Regulation of T cell function by complement C5A in mice during mycobacterial infection

Tuberculosis is the leading cause of death in the world due to a single infectious agent, making it critical to investigate all aspects of the immune response mounted against the causative agent, Mycobacterium tuberculosis , in order to better treat and prevent disease. Previous observations show a disparity in the ability to control mycobacterial growth between mouse strains sufficient in C5, such as C57BL/6 and B10.D2/nSnJ, and those naturally deficient in C5, such as A/J and B10.D2/nSnJ, with C5 deficient mice being more susceptible. It has been shown that during M. tuberculosis infection, C5 deficient macrophages have a defect in production of interleukin (IL)-12, a cytokine involved in the cyclical activation between infected macrophages and effector T cells. T cells stimulated by IL-12 produce interferon (IFN)-γ, the signature cytokine of T helper type 1 (Th1) cells. It is known that a cell-mediated Th1 response is crucial for control of M. tuberculosis in the lungs of humans and mice. This study demonstrates that murine T cells express detectable levels of CD88, a receptor for C5a (C5aR), following antigen presentation by macrophages infected with mycobacteria. T cells from C5 deficient mice infected with M. tuberculosis were found to secrete less IFN-γ and had a reduced Th1 phenotype associated with fewer cells expressing the transcription factor, T-box expressed in T cells (T-bet). The altered Th1 phenotype in M. tuberculosis infected C5 deficient mice coincided with a rise in IL-4 and IL-10 secretion from Th2 cells and inducible regulatory T cells, respectively. It was found that the ineffective T cell response to mycobacteria in C5 deficient mice was due indirectly to a lack of C5a via poor priming by infected macrophages and possibly by a direct interaction between T cells and C5a peptide. Therefore, these studies show a link between the cells of the innate and adaptive arms of the immune system, macrophages and T cells respectively, that was mediated by C5a using a mouse model of M. tuberculosis infection. ^

The relationship between oral contraceptives and pelvic inflammatory disease: Policy implications and recommendations

One of the most widely accepted noncontraceptive benefits of oral contraceptive use is the reduction in the development of pelvic inflammatory disease (PID) and its sequelae in users. While much of the research over the past forty years has found an association between oral contraceptive use and reduced rates of PID [Senanayake, 1980], more recent studies have qualified and even challenged this widely held belief. [Henry-Suchet, 1997; Ness 1997; Ness, 2001] PID, an infection in the upper genital tract causing infertility and ectopic pregnancy, affects over one million women in the United States each year, exacting an enormous toll on women's reproductive and emotional health, as well as our economy. [CDC Factsheet, 2007] This thesis examines the public health implications of pelvic inflammatory disease and the use of oral contraceptives. Sixteen original studies are reviewed and analyzed, thirteen of which found a protective benefit with oral contraceptive use against PID and three more recent studies which found no protective benefit or association between oral contraceptive use and PID. Analysis of the research findings suggests a need for additional research, provider and patient education, and an increased government role in addressing the ongoing and significant public health concerns raised by current rates of Chlamydia- and gonorrheal-PID. ^

Health education intervention to reduce risk of infectious disease transmission among community health workers and their clients

Indigent and congregate-living populations have high susceptibilities for disease and pose a higher risk for disease transmission to family, friends and to persons providing services to these populations. The adoption of basic infection control, personal hygiene, safe food handling and simple engineering practices will reduce the risk of infectious disease transmission to, from and among indigent and congregate-living populations. ^ The provision of social services, health promotion activities and other support services to indigent and congregate-living populations is an important aspect of many public health-related governmental, community-based and other medical care provider agencies. ^ In the interest of protecting the health of indigent and congregate-living populations, of personnel from organizations providing services to these populations and of the general community, an educational intervention is warranted to prevent the spread of blood-borne, air-borne, food-borne and close contact-borne infectious diseases. ^ An educational presentation was provided to staff from a community-based organization specializing in providing housing, health education, foodstuffs and meals and support services to disabled, low-income, homeless and HIV-infected individuals. The educational presentation delivered general best practices and standard guidelines. A pre and post test were administered to determine and measure knowledge pertinent to controlling the spread of infectious diseases between and among homeless shelter-living clients and between clients and the organization's staff. ^ Comparing pre-test and post-test results revealed areas of knowledge currently held by staff and other areas that staff would benefit from additional educational seminars and training. ^

