Recurrence patterns identify aggressive form of human papillomavirus-dependent vulvar cancer.

BACKGROUND: Vulvar cancer is rare and, as a result, is understudied. Treatment is predominantly surgery, irrespective of the type of vulvar cancer, and is associated with physical, emotional and sexual complications. A cluster of human papillomavirus (HPV)-dependent vulvar cancer patients was identified in Arnhem Land Northern Territory (NT), Australia, in which young Indigenous women were diagnosed at 70 times the national incidence rate. AIMS: To assess whether women from the Arnhem Land cluster differ from women with vulvar squamous cell carcinoma (VSCC) and vulvar intraepithelial neoplasia (VIN) resident elsewhere in the NT in recurrence after treatment, disease progression and mortality. MATERIALS AND METHODS: A retrospective cohort study of NT-resident women diagnosed with VIN or invasive vulvar cancer (VSCC) between 1 January 1993 and 30 June 2015 was undertaken. Time to recurrence was assessed using cumulative incidence plots and Fine and Gray competing risk regression models. Mean cumulative count was used to estimate the burden of recurrent events. RESULTS: Indigenous women from Arnhem Land experienced more recurrences after treatment than non-Indigenous women, the cancers recurred faster, and Indigenous women have worse survival at five years. CONCLUSIONS: In characterising the epidemiological features of this cluster, we have identified a particularly aggressive form of vulvar cancer. This provides a unique opportunity for elucidating the aetiopathological pathways driving vulvar cancer development that may ultimately lead to preventive and therapeutic targets for this neglected malignancy. Further, these findings have important implications for clinical practice and HPV vaccination policy in the affected population.

Perspectives of primary health care staff on the implementation of a sexual health quality improvement program: a qualitative study in remote aboriginal communities in Australia.

BACKGROUND: Young people living in remote Australian Aboriginal communities experience high rates of sexually transmissible infections (STIs). STRIVE (STIs in Remote communities, ImproVed and Enhanced primary care) was a cluster randomised control trial of a sexual health continuous quality improvement (CQI) program. As part of the trial, qualitative research was conducted to explore staff perceptions of the CQI components, their normalisation and integration into routine practice, and the factors which influenced these processes. METHODS: In-depth semi-structured interviews were conducted with 41 clinical staff at 22 remote community clinics during 2011-2013. Normalisation process theory was used to frame the analysis of interview data and to provide insights into enablers and barriers to the integration and normalisation of the CQI program and its six specific components. RESULTS: Of the CQI components, participants reported that the clinical data reports had the highest degree of integration and normalisation. Action plan setting, the Systems Assessment Tool, and the STRIVE coordinator role, were perceived as adding value to the program, but were less readily integrated or normalised. The remaining two components (dedicated funding for health promotion and service incentive payments) were seen as least relevant. Our analysis also highlighted factors which enabled greater integration of the CQI components. These included familiarity with CQI tools, increased accountability of health centre staff and the translation of the CQI program into guideline-driven care. The analysis also identified barriers, including high staff turnover, limited time involved in the program and competing clinical demands and programs. CONCLUSIONS: Across all of the CQI components, the clinical data reports had the highest degree of integration and normalisation. The action plans, systems assessment tool and the STRIVE coordinator role all complemented the data reports and allowed these components to be translated directly into clinical activity. To ensure their uptake, CQI programs must acknowledge local clinical guidelines, be compatible with translation into clinical activity and have managerial support. Sexual health CQI needs to align with other CQI activities, engage staff and promote accountability through the provision of clinic specific data and regular face-to-face meetings. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610000358044 . Registered 6/05/2010. Prospectively Registered.

Coinfection with Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis: a cross-sectional analysis of positivity and risk factors in remote Australian Aboriginal communities.

