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Original article
The epidemiology of gonococcal arthritis in an Indigenous Australian population
  1. Camilla S L Tuttle1,
  2. Thomas Van Dantzig2,
  3. Stephen Brady2,
  4. James Ward1,
  5. Graeme Maguire1,2,3
  1. 1Baker IDI Central Australia, Alice Springs Hospital, Alice Springs, Northern Territory, Australia
  2. 2Alice Springs Hospital, Alice Springs, Northern Territory, Australia
  3. 3School of Medicine, James Cook University, Cairns, Queensland, Australia
  1. Correspondence to Dr Graeme Maguire, Baker IDI Central Australia, Alice Springs Hospital, Rubuntja Building, Gap Road, Alice Springs, N T 0870, Australia; Graeme.maguire{at}bakeridi.edu.au

Abstract

Background Disseminated Gonococcal Infection (DGI) is caused by Neisseria gonorrhoeae bacteraemia. Typically the primary source is a sexually acquired mucosal infection. If not recognised and treated promptly DGI can be associated with significant morbidity and, in rare cases, death. Central Australia has one of the highest rates of gonococcal notifications in Australia. Despite this, the nature and prevalence of complications arising from gonococcal infections within this at-risk population is unknown.

Methods Enhanced surveillance and audit of patients with DGI discharged from Alice Springs Hospital between 2003 and 2012. Patient demographics and clinical management data were extracted from healthcare records and investigation databases.

Results DGI cases were significantly more likely to present in young (≤29 years) Indigenous women compared with young Indigenous men (χ2, p=0.020). Overall Indigenous women had nearly twice the risk of DGI compared with men (relative risk 1.92 (95% CI 1.45 to 2.53)). The incidence of DGI per all gonococcal notifications on average was 911/100 000 (95% CI 717 to 1142) gonococcal notifications.

Conclusions DGI represents a severe complication of N. gonorrhoeae infection. In Central Australia DGI is not a rare oddity but rather an important differential when dealing with patients with undefined sepsis and associated joint disease.

  • GONORRHOEA
  • SEXUAL HEALTH
  • ETHNICITY
  • GENDER
  • EPIDEMIOLOGY (CLINICAL)

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Background

Disseminated gonococcal infection (DGI) is caused by blood dissemination of the Gram-negative diplococcus Neisseria gonorrhoeae. Typically the infection is related to secondary dissemination from a primary sexually acquired mucosal infection.1 DGI develops in 0.5–3% of patients with a mucosal infection and is particularly seen in sexually active young women.1 In general patients with DGI present with severe polyarthritis that may be migratory or additive and can resolve spontaneously. In addition to polyarthritis, patients may also present with fever, maculopapular rash, tenosynovitis, sepsis and, occasionally, endocarditis.1–3 If not recognised and treated promptly DGI can lead to joint destruction and, in rare cases, uncontrolled and potentially life-threatening sepsis.4

In the 1970s DGI was a common cause of septic arthritis among young adults.5 However, since the implementation of control programmes and the birth of the antibiotic era the incidence of sexually transmissible gonococcal infections, a precursor for DGI, has decreased substantially in high-income and middle-income earning countries.1 Despite this, gonococcal notifications continue to rise in the socioeconomically disadvantaged populations of these countries. For example, the prevalence of gonorrhoea infections in Aboriginal Australians and Torres Strait Islanders (herein referred to as Indigenous) remains significantly higher than levels observed in non-Indigenous Australians.6 In particular the central desert region of Australia has some of the highest rate of sexually transmitted infections (STIs) in the country, attributed largely to its Indigenous population.6 Prevalence of STIs in the young Indigenous population of the Northern Territory (NT) has been reported to be as high as 16.5% in men and 21.9% in women.7

Despite the high notification rate of gonorrhoea within this area, the incidence of complications caused by this infection, such as DGI, within this population has never before been investigated. It was the aim of this study to determine the incidence and nature of DGI in Central Australia and identify individuals most at risk of developing this infection.

Methods

Setting

The NT is located in the central and central northern regions of Australia. Despite its large land mass (1.35 million square kilometres), the NT is sparsely populated (total population 211 943). However, the NT holds the highest proportion (30% of its total population) of Indigenous people in Australia.8

The Alice Springs Hospital (ASH), where this audit was conducted, is the primary hospital-based referral centre for the Central Australian region. It is a 180 bed hospital that services over 1.6 million square kilometres extending into the adjacent jurisdictions of Western Australian and South Australia.

Study design and data sources

Data for DGI cases between 2003 and 2012 were identified from the clinical information system maintained by the NT Department of Health. The term DGI is not defined in International classification of Diseases (ICD)-10-AM classification codes and therefore a range of non-genital gonococcal ICD-10-AM codes (A54.0, A54.1, A54.2, A54.3, A54.4, A54.5, A54.6, A54.8, A54.9, O98.2) was used to identify potential DGI cases. Data from potential cases were reviewed including written medical records and investigations. Using previously published definitions,2 Potential cases were defined as proven, probable or possible DGI:

  1. Proven Infection: Neisseria gonorrhoeae recovered from cultures or identified by Gram staining or nucleic acid amplification testing (NAAT) of specimens from blood, synovial fluid and/or skin lesions.

  2. Probable Infection: Clinical features of disseminated infection and typical response to antimicrobial treatment and N. gonorrhoeae identified from cultures of one or more mucosal site that included the cervix, urethra, anorectum or pharynx.

  3. Possible Infection: Clinical features of disseminated infection and typical response to antimicrobial treatment but N. gonorrhoeae not identified from any site.

Two neonatal infections were removed from the study cohort due to age and presumed vertical transmission.

Data collection

Data collected for cases of DGI included demographics, patient comorbidities, clinical features (including observational data and the site(s) of infection), laboratory investigations and management. The presence of clinical features including arthritis, tenosynovitis and maculopapular rash was based on medical record reporting. Fever was said to be present if a patient presented with a temperature of 37.7°C or greater.

Statistical analysis

The incidence of DGI in this Indigenous population was determined by dividing the number of cases of incident DGI by the total number of person-years accumulated in the study population. The study population was defined as the Indigenous population that resided within the ASH radius within the NT (Apatula, Barkly and Alice Springs regions as determined by the Australian census).8 Individuals living outside the NT were excluded from the analysis as it is not possible to determine the denominator population for cases residing in South and Western Australia. Due to their small numbers non-Indigenous patients (n=2) were excluded from incidence rate analysis. Incidence rates were further stratified by gender and age (5-year categories).

The incidence rate of DGI cases per all gonococcal notifications in this region was determined by dividing the number of reported DGI cases within a year by the number of reported gonococcal cases within this catchment area between 2003 and 2012.9 A direct standardised rate for DGI within this region was calculated using the WHO World Standard population data.10

Data analysis was undertaken using Stata V.13.0 (STATACorp LP, College Station, Texas, USA) and Graphpad Prism V. 6.0 (GraphPad Software, California, USA). Difference in the incidence of DGI between age groups and genders was calculated using the Pearson's χ2 test of association. Descriptive characteristics for the male and female cases were compared using the Pearson's χ2 test for categorical variables and the Student's t test for continuous variables. Results were considered statistically significant where p<0.05 and all tests were two-sided.

Results

Patient characteristics

Table 1 describes the patient demographics and clinical presentation of DGI cases is this setting. Between 2003 and 2012, 75 DGI cases were identified. In this setting the burden of DGI is particularly borne by Indigenous Australians with only 2.7% (95% CI 0.3% to 9.3%) of cases occurring in non-Indigenous Australians. Based on local population data and excluding cases from outside the NT the relative risk of DGI in Indigenous Australians in Central Australia compared with non-Indigenous Australians was 49.7 (95% CI 12.2 to 202.3).

Table 1

Patient demographics

Clinical presentation and treatment

Polyarthritis was the most common symptom associated with DGI (table 1). The knee and wrist joints were the joints most frequently affected by arthralgia. Approximately 30% of patients presented with fever and 13% of patients had tenosynovitis. Only one patient was recorded as having dermatitis and no patient presented with the classic DGI clinical triad of polyarthritis, tenosynovitis and dermatitis.1 ,2

Table 2 describes the laboratory investigations performed to confirm a diagnosis of DGI in this cohort. The most common method used to confirm DGI was NAAT for N. gonorrhoeae of a joint aspirate (proven DGI) followed by urinary NAAT (probable DGI). Men were significantly more likely to have a positive urine NAAT compared with women (p=0.03). In addition male cases of DGI also had significantly higher leucocyte (p=0.007) and neutrophil (p=0.002) counts compared with female cases.

Table 2

Laboratory investigations

Treatment of DGI typically involved cephalosporins (73%) followed by penicillin (43%). Forty-three per cent of patients were given a combination of penicillin and cephalosporin. Other antibiotics used included; macrolides (13%), fluoroquinolones (4%) and tetracyclines (4%).

Incidence of DGI in Central Australia

The average crude incidence rate of DGI for this region’s (Apatula, Barkley and Alice Springs, Census regions) Indigenous population was 39.9/100 000 person-years. Figure 1 outlines the age and gender stratified incidence rates of DGI. Individuals residing interstate were excluded from this analysis (n=7). The rate of DGI appeared higher in young girls, particularly those aged 10–14 years (74.7/100 000). DGI cases were significantly more likely to present in young (≤29 years) Indigenous women compared with young Indigenous men (χ2, p=0.020). In addition, Indigenous women under the age of 29 were significantly more likely to present with DGI compared with Indigenous women over the age of 30 years (χ2, p=0.021) (figure 1). Overall Indigenous women had nearly twice the risk of DGI compared with men (relative risk 1.92 (95% CI 1.45 to 2.53)).

Figure 1

Incidence of disseminated gonococcal infection (DGI)/100 000 (person-years) in Central Australia stratified by age and gender. Horizontal axis label ‘all men’ and ‘all women’ is reported as the mean/100 000 (95% CI).

Rates of DGI standardised to the WHO World Standard Population demonstrated an overall rate of DGI in Indigenous Australians residing within this region of 44/100 000 or 59/100 000 in women and 31/100 000 in men. The incidence of DGI per all gonococcal notifications in Central Australia is shown in figure 2 and on average was 911/100 000 (95% CI 717 to 1142) gonococcal notifications.

Figure 2

Annual incidence of disseminated gonococcal infection (DGI)/100 000 gonococcal notifications in Central Australia from 2003 to 2012. Horizontal axis label ‘All’ represents mean DGI/100 000 gonococcal notifications over the time frame with 95% CI.

Discussion

This is the first study to investigate the burden of DGI in Central Australia and identify those most at risk (young, Indigenous women) of developing DGI. The rate of DGI/100 000 gonococcal notifications reported here is more than twice that seen in previous reports.11 However, this finding is not unexpected given the endemic level of STIs in Central Australia.

Coinciding with previous studies, we found that DGI is largely a disease of young adults, particularly young women.1 ,2 However, it should be noted that some countries report a higher occurrence of DGI in the male population.12 Despite the average age of this cohort (27.8 years) being slightly older than previously described (22 years13 ,14), here we report that adolescent girls aged 10–14 years are particularly at risk of developing DGI. This finding highlights the need to consider DGI in adult patients and in a paediatric and an adolescent setting in Central Australia.

The presence of DGI in young, and presumably peripubertal, girls is concerning. However, this is not unexpected, given (A) prevalence of infections in remote communities; with almost one in four young women found to have an STI and (B) access to appropriate healthcare in these remote settings.15 ,16 Unfortunately, this also translates to an increased risk of STI-related gonorrhoea infections developing complications such as DGI.

Alternatively, an explanation for the higher rate of DGI in younger women in Central Australia may be a non-STI gonococcal infection, such as conjunctivitis. Goodyear-Smith17 has highlighted the occurrence of non-STI gonococcal infections in prepubertal children. There is evidence that such infections, particularly conjunctivitis, exist in remote Indigenous communities.18–20 In these cases the most likely mode of transmission is believed to be via hands, cloths and bush flies. Matters et al,21 have reported three cases whereby gonococcal conjunctivitis in this setting disseminated with a subsequent presentation of DGI.

Consistent with earlier studies this study also found that polyarthritis and tenosynovitis were the most common symptoms associated with a clinical presentation of DGI. Yet interestingly, the level of patients afflicted with tenosynovitis in this study is lower (13%) than that reported in prior investigations (61% and 33%).13 ,14 Suzaki et al12 outline the clinical course of DGI and suggest the clinical manifestation of DGI occurs in stages and report the onset of tenosynovitis occurring after arthralgia and arthritis. Thus, the lower level of tenosynovitis reported here may reflect early detection of DGI in our setting. This may also explain why the clinical triad (polyarthritis, tenosynovitis and dermatitis) of DGI was not observed in this cohort. Alternatively physicians may be unaware of the triad’s existence.

Despite, two decades passing between major DGI studies and this report, the microbial diagnosis and testing of DGI remains the same (blood, synovial fluid, urine), with the exception of rectal swabs. This study found that no diagnosis of DGI was made using rectal specimens; this coincides with the findings of a report by Belkacem et al.22 Interestingly, despite the use of laboratory confirmation to diagnose DGI, a relatively high proportion of patients with DGI from this study cohort had not been tested for HIV. This is of particular concern given DGI has previously been reported as the first presenting manifestation of HIV infection.23–25 Furthermore, there is also the tendency for different STIs to cluster in one individual15 ,16 ,26 and, as such, a cluster of STIs may alter treatment guidelines. Thus, anyone suspected of DGI should also have appropriate specimens collected and tested for other STIs and blood borne viruses, even if genitourinary symptoms are not present.

Overall, the antibiotics prescribed for most of the study cohort followed Australian guidelines. The current Australian recommendation for management of DGI is to initially use an intravenous third generation cephalosporin followed by an oral regime based on culture and susceptibility results for a total duration of therapy of at least 7 days.27 The increasing use of NAAT for diagnosis means susceptibility profiles are often not available. In remote areas of Australia where the prevalence of penicillin-resistant N. gonorrhoeae is low, as was found in this study,26 the use of a penicillin-based oral regime following initial use of a third generation cephalosporin may therefore be reasonable and appeared to reflect local practice seen here.

This study is not without limitations. The cases presented here reflect DGI cases that were admitted to ASH. As such people managed exclusively by primary or sexual healthcare clinics have not been included in this analysis. Therefore, the incidence of DGI in Central Australia could be higher than what has been reported here. However; recommended treatment guidelines for DGI require intramuscular or intravenous antibiotic administration for 24–48 h followed by oral therapy27 thus, it is thought that most cases of DGI would require inpatient hospital care. A conference abstract presented at the 2006 Australasian Sexual Health conference reported 20 DGI cases within the Alice Springs region between November of 2005 and June of 2006.28 This number of cases is substantially higher than those identified in this report for the same time period. However, it is unclear if consistent case definitions were used to define DGI in this abstract and thus, the relevance of these findings to our study is unclear. It is important to note, that 19% of our cohort has been classified as having a possible infection, where typical DGI symptoms were identified but a laboratory diagnosis could not confirm the clinical diagnosis. There is the possibility these ‘possible’ infections may have been caused by other bacteria known to cause septic arthritis such as Chlamydia trachomatis, Staphylococcus aureus and Streptococcus pyogenes.29

DGI represents a severe complication of N. gonorrhoeae infection. The key mechanism for preventing DGI is likely to lie in efforts to address the far more prevalent issue of sexually transmissible N. gonorrhoeae seen in this setting.9 While the current epidemic of gonorrhoea related urethritis and cervicitis persists it is likely that DGI rates will remain similarly high. Nonetheless data from STI programmes would indicate that a focus on condom use, case finding and early treatment is likely to reduce the overall burden of N. gonorrhoeae infection and related complications such as, DGI, pelvic inflammatory disease, infertility and HIV transmission.30 Thus, future research in this area should focus on behavioural data and developing effective prevention programmes for STIs.

Central Australia continues to face an epidemic of STIs of which gonorrhoea is one example. We have described the ‘tip of the iceberg’ with regards to gonorrhoea, a small but important group of people who develop secondary dissemination that requires inpatient care. In our setting DGI is not a rare oddity but rather an important differential when dealing with patients with undefined sepsis and associated joint disease.

Key messages

  • Disseminated gonococcal infection (DGI) is not a rare occurrence in remote communities but rather an important differential when dealing with undefined sepsis and associated joint disease.

  • Individuals most at risk of developing DGI in this setting are young (<29 years), Indigenous women.

  • When DGI is suspected, health practitioners should screen for other sexually transmitted infections as DGI is often the first presenting manifestation of a HIV infection.

  • The key mechanism for preventing DGI lies in efforts to address the far more prevalent issue of sexually transmissible Neisseria gonorrhoeae.

Acknowledgments

The authors thank Jillian Burgoyne the Health Information Services Manager at the Alice Springs Hospital, who assisted in separation data analysis. GM is supported by an NHMRC Practitioner Fellowship and the Margaret Ross Chair in Indigenous Health.

References

Footnotes

  • Handling editor Jackie Cassell

  • Contributors CSLT: Data collection, data analysis and manuscript preparation. TVD: Data collection and manuscript preparation. SB: Manuscript preparation. JW: Manuscript preparation. GM: Data analysis and manuscript preparation.

  • Competing interests None.

  • Ethics approval Central Australian Human Research Ethics Committee (HREC-13-185).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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