Nathan M. Thielman

Practice Guidelines for the Management of Infectious Diarrhea

The widening array of recognized enteric pathogens and the increasing demand for cost-containment sharpen the need for careful clinical and public health guidelines based on the best evidence currently available. Adequate fluid and electrolyte replacement and maintenance are key to managing diarrheal illnesses. Thorough clinical and epidemiological evaluation must define the severity and type of illness (e.g., febrile, hemorrhagic, nosocomial, persistent, or inflammatory), exposures (e.g., travel, ingestion of raw or undercooked meat, seafood, or milk products, contacts who are ill, day care or institutional exposure, recent antibiotic use), and whether the patient is immunocompromised, in order to direct the performance of selective diagnostic cultures, toxin testing, parasite studies, and the administration of antimicrobial therapy (the latter as for travelers diarrhea, shigellosis, and possibly Campylobacter jejuni enteritis). Increasing numbers of isolates resistant to antimicrobial agents and the risk of worsened illness (such as hemolytic uremic syndrome with Shiga toxin-producing Escherichia coli O157:H7) further complicate antimicrobial and antimotility drug use. Thus, prevention by avoidance of undercooked meat or seafood, avoidance of unpasteurized milk or soft cheese, and selected use of available typhoid vaccines for travelers to areas where typhoid is endemic are key to the control of infectious diarrhea.

Exploring Lack of Trust in Care Providers and the Government as a Barrier to Health Service Use

OBJECTIVES We examined associations between trust of health care providers and the government and health service use and outcomes. METHODS Interviews with a sample of 611 HIV-positive individuals included an attitudinal assessment measuring beliefs concerning the creation of AIDS, information being withheld about the disease, and trust of care providers. RESULTS Trust in care providers was associated with increased HIV-related out-patient clinic visits, fewer emergency room visits, increased use of antiretroviral medications, and improved reported physical and mental health. Trusting the government was associated with fewer emergency room visits and better mental and physical health. More than one quarter of the respondents believed that the government created AIDS to kill minorities, and more than half believed that a significant amount of information about AIDS is withheld from the public. Ten percent did not trust their provider to give them the best care possible. CONCLUSIONS Distrust may be a barrier to service use and therefore to optimal health. Distrust is not isolated in minority communities but also exists among members of nonminority communities and equally interferes with their use of services and health outcomes.

How trauma, recent stressful events, and PTSD affect functional health status and health utilization in HIV-infected patients in the south

Objective: In addition to biological markers of human immunodeficiency virus (HIV) disease progression, physical functioning, and utilization of health care may also be important indicators of health status in HIV-infected patients. There is insufficient understanding of the psychosocial predictors of health-related physical functioning and use of health services among those with this chronic disease. Therefore, the current study examines how trauma, severe stressful events, posttraumatic stress disorder (PTSD), and depressive symptoms are related to physical functioning and health utilization in HIV-infected men and women living in rural areas of the South. Methods: We consecutively sampled patients from 8 rural HIV clinics in 5 southern states, obtaining 611 completed interviews. Results: We found that patients with more lifetime trauma, stressful events, and PTSD symptoms reported more bodily pain, and poorer physical, role, and cognitive functioning. Trauma, recent stressful events, and PTSD explained from 12% to 27% of the variance in health-related functioning, over and above that explained by demographic variables. In addition, patients with more trauma, including sexual and physical abuse, and PTSD symptoms were at greater risk for having bed disability, an overnight hospitalization, an emergency room visit, and four or more HIV outpatient clinic visits in the previous 9 months. Patients with a history of abuse had about twice the risk of spending 5 or more days in bed, having an overnight hospital stay, and visiting the emergency room, compared with those without abuse. The effects of trauma and stress were not explained by CD4 lymphocyte count or HIV viral load; however, these effects appear to be largely accounted for by increases in current PTSD symptoms. Conclusion: These findings highlight the importance of addressing past trauma, stress, and current PTSD within clinical HIV care. PTSD = posttraumatic stress disorder; HIV = human immunodeficiency virus; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; OR = odds ratio; CI = confidence interval; SD = standard deviation.

