Search

To compare the findings of standard clinical assessments and of complementary clinical and laboratory methods for determining whether community-wide treatment for trachoma is warranted in a remote Queensland community.Three cross-sectional screening surveys, 2019-2021, complemented by laboratory pathology testing.Small community in northwest Queensland with geographic and cultural ties to Northern Territory communities where trachoma persists.Children aged 1-14 years; opportunistic screening of people aged 15 years or more.Prevalence of clinical signs of trachoma, Chlamydia trachomatis infection, ocular non-chlamydial infections, and seropositivity for antibodies to the C. trachomatis Pgp3 protein.During the three surveys, 73 examinations of 58 children aged 1-4 years, 309 of 171 aged 5-9 years, and 142 of 105 aged 10-14 years for trachoma were undertaken, as were 171 examinations of 164 people aged 15 years or more; 691 of 695 examinations were of Aboriginal or Torres Strait Islander people (99%), 337 were of girls or young women (48%). Clinical signs consistent with trachomatous inflammation-follicular were identified in 5-9-year-old children 23 times (7%), including in eleven with non-chlamydial infections and one with a C. trachomatis infection. One child (10-14 years) met the criteria for trachomatous scarring. Two of 272 conjunctival swab samples (all ages) were polymerase chain reaction-positive for C. trachomatis (0.7%). Two of 147 people aged 15 years or more examined in 2019 had trichiasis, both aged 40 years or more. Seven of 53 children aged 1-9 years in 2019 and seven of 103 in 2021 were seropositive for anti-Pgp3 antibodies.Despite the prevalence of clinical signs consistent with trachomatous inflammation-follicular among 5-9-year-old children exceeding the 5% threshold for community-wide treatment, laboratory testing indicated that childhood exposure to ocular C. trachomatis is rare in this community. Laboratory testing should be integrated into Australian trachoma guidelines.

Recent surveys identified trachomatous inflammation - follicular (TF) at endemic levels in the Torres Strait Islands; however, local health staff do not report trachomatous trichiasis (TT) in adults. We undertook a cross-sectional survey involving eye examination and microbiological testing to better understand this disconnect.We examined 169 of 207 (82%) residents and collected ocular swabs for polymerase chain reaction (PCR) testing for Chlamydia trachomatis. Other viral PCR tests and bacterial culture were also performed.TF prevalence in children aged 5-9 years was 23% (7/30). No ocular C. trachomatis was identified by PCR. For the 72 participants (43%) with follicles, bacterial culture was positive for 11 (15%) individuals. No individual had trachomatous trichiasis.Follicular conjunctivitis consistent with TF was prevalent but ocular C. trachomatis and cicatricial trachoma were absent. Non-chlamydial infections or environmental causes of follicular conjunctivitis may be causing TF in this community.In similar settings, reliance on simplified clinical assessment alone may lead to an overestimation of the public health problem posed by trachoma. Consideration should be given to incorporating C. trachomatis PCR, and in certain settings, a detailed clinical exam could be performed by an experienced ophthalmologist during prevalence surveys.

We undertook a screening program between 2016 and 2019 to determine if trachoma was endemic in the Torres Strait Islands of Queensland, Australia. Eleven screening surveys assessing trachoma prevalence were undertaken in seven communities using the World Health Organization (WHO) simplified grading tool. Additionally, an ophthalmologist performed a detailed clinical assessment including examination for Herbert’s pits and corneal pannus and, where clinically indicated, collection of conjunctival specimens to investigate the presence of Chlamydia trachomatis nucleic acid. Prevalence of trachomatous inflammation—follicular (TF) in children aged 5–9 years for the aggregated first survey across all communities was 6% (17/284). No child had trachomatous inflammation—intense, trachomatous scarring, corneal pannus, or Herbert’s pits. Of the 66 times any child was tested for C. trachomatis by polymerase chain reaction (PCR), the result was negative. No cicatricial trachoma was identified amongst the adults (n = 186) who were opportunistically offered examination. Whilst TF was present, the lack of intense inflammatory thickening in any child examined, the lack of end-stage trachomatous disease, and the lack of ocular C. trachomatis detection by PCR indicate trachoma is not endemic in the Torres Strait Islands, and no ongoing public health intervention is required. These findings add to a growing body of evidence suggesting that use of the WHO simplified grading tool alone in the peri-elimination setting may overestimate the community burden of trachoma.

