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Coinfection with Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis: a cross-sectional analysis of positivity and risk factors in remote Australian Aboriginal communities
  1. Rebecca Guy1,
  2. James Ward2,
  3. Handan Wand1,
  4. Alice Rumbold3,4,
  5. Linda Garton1,5,
  6. Belinda Hengel6,
  7. Bronwyn Silver3,
  8. Debbie Taylor-Thomson3,
  9. Janet Knox7,
  10. Skye McGregor1,
  11. Amalie Dyda1,
  12. Christopher Fairley8,9,
  13. Lisa Maher1,
  14. Basil Donovan1,10,
  15. John Kaldor1,
  16. on behalf of the STRIVE Investigator Group
  1. Correspondence to A/Professor Rebecca Guy, The Kirby Institute, University of New South Wales, Sydney NSW 2052, Australia; Rguy{at}kirby.unsw.edu.au

Abstract

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.

  • INFECTIOUS DISEASES
  • SCREENING
  • EPIDEMIOLOGY (GENERAL)

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Introduction

Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) are curable sexually transmitted infections (STIs) of public health importance. They are often asymptomatic1 for long time periods and, if untreated, can lead to serious complications. CT and NG infections have been associated with an increased risk of pelvic inflammatory disease (PID) and adverse neonatal outcomes,2 and untreated NG can also lead to disseminated infection.3 TV is associated with PID and also premature rupture of membranes, preterm premature rupture of membranes and small for gestational age,4 as well as urethritis in men.5 STIs can also create stigma and shame, play a role in relationship breakdowns and compromise social and emotional well-being.6 NG presents particular concerns for disease control because of its propensity to develop resistance to antibiotics.7

For more than two decades, Aboriginal and Torres Strait Islander people (hereafter referred to as ‘Aboriginal people’) in Australia have been diagnosed with STIs at much higher rates than the non-Indigenous population.8 By far the most affected populations are young people residing in remote and very remote communities, most of which are located in the central and northern part of the country.8 In the Aboriginal populations of these remote communities in 2011, the diagnosis rates of CT and NG based on routine notifiable disease reporting were respectively eight and 61 times greater than in the non-Indigenous population, and threefold and sixfold higher than rates in Aboriginal people residing in urban areas.8 A similar situation exists for TV in the Northern Territory, the only jurisdiction that requires notification of this infection.W1 Risk factors for STIs have been reported to include young age, substance abuse, alcohol use and a history of previous STIs.9 A survey of young Aboriginal people in remote communities in Far North Queensland suggested that there was lower STI knowledge and higher rates of partner change and unwanted sex in this population compared with Australian youth participating in a national school survey.10 Further, a recent study of 2877 Aboriginal people aged 16–29 years found lower levels of knowledge regarding STIs transmission among remote community residents compared with urban and regional residents.11

In 2011, the STIs in Remote communities: ImproVed and Enhanced primary health care (STRIVE) trial commenced,12 which aimed to assess whether a sexual health quality improvement programme could increase STI testing and in turn reduce the prevalence of STIs. The study involved 68 remote communities with predominantly Aboriginal populations in central and northern Australia and is being evaluated with a stepped wedge randomised cluster design. In the context of the STRIVE trial, we assessed coinfection patterns to guide clinical and public health responses in these remote Aboriginal communities and other similar settings.

To our knowledge, there have been only a few previous studies in remote Aboriginal communities that have estimated the prevalence of all three STIs (CT, NG and TV) in women using nucleic acid amplification tests (NAAT),13–15 but none in men. Two of these studies also examined the prevalence of coinfection overall but did not examine co-occurrence and relationships.13 ,15 We undertook a detailed cross-sectional analysis of the co-occurrence of the three infections in men and women using a unique laboratory data set from remote Aboriginal communities spanning three Australian states and territories.

Methods

Setting

The STRIVE trial has been conducted through clinics that serve 68 remote communities with predominantly Aboriginal populations in central and northern Australia. We performed a cross-sectional analysis of the results of all tests for CT, NG and TV in patients aged 16 or more years in 65 remote communities where laboratory data were available during the period January 2009 to October 2011. All of the communities are classified by the Australian Bureau of Statistics as ‘very remote’ and have a combined total population of around 28 000 people.W2

Each community is served by a single clinic, except one, which has two separate clinical services. The vast majority of patients (>90%) attending the services are Aboriginal. Health services joined the STRIVE trial through a signed agreement that provided access to de-identified laboratory records of STI testing for the purpose of supporting quality improvement and reporting trial outcomes.

