Do Tanzanian hospitals need healthcare ethics committees? report on the 2014 dartmouth/penn research ethics training and program development for tanzania (DPRET) workshop

Ethical issues are common in the global community. The shortage of human and medical resources when working with vulnerable populations requires institutional support to address the challenges that often arise in the patient-provider relationship. The 2014 Dartmouth/Penn Research Ethics Training and Program Development for Tanzania (DPRET) workshop centred on discussions about research and clinical ethics issues unique to Tanzanian healthcare providers. This article discusses some of the ethical challenges that workshop participants reported in their day-to-day work life with patients and families, such as truth-telling, disagreements over treatment plans and patient distrust of local physicians and hospital staff, among others. The Tanzanian participants recognised the need for supportive mechanisms within their local hospital environments. Further dialogue and research on the development ofinstitutional ethics committees within hospital systems is critically needed so that healthcare providers can meet their ethical and professional obligations to patients and families and address ethical conflicts that arise in a timely and productive fashion

An audit of pharyngeal gonorrhoea treatment in a public sexual health clinic in Adelaide, South Australia.

In recent times there have been changes to guidelines regarding the management of gonorrhoea, from both the Centers for Disease Control and Prevention in 2010 and the British Association for Sexual Health and HIV (BASHH) in 2011. Coinciding with their release we conducted a clinical audit of our treatment protocol for gonorrhoea. In 2010, local data on the minimum inhibitory concentrations for Neisseria gonorrhoeae indicated an increase in local isolates that were less sensitive to ceftriaxone (11.6% c.f. 5.3% in 2009). We have a long history of using 250 mg of ceftriaxone to treat all standard sites of gonorrhoea infection followed with tests of cure in all cases. In a retrospective clinical audit of an 11-year period from 2000 up to and including 2010 we identified six test-of-cure failures over 11 years after treating a total of 215 patients with pharyngeal gonorrhoea.

Mycoplasma genitalium: prevalence in men presenting with urethritis to a South Australian public sexual health clinic.

BACKGROUND/AIM: This study aimed to determine the prevalence of Mycoplasma genitalium infection among male patients with dysuria and/or urethral discharge. An analysis of the clinical, demographic and microbiological factors associated with M. genitalium infection was also conducted. METHOD: From May 2007 to June 2011, men presenting to the clinic with self-reported symptoms of dysuria and/or urethral discharge were identified and underwent urethral swab, which was microscopically assessed for objective non-gonococcal urethritis. A first-void urine sample was tested for Chlamydia trachomatis and Neisseria gonorrhoeae using the Aptima Combo-2 assay. A portion of the urine sample was sent for polymerase chain reaction analysis for M. genitalium. RESULTS: One thousand, one hundred and eighty-two men with dysuria and/or urethral discharge were tested for M. genitalium. Of those, 96 men (8.1%) were positive for M. genitalium. Men identifying as solely MSM (men who have sex with men) constituted 16.3% (n = 193) of the sample. Their infection rate was 3.1% (n = 6). The infection rate for heterosexual and bisexual men was 9.1%. For all men, the M. genitalium co-infection rate was 14.6% (n = 14) with C. trachomatis and 3.1% (n = 3) with N. gonorrhoeae. Factors associated with M. genitalium infection were analysed by univariate analysis. We determined that five investigated predictors were significantly associated with M. genitalium infection, urethral discharge, non-gonococcal urethritis on Gram stain of urethral smears, identification as heterosexual or bisexual, and absence of co-infection with C. trachomatis or N. gonorrhoeae. CONCLUSION: In Adelaide, M. genitalium is an important sexually transmitted infection among men with dysuria and/or urethral discharge, and is primarily an infection of heterosexual and bisexual men.

Nutritional status of HIV-infected women with tuberculosis in Dar es Salaam, Tanzania.