Background The epidemiology of trachoma in several Pacific Islands differs from other endemic settings, in that there is a high prevalence of clinical signs of trachoma, particularly trachomatous inflammation—follicular (TF), but few cases of trichiasis and limited evidence of ocular chlamydial infection. This so-called “Pacific enigma” has led to uncertainty regarding the appropriate public health response. In 2019 alongside Nauru’s national trachoma population survey, we performed bacteriological and serological assessments of children to better understand the typology of trachoma and to determine whether there is a need for trachoma interventions. Methods We used two-stage cluster sampling, examining residents aged ≥1 year and collecting household-level water, sanitation, and hygiene (WASH) variables. Children aged 1–9 years provided conjunctival swabs and finger-prick dried blood spots to investigate the presence of Chlamydia trachomatis nucleic acid and anti-Pgp3 antibodies, respectively. Principal Findings In 818 participants aged 1–9 years, the age-adjusted TF prevalence was 21.8% (95% CI 15.2–26.2%); ocular C. trachomatis prevalence was 34.5% (95% CI 30.6–38.9), and anti-Pgp3 antibody prevalence was 32.1% (95% CI 28.4%–36.3%). The age- and gender-adjusted prevalence of trichiasis in ≥15-year-olds was 0.3% (95% CI 0.00–0.85), but no individual with trichiasis had trachomatous scarring (TS). Multivariable analysis showed an association between age and both TF (OR per year of age 1.3 [95% CI 1.2–1.4]) and anti-Pgp3 positivity (OR 1.2 [95% CI 1.2–1.3]). There were high rates of access to water and sanitation and no WASH variable was associated with the presence of TF. Conclusions TF, nucleic acid, and age-specific antibody prevalence collectively indicate that high levels of C. trachomatis transmission among children present a high risk of ocular damage due to trachoma. The absence of trichiasis with trachomatous scarring suggest a relatively recent increase in transmission intensity.

Summary Background The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults. Methods In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18–50 years with a body-mass index of 18·0–35·0 kg/m2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1–4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538. Findings Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3–735·1) for cohort 1, 466·3 h (382·8–522·3) for cohort 2, 397·0 h (333·9–491·8) for cohort 3, and 466·7 h (351·0–889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6–592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study. Interpretation Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections. Funding Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program.

Background: The henipaviruses, Hendra virus and Nipah virus, are emerging zoonotic pathogens of bat origins that have been associated with poor clinical outcomes in humans. The monoclonal antibody (mAb) m102∙4 is a potent fully human antibody that neutralizes Hendra and Nipah viruses in vitro and in vivo. Clinical trials in humans represent the next stage in the utilization of this antibody in the prophylactic treatment and prevention of deaths from henipavirus infections. Methods: We performed a randomised, double-blind, placebo-controlled, singlecentre, dose escalation phase 1 study using the human monoclonal antibody m102∙4. Healthy adults aged 18-50 years with a body-mass index of 18.0 to ≤35.0 kg/m2 were assigned to one of five cohorts. A sentinel pair for each cohort was randomised in a 1:1 ratio to receive either active treatment or placebo. The remaining participants in each cohort were randomised 5:1 to receive m102∙4 or placebo. Cohorts 1 to 4 received a single intravenous infusion of m102∙4 at doses of 1, 3, 10, and 20 mg/kg respectively, and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg, 72 hours apart, with monitoring for 123 days. The primary objective was to assess the safety and tolerability of single and multiple IV doses of m102∙4 mAb. We also assessed pharmacokinetics, immunogenicity, and virus neutralisation. Analyses were completed according to protocol. Findings: Between April 15, 2015 and June 16, 2016, 77 healthy adults were screened and 40 participants were enrolled in the study; eight were assigned to each cohort (six randomised to receive m102∙4, and two randomised to receive placebo per cohort). A total of 86 treatment-emergent adverse events were reported by the 40 participants with similar rates between placebo and active treatment groups. Thirty-one events reported in 20 participants (50%) receiving m102∙4 were considered treatment-related, and six events were reported in five participants (50%) receiving placebo. A possible trend of treatment-related headaches with m102∙4 was noted; this was reported in 66.7% of participants administered singledose m102∙4 compared with 10% of those administered placebo. There was no increase in treatment-related headaches among those with repeat dosing. There were no deaths or severe adverse events leading to withdrawals or premature discontinuations during the study. Pharmacokinetics based on those receiving active treatment (n=30) were linear, with the mean halflife ranging from 16.5 to 27.6 days across Cohorts 1-4. There was small to moderate accumulation of monoclonal antibody in those receiving a repeat dose (Cohort 5), with elimination kinetics that were comparable to those receiving a single dose. Anti-m102∙4 antibodies were not detected at any time-point during the study. All serum samples at all time points exhibited virus-neutralisation activity when tested in vitro for both HeV and NiV. Interpretation: m102∙4 single and repeated dosing of up to two doses separated by 3 days appears to be safe and well tolerated when administered to healthy adult volunteers. A standard pharmacokinetic profile was observed with linear elimination kinetics. There was no evidence of an immunogenic response to m102∙4. Exploratory virus neutralisation studies confirmed that m102∙4 remained active for at least 8 days following administration of a clinically relevant dose. This study will inform future dosing regimens for m102∙4 to achieve prolonged exposure for systemic efficacy against henipaviruses. Trial Registration: The study was registered on the Australian New Zealand Clinical Trials Registry, registration number ACTRN12615000395538. Funding Statement: Queensland Department of Health, the National Health and Medical Research Council and the National Hendra Virus Research Program. Declaration of Interests: CCB is a US federal employee; and CCB and DSD are co-inventors on US patent Nos. 7,988,971 and 8,313,746 “Human monoclonal antibodies against Hendra and Nipah viruses”; assignees are The United States of America as represented by the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. (Bethesda, MD). All other authors declare no competing interests. Ethics Approval Statement: Ethics approval was obtained from the study site’s Human Research Ethics Committee at the QIMR Berghofer Medical Research Institute before participant enrolment commenced. The study was conducted under the Therapeutic Goods Administration (TGA) Clinical Trial Notification Scheme (CTN) and in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines, and the National Health and Medical Research (NHMRC) statement on ethical conduct in human research.