Evidence of secondary dengue infection and potential for association with clinical depression in a subset of a randomly selected cohort in South Texas

Globally, dengue is an emerging disease resulting in an estimated 50 million new cases and 22, 000 deaths each year. Anecdotally, depression has been reported as a possible sequelae of dengue virus infection. To test the association, we performed a cross-sectional analysis in a selected sub-set of participants from the Cameron County Hispanic Cohort (CCHC) in South Texas. All study subjects in the analysis had Center for Epidemiological Studies Depression scale (CES-D) scores and were tested for dengue antibodies using stored plasma. We found that 5.0% of participants tested either positive or equivocal for anti-dengue IgG antibodies using the capture antibody test, which detects acute secondary infections. Logistic regression identified that evidence of acute secondary dengue infection was not associated with depression (Odds Ratio [OR] = 0.97, 95%Confidence Interval [CI] 0.47-1.98); however, both being female (OR = 1.53, 95%CI 1.09-2.15) and obese body mass index (BMI > 30) (OR = 1.84, 95%CI 1.19-2.84) were associated with depression. ^

Host risk factors for rifamycin-resistant clostridium difficile infection: A case control study

Objective. To evaluate the host risk factors associated with rifamycin-resistant Clostridium difficile (C. diff) infection in hospitalized patients compared to rifamycin-susceptible C.diff infection.^ Background. C. diff is the most common definable cause of nosocomial diarrhea affecting elderly hospitalized patients taking antibiotics for prolonged durations. The epidemiology of Clostridium difficile associated disease is now changing with the reports of a new hypervirulent strain causing hospital outbreaks. This new strain is associated with increased disease severity and mortality. The conventional therapy for C. diff includes metronidazole and vancomycin but high recurrence rates and treatment failures are now becoming a major concern. Rifamycin antibiotics are being developed as a new therapeutic option to treat C. diff infection after their efficacy was established in a few in vivo and in vitro studies. There are some recent studies that report an association between the hypervirulent strain and emerging rifamycin resistance. These findings assess the need for clinical studies to better understand the efficacy of rifamycin drugs against C. diff.^ Methods. This is a hospital-based, matched case-control study using de-identified data drawn from two prospective cohort studies involving C. diff patients at St Luke's Hospital. The C. diff isolates from these patients are screened for rifamycin resistance using agar dilution methods for minimum inhibitory concentrations (MIC) as part of Dr Zhi-Dong Jiang's study. Twenty-four rifamycin-rifamycin resistant C. diff cases were identified and matched with one rifamycin susceptible C. diff control on the basis of ± 10 years of age and hospitalization 30 days before or after the case. De-identified data for the 48 subjects was obtained from Dr Kevin Garey's clinical study at St Luke's Hospital enrolling C. diff patients. It was reviewed to gather information about host risk factors, outcome variables and relevant clinical characteristic.^ Results. Medical diagnosis at the time of admission (p = 0.0281) and history of chemotherapy (p = 0.022) were identified as a significant risk factor while hospital stay ranging from 1 week to 1 month and artificial feeding were identified as an important outcome variable (p = 0.072 and p = 0.081 respectively). Horn's Index assessing the severity of underlying illness and duration of antibiotics for cases and controls showed no significant difference.^ Conclusion. The study was a small project designed to identify host risk factors and understand the clinical implications of rifamycin-resistance. The study was underpowered and a larger sample size is needed to validate the results.^

