Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system.

AIMS: Unavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need for optimization of formulations. The provisional Biopharmaceutics Classification System (BCS) can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical disease drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children). METHODS: Albendazole, benznidazole, ivermectin, nifurtimox, praziquantel and proguanil were selected from the 5th edition of the Model List of Essential Medicines for Children from the World Health Organization. Paediatric drug solubility classification was based on dose number calculation. Provisional permeability classification was based on log P comparison versus metoprolol log P value, assuming passive diffusion absorption mechanisms and no changes in passive membrane permeability between paediatric patients and adults. pBCS classes were estimated for each drug, according to different doses and volumes adapted for each age stage and were compared to the adult classification. RESULTS: All six drugs were classified into provisional pBCS in the three paediatric subpopulations. Three drugs maintained the same classification as for adults, ivermectin and benznidazole changed solubility class from low to high in neonates and proguanil changed from low to high solubility in all age stages. CONCLUSION: Provisional pBCS classification of these six drugs shows potential changes in the limiting factors in oral absorption in paediatrics, depending on age stage, compared to the adult population. This valuable information will aid the optimization of paediatric dosing and formulations and can identify bioinequivalence risks when comparing different formulations and paediatric populations.

Cryptosporidium SPP: en niños sanos menores de 10 años de la comuna 18 de Cali, Colombia / Cryptosporidium spp. in healthy children under 10 years of the Commune 18, Cali, Colombia

Introducción: El Cryptosporidium spp. (C. spp.) es uno de los principales agentes causales de diarrea enniños. En Colombia, hay pocos estudios de prevalencia en niños sanos. Objetivo: Determinar la prevalencia de C. spp. mediante ELISA en niños de Cali, Colombia. Materiales y métodos: Estudio descriptivo observacional de corte transversal en 107 niños sanos < 10 años, de la Comuna 18 de Cali, Colombia, quienes consultaron al Programa de Crecimiento y Desarrollo del Centro de Salud Lourdes. El análisis estadístico incluyó medidas de tendencia central, de dispersión y pruebas de asociación. Se incluyeron datos como edad, género, signos y síntomas, peso (P) y talla (T), y condiciones ambientales. Según las tablas de la NCHS fueron clasificados según grado de desnutrición (DNT). La identificación del C. spp., se realizó en materia fecal mediante la técnica de ELISA. Resultados: Fueron analizados 100 niños, 66% estrato 1, con edad = 4 años ± 2 meses, 50 niños, 30% en hacinamiento, 95% con agua potable, 85% con disposición de excretas, 52% con animales intradomiciliares, y 63% asisten a guardería o colegio. Ninguno de los niños C. spp. positivos, presentó síntomas. Tuvieron P = 16±6 kg y T = 97±18 cm, 40% con algún tipo de DNT. La prevalencia fue del 4% (IC 95% 0,1-7,89) sin diferencias significativas (p>0.05). Conclusiones: La prevalencia para C. spp. fue del 4% sin posibles asociaciones demográficas, ambientales o clínicas.

Introduction: Cryptosporidium spp. (C. spp.) is a major causative agents of diarrea in children. In Colombia, there are few prevalence studies in healthy children. Objective: To determine the prevalence ofC. spp. by ELISA in children of Cali, Colombia. Materials and methods: A cross-sectional observational in 107 healthy children < 10 years from the Commune 18 in Cali, Colombia, who consulted the Growth and Development Program of Centro de Salud Lourdes. Statistical analysis included measures of central tendency, dispersión and association tests. Data included age, gender,signs and symptoms, weight (W) and height (H), and environmental conditions. According to the NCHS tables were classified by degree of malnutrition (MNT). The identification of C. spp. was held in stool by ELISA. Results: 100 children were analyzed, 66% stratum 1, age = 4 years ± 2 months, 50 boys, 30% overcrowding, 95% with wáter, 85% with waste disposal, 52% with home animals, and 63% attend daycare or school. None of the children C. spp. positive had symptoms. The W were 16±6 kg and H were 97±18 cm, 40% were some form of MNT. The prevalence was 4% (95% CI 0.1 to 7,89) without significant differences (p>0.05). Conclusions: The prevalence of C. spp. was 4% without any demographic, environmental or clinics associations.

Biological agents as occupational hazards - selected issues.

