A comparison of chest radiographic findings in human immunodeficiency virus-positive and -negative children with pulmonary tuberculosis.

AIM: To compare chest radiography (CXR) findings in human immunodeficiency virus (HIV)-positive and HIV-negative children who had microbiologically confirmed pulmonary tuberculosis (PTB). MATERIALS AND METHODS: Retrospective analysis of CXRs from children with known HIV status and microbiologically confirmed PTB (culture or GeneXpert Xpert MTB/RIF positive), who were hospitalised or seen at a primary healthcare centre over a 5-year period. Radiological findings were compared according to HIV and nutritional status. RESULTS: CXRs of 130 children were analysed from 35 (27%) HIV- positive and 95 (73%) HIV-negative children with confirmed PTB, median age 45.7 months (interquartile range [IQR] 18-81.3 months). CXR changes consistent with PTB were reported in 21/35 (60%) of HIV-positive and 59/95 (62%) of HIV-negative patients, (p=0.81). Normal CXR was identified in 3/35 (8.6%) of HIV-positive and 5/95 (5.3%) of HIV-negative patients (p=0.81). Airway compression was present in 3/35 (8.6%) of HIV-positive and 7/95 (7.4%) of HIV-negative patients (p>0.99). Overall, lymphadenopathy was identified in 42/130 (32.3%) of patients, 11/35 (31.4 %) were HIV-positive compared with 31/95 (32.6%) HIV-negative patients. Airspace consolidation was present in 60% of both HIV-positive (21/35) and HIV-negative patients (57/95). Pleural effusion was present in 2/35 (5.7 %) of HIV-negative and 9/95 (9.5 %) of HIV-negative patients. There were no statistically significant radiological differences by HIV group. CONCLUSION: There were no significant differences in the CXR findings between the HIV-positive and HIV-negative children with confirmed PTB.

Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis.

IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3-6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.

Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients.

BACKGROUND: GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. OBJECTIVES: To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. METHODS: A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. RESULTS: A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225). CONCLUSION: GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery.

Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed-effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3-fold for sulfadoxine but decreased by 18% for pyrimethamine. Postpartum sulfadoxine clearance decreased gradually over 13 weeks. This finding, together with hematocrit-based scaling of plasma to whole-blood concentrations and allometric scaling of pharmacokinetics parameters with body weight, enabled site-specific differences in the pharmacokinetic profiles to be reduced significantly but not eliminated. Further research is necessary to explain residual site-specific differences and elucidate whether dose-optimization, to address the 3-fold increase in clearance of sulfadoxine in pregnant women, is necessary, viable, and safe with the current fixed dose combination of sulfadoxine/pyrimethamine.

Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients

Background. GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB.Objectives. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB.Methods. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology.Results. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225).Conclusion. GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB

The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients.

