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Jeffrey R Starke

Publications and source records attributed to Jeffrey R Starke.

13 recordsLinked to original sources
PubMed2005

Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease.

Relatively little is known about the human genetics of susceptibility to common diseases caused by bacterial pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. So far, genetic studies of tuberculosis susceptibility have largely been focused on adult patients despite the fact that tuberculosis is highly prevalent among children. To study the host genetic component of pediatric tuberculosis susceptibility, we enrolled 184 ethnically diverse families from the Greater Houston area with at least one child affected by pediatric tuberculosis disease. Using a family-based control design, we found allelic variants of the natural resistance-associated macrophage protein gene 1 (NRAMP1) (alias SLC11A1) significantly associated with tuberculosis disease in this pediatric patient population [P = 0.01; odds ratio = 1.75 (95% confidence interval, 1.10-2.77)]. The association of NRAMP1 with pediatric tuberculosis disease was significantly heterogeneous (P = 0.01) between simplex [P <0.0008; odds ratio = 3.13 (1.54-6.25)] and multiplex families (P = 1), suggesting an interplay between mechanisms of genetic control and exposure intensities. In striking contrast to previous studies in the adult population, we observed that the common alleles of NRAMP1 polymorphisms were risk factors for pediatric tuberculosis disease. To explain the different direction of allelic association between adult and pediatric disease, we hypothesize that NRAMP1 influences the speed of progression from infection to tuberculosis disease.

Adult↗
PubMed2005

Current concepts of childhood tuberculosis.

Tuberculosis (TB) is a social disease with medical implications. An estimated one-third of the world's population (2 billion people) is infected with the tubercle bacilli. In the year 2000 alone, an estimated 8.3 million new cases of TB occurred, of which 884,019 (10.7%) were in children. Of the total, 659,379 (75%) occurred in 22 high-burden countries, most of which were resource-poor. Despite a growing body of literature demonstrating the substantial impact made by addressing childhood TB, current guidelines are geared toward the treatment and control of TB in adults. This review focuses on TB disease among children younger than 15 years of age, the standard World Health Organization category for TB in children. The purpose of this work is to review the epidemiology, pathophysiology, and clinical presentation of childhood TB. The challenges of accurate surveillance, confirmation of diagnoses, and effective treatment of childhood TB in resource-poor settings are highlighted.

Adolescent↗
PubMed2005

Epidemiology of pediatric tuberculosis using traditional and molecular techniques: Houston, Texas.

OBJECTIVE: To investigate the transmission dynamics of pediatric tuberculosis (TB) by analyzing the clinical characteristics with the molecular profiles of Mycobacterium tuberculosis isolates during a 5-year period. METHODS: A retrospective review of a prospective population-based active surveillance and molecular epidemiology project was conducted in private and public pediatric clinics within Houston and Harris County, Texas. The study population consisted of patients who had pediatric TB diagnosed from October 1, 1995, through September 30, 2000. Cases and potential source cases (PSC) were interviewed using a standardized questionnaire. Available Mycobacterium tuberculosis isolates from cases and PSCs were characterized and compared by IS6110 restriction fragment length polymorphism, spoligotyping, and genetic group assignment. Clinical characteristics were described, and molecular characterizations were compared. Data were analyzed by using EpiInfo 6.02b and SAS 8.2. RESULTS: A total of 220 (92%) of 238 pediatric TB cases were included. Epidemiologic and clinical findings were consistent with previous studies. Molecular profiles from 3 cases did not match the profile of PSC. Four previously unknown PSCs were identified using molecular techniques. Fifty-one (71.8%) of 71 isolates matched at least 1 other Houston Tuberculosis Initiative TB database isolate and were grouped into 33 molecular clusters. Cases were more likely to be clustered when the patients were younger than 5 years, identified a source case, or were US born. CONCLUSIONS: Traditional contact tracing may not always be accurate, and molecular characterization can lead to identification of previously unrecognized source cases. Recent transmission plays a significant role in the transmission of TB to children as evident by the high degree of clustering found in our study population.

Adolescent↗
PubMed2004

Tuberculosis in children.

The natural history and clinical expression of infection due to Mycobacterium tuberculosis differ substantially in children compared with adults. The natural history depends upon the age at infection and the host immune status. Children infected prior to age 4 have a very high rate of developing immediate clinical or radiographic manifestations or both, but are unlikely to develop reactivation disease in adulthood. In contrast, children infected in preadolescence or adolescence are more prone to developing more severe adult-type pulmonary tuberculosis soon after infection or in adulthood. It is difficult to confirm the diagnosis of tuberculosis by current microbiological methods. Even in industrialized countries, the triad of a positive tuberculin skin test, radiographic and/or clinical manifestations consistent with tuberculosis, and establishing a recent link to a known infectious case of tuberculosis is the "gold standard" for diagnosis. Children with tuberculosis respond well to and tolerate the same basic treatment regimens as used for adults. Some prevention of childhood tuberculosis can be achieved by the use of the bacille Calmette-Guérin (BCG) vaccines, but the use of chemotherapy to treat recent tuberculosis infection, discovered via contact tracing, is of paramount importance even when BCG vaccines are used.