There are two main groups of biological agents regarded as occupational hazards: allergenic and/or toxic agents forming bioaerosols, and agents causing zoonoses and other infectious diseases. Bioaerosols occurring in the agricultural work environments comprise: bacteria, fungi, high molecular polymers produced by bacteria (endotoxin) or by fungi (ß-glucans), low molecular secondary metabolites of fungi (mycotoxins, volatile organic compounds) and various particles of plant and animal origin. All these agents could be a cause of allergic and/or immunotoxic occupational diseases of respiratory organ (airways inflammation, rhinitis, toxic pneumonitis, hypersensitivity pneumonitis and asthma), conjunctivitis and dermatitis in exposed workers. Very important among zoonotic agents causing occupational diseases are those causing tick-borne diseases: Lyme borreliosis, anaplasmosis, babesiosis, bartonellosis. Agricultural workers in tropical zones are exposed to mosquito bites causing malaria, the most prevalent vector-borne disease in the world. The group of agents causing other, basically not vector-borne zoonoses, comprises those evoking emerging or re-emerging diseases of global concern, such as: hantaviral diseases, avian and swine influenza, Q fever, leptospiroses, staphylococcal diseases caused by the methicillin-resistant Staphylococcus aureus (MRSA) strains, and diseases caused by parasitic protozoa. Among other infectious, non-zoonotic agents, the greatest hazard for health care workers pose the blood-borne human hepatitis and immunodeficiency viruses (HBV, HCV, HIV). Of interest are also bacteria causing legionellosis in people occupationally exposed to droplet aerosols, mainly from warm water.

[Tick borne diseases]. / Durch Zecken übertragene Krankheiten.

It is known for many years that tick-borne diseases have worldwide a high economical impact on farming industry and veterinary medicine. But only in the last twenty years the importance of such diseases were notified in human medicine by the medical community and the public with emerging of the tick borne encephalitis virus and the description of Borrelia burgdorferi. It is often forgotten that many other infectious agents as bacteria, virus, Rickettsia or protozoa can be transmitted by ticks. Such diseases are rarely diagnosed in Europe either they are overlooked and misdiagnosed or they are connected with special professional activities. The development of new regions for tourism with different out door activities (adventure trips, trekking, hunting) leads to an exposure to different tick borne diseases, which are often misdiagnosed.

Survey for intestinal parasites in Belize, Central America.

A stool survey was carried out in 5 villages in the Toledo district of the Central American country of Belize. Eighty-two percent of a total population of 672 participated. The stools were examined by the formalin-ethyl-acetate concentration technique. Sixty-six percent of the population was found to have one or more intestinal parasites. The most common infection was hookworm (55%) followed by Ascaris lumbricoides (30%), Entamoeba coli (21%), Trichuris trichiura (19%), Giardia lamblia (12%), Iodamoeba beutschlii (9%), and Entamoeba histolytica/dispar (6%). Other parasites found were Entamoeba hartmani, Strongyloides stercoralis, Endolimax nana, Isospora belli, and Chilomastix mesnili. Children were more often infected than adults and more females had hookworm infections. Sixty percent of 111 households surveyed had dirt floors, 43% were without toilets, 35% of the houses were overcrowded, and 10% obtained drinking water from streams. Cross-tabulation and logistic regression analyses were used to identify risk and protective factors associated with parasitoses. The risk factors were: being in the Mayan Ketchi population group, and abtaining housework and drinking water from streams. Protective factors were: drinking treated water and the wearing of shoes.

Redefining AIDS: towards a modification of the current AIDS case definition.

AIDS is defined by the occurrence of an opportunistic infection or tumor considered indicative of advanced infection with human immunodeficiency virus (HIV). Even though recent modifications have improved the widely used AIDS case definition issued by the World Health Organization and the Centers for Disease Control and Prevention, the modified version has fallen short of generating a globally functional instrument for the surveillance of HIV-related infections. The clinical AIDS case definition should be as comprehensive as possible. In many countries, only the diagnosis of an AIDS-defining illness will grant the affected patient social benefits or access to medical care. An expanded AIDS case definition is also likely to improve surveillance of HIV-associated morbidity and mortality; increase the awareness of emerging infections; increase the number of clinical endpoints in clinical trials; and facilitate the introduction of diagnostic tests, screening programs, and preventive measures. Examples of opportunistic infections and tumors that could be considered in future modifications of the AIDS case definition are discussed in detail.