BACKGROUND: Artemether-lumefantrine is currently the most widely recommended treatment of uncomplicated malaria. Lopinavir-based antiretroviral therapy is the commonly recommended second-line HIV treatment. Artemether and lumefantrine are metabolised by cytochrome P450 isoenzyme CYP3A4, which lopinavir/ritonavir inhibits, potentially causing clinically important drug-drug interactions. METHODS: An adaptive, parallel-design safety and pharmacokinetic study was conducted in HIV-infected (malaria-negative) patients: antiretroviral-naïve and those stable on lopinavir/ritonavir-based antiretrovirals. Both groups received the recommended six-dose artemether-lumefantrine treatment. The primary outcome was day-7 lumefantrine concentrations, as these correlate with antimalarial efficacy. Adverse events were solicited throughout the study, recording the onset, duration, severity, and relationship to artemether-lumefantrine. RESULTS: We enrolled 34 patients. Median day-7 lumefantrine concentrations were almost 10-fold higher in the lopinavir than the antiretroviral-naïve group [3170 versus 336 ng/mL; p = 0.0001], with AUC(0-inf) and Cmax increased five-fold [2478 versus 445 µg.h/mL; p = 0.0001], and three-fold [28.2 versus 8.8 µg/mL; p < 0.0001], respectively. Lumefantrine Cmax, and AUC(0-inf) increased significantly with mg/kg dose in the lopinavir, but not the antiretroviral-naïve group. While artemether exposure was similar between groups, Cmax and AUC(0-8h) of its active metabolite dihydroartemisinin were initially two-fold higher in the lopinavir group [p = 0.004 and p = 0.0013, respectively]. However, this difference was no longer apparent after the last artemether-lumefantrine dose. Within 21 days of starting artemether-lumefantrine there were similar numbers of treatment emergent adverse events (42 vs. 35) and adverse reactions (12 vs. 15, p = 0.21) in the lopinavir and antiretroviral-naïve groups, respectively. There were no serious adverse events and no difference in electrocardiographic QTcF- and PR-intervals, at the predicted lumefantrine Tmax. CONCLUSION: Despite substantially higher lumefantrine exposure, intensive monitoring in our relatively small study raised no safety concerns in HIV-infected patients stable on lopinavir-based antiretroviral therapy given the recommended artemether-lumefantrine dosage. Increased day-7 lumefantrine concentrations have been shown previously to reduce the risk of malaria treatment failure, but further evidence in adult patients co-infected with malaria and HIV is needed to assess the artemether-lumefantrine risk : benefit profile in this vulnerable population fully. Our antiretroviral-naïve patients confirmed previous findings that lumefantrine absorption is almost saturated at currently recommended doses, but this dose-limited absorption was overcome in the lopinavir group. TRIAL REGISTRATION: Clinical Trial Registration number NCT00869700. Registered on clinicaltrials.gov 25 March 2009.

Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy.

BACKGROUND: Only limited evidence is available regarding the cytokine repertoire of effector T cells associated with peanut allergy, and how these responses relate to IgE antibodies to peanut components. OBJECTIVE: To interrogate T cell effector cytokine populations induced by Ara h 1 and Ara h 2 among peanut allergic (PA) children in the context of IgE and to evaluate their modulation during oral immunotherapy (OIT). METHODS: Peanut-reactive effector T cells were analysed in conjunction with specific IgE profiles in PA children using intracellular staining and multiplex assay. Cytokine-expressing T cell subpopulations were visualized using SPICE. RESULTS: Ara h 2 dominated the antibody response to peanut as judged by prevalence and quantity among a cohort of children with IgE to peanut. High IgE (> 15 kU(A)/L) was almost exclusively associated with dual sensitization to Ara h 1 and Ara h 2 and was age independent. Among PA children, IL-4-biased responses to both major allergens were induced, regardless of whether IgE antibodies to Ara h 1 were present. Among subjects receiving OIT in whom high IgE was maintained, Th2 reactivity to peanut components persisted despite clinical desensitization and modulation of allergen-specific immune parameters including augmented specific IgG4 antibodies, Th1 skewing and enhanced IL-10. The complexity of cytokine-positive subpopulations within peanut-reactive IL-4(+) and IFN-γ(+) T cells was similar to that observed in those who received no OIT, but was modified with extended therapy. Nonetheless, high Foxp3 expression was a distinguishing feature of peanut-reactive IL-4(+) T cells irrespective of OIT, and a correlate of their ability to secrete type 2 cytokines. CONCLUSION: Although total numbers of peanut-reactive IL-4(+) and IFN-γ(+) T cells are modulated by OIT in highly allergic children, complex T cell populations with pathogenic potential persist in the presence of recognized immune markers of successful immunotherapy.

Effect of urban vs. rural residence on the association between atopy and wheeze in Latin America: findings from a case-control analysis.

