Interventions for Neglected Tropical Diseases Among Children and Adolescents: A Meta-analysis.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of communicable diseases affecting the poorest populations around the world. OBJECTIVE: To assess the effectiveness of interventions, including mass drug administration (MDA), water, sanitation, and hygiene (WASH), vector control, health education, and micronutrients supplementation, for NTDs among children and adolescents. METHODS: We conducted a literature search on the Cochrane Controlled Trials Register, Medline, and other databases until December 2020. We included randomized controlled trials and quasi-experimental studies conducted among children and adolescents. Two authors independently screened studies for relevance. Two authors independently extracted data, assessed the risk of bias, performed metaanalysis, and rated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: We included 155 studies (231 articles) involving 262 299 participants. For soil-transmitted helminthiasis, MDA may reduce the prevalence of Ascaris, Trichuris, and hookworm by 58%, 36%, and 57%, respectively. We are uncertain of the effect of health education, WASH, and iron supplementation on soil-transmitted helminthiasis prevalence. For Schistosomiasis, health education probably reduces the intensity and prevalence of S. mansoni, whereas micronutrient supplementation may reduce anemia prevalence and the infection intensity of S. hematobium compared with no supplementation. We are uncertain of the effect of MDA and vector control on Schistosomiasis outcomes. For trachoma, health education probably reduces the prevalence of active Trachoma, whereas we are uncertain of the effect of MDA, WASH, and vector control on Trachoma outcomes. There is limited data on the effectiveness of interventions for NTDs targeting children and adolescents. CONCLUSION: Future studies are needed to evaluate the relative effectiveness and cost-effectiveness of various interventions specifically targeting children and adolescents.

Trachoma Rapid Assessments in Venezuela, an Example of the Integration of Data Gathering with Service Delivery in Hard-to-reach Populations.

A) PURPOSE: The objective of the study was to assess the presence of trachoma in high priority districts in the Amazon state of Venezuela (the Bolivarian Republic of), and use trachoma data gathering platform to offer integrated primary health care services to underserved hard-to-reach populations living in the border with Colombia. B) METHODS: Trachoma Rapid Assessments (TRA) were conducted in indigenous communities of three municipalities of the Amazonas State of Venezuela from June 2018 to April 2019 using the World Health Organization (WHO) guidelines. Integrated health services were delivered based on the identified needs of the population of the assessed communities. C) RESULTS: 1,185 children aged 1-9 years were examined for trachoma in the three municipalities, of which 6.92% had active trachoma; 994 people 15 years and above were examined for trachomatous trichiasis (TT) finding two cases (0.2%). 1,635 people were examined for other health-related problems and the most common diagnoses were intestinal parasites (54.74%), eye diseases (16.81%), cavities (7.34%), scabies (5.56%), headache (4.40%), and malaria (2.81%); additionally, 2,233 vaccine doses were provided to children and adults to complete vaccination series. D) CONCLUSION: The results of the TRA in the Amazon state of Venezuela suggest that trachoma could be a public health problem and standardized population-based surveys to establish the prevalence and determine the interventions to implement are needed.

Environmental factors and hygiene behaviors associated with facial cleanliness and trachoma in Kongwa, Tanzania.

BACKGROUND: Having a clean face is protective against trachoma. In the past, long distances to water were associated with unclean faces and increased trachoma. Other environmental factors have not been extensively explored. We need improved clarity on the environmental factors associated with facial cleanliness and trachoma prevalence, especially when the disease burden is low. METHODOLOGY/PRINCIPLE FINDINGS: A cross-sectional survey focusing on household environments was conducted in all 92 villages in Kongwa, Tanzania, in a random selection of 1798 households. Children aged 0-5 years in these households were examined for facial cleanliness. In each of the 50 randomly-selected villages, 50 children aged 1-9 years were randomly selected and examined for trachoma. In a multivariate model adjusting for child age, we found that children were more likely to have clean faces if the house had a clean yard (OR 1.62, 95% CI 1.37-1.91), an improved latrine (OR 1.11, 95% CI 1.01-1.22), and greater water storage capacity (OR 1.02, 95% CI 1.00-1.04), and if there were clothes washed and drying around the house (OR 1.30, 95% CI 1.09-1.54). However, measures of crowding, wealth, time spent on obtaining water, or the availability of piped water was not associated with clean faces. Using a cleanliness index (clean yard, improved latrine, washing clothes, ≥1 child in the household having a clean face), the community prevalence of trachoma decreased with an increase in the average value of the index (OR 2.28, 95% CI 1.17-4.80). CONCLUSIONS/SIGNIFICANCE: Access to water is no longer a significant limiting factor in children's facial cleanliness in Kongwa. Instead, water storage capacity and the way that water is utilized are more important in facial cleanliness. A household cleanliness index with a holistic measure of household environment is associated with reduced community prevalence of trachoma.

Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS: In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (AzmR) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (AzmR 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes. CONCLUSIONS: Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of AzmR and iMLSB S. aureus. TRIAL REGISTRATION: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008.

Water-filtered infrared A reduces chlamydial infectivity in vitro without causing ex vivo eye damage in pig and mouse models.

Repeated ocular infections with Chlamydia trachomatis trigger the development of trachoma, the most common cause of infectious blindness worldwide. Water-filtered infrared A (wIRA) has shown positive effects on cultured cells and human skin. Our aim was to evaluate the potential of wIRA as a possible non-chemical treatment for trachoma patients. We both modeled ocular chlamydial infections using C. trachomatis B to infect human conjunctival epithelial cells (HCjE) and studied the effects of wIRA on non-infected ocular structures with two ex vivo eye models. We focused on the temperature development during wIRA irradiation in cell culture and perfused pig eyes to exclude potentially harmful side effects. Furthermore, cell viability of HCjE and cytotoxicity in mouse retina explants was analyzed. We demonstrated a significant wIRA-dependent reduction of chlamydial infectivity in HCjE cells. Moreover, we observed that wIRA treatment of HCjE prior to infection was sufficient to inhibit chlamydial infectivity and that visible light enhances the effect of wIRA. Irradiation did not reduce cell viability and there was no indication of retinal damage post treatment. Additionally, temperatures during wIRA exposure did not markedly exceed physiological eye temperatures, suggesting that hyperthermia-related lesions are unlikely. For clinical applications, further exploration of wIRA as a non-chemical treatment device in an experimental animal model is essential.

Natural products for the treatment of trachoma and Chlamydia trachomatis.

The neglected tropical disease (NTD) trachoma is currently the leading cause of eye disease in the world, and the pathogenic bacteria causing this condition, Chlamydia trachomatis, is also the most common sexually transmitted pathogenic bacterium. Although the serovars of this bacterial species typically vary between ocular and genital infections there is a clear connection between genital C. trachomatis infections and the development of trachoma in infants, such that the solutions to these infections are closely related. It is the unique life cycle of the C. trachomatis bacteria which primarily leads to chronic infections and challenges in treatment using conventional antibiotics. This life cycle involves stages of infective elementary bodies (EBs) and reproductive reticulate bodies (RBs). Most antibiotics only target the reproductive RBs and this often leads to the need for prolonged therapy which facilitates the development of drug resistant pathogens. It is through combining several compounds to obtain multiple antimicrobial mechanisms that we are most likely to develop a reliable means to address all these issues. Traditional and ethnobotanical medicine provides valuable resources for the development of novel formulations and treatment regimes based on synergistic and multi-compound therapy. In this review we intend to summarize the existing literature on the application of natural compounds for controlling trachoma and inhibiting chlamydial bacteria and explore the potential for the development of new treatment modalities.

Australian Football League clinics promoting health, hygiene and trachoma elimination: the Northern Territory experience.