Risk factors for encephalitis and death from West Nile virus infection: An analysis of hospitalized cases in Houston, Texas from 2002--2008

We conducted a nested case-control study to determine the significant risk factors for developing encephalitis from West Nile virus (WNV) infection. The purpose of this research project was to expand the previously published Houston study of 2002–2004 patients to include data on Houston patients from four additional years (2005–2008) to determine if there were any differences in risk factors shown to be associated with developing the more severe outcomes of WNV infection, encephalitis and death, by having this larger sample size. A re-analysis of the risk factors for encephalitis and death was conducted on all of the patients from 2002–2008 and was the focus of this proposed research. This analysis allowed for the determination to be made that there are differences in the outcome in the risk factors for encephalitis and death with an increased sample size. Retrospective medical chart reviews were completed for the 265 confirmed WNV hospitalized patients; 153 patients had encephalitis (WNE), 112 had either viral syndrome with fever (WNF) or meningitis (WNM); a total of 22 patients died. Univariate logistic regression analyses on demographic, comorbidities, and social risk factors was conducted in a similar manner as in the previously conducted study to determine the risk factors for developing encephalitis from WNV. A multivariate model was developed by using model building strategies for the multivariate logistic regression analysis. The hypothesis of this study was that there would be additional risk factors shown to be significant with the increase in sample size of the dataset. This analysis with a greater sample size and increased power supports the hypothesis in that there were additional risk factors shown to be statistically associated with the more severe outcomes of WNV infection (WNE or death). Based on univariate logistic regression results, these data showed that even though age of 20–44 years was statistically significant as a protecting effect for developing WNE in the original study, the expanded sample lacked significance. This study showed a significant WNE risk factor to be chronic alcohol abuse, when it was not significant in the original analysis. Other WNE risk factors identified in this analysis that showed to be significant but were not significant in the original analysis were cancer not in remission > 5 years, history of stroke, and chronic renal disease. When comparing the two analyses with death as an outcome, two risk factors that were shown to be significant in the original analysis but not in the expanded dataset analysis were diabetes mellitus and immunosuppression. Three risk factors shown to be significant in this expanded analysis but were not significant in the original study were illicit drug use, heroin or opiate use, and injection drug use. However, with the multiple logistic regression models, the same independent risk factors for developing encephalitis of age and history of hypertension including drug induced hypertension were consistent in both studies.^

Identification and characterization of virulence determinants in the Lyme disease spirochete Borrelia burgdorferi

Borrelia burgdorferi is the etiological agent of Lyme disease, the most common tick-borne disease in the United States. Although the most frequently reported symptom is arthritis, patients can also experience severe cardiac, neurologic, and dermatologic abnormalities. The identification of virulence determinants in infectious B. burgdorferi strains has been limited by their slow growth rate, poor transformability, and general lack of genetic tools. The present study demonstrates the use of transposon mutagenesis for the identification of infectivity-related factors in infectious B. burgdorferi, examines the potential role for chemotaxis in mammalian infection, and describes the development of a novel method for the analysis of recombination events at the Ids antigenic variation locus. A pool of Himar1 mutants was isolated using an infectious B. burgdorferi clone and the transposon vector pMarGent. Clones exhibiting reduced infectivity in mice possessed insertions in virulence determinants putatively involved in host survival and dissemination. These results demonstrated the feasibility of extensive transposon mutagenesis studies for the identification of additional infectivity-related factors. mcp-5 mutants were chosen for further study to determine the role of chemotaxis during infection. Animal studies indicated that mcp-5 mutants exhibited a reduced infectivity potential, and suggested a role for mcp-5 during the early stages of infection. An in vitro phenotype for an mcp-5 mutant was not detected. Genetic complementation of an mcp-5 mutant resulted in restoration of Mcp-5 expression in the complemented clone, as demonstrated by western blotting, but the organisms were not infectious in mice. We believe this result is a consequence of differences in expression between genes located on the linear chromosome and genes present on the circular plasmid used for trans-complementation. Overall, this work implicates mcp-5 as an important determinant of mammalian infectivity. Finally, the development of a computer-assisted method for the analysis of recombination events occurring at the B. burgdorferi vls antigenic variation locus has proven highly valuable for the detailed examination of vls gene conversion. The studies described here provide evidence for the importance of chemotaxis during infection in mice and demonstrate advances in both genetic and computational approaches for the further characterization of the Lyme disease spirochete. ^