Predictors of Incomplete Adherence, Virologic Failure, and Antiviral Drug Resistance among HIV-Infected Adults Receiving Antiretroviral Therapy in Tanzania

BACKGROUND Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence, virologic failure, and antiviral drug resistance is essential to achieving long-term success. METHODS A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment, and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level >400 copies/mL; for patients with an HIV RNA level >1000 copies/mL, genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. RESULTS A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR], 19.8; P<.01) and the proportion of months receiving self-funded treatment (AOR, 23.5; P=.04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR, 3.6; P=.03) and the proportion of months receiving self-funded antiretroviral therapy (AOR, 13.0; P=.02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR, 0.10; P=.04). CONCLUSIONS Self-funded treatment was associated with incomplete adherence and virologic failure, and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure.

A Comparison of the Wellbeing of Orphans and Abandoned Children Ages 6–12 in Institutional and Community-Based Care Settings in 5 Less Wealthy Nations

Background Leaders are struggling to care for the estimated 143,000,000 orphans and millions more abandoned children worldwide. Global policy makers are advocating that institution-living orphans and abandoned children (OAC) be moved as quickly as possible to a residential family setting and that institutional care be used as a last resort. This analysis tests the hypothesis that institutional care for OAC aged 6–12 is associated with worse health and wellbeing than community residential care using conservative two-tail tests. Methodology The Positive Outcomes for Orphans (POFO) study employed two-stage random sampling survey methodology in 6 sites across 5 countries to identify 1,357 institution-living and 1,480 community-living OAC ages 6–12, 658 of whom were double-orphans or abandoned by both biological parents. Survey analytic techniques were used to compare cognitive functioning, emotion, behavior, physical health, and growth. Linear mixed-effects models were used to estimate the proportion of variability in child outcomes attributable to the study site, care setting, and child levels and institutional versus community care settings. Conservative analyses limited the community living children to double-orphans or abandoned children. Principal Findings Health, emotional and cognitive functioning, and physical growth were no worse for institution-living than community-living OAC, and generally better than for community-living OAC cared for by persons other than a biological parent. Differences between study sites explained 2–23% of the total variability in child outcomes, while differences between care settings within sites explained 8–21%. Differences among children within care settings explained 64–87%. After adjusting for sites, age, and gender, institution vs. community-living explained only 0.3–7% of the variability in child outcomes. Conclusion This study does not support the hypothesis that institutional care is systematically associated with poorer wellbeing than community care for OAC aged 6–12 in those countries facing the greatest OAC burden. Much greater variability among children within care settings was observed than among care settings type. Methodologically rigorous studies must be conducted in those countries facing the new OAC epidemic in order to understand which characteristics of care promote child wellbeing. Such characteristics may transcend the structural definitions of institutions or family homes.

Minorities, the poor, and survivors of abuse: HIV-infected patients in the US deep South

Background: The HIV/AIDS epidemic in the U.S. South is undergoing a marked shift toward a greater proportion of new HIV/AIDS cases in women, African-Americans, and through heterosexual transmission. Methods: Using consecutive sampling, 611 participants were interviewed from eight Infectious Diseases clinics in five southeastern states in 2001 to 2002. Results: Sixty four percent of participants were African-American, 31% were female, and 43% acquired HIV through heterosexual sex; 25% had private health insurance. Eighty-one percent were on antiretroviral therapy, and 46% had HIV RNA viral loads (VL) <400. Women and racial/ethnic minorities were less likely to be on antiretrovirals and to have VL <400. Probable psychiatric disorders (54%) and history of childhood sexual (30%) and physical abuse (21%) were common. Conclusions: Prevention and care systems need to address the HIV epidemic’s shift into poor, minority, and female populations. High levels of trauma and probable psychiatric disorders indicate a need to assess for and address these conditions in HIV clinical care.

Overload: impact of incident stressful events on antiretroviral medication adherence and virologic failure in a longitudinal, multisite human immunodeficiency virus cohort study.