Australia is the only developed country to suffer trachoma and it is only found in remote Indigenous communities. In 2009, trachoma prevalence was 14%, but through screening, treatment and health promotion, rates had fallen to 4% in 2012. More work needs to be done to sustain these declining rates. In 2012, 25% of screened communities still had endemic trachoma and 8% had hyperendemic trachoma. In addition, only 58% of communities had reached clean face targets in children aged 5-9 years. Australian Football League (AFL) players are highly influential role models and the community love of football provides a platform to engage and strengthen community participation in health promotion. The University of Melbourne has partnered with Melbourne Football Club since 2010 to run trachoma football hygiene clinics in the Northern Territory (NT) to raise awareness of the importance of clean faces in order to reduce the spread of trachoma. This activity supports Federal and state government trachoma screening and treatment programs. Between 2010 and 2013, 12 football clinics were held in major towns and remote communities in the NT. Almost 2000 children and adults attended football clinics run by 16 partner organisations. Awareness of the football clinics has grown and has become a media feature in the NT trachoma elimination campaign. The hygiene station featured within the football clinic could be adapted for other events hosted in remote NT community events to add value to the experience and reinforce good holistic health and hygiene messages, as well as encourage interagency collaboration.

Does mass azithromycin distribution impact child growth and nutrition in Niger? A cluster-randomized trial.

BACKGROUND: Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. METHODOLOGY: In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6-60 months of age. PRINCIPAL FINDINGS: We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). CONCLUSIONS/SIGNIFICANCE: We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association.

Is there evidence for resistance of ocular Chlamydia trachomatis to azithromycin after mass treatment for trachoma control?

BACKGROUND: Trachoma, caused by repeated infections with ocular Chlamydia trachomatis, is targeted for elimination using multiple annual rounds of mass drug administration (MDA) in endemic communities. Infection rates do not decline as expected in some communities, leading to concerns about azithromycin resistance. METHODS: After 3 yearly MDAs in 32 communities in Tanzania, 107 children were identified 1 year later with infection. All were provided MDA again, and 90 were seen again at 2 months, of whom 30 had infection. Chlamydia trachomatis isolates were obtained before and after MDA in 15 paired samples and were tested for antimicrobial susceptibility. The infectious load of C. trachomatis before MDA was determined in 30 children who had infection at both times and 60 whose infection cleared. RESULTS: The median load was 8.6 genome copies per polymerase chain reaction in the consistently infected, and 8.4 in those whose infection cleared (P = .86). For the consistently infected, the average minimum inhibitory concentration was 0.26 µg/mL for azithromycin before and 0.20 µg/mL after MDA. All isolates had minimum inhibitory concentration ≤0.50 µg/mL. CONCLUSIONS: There is no evidence that continued infection after MDA was due either to resistance to azithromycin or to a heavier load of organism before treatment. Other potential causes of persistent infection need to be evaluated.

Trachoma elimination in remote Indigenous Northern Territory communities: baseline health-promotion study.

Identify trachoma knowledge, attitudes and practice of staff in clinics, schools and community workplace settings to optimise trachoma-elimination health-promotion programs in the Katherine West Health Board region of the Northern Territory. Prior to the introduction of a suite of health promotion resources the Indigenous Eye Health Unit and Katherine West Health Board conducted a baseline survey of open, multi-choice and closed questions regarding knowledge, attitudes and practices in relation to trachoma with 72 staff members over a 6-month period in 2010-11. Data were analysed for differences between settings. Two significant barriers and one enabling factor were identified. One in five staff members in clinics and 29% of staff members in schools were unaware they lived and worked in a trachoma-endemic area. One-third of school staff and 38% of clinic staff considered it normal for children to have dirty faces. However, the majority of participants felt comfortable talking about hygiene issues with others. The presence of dirty faces in young Indigenous children underpins the continuing prevalence of trachoma. Increasing the awareness of the health effects of children's nasal and ocular secretions and changing community acceptance of dirty faces as the norm will reduce the risk of trachoma and other childhood infections. Staff in clinics, schools and community work settings can play a role in trachoma elimination by actively encouraging clean faces whenever they are dirty and by including face washing in holistic hygiene and health education. Staff in schools may need additional support. Trachoma-elimination health promotion should increase awareness of trachoma prevalence and encourage all who work and live in remote Indigenous communities to take action to promote facial cleanliness and good hygiene practices.

The added value of water, sanitation, and hygiene interventions to mass drug administration for reducing the prevalence of trachoma: a systematic review examining.

