Opportunistic infections and organ-specific diseases in HIV-1-infected children: a cohort study (1990-2006).

OBJECTIVES: Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. METHODS: An observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990-1996: no patients on HAART), CP2 (1997-1999: <60% on HAART) and CP3 (2000-2006: >60% on HAART). RESULTS: Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV-associated encephalopathy) were lower in CP2 and CP3 than in CP1. CONCLUSIONS: This study provides evidence of improved clinical outcomes in HIV-infected children over time and shows that mortality, AIDS, opportunistic infections and organ-specific diseases declined as HAART was progressively instituted in this population.

[HIV-1 genetic variability in non Spaniard infected children]. / Identificación de las diferentes variantes geneticas del VIH-1 en niños de procedencia no española.

INTRODUCTION: The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, because of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant's response remain undocumented. AIMS: To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. PATIENTS AND METHOD: Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. RESULTS: HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtype C in one (Equatorial Guinea) and CRF13_cpx in last one (India). DISCUSSION: Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient's clinical, immunological and virological evolution.

[Antiretroviral drug toxicity in human immunodeficiency virus infected children]. / Toxicidad de fármacos antirretrovirales en niños infectados por el virus de la inmunodeficiencia humana.

Paediatric Human Immunodeficiency Virus infection (HIV) nowadays is a chronic disease with an excellent long term prognosis, but lifelong combined antiretroviral treatment is required. However, an improved quality of life in this population is limited by adverse drug effects. The highest risk of treatment toxicity is developing a complete metabolic syndrome including: Hyperlipemia, lipodystrophy, insulin resistance, lactic acidosis, osteopenia, hypertension, and specific system and organ toxicity, such as the kidney, liver, CNS or bone marrow. The risk of cardiovascular disease adult life and also definitive bone mass damage are the most significant metabolic costs that have to paid for increased survival. Most of these toxicities were able to be adequately treated but, pharmacological interferences, patient intolerance and the high number of drugs are the problems that limit the adherence to treatment, which is essential for a good therapeutical efficacy. In this article, we present four HIV paediatric patients who presented with almost the whole range of metabolic toxicities, and a practical overview of therapeutical management.

[Exposure to multiresisant tuberculosis: study and follow-up of nine children]. / Exposición a tuberculosis multirresistente: estudio y seguimiento de nueve niños.

A world increase in multidrug-resistant tuberculosis (MDR-TB) has been reported over the last few years. A larger number of diagnoses are being seen in Spain, due to the increase of immigration from high endemic TB countries. Articles published on this are anecdotal in children, and there is no clear directives for treatment of MDR-TB, or latent tuberculosis infection (ITBL) or on prophylaxis after exposure to active pulmonary MDR-TB. We present the initial management and progression of nine children after close contact exposure to an Ecuadorian woman diagnosed with active pulmonary TB, resistant to Isoniazid, Rifampicin and Pyrazinamide.

Salvage therapy with abacavir and other reverse transcriptase inhibitors for human immunodeficiency-associated encephalopathy.

BACKGROUND: HIV-associated encephalopathy (HIV-AE) is a severe neurologic condition that affects HIV-infected children. The potential benefit of antiretroviral (ARV) agents with good cerebrospinal fluid (CSF) penetration remains to be defined. Abacavir (ABC) achieves good CSF concentrations and studies of high-dose ABC showed benefit in adults with HIV dementia. The present study evaluated the safety and virologic, immunologic and neuropsychological responses of an ARV regimen including high-dose ABC in children with HIV-AE. METHODS: Children between 3 months and 18 years old and abacavir-naive with HIV-AE and virologic failure were eligible. RESULTS: : Seventeen children (16 ARV-experienced) were enrolled and 14 children completed 48 weeks of therapy. The overall tolerability was good; 2 children had a possible hypersensitivity reaction. At week 48, 53% and 59% of the children achieved HIV RNA levels below the limit of quantitation in plasma and CSF, respectively. The median (25%-75% range) change of HIV RNA from baseline to week 48 was -2.29 (-0.81 to -2.47) log10 copies/mL in plasma and -0.94 (0 to -1.13) log10 copies/mL in CSF. The mean increases in CD4 (+/-standard error of mean) cell count and CD4% were 427 (+/-169) cells/mm and 8% (+/-2), respectively. Concentrations of soluble tumor necrosis factor receptor II were reduced in plasma and CSF. Children less than 6 years of age demonstrated significant neuropsychological improvement at week 48. CONCLUSIONS: In the present study with a limited number of children, highly active ARV therapy including high-dose ABC showed a safety profile similar to standard dose ABC and provided clinical, immunologic and virologic response in children with HIV-AE at week 48. Children less than 6 years of age also demonstrated significant neuropsychological improvement.

