INTRODUCTION

The WHO’s current goal for the global trachoma programme is elimination as a public health problem by 2020.^{1 2} The definition of elimination as a public health problem for trachoma is (1) reduction in prevalent of trachomatous inflammation—follicular (TF) in 1–9-year-olds to <5% in each formerly endemic evaluation unit (a rough equivalent of a health district); (2) reduction in prevalent of trachomatous trichiasis unknown to the health system in ≥15-year-olds to <0.2% in each formerly endemic evaluation unit; and (3) a system to identify and manage incident cases of TT. It is estimated that >150 Chlamydia trachomatis infections in a single eye are required to cause the conjunctival scarring-induced trichiasis that can lead to trachomatous blindness,³ and that experiencing this number of infections would be an uncommon occurrence when the prevalent of TF is <5%. The previous restriction of our ambition for active trachoma to this target (TF prevalent <5%) therefore has some theoretical foundation, although specific targets were based on expert consensus.

In infectious diseases, control typically refers to reduction in incidence or prevalent to an acceptable level via specific public health intervention.⁴ For control of an infectious disease to be maintained, ongoing public health intervention is required. Alternative goals for an infectious disease include elimination, defined as reduction in incidence of infection to zero in a defined geographic region, and eradication, defined as permanent reduction to zero worldwide.⁴ Though it includes the word ‘elimination’, strictly speaking, ‘elimination of trachoma as a public health problem’ is a control goal. For trachoma, in some settings, control may not be sustainable in the absence of continued intervention, due to the potential for resurgence from even low levels of transmission.^5–8 In other settings, trachoma is disappearing and may continue to disappear even in the absence of ongoing intervention, leading to the hypothesis that some districts achieving control may have actually eliminated the pathogen.^9–14 Since the prevalent of inflammation tends to lag behind that of infection, districts that still have low levels of TF may have no transmission of ocular C. trachomatis.

Although once endemic, endogenous transmission of ocular C. trachomatis has not been observed in the United States or Europe for decades.¹⁵ More recently, mass drug administration of azithromycin has been shown to dramatically reduce the prevalent of ocular C. trachomatis infection in endemic populations.^16–18 Local elimination of ocular chlamydial infection, and ultimately worldwide eradication of the organism, may therefore, at least hypothetically, be a reasonable goal.¹⁹

The neglected tropical diseases community is currently setting goals for 2021–2030. To better understand current attitudes regarding the feasibility of eradication trachoma, which would represent a first step towards considering a change in focus from control to eradication, we conducted a survey of trachoma experts and other stakeholders.

RESULTS

Of 59 surveys distributed, 56 (95%) were returned. Respondents included individuals working in research (34%), trachoma programme implementation (46%) or both (16%); 8% were involved in policymaking (respondents could select more than one work area and thus percentages do not total 100%). The majority (94%) of respondents reported that they undertook trachoma-related work in sub-Saharan Africa. Participants also undertook trachoma-related work in East/Southeast Asia (32%), North Africa/Middle East (21%), South Asia (19%), South America (17%) and Australia (11%). Approximately, half (56%) had a doctoral degree (MD and/or PhD or equivalent).

Most participants reported that the most important goal of azithromycin mass drug administration for trachoma was control (N=22, 41%) or local elimination (N=27, 50%), and 9% (N=5) reported that the most important goal was global eradication. When asked when global eradication would occur, 76% (N=42) of all respondents reported an estimated year (figure 1). The remaining 24% (N=13) reported that global eradication was not possible. Of those who indicated that global eradication was possible, 14% reported that it would occur before 2030, 40% by 2040, 21% by 2050, while 24% reported that it would take until 2060 or later.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

Density plot of estimates for year of achievement of trachoma eradication. Grey shaded area indicates 95% CI.

The most frequently cited barriers to global eradication were a lack of appropriate surveillance tools to confirm interruption of transmission or monitor for subsequent re-emergence (32%) and lack of resources (23%). Other identified barriers included politics and war/insecurity (19%), antimicrobial resistance (15%), lack of community awareness/involvement (13%) and ineffective interventions (9%).

DISCUSSION

Most trachoma stakeholders surveyed did not believe that eradication of ocular C. trachomatis was the principal goal of azithromycin mass drug administration. However, approximately three-quarters of participants indicated, at least implicitly, that they believed that global eradication is feasible by providing a date by which they thought it could be achieved. These findings are not necessarily contradictory. The current goal of mass drug administration for trachoma is elimination as a public health problem, a control goal, and the fact that most respondents felt this was the primary goal of the current programme is in line with global policy.²¹ Participants who believed that eradication was a possibility generally thought that it could happen between 2040 and 2050. Although eradication by 2030 is likely unrealistic, global elimination as a public health problem by 2030 (a change from the current 2020 goal) and global eradication by 2050 might be targets around which consensus could be built. Reduction in ocular C. trachomatis transmission to zero should be followed, after a delay, by a reduction to zero in the incidence of trachomatous trichiasis.