Trachoma is the leading cause of infectious blindness worldwide. The SAFE strategy, the World Health Organization-recommended method to eliminate blinding trachoma, combines developments in water, sanitation, surgery, and antibiotic treatment. Current literature does not focus on the comprehensive effect these components have on one another. The present systematic review analyzes the added benefit of water, sanitation, and hygiene education interventions to preventive mass drug administration of azithromycin for trachoma. Trials were identified from the PubMed database using a series of search terms. Three studies met the complete criteria for inclusion. Though all studies found a significant change in reduction of active trachoma prevalence, the research is still too limited to suggest the impact of the "F" and "E" components on trachoma prevalence and ultimately its effects on blindness.

Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in young children 6 months after treatment.

BACKGROUND: Emerging evidence suggests that the mass distribution of azithromycin for trachoma control (MDA) may increase circulation of macrolide resistance in bacteria associated with severe pediatric infections in treated communities. METHODS: We examined the effect of MDA on nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among 1015 young children living in rural Tanzania. MDA with a single dose of oral azithromycin was provided in 4 of 8 communities where trachoma prevalence was ≥10%. Isolates were tested for susceptibility to azithromycin (AZM) and commonly used antibiotics by disk diffusion and Etest. We calculated the proportion of antibiotic-resistant S. pneumoniae carriage at baseline and again 1, 3, and 6 months after treatment, and at comparable intervals in the untreated villages. RESULTS: The proportion of AZM-resistant isolates was similar between groups at baseline (MDA: 35.8% vs non-MDA: 35.4%), however, this proportion was greater in the MDA group in all subsequent surveys. At 6 months, the percentage of AZM-resistant isolates was significantly higher in the MDA group (81.9% vs 46.9%, P < .001). The odds of AZM-resistant carriage was 5-fold greater in the MDA group (odds ratio, 4.95 [95% confidence interval, 3.23-7.61]). The proportion of isolates clinically resistant to AZM (minimum inhibitory concentration ≥16 µg/mL) was also significantly greater in the MDA group at 6 months (35.3% vs 12.4%, P < .006). CONCLUSIONS: Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Preventive chemotherapy and the fight against neglected tropical diseases.

Preventive chemotherapy is the public health strategy recommended by the WHO against a set of neglected tropical diseases that includes four groups of helminth infections (lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis) and one chlamydial (trachoma) infection. This article presents the characteristics of preventive chemotherapy interventions directed against each disease targeted by this strategy and provides an update on the status of their implementation worldwide.

Fred Loe, MD, and the history of trachoma.

Trachoma has been one of the most blinding diseases in the history of ophthalmology. From its initial description in antiquity until the late 1930s, no specific treatment or effective cure had been known, and the only expedient had been to destroy the diseased tissue containing the infectious agent, rendering the disease inactive. Virtually all medical, mechanical, and surgical treatments were unsatisfactory, with cure rates of approximately 20%. Therapy for trachoma had barely advanced from the measures used by the ancient Egyptian, Greek, and Roman physicians. All prior therapies became obsolete in 1938 when Fred Loe, MD, working on an American Indian reservation, introduced sulfanilamide as a treatment of trachoma, achieving a 90% cure rate. One of the most unusual aspects of Loe's career was that he had no formal training in ophthalmology and was completely self-taught as an ophthalmologist.

Mass treatment of trachoma with azithromycin 1.5% eye drops in the Republic of Cameroon: feasibility, tolerance and effectiveness.

AIMS: An epidemiological study carried out in 2006 indicated a high prevalence of blinding trachoma in the Kolofata Health District, Far North Region, Republic of Cameroon. As a result, the national blindness control programme of Cameroon instituted a trachoma elimination programme using the SAFE strategy. METHODS: A campaign to treat the entire district population with azithromycin 1.5% eye drops was undertaken in February 2008. To measure the effectiveness of treatment on the prevalence of active trachoma, two epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the treatment campaign and the second study was performed 1 year later. RESULTS: The prevalence of active forms of trachoma (trachomatous inflammation--follicular (TF) + TF/trachomatous inflammation--intense (TI)) dropped from 31.5 (95% CI 26.4 to 37.5)% before treatment to 6.3 (95% CI 4.1 to 9.6)% 1 year after treatment-a reduction of nearly 80%. There were no reports of serious or systemic side effects. Tolerance was excellent and no treatment was interrupted. CONCLUSION: Mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated and effective.