Journal Article↗
PubMed2002

Tuberculosis among adult visitors of children with suspected tuberculosis and employees at a children's hospital.

OBJECTIVE: Few children with tuberculosis (TB) have communicable disease, and most do not require isolation within the hospital. However, parents or adult visitors with unrecognized pulmonary TB may be a threat to hospital staff and other patients. We prospectively evaluated adults accompanying children hospitalized for suspected TB at a children's hospital to determine the frequency of undiagnosed, potentially contagious disease. METHODS: From 1992 to 1998, chest radiographs were obtained from adult caretakers accompanying 59 consecutive children admitted to Texas Children's Hospital with suspected TB. A child and his or her family were placed under Airborne Precautions only if the child or the accompanying adult exhibited characteristics of potentially contagious disease. Annual rates of tuberculin skin test conversion in hospital employees were obtained for the same period. RESULTS: Of the 105 screened adults, 16 (15%) had previously undetected pulmonary TB. These adults were associated with 14 (24%) of the 59 children. In all instances in which the adult was the patient's parent, he or she was the source of infection to the child. Only 8 (13.5%) of the 59 children required isolation. Tuberculin skin test conversion from a negative to a positive reaction occurred in 127 employees (8 per 1,000 employee-years at risk). Only 4 of these 127 employees performed activities involving direct patient contact. None was in contact with families with a known potentially contagious adult or pediatric patient. CONCLUSIONS: The risk of infection of healthcare workers from pediatric patients with primary TB appeared to be minimal, and most children with TB did not need isolation. Infection control efforts should be focused on accompanying adults and adult visitors.

Adolescent↗
PubMed2002

Treatment of childhood tuberculosis with a six month directly observed regimen of only two weeks of daily therapy.

BACKGROUND: Recommended treatment of childhood tuberculosis is 6 months in duration with at least 3 drugs. We studied a regimen requiring as few as 58 doses, given entirely by directly observed therapy (DOT), under program conditions. METHODS: An observational trial was conducted to determine the effectiveness of a completely DOT 6-month regimen for pulmonary, pleural and lymph node tuberculosis in children with the use of 2 weeks of daily isoniazid, rifampin and pyrazinamide therapy; then 6 weeks of twice weekly isoniazid, rifampin and pyrazinamide therapy; followed by 16 weeks of twice weekly isoniazid and rifampin. All therapy was given by workers from the health department, and patients were followed by the Children's Tuberculosis Clinic in Houston, TX. Patients were evaluated for changes in symptoms, weight, clinical or radiographic findings and adherence to therapy. RESULTS: Of the 175 evaluable children (159 pulmonary/thoracic node, 4 pleural, 12 cervical lymph node), 81% of children completed treatment in 6 months. Of the 33 patients who received extended treatment, 3 did so because of physician choice, 17 had an inadequate response to initial therapy, 2 had significant adverse reactions to drugs and 16 had poor adherence to the DOT. Only 37% of patients had complete resolution of disease at the end of treatment, but all continued to improve after therapy was stopped. There was only 1 patient who relapsed after 4 years. CONCLUSION: This regimen had results comparable with those of 6-month regimens with longer durations of daily therapy. Determining treatment response in pediatric tuberculosis is difficult because of the slow resolution of chest radiograph abnormalities. DOT is an important aspect of treatment but does not solve all problems with treatment adherence.

Adolescent↗
PubMed2002

Population pharmacokinetic modeling of pyrazinamide in children and adults with tuberculosis.

STUDY OBJECTIVE: To determine population pharmacokinetic parameters of pyrazinamide after multiple oral doses given to children and adults with tuberculosis. DESIGN: Prospective, multiple-dose population pharmacokinetic study. SETTING: Five hospitals in the United States. PATIENTS: Sixty-seven adults and 23 children with active tuberculosis. INTERVENTION: The 90 patients received multiple oral doses of pyrazinamide as part of their treatment, based on the best clinical judgment of the attending physicians and in keeping with standard clinical practices at each institution. The patients also received other antituberculosis drugs empirically or based on in vitro susceptibility data. MEASUREMENTS AND MAIN RESULTS: Serum samples were collected over 12 hours after dosing and were assayed with a validated gas chromatography assay with mass selective detection. Concentration-time data were analyzed by using population methods. Pyrazinamide concentrations increased linearly with increasing oral doses (185-3550 mg). Median maximum serum concentration values were 41.0 microg/ml with daily dosing and 66.1 microg/ml with larger, twice-weekly dosing. Incomplete (18%) or delayed (30%) absorption was more common in children than in adults (1% for each). Pharmacokinetic parameters of pyrazinamide were independent of human immunodeficiency virus status and patient demographics, except for body weight. Population elimination half-life values in pediatric and adult patients were 3.5 and 6.0 hours, respectively. Median volume of distribution (L/kg) was 32% larger in children, and median clearance (L/hr/kg) was 106% larger in children, with a resultant median half-life 43% shorter in children. CONCLUSION: Pyrazinamide concentrations and most pharmacokinetic parameters were comparable to those previously published. Apparent half-life was somewhat shorter than that in previous reports. Compared with adults, absorption of pyrazinamide in children appeared more likely to be incomplete or delayed.

Adult↗