Viral phenotype, antiretroviral resistance and clinical evolution in human immunodeficiency virus-infected children.

BACKGROUND: The syncytium-inducing (SI) viral phenotype and the emergence of viral strains resistant to zidovudine have been described in persons infected with HIV, and in some cases they have been associated with poor prognosis. METHODS: HIV isolates obtained from 37 HIV-infected children were analyzed to determine whether the SI viral phenotype and the mutation on the 215 position of the reverse transcriptase (M215) could be used as markers of disease progression. We performed peripheral blood coculture mononuclear cells, and we analyzed the induction of syncytia using the MT-2 cell line. The emergence of mutations on the 215 position was determined by PCR. RESULTS: We found a statistically significant association (P < 0.05) between SI viral phenotype and (1) recurrent serious bacterial infections, (2) absolute CD4+ cell counts <2 SD, (3) progression to AIDS and (4) death. Sixty percent of the children treated with zidovudine developed 215 mutant viral strains without statistically significant association with clinical or immunologic findings. The SI viral phenotype was statistically associated with the presence of the 215 mutation (P < 0.05). CONCLUSIONS: SI viral phenotype is a marker associated with a poor clinical and immunologic progression of the disease and it may facilitate the emergence of mutant strains in children treated with zidovudine.

Internationally adopted children: what vaccines should they receive?

It is of paramount importance to know the vaccination status in internationally adopted children, so that they can be correctly immunized. This study ascertains the seroprotection rate for vaccine-preventable diseases and the validity of the immunization cards in 637 adopted children. The absence of the immunization card (13% of children) correlated with a poor global vaccine protection. Children with immunization records (87%) had a better global seroprotection but the information obtained from the card did not accurately predict seroprotection for each particular antigen. The best variable to predict the status of seroprotection was the country of origin. The highest rate of protection was found in children from Eastern Europe and, in descending order, India, Latin America, China and Africa. General recommendations for immunization of internationally adopted children are difficult to establish. Actions for vaccination have to be mainly implemented on the basis of the existence of the immunization card and of the country of origin.

[A case of chloroquine-resistant malaria of type R3 originating in Cameroon]. / A propos d'un cas de paludisme chloroquino-résistant de type R3 provenant du Cameroun.

World areas with chloroquine-resistant falciparum malaria are progressively spreading, in Africa from East to West. We are reporting here a new case of resistance, grade III, from Cameroon, carried out in vitro by the WHO standard macrotest. Resistance is determined by the ability of trophozoites to develop into schizonts when therapeutic doses of chloroquine have been administered.

[Malaria in childhood. Report of 26 cases]. / Paludismo en la edad pediátrica. Communicación de 26 casos.

It's known that there has been a resurgence of malaria in the world. Purpose of this article is to point out the increase in number of cases of imported malaria in children in Spain. Authors performed a clinical study and review up to date treatment and prophylaxis of the disease. They communicate cases of three children infected by Plasmodium falciparum resistant to chloroquine, proceeding from areas that up to one year ago were considered to be not resistant. Data published on prevention and selective primary health care of malaria in the world are revised.

[The halofantrine treatment of Plasmodium falciparum malaria. Clinical experience]. / Tratamiento con halofantrina del paludismo por el Plasmodium falciparum. Experiencia clínica.