SETTING: Tuberculosis (TB) treatment clinics in Dar es Salaam, Tanzania. OBJECTIVE: To quantify anthropometrics and intake of en-ergy and protein among human immunodeficiency virus (HIV) positive women with TB. DESIGN: HIV-positive women with newly diagnosed TB were assessed on their anthropometric characteristics and dietary intake. Energy and protein intake were determined using Tanzania food composition tables and compared with standard recommendations. Patients were re-evaluated after 4-6 months of anti-tuberculosis treatment. RESULTS: Among 43 women, the baseline median CD4 count was 209 cells/µl (range 8-721); 19 (44%) had a CD4 count of <200; 20 (47%) were on antiretroviral therapy. Body mass index was <18.5 kg/m(2) in 25 (58%); the median food insecurity score was 6. The median level of kcal/day was 1693 (range 1290-2633) compared to an estimated need of 2658; the median deficit was 875 kcal (range -65-1278). The median level of protein/day was 42 g (range 27-67) compared to 77 g estimated need; the median protein deficit was 35 g (range 10-50). The median weight gain among 29 patients after 4-6 months was 6 kg. CONCLUSION: HIV-positive women with TB have substantial 24-h deficits in energy and protein intake, report significant food insecurity and gain minimal weight on anti-tuberculosis treatment. Enhanced dietary education together with daily supplementation of 1000 kcal with 40 g protein may be required.

Completion of isoniazid preventive therapy and survival in HIV-infected, TST-positive adults in Tanzania.

SETTING: The World Health Organization recommends the use of isoniazid preventive therapy (IPT) for human immunodeficiency virus (HIV) infected patients with a positive tuberculin skin test (TST). However, due to concerns about the effectiveness of IPT in community health care settings and the development of drug resistance, these recommendations have not been widely implemented in countries where tuberculosis (TB) and HIV co-infection is common. OBJECTIVE: To evaluate the effectiveness of IPT on survival and TB incidence among HIV-infected patients in Tanzania. DESIGN: A cohort study nested within a randomized trial of HIV-infected adults with baseline CD4 counts of ≥ 200 cells/µ l was conducted to compare survival and incidence of active TB between TST-positive subjects who did or did not complete 6 months of IPT in the period 2001-2008. RESULTS: Of 558 TST-positive subjects in the analytic cohort, 488 completed 6 months of IPT and 70 did not. Completers had a decrease in mortality compared to non-completers (HR 0.4, 95%CI 0.2-0.8). However, the protective effect of IPT on the incidence of active TB was non-significant (HR 0.6, 95%CI 0.3-1.3). CONCLUSION: Completion of IPT is associated with increased survival in HIV-infected adults with CD4 counts ≥ 200 cells/µ l and a positive TST.

Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality.

BACKGROUND: Disseminated tuberculosis (TB) is a major cause of death in patients with the acquired immune-deficiency syndrome (AIDS), but its pathogenesis and clinical features have not been defined prospectively. METHODS: Human immunodeficiency virus (HIV) infected adults with a CD4 count ≥ 200 cells/µl and bacille Calmette-Guérin scar underwent immunologic evaluation and subsequent follow-up. RESULTS: Among 20 subjects who developed disseminated TB, baseline tuberculin skin tests were ≥15 mm in 14 (70%) and lymphocyte proliferative responses to Mycobacterium tuberculosis were positive in 14 (70%). At the time of diagnosis, fever ≥2 weeks plus ≥5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/µl (range 1-122). By insertion sequence (IS) 6110 analysis, 14 (70%) blood isolates were clustered and 3/8 (37%) concurrent sputum isolates represented a different strain (polyclonal disease). Empiric TB treatment was given to eight (40%) patients; 11 (55%) died within a month. CONCLUSIONS: Disseminated TB in HIV occurs with cellular immune responses indicating prior mycobacterial infection, and IS6110 analysis suggests an often lethal combination of reactivation and newly acquired infection. Control will require effective prevention of both remotely and recently acquired infection, and wider use of empiric therapy in patients with advanced AIDS and prolonged fever.

Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register.

