Enteric pathogen infection and consequences for child growth in young Aboriginal Australian children: a cross-sectional study.

BACKGROUND: To determine the prevalence of enteric infections in Aboriginal children aged 0-2 years using conventional and molecular diagnostic techniques and to explore associations between the presence of pathogens and child growth. METHODS: Cross-sectional analysis of Aboriginal children (n = 62) residing in a remote community in Northern Australia, conducted from July 24th - October 30th 2017. Stool samples were analysed for organisms by microscopy (directly in the field and following fixation and storage in sodium-acetate formalin), and by qualitative PCR for viruses, bacteria and parasites and serology for Strongyloides-specific IgG. Child growth (height and weight) was measured and z scores calculated according to WHO growth standards. RESULTS: Nearly 60% of children had evidence for at least one enteric pathogen in their stool (37/62). The highest burden of infection was with adenovirus/sapovirus (22.9%), followed by astrovirus (9.8%) and Cryptosporidium hominis/parvum (8.2%). Non-pathogenic organisms were detected in 22.5% of children. Ten percent of children had diarrhea at the time of stool collection. Infection with two or more pathogens was negatively associated with height for age z scores (- 1.34, 95% CI - 2.61 to - 0.07), as was carriage of the non-pathogen Blastocystis hominis (- 2.05, 95% CI - 3.55 to - 0.54). CONCLUSIONS: Infants and toddlers living in this remote Northern Australian Aboriginal community had a high burden of enteric pathogens and non-pathogens. The association between carriage of pathogens/non-pathogens with impaired child growth in the critical first 1000 days of life has implications for healthy child growth and development and warrants further investigation. These findings have relevance for many other First Nations Communities that face many of the same challenges with regard to poverty, infections, and malnutrition.

Practical Guidance for Clinical Microbiology Laboratories: Laboratory Diagnosis of Parasites from the Gastrointestinal Tract

This Practical Guidance for Clinical Microbiology document on the laboratory diagnosis of parasites from the gastrointestinal tract provides practical information for the recovery and identification of relevant human parasites. The document is based on a comprehensive literature review and expert consensus on relevant diagnostic methods. However, it does not include didactic information on human parasite life cycles, organism morphology, clinical disease, pathogenesis, treatment, or epidemiology and prevention. As greater emphasis is placed on neglected tropical diseases, it becomes highly probable that patients with gastrointestinal parasitic infections will become more widely recognized in areas where parasites are endemic and not endemic. Generally, these methods are nonautomated and require extensive bench experience for accurate performance and interpretation.

The impact of anti-tuberculous antibiotics and corticosteroids on cytokine production in QuantiFERON-TB Gold In Tube assays.

INTRODUCTION: The ability to monitor and confirm adequate treatment of latent TB infection (LTBI) would be a major advance. The potential immunomodulatory effects of anti-tuberculous drugs and steroids need to be considered in assessing the utility of cytokine-based assays for this purpose. METHODS: We determined whether anti-tuberculous antibiotics or dexamethasone affect the production of IFN-γ and other potential cytokine biomarkers (TNF-α, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1ß) in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay. Blood from ten adults with LTBI was added to one standard set of QFT-IT tubes and five further sets containing therapeutic concentrations of either isoniazid, rifampicin, isoniazid and rifampicin, ciprofloxacin or dexamethasone. Resulting supernatants were analysed by ELISA (QFT-IT assay IFN-γ) and xMAP-Luminex assays (all cytokines). RESULTS: Anti-tuberculous antibiotics had only a limited effect on categorical QFT-IT assay results and the production of cytokines. In contrast, dexamethasone resulted in a change in categorical results from positive to negative in four of ten patients, and caused a marked reduction in IL-13 and IL-1ra responses. CONCLUSION: Substantial changes in TB-antigen-induced IFN-γ and other cytokine responses during treatment likely primarily reflect host immunological changes rather than immunomodulatory effects of anti-tuberculous antibiotics. Results from cytokine-based assays in patients on corticosteroids should be interpreted with caution.

Latent Tuberculosis screening using interferon-gamma release assays in an Australian HIV-infected cohort: is routine testing worthwhile?