Objective: To examine the influence of incident stressful experiences on antiretroviral medication adherence and treatment outcomes. Past trauma history predicts poorer medication adherence and health outcomes. Human immunodeficiency virus (HIV)-infected individuals experience frequently traumatic and stressful events, such as sexual and physical assault, housing instability, and major financial, employment, and legal difficulties. Methods: We measured prospectively incident stressful and traumatic events, medication adherence, and viral load over 27 months in an eight-site, five-state study. Using multivariable logistic and generalized estimating equation modeling, we assessed the impact of incident stressful events on 27-month changes in self-reported medication adherence and virologic failure (viral load = ≥400 c/mL). Results: Of 474 participants on antiretroviral therapy at baseline, 289 persons were interviewed and still received treatment at 27 months. Participants experiencing the median number of incident stressful events (n = 9) had over twice the predicted odds (odds ratio = 2.32) of antiretroviral medication nonadherence at follow-up compared with those with no events. Stressful events also predicted increased odds of virologic failure during follow-up (odds ratio = 1.09 per event). Conclusions: Incident stressful events are exceedingly common in the lives of HIV-infected individuals and negatively affect antiretroviral medication adherence and treatment outcomes. Interventions to address stress and trauma are needed to improve HIV outcomes. ARV = antiretroviral therapy; ASI = Addiction Severity Index; BSI = Brief Symptoms Inventory; CHASE = coping with HIV/AIDS in the Southeast; CI = Confidence Interval; OR = odds ratio; PLWHA = people living with HIV/AIDS; VL = viral load.

Prevalence of childhood sexual abuse and physical trauma in an HIV-positive sample from the deep south

We examined prevalence and predictors of trauma among HIV-infected persons in the Deep South using data from the Coping with HIV/AIDS in the Southeast (CHASE) study. Over 50% of CHASE participants were abused during their lives, with approximately 30% experiencing abuse before age 13, regardless of gender. Caregiver characteristics were associated with childhood abuse. Abuse is related to increases in high-HIV-risk activities. The findings help explain why people engage in such high-risk activities and can provide guidance in designing improved care and prevention messages.

Coping Strategies and Patterns of Alcohol and Drug Use among HIV-Infected Patients in the United States Southeast

Alcohol and drug use are common among HIV-infected patients and are important determinants of secondary transmission risk and medication adherence. As part of the Coping with HIV/AIDS in the Southeast (CHASE) Study, 611 HIV-infected patients were consecutively recruited from eight clinical care sites in five southeastern U.S. states in 2001-2002. We examined the distribution and predictors of alcohol and drug use in this sample with an emphasis on psychosocial predictors of use. In the prior 9 months, 27% of participants drank alcohol and 7% drank to intoxication at least weekly. The most common drugs used at least weekly were marijuana (12%) and crack (5%); 11% used a non-marijuana drug. 7% reported polysubstance use (use of multiple substances at one time) at least weekly. Injection drug use was rare (2% injected at least once in the past 9 months). There were few differences in alcohol and drug use across sociodemographic characteristics. Stronger adaptive coping strategies were the most consistent predictor of less frequent alcohol and drug use, in particular coping through action and coping through relying on religion. Stronger maladaptive coping strategies predicted greater frequency of drinking to intoxication but not other measures of alcohol and drug use. Those with more lifetime traumatic experiences also reported higher substance use. Interventions that teach adaptive coping strategies may be effective in reducing alcohol and substance use among HIV-positive persons.

AIDS-associated diarrhea and wasting in northeast Brazil is associated with subtherapeutic plasma levels of antiretroviral medications and with both bovine and human subtypes of Cryptosporidium parvum

Advanced HIV infection is frequently complicated by diarrhea, disruption of bowel structure and function, and malnutrition. Resulting malabsorption of or pharmacokinetic changes in antiretroviral agents might lead to subtherapeutic drug dosing and treatment failure in individual patients, and could require dose adjustment and/or dietary supplements during periods of diarrheal illness. We determined the plasma levels of antiretroviral medications in patients that had already been started on medication by their physicians, in an urban infectious diseases hospital in northeast Brazil. We also obtained blood samples from patients hospitalized for diarrhea or AIDS-associated wasting, and we found reduced stavudine and didanosine levels in comparison with outpatients without diarrhea or wasting who had been treated at the same hospital clinic. There was a predominance of the protozoal pathogens Cryptosporidium and Isospora belli, typical opportunistic pathogens of AIDS-infected humans, in the stool samples of inpatients with diarrhea. We conclude that severe diarrhea and wasting in this population is associated with both protozoal pathogens and subtherapeutic levels of antiretroviral medications.