OBJECTIVES: To determine the co-occurrence and epidemiological relationships of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) in a high-prevalence setting in Australia. METHODS: In the context of a cluster randomised trial in 68 remote Aboriginal communities, we obtained laboratory reports on simultaneous testing for CT, NG and TV by nucleic acid amplification tests in individuals aged ≥16 years and examined relationships between age and sex and the coinfection positivity. ORs were used to determine which infections were more likely to co-occur by demographic category. RESULTS: Of 13 480 patients (median age: 30 years; men: 37%) tested for all three infections during the study period, 33.3% of women and 21.3% of men had at least one of them, highest in patients aged 16-19 years (48.9% in women, 33.4% in men). The most frequent combination was CT/NG (2.0% of women, 4.1% of men), and 1.8% of women and 0.5% of men had all three. In all co-combinations, coinfection positivity was highest in patients aged 16-19 years. CT and NG were highly predictive of each other's presence, and TV was associated with each of the other two infections, but much more so with NG than CT, and its associations were much stronger in women than in men. CONCLUSIONS: In this remote high-prevalence area, nearly half the patients aged 16-19 years had one or more sexually transmitted infections. CT and NG were more common dual infections. TV was more strongly associated with NG coinfections than with CT. These findings confirm the need for increased simultaneous screening for CT, NG and TV, and enhanced control strategies. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610000358044.

Incidence of curable sexually transmissible infections among adolescents and young adults in remote Australian Aboriginal communities: analysis of longitudinal clinical service data.

OBJECTIVES: To undertake the first comprehensive analysis of the incidence of three curable sexually transmissible infections (STIs) within remote Australian Aboriginal populations and provide a basis for developing new control initiatives. METHODS: We obtained all results for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) testing conducted during 2009-2011 in individuals aged ≥16 years attending 65 primary health services across central and northern Australia. Baseline prevalence and incidence of all three infections was calculated by sex and age group. RESULTS: A total of 17 849 individuals were tested over 35 months. Baseline prevalence was 11.1%, 9.5% and 17.6% for CT, NG and TV, respectively. During the study period, 7171, 7439 and 4946 initially negative individuals had a repeat test for CT, NG and TV, respectively; these were followed for 6852, 6981 and 6621 person-years and 651 CT, 609 NG and 486 TV incident cases were detected. Incidence of all three STIs was highest in 16-year-olds to 19-year-olds compared with 35+ year olds (incident rate ratio: CT 10.9; NG 11.9; TV 2.5). In the youngest age group there were 23.4 new CT infections per 100 person-years for men and 29.2 for women; and 26.1 and 23.4 new NG infections per 100 person-years in men and women, respectively. TV incidence in this age group for women was also high, at 19.8 per 100 person-years but was much lower in men at 3.6 per 100 person-years. CONCLUSIONS: This study, the largest ever reported on the age and sex specific incidence of any one of these three curable infections, has identified extremely high rates of new infection in young people. Sexual health is a priority for remote communities, but will clearly need new approaches, at least intensification of existing approaches, if a reduction in rates is to be achieved.

Runs of homozygosity and a cluster of vulvar cancer in young Australian Aboriginal women.

OBJECTIVE: A cluster of vulvar cancer exists in young Aboriginal women living in remote communities in Arnhem Land, Australia. A genetic case-control study was undertaken involving 30 cases of invasive vulvar cancer and its precursor lesion, high-grade vulvar intraepithelial neoplasia (VIN), and 61 controls, matched for age and community of residence. It was hypothesized that this small, isolated population may exhibit increased autozygosity, implicating recessive effects as a possible mechanism for increased susceptibility to vulvar cancer. METHODS: Genotyping data from saliva samples were used to identify runs of homozygosity (ROH) in order to calculate estimates of genome-wide homozygosity. RESULTS: No evidence of an effect of genome-wide homozygosity on vulvar cancer and VIN in East Arnhem women was found, nor was any individual ROH found to be significantly associated with case status. This study found further evidence supporting an association between previous diagnosis of CIN and diagnosis of vulvar cancer or VIN, but found no association with any other medical history variable. CONCLUSIONS: These findings do not eliminate the possibility of genetic risk factors being involved in this cancer cluster, but rather suggest that alternative analytical strategies and genetic models should be explored.

STI in remote communities: improved and enhanced primary health care (STRIVE) study protocol: a cluster randomised controlled trial comparing 'usual practice' STI care to enhanced care in remote primary health care services in Australia.

