Trachoma decline and widespread use of antimicrobial drugs.
Trachoma trachoma (trəkō`mə), infection of the mucous membrane of the eyelids caused by the bacterium Chlamydia trachomatis. Trachoma infects more than 150 million people worldwide. is disappearing in many parts of the world, even in the absence of specific control programs. Following mass antimicrobial drug treatments for trachoma in western Nepal, the prevalence of trachoma declined far more rapidly than could be attributed to the control program alone. Pharmacy surveys in the same region found that children received more antichlamydial drugs from sources outside the trachoma program than they did from the program itself. We demonstrate that high background antimicrobial drug use may be responsible for much of the observed decline in trachoma and discuss its potential role in eliminating this infectious disease Infectious disease
A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. .
Trachoma is disappearing in many parts of the world, even in the absence of specific control programs. It is a disease of the rural poor, and as living conditions living conditions npl → condiciones fpl de vida
living conditions npl → conditions fpl de vie
living conditions living have improved during the last century, a corresponding decline in trachoma has occurred (1-4). In Western Europe Western Europe
The countries of western Europe, especially those that are allied with the United States and Canada in the North Atlantic Treaty Organization (established 1949 and usually known as NATO). and the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. , trachoma virtually disappeared by the late 20th century. Other infectious diseases infectious diseases: see communicable diseases. such as syphilis, chancroid chancroid: see sexually transmitted disease. , tuberculosis, and leprosy leprosy or Hansen's disease (hăn`sənz), chronic, mildly infectious malady capable of producing, when untreated, various deformities and disfigurements. also began to subside in Europe and the United States during this time. This downward trend seems to have begun before, and continued into, the antimicrobial drug age. Therefore, many attribute this decline to socioeconomic factors, such as improved sanitation and social changes, and even to legislation to control venereal disease venereal disease (vənēr`ēəl): see sexually transmitted disease. , rather than to antimicrobial drugs. Addressing the importance of antimicrobial agents Antimicrobial agents
Chemical compounds biosynthetically or synthetically produced which either destroy or usefully suppress the growth or metabolism of a variety of microscopic or submicroscopic forms of life. in the disappearance of these infectious diseases retrospectively is difficult. In the case of trachoma, we have a unique opportunity to observe the effect of rising antimicrobial pressure in the community on a disease that is in decline but has not yet disappeared.
From 1998 to 2001, a region of western Nepal was monitored for trachoma prevalence, following mass antimicrobial drug distribution for trachoma. A dramatic fall in disease prevalence was observed that could not be attributed to the effect of the trachoma control program alone (5). We conducted a survey of pharmacies in the same region and found a surprisingly large quantity of antimicrobial drugs were being used for indications other than trachoma control (6). Here, we evaluate whether this background antimicrobial use may be responsible for the downward secular trend secular trend
The relatively consistent movement of a variable over a long period. A stock in a secular uptrend is an indicator that the security has experienced an extended period of rising prices. in the prevalence of trachoma.
Analysis of Decline in Trachoma Prevalence in Western Nepal
From May 1998 to May 2001, a total of 25 villages from three subdistricts (known as Village Development Committees) in the Kailali and Konchapur districts of far-western Nepal were monitored for clinically active trachoma. During this time, an annual mass azithromycin treatment program began. At each visit, all children 1-10 years of age were examined for signs of clinically active trachoma by using the World Health Organization (7) simplified trachoma grading system (8). In total, >20,000 examinations were performed; 180-650 children were examined during each village visit (5). The presence of a secular trend, a downward trend independent of the trachoma program, was evaluated by monitoring one third of the villages for 6 months before any antimicrobial drug treatment was given. Seasonal variation was determined by performing village visits in both the spring and the fall. No other specific trachoma prevention activities such as hygiene, fly control, or water supply programs were instituted during the course of this study (9).
Trachoma prevalence data were analyzed by using a multivariate autoregression (AR1) model with the following covariates: effect of the trachoma program, seasonal variation, and secular trend. The analysis showed that the trachoma program's distributions of antimicrobial drugs alone could account for some, but not all, of the observed reduction in clinically active trachoma (5). A substantial proportion of the decrease in trachoma prevalence 6 months posttreatment was attributable to a secular trend, independent of the trachoma program's effect and seasonal changes (26% decrease, p < 0.001, 95% confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [CI] 15%-35% decrease).
Antimicrobial Pressure from Outside the Trachoma Program
From February to May 2000, all pharmacies and government health posts in the Geta subdistrict of Kailali were surveyed to establish the total quantity of antimicrobial drugs distributed. All of these will be called pharmacies for the purposes of this article. Information obtained included the number of years each medicine hall had been open and, for each patient, age, antimicrobial agent, amount distributed, and patient's village. Pharmacy purchase receipts from this time period were also collected for analysis. The survey was repeated in September 2001 to gain additional patient information and to ensure that no gross seasonal variations occurred (6).