Evaluation of the T-SPOT(RTM).TB test in the diagnosis of latent tuberculosis infection in HIV-infected children in Uganda

Background. About a third of the world’s population is infected with tuberculosis (TB) with sub-Saharan Africa being the worst hit. Uganda is ranked 16th among the countries with the biggest TB burden. The burden in children however has not been determined. The burden of TB has been worsened by the advent of HIV and TB is the leading cause of mortality in HIV infected individuals. Development of TB disease can be prevented if TB is diagnosed during its latent stage and treated with isoniazid. For over a century, latent TB infection (LTBI) was diagnosed using the Tuberculin Skin Test (TST). New interferon gamma release assays (IGRA) have been approved by FDA for the diagnosis of LTBI and adult studies have shown that IGRAs are superior to the TST but there have been few studies in children especially in areas of high TB and HIV endemicity. ^ Objective. The objective of this study was to examine whether the IGRAs had a role in LTBI diagnosis in HIV infected children in Uganda. ^ Methods. Three hundred and eighty one (381) children were recruited at the Baylor College of Medicine-Bristol Meyers Squibb Children’s Clinical Center of Excellence at Mulago Hospital, Kampala, Uganda between March and August 2010. All the children were subjected to a TST and T-SPOT ®.TB test which was the IGRA chosen for this study. Sputum examination and chest x-rays were also done to rule out active TB. ^ Results. There was no statistically significant difference between the tests. The agreement between the two assays was 95.9% and the kappa statistic was 0.7 (95% CI: 0.55–0.85, p-value<0.05) indicating a substantial or good agreement. The TST was associated with older age and higher weight for age z-scores but the T-SPOT®. TB was not. Both tests were associated with history of taking anti-retroviral therapy (ART). ^ Conclusion. Before promoting use of IGRAs in children living in HIV/TB endemic countries, more research needs to be done. ^

A movement from traditional malarial chemoprophylaxis to the use of intermittent preventive treatment as a method of protection for children diagnosed with sickle-cell disease: A proposal for consideration based on a systematic review of the literature

Approximately 200,000 African children are born with sickle-cell anemia each year. Research has shown that individuals with hemoglobin disorders, particularly sickle-cell anemia, have increased susceptibility to contracting malaria. Currently it is recommended that patients diagnosed with sickle-cell anemia undergo malaria chemoprophylaxis in order to decrease their chances of malarial infection. However, studies have shown that routine administration of these drugs increases the risk of drug resistance and could possibly impair the development of naturally acquired immunity. Clinical trials have shown intermittent preventive treatment (IPT) to be an effective method of protection against malaria. The objective of this report was to review previously conducted clinical trials that study the effects of intermittent preventive treatment on malaria and anemia in infants and children. Based on the review, implications for its appropriateness as a protective measure against malaria for infants and children diagnosed with sickle-cell disease were provided.^ The 18 studies reviewed were randomized controlled trials that focused on IPT’s effect on malaria (7 studies), anemia (1 study), or both (8 studies). In addition to these 16, one study looks at IPT’s effect on molecular resistance to malaria, and another study is a follow-up to a study in order to review IPT’s potential to cause a rebound effect. The 18 th study in this review specifically looks at IPT’s protective efficacy in children with SCA. The studies in this report were restricted to randomized controlled trials that have been performed from 2000 to 2010. Reports on anemia were included to illustrate possible added benefits of the use of IPT specific to burdens associated with SCA other than malaria susceptibility. The outcomes of these studies address several issues of concern involving the administration of IPT: protective efficacy (in reference to age, seasonal versus perennial malaria regions, and overall effectiveness against malaria and anemia), drug resistance, drug rebound effect, drug side-effects, and long-term effects. Overall, these showed that IPT has a significant level of protective efficacy against malaria and/or anemia in children. More specifically, the IPT study evaluating children diagnosed with sickle-cell anemia proved IPT to be a more effective method of protection than traditional chemoprophylaxis. ^

