RESUMEN
BACKGROUND: Trachoma causes blindness due to repeated conjunctival infection by Chlamydia trachomatis (Ct). Transmission intensity is estimated, for programmatic decision-making, by prevalence of the clinical sign trachomatous inflammation-follicular (TF) in children aged 1-9 years. Research into complementary indicators to field-graded TF includes work on conjunctival photography, tests for ocular Ct infection, and serology. The perceived acceptability and feasibility of these indicators among a variety of stakeholders is unknown. METHODOLOGY: Focus group discussions (FGDs) with community members and in-depth interviews (IDIs) with public health practitioners in Tanzania were conducted. FGDs explored themes including participants' experience with, and thoughts about, different diagnostic approaches. The framework method for content analysis was used. IDIs yielded lists of perceived strengths of, and barriers to, implementation for programmatic use of each indicator. These were used to form an online quantitative survey on complementary indicators distributed to global stakeholders via meetings, mailing lists, and social media posts. RESULTS: Sixteen FGDs and 11 IDIs were conducted in October-November 2022. In general, all proposed sample methods were deemed acceptable by community members. Common themes included not wanting undue discomfort and a preference for tests perceived as accurate. Health workers noted the importance of community education for some sample types. The online survey was conducted in April-May 2023 with 98 starting the questionnaire and 81 completing it. Regarding barriers to implementing diagnostics, the highest agreement items related to feasibility, rather than acceptability. No evidence of significant differences was found in responses pertaining to community acceptability based on participant characteristics. CONCLUSIONS: All of the indicators included were generally deemed acceptable by all stakeholders in Tanzania, although community education around the benefits and risks of different sample types, as well as addressing issues around feasibility, will be key to successful, sustainable integration of these indicators into trachoma programs.
Asunto(s)
Fotograbar , Tracoma , Tracoma/diagnóstico , Humanos , Tanzanía/epidemiología , Femenino , Masculino , Adulto , Niño , Grupos Focales , Preescolar , Estudios de Factibilidad , Pruebas Serológicas/métodos , Chlamydia trachomatis/aislamiento & purificación , Lactante , Persona de Mediana Edad , Adulto Joven , AdolescenteRESUMEN
Trachoma is targeted for elimination as a public health problem worldwide by 2030. In Nigeria, elimination activities are implemented at the local government area (LGA) level. They started in 2002 by conducting baseline population-based prevalence surveys (PBPSs), which continued in a systematic manner with engagement from the Global Trachoma Mapping Project in 2013, and subsequently Tropical Data. The results led to the development of Nigeria's first trachoma action plan and its subsequent revision with additional information. Following 449 baseline PBPSs, 122 LGAs had an active trachoma prevalence above the elimination threshold, requiring interventions, while 231 LGAs required community-based interventions for trichiasis management. By 2021, >34 million antibiotic treatments had been provided in 104 LGAs, with 89 LGAs eliminating active trachoma. Nationally, water and sanitation coverages increased by 3% and 18%, respectively, in 7 y. Systematic trichiasis case finding and management were carried out in 231 LGAs, resulting in the management of 102 527 people. Fifty-four LGAs decreased trichiasis prevalence unknown to the health system to <0.2% in persons ≥15 y of age. Where this elimination prevalence threshold was reached, trichiasis services were transitioned to routine eye/healthcare systems. Such progress relied on strong leadership and coordination from the national trachoma program and tremendous support provided by partners. Attaining elimination of trachoma as a public health problem in Nigeria by 2030 is feasible if funding support is sustained.