Neglected diseases caused by bacterial infections.

Bacterial infections represent a major health problem, especially in third world countries. In endemic regions, large populations of people are greatly affected, but the medical care is very limited. In this review, the neglected diseases buruli ulcer and trachoma are elucidated. Buruli ulcer is caused by Mycobacterium ulcerans which produces an outstanding immunosuppressive toxin mycolactone that induces an ulcerative, necrotic skin disease. Until today, only the combination of rifampin/streptomycin is used to treat buruli ulcer. However, this therapy is ineffective and expensive. Here, we report new findings that suggest pharmaceutical formulations such as rifapentine, in combination with clarithromycin or moxifloxacin that have shown promising results in mice footpad trials. Moreover, alternative treatment options such as heat therapy, nitric oxide cremes and French clay show bactericidal effects. The genotyping of M. ulcerans also promises new ways of finding drug targets and vaccines. Trachoma, induced by the bacterium Chlamydia trachomatis, is the primary infectious cause of blindness worldwide. Recurrent infections lead to chronic inflammation of the upper tarsal conjunctiva. As a consequence, scarring and distortion of the eye lids occur, eventually resulting in blindness. First-line medications for trachoma treatment are bacteriostatic agents such as topically applied tetracylines and systematically administered azithromycin. Surgery, environmental improvements and personal hygiene are further crucial factors in controlling trachoma. Moreover, efforts are being undertaken towards the development of vaccine systems, with the major outer membrane protein and the polymorphic membrane protein acting as attractive candidates.

Pattern of Corneal Blindness in Goro District; Gurage Zone; Southern Ethiopia

There are about 37 million blind people in the world. In Ethiopia there are 1.15 million blind people; corneal blindness accounted for 19of cases. The objective is to identify determinants and pattern of corneal blindness in Goro district; Gurage Zone in Southern Ethiopia. A cross sectional descriptive study and multistage sampling technique were used to identify the study units and subjects. The prevalence of blindness in the study area was 1.5and out of which corneal blindness accounted for 20.8of the blindness. Trachomal had caused 80of the corneal blindness. Determinants like application of herbal medicine; recurrent painful red eye or ocular trauma was not reported to cause bilateral corneal blindness. The prevalence of monocular blindness was 1.89. Corneal blindness accounted for 36.7of the cases. Trauma and trachoma were found in 31.6and 15.8of unilateral corneal blindness respectively. Trachoma is the leading cause of bilateral corneal blindness. Non trachomatous corneal opacity is the major cause of unilateral corneal blindness. Health education and training mid level health workers on the management of treatable and preventable cause of corneal blindness is highly recommended

Dracunculiasis, onchocerciasis, schistosomiasis, and trachoma.

The four diseases discussed in this chapter (dracunculiasis, onchocerciasis, schistosomiasis, and trachoma) are among the officially designated "Neglected Tropical Diseases," and each is also both the result of and a contributor to the poverty of many rural populations. To various degrees, they all have adverse effects on health, agricultural productivity, and education. The Carter Center decided to work on these health problems because of their adverse effect on the lives of poor people and the opportunity to help implement effective interventions. As a result of the global campaign spearheaded by the Carter Center since 1986, the extent of dracunculiasis has been reduced from 20 to five endemic countries and the number of cases reduced by more than 99%. We have helped administer nearly 20% of the 530 million Mectizan (ivermectin) doses for onchocerciasis, which is now being controlled throughout most of Africa, and is progressing toward elimination in the Americas. Since 1999, two Nigerian states have been using village-based health workers originally recruited to work on onchocerciasis to also deliver mass treatment and health education for schistosomiasis and lymphatic filariasis. They now also distribute vitamin A supplements and bed nets to prevent malaria and lymphatic filariasis. Ethiopia aims to eliminate blinding trachoma in the Amhara Region of that highest-endemicity country by 2012, already constructing more than 300,000 latrines and other complementary interventions. Because of the synergy between these diseases and poverty, controlling or eliminating the disease also reduces poverty and increases self-reliance.