Respiratory syncytial virus infection in hematopoietic stem cell transplant patients

Respiratory Syncytial Virus (RSV) is a major cause of respiratory tract infections in immunocompromised patients such as children less than 2 years, premature infants with congenital heart disease and chronic lung disease, elderly patients and patients who have undergone hematopoietic stem cell transplant (HSCT). HSCT patients are at high risk of RSV infection, at increased risk of developing pneumonia, and RSV-related mortality. Immunodeficiency can be a major risk factor for severe infection & mortality. Therapy of RSV infection with Ribavirin, Palivizumab and Immunoglobulin has shown to reduce the risk of progression to LRI and mortality, especially if initiated early in the disease. Data on RSV infection in HSCT patients is limited, especially at various levels of immunodeficiency. 323 RSV infections in HSCT patients have been identified between 1/1995 and 8/2009 at University of Texas M D Anderson Cancer Center (UTMDACC). In this proposed study, we attempted to analyze a de-identified database of these cases and describe the epidemiologic characteristics of RSV infection in HSCT patients, the course of the infection, rate of development of pneumonia and RSV-related mortality in HSCT patients at UTMDACC.^ Key words: RSV infections, HSCT patients ^

Impact of maternal Tdap vaccination on pertussis infection in young infants

Undiagnosed infected mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention (CDC) recommends Tdap vaccine for post-partum women before hospital discharge. This intervention has been implemented at Ben Taub General Hospital (BTGH) in Houston, TX since January 2008. Our objective was to compare the proportion of infants born at BTGH and developing pertussis to the total number of pertussis cases before and after the intervention. Methods. We conducted a cross-sectional comparative study between the pre-intervention (7/2000 to 12/2007) and post-intervention (1/2008 to 5/2009) periods. Information on pertussis diagnosis was determined using ICD-9 codes, infection control records, and molecular microbiology reports from Texas Children's Hospital (TCH) and BTGH. Only patients ≤ 6 months of age with laboratory-confirmed B. pertussis infection were included in the study. Results. 481 infants had pertussis illness; 353 (73.3%) during pre-intervention and 128 (26.6%) during post-intervention years. The groups were comparable in all measures including age (median 73 vs. 62.5 days; p=0.08), gender (males 54.2%; p=0.47), length of hospitalization (median 9.8 vs. 4 9.5 days; p=0.5), outcomes (2 deaths in each period; p=0.28) and pertussis illness at TCH (95.2% vs. 95.3%; p=0.9). The proportion of pertussis patients born at BTGH, and thus amenable to protection by the intervention, was not statically different between the two periods after adjusting for age, gender and ethnicity (7.3% vs. 9.3%; an OR=1.05, 95% CI 0.5-2.1, p=0.88). Conclusions. Vaccinating only mothers with Tdap in the post-partum period does not reduce the proportion of pertussis in infants age ≤ 6 months. Efforts should be directed at Tdap immunization of not only mothers, but also all household and key contacts of newborns to protect them against pertussis illness before the primary DTaP series is completed.^

The relationship between enterotoxigenic {\it Escherichia coli\/} infection and environmental risk factors in Bilbeis, Egypt, 1981--1983