RESUMEN
PURPOSE: The prevalence of trachomatous inflammation-follicular (TF) in Papua New Guinea (PNG) suggests antibiotic mass drug administration (MDA) is needed to eliminate trachoma as a public health problem but the burden of trichiasis is low. As a result, WHO issued bespoke recommendations for the region. If ≥ 20% of 10-14-year-olds have both any conjunctival scarring (C1 or C2 or C3) and corneal pannus and/or Herbert's pits, MDA should be continued. Equally, if ≥ 5% of that group have both moderate/severe conjunctival scarring (C2 or C3) and corneal pannus and/or Herbert's pits, MDA should be continued. METHODS: We identified 14 villages where > 20% of 1-9-year-olds had TF during baseline mapping undertaken 4 years and 1 month previously. Every child aged 10-14 years in those villages was eligible to be examined for clinical signs of corneal pannus, Herbert's pits and conjunctival scarring. A grading system that built on existing WHO grading systems was used. RESULTS: Of 1,293 resident children, 1,181 (91%) were examined. Of 1,178 with complete examination data, only one (0.08%) individual had concurrent scarring and limbal signs. CONCLUSIONS: The WHO-predefined criteria for continuation of MDA were not met. Ongoing behavioural and environmental improvement aspects of the SAFE strategy may contribute to integrated NTD control. Surveillance methods should be strengthened to enable PNG health authorities to identify future changes in disease prevalence.
RESUMEN
BACKGROUND: Photography could be used to train individuals to diagnose trachomatous inflammation-follicular (TF) as trachoma prevalence decreases and to ensure accurate field TF grading in trachoma prevalence surveys. We compared photograph and field TF grading and determined the acceptability and feasibility of eyelid photography to community members and trachoma survey trainers. METHODS: A total of 100 children ages 1-9 y were examined for TF in two Maasai villages in Tanzania. Two images of the right everted superior tarsal conjunctiva of each child were taken with a smartphone and a digital single-lens reflex (DSLR) camera. Two graders independently graded all photos. Focus group discussions (FGDs) were conducted with community members and Tropical Data trainers. RESULTS: Of 391 photos, one-fifth were discarded as ungradable. Compared with field grading, photo grading consistently underdiagnosed TF. Compared with field grading, DSLR photo grading resulted in a higher prevalence and sensitivity than smartphone photo grading. FGDs indicated that communities and trainers found photography acceptable and preferred smartphones to DSLR in terms of practicalities, but image quality was of paramount importance for trainers. CONCLUSIONS: Photography is acceptable and feasible, but further work is needed to ensure high-quality images that enable accurate and consistent grading before being routinely implemented in trachoma surveys.
Asunto(s)
Estudios de Factibilidad , Fotograbar , Tracoma , Humanos , Tracoma/diagnóstico , Tracoma/epidemiología , Tanzanía/epidemiología , Fotograbar/métodos , Preescolar , Niño , Lactante , Femenino , Masculino , Grupos Focales , Prevalencia , Teléfono InteligenteRESUMEN
Among ocular infections, trachoma is the main cause of blindness. Repeated conjunctival Chlamydia trachomatis infections lead to trichiasis, corneal opacification, and visual impairment. Surgery is often needed to relieve discomfort and preserve vision; however, a high postoperative trachomatous trichiasis (PTT) rate has been observed in various settings. We wanted to know why, whether PTT rates could be reduced, and how to manage the PTT that occurs. We performed a search of the literature. Of 217 papers screened, 59 studies were identified for inclusion as potentially relevant, the majority having been excluded for not directly concerning PTT in humans. Preventing PTT is a major challenge. Only one published trial, the STAR trial in Ethiopia, has reported a cumulative PTT rate <10% one year after surgery. The literature on the management of PTT is sparse. Though no PTT management guidelines are available, high-quality surgery with a low rate of unfavorable outcomes for PTT patients is likely to require enhanced training of a smaller group of highly-skilled surgeons. Based on the surgical complexity and the authors' own experience, the pathway for patients suffering from PTT should be studied further for improvement.
Asunto(s)
Tracoma , Triquiasis , Baja Visión , Humanos , Tracoma/complicaciones , Tracoma/prevención & control , Triquiasis/cirugía , Triquiasis/etiología , Conjuntiva , CegueraRESUMEN
BACKGROUND: Following interventions to eliminate trachoma in Somali region, Ethiopia, we aimed to re-estimate the prevalence of trachomatous trichiasis (TT) and trachomatous inflammation-follicular (TF) at woreda level and identify the factors associated with the disease. METHODS: We implemented cross-sectional community-based surveys in 50 trachoma-endemic woredas, using a standardized survey. Households were the secondary sampling unit. Surveys were undertaken through a combination of interviews of household heads and direct inspection of water, sanitation and hygiene (WASH) access, plus clinical evaluation of eligible household members for TT and TF. RESULTS: Overall, 41 (82%) of the 50 woredas had met the WHO-recommended active trachoma elimination threshold (prevalence of TF <5% in 1-9-y-olds) and 42 (84%) had met the TT threshold (prevalence of TT unknown to the health system <0.2% in ≥15-y-olds). Only 18% of households had access to an improved drinking water source within a 30-min trip and only 25% had an improved latrine. CONCLUSIONS: Additional rounds of antibiotic mass drug administration, plus interventions to enhance facial cleanliness and improve the environment, are required in nine woredas. TT surgical campaigns are needed in eight woredas. Greater access to WASH is required across all the woredas that were surveyed.