UNLABELLED: The objective of this study was to evaluate the efficacy of halofantrine in the treatment of malaria caused by Plasmodium falciparum since the resistance of these plasmodium to chloroquine is increasing in countries of Western Africa. MATERIAL AND METHOD: Between January 1991 and June 1994 we studied 50 children from Equatorial Guinea. All of them were black and between the ages of 8 months and 13 years. They were treated with 3 doses of halofantrine (8 mg/kg every 6 hours). The definitive diagnosis was made by the demonstration of the parasites on thick and thin blood smears, stained by standard methods, repeated every 24-72 yours after therapy. We considered the disappearance of fever and the clearance of plasmodium from the red blood cells as signs of response to the treatment. We also monitored the tolerance and the adverse side effects of the drug. RESULTS: All of the patients responded favorably with the disappearance of the fever after 24 hours and after 72 hours no parasites were seen in red blood cells. Only one patient had a recurrence, which occurred on the 10th day. All patient satisfactorily tolerated the drug and only 3 children showed an increase of aminotransferases that was spontaneously cured. CONCLUSIONS: We conclude that halofantrine is a safe and efficient drug for the treatment of children diagnosed with malaria caused by Plasmodium falciparum.

[Human immunodeficiency virus infection in children. Clinical and immunological markers of disease progression]. / Infección por el virus de la inmunodeficiencia humana en niños. Marcadores clínicos e inmunológicos de progresión de la enfermedad.

OBJECTIVE: The aim of this study was to analyze the prognostic value of the clinical manifestations and of the lymphocyte CD4 count in a cohort of HIV infected children. PATIENTS AND METHODS: We performed a prospective study in 37 HIV infected children during a 6 year period. We studied the statistical association between mortality and clinical and immunological parameters according to Fisher's test (p < 0.05). We performed a survival analysis according to Kaplan-Meier curves (p < 0.05). RESULTS: We have found that a high risk of mortality is associated with recurrent and severe bacterial infections (p = 0.0001), failure to thrive (p = 0.0057), opportunistic infections (p = 0.0008) and AIDS (p < 0.0001). The survival analysis has shown a low probability of survival in HIV-encephalopathy (p = 0.000053) and high in one case of lymphocytic interstitial pneumonia (p = 0.07). An age-related CD4 count less than 2 SD was associated significantly with a bad prognosis (p = 0 .0017). CONCLUSIONS: The clinical manifestations and age-matched CD4 count continue being good surrogate markers for the indication of prophylaxis, antiretroviral treatment and as prognostic values of the disease in HIV infected children until new techniques, especially plasma viremia, can be widely available.

Filariosis en pacientes procedentes de área endémica. Presentación de una serie de 14 casos / Filarial infestation in patients emanating from endemic area. 14 cases series presentation

Introducción: Los flujos migratorios determinan la aparición de enfermedades emergentes. Una de éstas es la filariosis, de rara presentación en la edad pediátrica debido a su ciclo biológico. Se realiza una revisión de los casos de filariosis diagnosticados en los últimos años en una Unidad de Pediatría Tropical. Material y método: Estudio retrospectivo de 14 pacientes diagnosticados de filariosis entre 1995 y 2007 en el Servicio de Pediatría del Hospital Carlos III (Madrid). Se analizan diferentes variables y se atienden las características clínicas, epidemiológicas, terapéuticas y evolutivas. Resultados: Todos los pacientes del estudio procedían de Guinea Ecuatorial, con edades comprendidas entre 3 y 15 años. Las especies aisladas fueron 6 casos de Onchocerca volvulus, 8 casos de Mansonella perstans y 2 casos de Loa loa. Dos casos presentaron filariosis mixta. El prurito fue el síntoma guía en el 71% de los casos. En el 78% de los pacientes se observó eosinofilia y fue L. loa la especie con cifras más elevadas. El 85% de los pacientes presentaba coparasitación, y la intestinal fue la más frecuente. El diagnóstico se realizó mediante biopsia epidérmica, detección de microfilaremia, visualización directa y serología. Los fármacos utilizados han sido mebendazol para los casos de mansonellosis e ivermectina o dietilcarbamacina para el resto de las especies. En los 8 casos que pudieron seguirse evolutivamente se demostró curación. Conclusiones: Es obligatorio realizar cribado de filariosis en todo paciente procedente de área endémica, especialmente en aquellos que presenten eosinofilia. El diagnóstico en la edad pediátrica, aunque difícil, permite prevenir el desarrollo de la enfermedad, las complicaciones graves como la ceguera e interrumpir el ciclo vital del parásito (AU)

