Safety of integrated preventive chemotherapy for neglected tropical diseases.

BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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%). CONCLUSIONS: 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.

An observational assessment of the safety of mass drug administration for trachoma in Ethiopian children.

BACKGROUND: The International Trachoma Initiative (ITI) provides azithromycin for mass drug administration (MDA) to eliminate trachoma as a public health problem. Azithromycin is given as tablets for adults and powder for oral suspension (POS) is recommended for children aged <7 y, children <120 cm in height (regardless of age) or anyone who reports difficulty in swallowing tablets. An observational assessment of MDA for trachoma was conducted to determine the frequency with which children aged 6 mo through 14 y received the recommended dose and form of azithromycin according to current dosing guidelines and to assess risk factors for choking and adverse swallowing events (ASEs). METHODS: MDA was observed in three regions of Ethiopia and data were collected on azithromycin administration and ASEs. RESULTS: A total of 6477 azithromycin administrations were observed; 97.9% of children received the exact recommended dose. Of children aged 6 mo to <7 y or <120 cm in height, 99.6% received POS. One child experienced choking and 132 (2%) experienced ≥1 ASEs. Factors significantly associated with ASEs included age 6-11 mo or 1-6 y, non-calm demeanor and requiring coaxing prior to drug administration. CONCLUSIONS: There is a high level of adherence to the revised azithromycin dosing guidelines and low incidence of choking and ASEs.

Shifting patterns of Aedes aegypti fine scale spatial clustering in Iquitos, Peru.

BACKGROUND: Empiric evidence shows that Aedes aegypti abundance is spatially heterogeneous and that some areas and larval habitats produce more mosquitoes than others. There is a knowledge gap, however, with regards to the temporal persistence of such Ae. aegypti abundance hotspots. In this study, we used a longitudinal entomologic dataset from the city of Iquitos, Peru, to (1) quantify the spatial clustering patterns of adult Ae. aegypti and pupae counts per house, (2) determine overlap between clusters, (3) quantify the temporal stability of clusters over nine entomologic surveys spaced four months apart, and (4) quantify the extent of clustering at the household and neighborhood levels. METHODOLOGIES/PRINCIPAL FINDINGS: Data from 13,662 household entomological visits performed in two Iquitos neighborhoods differing in Ae. aegypti abundance and dengue virus transmission was analyzed using global and local spatial statistics. The location and extent of Ae. aegypti pupae and adult hotspots (i.e., small groups of houses with significantly [p<0.05] high mosquito abundance) were calculated for each of the 9 entomologic surveys. The extent of clustering was used to quantify the probability of finding spatially correlated populations. Our analyses indicate that Ae. aegypti distribution was highly focal (most clusters do not extend beyond 30 meters) and that hotspots of high vector abundance were common on every survey date, but they were temporally unstable over the period of study. CONCLUSIONS/SIGNIFICANCE: Our findings have implications for understanding Ae. aegypti distribution and for the design of surveillance and control activities relying on household-level data. In settings like Iquitos, where there is a relatively low percentage of Ae. aegypti in permanent water-holding containers, identifying and targeting key premises will be significantly challenged by shifting hotspots of Ae. aegypti infestation. Focusing efforts in large geographic areas with historically high levels of transmission may be more effective than targeting Ae. aegypti hotspots.