We analyzed these data to determine what percentage of the total antimicrobial agents distributed had antichlamydial activity. Susceptibility testing suggested that trimethoprim-sulfonamide combinations, tetracycline tetracycline (tĕ'trəsī`klēn), any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein , macrolides, chloramphenicol chloramphenicol (klōr'ămfĕn`əkŏl'), antibiotic effective against a wide range of gram-negative and gram-positive bacteria (see Gram's stain). It was originally isolated from a species of Streptomyces bacteria. , and amoxicillin amoxicillin /amox·i·cil·lin/ (ah-mok?si-sil´in) a semisynthetic derivative of ampicillin effective against a broad spectrum of gram-positive and gram-negative bacteria.
n. are all effective against chlamydia chlamydia (kləmĭd`ēə), genus of microorganisms that cause a variety of diseases in humans and other animals. Psittacosis, or parrot fever, caused by the species Chlamydia psittaci, . Also, other penicillins, cephalosporins Cephalosporins Definition
Cephalosporins are medicines that kill bacteria or prevent their growth.
Cephalosporins are used to treat infections in different parts of the body—the ears, nose, throat, lungs, sinuses, and , and the fluoroquinolones (ciprofloxacin ciprofloxacin /cip·ro·flox·a·cin/ (sip?ro-flok´sah-sin) a synthetic antibacterial effective against many gram-positive and gram-negative bacteria; used as the hydrochloride salt.
n. and norfloxacin) are less effective antichlamydial agents (10). However, susceptibility testing for chlamydia has been difficult to standardize (11), and alternative assumptions could alter these percentages somewhat. For example, including ciprofloxacin, which has some effect against Chlamydia trachomatis Chlamydia tra·cho·ma·tis
A species of Chlamydia that causes trachoma, inclusion conjunctivitis, lymphogranuloma venereum, nonspecific urethritis, and proctitis in humans. , would have increased the proportion effective against chlamydia by 12%, but we used the lower, more conservative figure for analysis. To facilitate direct comparison of different antimicrobial agents, the total amount of antichlamydial antimicrobial drugs was converted into the standardized unit of defined daily doses Defined daily doses (DDDs) are a WHO statistical measure of drug consumption. DDDs are used to standardise the comparative usage of various drugs between themselves or between different healthcare environments. (DDD DDD Direct Distance Dialing
DDD Digital/Digital/Digital (audio CD format, recording/mixing/mastering)
DDD Degenerative Disc Disease
DDD Domain Driven Design
DDD Data Display Debugger (GNU Project) ). DDD is defined as the assumed average maintenance dose per day for a drug used for its main indication in adults (12). For children, the number of prescriptions given per child per year was calculated with 1998 census data. Both DDDs and the prescriptions per person-year are convenient measures to compare antimicrobial pressure, although neither is ideal; DDDs do not take into account the duration of each drug's antichlamydial activity, and prescriptions are not for a uniform amount of medication.
We estimated that pharmacies in Geta distributed 3.0 DDD of antimicrobial drugs per person per year in 2000 (Table). Sixty-eight percent of these prescriptions were effective against chlamydia (Figure 1). Thus, pharmacies distributed 2.0 DDD per person per year of antichlamydial agents. Forty-nine percent of all antimicrobial agents were distributed to children 0-10 years of age, and 33% to preschool children 0-5 years of age. We estimated that on average 1.2 prescriptions ofantichlamydial agent are given to each preschool child per year (Table).
The number of pharmacies in Geta subdistrict has increased from 2 to 14 within the last 20 years, coinciding with the decrease in trachoma prevalence in the Tarai region of Nepal (Figure 2) (2). Eight of these pharmacies (57%) have been open for [less than or equal to] 5 years, and 10 (71%) for [less than or equal to] 10 years. In the last 20 years, the Years, The
the seven decades of Eleanor Pargiter’s life. [Br. Lit.: Benét, 1109]
See : Time number of pharmacies has increased sevenfold sevenfold
1. having seven times as many or as much
2. composed of seven parts
by seven times as many or as much
Adj. 1. , while the population of Geta has grown by approximately twofold, which suggests that more than three times as many pharmacies exist per person currently than in 1980.
[FIGURE 2 OMITTED]
Antimicrobial Drug Use within the Trachoma Program
The trachoma control program in Kailali and Konchapur distributed single-dose oral azithromycin annually, as per World Health Organization (WHO) guidelines and covered an estimated 80% of the targeted population with its antimicrobial treatments (5,9). One gram of azithromycin is the recommended single dose in an adult to treat ocular chlamydial chlamydial
pertaining to members of the family Chlamydiaceae.
abortion in cows, ewes, sows and goat does caused by Chlamydophila abortus and C. pecorum. See enzootic abortion of ewes. infection. This dose is equivalent to 3.3 DDD/person (12). For children, the recommended single dose of azithromycin is 20 mg/kg. The average dose for all ages (adults and children) was found to be approximately 2.3 DDD/person (9). With a treatment coverage of 80% of the entire population as recommended by WHO, a trachoma program would therefore administer 1.8 DDD/person at each mass distribution of antimicrobial agents.
