Veterinary growth promoters in cattle feedlot runoff: estrogenic activity and potential effects on the rat male reproductive system.

The contribution of veterinary growth promoters (VGP) to the environmental burden of endocrine-disrupting chemicals (EDCs) is largely unknown. At cattle feedlots, the excrement of cattle may contain VGPs, which can contaminate aquatic systems and pose reproductive health risks. The study identifies VGPs used at cattle feedlots in South Africa and confirms associated estrogenic activity in feedlot runoff water. Using a rat model, we investigate the potential reproductive health effects and thyroid function of an environmentally relevant mixture of VGPs. Collected water samples had low levels of selected VGPs, and estrogenic activity was detected in the T47D-KBluc bioassay. Rats exposed to VGP had significant adverse effects on male reproductive health, including shortened anogenital distance, lowered sperm counts, disorganized seminiferous tubules, and thyroid parameters. In conclusion, VGP can contribute to complex environmental EDC mixtures and may adversely affect the reproductive and thyroid health of both humans and wildlife. The varied topography of individual cattle feedlots will govern the rate and extent of effluent runoff, thus continuous monitoring of VGPs in aquatic systems surrounding cattle feedlots is necessary.

Severe manifestations of extrapulmonary tuberculosis in HIV-infected children initiating antiretroviral therapy before 2†years of age.

BACKGROUND: Early initiation of antiretroviral therapy (ART) in HIV-infected infants reduces mortality and opportunistic infections including tuberculosis (TB). However, young HIV-infected children remain at high risk of TB disease following mycobacterial infection. We document the spectrum of TB disease in HIV-infected children <2 years of age on ART. METHODS: Retrospective cohort study; records of children <2 years of age initiating routine ART at Tygerberg Children's Hospital, Cape Town, January 2003-December 2010 were reviewed. Clinical data at ART initiation (baseline) and TB episodes after ART initiation, to June 2012, were recorded. TB immune reconstitution syndrome (TB-IRIS) and incident TB were defined as TB diagnosed within 3 months, and >3 months after, ART initiation respectively. Baseline characteristics were compared in children with TB-IRIS and those with incident TB. RESULTS: In 494 children, median follow-up time on ART was 10.7 months. Fifty-five TB treatment episodes occurred after ART initiation: 23 (42%) TB-IRIS (incidence 21.9/100 person years (py)) and 32 (58%) incident TB (incidence 3.9/100 py). Children with TB-IRIS and those with incident TB had similar baseline characteristics. Eight of 10 cases of extrapulmonary TB were severe: 4 IRIS (2 meningitis, 1 disseminated, 1 pericarditis) and 4 incident cases (1 each miliary, meningitis, pericarditis and spinal). Fifty-one children (10%) died (mortality rate 5.96/100 py). Starting ART at <1 year of age approached significance as a risk factor for TB-IRIS (adjusted OR (AOR) 8.64, p=0.06); weight-for-age Z score <-2 predicted death (AOR 6.37, p<0.001). CONCLUSIONS: Severe TB manifestations were observed among young HIV-infected children on ART.

Does an isoniazid prophylaxis register improve tuberculosis contact management in South African children?

SETTING: We compared the change in child household contact management of pulmonary tuberculosis (TB) cases before and after the implementation of an isoniazid preventive therapy (IPT) register in an urban clinic setting in Cape Town, South Africa. OBJECTIVES: We determined if the presence of an IPT register was associated with an increase in the number of child contacts identified per infectious case and the proportion of identified children who were started on IPT. DESIGN: We reviewed routine programme data on IPT delivery to children during two time periods (May 2008-October 2008 and May 2011-October 2011), before and after the implementation of an IPT register used by routine clinic personnel. RESULTS: Adult TB case demographic and clinical characteristics from the two observation periods were similar. During the post-register period, more child contacts per adult case were identified (0.7 (54 children) vs. 0.3 (24 children)), more of the identified children were started on IPT (54 vs. 4) and 37% of those who started, completed six months of treatment compared to the pre-register period where no adherence information was recorded. CONCLUSIONS: After pilot implementation of an IPT register, documented identification of child contacts, IPT initiation and IPT adherence documentation in TB exposed children was improved. Our findings support further exploration of the potential impact of using standardised IPT recording and reporting in routine clinics in high-burden TB settings to improve TB prevention efforts targeted at young children. Future efforts to improve IPT delivery should be systematic and comprehensive in order to support a change in current operational IPT delivery practices in TB programs.

Detecting tuberculosis infection in HIV-infected children: a study of diagnostic accuracy, confounding and interaction.

BACKGROUND: Accurate identification of Mycobacterium tuberculosis infection in young and HIV-infected children could guide delivery of preventive therapy, improve resource utilization and help prevent tuberculosis. METHODS: We assessed the performance of the tuberculin skin test (TST) and interferon-γ release assays (IGRAs) for identifying M. tuberculosis infection in South African children presenting for outpatient care. Tuberculosis contact was quantified using a standardized measure of M. tuberculosis exposure. Logistic regression assessed the association among test positivity, age, nutritional and HIV status, while controlling for M. tuberculosis exposure, bacille Calmette-Guérin vaccination and prior tuberculosis treatment. RESULTS: Among 250 (130 HIV infected) children (age 0.25-14.6 years, median 39 months), the proportion positive for each test varied: 34% (TST), 21% (T-SPOT.TB) and 25% (QuantiFERON-TB Gold In-Tube). IGRAs were more likely to be positive in HIV-uninfected compared with HIV-infected children; TST positivity did not differ between these groups. Agreement between tests was good-to-excellent in HIV-uninfected children and poor-to-good in HIV-infected children. In adjusted models, TST and T-SPOT.TB were positively associated with age; this effect varied by HIV status. The QuantiFERON-TB Gold In-Tube was negatively associated with chronic malnutrition; this effect varied by HIV status. Because 93% of children had received bacille Calmette-Guérin, we could not assess the contribution of bacille Calmette-Guérin to false-positive TST results. CONCLUSIONS: Our findings indicate that the TST and IGRAs perform similarly for the detection of M. tuberculosis infection in well-nourished HIV-uninfected children, but test performance is differentially affected by chronic malnutrition, HIV infection and age. Similar to TST interpretation, clinicians and researchers should interpret IGRAs in children with caution taking age, nutritional and HIV status into consideration.

Operational challenges in managing Isoniazid Preventive Therapy in child contacts: a high-burden setting perspective.

BACKGROUND: The study was conducted at a high TB-HIV burden primary health community clinic in Cape Town, South Africa. We describe the management of children under five years of age in household contact with a smear and/or culture-positive adult TB case. METHODS: This study was a record review of routinely-collected programme data. RESULTS: A total of 1094 adult TB case folders were reviewed. From all identified contacts, 149 children should have received IPT based on local guidelines; in only 2/149 IPT was initiated. Management of child contacts of sputum smear and/or culture-positive compared to sputum-negative TB patients were similar. CONCLUSIONS: IPT delivery to children remains an operational challenge, especially in high TB-HIV burden communities. A tool to improve IPT management and targeting sputum smear and/or culture-positive TB child contacts may overcome some of these challenges and should be developed and piloted in such settings.