Diarrheal disease associated with enterotoxigenic Escherichia coli (ETEC) infection is one of the major public health problems in many developing countries, especially in infants and young children. Because tests suitable for field laboratories have been developed only relatively recently, the literature on the environmental risk factors associated with ETEC is not as complete as for many other pathogens or for diarrhea of unspecified etiology.^ Data from a diarrheal disease surveillance project in rural Egypt in which stool samples were tested for a variety of pathogens, and in which an environmental questionnaire was completed for the same study households, provided an opportunity to test for an association between ETEC and various risk factors present in those households. ETEC laboratory-positive specimens were compared with ETEC laboratory-negative specimens for both symptomatic and asymptomatic children less than three years of age at the individual and household level using a case-comparison design.^ Individual children more likely to have LT infection were those who lived in HHs that had cooked food stored for subsequent consumption at the time of the visit, where caretakers used water but not soap to clean an infant after a diarrheal stool, and that had an indoor, private water source. LT was more common in HHs where the caretaker did not clean an infant with soap after a diarrheal stool, and where a sleeping infant was not covered with a net. At both the individual and HH level, LT was significantly associated with good water supply in terms of quantity and storage.^ ST was isolated more frequently at the individual level where a sleeping infant was covered with a net, where large animals were kept in or around the house, where water was always available and was not potable, and where the water container was not covered. At the HH level, the absence of a toilet or latrine and the indiscriminate disposal of animal waste decreased risk. Using animal feces for fertilizer, the presence of large animals, and poor water quality were associated with ST at both the individual and HH level.^ These findings are mostly consistent with those of other studies, and/or are biologically plausible, with the obvious exception of those from this study where poorer water supplies are associated with less infection, at least in the case of LT. More direct observation of how animal ownership and feces disposal relates to different types of water supply and usage might clarify mechanisms through which some ETEC infection could be prevented in similar settings. ^

Sickle cell disease: Its signs, symptoms and varied manifestations

Seventy-five sickle cell patients, age 3-36 years from Houston, Texas, participated in the research study to investigate sickle cell manifestations, conducted between November 1989 and August 1990. All the participants were blacks. There were 35 females and 39 males among the participants in this research study. One of the participants did not document the gender.^ The sickle cell history questionnaire was administered to the participants. Data collected from this study were statistically analyzed using frequencies, percentages, crosstabulations and chi-squares.^ Regular source of health care influences the time of diagnosis of sickle cell disease. Early diagnosis of sickle cell disease with proper care and management will reduce the morbidity and mortality rate of the disease.^ Fevers, bacterial infection, pneumoniae, anemiae, pains, ulcers and cardiovascular problems are common causes of hospitalizations. The average length of stay in the hospital on admission were higher among the sickle cell patients than their family members who themselves did not have sickle cell disease. ^

Is family medicine meeting the HIV/AIDS challenge? A national survey of family physicians' beliefs, clinical competence, and experience regarding HIV disease