Asunto(s)
Tracoma , Triquiasis , Humanos , Lactante , Tracoma/epidemiología , Tracoma/prevención & control , Prevalencia , Etiopía/epidemiología , Estudios Transversales , Somalia/epidemiología , Agua , Triquiasis/epidemiología , Encuestas EpidemiológicasRESUMEN
PURPOSE: Trachoma is an infectious eye disease caused by Chlamydia trachomatis. Infection causes conjunctival inflammation, which can be manifested by the sign known as trachomatous inflammation-follicular (TF). Repeated inflammation leads to eyelid scarring, which in susceptible individuals can cause in-turning of the eyelashes, referred to as trachomatous trichiasis (TT). This article describes 23 population-based surveys conducted in northern and central Benin to determine TF and/or TT prevalence for trachoma elimination purposes. METHODS: A total of 18 surveys estimated the prevalence of both TF and TT: two baseline surveys, eight impact surveys after implementation of interventions against trachoma, and eight surveillance surveys. Five other evaluation units (EUs) were surveyed for TT only. To estimate the TF prevalence, a target sample size of 1701 (baseline) and 1164 1-9-year-olds (impact and surveillance) was required, whereas 2818 ≥ 15-year-olds were required to estimate the less prevalent TT. In each EU, individuals were selected by two-stage cluster sampling and examined by certified graders for TF and/or TT. RESULTS: A total of 68,613 people were examined. TF prevalence estimates were under the 5% elimination threshold in all surveys. TT prevalence estimates were above the 0.2% elimination threshold in all five TT-only surveys and in four impact surveys, ranging from 0.2-0.57. CONCLUSION: TF prevalence in Benin is low, but TT was above 0.2% in nine districts. Increased case-finding and continuing efforts to improve surgery accessibility will be needed to reduce the burden of TT in Benin.
RESUMEN
BACKGROUND: Following baseline surveys in 2013 and 2014, trachoma elimination interventions, including three rounds of azithromycin mass drug administration (MDA), were implemented in 13 woredas (administrative districts) of Gambella Regional State, Ethiopia. We conducted impact surveys to determine if elimination thresholds have been met or if additional interventions are required. METHODS: Cross-sectional population-based surveys were conducted in 13 woredas of Gambella Regional State, combined into five evaluation units (EUs), 6â12 months after their last MDA round. A two-stage systematic (first stage) and random (second stage) sampling technique was used. WHO-recommended protocols were implemented with the support of Tropical Data. Household water, sanitation and hygiene (WASH) access was assessed. RESULTS: The age-adjusted prevalence of trachomatous inflammation - follicular (TF) in 1-9-year-olds in the five EUs ranged from 0.3-19.2%, representing a general decline in TF prevalence compared to baseline estimates. The age- and gender-adjusted prevalence of trachomatous trichiasis (TT) unknown to the health system in those aged ≥ 15 years ranged from 0.47-3.08%. Of households surveyed, 44% had access to an improved drinking water source within a 30-minute return journey of the house, but only 3% had access to an improved latrine. CONCLUSION: In two EUs, no further MDA should be delivered, and a surveillance survey should be conducted after two years without MDA. In one EU, one further round of MDA should be conducted followed by another impact survey. In two EUs, three further MDA rounds are required. Surgery, facial cleanliness and environmental improvement interventions are needed throughout the region.
RESUMEN
Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required multiple distinct campaigns, each targeting one or more NTDs, representing a strain on both the recipient communities and the local health workforce implementing the distribution. We explored perceptions and attitudes surrounding combined MDA among these two groups of stakeholders. Our qualitative study was nested within a cluster randomized non-inferiority safety trial of combined ivermectin, albendazole and azithromycin MDA. Using semi-structured question guides, we conducted 16 key informant interviews with selected individuals involved in implementing MDA within the participating district. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key community groups. Individuals were selected from both the trial arm (integrated MDA) and the control arm (standard MDA) to provide a means of comparison and discussion. All interviews and focus group discussions were led by fluent Afaan oromo speakers. Interviewers transcribed and later translated all discussions into English. The study team synthesized and analyzed the results via a coding framework and software. Most respondents appreciated the time and effort saved via the co-administered MDA strategy but there were some misgivings amongst community beneficiaries surrounding pill burden. Both the implementing health work force members and beneficiaries reported refusals stemming from lack of understanding around the need for the new drug regimen as well as some mistrust of government officials among the youth. The house-to-house distribution method, adopted as a COVID-19 prevention strategy, was by far preferred by all beneficiaries over central-point MDA, and may have led to greater acceptability of co-administration. Our data demonstrate that a co-administration strategy for NTDs is acceptable to both communities and health staff.
Asunto(s)
COVID-19 , Ivermectina , Adolescente , Humanos , Administración Masiva de Medicamentos , Albendazol , Azitromicina/uso terapéutico , Etiopía , Fuerza Laboral en Salud , Tratamiento Farmacológico de COVID-19RESUMEN
Several countries have come close to eliminating leprosy, but leprosy cases continue to be detected at low levels. Due to the long, highly variable delay from infection to detection, the relationship between observed cases and transmission is uncertain. The World Health Organization's new technical guidance provides a path for countries to reach elimination. We use a simple probabilistic model to simulate the stochastic dynamics of detected cases as transmission declines, and evaluate progress through the new public health milestones. In simulations where transmission is halted, 5 years of zero incidence in autochthonous children, combined with 3 years of zero incidence in all ages is a flawed indicator that transmission has halted (54% correctly classified). A further 10 years of only occasional sporadic cases is associated with a high probability of having interrupted transmission (99%). If, however, transmission continues at extremely low levels, it is possible that cases could be misidentified as historic cases from the tail of the incubation period distribution, although misleadingly achieving all three milestones is unlikely (less than 1% probability across a 15-year period of ongoing low-level transmission). These results demonstrate the feasibility and challenges of a phased progression of milestones towards interruption of transmission, allowing assessment of programme status. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
Asunto(s)
Lepra , Salud Pública , Niño , Humanos , Lepra/epidemiología , Lepra/prevención & control , Londres , Modelos Estadísticos , Enfermedades Desatendidas/epidemiologíaRESUMEN
[This corrects the article DOI: 10.1016/j.eclinm.2023.101984.].
RESUMEN
BACKGROUND: Trachoma is the commonest infectious cause of blindness worldwide. Efforts are being made to eliminate trachoma as a public health problem globally. However, as prevalence decreases, it becomes more challenging to precisely predict prevalence. We demonstrate how model-based geostatistics (MBG) can be used as a reliable, efficient, and widely applicable tool to assess the elimination status of trachoma. METHODS: We analysed trachoma surveillance data from Brazil, Malawi, and Niger. We developed geostatistical Binomial models to predict trachomatous inflammation-follicular (TF) and trachomatous trichiasis (TT) prevalence. We proposed a general framework to incorporate age and gender in the geostatistical models, whilst accounting for residual spatial and non-spatial variation in prevalence through the use of random effects. We also used predictive probabilities generated by the geostatistical models to quantify the likelihood of having achieved the elimination target in each evaluation unit (EU). RESULTS: TF and TT prevalence varied considerably by country, with Brazil showing the lowest prevalence and Niger the highest. Brazil and Malawi are highly likely to have met the elimination criteria for TF in each EU, but, for some EUs, there was high uncertainty in relation to the elimination of TT according to the model alone. In Niger, the predicted prevalence varied significantly across EUs, with the probability of having achieved the elimination target ranging from values close to 0% to 100%, for both TF and TT. CONCLUSIONS: We demonstrated the wide applicability of MBG for trachoma programmes, using data from different epidemiological settings. Unlike the standard trachoma prevalence survey approach, MBG provides a more statistically rigorous way of quantifying uncertainty around the achievement of elimination prevalence targets, through the use of spatial correlation. In addition to the analysis of existing survey data, MBG also provides an approach to identify areas in which more sampling effort is needed to improve EU classification. We advocate MBG as the new standard method for analysing trachoma survey outputs.