Although there is a substantial research literature on the effects of random responding on the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen,Kaemmer, 1989), there are very few studies available on this topic with the MMPI-A (Butcher et al., 1992). Archer and Elkins (1999) found that MMPI-A validity scales F and VRIN were particularly useful in detecting entirely random profiles from those derived standardly in clinical settings but noted that "all random" protocols could not be used to evaluate the usefulness of the T-score difference between the first half (F1) and the second half (F2) of the MMPI-A test booklet. Following up on this issue, this study extended the methodology of previous research by examining the hit rate, positive predictive power, negative predictive power, sensitivity, and specificity of VRIN, F, F1, F2 and the absolute value of the T-score difference between F1 and F2 (denoted as IF1-F21) in 5 samples varying in the degree of protocol randomness. One of the samples consisted of 100 adolescent inpatients administered the MMPI-A under standard instructions, and another sample consisted of 100 protocols randomly generated by computer. The additional 3 samples of 100 protocols each contained varying degrees of computer-generated randomness introduced in the latter half of the MMPI-A item pool. Over- all, the results generally indicate that several MMPI-A validity scales are useful in detecting protocols that are largely random, but all of these validity scales are more limited in detecting partially random responding that involves less than half the total item pool located in the second half of the test booklet. Clinicians should be particularly cautious concerning validity inferences based on the observed T-score difference that occurs for the F1 and F2 subscales and current findings do not support the clinical usefulness of this index.

The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher et al., 1992) was released in 1992 and has rapidly become the most widely used objective personality assessment instrument with adolescents. Although the MMPI-A reduced or eliminated several problems associated with the use of the original MMPI (Hathaway & McKinley, 1943) with adolescents, the MMPI-A does produce a high frequency of within normal limits basic scale profiles for individuals with substantial psychopathology including adolescents in inpatient psychiatric settings. To better understand the reasons for this phenomenon, we compared the item endorsement frequencies for the MMPI-A normative sample with results from two adolescent clinical samples, and these results were contrasted to the item endorsement frequencies for the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) normative sample and a clinical sample of adult psychiatric inpatients. Results showed that the MMPI-A contains a substantial number of items that do not show a significant difference in item endorsement frequency between normative and clinical samples. Furthermore, MMPI-A basic and content scales generally show a much lower percentage of effective items than do the corresponding scales for the MMPI-2. We discuss the findings in relation to the frequent occurrence of low range MMPI-A profiles in clinical samples and the potential usefulness of these results in future efforts to develop viable short forms for the MMPI-A.