OBJECTIVE: In the general population, folic acid supplementation during pregnancy has been demonstrated to reduce the frequency of neural tube defects (NTDs) and other major congenital malformations (MCMs). It is recommended that women with epilepsy contemplating pregnancy take supplemental folic acid because of the known antifolate effect of some antiepileptic drugs (AEDs). Here the aim was to determine the effectiveness of this practice. METHODS: This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant and who are referred before outcome of the pregnancy is known. The main outcome measure is the MCM rate. Outcomes were analysed against folic acid exposure, malformation type and drug group for the most commonly used monotherapy AEDs. RESULTS: In 1935 cases reported to have received preconceptual folic acid, 76 MCMs (3.9%; 95% CI 3.1 to 4.9) and eight NTDs (0.4%; 95% CI 0.2 to 0.8) were identified. For 2375 women who were reported to have received folic acid but not until later in the pregnancy (n = 1825) or not at all (n = 550), there were 53 outcomes with an MCM (2.2%; 95% CI 1.7 to 2.9) and eight NTDs (0.34%; 95% CI 0.2 to 0.7). CONCLUSIONS: The study supports the view that extrapolation from studies carried out in the general population to groups of women with epilepsy may be questionable. It may be that the increased risk of MCM recorded in this group occurs through mechanisms other than that of folic acid metabolism.

Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register.

OBJECTIVES: Topiramate (Topamax) is licensed to be used, either in monotherapy or as adjunctive treatment, for generalized tonic clonic seizures or partial seizures with or without secondary generalization and for prevention of migraine. The safety of topiramate in human pregnancy is largely unknown. Here we report on our experience of pregnancies exposed to topiramate. METHODS: This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant while taking topiramate either singly or along with other antiepileptic drugs (AEDs), and who are referred before outcome of the pregnancy is known. The main outcome measure is the major congenital malformation (MCM) rate. Secondary outcomes include risk of specific MCM, minor malformation rate, birthweight, and gestational age at delivery. RESULTS: Full outcome data are available on 203 pregnancies. Of these, 178 resulted in live birth; 16 had an MCM (9.0%; 95% CI 5.6% to 14.1%). Three MCMs were observed in 70 monotherapy exposures (4.8%; 95% CI 1.7% to 13.3%) and 13 in cases exposed to topiramate as part of a polytherapy regimen (11.2%; 95% CI 6.7% to 18.2%). Four of the MCMs were oral clefts (2.2%; 95% CI 0.9% to 5.6%). Four cases of hypospadias were reported (5.1%; 95% CI 0.2% to 10.1%) among 78 known live male births of which two were classified as major malformations. CONCLUSIONS: The number of outcomes of human pregnancies exposed to topiramate is low, but the major congenital malformation rate for topiramate polytherapy raises some concerns. Overall, the rate of oral clefts observed was 11 times the background rate. Although the present data provide new information, they should be interpreted with caution due to the sample size and wide confidence intervals.

Levetiracetam in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register.

It is not known whether the antiepileptic drug (AED) levetiracetam can be used safely in human pregnancy. As part of a study to determine the risks of major congenital malformations (MCMs) for infants exposed to AEDs in utero, we identified all cases exposed to levetiracetam. Three of 117 exposed pregnancies had an MCM (2.7%; 95% CI 0.9% to 7.7%); all 3 were exposed to other AEDs.

An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women.

Our objective was to determine the optimal duration of treatment with imiquimod for external genital warts over 4, 8, 12 or 16 weeks. A total of 120 women with a history of genital warts for a median of 3-6 months and prior alternative treatments in 73% were evaluated for total clearance rates. There was no statistically significant difference in complete clearance rates after 16-week follow-up across treatment groups: four weeks (40.0%), eight weeks (48.4%), 12 weeks (39.3%) and 16 weeks (51.6%). Imiquimod was well tolerated, and in those treated for four weeks there was a lower incidence of local skin reactions such as erythema and erosion, and no incidences of pain. These preliminary results suggest that a four-week treatment course of imiquimod applied thrice weekly for women with external genital warts may provide a reasonable approach with comparable efficacy and compliance, and minimal adverse events, drug costs and clinic visits.

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register.