Asunto(s)
Tracoma , Triquiasis , Humanos , Lactante , Tracoma/epidemiología , Tracoma/prevención & control , Estudios Transversales , Salud Pública , Encuestas y Cuestionarios , Malaui/epidemiología , Triquiasis/epidemiología , Triquiasis/prevención & control , PrevalenciaRESUMEN
Baseline mapping in the two major population centers of Kiribati showed that trachoma was a public health problem in need of programmatic interventions. After conducting two annual rounds of antibiotic mass drug administration (MDA), Kiribati undertook trachoma impact surveys in 2019, using standardized two-stage cluster surveys in the evaluation units of Kiritimati Island and Tarawa. In Kiritimati, 516 households were visited and in Tarawa, 772 households were visited. Nearly all households had a drinking water source and access to an improved latrine. The prevalence of trachomatous trichiasis remained above the elimination threshold (0.2% in ≥15-year-olds) and was virtually unchanged from baseline. The prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds decreased by approximately 40% from baseline in both evaluation units but remained above the 5% TF prevalence threshold for stopping MDA. TF prevalence at impact survey was 11.5% in Kiritimati and 17.9% in Tarawa. Infection prevalence in 1-9-year-olds by PCR was 0.96% in Kiritimati and 3.3% in Tarawa. Using a multiplex bead assay to measure antibodies to the C. trachomatis antigen Pgp3, seroprevalence in 1-9-year-olds was 30.2% in Kiritimati and 31.4% in Tarawa. The seroconversion rate, in seroconversion events/100 children/year, was 9.0 in Kiritimati and 9.2 in Tarawa. Seroprevalence and seroconversion rates were both assessed by four different assays, with strong agreement between tests. These results show that, despite decreases in indicators associated with infection at impact survey, trachoma remains a public health problem in Kiribati, and provide additional information about changes in serological indicators after MDA.
Asunto(s)
Tracoma , Niño , Humanos , Lactante , Tracoma/tratamiento farmacológico , Tracoma/epidemiología , Azitromicina/uso terapéutico , Administración Masiva de Medicamentos , Estudios Seroepidemiológicos , Chlamydia trachomatis , Antibacterianos/uso terapéutico , Prevalencia , MicronesiaRESUMEN
PURPOSE: Trachoma is an eye disease caused by the bacterium Chlamydia trachomatis (Ct). It can lead to permanent vision loss. Since 2007, Burundi has included trachoma elimination as part of its fight against neglected tropical diseases and blindness. This study presents the results of trachoma baseline, impact and surveillance surveys conducted in Burundi between 2018 and 2021. METHODS: Areas were grouped into evaluation units (EU) with resident populations of between 100,000 and 250,000 people. Baseline surveys were conducted in 15 EUs, impact surveys in 2 EUs and surveillance surveys in 5 EUs; in each survey, 23 clusters of about 30 households were included. Consenting residents of those households were screened for clinical signs of trachoma. Access to water, sanitation and hygiene (WASH) was recorded. RESULTS: A total of 63,800 individuals were examined. The prevalence of TF in 1-9-year-olds was above the elimination threshold of 5% in a single EU at baseline, but fell below the threshold in subsequent impact and surveillance surveys. The prevalence of TT was below the 0.2% elimination threshold in ≥15-year-olds in all EUs surveyed. A high proportion (83%) of households had access to safe drinking water, while only a minority (~8%) had access to improved latrines. CONCLUSION: Burundi has demonstrated the prevalence levels necessary for trachoma elimination status. With continued effort and the maintenance of existing management plans, trachoma elimination in Burundi is within reach.
