Publications by authors named "Nathan Lo"

147 Publications

Enhanced mutation rate, relaxed selection, and the 'domino effect' drive gene loss in Blattabacterium, a cockroach endosymbiont.

Mol Biol Evol 2021 May 26. Epub 2021 May 26.

Okinawa Institute of Science & Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa, 904-0495, Japan.

Intracellular endosymbionts have reduced genomes that progressively lose genes at a timescale of tens of million years. We previously reported that gene loss rate is linked to mutation rate in Blattabacterium, however, the mechanisms causing gene loss are not yet fully understood. Here, we carried out comparative genomic analyses on the complete genome sequences of a representative set of 67 Blattabacterium strains, with sizes ranging between 511kbp and 645kbp. We found that 200 of the 566 analysed protein-coding genes were lost in at least one lineage of Blattabacterium, with the most extreme case being one gene that was lost independently in 24 lineages. We found evidence for three mechanisms influencing gene loss in Blattabacterium. First, gene loss rates were found to increase exponentially with the accumulation of substitutions. Second, genes involved in vitamin and amino acid metabolism experienced relaxed selection in Cryptocercus and Mastotermes, possibly triggered by their vertically-inherited gut symbionts. Third, we found evidences of epistatic interactions among genes leading to a 'domino effect' of gene loss within pathways. Our results highlight the complexity of the process of genome erosion in an endosymbiont.
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http://dx.doi.org/10.1093/molbev/msab159DOI Listing
May 2021

Comparison of infection control strategies to reduce COVID-19 outbreaks in homeless shelters in the United States: a simulation study.

BMC Med 2021 05 7;19(1):116. Epub 2021 May 7.

Department of Medicine, University of California, San Francisco, San Francisco, CA, 94110, USA.

Background: COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks.

Methods: We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing.

Results: The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number (R) estimates of 2.9-6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk (R = 1.5), moderate-risk (R = 2.9), and high-risk (R = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility (R) within the simulated shelter and increasing incidence in the local community.

Conclusions: In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.
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http://dx.doi.org/10.1186/s12916-021-01965-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103431PMC
May 2021

Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation study.

Lancet Infect Dis 2021 07 23;21(7):929-938. Epub 2021 Mar 23.

Department of Medicine, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Background: Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown.

Methods: In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection).

Findings: We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144-12831) infectious days with 649 (505-950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917-8677), a reduction of 36% (29-41) compared with the base case, and identified 569 (88% [76-92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849-4158), a reduction of 70% (64-75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126-9081), a reduction of 32% (26-38) compared with the base case, and identified 560 (86% [83-89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356-495), a reduction of 63% (58-66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714-7679), a reduction of 42% (35-49) compared with the base case.

Interpretation: Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting.

Funding: University of California, San Francisco.
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http://dx.doi.org/10.1016/S1473-3099(21)00134-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984872PMC
July 2021

Evolutionary Rates are Correlated Between Buchnera Endosymbionts and the Mitochondrial Genomes of Their Aphid Hosts.

J Mol Evol 2021 Jun 17;89(4-5):238-248. Epub 2021 Mar 17.

School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.

The evolution of bacterial endosymbiont genomes is strongly influenced by host-driven selection. Factors affecting host genome evolution will potentially affect endosymbiont genomes in similar ways. One potential outcome is correlations in molecular rates between the genomes of the symbiotic partners. Recently, we presented the first evidence of such correlations between the mitochondrial genomes of cockroaches and the genomes of their endosymbiont (Blattabacterium cuenoti). Here we investigate whether similar patterns are found in additional host-symbiont partners. We use partial genome data from multiple strains of the bacterial endosymbionts Buchnera aphidicola and Sulcia muelleri, and the mitochondrial genomes of their sap-feeding insect hosts. Both endosymbionts show phylogenetic congruence with the mitochondria of their hosts, a result that is expected due to their identical mode of inheritance. We compared root-to-tip distances and branch lengths of phylogenetically independent species pairs. Both analyses showed a highly significant correlation of molecular rates between the genomes of Buchnera and the mitochondrial genomes of their hosts. A similar correlation was detected between Sulcia and their hosts, but was not statistically significant. Our results indicate that evolutionary rate correlations between hosts and long-term symbionts may be a widespread phenomenon.
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http://dx.doi.org/10.1007/s00239-021-10001-9DOI Listing
June 2021

Phylogenomic Analysis of Concatenated Ultraconserved Elements Reveals the Recent Evolutionary Radiation of the Fairy Wrasses (Teleostei: Labridae: Cirrhilabrus).