OBJECTIVE: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). METHODS: Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. RESULTS: Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p<0.001); adjusted OR = 2.97 (p<0.001)). There were fewer MCMs for pregnancies exposed only to lamotrigine than only to valproate. A positive dose response for MCMs was found for lamotrigine (p = 0.006). Polytherapy combinations containing valproate carried a higher risk of MCM than combinations not containing valproate (OR = 2.49 (1.31 to 4.70)). CONCLUSIONS: Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.

Sources of disseminated Mycobacterium avium infection in AIDS.

OBJECTIVES: To identify the sources of disseminated Mycobacterium avium complex (MAC) infection in AIDS. METHODS: HIV positive subjects with CD4 counts <100/mm(3) in Atlanta, Boston, New Hampshire and Finland were entered in a prospective cohort study. Subjects were interviewed about potential MAC exposures, had phlebotomy performed for determination of antibody to mycobacterial lipoarabinomannin and for culture. Patient-directed water samples were collected from places of residence, work and recreation. Patients were followed for the development of disseminated MAC. Univariate and multivariate risk factors for MAC were analyzed. RESULTS: Disseminated MAC was identified in 31 (9%) subjects. Significant risks in univariate analysis included prior Pneumocystis carinii pneumonia (PCP) (hazard ratio 1.821), consumption of spring water (4.909), consumption of raw seafood (34.3), gastrointestinal endoscopy (2.894), and showering outside the home (0.388). PCP, showering and endoscopy remained significant in a Cox proportional hazards model. There was no association between M. avium colonization of home water and risk of MAC. In patients with CD4<25, median OD antibody levels to lipoarabinomannin at baseline were 0.054 among patients who did not develop MAC and 0.021 among patients who did develop MAC (P=0.077). CONCLUSIONS: MAC infection results from diverse and likely undetectable environmental and nosocomial exposures. Mycobacterial infection before HIV infection may confer protection against disseminated MAC in advanced AIDS.

The effect of nitrostyrene on cell proliferation and macrophage immune responses.

The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent in society. These compounds are known to produce serious psychological and physiological problems in users, which can, in some circumstances result in death. While there has been much research into the effects of these drugs on the body, little if any research has investigated the effect of the side products and synthetic reaction by-products which are a consequence of there illegal production. In the study the effects of nitrostyrene, a reaction by-product in one of the routes to synthesis of amphetamine sulphate, on cell viability and macrophage function was determined. Treatment with nitrostyrene at doses >0.75 microg/mL had a significant suppressive effect on the proliferation of stomach cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6 and nitrite production, even using doses < 0.5 microg/mL. Thus ranking of the three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6. Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user.

Soil bacteria Pseudomonas putida and Alcaligenes xylosoxidans subsp. denitrificans inactivate triclosan in liquid and solid substrates.

Triclosan is a broad-spectrum antimicrobial agent that has been incorporated into many household and medical products. Bacteria with high levels of triclosan resistance were isolated from compost, water, and soil samples. Two of these bacteria, Pseudomonas putida TriRY and Alcaligenes xylosoxidans subsp. denitrificans TR1, were able to use triclosan as a sole carbon source and clear particulate triclosan from agar. A decrease in triclosan concentration was measured by HPLC within 6 h of inoculation with strain TriRY and 24 h with strain TR1. Bioassays demonstrated that triclosan was inactivated in liquid cultures and/or embedded in plastic by the growth of strain TriRY and strain TR1, permitting the growth of triclosan-sensitive bacteria.

Time trends in HIV incidence among homosexually active men seen at sexual health clinics in Australia, 1993-1999.