BACKGROUND: The association between atopy and asthma is attenuated in non-affluent populations, an effect that may be explained by childhood infections such as geohelminths. OBJECTIVE: To investigate the association between atopy and wheeze in schoolchildren living in urban and rural areas of Ecuador and examine the effects of geohelminths on this association. METHODS: We performed nested case-control studies among comparable populations of schoolchildren living in rural communities and urban neighbourhoods in the Province of Esmeraldas, Ecuador. We detected geohelminths in stool samples, measured recent wheeze and environmental exposures by parental questionnaire, and atopy by specific IgE (sIgE) and skin prick test (SPT) reactivity to aeroallergens. RESULTS: Atopy, particularly sIgE to house dust mite (HDM), was more strongly associated with recent wheeze in urban than rural schoolchildren: (urban, adj. OR 5.19, 95% CI 3.37-8.00, P < 0.0001; rural, adj. OR 1.81, 95%CI 1.09-2.99, P = 0.02; interaction, P < 0.001). The population fractions of wheeze attributable to atopy were approximately two-fold greater in urban schoolchildren: SPT to any allergen (urban 23.5% vs. rural 10.1%), SPT to HDM (urban 18.5% vs. rural 9.6%), and anti-HDM IgE (urban 26.5% vs. rural 10.5%), while anti-Ascaris IgE was related to wheeze in a high proportion of rural (49.7%) and urban (35.4%) children. The association between atopy and recent wheeze was attenuated by markers of geohelminth infections. CONCLUSIONS: Our data suggest that urban residence modifies the association between HDM atopy and recent wheeze, and this effect is explained partly by geohelminth infections.

Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy: a pilot study.

SETTING: Tuberculosis (TB) is a common cause of mortality and morbidity in children infected with the human immunodeficiency virus (HIV). Data on isoniazid preventive therapy (IPT) efficacy in HIV-infected children receiving antiretroviral therapy (ART) are inconclusive. OBJECTIVE: To assess the efficacy, tolerability and safety of isoniazid (INH) in HIV-infected children on ART. DESIGN: A pilot randomised controlled study of INH was undertaken in HIV-infected children on ART. The primary outcome measure was TB disease or death. RESULTS: A total of 167 children were randomised to receive INH (n = 85) or placebo (n = 82), and followed for a median of 34 months (interquartile range [IQR] 24-52). The median age was 35 months (IQR 15-65). There was one death in a child on INH and none in the placebo group. Eleven (6.6%) cases of TB occurred, 4 (5%) in the INH and 7 (9%) in the placebo group. Among the TB cases, 5 were culture confirmed-2 in the INH group and 3 in the placebo group, all susceptible to INH. Severe adverse events occurred rarely (n = 6; 2%). CONCLUSION: IPT is safe and well tolerated in HIV-infected children on concomitant ART. This study supports the need for a larger study to assess efficacy in HIV-infected children living in TB-endemic areas.

Safety and efficacy of induced sputum in young children hospitalised with suspected pulmonary tuberculosis.

BACKGROUND: Induced sputum (IS) is increasingly used to provide specimens for microbiological confirmation of Mycobacterium tuberculosis. The aim of this study was to investigate the safety of and yield from IS in children hospitalised with suspected pulmonary tuberculosis (PTB). METHODS: In a prospective study of children hospitalised with suspected PTB in Cape Town, South Africa, between February 2009 and February 2012, two IS specimens were obtained on consecutive days or at intervals of at least 4 hours. Specimens were investigated for M. tuberculosis using concentrated fluorescent acid-fast smear, liquid culture and GeneXpert(®) MTB/RIF. The safety of IS was assessed by recording clinical signs and symptoms before and for 30 min after sputum induction. RESULTS: Among 843 children enrolled, at least one IS was performed for 823 (97.6%). The safety of sputum induction was recorded for 690 children (median age 27.3 months [IQR 13.4-64.2]), representing a total of 1270 IS procedures. Of these, 129 (18.7%) had at least one sputum culture positive for M. tuberculosis. Side effects were epistaxis (249, 19.4%) or wheezing (14, 1.1%). The median drop in oxygen saturation during the IS procedure was 1%. CONCLUSION: Sputum induction is a safe and useful method for the microbiological confirmation of tuberculosis (TB) in young children.

Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is common in children; however, persistence of AD with or without asthma is less common. Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship with asthma. OBJECTIVE: To use a cross-sectional study design of children with active AD to analyse age-related differences in IgE antibodies and relation to wheeze. METHODS: IgE antibodies to food and inhalant allergens were measured in children with active AD (5 months to 15 years of age, n = 66), with and without history of wheeze. RESULTS: Whereas IgE antibodies to foods persisted at a similar prevalence and titre throughout childhood, IgE antibodies to all aeroallergens rose sharply into adolescence. From birth, the chance of sensitization for any aeroallergen increased for each 12-month increment in age (OR ≥ 1.21, P < 0.01), with the largest effect observed for dust mite (OR = 1.56, P < 0.001). A steeper age-related rise in IgE antibody titre to dust mite, but no other allergen was associated with more severe disease. Despite this, sensitization to cat was more strongly associated with wheeze (OR = 4.5, P < 0.01), and linked to Fel d 1 and Fel d 4, but not Fel d 2. Comparison of cat allergic children with AD to those without, revealed higher IgE levels to Fel d 2 and Fel d 4 (P < 0.05), but not Fel d 1. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in sensitization to cat and dust mite among young children with AD may aid in identifying those at increased risk for disease progression and development of asthma. Early sensitization to cat and risk for wheeze among children with AD may be linked to an increased risk for sensitization to a broader spectrum of allergen components from early life. Collectively, our findings argue for early intervention strategies designed to mitigate skin inflammation in children with AD.

Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study.

BACKGROUND: Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. OBJECTIVE: To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. METHODS: A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7-19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. RESULTS: The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33-3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49-11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. CONCLUSIONS AND CLINICAL RELEVANCE: Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.

Tuberculosis case finding for vaccine trials in young children in high-incidence settings: a randomised trial.

SETTING: A high tuberculosis (TB) burden rural area in South Africa. OBJECTIVE: To compare TB case yield and disease profile among bacille Calmette-Guérin (BCG) vaccinated children using two case-finding strategies from birth until 2 years of age. DESIGN: BCG-vaccinated infants were enrolled within 2 weeks of birth and randomised to 3-monthly home visits for questionnaire-based TB screening plus record surveillance of TB registers, hospital admission and X-ray lists at health facilities for TB suspects and cases (Group 1), or record surveillance (as above) only (Group 2). Both groups received a close-out visit after 2 years. Participants were evaluated for suspected TB disease using standardised investigations. RESULTS: A total of 4786 infants were enrolled: 2392 were randomised to Group 1 and 2394 to Group 2. The case-finding rate was significantly greater in Group 1 (2.2/100 py) than in Group 2 (0.8/100 py), with a case-finding rate ratio of 2.6 (95%CI 1.8-4.0, P < 0.001). Although the proportion of cases with bacteriological confirmation was lower in Group 1, this difference did not reach statistical significance. There was also no significant difference in the proportions with TB symptoms and signs. CONCLUSION: Home visits combined with record surveillance detected significantly more cases than record surveillance with a single study-end visit. The TB case profile did not differ significantly between the two groups.

Tuberculin skin test and QuantiFERON® assay in young children investigated for tuberculosis in South Africa.

SETTING: Although the literature on interferon-gamma release assays on tuberculosis (TB) in children has increased, data pertaining to young children remain relatively limited. OBJECTIVE: To compare results from the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube assay (QFT) in children aged <3 years investigated for TB disease. DESIGN: TB suspects were evaluated by medical history and examination, TST, QFT, chest radiography, induced sputum and gastric washings for smear and culture for Mycobacterium tuberculosis. RESULTS: A total of 400 children were enrolled. Among 397 children with both test results, 68 (17%) were QFT-positive and 72 (18%) were TST-positive (≥10 mm). Agreement between the tests was excellent (94%, κ = 0.79, 95%CI 0.69-0.89). TB disease was diagnosed in 52/397 (13%) participants: 3 definite, 35 probable and 14 possible TB. QFT sensitivity and specificity for TB disease were respectively 38% and 81%. TST sensitivity and specificity were respectively 35% and 84%. CONCLUSION: While TST and QFT had excellent concordance in this population, both tests had much lower sensitivity for TB disease than has been reported for other age groups. Our results suggested equivalent performance of QFT and TST in the diagnosis of TB disease in young children in a high-burden setting.

