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Biomedical subjects

J P Cegielski

Publications and source records attributed to J P Cegielski.

At least 19 recordsLinked to original sources

Capacity building for international tuberculosis control through operations research training.

SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the national, provincial, and even district levels have the basic analytical and epidemiological skills necessary for collecting and analyzing quality data pertaining to national TB control program (NTP) improvements. This includes setting program priorities, operations planning, and implementing and evaluating program activities. OBJECTIVES: To present a model course for building capacity in basic epidemiology and operations research (OR). DESIGN: A combination of didactic lectures and applied field exercises were used to achieve the main objectives of the 6-day OR course. These were to increase the understanding of quantitative and qualitative research concepts, study design, and analytic methods, and to increase awareness of how these methods apply to the epidemiology and control of TB; and to demonstrate the potential uses of OR in answering practical questions on NTP effectiveness. As a final outcome, course participants develop OR proposals that are funded and later implemented. RESULTS: Since 1997, this OR course has been conducted nine times in five countries; 149 key NTP and laboratory staff have been trained in OR methods, and 44 OR protocols have been completed or are underway. CONCLUSION: This low-cost model course can be adapted to a wide range of public health issues.

Health Priorities↗

Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis.

SETTING: Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist. OBJECTIVE: To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy. DESIGN: Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement. RESULTS: Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs. CONCLUSION: Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.

Cohort Studies↗

Population-based risk factors for tuberculosis and adverse outcomes among Tibetan refugees in India, 1994-1996.

SETTING: Tibetan refugees in India, 1994-1996. OBJECTIVE: To determine tuberculosis (TB) incidence, independent risk factors for TB, and predictors of adverse outcomes. DESIGN: Data from a house-to-house census/demographic survey were merged with TB patient data. Separate multivariable models for each birthplace were developed for outcomes of interest. RESULTS: From 1994 to 1996, 47,491 Tibetans were surveyed and 1197 TB cases confirmed (incidence 835/ 100,000). Risk factors for TB in separate multivariable models differed by place of birth. Independent predictors of death for Tibet-born refugees included age >50 years, extra-pulmonary TB, and second-line therapy, while for India-born refugees they included second-line therapy and no improvement at the end of treatment. No significant risk factors for default were identified for Tibet-born refugees, while region of residence and the absence of a BCG scar were independent predictors among those born in India. Predictors of receipt of second-line therapy among Tibet-born refugees included region, years in camps, and prior TB, while among those born in India they were region, age > or =20 years, sputum-positive at diagnosis, and previous TB. CONCLUSIONS: TB incidence in Tibetan refugee settlements exceeds the highest national TB rates, and country of birth determines risk factors. TB control efforts in India should include this population.

Adult↗

The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals.

The oral traditions of medicine and public health have it that malnutrition is an important risk factor for the development of tuberculosis (TB). Malnutrition profoundly affects cell-mediated immunity (CMI), and CMI is the principle host defense against TB. It makes biological sense. Although most health professionals readily accept this principle, much of this belief is based on uncontrolled observations such as disaster situations or on backwards logic from the cachexia common among TB patients. In fact, the evidence in humans is surprisingly thin from the perspective of scientific rigor. And few data, if any, quantify the extent of the relative or attributable risk of TB due to malnutrition. Moreover, until recently, data from experimental animals were based on animal models that were largely not relevant to human TB infection and disease. This article reviews the scientific data supporting the contention that malnutrition is an important risk factor for TB concentrating on observations in humans and on experimental animal studies based on a highly relevant animal model. If it is true, malnutrition may account for a greater population attributable risk of TB than HIV infection, and certainly a much more correctable one.

Animals↗

HIV-1 incidence among opiate users in northern Thailand.

The incidence of human immunodeficiency virus type 1 (HIV-1) infection among opiate users was determined in a retrospective cohort of 436 patients with multiple admissions to the only inpatient drug treatment program in northern Thailand between October 1993 and September 1995. During 323.4 person-years of follow-up, 60 patients presenting for detoxification acquired HIV-1 infection, for a crude incidence rate of 18.6 per 100 person-years (95% confidence interval 14.4-23.9). All seroconverters were male. HIV-1 incidence varied by the current route of drug administration: 31.3 per 100 person-years for injectors and 2.8 per 100 person-years for noninjectors (smoking and ingestion). Significant differences were found by ethnicity: HIV-1 incidence was 29.3 per 100 person-years for Thai lowlanders and 8.5 per 100 person-years for hill tribes. Multivariate relative risk estimates showed that injecting opiates (vs. use by other routes), being unmarried, being under age 40 years, being a Thai lowlander, having a primary and secondary education, and being employed in the business sector were each independently associated with human immunodeficiency virus seroconversion. This HIV-1 incidence rate is double that reported for Bangkok and suggests that prevention and control programs for drug users need to be expanded throughout Thailand. Improved availability of more-effective treatment regimens and increased access to sterile injection equipment are needed to confront the HIV-1 epidemic among opiate users in northern Thailand.

