Collateral benefits arising from mass administration of azithromycin in the control of active trachoma in resource limited settings

Introduction The benefits of the use of antibiotics in the mass treatment for active trachoma and other diseases have been documented, but the secondary effects arising from such a programme have not been fully elucidated. The purpose of this study was to investigate the potential secondary benefits arising from the use of azithromycin in mass treatment of active trachoma in an economically challenged Kenyan nomadic community. Methods Health information reports for January 2005 to December 2010 were reviewed to determine the annual trends of infectious diseases in the two districts, Narok and Transmara. The year 2007 was considered as the baseline for mass drug administration (MDA). Odds ratios (OR) were used to describe the association. Results The mass distribution coverage in Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR = 1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06), urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms (OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR, 1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment, indicating a better outcome. Before the intervention, there was a reducing trend in the odds for respiratory diseases. In Transmara (control), there was an increase in odds for malaria, respiratory infections, UTIs and intestinal worms. The odds for diarrhoeal diseases, skin diseases and pneumonia decreased throughout the study period. Conclusion Mass distribution of azithromycin may have contributed to the decrease in the prevalence of the respiratory infections in Narok District.


Introduction
The mass administration of antibiotics has been used in the prevention and treatment of bacterial diseases. It has been recognized as a potentially vital and important public health strategy towards the control of neglected tropical diseases and other coinfections in sub-Saharan Africa, whereby the provision of universal healthcare is still a major challenge. It has also been considered as The F&E components had not been fully implemented in the entire district at the time of this study. The findings were compared with those of neighbouring Transmara district, which is trachomaendemic but had no trachoma control project.
Trachoma is still endemic in developing countries and is the common cause of infectious blindness. Most of the afflicted are poor people with low hygiene and inadequate access to clean water.
They are therefore vulnerable to several other infections [1,2]. As a strategy to eradicate trachoma, the World Health Organization (WHO) adopted the SAFE programme consisting of Surgery, Antibiotics for infectious trachoma, Facial cleanliness to reduce transmission and Environmental cleanliness to improve hygiene and sanitation. It recommends mass distribution of antibiotic in affected areas with prevalence of active trachoma of more than 10% in children aged 1 to 9 years in a district, or 5% for the community [3,4] .
Trachoma control programs in some of districts are currently on going in Kenya. The SAFE programme, implemented in Shampole, Kajiado district reported reduction in prevalence of active trachoma from 46% to 16% and the potentially blinding trachoma from 4.5% to 1.7% over a period of one year with low incidences of recurrences [5]. SAFE strategy programme in the greater Narok district began in 2008 and proceeded annually for three years, with the support from Operation Eyesight Universal (OEU). The prevalence of trachoma in Narok district is 30.5% [6]. Azithromycin is currently the antibiotic of choice administered in repeated annual community mass treatment for a period of three years [7]. It is administered as a single dose of 1 gm for adults whereas the children's dose is 20 mg/kg. Expectant mothers and children less than six months are put on tetracycline eye ointment [8]. The F&E activities involve preventive measures to reduce disease transmission which includes the provision of water, health promotion and education. The full benefits of the F&E activities generally take a longer period to be realized owing to the challenges of its implementation [9][10][11].
Previous studies have demonstrated that azithromycin markedly decreases the prevalence of ocular strains of Chlamydia trachomatis, the causative agent for trachoma [12,13]. Whereas mass treatment has been shown to reduce the prevalence of trachoma, the potential secondary health benefits of such treatment have not been well documented. Previous studies regarding its impact on the prevalence of respiratory infections have been inconclusive. In a study among children in Ethiopia, the authors reported a decline in the overall mortality, perhaps due to respiratory infections, diarrhoea and malaria [14,15]. An indirect protective effect against trachoma among untreated children residing in villages where most individuals have been treated, and decline in pneumococcal resistance has also been reported after mass treatment in Ethiopia [16,17]. However, other authors in related studies concluded that it may lead to the emergence of resistant strains of Streptococcus pneumonia [18,19]. The aim of this study therefore, was to investigate the potential secondary benefits arising from the mass treatment.

Methods
This community based operational research was conducted in the Additionally, the 2007 to 2010 trend was compared with that for Transmara to determine whether the treatment was beneficial or not. At the time of the study, F&E activities in Narok were at its inception and had not achieved a wider coverage. In both Narok and Transmara districts, there were F&E activities being provided under the National Community Health Strategy programme. It was therefore assumed that any change in disease patterns was attributable to the MDA. We also reported the trends in the diseases.

Statistical analysis
The number of patients treated in each month was aggregated to the totals for the year. The base year analysis was set to 2007, which was the year used to compute the test statistics. Analysis was performed using STATA software version.10 (STATACorp, College Station, Texas 7784) in order to compare the proportions of the various diseases before and after the intervention. Chi-square test was used to determine the association between respective years and the base year (2007) in respect of the various diseases. Odds ratios and significance of the chi-square test were used as indicators of prevalence. For years after 2007, an OR>1 implied that the intervention had a beneficial effect, meaning that the proportion of cases in the following respective year was lower, or a decline in prevalence following the treatment/intervention. An OR<1 implied that the intervention had no impact in the successive year (the proportion of the case in that year were significantly higher than the base year). The converse was true for the years before 2007. An (OR>1) implied that the prevalence before the intervention was lower, that is the proportion of cases in 2007 was significantly higher than those in the prior year. An OR<1 implied that the proportion was higher before the intervention.

Results
The mass distribution coverage in Narok district decreased over the study period; 83% in 2008, 74% in 2009 and 63% in 2010.
Respiratory diseases and malaria were the most prevalent diseases.
The prevalence of pneumonia was between 5% and 7% while that of the other diseases of the respiratory system ranged from 30% to 34%. Malaria had a prevalence of between 22% and 29% over the study period. The prevalence of the other infections recorded is as in Table 1. Apart from the diarrhoeal diseases, there was a general decline in all the other recorded infectious diseases after the third year from the baseline, despite the decreased percentage coverage over the period (Table 1, Figure 1). Respiratory diseases were significantly more prevalent in the years prior to the intervention compared to the period after the use of antibiotics. The proportions of patients with malaria decreased throughout the study period. The prevalence for both diseases rose proportionately with the corresponding decrease in coverage from the second to the third round (malaria 25% vs. 22%, respiratory diseases 31% vs. 30%).
There was a statistically significant increase in proportion of pneumonia during this period (Figure 1).There were statistically significant changes in the odds for all diseases except skin diseases three rounds after the intervention. The odds for malaria (68580(27%) vs. 63900(25%); OR, 1.13; 95% CI 1.12-1.14),   Table 2). There was a change from manual to electronic data recording in 2008 which could have resulted in the loss of some data. This may explain the comparatively low numbers recorded in 2008.

Discussion
The provision of basic healthcare is still a major challenge in  [14,17]. In a separate study conducted in Gambia, the authors concluded that it reduced the childhood morbidity [34]. A recent study, also conducted in Ethiopia concluded that mass administration of azithromycin in a trachoma control programme reduced all-cause and infections childhood mortality [15]. We

Conclusion
Our findings demonstrate that the mass distribution of azithromycin may have contributed to the decrease in the prevalence of the respiratory infections in Narok District.

Competing interests
The authors declare that there are no competing interests.  Table 1: proportion of patients with various illnesses at the baseline and after mass administration of azithromycin in Narok District