Antimicrobial Drug Use Necessary for Elimination of Trachoma in Western Nepal
Using a previously described mathematical model
The amount of antichlamydial drugs given out by pharmacies in Geta (2.0 DDD/person/year) is slightly more than the estimated amount that would bring about the elimination of ocular chlamydial infection in this region of western Nepal (1.9 DDD/person/year). Children, in particular preschool children, are by far the most likely to harbor ocular chlamydia. Pharmacies distributed nearly one half of the total antimicrobial agents to children 0-10 years of age, and one third to children 0-5 years of age. Preschool children received 1.2 prescriptions per year of antimicrobial drugs that are effective against chlamydia, which is far more than the estimated 0.6 per year that would eliminate infection. We therefore conclude that antibiotics given for reasons other than trachoma control may play a role in the disappearance of trachoma in this region.
The prevalence of active trachoma has decreased in many regions of the world in the absence of programs specifically targeting this disease (1-4,14,15). From 1981 to 1996, active trachoma in children declined from 30% to <10% in each of two adjacent districts of western Nepal; one district had an intense trachoma control program; the other district did not (2). Surveys in the Kailali and Konchapur districts of western Nepal have shown a large secular trend, suggesting that active trachoma would have disappeared rapidly even if a trachoma program had not been implemented (5). This situation is not unique to Nepal. A village in Gambia had hyperendemic trachoma in 1959 (66% prevalence in children), yet a followup survey in 1987 found that active disease had nearly disappeared, after only a modest 2-year control program of tetracycline administration (1). A study in Malawi showed a 50% reduction in active trachoma over a 16-year period in the absence of a specific trachoma program (4).
What might be the cause of this secular trend seen in so many countries? Various socioeconomic factors have been associated with the disappearance of trachoma, but studies have had difficulty establishing causality for any of them (16-18). In particular, facial hygiene and fly density are both believed to be related to trachoma activity (19-21). Several studies have associated dirty faces with active trachoma (22,23), but a trial involving intensive face-washing produced a modest (and statistically insignificant) decrease in clinically active trachoma at 1 year (21). The face fly (Musca sorbens) has been implicated im·pli·cate
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.
2. as a vector of trachoma (24,25). A recent study in the Gambia found that regular insecticide spraying in villages did reduce active trachoma (25); however, future controlled studies are necessary to determine the sustainability of this promising measure.
What role have antimicrobial agents played in the disappearance of trachoma? In a person, ocular chlamydial infection can be successfully treated with a single dose of azithromycin (26,27). At the community level, controlled trials in Tanzania, Gambia, and Egypt have shown that a single course of azithromycin can markedly reduce ocular chlamydial infection, even 1 year later (28). Our findings in this study support the hypothesis that the rising use of antimicrobial drugs in the community for indications other than trachoma may contribute to the disappearance of this disease.
Several of the principal antimicrobial drugs used in Nepal for systemic infectious diseases have antichlamydial action. National treatment guidelines for childhood pneumonia recommend co-trimoxazole (a combined preparation of sulfonamide sulfonamide /sul·fon·amide/ (sul-fon´ah-mid) a compound containing the sbondSO2NH2 group. The sulfonamides, or sulfa drugs, are derivatives of sulfanilamide, competitively inhibit folic acid synthesis in microorganisms, and formerly were and trimethoprim trimethoprim /tri·meth·o·prim/ (-meth´o-prim) an antibacterial closely related to pyrimethamine; almost always used in combination with a sulfonamide, primarily for the treatment of urinary tract infections. ) as the treatment of choice, followed by amoxicillin or oral chloramphenicol as second-line therapy (29). Other childhood infectious diseases are treated according to according to
1. As stated or indicated by; on the authority of: according to historians.
2. In keeping with: according to instructions.
3. the adapted WHO Integrated Management of Childhood Illness Integrated Management of Childhood Illness of IMCI is a systematic approach to children's health which focuses on the whole child. This means not only focusing on curative care but also on prevention of disease. (30). WHO recommends chloroquine chloroquine /chlo·ro·quine/ (klor´o-kwin) an antiamebic and anti-inflammatory used in the treatment of malaria, giardiasis, extraintestinal amebiasis, lupus erythematosus, and rheumatoid arthritis; used also as the hydrochloride and as the first-line therapy for malaria in Nepal, and sulfadoxine-pyrimethamine for chloroquine-resistant cases (31). The latter drug has antichlamydial activity through its sulfonamide component, sulfadoxine.