A national sample of family physicians was surveyed to (1) assess family physicians' beliefs about the human immunodeficiency virus (HIV) and individuals at risk for infection, their clinical competence regarding HIV-related issues, and their experiences with HIV disease; (2) present conclusions to the American Academy of Family Physicians (AAFP) to effect the development of an early clinical care protocol and a continuing medical education curriculum; and (3) collect base-line data for use in the evaluation of an early clinical care protocol and a continuing medical education curriculum, in the case that such programs are developed and disseminated. After considering retired or deceased respondents, of the 2,660 physicians surveyed, 1,678 (63.7%) responded. The resulting sample was representative of the active members of the AAFP. About 77% of the respondents were unable to accurately identify the universal precautions for blood and body fluids to prevent occupational transmission of HIV or hepatitis B virus (HBV). Residency trained and board certified physicians expressed fewer "external constraints," such as fear of losing patients, obviating them from providing treatment to individuals with HIV disease (p =.004 and p $<$.001, respectively). These physicians also manifested fewer "internal constraints" to the provision of HIV treatment, such as fear of becoming infected (p $<$.001 and p =.012, respectively). Residency trained physicians also expressed a greater comfort with discussing sexually-related topics with their patients than did non-residency trained physicians (p $<$.001). There were 67.1% of the physicians surveyed who reported never providing treatment to an individual with HIV disease. Residency trained and board certified physicians expressed a greater likelihood to provide treatment to HIV-infected patients (p $<$.001) than non-residency trained and non-board certified physicians.^ Among the various primary care specialties, family medicine is especially vulnerable to the current challenges of HIV/AIDS. These challenges are augmented by the epidemiologic pattern that characterizes AIDS. For the past several years, we have seen AIDS in this country assume a similar pattern to that seen in most other countries; HIV is becoming increasingly prevalent in the heterosexual population as well as in locations removed from metropolitan centers. This current phase of the epidemic generates greater pressures upon primary care physicians, particularly family physicians, to become better acquainted with the means to provide early care to HIV/AIDS patients and to prevent HIV/AIDS among their patients. Family medicine is especially appropriate for providing care to HIV patients because family medicine involves treatment to all age groups and conditions; other primary care specialties focus on limited patient populations or specific conditions. Family physicians should be armed with the expertise to confront HIV/AIDS. However, family physicians' clinical competence and experience with HIV is not known. The data collected in this survey describes their competencies, attitudes, and experiences. ^

Role of {\it Mycobacterium avium-intracellulare\/} complex infection in AIDS mortality

Disseminated MAC (dMAC) is the third most prevalent opportunistic infection in AIDS patients. In order to understand the role MAC infection plays in affecting survival of AIDS patients, a cohort of 203 suspected dMAC veterans seen at the Houston Veterans Affairs Medical Center between August 14, 1987 and December 31, 1991 were analyzed. The criteria for suspected dMAC infection was HIV+ men having a CD4+ level $\le$200 cells/mm$\sp3,$ on zidovudine treatment $\ge$1 month and who had any of the following: (a) a confirmed respiratory MAC infection, (b) fever $\ge$101$\sp\circ\rm F$ for $\ge$48 hours, (c) unexplained weight loss of 10 lbs or $\ge$10% BW over 3 months or (d) Hgb $\le$7.5 g/dl or decrease in Hgb $\ge$3.0 g/dl, while on 500-600 mg/day AZT. The study was conducted before the commencement of an effective MAC anti-mycobacterial therapy, so the true course of MAC infection was seen without the confounder of a therapeutic regimen. Kaplan-Meier and Cox regression survival analysis was used to compare 45 MAC culture positive and 118 MAC culture negative veterans. The 1 year survival rate of veterans with documented dMAC infection was 0.37 compared to 0.50 for veterans not acquiring dMAC infection. Significant differences between subgroups were also seen with the variables: PCP prophylaxis, the AIDS indicator disease Candida esophagitis, CD4+ lymphocyte level, CD4 percent lymphocyte level, WBC level, Hgb and Hct levels. Using multivariate modeling, it was determined that PCP prophylaxis (RR = 6.12, CI 2.24-16.68) was a predictor of survival and both CD4% lymphocytes $\le$6.0% (RR = 0.33, CI 0.17-0.68) and WBC level $\le$3000 cells/mm$\sp3$ (RR = 0.60, CI 0.39-0.93) were predictors of mortality. CD4+ level $\le$50 cells/mm$\sp3$ was not a significant predictor of mortality. Although MAC culture status was a significant predictor of mortality in the univariate model, a positive dMAC culture was not a significant predictor of AIDS mortality in the multivariate model. A positive dMAC culture, however, did affect mortality in a stratified analysis when baseline laboratory values were: CD8+ lymphocytes $>$600 cells/mm$\sp3,$ Hgb $>$11.0 g/dl, Hct $>$31.0% and WBC level $>$3000 cells/mm$\sp3.$ ^