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Lutte contre le trachome en Afrique subsaharienne

 | 
Anne-Marie Moulin
, 
Jeanne Orfila
, 
Doulaye Sacko
, 
et al.

Seconde partie. Chapitres analytiques

Chapitre 22. How can the effectiveness of azithromycin be evaluated: evaluation methods, documented experience, long- and short-term effectiveness in public health? [Comment évaluer l'efficacité de l'azithromycine : méthodes d'évaluation, expériences documentées, efficacité en santé publique à court et à long terme ?]

Thomas Lietman

Texte intégral

1The efficacy of azithromycin can be evaluated in an individual, in a community, in the short term (1 year or less) and in the long term (several years). The sexually transmitted disease literature suggests that infection can be eliminated with a single dose of oral azithromycin 92-98 % of time (Steingrimsson et al., 1994 ; Stamm et al., 1995 ; Bianchi et al., 1998 ; Erdogru et al., 1995 ; Magid et al., 1996 ; Thorpe et al., 1996). There are fewer studies for ocular chlamydia, although the results are consistent with this (Schachter et al., 1999; Dawson et al., 1997). It should be noted that this does not mean that clinical activity (TF/TI) will be eliminated 95 % of the time, as follicles are known to persist even after there is no ocular chlamydial detectable by even the most sensitive lab test (Bailey et al., 1993).

2Clearly evaluating infection (by nucleic acid amplification tests, for example, the polymerase chain reaction or PCR) is a more sensitive indicator of treatment efficacy than is the clinical exam. This is because while antibiotics directly eliminate the chlamydial organism, it may take weeks or months for the clinical signs of activity to disappear, and because other conjunctivities can mimic the signs of trachoma. There is little doubt that a high prevalence of clinical activity (TF/TI) in a village before treatment implies a high prevalence of ocular chlamydia (Bird et al., 2003). However, it is not clear that the clinical activity is an accurate indicator of infection in low prevalent areas or after mass antibiotic treatment (Bird et al., 2003; Baral et al., 1999).

3A single mass treatment of oral azithromycin (or a course of 3 doses over 3 weeks) distributed throughout a community has also been shown to be extremely effective, at least in the setting of extraordinarily high coverage levels of >90 %. Perhaps the best demonstration of this was in the azithromycin for the Control of Trachoma (ACT) study performed in Tanzania, the Gambia, and Egypt (Schachter et al., 1999). In all three countries, infection was reduced dramatically 2-4 months after a mass antibiotic treatment (see Egyptian results in figure below). In fact, infection had not returned to anywhere near its pre-treatment levels even at 24 months (personnel communication, Chandler Dawson). Treatment has also been shown to be effective in the short term reducing clinical activity in Morocco, Nepal, Tunisia, and the Gambia.

Fig. 6 : Clinical Activity and Nucleic Acid Amplification Test after treatment in Egypt

4Longer term results are difficult to come by. Morocco has experienced great success with repeated treatment, although these results have yet to be published (WHO, 2001). In Western Nepal, three annual treatments were very effective (Gaynor et al., 2003). In one village (see figure below), only a single infection could be identified in children after 3 annual treatments. Data from work in Tanzania implies that coverage is crucial for success: clinical activity was not reduced at 12 months in villages with <65 % coverage (personnel communication, Sheila West).

Effect of azithromycin distributions on public health1

  • 1 Pour plus de détails se reporter au chapitre de J. Orfila.

5There are potential positive and negative benefits of mass azithromycin treatment. Azithromycin may have an effect on diseases other than chlamydia, such as malaria, upper respiratory infections, and diarrhea. However, mass distributions may increase the amount of macrolide resistance in other bacteria such as pneumococcus.

Potential bénéficial effects

6Mass azithromycin distributions have been shown to reduce the prevalence of pneumococcus and Haemophilus influenzae at least in the first few months after treatment. This has been demonstrated in the upper respiratory tract (Adegola et al., 1995; Leach et al., 1997; Fry et al., 2002) and the conjunctiva (Chern et al., 1999). This reduction is apparently short-lived, as infection prevalences return to baseline 6 months after treatment. Symptoms of diarrhea and upper respiratory infection also decrease 2 weeks after treatment in treated children compared to untreated children (Fry et al., 2002), although it is not expected that these effects would persist for a long period of time. Azithromycin has activity against malaria and tuberculosis, although the effect on these two important causes of morbidity and mortality have not been studied. Interestingly, gastrointestinal symptoms were fewer in the azithromycin-treated cohort, even though these are a well-recognized side effect of azithromycin.

Négative benefits

7There have been no reported serious side effects from azithromycin distributions, although it is not clear that programs have an easy way to assess a relatively rare side effect.

8Antibiotic resistance. Any program that distributes antimicrobial agents to entire communities must address possible adverse effects of the medication, including the emergence of drug-resistant organisms. Mass distribution of oral sulfonamides to combat trachoma in northern Africa and the southwest United States in the 1950's and early 1960's was eventually halted, in part because of an unacceptable rate of side effects (most notably Stevens-Johnson Syndrome, personnel communication, Chandler Dawson). The worldwide anti-malarial campaigns of the 1960's and 1970's never achieved their most optimistic goals at least partly because of emerging resistance (Farid, 1980). Possible chlamydial resistance or resistance in other organisms such as pneumococcus will be considered elsewhere in this report.