BACKGROUND: There are limited data from high-income countries on the performance of interferon-gamma release assays in screening for latent tuberculosis infection (LTBI). We analyzed the routine application of the Quantiferon-TB Gold (QFT-G) assay to detect and predict latent and active TB among HIV-infected patients in Australia. METHODS: A retrospective cohort study included all HIV-infected patients attending the Melbourne Sexual Health Service between March 2003 and February 2011 who were screened for LTBI using QFT-G. Clinical data were analyzed in multivariable models to determine predictors for QFT-G positivity using logistic regression and active TB development using Cox proportional hazards. RESULTS: Nine hundred seventeen HIV-infected patients had ≥1 QFT-G performed, of whom 884 (96.4%) were negative, 29 (3.2%) positive, and 4 (0.4%) indeterminate. The mean age was 40.9 years and 88% were male, with median follow-up of 26.4 (interquartile range 15.4-30.7) months. Five hundred fifty (63%) were Australian born, whereas 198 (23%) were born in Asia or Africa. QFT-G was positive in 2.0% of Australian-born, 5.3% of overseas-born [odds ratio: 2.6, 95% confidence interval (CI): 1.2 to 5.6, P = 0.017], and 12.7% of African-born patients (odds ratio 7.1, 95% CI: 2.9 to 17.3, P < 0.001). Two cases of culture-positive TB occurred after QFT-G screening in 3.4% of QFT-G-positive and 0.1% of QFT-G-negative patients (adjusted hazard ratio: 42.4, 95% CI: 2.2 to 827, P = 0.013), a rate of 111 (95% CI: 27.8 to 445) per 100,000 person-years. CONCLUSIONS: In this context, QFT-G has a high negative predictive (99.9%) value with few indeterminate results. A risk stratification approach to LTBI screening, where HIV-infected patients with epidemiological risk factors for TB infection undergo QFT-G testing, might be clinically appropriate and potentially cost effective in similar settings.

Molecular subtyping of Treponema pallidum during a local syphilis epidemic in men who have sex with men in Melbourne, Australia.

Treponema pallidum is the causative agent of syphilis, a sexually transmitted infection of significant public health importance. Since 2000 there has been a marked increase in the number of cases of syphilis infections notified in Victoria, Australia, with the majority of cases occurring in men who have sex with men (MSM) and the highest incidence being in HIV-infected MSM. The molecular subtyping method described by Pillay et al. (A. Pillay et al., Sex. Transm. Dis. 25:408-414, 1998) has been used in this study to determine the diversity of T. pallidum subtypes circulating locally and to look for any relationship between T. pallidum subtypes and HIV status over a 6-year period (2004 to 2009). Treponema pallidum DNA was detected in 303 patient specimens (n = 3,652), and full subtyping profiles were obtained from 90 of these (from 88 patients). A total of 11 T. pallidum subtypes were identified: types 14e (28, 31.1%), 14d (15, 16.7%), 14k (13, 14.4%), 14p (12, 13.3%), 14i (7, 7.8%) 14b (6, 6.7%), 14l (5, 5.6%), and 12i, 13b, 13i, and 13e (1 each, 1.1%). This study showed a similar level of variation among circulating T. pallidum strains compared with that in other studies using the same methodology. A different mix of strains and different predominating strains have been found at each geographical study location, with type 14e emerging as the predominant local strain in Victoria. There was no detectable trend between T. pallidum subtypes and the specimen collection site or stage of syphilis (where known), nor was there any relationship between particular strains and HIV status.

Undiagnosed and potentially lethal parasite infections among immigrants and refugees in Australia.

Intestinal parasite infections are a major cause of ill health in many resource-poor countries. This study compares the types and rates of these infections and their risk factors in recently arrived and long-term immigrants in Australia. Cross-sectional surveys of 127 East African and 234 Cambodian immigrants and refugees were undertaken in 2000 and 2002, respectively, to assess the burden of intestinal parasites and collect demographic information. Serum samples were assessed for eosinophilia and Strongyloides stercoralis and Schistosoma antibodies, and feces examined for ova, cysts, and parasites. Intestinal parasites were identified in 77/117 fecal samples from East African and in 25/204 samples collected from Cambodian participants. Eleven percent (14/124) of East Africans and 42% (97/230) of Cambodians had positive or equivocal serology for S stercoralis. Schistosoma serology was positive or equivocal in 15% (19/124) of East African participants. Potentially serious intestinal parasite infections are common among recent and longer term immigrants despite multiple visits to health care providers. Immigrants and refugees from high-risk countries would benefit from comprehensive health checks soon after resettlement.