All health services undertook STI testing following published clinical guidelines. In men, testing was via collection of urine specimens, and in women it was via a self-collected vaginal swab or urine specimen, unless a pelvic examination was being undertaken, in which case an endocervical swab was the preferred specimen. Specimens were transferred to a city-based pathology laboratory and, depending on clinician request, tested for the presence of CT, NG and TV. Three laboratories provided testing for the health services involved in STRIVE, and all had over a decade's experience in the NAAT detection of these infections. One laboratory, which conducted the majority of testing, used the transcription-mediated amplification and hybridisation protection assay test for CT/NG/TV diagnosis (Gen-probe PANTHER).16

Data

We obtained data on testing for CT, NG and TV among individuals aged ≥16 years from the laboratories in line record form. The data set did not include names but contained an anonymous identifier to allow records for the same individual to be linked within health services. Other information collected included usual community of residence, age, sex, date of test and result.

Analysis

All analyses focused on the first episode of testing that included all three STI infections in the same specimen among individuals aged ≥16 years.

Test positivity was the proportion of unique patients tested with a positive result; single infection was the proportion of unique patients tested with a positive result for only one infection (and negative for the other two); dual infection was the proportion of unique patients tested with a positive result for two infections (and negative for the third) and triple infection was the proportion of unique patients tested with a positive result for all three infections. Coinfection was the proportion of unique patients tested positive for one infection with a positive result for another infection.

In further analyses, we used ORs to determine which infections were more likely to occur as coinfections than as single infections and any relationship to age or sex. For example, we determined the odds of a person having NG infection among those with CT infection compared with NG infection among those without CT infection and examined the corresponding OR by age and sex. CIs and Woolf test statistics for the ORs were calculated using the methods described by Armitage and Berry,W3 based on the normal approximation to the distribution of the natural logarithm of the OR.W4

Analyses were carried out using the SAS software V.9.1.3 (SAS Institute, Cary, North Carolina, USA) and Stata V.10.0 (College Station, Texas, USA).W5

Results

During the study period, a total of 17 848 patients (10 396 women, 7452 men) seen at the 65 participating remote health services were recorded as having been tested at least once for either CT, NG or TV. Virtually all had been tested at least once for CT (100%) and NG (99.6%), with 75.6% tested at least once for TV. Overall, 13 480 (75.5%) had been tested for all three infections at least once in the period, and this group formed the basis for the remaining analyses.

Of the 13 480 patients, 37% were men, 35% were aged 16–25 years, 29% 25–34 years and 36% 35 years and above.

Positivity

Of the 13 480 patients tested for all three STIs, 11.5% tested positive for CT (12.3% in women, 10.1% in men), 10.1% for NG (9.4% in women, 11.4% in men) and 17.6% for TV (23.9% in women, 6.7% in men).

For both CT and NG, the positivity in both men and women was strongly inversely associated with age, being above 20% in those under 20 years of age, and falling nearly 10-fold in those aged 35 and above (figure 1). Positivity for NG was similar for men and women in all age groups. CT and NG positivity was similar in men, while CT was slightly higher than NG in women, particularly in the younger age groups. Patterns for TV were very different, with positivity 3.6 times higher in women than men, a weak inverse relationship with age in women and no relationship between positivity and age in men (figure 1).

Figure 1

Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) positivity with 95% CIs, by age group and sex.

Any of the three STIs

One-third of women (33%) were detected as having at least one of the three infections (33.3% of women and 21.3% of men), most frequently in those aged 16–19 years at 48.9%, declining to 24.1% in those aged above 35 years. In men, 21.3% had one or more STI, highest in those aged 16–19 years at 33.4%, declining to 12.6% in those aged 35 years and above (table 1).

Table 1

CT, NG and TV dual-infection* and triple-infection† positivity, by age group and sex

Dual infections

Dual infection with the various pairings of the three infections was most common in younger age groups, declining steadily with increasing age, except for combinations involving TV, for which the decline was less pronounced. The most frequent dual infection was CT and NG, which was nearly twice as common in men (4.1%, and highest in 16-year-olds to 19-year-olds at 9.8%) as in women (2.0% overall and 4.3% in 16-year-olds to 19-year-olds; table 1).

Triple infections

Having three infections was also much more common in the younger age groups, with the proportion being 22-fold higher in women aged 16–19 years and 16-fold higher in men aged 16–19 years compared with women and men above the age of 35 years, respectively (table 1).