Why trachoma is disappearing should be investigated before it is gone, so that this knowledge can be applied to other diseases. If infection in a region is already in decline, the effect attributed to a trachoma control program may be exaggerated, and the program's success may not be duplicated in less fortunate areas. Conversely, beneficial factors could be introduced in areas where a downward secular trend does not already exist. Much discussion has taken place about the dangers associated with the indiscriminate use of antimicrobial drugs. These problems should be balanced against the benefits. The widespread use of antimicrobial drugs in developing countries for indications other than trachoma may play a role in eradicating one of the world's leading causes of preventable blindness.
Table. Comparison of antimicrobial drug use within and outside a trachoma program (a) Prescriptions/ person/year DDD/person/year to preschool to all ages children Antimicrobial pressure from pharmacies All antimicrobial drug prescriptions (from survey) 3.0 1.8 Antichlamydial prescriptions (from survey) 2.0 1.2 Antimicrobial pressure from trachoma program Annual azithromycin treatment with 100% coverage (theoretical) 2.3 1 Annual azithromycin treatment with 80% coverage (theoretical) 1.9 0.8 (a) Pharmacy survey data showing the total quantity of antimicrobial drugs used in Geta subdistrict and the proportion of antimicrobial drug with antichlamydial activity. An annual trachoma program theoretically gives 1 g of azithromycin to every adult (3.3 DDDs) and a lower dosage to children, averaging approximately 2.3 DDDs per person for all ages. We estimate from a mathematical model that mass antimicrobial treatment every 1.7 years would be sufficient to eventually eliminate ocular chlamydial infection from this region (13). DDD, defined daily dose, the average adult daily dosage for a drug's primary indication. Figure 1. Antimicrobial drug use in Geta, Nepal. Antimicrobial drug sales in a 3-month period (mid-February to mid-May 2000) from all pharmacies in the Geta subdistrict, expressed as defined daily doses (DDDs) and as a percentage of the total DDDs sold (6). The shaded region represents antimicrobial drugs that are effective against Chylmydia trachomatis. Antichlamydial Non-antichlamydial agents agents Macrolides 836 DDDs 3.9% Tetracyclines 2,546 DDDs 12% Sulfas 2,721 DDDs 13% Amoxicillin 8.088 DDDs 37% Other Penicillins 406 DDDs 2% Cephalosporins 748 DDDs 3.5% Quinolones 5,613 DDDs 27% Chloramphenicol 121 DDDs 0.6% Note: Table made from pie chart.
We especially thank Stephanie Costanza for her administrative and editorial support.
This project was carried out through the generous support of Geta Eye Hospital, Helen Keller International Helen Keller International (HKI) combats the causes and consequences of blindness and malnutrition by establishing programs based on evidence and research in vision, health and nutrition. , Nepal Netra Jyoti Sangh The term Sangh or Sangha means an assembly or congregation. The usage of the term includes:
South Asia, also known as Southern Asia Research Fund.
Dr. Chidambaram is a postdoctoral research fellow in ophthalmic epidemiology at the F. I. Proctor Foundation, University of California, San Francisco . Her research interests include trachoma and the epidemiology of corneal corneal
pertaining to the cornea. See also keratitis, keratopathy.
includes microcornea, coloboma, megalocornea, dermoid, congenital opacity.
corneal black body
see corneal sequestrum (below). and external eye diseases.
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Used to express impatient rejection or contempt.
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Address for correspondence: Thomas Lietman, Director, WHO Collaborating Center for the Prevention of Blindness, F.]. Proctor Foundation, 95 Kirkham St., Room 307, University of California The University of California has a combined student body of more than 191,000 students, over 1,340,000 living alumni, and a combined systemwide and campus endowment of just over $7.3 billion (8th largest in the United States). San Francisco San Francisco (săn frănsĭs`kō), city (1990 pop. 723,959), coextensive with San Francisco co., W Calif., on the tip of a peninsula between the Pacific Ocean and San Francisco Bay, which are connected by the strait known as the Golden , San Francisco, CA 94143-0944, USA; fax: 415-476-0527; email: firstname.lastname@example.org
Jaya D. Chidambaram, * Mariko Bird, * Vivian Schiedler, * Alicia M. Fry, ([dagger]) Travis Porco, ([double dagger double dagger
A reference mark () used in printing and writing. Also called diesis.
Noun 1. ]) Ramesh C. Bhatta, ([section]) Hem Jha, ([section]) J.S.P. Chaudary, ([section]) Bruce Gaynor, * Elizabeth Yi, * John P. Whitcher, * Susie Osaki-Holm, * and Thomas M. Lietman *
* University of California, San Francisco, California, USA; ([dagger]) Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. , Atlanta, Georgia, USA; ([double dagger]) California Department of Health Services Department of Health Services may refer to: