínicas de Inmunología) para pacientes infectados por el VIH y los edificios administrativos. Todo ello en conjunto representa la principal infraestructura de atención sanitaria de carácter público en la Región de Salud de Bayamón. Resultados. La frecuencia de nuevos casos de sida se redujo notablemente entre los dos períodos en cada una de las cuatro poblaciones estudiadas. La reducción de 48,1% observada en Puerto Rico superó a la de 40,9% observada en los Estados Unidos en general. La reducción en Puerto Rico obedeció probablemente a la mayor disponibilidad y aplicación de la TARGA y a la provisión de atención sanitaria de manera integrada a pacientes de sida o con infección por el VIH en cada clínica ambulatoria regional. A pesar de estas mejoras, sin embargo, el número absoluto de pacientes de sida en la isla sigue siendo elevado. Hacen falta cuantiosos recursos para proporcionar tratamiento y aplicar medidas de prevención. La proporción de casos de sida nuevos fue menor entre las mujeres, las personas de 40 años de edad o mayores, las personas con menos escolaridad y las que vivían solas. El uso de drogas inyectadas sigue siendo la principal vía de transmisión en Puerto Rico. Conclusiones. En Puerto Rico, cualquier adelanto futuro en la lucha contra el sida dependerá de la capacidad de la isla para reducir la transmisión ocasionada por el uso de drogas inyectadas; de la administración de la TARGA a un gran número de pacientes vulnerables, especialmente a usuarios de drogas intravenosas; de intervenciones educativas para mejorar la observancia del tratamiento en ciertos grupos en riesgo; y de medidas orientadas a reducir la frecuencia del uso de drogas inyectadas

Objectives. To compare the occurrence of AIDS as well as the sociodemographic and clinical profiles of AIDS patients in Puerto Rico before and after the introduction of highly active antiretroviral therapy (HAART) and the privatization of the island's public health care system. Methods. We compared the incident AIDS cases for two three-year periods, 1992­1994 and 1998­2000, in four populations: (1) entire United States, (2) Puerto Rico, (3) Bayamón Health Region (located in north-central Puerto Rico, it includes 11 of the island's 78 municipalities), and (4) an HIV cohort enrolled at the Universidad Central del Caribe (UCC) School of Medicine. The UCC is located in Bayamón, Puerto Rico, within an academic medical complex that houses the teaching hospital (Ramón Ruíz Arnaú University Hospital), the ambulatory health care facilities (Immunology Clinics) for patients with HIV, and administrative buildings. This represents the major government-sponsored health care infrastructure within the Bayamón Health Region. Results. Incident AIDS declined substantially between the two periods in each of the four populations studied. The 48.1% decline in Puerto Rico exceeded the 40.9% decline in the United States. The decline in Puerto Rico likely resulted from increased availability and implementation of HAART and the delivery of health care to HIV/AIDS patients in an integrated fashion within each regional ambulatory clinic. In spite of this improvement, the absolute number of patients with AIDS on the island remains high. Substantial resources for treatment and prevention are required. The proportion of new AIDS cases was lower among women, persons 40 years of age or older, the less educated, and those living alone. Injection drug use remains the predominant mode of transmission in Puerto Rico. Conclusions. Further gains in Puerto Rico's fight against AIDS will depend on the island's ability to reduce the transmission that occurs through injection drug use; the use of HAART on a larger number of vulnerable patients, particularly intravenous drug users; educational interventions to improve medication compliance in certain risk groups; and specific measures aimed at decreasing the rate of injection drug use

Distribution of naïve (CD45RA+) and memory (CD45RO+) T-cells in HIV-infected Puerto Rican population

HIV infection usually results in a gradual deterioration of the immune system. It is evident that early recognition of progression markers during HIV infection from asymptomatic to symptomatic state is needed. In the present cross-sectional study, peripheral blood lymphocytes from 63 HIV-infected Puerto Rican individuals were analyzed by two-color flow cytometry to study the co-expression CD45RA and CD45RO on both CD4+ and CD8+ T-cells and its correlation with age, gender, CD4 count, CD4:CD8 ratio, anti-retroviral therapy, clinical status, and viral load. Measurement of T-cell subsets in these patients showed an excessive increase of CD3+CD8+, CD8+CD45RA+, and CD8+CD45RO+ T-cells as disease progresses. In contrast, it was also observed a significant decrease in CD3+CD4+, CD4+CD45RA+ and CD4+CD45RO+ T-cells. The distribution of CD8+CD45RA+ T-cells did not change significantly between HIV and AIDS cases suggesting that this T-cell subset is not a good progression marker. Interestingly, CD4+CD45RA+ T-cells were significantly difference between genders, and CD44+CD45RA+ and CD8+CD45RO+ T-cells were influenced by age. In conclusion, the distribution of naïve/memory CD4+ T-cells and memory CD8+ T-cells significantly correlate with HIV infection in disease progression. It is also important to mention that these T-cell subpopulations may be influenced by both gender and age. Overall, these results suggest that a loss in the generation of new immune response and function may be occurring during disease progression. This study open new windows of understanding that will be beneficial for future studies on immunopathogenesis, diagnosis, prognosis, and treatment monitoring for HIV/AIDS.

Abnormal immunological response to Mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis

The pathogenic mechanisms of immunosuppression leading to susceptibility of Mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4+, CD8+, TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4+, V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens-stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4+ and CD8+. T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders.

Plants from Puerto Rico with anti-Mycobacterium tuberculosis properties

OBJECTIVE: This study assesses the antitubercular potential of natural products obtained from plants reputed to have medicinal properties and collected from the tropical flora of Puerto Rico. BACKGROUND: The increase in persons infected with Mycobacterium tuberculosis (MTB) the world over and the development of resistance to antibiotics by this microbe and other infectious bacteria has created the need for new drugs to replace those which have lost effectiveness. METHOD: In Phase I of this study, ethanolic leaf extracts of fifty local plants were submitted to preliminary screening to assess their in vitro Mycobacterium smegmatis inhibitory activity using the Bauer-Kirby disk diffusion method. In Phase II, the definitive screening of the six most promising extracts which inhibited M. smegmatis were assayed for their MTB inhibitory activity using the BACTEC 460 susceptibility test method. The brine shrimp bioassay was used as a toxicity bioassay and the mice inoculation test was used to determine mice tolerance to the effect of the daily intraperitoneal inoculations of the plant extracts. RESULTS: MTB showed varying degrees of susceptibility to each plant extract. This effect was dependent upon the plant species, dose and time of exposure. Evidence is provided suggesting that: (1) Six crude plant extracts (12 per cent) tested possessed inhibitory capacity at the amount of 500 micrograms per disc; (2) Mammea americana extract yielded the strongest inhibitory effect at 50 micrograms per disc, followed by Marchantia polymorpha, Mangifera indica, Callistemon citrinus, Syzygium jambos and Momordica charantia; (3) the bactericidal inhibitory pattern of MTB growth, exposed to Mammea americana extract, was comparable to streptomycin; and (4) the transitory reduction pattern of MTB growth, produced by Callistemon citrinus, Marchantia polymorpha extracts at 100 micrograms and 250 micrograms, was similar to that of bacteriostatic agents. CONCLUSION: Of 50 plants screened six extracts tested for their anti-MTB activity yielded positive results with varying degrees of inhibition. Mammea americana showed the greatest inhibitory activity suggesting that certain plant species yield valuable anti-Mycobacterium tuberculosis substances. The procedures employed in this study, including the BACTEC 460 modified method, are useful for in vitro screening of plant extracts with potential antitubercular activity.

Interferón y su uso potencial en el tratamiento de enfermedades infecciosas / Interferon and its potential use in the treatment of infectious diseases

Modern recombinant biotechnology has made possible the production of large amount of interferons and their use as immunotherapeutic agents. Most of the biological, physical and chemical characteristics of interferons has been established, including their classification, genetic structure, chemical composition and possible mechanisms of action. Interferons have been utilized in clinical studies with human and experimental animals against bacterial, mycotic, parasitic and viral infections. Success has been reported mainly when administered prophylactically against acute infections. Favorable results have been obtained, both prophylactic and therapeutically, in some chronic diseases and in those in which the microorganism has an intracellular phase during its life cycle. Moreover, a promising future has been suggested for the combined use of interferon with other antimicrobial drugs

Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): I. Utilization of cimetidine and cyclosporine A

Hemos utilizado cimetidina (CMT), ciclosporina a (CsA) e interleuquina 2 (IL-2) para caracterizar el efecto anticanceroso de un inmunomodular poliantigéncio (polyantigenic immunomodulator, PAI). PAI consiste de una mezcla inactivada de bacterias y virus de influenza, emulsificada en una preparación de aceite de maní-arlacel A-monoesterato de alumini. La actividad antitumoral fue evaluada utilizando el tumor ascítico de Ehrlich implantado en ratones Swiss-Webster (alogenéicos) o C57BL/6J (singenéicos). La actividad antitumoral de PAI aumentó con la CMT actuando sinergisticamente al reducir sustancialmente el crecimiento tumoral e incrementar el porciento de sobrevivencia de los ratones, mientras que la CsA suprimió esta actividad. PAI o sus componentes individuales indujeron blastogénesis en linfocitos de bazo de ratón C57BL/6J e interleuquina 2 aumentó considerablemente esa respuesta. Los resultados sugieren que PAI actúa a nivel de la inmunidad celular

Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): II. Involvement of NK cells and adoptive immunotherapy

La actividad de células naturales (natural Killer cells, NK) y la inmunoterapia adoptiva fueron utilizados para caracterizar el efecto antitumoral del inmunomodulador poliantigénic immunomodulator, PAI). PAI consiste de una mezcla inactivada de bacterias y virus de influenza, emulsificada de bacterias y virus de influenza, emulsificada en una preparación de aceite de maní - arlacel A-monoesterato de aluminio, la cual se ha demostrado previamente que posée actividad antitumoral enratones implantados con el tumor de ascites de Ehrlich. La administración de PAI, su componente de Ehrlich. La administración de PAI, su componente bacteriano o el viral injectados en ratones Swiss-Webster (alogenéicos) y C57BL/6J (singenéicos) aumentaron maracadamente la actividad in vitro de células NK del bazo, especialmente durante el período temprano post-inducción. Además, linfocitos alogenéicos o singenéicos sensitizados por PAI fueron efectivos en ser transferidos a ratones con tumor ascítico de Ehrlich reduciendo el crecimiento tumoral e incrementando la sobrevivencia. Estos resultados confirman nuestra previa sugerencia de que PAI actua a nivel de inmunidad celular. Por lo tanto substancias poliantigénicas complejas, tal como PAI, podrían utilizarse directamente solas, en combinación con otros inmunoadyuvantes o para sensitizar en una forma global células immunocompetentes para ser utilizadas en inmunoterapia adoptivas