zithromax and Neglected-Diseases

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.. 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.. 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.. 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.

Topics: Albendazole; Azithromycin; Drug Therapy, Combination; Elephantiasis, Filarial; Feasibility Studies; Humans; Ivermectin; Mass Drug Administration; Neglected Diseases

Preventive chemotherapy (PC) is a central strategy for control and elimination of neglected tropical diseases (NTDs). Increased emphasis has been given to "integration" of NTD programs within health systems and coadministration of NTD drugs offers significant programmatic benefits. Guidance from the World Health Organization (WHO) reflects current evidence for safe drug coadministration and highlights measures to prevent choking of young children during PC.. To understand how coadministration of NTD drugs might affect PC safety, we reviewed literature on choking risk in young children and safety of coadministered NTD drugs. To understand current practices of drug coadministration, we surveyed 15 NTD program managers and implementing partners.. In high-income countries, choking on medication is an infrequent cause of death in young children. In low-resource settings, data are limited, but age-appropriate drug formulations are less available. During PC, fatal choking, although infrequent, occurs primarily in young children; forcing them to swallow tablets appears to be the major risk factor. The WHO currently recommends 6 drugs and 5 possible drug combinations for use in PC. Of 105 nations endemic for the 5 PC-NTDs, 72 (68.6%) are co-endemic for 2 or more diseases and could benefit from drug coadministration during PC. All 15 survey respondents reported coadministering medications during PC. Reported responses to a child refusing to take medicine included: not forcing the child to do so (60.0%), encouraging the child (46.7%), bringing the child back later (26.7%), offering powder for oral suspension (POS) for azithromycin (13.3%), and having parents or community members intervene to calm the child (6.7%).. Coadministration of NTD drugs during PC appears to be increasingly common. Safety of coadministered PC drugs requires attention to choking prevention, use of approved drug combinations, and increased access to age-appropriate drug formulations.

Topics: Azithromycin; Chemoprevention; Child; Child, Preschool; Family; Humans; Neglected Diseases; Powders

Scrub typhus, caused by Orientia tsutsugamushi, is a widely neglected disease which is gaining global momentum because of its resurgence patterns. The disease is now being reported in newer regions as well as areas previously endemic areas. In this review, we aim to comprehensively review the data available to assist physicians in making an accurate diagnosis and appropriate management of the disease.. Several diagnostic tests have been developed for confirming scrub typhus. However, there is lack of clarity on which tests are most appropriate in a given clinical scenario. A recent study has demonstrated that in early disease (<7 days) when serological tests remain negative, the quantitative polymerase chain reaction is the most sensitive test. Among the serological tests, both IgM enzyme-linked immunosorbent assay as well as rapid diagnostic tests revealed excellent sensitivities and specificities.. With the reemergence of scrub typhus, a high degree of clinical suspicion is required to appropriately diagnose this disease which presents as an acute febrile illness. It can progress to develop various complications leading to multi-organ dysfunction syndrome. Mild illness responds well to antibiotic treatment with doxycycline and azithromycin. Further studies are required to determine the most optimal therapy in severe scrub typhus infections and superiority of one drug over the other.

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Global Health; Humans; Male; Neglected Diseases; Orientia tsutsugamushi; Polymerase Chain Reaction; Scrub Typhus; Sensitivity and Specificity; Serologic Tests; Skin; Travel

Yaws, a chronic and debilitating infectious disease caused by Treponema pallidum subsp. pertenue, and closely related to syphilis, although transmitted by skin-to-skin contact, remains an important public health challenge, causing a significant burden of morbidity in children in certain areas of the Pacific and Africa. Recent advances in its diagnosis and treatment have led to an enthusiastic upsurge of activities related to its control, and exciting perspectives of global eradication. Although possibly considered among the most neglected of all neglected diseases during decades, there seems to be now agreement that massive drug administration of the antibiotic azithromycin, coupled with adequate surveillance of foci of transmission could result in its eradication. In this review, we summarize current knowledge regarding the therapeutics of yaws and its diagnosis.

Topics: Africa; Anti-Bacterial Agents; Azithromycin; Child; Disease Eradication; Drug Administration Schedule; Forecasting; Humans; Neglected Diseases; Papua New Guinea; Treatment Outcome; Treponema pallidum; Yaws

Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.. A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.. Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)-confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR-positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.. In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.. ISRCTN47812566.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Doxycycline; Female; Humans; Laos; Male; Neglected Diseases; Prospective Studies; Typhus, Endemic Flea-Borne; Young Adult

In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed.. The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7-14 days apart using weight-based bands, or 5% permethrin cream 7-14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505).. During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5-99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4-84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7-37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6-53·1).. Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies.. International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust.