BACKGROUND: Despite two decades of interventions, rates of sexually transmissible infections (STI) in remote Australian Aboriginal communities remain unacceptably high. Routine notifications data from 2011 indicate rates of chlamydia and gonorrhoea among Aboriginal people in remote settings were 8 and 61 times higher respectively than in the non-Indigenous population. METHODS/DESIGN: STRIVE is a stepped-wedge cluster randomised trial designed to compare a sexual health quality improvement program (SHQIP) to usual STI clinical care delivered in remote primary health care services. The SHQIP is a multifaceted intervention comprising annual assessments of sexual health service delivery, implementation of a sexual health action plan, six-monthly clinical service activity data reports, regular feedback meetings with a regional coordinator, training and financial incentive payments. The trial clusters comprise either a single community or several communities grouped together based on geographic proximity and cultural ties. The primary outcomes are: prevalence of chlamydia, gonorrhoea and trichomonas in Aboriginal residents aged 16-34 years, and performance in clinical management of STIs based on best practice indicators. STRIVE will be conducted over five years comprising one and a half years of trial initiation and community consultation, three years of trial conditions, and a half year of data analysis. The trial was initiated in 68 remote Aboriginal health services in the Northern Territory, Queensland and Western Australia. DISCUSSION: STRIVE is the first cluster randomised trial in STI care in remote Aboriginal health services. The trial will provide evidence to inform future culturally appropriate STI clinical care and control strategies in communities with high STI rates. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610000358044.

Investigating a cluster of vulvar cancer in young women: a cross-sectional study of genital human papillomavirus prevalence.

BACKGROUND: Vulvar cancer is a relatively rare malignancy, which occurs most often in postmenopausal women. We have previously identified a geographic cluster of vulvar cancer in young Indigenous women living in remote communities in the Arnhem Land region of Australia. In this population, we investigated the prevalence of oncogenic human papillomavirus (HPV) infection in anogenital samples (vulvar/vaginal/perianal area and cervix) and compared the overall, type-specific and multiple infection prevalence between sites. METHODS: A cross-sectional survey of 551 Indigenous women aged 18-60 years was undertaken in 9 Arnhem Land communities. Women were consented for HPV detection and genotyping collected by a combined vulvar/vaginal/perianal (VVP) sweep swab and a separate PreservCyt endocervical sample collected during Pap cytology screening. HPV DNA testing was undertaken using PCR with broad spectrum L1 consensus PGMY09/11 primers with genotyping of positive samples by Roche Linear Array. The primary outcomes were the prevalence of cervical and VVP high-risk (HR) HPV. RESULTS: The prevalence of VVP HR-HPV was 39%, which was significantly higher than the cervical HR-HPV prevalence (26%, p<0.0001). HPV-16 was the most common genotype detected in both sites (VVP 11%, cervical 6%). HPV-16 infection peaked in women aged <20 years; however, there was a marked decline in cervical HPV-16 prevalence with age (p=0.007), whereas following an initial decline, the prevalence of VVP HPV-16 remained constant in subsequent age-groups (p=0.835). CONCLUSIONS: In this population experiencing a cluster of vulvar cancer, the prevalence of cervical oncogenic HPV infection was similar to that reported by studies of other Australian women; however there was a significantly higher prevalence of vulvar/vaginal/perianal infection to cervical. The large discrepancy in HPV prevalence between anogenital sites in this population may represent more persistent infection at the vulva. This needs further investigation, including the presence of possible environmental and/or genetic factors that may impair host immunity.

Strategies to improve control of sexually transmissible infections in remote Australian Aboriginal communities: a stepped-wedge, cluster-randomised trial.