An outbreak of Legionnaires' disease at the Melbourne Aquarium, April 2000: investigation and case-control studies.

OBJECTIVE: To investigate the source and risk factors associated with Australia's largest outbreak of Legionnaires' disease. DESIGN AND SETTING: Epidemiological and environmental investigation of cases of Legionnaires' disease associated with visits to the Melbourne Aquarium; two case-control studies to confirm the outbreak source and to investigate risk factors for infection, respectively. PARTICIPANTS: Patients with confirmed Legionnaires' disease who visited the Melbourne Aquarium between 11 and 27 April 2000 were compared (i) with control participants from the community, and (ii) with control participants selected from other visitors to the Aquarium during this period. MAIN OUTCOME MEASURES: Risk factors for acquiring Legionnaires' disease. RESULTS: There were 125 confirmed cases of Legionnaires' disease caused by Legionella pneumophila serogroup 1 associated with the Aquarium; 76% of patients were hospitalised, and four (3.2%) died. The Aquarium cooling towers were contaminated with this organism. Visiting the Aquarium was significantly associated with disease (odds ratio [OR], 207; 95% CI, 73-630). The case-control study indicated that current smoking was a dose-dependent risk (multivariable OR for currently smoking > 70 cigarettes/week, 13.5; 95% CI, 5-36), but chronic illness and duration of exposure at the site were not significant risks. CONCLUSIONS: This study showed an association between poorly disinfected cooling towers at the Aquarium and Legionnaires' disease in visitors, and confirmed current smoking as a critical risk factor. The rapid response, publicity, and widespread urinary antigen testing may have resulted in detection of milder cases and contributed to the relatively low apparent morbidity and mortality rates. The urinary antigen test allows rapid identification of cases and may be changing the severity of illness recognised as Legionnaires' disease and altering who is considered at risk.

An assessment of the Roche Amplicor Chlamydia trachomatis/Neisseria gonorrhoeae multiplex PCR assay in routine diagnostic use on a variety of specimen types.

The Roche Cobas Amplicor Chlamydia trachomatis/Neisseria gonorrhoeae polymerase chain reaction (PCR) assay can simultaneously detect both C. trachomatis and N. gonorrhoeae, and has been cleared by United States Food and Drug Administration (FDA) for the testing of endocervical and urethral swabs and urine specimens. The Amplicor N. gonorrhoeae PCR target sequence is known to be present in some strains of commensal Neisseria species, including N. cinerea and N. subflava, necessitating the use of a second PCR assay to confirm positive results. This study analyses the performance of the assay on 7,007 unselected specimens submitted to the laboratory for the PCR diagnosis of N. gonorrhoeae and C. trachomatis; compares the PCR assay with culture for the detection of N. gonorrhoeae; examines the performance of the assay with specimens from different body sites; and briefly compares two confirmatory PCR assays. Confirmation rates for an initial Amplicor N. gonorrhoeae positive result varied widely by specimen type, ranging from 86.2 per cent for penile/urethral swabs to 5.6 per cent for oropharyngeal swabs, indicating all positive Amplicor N. gonorrhoeae results should be confirmed by a second method to maintain adequate specificity. Overall there was 98.1 per cent agreement between the confirmed PCR assay and culture, with confirmed PCR showing a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 81.7 per cent, 99.5 per cent, 92.7 per cent and 98.5 per cent respectively, compared with N. gonorrhoeae culture. When confirmed C. trachomatis/N. gonorrhoeae PCR assay performance was analysed against culture using only FDA-cleared specimens (553 penile/ urethral swabs, urines and cervical/vaginal swabs), sensitivity, specificity, PPV and NPV and percent agreement were 96.7 per cent, 99.8 per cent, 98.9 per cent, 99.4 per cent and 99.3 per cent respectively. No significant differences were found between the two confirmatory PCR assays used during the study period. Limitations of Amplicor for the detection of N. gonorrhoeae and the appropriate use of combined C. trachomatis/N. gonorrhoeae PCR in a routine diagnostic setting are discussed.