RESUMEN
INTRODUCTION: Trichiasis is present when in-turned eyelashes touch the eyeball. It may result in permanent vision loss. Trachomatous trichiasis (TT) is caused by multiple rounds of inflammation associated with conjunctival Chlamydia trachomatis infection. Surveys have been designed to estimate the prevalence of TT in evaluation units (EUs) of trachoma-endemic countries in order to help develop appropriate programme-level plans. In this study, TT-only surveys were conducted in five EUs of The Gambia to determine whether further intensive programmatic action was required. METHODS: Two-stage cluster sampling was used to select 27 villages per EU and ~25 households per village. Graders assessed the TT status of individuals aged ≥15 years in each selected household, including the presence or absence of conjunctival scarring in those with TT. RESULTS: From February to March 2019, 11595 people aged ≥15 years were examined. A total of 34 cases of TT were identified. All five EUs had an age- and gender-adjusted prevalence of TT unknown to the health system <0.2%. Three of five EUs had a prevalence of 0.0%. CONCLUSION: Using these and other previously collected data, in 2021, The Gambia was validated as having achieved national elimination of trachoma as a public health problem. Trachoma is still present in the population, but as its prevalence is low, it is unlikely that today's youth will experience the exposure to C. trachomatis required to precipitate TT. The Gambia demonstrates that with political will and consistent application of human and financial resources, trachoma can be eliminated as a public health problem.
RESUMEN
PURPOSE: Trachoma is a public health problem in 42 countries. Inflammation associated with repeated ocular infection with Chlamydia trachomatis can cause the eyelid to scar and turn inwards, resulting in the eyelashes rubbing against the eyeball, known as trachomatous trichiasis (TT). In Guinea, baseline surveys conducted in 2013 reported inflammatory trachoma prevalences below the World Health Organization (WHO) threshold for elimination, but TT prevalences above threshold. Given this epidemiological context and time since baseline survey, TT-only surveys were conducted in selected districts to determine current TT prevalence. The results of this study provide critical data for assessing Guinea's achievement of trachoma elimination targets. METHODS: Four health districts, consisting of six evaluation units (EU), were surveyed. In each EU, field teams visited 29 clusters with a minimum 30 households included in each. Participants aged≥15 years were examined by certified graders trained to identify TT and determine whether management had been offered. RESULTS: A total of 22,476 people were examined, with 48 TT cases across the six EUs identified. Five of six EUs had an age-and-gender adjusted TT-prevalence unknown to the health system less than 0.2%, whereas one EU, Beyla 2, had an adjusted TT prevalence of 0.24%. CONCLUSION: These TT-only surveys, along with findings from other trachoma interventions, suggest that Guinea is close to achieving elimination of trachoma as a public health problem. This study demonstrates the value of undertaking TT-only surveys in settings where baseline surveys indicated active trachoma prevalences below WHO elimination threshold, but TT prevalences above it.
RESUMEN
INTRODUCTION: Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) as separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration. METHODOLOGY: We aimed to compile and summarize existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observational studies conducted in NTD-endemic populations. We searched PubMed, Google Scholar, research and conference abstracts, gray literature, and national policy documents. We limited the publication language to English and used a search period from January 1st, 1995 through October 1st, 2022. Search terms were: azithromycin and ivermectin and albendazole, mass drug administration co-administration trials, integrated mass drug administration, mass drug administration safety, pharmacokinetic dynamics, and azithromycin and ivermectin and albendazole. We excluded papers if they did not include data on co-administration of azithromycin and both albendazole and ivermectin, or azithromycin with either albendazole or ivermectin alone. RESULTS: We identified a total of 58 potentially relevant studies. Of these we identified 7 studies relevant to the research question and which met our inclusion criteria. Three papers analyzed pharmacokinetic and pharmacodynamic interactions. No study found evidence of clinically significant drug-drug interactions likely to impact safety or efficacy. Two papers and a conference presentation reported data on the safety of combinations of at least two of the drugs. A field study in Mali suggested the rates of adverse events were similar with combined or separate administration, but was underpowered. A further field study in Papua New Guinea used all three drugs as part of a four-drug regimen also including diethylcarbamazine; in this setting, co-administration appeared safe but there were issues with the consistency in how adverse events were recorded. CONCLUSION: There are relatively limited data on the safety profile of co-administering ivermectin, albendazole and azithromycin as an integrated regimen for NTDs. Despite the limited amount of data, available evidence suggests that such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. Integrated MDA may be a viable strategy for national NTD programmes.
