Mathematical Modeling of Infectious Diseases.
T.M. Lietman, K. Maxey, Kevin Hong, and T. Porco
The World Health Organization (WHO) recommends mass administration of single-dose oral antibiotics in trachoma endemic areas. However, it is not clear how often mass treatment should be administered. Program results may provide useful information, but will take years to complete and may be prohibitively expensive. This research focuses on the use of mathematical models to determine the frequency of mass drug administration necessary to eliminate trachoma. These studies suggest that to eliminate infectious trachoma, mass antibiotic treatment will have to be repeated (annually in areas of moderate disease, and perhaps even biannually in hyperendemic areas). Further operations research (see below) is being done to determine if these estimates are indeed accurate. Dr. Lietman and colleagues have also shown with mathematical models that if infection is eliminated from a core group of children, then it should disappear from the rest of the community as well. Ms. Ray and Drs. Porco and Lietman are working with investigators at the London School of Hygiene and Tropical Medicine, fitting models to data collected from Ethiopia, Tanzania, and the Gambia. When studying elimination, it is important to include the effects of chance, so we have recently published stochastic models of these epidemics.
A single dose of azithromycin is extremely effective in eliminating the causative agent of trachoma, Chlamydia trachomatis, from an individual. In addition to C. trachomatis, azithromycin has antibacterial activity against many bacterial species including pathogenic bacteria that are routinely found in trachoma endemic communities. While Chlamydia has remained sensitive to macrolides and azalides including azithromycin, other bacteria may develop resistance, and there is some concern that large-scale trachoma programs may interfere with bacterial flora. Drs. Porco and Lietman are using mathematical models of chlamydia and streptococcus transmission to estimate the amount of drug resistance caused by trachoma programs. They are currently processing specimens from villages that have been treated 4 times and villages that have never been treated, to see if the mathematical models indeed predict observed resistance.
Moisture-seeking Musca sorbens flies congregate on the head and face of an Ethiopian child
Trachoma Community Treatment Strategies
J. House, T.M. Lietman, K. Hong, Z. Zhou,
J.P. Whitcher, B. Gaynor, T. Porco,
ORBIS-Ethiopia, and Carter Center-Ethiopia
It is uncertain if annual repeat treatment of trachoma with mass azithromycin distribution will eliminate ocular Chlamydia from a community, particularly in hyperendemic areas. In the TEF study the Proctor team is monitoring biannual and annual treatments in Ethiopia, where trachoma is as severe as anywhere in the world, to determine whether treatments progressively reduce infection. So far, after 3 years of treatments, we have reduced infection from 50% of children to <5% of children. In some villages, we can find no evidence of infection remaining. In addition, the Proctor team has just set up a second trial (the TANA study) to determine whether or not children form a core group for trachoma—that is, if you eliminate infection in children, will it disappear in the rest of the community? This study would also monitor mortality changes with antibiotic administrations, as the diarrhea, respiratory infection, and malaria are all major causes of infant mortality.
Gurage child with acute trachoma and typical nasal discharge
Village workers headed to field clinic
 
Proctor Field Studies in the Gurage Zone
 
Proctor Cornea Team in Action
Examine children for signs of trachoma
Gurage women and children waiting to have
their eyes examined for trachoma
Steroids for Corneal Ulcer Trial and Mycotic Ulcer Treatment Trial
N. Acharya, T.M. Lietman, K. Hong, J. P. Whitcher, M. Zegans,
S. McLeod, and M. Srinivasan
Antimicrobial treatment of a bacterial corneal ulcer is generally effective in eradicating infection. However, “successful” treatment is not always associated with a good visual outcome. The scarring that accompanies the resolution of infection leaves many eyes blind. Some corneal specialists advocate the use of topical corticosteroids along with antibiotics in an effort to reduce immune-mediated tissue damage and scarring. Others fear using steroids to reduce the cornea’s immune response will prolong or even exacerbate infection. Ophthalmologists have been divided on this issue for more than 30 years, and both approaches are acceptable according to the American Academy of Ophthalmology’s Preferred Practice Patterns. Evidence from animal and human reports is mixed. A single randomized trial saw a non-significant benefit to steroids but was drastically underpowered (20 patients per study arm). This group has just started a large, NIH-sponsored, randomized controlled trial to evaluate whether topical steroid use can improve the outcome of bacterial corneal ulcer treatment, at Aravind Eye Hospital in South India (SCUT trial). In the first year of the study, they enrolled 140 cases (of a total of 500). Dr. Nisha Acharya is doing several ancillary studies on this trial as art of her NEI Career Development Award.
Dr. Lietman and colleagues are evaluating which topical agent, voriconazole or
natamycin, is superior treatment for fungal keratitis in a randomized, masked, controlled trial. Historically, fungal ulcers are relatively uncommon inn the United States. For example, they make up about 8% of infectious ulcers seen at the Proctor Foundation at UCSF prior to 2005. However, in the past year, there has been an epidemic of keratitis due to Fusarium spp. In the U.S., and caring for these patients has become a particular concern for corneal specialists. In warmer, tropical climates, fungal ulcers have always been endemic. In settings such as South India, as many as one-half of infectious ulcers are fungal. The Aravind Eye Hospital in Tamil Nadu is the ideal partner for this project.
 
Proctor team and village workers
Typical Gurage Home
Gurage family
  Young boy at work Villagers on route to field clinic
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