Although global elimination of trachoma as a public health problem will not be achieved by December 2020, trachoma programmes have made tremendous progress.²² In many districts, the prevalent of trachoma is declining rapidly, in some areas even in the absence of active intervention.^{9 23 24} The number of people living in districts worldwide in which the TF prevalent was ≥5% declined by 91% between 2002 and 2019.²⁵ That global elimination as a public health problem will not be achieved by 2020 should not be taken as evidence that elimination as a public health problem or eradication are impossible—to the contrary, the current epidemiological evidence suggests that the targets set for elimination as a public health problem will be reached in all but a handful of districts in the next decade.²⁶ Refocusing efforts in remaining high-prevalent districts by intensifying interventions (which might include, eg, more frequent antibiotic distribution) could facilitate elimination and eventually global eradication.²⁷

The likely barriers to global eradication of ocular C. trachomatis identified by participants are worth thinking through. First among these was inadequate surveillance systems. Because of a lack of validated tools to measure ocular C. trachomatis transmission intensity, programmes currently undertake surveillance by conducting serial population-based surveys in which prevalent of the clinical sign TF is the primary outcome measure.²⁸ Confirming eradication would potentially require far more intense surveillance with identification of individual cases of infection, as was done in the smallpox eradication programme.²⁹ Alternatively, smarter approaches may now be possible: serological markers of C. trachomatis exposure hold promise,^{30 31} for example, but have not yet been used to monitor trachoma systematically and at scale. One shortcoming is that currently available serological tests cannot distinguish between exposure to genital and ocular C. trachomatis biovars, although this is less of an issue among children, who are considered the target population for serological surveillance for trachoma. Development of a test that could discriminate between these strains would represent a major advance. Second, a lack of financial resources to support an eradication goal was cited. Current district-level surveys cost a median of $8298 (IQR: $6532–$10 111, 2017 USD).³² Surveys to support confirmation of eradication could be much more resource-intensive, since the required sample sizes would be likely to be considerably greater. This would hinder both implementation of interventions to interrupt transmission and subsequent ongoing surveillance to detect potential resurgence. Eradication would undoubtedly be more resource-intensive than control. Whether an eradication goal would be perceived as being too lofty and thus demotivating or a more sustainable solution that would galvanise the public health community is a question that can only be answered through wider discussion. Third, politics and insecurity are undoubtedly problematic. Political engagement and programmatic work have commenced, however, in some very challenging environments, including areas experiencing political instability and humanitarian crises; we are hopeful that this will continue. Fourth, taking measures to avoid worsening antimicrobial resistance is a global priority.³³ Evidence generated alongside azithromycin mass drug administration for trachoma to date has generally shown that mass azithromycin distribution selects for macrolide resistance, but that prevalent of resistant strains returns to baseline levels once antibiotic selection pressure is removed.³⁴ However, we agree that vigilance will be needed, regardless of the programmatic goal. Fifth, inadequate community engagement could threaten eradication, for example, if communities are suspicious of trachoma programme activities as has been observed in some communities in polio vaccination campaigns.³⁵

Is deliberate identification and treatment of every last infection required for global eradication? In the United States and Europe, where trachoma was once endemic, there has been no evidence of endogenous transmission for decades.³⁶ Despite the absence of systematic surveillance, infection has disappeared. Ocular chlamydia transmission occurs slowly and once brought to a low level, re-establishment of infection may be difficult.³⁷ Instead, it is possible that it will disappear in the absence of specific intervention.³⁸ Demonstrating the possibility of this phenomenon at district-level (or larger) scale would be helpful to inform future policy debate. If identification and treatment of all infections were not required for trachoma eradication, costs associated with declaring eradication would be significantly lower.

This study had several limitations. It was conducted in a single session of a single operational research meeting and was unlikely to be representative of all trachoma experts, perhaps particularly excluding those not involved in operational research. The COR-NTD meeting involves diverse expertise ranging from academic scientists to trachoma programme managers. While individuals with different expertise may have different understandings of and experience with definitions used for infectious disease control, elimination, and eradication, responses to this survey also reflect those of individuals on the ground implementing trachoma programmes. The location of the meeting may also have led to under-representation of experts who are nationals of countries where trachoma is endemic, as securing a visa can be an obstacle to conference attendance,³⁹ and flights and accommodation can be prohibitively expensive. Although we asked participants where the bulk of their trachoma work was conducted, we did not ask about where they were based. Trachoma programmes typically refer to ‘elimination as a public health problem’ as the end-goal for trachoma control, which refers to disease- and service-related targets, not true elimination of infection. Participants who are used to seeing ‘elimination’ used to refer to trachoma control may have confused the definitions used in this survey. We did not verify if participants were using the definitions of eradication printed on the survey itself and projected on the meeting room wall. However, the primary goal of the survey was to understand perceptions related to eradication of infection, not elimination. Finally, the survey was administered during a session on trachoma eradication. Attendees presumably had some enthusiasm for the topic, with ‘trachoma eradication’ naysayers potentially staying away.

Although most trachoma experts surveyed here did not report that global eradication was the rationale for azithromycin mass drug administration, most reported a date by which they believed trachoma would be globally eradicated. Continued investment in trachoma control efforts, coupled with identification of new ways to assess transmission and development of more effective interventions, could strengthen support for adopting a formal eradication goal.