On Trachoma elimination

Apr 27, 2021, 12:00 PM

Trachoma was once the leading cause of blindness, endemic in nearly every country of the world.
As recently as the 1990s, trachoma still ranked second only to cataract as a cause of blindness.

Two decades ago, the World Health Organization (WHO) initiated a program to control the disease by 2020.

Although that goal will not be met on time, recent developments suggest that even loftier goals could be possible in the near future. Global eradication of the strains of Chlamydia that cause trachoma can be achieved, and sooner than previously thought, if we step up interventions in the most affected areas.

Most trachoma programs follow a WHO strategy that aims for control, defined as bringing infection to a low enough level that resulting disease is not a public health concern.

Elimination indicates that infection, or at least transmission of infection, is brought to zero in a geographical area. Eradication implies elimination of infection worldwide—at least outside of the laboratory. Smallpox remains the only infectious disease of humans eradicated by a public health program. A number of other infectious diseases are now on the ropes, including Guinea worm, polio, and onchocerciasis (river blindness).

Trachoma has several characteristics that make eradication at least feasible. Humans are the only host. Antibiotics are effective against Chlamydia, and no antibiotic resistance to azithromycin has yet emerged. Perhaps most importantly, trachoma benefits from an enormous secular trend. Trachoma disappeared in many regions without the benefit of specific trachoma programs. Where monitored longitudinally without active intervention, trachoma seems to be disappearing. Many agree that trachoma eventually will disappear with or without a public health program, although in the latter case, perhaps not for decades.

The cornerstone of the WHO program is mass treatment with a single-dose of oral a zithromycin. Azithromycin was shown to be effective in clearing ocular chlamydial infection from most individuals.

Three weekly mass drug administrations (MDAs) appeared to be as effective as 6 weeks of the then standard-of-care topical tetracycline.

Subsequent community-randomized trials confirmed efficacy of mass distribution with a single dose of azithromycin.

Mathematical models suggested that annual distribution eventually could eliminate infection in most communities worldwide, although some may require more frequent treatment.

The International Trachoma Initiative and Pfizer, Inc. (New York, NY), have donated nearly 1 billion doses of azithromycin to the cause. After 20 years of distributions, districts that remain endemic now can be divided into those where infection will disappear regardless of any future MDA, those where infection will disappear with continued annual MDA, and those where infection will not disappear without more intensive intervention. The vast majority of endemic districts now fall into the first 2 categories.

The WHO relies on the clinical signs of trachoma to declare that a district has obtained control.

Specifically, control requires reducing the prevalence of follicular trachoma in the upper conjunctiva (TF) to be less than 5% in children. But TF can linger long after infection has been cleared. Thus, the community-level prevalence of TF is a lagging indicator.

In communities with a low prevalence of TF, infection often is impossible to find even with polymerase chain reaction analysis. Moreover, any association between TF and actual infection decreases after MDA.

Previously endemic countries, such as Nepal, Mexico, Ghana, Uganda, and the Gambia, recently performed population-based surveys as part of their dossiers to declare trachoma control. In each, polymerase chain reaction–determined prevalence of chlamydia in children was less than the false-positive rate of the test.

Ironically, by the time a country has been certified as controlled, elimination already may have occurred.

A Guest Editorial

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