Adult↗

Cryptosporidium, enterocytozoon, and cyclospora infections in pediatric and adult patients with diarrhea in Tanzania.

Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously.

Acute Disease↗

Evidence from molecular fingerprinting of limited spread of drug-resistant tuberculosis in Texas.

To determine the contribution of recent transmission to spread of drug-resistant tuberculosis in Texas, we performed IS6110-based and pTBN12-based restriction fragment length polymorphism (RFLP) analyses on Mycobacterium tuberculosis isolates. Isolates collected from 201 patients in Texas between 1992 and 1994 were studied. The distribution of cases was strikingly focal. All cases were reported from 35 of the 254 counties in Texas, and 74% (148 of 201) were reported from only 9 counties. One hundred sixty-one (80%) of the patients had M. tuberculosis isolates with unique RFLP patterns, and 41 (20%) patients were in 20 clusters, each comprising 2 to 3 patients. The largest number of cases of drug-resistant tuberculosis were reported in counties bordering Mexico, but the percentage of clustered cases was highest in northeast Texas and in counties that included the cities of Dallas, Fort Worth, and Houston. Compared to nonclustered patients, clustered patients were more likely to be African American and to have been born in the United States. Clustered patients were significantly more likely to be from the same geographic area, and clustered patients from the same geographic area were more likely to have isolates with identical drug susceptibility patterns, suggesting that they were linked by recent transmission. In 11 of 20 clusters, clustered patients were from geographically separate regions, and most isolates did not have identical drug susceptibility patterns, suggesting that tuberculosis was contracted from a common source in the remote past. Based on the low percentage of clustered cases and the small cluster size, we conclude that there is no evidence for the extensive transmission of drug-resistant tuberculosis in Texas.

Adolescent↗

A tuberculosis hotline in Tyler: a Texas resource for primary health care providers for the control of infectious diseases.

The Center for Pulmonary and Infectious Disease Control (CPIDC), located on the campus of The University of Texas Health Center in Tyler, manages a toll-free infectious disease consultation hotline advertised to public and private physicians and to health care agencies throughout the state. From January 1994 through December 1996, as part of a statewide initiative to curb an unprecedented increase in the incidence of tuberculosis observed since 1985, a concentrated effort was made to solicit health care providers for consultation requests that involved the diagnosis and management of tuberculosis, in particular, drug-resistant varieties. During that period, 3447 calls were made to the CPIDC by 1682 physicians and nurses. While most of the calls originated from 4 major urban areas plus health care facilities along the border, calls were received from more than half of all the counties in Texas. The value of providing an infectious disease consultation service, readily available, without charge, to all members of the health care community is discussed.

Communicable Disease Control↗

Gender differences in early suspicion of tuberculosis in hospitalized, high-risk patients during 4 epidemic years, 1987 to 1990.

OBJECTIVES: To assess the degree to which, from 1987 to 1990, physicians suspected tuberculosis (TB) in the first 2 hospital days in human immunodeficiency virus (HIV)-infected patients with pulmonary disease. DESIGN: Retrospective cohort study. SETTING: 96 hospitals in five US cities. PATIENTS: 2,174 adult patients with acquired immunodeficiency syndrome discharged with a diagnosis of Pneumocystis carinii pneumonia from 1987 to 1990. The diagnosis generally was not known on admission. RESULTS: Physicians suspected TB in the first 2 hospital days in 66% of these patients in 1987, a rate that increased steadily to 74% in 1990. However, the extent to which physicians considered TB among female patients decreased from 76% to 71% over the 4 years. Controlling for confounding variables by multiple logistic regression, the odds that TB would be suspected early increased 1.8-fold among men (odds ratio [OR], 1.8; 95% confidence interval [CI95], 1.4-2.4), but not in women (OR, 0.6; CI95, 0.2-1.9). Among the five cities, the odds of early suspicion of TB increased most in New York City (OR, 3.9; CI95, 2.0-7.9). CONCLUSIONS: Physicians considered TB in a timely manner in an increasing majority of male, but not female, high-risk patients during the first years of TB resurgence in the United States. Physicians must be aware of the changing epidemiology of HIV and TB, as well as their practice patterns, to prevent nosocomial transmission of this disease.