Introduction: The migration causes the emergence of new diseases in our environment. One of them is the filariosis which, due to the biologic cycle peculiarity, it’s weird its appearance in pediatrics. This studio accomplishes a review of all the filariosis cases diagnosed the last years in an Unit specialized in Tropical Pediatrics Diseases. Material and methods: Retrospective analysis comprising 14 patients than were diagnosed with filariosis from 1995 to 2007 in the Pediatrics Unit of Carlos III Hospital (Madrid). They have been analyzed several variables to cope with clinic-epidemiological, therapeutics and evolutional characteristics. Results: All patients in the study came from Equatorial Guinea, their ages were between 3 and 15 years old. The isolated species were: 6 cases with O. volvulus, 8 with M. perstans and 2 with Loa-loa. The pruritus was the main symptom in the 71% of the cases. The eosinophilia was detected in the 78% of the patients, and the Loa-loa was the specie with higher figures. The 85% of the patients showed co-parasitation, being the intestinal the most frecuent. The diagnostics was established by epidermic biopsy, microfilaremia detection, direct visualization and serology. The utilized drugs were: Mebendazole for the cases with M. perstans and Ivermectin or Dietylcarbamazine for the rest of the species. One child showed mixed filariosis. The cure was successful in the 8 cases that could be followed up (AU)

Identificación de las diferentes variantes geneticas del VIH-1 en niños de procedencia no española / HIV-1 genetic variability in non Spaniard infected children

Introducción: la prevalencia de las nuevas infecciones por subtipos distintos de B del VIH-1 y recombinantes entre subtipos del VIH-1 se está incrementando en Europa occidental. Esto se debe principalmente a los movimientos migratorios desde zonas donde estas variantes genéticas son endémicas. Existe una amplia base teórica sobre la probablemente peor respuesta inmunovirológica de los subtipos distintos de B del VIH-1, pero esto no se ha demostrado en la experiencia clínica. Objetivos: identificar las diferentes variantes genéticas del VIH-1 y su evolución clínica en una serie de niños infectados por VIH-1 de procedencia no española. Pacientes y método: estudio retrospectivo de las historias clínicas y caracterización del subtipo del VIH-1 en 12 pacientes infectados entre enero de 1988 y diciembre de 2006, menores de 18 años al diagnóstico y de procedencia no española. Resultados: se aisló un subtipo del VIH-1 distinto de B en 5 (42%) niños: el recombinante CRF2_AG se aisló en 3 casos (Guinea Ecuatorial), el subtipo C en 1 (Guinea Ecuatorial) y el recombinante CRF13_cpx en 1 (India). Discusión: debido al aumento creciente de la inmigración y de las adopciones internacionales, es previsible que asistamos a un incremento en el número de infecciones pediátricas por VIH-1 de subtipos distintos de B y recombinaciones del VIH-1. La caracterización del subtipo genético del VIH-1 debería realizarse dentro de la rutina clínica en niños infectados o expuestos al VIH-1 cuyo origen sea de áreas geográficas con alta prevalencia de subtipos distintos del B. Estudios con un mayor número de pacientes permitirían detectar, en caso de que las hubiera, diferencias en la evolución clínica, inmunológica y virológica (AU)

Introduction: The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, beause of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant’s response remain undocumented. Aims: To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. Patients and method: Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. Results: HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtyoe C in one (Equatorial Guinea) and CRF13_cpx in last one (India). Discussion: Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient’s clinical, immunological and virological evolution (AU)