Re-emergence of Chlamydia trachomatis infection after mass antibiotic treatment of a trachoma-endemic Gambian community: a longitudinal study.

BACKGROUND: Community-wide mass antibiotic treatment is a central component of trachoma control. The optimum frequency and duration of treatment are unknown. We measured the effect of mass treatment on the conjunctival burden of Chlamydia trachomatis in a Gambian community with low to medium trachoma prevalence and investigated the rate, route, and determinants of re-emergent infection. METHODS: 14 trachoma-endemic villages in rural Gambia were examined and conjunctival swabs obtained at baseline, 2, 6, 12, and 17 months. Mass antibiotic treatment with azithromycin was given to the community at baseline. C trachomatis was detected by qualitative PCR and individual infection load then estimated by real-time quantitative PCR. FINDINGS: C trachomatis was detected in 95 (7%) of 1319 individuals at baseline. Treatment coverage was 83% of the population (1328 of 1595 people). The effect of mass treatment was heterogeneous. In 12 villages all baseline infections (34 [3%] of 1062 individuals) resolved, and prevalence (three [0.3%]) and infection load remained low throughout the study. Two villages (baseline infection: 61 [24%] of 257 individuals) had increased infection 2 months after treatment (74 [30%]), after extensive contact with other untreated communities. Subsequently, this value reduced to less than half of that before treatment (25 [11%]). INTERPRETATION: Mass antibiotic treatment generally results in effective, longlasting control of C trachomatis in this environment. For low prevalence regions, one treatment episode might be sufficient. Infection can be reintroduced through contact with untreated populations. Communities need to be monitored for treatment failure and control measures implemented over wide geographical areas.

The long-term natural history of trachomatous trichiasis in the Gambia.

PURPOSE: Trachoma is the leading infectious cause of blindness. However, there are few data on the natural history of trachomatous trichiasis to guide program planning or that investigate its pathogenesis. METHODS: A cohort of Gambians with trichiasis in one or both eyes who had declined surgery was observed. Clinical examinations were performed at baseline and 4 years later. Conjunctival swab samples were collected for Chlamydia trachomatis PCR and bacteriology. RESULTS: One hundred fifty-four people were examined at baseline and 4 years later (241 nonsurgical eyes). At baseline 124 (52%) eyes had major trichiasis (5+ lashes), 75 (31%) minor trichiasis (1-4 lashes), and 42 (17%) no trichiasis. By 4 years, trichiasis had developed in 12 (29%) of 42 previously unaffected eyes. Minor trichiasis progressed to major in 28 (37%) of 75 eyes. New corneal opacification more commonly developed in eyes that had major (10%) compared to minor (5%) trichiasis at baseline. Bacterial infection was common (23%), becoming more frequent with increasing trichiasis. C. trachomatis infection was rare (1%). Conjunctival inflammation was common (29%) and was associated with progressive trichiasis and corneal opacification. CONCLUSIONS: Trichiasis progressed in the long-term in this environment, despite a low prevalence of C. trachomatis. Blinding corneal opacification develops infrequently, unless major trichiasis is present. Epilation and early surgery need to be formally compared for the management of minor trichiasis. The pathologic correlates and promoters of conjunctival inflammation need to be investigated.

Detection, quantification and genotyping of Herpes Simplex Virus in cervicovaginal secretions by real-time PCR: a cross sectional survey.