Acquired Immunodeficiency Syndrome↗

TB or not TB? Increasing door-to-door response to screening.

Tuberculosis (TB) has made a disconcerting come-back in the United States in recent years. In 1994, Texas ranked third nationally in total number of TB cases and fifth in annual TB case rates. This is of great concern to the Texas Department of Health (TDH) and has led to the development of TB Innovative Demonstration Projects under the Tuberculosis Elimination Division of the TDH. One such project involves identifying high-risk communities by utilizing a computer-based geographic information system and then sending field-workers door-to-door offering free skin testing. Because this project was so successful in identifying positive skin test reactors, numerous requests have been made to duplicate its methods. One area of improvement is to increase individual and family participation. The purpose of this article is to present a survey of the literature on nonresponse in door-to-door soliciting, analyze the project's methods of soliciting and nonresponse, and propose ways nonresponse can be decreased in future projects of this nature.

Attitude to Health↗

Comparison of PCR, culture, and histopathology for diagnosis of tuberculous pericarditis.

Nucleic acid amplification techniques for the diagnosis of tuberculosis (TB) are rapidly being developed. Scant work, however, has focused on pericardial TB. Using cryopreserved specimens from a prior study of pericarditis, we compared PCR to culture and histopathology for the diagnosis of tuberculous pericarditis in 36 specimens of pericardial fluid and 19 specimens of pericardial tissue from 20 patients. Fluid and tissue were cultured on Lowenstein-Jensen and Middlebrook solid media and in BACTEC radiometric broth. Tissue specimens were stained with hematoxylin-eosin, Ziehl-Neelsen, auramine O, and Kinyoun stains and were examined for granuloma formation and acid-fast bacilli. PCR was performed with both fluid and tissue with IS6110-based primers specific for the Mycobacterium tuberculosis complex by published methods. Sixteen of the 20 patients had tuberculous pericarditis and 4 patients had other diagnoses. TB was correctly diagnosed by culture in 15 (93%) patients, by PCR in 13 (81%) patients, and by histology in 13 of 15 (87%) patients. PCR gave one false-positive result for a patient with Staphylococcus aureus pericarditis. Considering the individual specimens as the unit of analysis, M. tuberculosis was identified by culture in 30 of 43 specimens (70%) from patients with tuberculous pericarditis and by PCR in 14 of 28 specimens (50%) from patients with tuberculous pericarditis (P > 0.15). The sensitivity of PCR was higher with tissue specimens (12 of 15; 80%) than with fluid specimens (2 of 13; 15%; P = 0.002). In conclusion, the overall accuracy of PCR approached the results of conventional methods, although PCR was much faster. Therefore, PCR merits further development in this regard. The sensitivity of PCR with pericardial fluid was poor, and false-positive results with PCR remain a concern.

Adolescent↗

Delayed-type hypersensitivity testing in Tanzanian adults with HIV infection.

Delayed-type hypersensitivity (DTH) testing and total lymphocyte counts as measures of cell-mediated immune function were assessed for medical patients in Dar es Salaam, Tanzania. DTH testing was performed with the Multitest CMI device which simultaneously administers seven antigens. Of 201 patients completing DTH testing, 90 were HIV seropositive. Anergy occurred more frequently among HIV-seropositive patients (39 of 90) as compared with HIV-seronegative patients (17 of 111). DTH skin test reactivity, measured by anergy, the number of positive antigens, and the combined DTH response induration, was significantly related to the clinical stage of HIV disease. Median total lymphocyte counts were significantly lower in HIV-seropositive patients than in HIV-seronegative patients (1,130 vs. 1,680 lymphocytes x 10(6)/L). Total lymphocyte counts decreased with increasing severity of HIV disease. In multivariable analysis, the number of positive antigens in DTH testing and lymphopenia significantly predicted HIV infection. The findings suggest that DTH testing and total lymphocyte counts may be useful, inexpensive tests of immune function in African patients with HIV disease.

Adult↗

Pulmonary complications of HIV infection in Dar es Salaam, Tanzania. Role of bronchoscopy and bronchoalveolar lavage.

To determine the pulmonary complications in HIV-1-infected patients in Dar es Salaam, Tanzania, and to evaluate the diagnostic utility of bronchoscopy and bronchoalveolar lavage, we carried out a prospective study of 237 patients with acute respiratory disease who were hospitalized at Muhimbili Medical Center (MMC). Diagnoses were made using well-defined criteria. Of the total, 127 (54%) were HIV-1-seropositive and 110 (46%) were seronegative. Tuberculosis was the most common diagnosis occurring in 95 (75%) HIV-1-seropositive and 87 (79%) seronegative patients. Bacterial pneumonia was the next most common diagnosis occurring in 18 (14%) HIV-1-seropositive and 17 (15%) seronegative patients. Pneumocystis carinii pneumonia was diagnosed in one and Kaposi's sarcoma was seen in only two HIV-1-seropositive patients. Bronchoscopy with bronchoalveolar lavage was the sole source of a diagnosis in nine (8%) seropositive and six (5%) seronegative patients. We conclude that the HIV seroprevalence rate among patients hospitalized for acute respiratory disease at MMC is extremely high. Tuberculosis was the most common cause of pulmonary disease, regardless of HIV serostatus, and other HIV-associated opportunistic pulmonary infections were unusual. Bronchoscopy with bronchoalveolar lavage added little to the diagnosis and thus should not be high-priority procedures for the routine workup in resource-poor areas where tuberculosis is endemic.

AIDS-Related Opportunistic Infections↗

Diagnosis and screening of HIV/AIDS using clinical criteria in Tanzanian adults.

The clinical utility of the World Health Organization (WHO) clinical case definition (CCD) of acquired immune deficiency syndrome (AIDS) in Africa, several proposed modifications of the WHO CCD, and two proposed screening algorithms for human immunodeficiency virus (HIV) infection were examined in adult medical inpatients in Dar es Salaam, Tanzania. Sensitivity, specificity, and positive and negative predictive values were determined for the CCDs and screening algorithms. Multivariable analysis identified factors with high accuracy for HIV infection. Of 223 patients enrolled in the study, 95 were seropositive for HIV infection. The WHO CCD and the modified CCDs had low sensitivities (14.7-32.6%) but high specificities (95.3-99.2%) and positive predictive values (83.8-94.7%). The screening algorithms had moderate sensitivities (66.3-77.9%) and poor specificities (46.1-79.7%). Multivariable analysis consistently identified oral candidiasis and lymphadenopathy as the best predictors of HIV infection. Although patients with asymptomatic or early HIV infection may be missed by clinical criteria, in a high prevalence population, AIDS may be diagnosed accurately clinically because of the effect of prevalence on the positive predictive values of the CCDs. Furthermore, selection of patients for HIV serologic testing may be guided by simple combinations of clinical features.

Acquired Immunodeficiency Syndrome↗

Tuberculous pericarditis in Tanzanian patients with and without HIV infection.

SETTING: Large academic medical center in Tanzania. OBJECTIVES: To determine the etiologies and outcomes of large pericardial effusions in HIV-infected and uninfected patients. DESIGN: Prospective cohort study of patients admitted with new large pericardial effusions, confirmed echocardiographically. Patients had pericardial biopsies and drainage with extensive analysis of tissue and fluid specimens, and were followed with clinical and echocardiographic examinations. RESULTS: Of 28 patients with large pericardial effusions, 19 were infected with HIV-1. 22 had invasive diagnostic procedures: 14 of 14 HIV-infected patients, but only 4 of 8 non-HIV-infected patients, had tuberculous pericarditis (P = 0.01). All but 1 of the HIV-infected patients had strongly positive tuberculin skin tests, and short-term outcomes were similar in the 2 groups. CONCLUSION: TB is the predominant cause of large pericardial effusion in HIV-infected patients in this setting; non-HIV-infected patients are more likely to have other etiologies. These patients were at an early stage of HIV infection and responded well to treatment. In settings where microbiological studies are not routinely available, HIV-infected patients with large pericardial effusions may be treated empirically for tuberculosis and monitored for improvement. If improvement does not follow within 2-4 weeks further studies are indicated. HIV-negative patients should undergo diagnostic evaluation initially.

Adolescent↗