BACKGROUND: Increases in sexual risk behaviour have recently been reported among homosexually active men in Australia and in other industrialised countries, potentially facilitating an increase in HIV incidence. OBJECTIVE: To monitor HIV incidence among homosexually active men seen through a network of sexual health clinics in Australia. STUDY DESIGN: Selected metropolitan public sexual health clinics provided counts of the number of people seen at the clinics during a calendar year, the number voluntarily tested for HIV antibody and the number newly diagnosed with HIV infection, broken down by sex, age group, HIV exposure category and HIV antibody testing history. HIV incidence was estimated among homosexually active men with a history of a negative test in the 12 months prior to last being seen in a calendar year. RESULTS: Of 23924 men seen at the clinics in 1993-1999 with a reported history of male homosexual contact, 7440 (31.1%) had a negative test in the 12 months prior to last being seen in a calendar year. The percentage of men with a recent negative test declined significantly over time, from more than 33% in 1994-1996 to 29% in 1999 (P=0.003), and with increasing age, from 34.3% among men aged 25-29 years to 27.4% among men aged 40 years or older (P<0.0005). A total of 5346 (71.9%) men were retested for HIV antibody within 12 months of the last negative test. The percentage of men retested declined significantly over time, from 77.8% in 1994 to 67.2% in 1999 (P=0.021) but did not change by age group (P=0.132). Overall, 56 men were newly diagnosed with HIV infection. Estimated HIV incidence was 2.1% in 1993-1999; incidence did not change significantly by year (P=0.498) or age group (P=0.757). CONCLUSION: HIV incidence has remained stable among homosexually active men seen through a network of sexual health clinics in Australia.

Bacteremia due to Mycobacterium tuberculosis or M. bovis, Bacille Calmette-Guérin (BCG) among HIV- positive children and adults in Zambia.

BACKGROUND: Among adults with advanced HIV infection in developing countries, bacteremia due to Mycobacterium tuberculosis (MTB) is common and bacteremia due to M. bovis (bacille Calmette-Guérin; BCG) is rare. Comparable data are not available for children with HIV. OBJECTIVE: To compare the prevalence of bacteremia due to M. tuberculosis or M. bovis BCG in hospitalized children and adults with HIV infection in a developing country with a high prevalence of tuberculosis and HIV and > 95% BCG immunization coverage. DESIGN: Descriptive cross-sectional study. METHODS: Prospectively hospitalized patients in Lusaka, Zambia who were suspected to have HIV infection underwent phlebotomy for HIV ELISA, HIV viral load, and lysis-centrifugation blood culture for mycobacteria. Histories were obtained and patients were examined for BCG scars. Mycobacterial isolates were identified using DNA probes for MTB complex (MTBC), multiplex PCR and IS6110 typing. RESULTS: The median age of 387 HIV-positive children was 15 months; 98% were BCG immunized. The median age of 344 HIV-positive adults was 32 years; 44% were BCG immunized. Blood cultures were positive for mycobacteria in six children (2%) and 38 adults(11%) (P < 0.001). The six pediatric isolates included five MTBC (40% clustered) and one BCG. The 38 adult isolates included 36 MTBC (16% clustered) and two M. avium complex. CONCLUSION: Bacteremia due to MTB is less common among children than adults with advanced HIV infection in Zambia. Bacteremia due to M. bovis BCG is rare even among children with recent BCG immunization and symptomatic HIV infection.

Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States.

SETTING: Health care workers and medical students in the United States subject to annual tuberculin skin testing. OBJECTIVE: To use skin testing with Mycobacterium avium sensitin (MAS) to determine contemporary rates of infection with non-tuberculous mycobacteria (NTM) and their effect on reactions to M. tuberculosis purified protein derivative (PPD). DESIGN: Dual skin testing was performed with PPD and MAS on 784 health care workers and medical students in the northern and southern US. MAS reactions that were > or = 5 mm and also > or = 3 mm larger than the PPD reaction were defined as MAS dominant and due to NTM. RESULTS: MAS reactions were > or = 5 mm in 40% and > or = 15 mm in 18% of subjects; 95% were MAS dominant. MAS dominant reactions were more common in the south than the north (P < 0.001). PPD reactions were > or = 15 mm in 3% of subjects. PPD reactions > or = 15 mm were more common among males, foreign born subjects and subjects with BCG immunization (all P < 0.001). MAS dominant reactions were found in 82% of subjects with 5-9 mm PPD reactions and 50% with 10-14 mm PPD reactions; these reactions were more common among whites (P = 0.046), US-born (P = 0.038) and subjects without BCG immunization (P = 0.004). CONCLUSIONS: Infections with NTM are responsible for the majority of 5-14 mm PPD reactions among US-born health care workers and medical students subject to annual tuberculin testing.