Induced sputum or gastric lavage for community-based diagnosis of childhood pulmonary tuberculosis?

OBJECTIVES: To compare the diagnostic yield of Mycobacterium tuberculosis from induced sputum (IS) and gastric lavage (GL) among children in a community setting. METHODS: Specimen-collection methods for bacteriological confirmation of pulmonary tuberculosis (PTB) were compared during a tuberculosis vaccine trial near Cape Town, South Africa (2001-2006). Children with a tuberculosis contact or compatible symptoms were investigated for suspected PTB. Diagnostic yields from 764 paired IS and GL specimens were compared in 191 culture-confirmed cases. MEASUREMENTS AND MAIN RESULTS: The crude yield of M tuberculosis was 10.4%, n = 108 by IS (5.8%) and n = 127 by GL (6.8%), from a total of 194 cases, of which three had incomplete IS/GL specimen pairs. Agreement between IS and GL was poor (kappa = 0.31). The comparative yield of a single IS sample (38%) was equivalent to a single GL sample (42%), with a difference in yield of -4% (95% CI -15% to +7%). The combined yield of same-day IS and GL specimens (67%) was equivalent to two consecutive GL specimens (66%), with a difference in yield of 1% (95% CI -9% to 11%), but significantly greater than two consecutive IS specimens (55%), with a difference in yield of 12% (95% CI 2% to 21%). The adjusted odds of a M tuberculosis culture were increased by a positive tuberculin skin test or chest radiograph compatible with PTB. CONCLUSIONS: In this community setting, the diagnostic yield of a single IS sample was equivalent to that of a single GL sample. The optimal diagnostic yield may be obtained from paired IS and GL specimens taken on a single day or two GL specimens taken on consecutive days.

How do experiences in Iraq affect alcohol use among male UK armed forces personnel?

OBJECTIVES: This paper reports on a statistically significant association between alcohol use and deployment to the 2003 Iraq War. It assesses the occupational factors and deployment experiences associated with heavy drinking in regular UK servicemen deployed to Iraq in the first phase of the 2003 Iraq War (Operation TELIC 1, the military codename for the conflict in Iraq). METHODS: A random representative sample of 3578 regular male UK Armed Forces personnel who were deployed to Iraq during Operation TELIC 1 participated in a cross-sectional postal questionnaire study (response rate 61%). Participants completed a questionnaire, between June 2004 and March 2006 (ie, after deployment), about their health, including a measure of alcohol use (Alcohol Use Disorders Identification Test, AUDIT) and questions about their experiences on deployment to Iraq. Heavy drinkers were identified as those scoring 16 or above on the AUDIT. RESULTS: After adjustment for sociodemographic and military factors, and the presence of psychological distress, heavy drinkers were more likely to have had major problems at home during (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.04 to 1.70) and following their deployment (OR 1.68, 95% CI 1.32 to 2.14). Being deployed with their parent unit (OR 1.28, 95% CI 1.02 to 1.61), medium to high in-theatre unit comradeship (medium: OR 1.35, 95% CI 1.04 to 1.77; high: OR 1.35, 95% CI 1.02 to 1.79) and poor unit leadership (OR 1.78, 95% CI 1.37 to 2.31) were also associated with heavy drinking. CONCLUSIONS: Deployment experiences and problems at home during and following deployment, as well as the occupational milieu of the unit, influence personnel's risk of heavy drinking.

Prevalence of bacterial contamination of powdered infant feeds in a hospital environment.