Epizootiology of protozoans in farmed salmonids at northern latitudes.

Protozoan ectoparasites were examined in a northern salmonid fish farm over a 10-year period, June 1984-May 1994, by the same researcher, with similar catching and sampling procedures throughout. Husbandry procedures remained constant during the study, e.g., fingerlings were kept in steel tanks and yearlings in both steel tanks and earth ponds. Ichthyobodo necator, Chilodonella hexasticha and Ichthyophthirius multifiliis infections were treated with formalin, salt and malachite green-formalin baths, respectively, whenever any parasites were found. Altogether 10,790 randomly sampled salmon (Salmo solar), sea trout (S. trutta m. trutta) and brown trout (S. trutta m. lacustris) were studied. Higher prevalences were found in yearlings than in fingerlings, except in I. necator infections, which were higher in fingerlings (e.g., 26% vs 6% in sea trout). C. hexasticha occurred less often and was found most commonly on brown trout fingerlings. Trichodina nigra occurred more often in salmon of both age groups and Riboscyphidia arctic in trout. The results show that the occurrence of protozoan parasites in a fish farm is predictable and is influenced by the fish species, the age group of the fish, the season and the tank type. Parasite burden increased up to 7 species per brown trout, e.g., when fish were studied from hatching until stocking at the age of 2 years.

Vacunas contra parasitosis humanas / Vaccines again human parasythosis

A pesar del notorio avance en el conocimiento de la respuesta inmunológica que se genera contra protozoarios y helmintos parásitos, así como en la clonación molecular de genes que codifican para las proteínas de esos organismos, las cuales resultan potencialmente protectoras, todavía no se ha logrado la producción de vacunas operacionales contra las enfermedades parasitarias humanas más importantes (leishmaniasis, enfermedad de Chagas, toxoplasmosis, filariasis, triquinelosis, esquistosomiasis y cisticercosis). De hecho, no existe una sola vacuna inocua y eficaz de uso corriente que permita la protección específica de los individuos que viven en zonas endémicas. Las vacunas contra parásitos constituyen una imperiosa necesidad de salud pública, ya que constituyen causas muy importantes de morbilidad en prácticamente todos los países en vías de desarrollo. La complejidad molecular y estructural de los parásitos y de su relación con el hospedero ha dificultado la producción de vacunas equivalentes a las que están en uso contra virus y bacterias. En este capítulo se revisan los avances que se han generado en el conocimiento de la inmunología de algunas parasitosis propias de los seres humanos -que por razones obvias se han analizado con mucho más detalle con el uso de modelos animales y en el desarrollo de varios tipos de vacunas, desde vivas hasta moleculares, que también han siodo evaluadas sólo en el nivel experimental. Por último, en este capítulo se incluye una sección que analiza por qué para algunas parasitosis ha sido (y probablemente será) muy difíicil el desarrollo de vacunas para su control, que sean eficaces y de uso común

Epidemiology and pathogenicity of Blastocystis hominis.

A prospective study was performed on a large outpatient population to evaluate the epidemiology and pathogenicity of Blastocystis hominis. Patients with stool specimens positive for B. hominis and negative for other bacterial and parasitic pathogens were sent a questionnaire and were requested to submit a follow-up specimen for ova-and-parasite examination. B. hominis was identified in 530 of 16,545 specimens (3.2%). There was a spectrum of clinical-pathological presentations in the 143 patients evaluated. An asymptomatic carrier state was seen in 19 patients. Fifteen patients had an illness consistent with acute self-limited B. hominis gastroenteritis, and 21 patients had chronic gastroenteritis associated with B. hominis. In the epidemiological evaluation of 130 patients, the most common symptoms were watery diarrhea, abdominal pain, and gas. We did not find a statistically significant association between the number of organisms present and the disease state. In summary, our results are consistent with a role for B. hominis in acute and chronic gastroenteritis; however, further detailed studies are necessary to determine whether that role is one of association or causation.

Manual de infecciones parasitarias / Parasitic infection manual

Los autores han realizado este manual con referencia especial a la práctica pediatrica, sobre las infecciones parasitarias más comunes enel país y que sean de utilidad al estudiante de medicina