Syst Biol 2021 Feb 23. Epub 2021 Feb 23.

School of Life and Environmental Sciences, University of Sydney, New South Wales 2006, Australia.

The fairy wrasses (genus Cirrhilabrus) are among the most successful of the extant wrasse lineages (Teleostei: Labridae), with their 61 species accounting for nearly 10% of the family. Although species complexes within the genus have been diagnosed on the basis of coloration patterns and synapomorphies, attempts to resolve evolutionary relationships among these groups using molecular and morphological data have largely been unsuccessful. Here we use a phylogenomic approach with a data set comprising 991 ultraconserved elements (UCEs) and mitochondrial COI to uncover the evolutionary history and patterns of temporal and spatial diversification of the fairy wrasses. Our analyses of phylogenetic signal suggest that most gene-tree incongruence is caused by estimation error, leading to poor resolution in a summary-coalescent analysis of the data. In contrast, analyses of concatenated sequences are able to resolve the major relationships of Cirrhilabrus. We determine the placements of species that were previously regarded as incertae sedis and find evidence for the nesting of Conniella, an unusual, monotypic genus, within Cirrhilabrus. Our relaxed-clock dating analysis indicates that the major divergences within the genus occurred around the Miocene-Pliocene boundary, followed by extensive cladogenesis of species complexes in the Pliocene-Pleistocene. Biogeographic reconstruction suggests that the fairy wrasses emerged within the Coral Triangle, with episodic fluctuations of sea levels during glacial cycles coinciding with shallow divergence events but providing few opportunities for more widespread dispersal. Our study demonstrates both the resolving power and limitations of UCEs across shallow timescales where there is substantial estimation error in individual gene trees.
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http://dx.doi.org/10.1093/sysbio/syab012DOI Listing
February 2021

Frequency of Routine Testing for Coronavirus Disease 2019 (COVID-19) in High-risk Healthcare Environments to Reduce Outbreaks.

Clin Infect Dis 2020 Oct 26. Epub 2020 Oct 26.

Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Routine asymptomatic testing strategies for COVID-19 have been proposed to prevent outbreaks in high-risk healthcare environments. We used simulation modeling to evaluate the optimal frequency of viral testing. We found that routine testing substantially reduces risk of outbreaks, but may need to be as frequent as twice weekly.
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http://dx.doi.org/10.1093/cid/ciaa1383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797732PMC
October 2020

Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation analysis.

medRxiv 2020 Dec 11. Epub 2020 Dec 11.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Background: Airline travel has been significantly reduced during the COVID-19 pandemic due to concern for individual risk of SARS-CoV-2 infection and population-level transmission risk from importation. Routine viral testing strategies for COVID-19 may facilitate safe airline travel through reduction of individual and/or population-level risk, although the effectiveness and optimal design of these "test-and-travel" strategies remain unclear.

Methods: We developed a microsimulation of SARS-CoV-2 transmission in a cohort of airline travelers to evaluate the effectiveness of various testing strategies to reduce individual risk of infection and population-level risk of transmission. We evaluated five testing strategies in asymptomatic passengers: i) anterior nasal polymerase chain reaction (PCR) within 3 days of departure; ii) PCR within 3 days of departure and PCR 5 days after arrival; iii) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection); iv) rapid antigen test on the day of travel and PCR 5 days after arrival; and v) PCR within 3 days of arrival alone. The travel period was defined as three days prior to the day of travel and two weeks following the day of travel, and we assumed passengers followed guidance on mask wearing during this period. The primary study outcome was cumulative number of infectious days in the cohort over the travel period (population-level transmission risk); the secondary outcome was the proportion of infectious persons detected on the day of travel (individual-level risk of infection). Sensitivity analyses were conducted.