Topics: Adolescent; Adult; Anti-Infective Agents; Azithromycin; Child; Community Health Services; Female; Humans; Impetigo; Ivermectin; Male; Mass Drug Administration; Melanesia; Neglected Diseases; Prevalence; Program Evaluation; Scabies; Treatment Outcome; Young Adult

Mass drug administration has made a major contribution to the public health control of several important neglected tropical diseases. For settings with more than one endemic disease, combined mass drug administration has potential practical advantages compared with separate programmes but needs confirmation of feasibility and safety. We undertook a study of mass drug administration in the Solomon Islands for trachoma and scabies control using ivermectin and azithromycin, key drugs in the control of neglected tropical diseases worldwide.. The entire population of Choiseul province, Solomon Islands, was eligible to participate. An azithromycin-based mass drug administration regimen was offered in line with standard recommendations for trachoma elimination (oral azithromycin or topical tetracycline). An ivermectin-based mass drug administration regimen was offered at the same time (oral ivermectin or topical permethrin), with a further dose 7-14 days later, using a modified version of a regimen demonstrated to be effective for scabies control. All participants underwent safety assessments 7-14 days later. Participants in ten randomly selected sentinel villages underwent a more detailed safety assessment. Routine health system reports of hospital or clinic admissions and deaths were also obtained to compare health outcomes in the 12 month period before and after the mass drug administration.. The study enrolled 26 188 participants, 99·3% of the estimated resident population as determined at the 2009 census. Of those enrolled, 25 717 (98·2%) received the trachoma regimen and 25 819 (98·6%) received the first dose of the scabies regimen between Sept 1, and Oct 2, 2015. A second dose of the scabies regimen was received by 21 931 (83·7%) of participants. Adverse events, all mild and transient, were recorded in 571 (2·6%) of the entire study population and 58 (4·1%) of participants in the ten sentinel villages. In the 12 months before and after the mass drug administration the numbers of hospital admissions (1530 vs 1602) and deaths (73 vs 83) were similar. In the month after the mass drug administration, 84 individuals were admitted to hospital and two died, compared with a monthly median of 116 admissions (IQR 106-159) and six deaths (IQR 4-7) in the 12 months before and after the mass drug administration.. In the largest trial so far involving coadministration of regimens based on ivermectin and azithromycin, the combination was safe and feasible in a population of more than 26 000 people. Coadministration of mass drug administration based on these two drugs opens up new potential for the control of neglected tropical diseases.. International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, Wellcome Trust.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Therapy, Combination; Endemic Diseases; Feasibility Studies; Female; Humans; Infant; Infant, Newborn; Ivermectin; Male; Mass Drug Administration; Melanesia; Neglected Diseases; Scabies; Tetracycline; Trachoma; Young Adult

Immigrants and travelers may be sources of re-emergent infection in trachoma-endemic communities close to trachoma elimination. The primary objective of the A Surveillance and Azithromycin Treatment for Newcomers and Travelers Evaluation (ASANTE) trial was to determine whether a newcomer and traveler surveillance and treatment program in addition to annual mass drug administration (MDA) would reduce Chlamydia trachomatis infection when compared to MDA alone.. ASANTE was a randomized controlled trial in 52 communities in Kongwa, Tanzania. In 26 intervention communities, monitors treated everyone in new households, in-coming children and guardians in existing households, and all persons in households who had traveled between annual MDA events. A total of 26 usual practice communities received MDA only. Surveys of 100 1-9-year-olds from each community were conducted at baseline and every 6 months up to 2 years to assess clinical trachoma and C. trachomatis infection. Data on demographics and environmental factors were also collected.. Mean prevalences of trachomatous inflammation - follicular (TF) and C. trachomatis were equivalent between the two arms (5.2% and 3.7% in intervention, and 4.9% and 3.6% in usual practice communities, respectively). Of 318 children with TF, 36.5% tested positive for C. trachomatis. TF prevalence was higher among households without a bicycle (p = 0.03) and lower with increasing child's age (p < 0.001). Infection prevalence was higher among households >30 minutes from water (p = 0.015). TF and infection prevalence decreased with increasing years of education (p = 0.004 and p = 0.002, respectively).. The ASANTE trial will inform guidance on the surveillance and treatment of persons traveling or newly arriving to communities hypo-endemic for trachoma.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Emigrants and Immigrants; Female; Humans; Infant; Male; Neglected Diseases; Population Surveillance; Prevalence; Risk Factors; Tanzania; Trachoma

Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas.. 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone.. These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended.. ClinicalTrials.gov; NCT01586169.