BACKGROUND: Herpes Simplex Virus (HSV) Genital Ulcer Disease (GUD) is an important public health problem, whose interaction with HIV results in mutually enhancing epidemics. Conventional methods for detecting HSV tend to be slow and insensitive. We designed a rapid PCR-based assay to quantify and type HSV in cervicovaginal lavage (CVL) fluid of subjects attending a Genito-Urinary Medicine (GUM) clinic. Vaginal swabs, CVL fluid and venous blood were collected. Quantitative detection of HSV was conducted using real time PCR with HSV specific primers and SYBR Green I. Fluorogenic TaqMan Minor Groove Binder (MGB) probes designed around a single base mismatch in the HSV DNA polymerase I gene were used to type HSV in a separate reaction. The Kalon test was used to detect anti-HSV-2 IgG antibodies in serum. Testing for HIV, other Sexually Transmitted Infections (STI) and related infections was based on standard clinical and laboratory methods. RESULTS: Seventy consecutive GUM clinic attendees were studied. Twenty-seven subjects (39%) had detectable HSV DNA in CVL fluid; HSV-2 alone was detected in 19 (70%) subjects, HSV-1 alone was detected in 4 (15%) subjects and both HSV types were detected in 4 (15%) subjects. Eleven out of 27 subjects (41%) with anti-HSV-2 IgG had detectable HSV-2 DNA in CVL fluid. Seven subjects (10%) were HIV-positive. Three of seven (43%) HIV-infected subjects and two of five subjects with GUD (40%) were secreting HSV-2. None of the subjects in whom HSV-1 was detected had GUD. CONCLUSION: Quantitative real-time PCR and Taqman MGB probes specific for HSV-1 or -2 were used to develop an assay for quantification and typing of HSV. The majority of subjects in which HSV was detected had low levels of CVL fluid HSV, with no detectable HSV-2 antibodies and were asymptomatic.

Which members of a community need antibiotics to control trachoma? Conjunctival Chlamydia trachomatis infection load in Gambian villages.

PURPOSE: Trachoma is the leading cause of infectious blindness worldwide. Control strategies target antibiotic therapy to individuals likely to be infected with Chlamydia trachomatis on the basis of clinical signs. However, many studies have found chlamydial infection in the absence of clinical disease. It has been unclear whether such individuals represent a significant reservoir of infection. In the current study, a quantitative polymerase chain reaction (PCR) assay was used to investigate the distribution and determinants of chlamydial infection load in an endemic community, and the findings were used to evaluate the potential effectiveness of different control strategies. METHODS: Members of a trachoma-endemic community (n = 1319) in a rural area of The Gambia were examined for signs of disease, and tarsal conjunctival swab samples were collected. C. trachomatis was initially detected by qualitative PCR. The load of infection was then estimated by real-time quantitative PCR. RESULTS: Chlamydial infection was detected in 7.2% of the population. The distribution of infection load was skewed, with a few individuals having high loads. Only 24% of infected individuals had signs of active trachoma. Infection loads were higher in those with clinically active disease and were highest among those with severe inflammatory trachoma. High infection loads were associated with having no accessible latrine and living with a person with active disease. CONCLUSIONS: In this low-prevalence setting, infected individuals without signs of active trachoma constitute a significant reservoir of infection. Treatment of a defined unit of people who live with someone with clinically active trachoma would effectively target antibiotic treatment to infected people without signs of disease.

Profound and sustained reduction in Chlamydia trachomatis in The Gambia: a five-year longitudinal study of trachoma endemic communities.

BACKGROUND: The elimination of blinding trachoma focuses on controlling Chlamydia trachomatis infection through mass antibiotic treatment and measures to limit transmission. As the prevalence of disease declines, uncertainty increases over the most effective strategy for treatment. There are little long-term data on the effect of treatment on infection, especially in low prevalence settings, on which to base guidelines. METHODOLOGY/PRINCIPAL FINDINGS: The population of a cluster of 14 Gambian villages with endemic trachoma was examined on seven occasions over five years (baseline, 2, 6, 12, 17, 30 and 60 months). Mass antibiotic treatment was given at baseline only. All families had accessible clean water all year round. New latrines were installed in each household after 17 months. Conjunctival swab samples were collected and tested for C. trachomatis by PCR. Before treatment the village-level prevalence of follicular trachoma in 1 to 9 year olds (TF(%1-9)) was 15.4% and C. trachomatis was 9.7%. Antibiotic treatment coverage was 83% of the population. In 12 villages all baseline infection cleared and few sporadic cases were detected during the following five years. In the other two villages treatment was followed by increased infection at two months, which was associated with extensive contact with other untreated communities. The prevalence of infection subsequently dropped to 0% in these 2 villages and 0.6% for the whole population by the end of the study in the absence of any further antibiotic treatment. However, several villages had a TF(%1-9) of >10%, the threshold for initiating or continuing mass antibiotic treatment, in the absence of any detectable C. trachomatis. CONCLUSIONS/SIGNIFICANCE: A single round of mass antibiotic treatment may be sufficient in low prevalence settings to control C. trachomatis infection when combined with environmental conditions, which suppress transmission, such as a good water supply and sanitation.