BACKGROUND: Remote Australian Aboriginal communities have among the highest diagnosed rates of sexually transmissible infections (STIs) in the world. We did a trial to assess whether continuous improvement strategies related to sexual health could reduce infection rates. METHODS: In this stepped-wedge, cluster-randomised trial (STIs in remote communities: improved and enhanced primary health care [STRIVE]), we recruited primary health-care centres serving Aboriginal communities in remote areas of Australia. Communities were eligible to participate if they were classified as very remote, had a population predominantly of Aboriginal people, and only had one primary health-care centre serving the population. The health-care centres were grouped into clusters on the basis of geographical proximity to each other, population size, and Aboriginal cultural ties including language connections. Clusters were randomly assigned into three blocks (year 1, year 2, and year 3 clusters) using a computer-generated randomisation algorithm, with minimisation to balance geographical region, population size, and baseline STI testing level. Each year for 3 years, one block of clusters was transitioned into the intervention phase, while those not transitioned continued usual care (control clusters). The intervention phase comprised cycles of reviewing clinical data and modifying systems to support improved STI clinical practice. All investigators and participants were unmasked to the intervention. Primary endpoints were community prevalence and testing coverage in residents aged 16-34 years for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. We used Poisson regression analyses on the final dataset and compared STI prevalences and testing coverage between control and intervention clusters. All analyses were by intention to treat and models were adjusted for time as an independent covariate in overall analyses. This study was registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12610000358044. FINDINGS: Between April, 2010, and April, 2011, we recruited 68 primary care centres and grouped them into 24 clusters, which were randomly assigned into year 1 clusters (estimated population aged 16-34 years, n=11 286), year 2 clusters (n=10 288), or year 3 clusters (n=13 304). One primary health-care centre withdrew from the study due to restricted capacity to participate. We detected no difference in the relative prevalence of STIs between intervention and control clusters (adjusted relative risk [RR] 0·97, 95% CI 0·84-1·12; p=0·66). However, testing coverage was substantially higher in intervention clusters (22%) than in control clusters (16%; RR 1·38; 95% CI 1·15-1·65; p=0·0006). INTERPRETATION: Our intervention increased STI testing coverage but did not have an effect on prevalence. Additional interventions that will provide increased access to both testing and treatment are required to reduce persistently high prevalences of STIs in remote communities. FUNDING: Australian National Health and Medical Research Council.

Patient, staffing and health centre factors associated with annual testing for sexually transmissible infections in remote primary health centres.

BACKGROUND: In high-incidence Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) settings, annual re-testing is an important public health strategy. Using baseline laboratory data (2009-10) from a cluster randomised trial in 67 remote Aboriginal communities, the extent of re-testing was determined, along with the associated patient, staffing and health centre factors. METHODS: Annual testing was defined as re-testing in 9-15 months (guideline recommendation) and a broader time period of 5-15 months following an initial negative CT/NG test. Random effects logistic regression was used to determine factors associated with re-testing. RESULTS: Of 10559 individuals aged ≥16 years with an initial negative CT/NG test (median age=25 years), 20.3% had a re-test in 9-15 months (23.6% females vs 15.4% males, P<0.001) and 35.2% in 5-15 months (40.9% females vs 26.5% males, P<0.001). Factors independently associated with re-testing in 9-15 months in both males and females were: younger age (16-19, 20-24 years); and attending a centre that sees predominantly (>90%) Aboriginal people. Additional factors independently associated with re-testing for females were: being aged 25-29 years, attending a centre that used electronic medical records, and for males, attending a health centre that employed Aboriginal health workers and more male staff. CONCLUSIONS: Approximately 20% of people were re-tested within 9-15 months. Re-testing was more common in younger individuals. Findings highlight the importance of recall systems, Aboriginal health workers and male staff to facilitate annual re-testing. Further initiatives may be needed to increase re-testing.

Improving access to medicines among clients of remote area Aboriginal and Torres Strait Islander Health Services.

Despite unequivocally worse health, expenditure on Indigenous people through the Pharmaceutical Benefits Scheme (PBS) is considerably less than for other Australians. We report on the effectiveness of a program to supply PBS medicines to remote Aboriginal and Torres Strait Islander Health Services (ATSIHSs) under section 100 (s. 100) of the National Health Act 1953. THE PROGRAM: Under the special PBS arrangements (SPBSAs), approved ATSIHSs are able to order PBS medicine in bulk through local pharmacies and supply them as needed to patients on-site. The usual co-payment associated with PBS medicine is not charged and the pharmacist remuneration structure is different. METHODS: The project involved consultation with the evaluation reference group and other stakeholders at all stages. There were six main data collection components: public submissions; interviews with government and other key stakeholders; pharmacist survey; medicine utilisation and expenditure data; national ATSIHS minimum dataset; and case studies of ATSIHSs. RESULTS: These SPBSA potentially benefit 36% of the Aboriginal and Torres Strait Islander population. They have resulted in improved access to much-needed medicines, representing an increase of dollar 36.5 million in expenditure on Aboriginal and Torres Strait Islander people through the PBS between 2000/01 and 2002/03. They have further ensured that dollar 8.3 million of State and Territory expenditure formerly directed at medicine can be spent on prevention and primary care. CONCLUSION: Overall, the SPBSAs have been very successful and demonstrates an effective model for the development of Indigenous health policy.

High chlamydia and gonorrhoea repeat positivity in remote Aboriginal communities 2009-2011: longitudinal analysis of testing for re-infection at 3 months suggests the need for more frequent screening.