BACKGROUND: The study arose as part of a best-practice nutrition model regarding the introduction of ready-to-use (RTU) infant feeds in place of powdered infant feeds (PIFs) as a standard formula for infants under the age of 1 year who are unable to be breastfed. Internationally and locally there is grave concern regarding the safety and efficacy of mixing PIFs, especially in a hospital setting, and the resultant bacterial contamination causing enteric infections, especially in premature, immunocompromised and sick infants. OBJECTIVE: To evaluate the prevalence of bacterial contamination of PIFs given to infants at Red Cross War Memorial Children's Hospital, Cape Town. METHODS: Quantitative levels of bacterial contamination were determined and were expressed as colony-forming units (CFUs) per millilitre of sample. Aliquots of milk were inoculated onto agar, and the milk samples were then incubated at 25 degrees C overnight (N = 10), 30 degrees C overnight (N = 48) and 30 degrees C for 6 hours (N = 34). Post-incubation milk samples were cultured again. Contamination was defined as any positive culture before administration (i.e. pre incubation) or > 10(2) CFU/ ml after administration (i.e. post incubation). RESULTS: Fifty samples of PIFs (N = 82) were contaminated pre incubation, with 25/82 samples (30.4%) being heavily contaminated ( >or= 10(4) CFU/ml). Post incubation, 43/92 samples (46.7%) were contaminated with > 102 CFU/ml. The acidified PIFs appeared to have some bactericidal effect against some of the organisms, but not all. CONCLUSIONS: RTU infant feeds are sterile and are recommended for use in all hospitalised infants. The results of this study indicate that even when milk is prepared in a controlled environment there is significant bacterial contamination of PIFs post production. As RTU feeds are now readily available in South Africa every attempt should be made to use a sterile RTU system for hospitalised infants.

Determining the prevalence of malnutrition in hospitalized paediatric patients.

AIM: To determine the prevalence of malnutrition in hospitalised paediatric patients at Red Cross War Memorial Children's Hospital. METHOD: A 1-day cross-sectional survey was completed in all medical and surgical wards and some specialist outpatient clinics. RESULTS: A total of 227 children participated in the study. Thirty-five per cent of patients were moderately malnourished (< or = -2 z-score), of whom 70% had no road to health card with them. Thirty-four per cent of children under 60 months of age received supplements in addition to a normal ward diet, 7.8% were enterally fed and less than 1% were parenterally fed. Almost 14% of children were found to be overweight/obese, which is higher than the national average of 6%. The prevalence of HIV infection on the day of the audit was 18% across all age groups compared with the Western Cape antenatal prevalence of 15.7% (2005). CONCLUSION: The overall prevalence of undernutrition was 34%, which is comparable with similar studies. However, the proportion of overweight children (14%) was greater than the national average. In view of the level of malnutrition seen, a nutrition risk-screening tool, identifying risk factors for malnutrition such as food access and vulnerability, should be developed. The tool should be used to assess nutrition status and risk during the course of hospitalisation, in addition to planning appropriate nutrition care plan interventions for discharge.

Gonadotropin subunit transcriptional responses to calcium signals in the rat: evidence for regulation by pulse frequency.

Alterations in the frequency of calcium influx signals to rat pituitary cells can regulate the expression of gonadotropin subunit mRNAs in a differential manner, producing effects that are similar to those previously found for GnRH. The present study was conducted to investigate whether this reflects a transcriptional response to calcium pulse frequency, as determined by alterations in primary transcript (PT) expression. Perifused rat pituitary cells were given pulses of the calcium channel-activator Bay K 8644 (BK; with 10 mM KCl in the injectate) for 6 h. The response to alterations in pulse dose was examined by giving pulses of 1, 3, or 10 microM BK at 60-min intervals. Maximal increases in LHbeta and FSHbeta PTs were obtained with the 3-microM BK pulse dose and with the 10-microM dose for alpha. To investigate the effect of calcium pulse frequency, 3-microM BK pulses were given at intervals of 15, 60, or 180 min. Alpha PT was selectively stimulated by 15-min pulses and LHbeta by 15- and 60-min pulses of BK. In contrast, FSHbeta PT was maximally stimulated by the slower, 180-min pulse interval. These findings reveal that pulsatile increases in intracellular calcium stimulate alpha, LHbeta, and FSHbeta transcription in a differential manner. Thus, intermittent changes in intracellular calcium appear to be important in the transmission of GnRH pulse signals from the plasma membrane to the gene, and they may mediate the differential actions of pulse frequency on gonadotropin subunit gene expression.