Asunto(s)
Filariasis Linfática , Ivermectina , Humanos , Ivermectina/efectos adversos , Albendazol/efectos adversos , Azitromicina/efectos adversos , Administración Masiva de Medicamentos , Estudios de Factibilidad , Quimioterapia Combinada , Enfermedades Desatendidas/tratamiento farmacológico , Filariasis Linfática/tratamiento farmacológicoRESUMEN
Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1-9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( >90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.
Asunto(s)
Tracoma , Niño , Humanos , Lactante , Preescolar , Tracoma/diagnóstico , Tracoma/epidemiología , Estudios Seroepidemiológicos , Antígenos Bacterianos , Anticuerpos Antibacterianos , Chlamydia trachomatis , PrevalenciaRESUMEN
Background: Neglected Tropical Disease (NTD) programs require separate and distinct drug regimens for treatment. This has required countries to undertake multiple independent mass drug administration (MDA) programmes, each targeting one or more diseases. The possibility of safely combining different drug regimens together in one MDA may offer several advantages to national programs. We conducted a study to assess the safety of combining ivermectin, albendazole and azithromycin in one integrated MDA. Methods: We conducted an open-label, non-inferiority cluster-randomised trial comparing the frequency of adverse events in communities receiving co-administered ivermectin, albendazole and azithromycin to that in communities given albendazole and ivermectin MDA followed by azithromycin MDA after a two-week interval. The study took place in 58 gares (small administrative units) across two kebeles (sub-districts) in Kofele woreda (district) in the Oromia region of Ethiopia. We randomly assigned 29 gares to the combined treatment arm and 29 gares to the control arm. The study team revisited all individuals within 48 h and actively collected data on the occurrence of adverse events using a dedicated questionnaire and a pre-specified list of adverse events. The study team followed the same process in the control arm for the azithromycin distribution and again after the ivermectin plus albendazole distribution. Following this initial active surveillance, passive surveillance was undertaken for one week after the first visit. The primary outcome was the frequency of adverse events occurring following MDA. The study team determined that the safety of the combined MDA would be non-inferior to that of separate MDAs if the upper limit of the two-sided CI for the difference in rates was equal to or lower than 5%. The trial was registered with ClinicalTrials.gov, NCT03570814. Findings: The study took place from December 2021 to January 2022. The combined MDA arm consisted of 7292 individuals who were eligible to participate, of whom 7068 received all three medications. The separate MDA arm consisted of 6219 eligible individuals of whom 6211 received ivermectin and albendazole and 4611 received azithromycin two weeks later. Overall, adverse events were reported by 197 (1.2%) of individuals. The most commonly reported adverse events included headache, gastrointestinal disturbance and dizziness. There were no serious adverse events in either arm. The cluster-level mean frequency of reported adverse events varied markedly between clusters, ranging from 0.1 to 10.4%. The cluster-level mean frequency of adverse events was 1.4% in the combined MDA arm and 1.2% following ivermectin and albendazole MDA (absolute difference 0.2%, 95% confidence interval [CI] -0.6% to +1.1%). This met the pre-defined 1.5% non-inferiority margin. For the combined MDA comparison to the stand-alone azithromycin MDA the absolute difference was -0.4% (1.4 versus 1.8%, 95% CI -0.8 to +1.5) which also met the pre-specified non-inferiority margin. Interpretation: This study is the largest of its kind to date and demonstrates that the safety of combined MDA of azithromycin, ivermectin and albendazole is non-inferior to the safety of ivermectin-plus-albendazole MDA then azithromycin MDA conducted separately although we may not have been powered to detect very small differences between arms. Co-administration of these three medicines is safe and feasible in this setting and allows national programs to develop new strategies for integrated MDA programs. Funding: Ivermectin (Mectizan) was donated by the Mectizan Donation Program, albendazole was donated by GlaxoSmithKline, and azithromycin (Zithromax®) was donated by Pfizer via the International Trachoma Initiative (ITI). The trial was funded by ITI using operational research funds from the Bill and Melinda Gates Foundation.