Background Extremely high rates of diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been recorded in remote communities across northern and central Australia. Re-testing at 3 months, after treatment administered, of CT or NG is recommended to detect repeat infections and prevent morbidity and ongoing transmission. METHODS: Baseline CT and NG laboratory data (2009-2010) from 65 remote health services participating in a cluster randomised trial was used to calculate the proportion of individuals re-tested after an initial CT or NG diagnosis at <2 months (not recommended), 2-4 months (recommended) and 5-12 months and the proportion with repeat positivity on re-test. To assess if there were difference in re-testing and repeat positivity by age group and sex, t-tests were used. RESULTS: There was a total of 2054 people diagnosed with CT and/or NG in the study period; 14.9% were re-tested at 2-4 months, 26.9% at 5-12 months, a total of 41.8% overall. Re-testing was higher in females than in males in both the 2-4-month (16.9% v. 11.5%, P<0.01) and 5-12-month (28.9% v. 23.5%, P=0.01) periods. Women aged 25-29 years had a significantly higher level of re-testing 5-12 months post-diagnosis than females aged 16-19 years (39.8% v. 25.4%, P<0.01). There was a total of 858 people re-tested at 2-12 months and repeat positivity was 26.7%. There was higher repeat NG positivity than repeat CT positivity (28.8% v. 18.1%, P<0.01). CONCLUSIONS: Just under half the individuals diagnosed with CT or NG were re-tested at 2-12 months post-diagnosis; however, only 15% were re-tested in the recommended time period of 2-4 months. The higher NG repeat positivity compared with CT is important, as repeat NG infections have been associated with higher risk of pelvic inflammatory disease-related hospitalisation. Findings have implications for clinical practice in remote community settings and will inform ongoing sexual health quality improvement programs in remote community clinics.

Barriers and facilitators of sexually transmissible infection testing in remote Australian Aboriginal communities: results from the Sexually Transmitted Infections in Remote Communities, Improved and Enhanced Primary Health Care (STRIVE) Study.

UNLABELLED: Background Remote Australian Aboriginal communities experience high rates of bacterial sexually transmissible infections (STI). A key strategy to reduce STIs is to increase testing in primary health care centres. The current study aimed to explore barriers to offering and conducting STI testing in this setting. METHODS: A qualitative study was undertaken as part of the STI in Remote communities, Improved and Enhanced Primary Health Care (STRIVE) project; a large cluster randomised controlled trial of a sexual health quality improvement program. We conducted 36 in-depth interviews in 22 participating health centres across four regions in northern and central Australia. RESULTS: Participants identified barriers including Aboriginal cultural norms that require the separation of genders and traditional kinship systems that prevent some staff and patients from interacting, both of which were exacerbated by a lack of male staff. Other common barriers were concerns about client confidentiality (lack of private consulting space and living in small communities), staff capacity to offer testing impacted by the competing demands for staff time, and high staff turnover resulting in poor understanding of clinic systems. Many participants also expressed concerns about managing positive test results. To address some of these barriers, participants revealed informal strategies, such as team work, testing outside the clinic and using adult health checks. CONCLUSIONS: Results identify cultural, structural and health system issues as barriers to offering STI testing in remote communities, some of which were overcome through the creativity and enthusiasm of individuals rather than formal systems. Many of these barriers can be readily addressed through strengthening existing systems of cultural and clinical orientation and educating staff to view STI in a population health framework. However others, particularly issues in relation to culture, kinship ties and living in small communities, may require testing modalities that do not rely on direct contact with health staff or the clinic environment.

Reasons for delays in treatment of bacterial sexually transmissible infections in remote Aboriginal communities in Australia: a qualitative study of healthcentre staff.