Topics: Adolescent; Adult; Aged; Albendazole; Anthelmintics; Anti-Bacterial Agents; Azithromycin; Chemoprevention; Child; Child, Preschool; Coinfection; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Elephantiasis, Filarial; Female; Humans; Ivermectin; Male; Mali; Middle Aged; Neglected Diseases; Trachoma; Young Adult

Yaws is targeted for eradication by 2030, using a strategy based on mass drug administration (MDA) with azithromycin. New diagnostics are needed to aid eradication. Serology is currently the mainstay for yaws diagnosis; however, inaccuracies associated with current serological tests makes it difficult to fully assess the need for and impact of eradication campaigns using these tools. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases(NTDs), a working group was assembled and tasked with agreeing on priority use cases for developing target product profiles (TPPs) for new diagnostics tools.. The working group convened three times and established two use cases: identifying a single case of yaws and detecting azithromycin resistance. One subgroup assessed the current diagnostic landscape for yaws and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. To identify a single case of yaws, the test should be able to detect an analyte which confirms an active infection with at least 95% sensitivity and 99.9% specificity. The high specificity was deemed important to avoid a high false positive rate which could result in unnecessary continuation or initiation of MDA campaigns. If used in settings where the number of suspected cases is low, further testing could be considered to compensate for imperfect sensitivity and to improve specificity. The test to detect azithromycin resistance should be able to detect known genetic resistance mutations with a minimum sensitivity and specificity of 95%, with the caveat that all patients with suspected treatment failure should be treated as having resistant yaws and offered alternative treatment.. The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Mass Drug Administration; Neglected Diseases; Treponema pallidum; Yaws

Infants ages < 6 months do not receive azithromycin as part of trachoma control and thus may serve as an infection reservoir in persistently endemic districts. The aim of this study was to determine the population-based Chlamydia trachomatis infection prevalence and infectious load among infants ages 1-12 months in persistently trachoma endemic districts in Amhara, Ethiopia. Across six districts, 475 infants were enumerated, and of these 464 (97.7%) were swabbed for infection testing. The C. trachomatis infection prevalence in the study area among infants was 0.2% (95% CI: 0.0-1.5). Among children ages 0-5 years positive for C. trachomatis, the median load was 31 elementary bodies (EB) (Inter quartile range: 7-244 EB), and the infection-positive infant had a load of 7,755 EB. While it is worth reconsidering azithromycin treatment recommendations for the potential mortality benefits, these results do not support lowering the treatment age for trachoma control.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chlamydia trachomatis; Ethiopia; Eye; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Neglected Diseases; Prevalence; Trachoma

Progress towards elimination of trachoma as a public health problem has been substantial, but the coronavirus disease 2019 (COVID-19) pandemic has disrupted community-based control efforts.. We use a susceptible-infected model to estimate the impact of delayed distribution of azithromycin treatment on the prevalence of active trachoma.. We identify three distinct scenarios for geographic districts depending on whether the basic reproduction number and the treatment-associated reproduction number are above or below a value of 1. We find that when the basic reproduction number is <1, no significant delays in disease control will be caused. However, when the basic reproduction number is >1, significant delays can occur. In most districts, 1 y of COVID-related delay can be mitigated by a single extra round of mass drug administration. However, supercritical districts require a new paradigm of infection control because the current strategies will not eliminate disease.. If the pandemic can motivate judicious, community-specific implementation of control strategies, global elimination of trachoma as a public health problem could be accelerated.

Topics: Anti-Bacterial Agents; Azithromycin; Communicable Disease Control; COVID-19; Humans; Mass Drug Administration; Neglected Diseases; Pandemics; Prevalence; Public Health; SARS-CoV-2; Trachoma

Topics: Anti-Bacterial Agents; Antinematodal Agents; Azithromycin; Chemoprevention; Child; Child Mortality; Humans; Mass Drug Administration; Neglected Diseases; Nematode Infections; Trachoma; Tropical Medicine

Topics: Azithromycin; Humans; Ivermectin; Mass Drug Administration; Neglected Diseases; Tropical Medicine

Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R

Topics: Anti-Bacterial Agents; Azithromycin; Computer Simulation; Disease Eradication; Female; Humans; Male; Markov Chains; Models, Statistical; Neglected Diseases; Recurrence; Treponema pallidum; Tropical Climate; Yaws