Bibliographie

References

Adegbola R.A., Mulholland E.K., Bailey R., Secka O., Sadiq T., Glasgow K., Mabey, D., 1995 – Effect of azithromycin on pharyngeal microflora. Pediatric Infectious Disease Journal, 14(4): 335-337.

Bailey R.L., Arullendran P., Whittle H.C., Mabey D.C., 1993 – Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Lancet, 342(8869): 453-456.

Baral K. Osaki S., Shreshta B., Panta C.R., Boulter A., Pang F., Cevallos V., Schachter J., Lietman T., 1999 – Reliability of clinical diagnosis in identifying infectious trachoma in a low-prevalence area of Nepal. Bulletin of the World Health Organization, 77(6): 461-466.

Bianchi A., Bogard M., Cessot G., Bohbot J.M., Malkin J.E., Alonso J.M., 1998 – Kinetics of chlamydia trachomatis clearance in patients with azithromycin, as assessed by first void urine testing by PCR and transcription-mediated amplification. Sexually Transmitted Diseases, 25(7): 366-367.

Bird M., Dawson C.R., Schachter J.S., Miao Y., Shama A., Osman A., Bassem A., Lietman T.M., 2003 – Does the diagnosis of trachoma adequately identify ocular chlamydial infection in trachoma-endemic areas? The Journal of infectious diseases, 187(10): 1669-1673.

Chern K.C., Shrestha S.K., Cevallos V., Dhami H.L., Tiwari P., Chern L., Whitcher J.P., Lietman T.M., 1999 – Alterations in the conjunctival bacterial flora following a single dose of azithromycin in a trachoma endemic area. British Journal of Ophthalmology, 83(12): 1332-1335.

Dawson C.R., Schachter J., Sallam S., Sheta A., Rubinstein R.A., Washton H., 1997 – A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children. Clinical Infectious Diseases, 24(3): 363-368.

Erdogru T., Agaçfidan A., Onel M., Badur S., Ang O., Telalloglu S., 1995 – The treatment of non-gonococcal urethritis with single dose oral azithromycin. Journal of International Medical Research, 23(5): 386-393.

Farid M. 1980 – The malaria program: From euphoria to anarchy. World Health Forum, 1: 8-33

Fry A.M., Jha H.C., Lietman T., Chaudary J., Bhatta R.C., Elliott J., Hyde T., Schuchat A., Pokhrel G., Gaynor B., Dowell S., 2002 - Secondary effects of mass chemoprophylaxis with azithromycin to eliminate blindness due to trachoma in Nepal: Adverse and beneficial effects. Clinical Infectious Diseases, 35: 395-402.

Gaynor B.D., Miao Y., Cevallos V., Jha H., Chaudary J.S., Bhatta R., Osakiholm S., Yi E., Schachter J., Whitcher J.P., Lietman T., 2003 – Eliminating trachoma in areas with limited disease. Emerging Infectious Disease, 9(5): 596-598

Leach A.J., Shelby-James T.M., Mayo M., Gratten M., Laming A.C., Currie B.J., Mathews J.D., 1997 – A prospective study of the impact of community-based azithromycin treatment of Trachoma on carriage and resistance of Streptococcus pneumoniae. Clinical Infectious Diseases, 24(3): 356-362.

Magid D., Douglas J.M. Jr., Schwartz J.S., 1996 – Doxycycline compared with azithromycin for treating women with genital Chlamydia trachomatis infections : An incremental cost-effectiveness analysis. Annals of Internal Medicine 124(4): 389-99.

Schachter J., West S.K., Mabey D., Dawson C.R., Bobo L., Bailey R., Vitale S., Quinn T.C., Sheta A., Sallam S., Mkocha H., Mabey D., Faal H., 1999 – Azithromycin in control of trachoma. Lancet, 354(9179): 630-635.

Stamm W.E., Hicks C.B., Martin D.H., Leone P., Hook E.W. 3RD, Cooper R.H., Cohen M.S., Batteiger B.E., Workowski K., Mccormack W.M., 1995 – Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study. Jama, 274(7): 545-549.

Steingrímsson O., Olafsson J.H., Thórarinsson H., Ryan R.W., Johnson R.B., Tilton R.C., 1994 – Single dose azithromycin treatment of gonorrhea and infections caused by C. trachomatis and U. urealyticum in men. Sexually Transmitted Diseases, 21(1): 43-46.

Thorpe E.M. Jr., Stamm W.E., Hook E.W. 3RD, Gall S.A., Jones R.B., Henry K., Whitworth G., Johnson R.B., 1996 – Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises. Genitourinary Medicine, 72(2): 93-97.

Notes

1 Pour plus de détails se reporter au chapitre de J. Orfila.

Table des illustrations

Légende Fig. 6 : Clinical Activity and Nucleic Acid Amplification Test after treatment in Egypt
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