Coinfections

Of the women with CT infection, a quarter also had an NG infection and one-third had TV infection, and of men with CT, one-third had NG infection but a lower proportion (8.4%) had TV infections. Results were similar when focusing on NG and coinfection with CT, and NG and coinfection with TV (table 2).

Table 2

CT, NG and TV coinfection* positivity by age group and sex

Associations between coinfections and single infections

When we assessed the odds of having NG infection among those with CT infection (coinfection) versus NG infection among those without CT infection (single infection), in all age groups and in both men and women, CT and NG were highly predictive of each other, with slightly stronger associations in older men (table 3). TV was associated with each of the other two infections, but the association was much stronger with NG than with CT, in virtually all age groups. In men, TV was associated with each of the other two infections in those aged <25 years, but not in older men (25 years and above) (table 3).

Table 3

Odds of having a coinfection* versus single infections†

Discussion

The study took place in a region that has long been known to have high prevalence of all three infections. Most common were CT and NG dual infections, with a peak in those aged 16–19 years. The least common dual infections were those involving TV, which occurred primarily in women in older age groups, where CT and NG infections were less common. TV was associated with the presence of the other two infections, but much more strongly so with NG than with CT.

An extremely high proportion of patients had one or more of the three STIs, with nearly half of 16-year-old to 19-year-old women and a third of 16-year-old to 19-year-old men affected, decreasing with older age, but still remaining high at 24% and 13% in women and women aged 35 years and above, respectively. Women had a greater positivity for any of the three STIs than men largely due to the higher TV positivity in women in all age groups. Of the NG-infected women, around a third were co-infected with CT; but among those with CT, a lower proportion were co-infected with NG, which is similar to other studies.17 ,18 However, of the men with CT infection, a higher proportion had NG. Younger age and female gender have also been described in the literature as risk factors for coinfection.17 ,19

There have only been two prior studies of CT/NG/TV coinfection based on NAAT in remote Australian Aboriginal communities to our knowledge, and both have been in women only. Bowden et al13 showed that among Aboriginal women diagnosed with one of these STIs in 1996, 26% had two or more STIs (CT, NG or TV) and Panaretto et al15 showed among Aboriginal pregnant women diagnosed with one of these STIs in 2000–2003, 23% had two or more STIs. In these two studies, no further analysis was reported of specific combinations of coinfections, dual and triple infections and no data were available for men.13 ,15 More recently, Ginocchio et al showed that among women in the USA the prevalence of dual infections was five times higher in African-American women aged 18–89 years than Caucasians: CT/TV (3.6% vs 0.6%), CT/NG (1.7% vs 0.4%), TV/NG (1.7% vs 0.5%), but no data were available on age-specific relationships, nor in men.20 High prevalence of CT and NG coinfections (but no corresponding TV data) have been reported in the UK among people of black Caribbean ethnic origin21 and in the Netherlands among people of Surinam or Antillean origin.22 In many of these settings, the higher prevalences of STIs and coinfections in ethnic minority groups are believed to be due to inequities in access to healthcare.23 ,24

We found that NG and CT were closely associated in all age groups and in both men and women. TV was generally associated with NG and CT only in younger men, and TV was associated with both NG and CT in nearly all age groups of women, but the NG association was much stronger than CT. These findings suggest that there may be a stronger biological link between the factors related to transmission or acquisition of NG and TV than those related to CT.

The high CT and NG positivity estimates reported here are consistent with the findings of other screening programmes in remote Aboriginal communities 9 ,14 ,25 which have found prevalence to be 10%–15% in the age group 14–35 years, which are respectively about 10 times and 18 times greater than estimates for non-Indigenous heterosexual populations in a similar age group.26 ,27 Despite its importance as a cause of long-term reproductive and perinatal health consequences,4 TV infections are not reportable to public health officials and, in most areas of the world, are not part of routine STI screening using NAAT. In addition, wet mount procedures are widely used in routine gynaecological examinations, but will underestimate TV prevalence due to the insensitivity of the method. In our study, TV was the most common STI with 24% of women infected. These findings are consistent with studies conducted in low-income settings internationally.28 ,29 TV positivity was >20% in all women age groups, but highest in those aged 16–19 years. This is in contrast to a study by Bowden et al,13 who found that TV prevalence was actually higher in women aged over 40 years than in younger women, and studies in other countries.20 However, the Bowden study was only in one region of northern Australia and conducted at a time where TV screening was not routine, suggesting that the recent screening activity may have been sufficient to reduce infections rates in this older age group. TV positivity in our study was also 3.6 times lower in men than women, suggesting gender differences in the clearance rates of TV. Natural history studies have demonstrated spontaneous resolution of TV is common in men.30

The strengths of this study include the large contemporary data set of patients with STIs from 65 remote Aboriginal communities spanning three states and territories, and detailed exploration of the relationships between these three common STIs. Limitations include the fact that the analysis was based on routine testing data and it is likely that symptomatic patients were screened at a greater rate than lower-risk patients. Accordingly, our estimates may overestimate the true prevalence, particularly for NG in men, which is more likely to be symptomatic.1 Although we were unable to determine whether a patient was sexually active, the median age of sexual debut in young Aboriginal people was recently reported to be 15 years of age (IQR of 13–17 years)11 and local guidelines recommend screening only if sexually active.W6

Although these findings may not be generalisable to all high-prevalence settings, they provide insights into the epidemiology of these infections in such settings and have important public health implications. Understanding STI coinfection patterns is a prerequisite to effective clinical and public health responses to highly treatable infections. Two programmes in remote Aboriginal communities involving continuous (throughout the year) opportunistic clinic-based screening and annual mass screening in the community over short periods as part of comprehensive STI programmes have demonstrated reductions in CT and NG prevalence.25

In conclusion, we have estimated the coinfection positivity of three important, curable STIs in a high-prevalence setting. The known morbidity associated with these STIs, combined with high coinfection positivity, confirms the need for increased simultaneous screening for CT, NG and TV, and enhanced strategies to control these highly prevalent infections.

Key messages

  • In this remote high-prevalence area, nearly half of 16-year-old to 19-year-old women and a third of 16-year-old to 19-year-old men had one or more STI.

  • Trichomonas vaginalis (TV) was the most common single STI with 24% of 16-year-old to 34-year-old women infected, yet the least common dual infections were those involving TV, as TV positivity was high in older age groups but positivity of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) was lower. TV was more strongly associated with Neisseria gonorrhoeae (NG) coinfections than with Chlamydia trachomatis (CT).

  • The known morbidity associated with these STIs, combined with high coinfection positivity, confirms the need for increased simultaneous screening for CT, NG and TV, and enhanced strategies to control these highly prevalent infections.

Acknowledgments

STRIVE is a collaboration between researchers named in the authorship list, conducted in partnership with the Northern Territory Department of Health, the Aboriginal Medical Services Alliance of the Northern Territory, Apunipima Cape York Health Council, Kimberley Aboriginal Medical Services Council and the Western Australia Country Health Service. The study would not have been possible without the commitment of all participating health services and their staff and the ongoing support and advice from our partners. The authors acknowledge the important contributions of the STRIVE Executive Committee. The authors are grateful to Western Diagnostic Pathology, Pathwest Laboratory Medicine WA, SA Pathology and Queensland Health Pathology and Scientific Services, and their staff that undertook testing for STIs on behalf of participating health services, and provided the anonymous line record data that formed the basis for the analyses reported here.

References

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Footnotes

  • Correction notice Contributors statement has been corrected since published Online First.

  • Handling editor Jackie A Cassell

  • Collaborators Additional STRIVE Investigators (not named as authors): Donna Ah Chee, John Boffa, David Glance, Mathew Law, Robyn McDermott and Steven Skov.

  • Contributors JMK, JW, RJG, AR, SM, BJS, LG, BH and DTT developed the STRIVE study protocol which led to the current data set being available. RJG conceived the idea for this analysis. RJG, HW and JMK were responsible for the study design and planning for this analysis. HW did the primary data analysis. RJG wrote the first draft. LG, BH, JK, BJS, DTT were involved in study implementation and field data collection, and SM and AD were involved in overall data management and analysis. All authors reviewed and revised drafts, contributed to the interpretation of the results and read and approved the final manuscript. RJG prepared the final manuscript and processed the submission.

  • Funding Australian National Health and Medical Research Council (NHMRC), Project Grant ID: 568806. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this publication are those of the authors and do not reflect the views of NHMRC. JMK, RJG, ARR, BD and LM are supported by NHMRC fellowships.

  • Competing interests None.

  • Ethics approval Central Australian Human Research Ethics Committee, the Human Research Ethics Committee of the Northern Territory Department of Health and Families and Menzies School of Health Research, Cairns and Hinterland Health Service District Human Research Ethics Committee, Western Australian Country Health Service Board Research Ethics Committee, Western Australian Aboriginal Health Information and Ethics Committee and the University of New South Wales Human Research Ethics Committee.

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

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