UNLABELLED: Background Remote Aboriginal communities in Australia experience high rates of bacterial sexually transmissible infections (STIs). To control the transmission and decrease the risk of complications, frequent STI testing combined with timely treatment is required, yet significant delays in treatment have been reported. Perceived barriers to timely treatment for asymptomatic patients in remote communities were explored. METHODS: A qualitative study was undertaken as part of the STRIVE (STIs in Remote communities, ImproVed and Enhanced primary health care) project; a cluster randomised controlled trial of a sexual health quality improvement program. During 2012, we conducted 36 in-depth interviews with staff in 22 clinics in remote Australia. RESULTS: Participants included registered nurses (72%) and Aboriginal health practitioners (28%). A key barrier to timely treatment was infrequent transportation of specimens to laboratories often hundreds of kilometres away from clinics. Within clinics, there were delays checking and actioning test results, and under-utilisation of systems to recall patients. Participants also described difficulties in physically locating patients due to: (i) high mobility between communities; and (ii) low levels of community knowledge created by high staff turnover. Participants also suggested strategies to overcome some barriers such as dedicated clinical time to follow-up recalls and taking treatment out to patients. CONCLUSIONS: Participants identified barriers to timely STI treatment in remote Aboriginal communities, and systems to address some of the barriers. Innovative strategies such as point-of-care testing or increased support for actioning results, coupled with incentives to individual patients to attend for results, may also assist in decreasing the time to treatment.

Investigating a cluster of vulvar cancers in young women: distribution of human papillomavirus and HPV-16 variants in vulvar dysplastic or neoplastic biopsies.

BACKGROUND: A high incidence of vulvar cancer, and its precursor lesion, high-grade vulvar intraepithelial neoplasia (VIN) has been identified in young Indigenous women living in the Arnhem Land region of the Northern Territory (NT) of Australia. This clustering is restricted to women aged <50 years, suggesting that oncogenic human papillomavirus (HPV) is a key causal factor. This study compared the HPV genotype prevalence, HPV-16 variant distribution and p16(INK4a)expression in stored vulvar cancer and high-grade VIN biopsy specimens from women residing in Arnhem Land, with specimens taken from Indigenous and non-Indigenous women in other regions of NT where there is no observed increase in vulvar cancer incidence. METHODS: Twenty high-grade VIN and 10 invasive cancer biopsies were assessed from Arnhem Land along with 24 high-grade VIN and 10 invasive cancer biopsies from other regions of NT. RESULTS: Biopsies from Arnhem Land were similar to those from other regions in the detection of high-risk (HR) or possible HR HPV (VIN: 95% and 84% respectively for Arnhem Land and other regions, P=0.356; invasive cancer: 100% and 80%, P=0.473), HPV-16 (VIN: 60% and 80%, P=0.364; invasive cancer: 70% and 70%, P=1.0) and p16(INK4a) expression (VIN: 90% and 84%, P=0.673; invasive cancer: 100% and 80%, P=0.474). All HPV-16 variants were of the European prototype. CONCLUSION: Comparison of biopsies revealed no significant difference in the frequency of oncogenic HPVs or HPV-16 variant types between Arnhem Land and other regions, suggesting another cofactor in this cluster.

Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections: comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context.

BACKGROUND: A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). METHODS: CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. RESULTS: Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. CONCLUSIONS: WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided.

Rates of radiologically confirmed pneumonia as defined by the World Health Organization in Northern Territory Indigenous children.

OBJECTIVE: To determine the burden of hospitalised, radiologically confirmed pneumonia (World Health Organization protocol) in Northern Territory Indigenous children. DESIGN, SETTING AND PARTICIPANTS: Historical, observational study of all hospital admissions for any diagnosis of NT resident Indigenous children, aged between > or = 29 days and < 5 years, 1 April 1997 to 31 March 2005. INTERVENTION: All chest radiographs taken during these admissions, regardless of diagnosis, were assessed for pneumonia in accordance with the WHO protocol. MAIN OUTCOME MEASURE: The primary outcome was endpoint consolidation (dense fluffy consolidation [alveolar infiltrate] of a portion of a lobe or the entire lung) present on a chest radiograph within 3 days of hospitalisation. RESULTS: We analysed data on 24,115 hospitalised episodes of care for 9492 children and 13,683 chest radiographs. The average annual cumulative incidence of endpoint consolidation was 26.6 per 1000 population per year (95% CI, 25.3-27.9); 57.5 per 1000 per year in infants aged 1-11 months, 38.3 per 1000 per year in those aged 12-23 months, and 13.3 per 1000 per year in those aged 24-59 months. In all age groups, rates of endpoint consolidation in children in the arid southern region of NT were about twice that of children in the tropical northern region. CONCLUSION: The rates of severe pneumonia in hospitalised NT Indigenous children are among the highest reported in the world. Reducing this unacceptable burden of disease should be a national health priority.