Findings: Assuming a community SARS-CoV-2 incidence of 50 daily infections, we estimated that in a cohort of 100,000 airline travelers followed over the travel period, there would be a total of 2,796 (95% UI: 2,031, 4,336) infectious days with 229 (95% UI: 170, 336) actively infectious passengers on the day of travel. The pre-travel PCR test (within 3 days prior to departure) reduced the number of infectious days by 35% (95% UI: 27, 42) and identified 88% (95% UI: 76, 94) of the actively infectious travelers on the day of flight; the addition of PCR 5 days after arrival reduced the number of infectious days by 79% (95% UI: 71, 84). The rapid antigen test on the day of travel reduced the number of infectious days by 32% (95% UI: 25, 39) and identified 87% (95% UI: 81, 92) of the actively infectious travelers; the addition of PCR 5 days after arrival reduced the number of infectious days by 70% (95% UI: 65, 75). The post-travel PCR test alone (within 3 days of landing) reduced the number of infectious days by 42% (95% UI: 31, 51). The ratio of true positives to false positives varied with the incidence of infection. The overall study conclusions were robust in sensitivity analysis.

Interpretation: Routine asymptomatic testing for COVID-19 prior to travel can be an effective strategy to reduce individual risk of COVID-19 infection during travel, although post-travel testing with abbreviated quarantine is likely needed to reduce population-level transmission due to importation of infection when traveling from a high to low incidence setting.
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http://dx.doi.org/10.1101/2020.12.08.20246132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743095PMC
December 2020

Termites Are Associated with External Species-Specific Bacterial Communities.

Appl Environ Microbiol 2021 01 4;87(2). Epub 2021 Jan 4.

Faculty of Tropical AgriSciences, Czech University of Life Sciences, Prague, Czech Republic

All termites have established a wide range of associations with symbiotic microbes in their guts. Some termite species are also associated with microbes that grow in their nests, but the prevalence of these associations remains largely unknown. Here, we studied the bacterial communities associated with the termites and galleries of three wood-feeding termite species by using 16S rRNA gene amplicon sequencing. We found that the compositions of bacterial communities among termite bodies, termite galleries, and control wood fragments devoid of termite activities differ in a species-specific manner. Termite galleries were enriched in bacterial operational taxonomic units (OTUs) belonging to and , which were often shared by several termite species. The abundance of several bacterial OTUs, such as , , , and , was reduced in termite galleries. Our results demonstrate that both termite guts and termite galleries harbor unique bacterial communities. As is the case for all ecosystem engineers, termites impact their habitat by their activities, potentially affecting bacterial communities. Here, we studied three wood-feeding termite species and found that they influence the composition of the bacterial communities in their surrounding environment. Termite activities have positive effects on and abundance and negative effects on the abundance of several ubiquitous genera, such as , , , and Our results demonstrate that termite galleries harbor unique bacterial communities.
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http://dx.doi.org/10.1128/AEM.02042-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783351PMC
January 2021

Unmapped RNA Virus Diversity in Termites and their Symbionts.

Viruses 2020 10 9;12(10). Epub 2020 Oct 9.

Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, New South Wales, Australia.

Despite their ecological importance, nothing is known about the diversity and abundance of RNA viruses in termites (Termitoidae). We used a metatranscriptomics approach to determine the RNA virome structure of 50 diverse species of termite that differ in both phylogenetic position and colony composition. From these samples, we identified 67 novel RNA viruses, characterized their genomes, quantified their abundance and inferred their evolutionary history. These viruses were found within or similar to those from the , and . However, all viruses identified were novel and divergent, exhibiting only 20% to 45% amino acid identity to previously identified viruses. Our analysis suggested that 17 of the viruses identified were termite-infecting, with the remainder likely associated with the termite microbiome or diet. Unclassified sobemo-like and bunya-like viruses dominated termite viromes, while most of the phylogenetic diversity was provided by the picobirna- and mitovirus-like viruses. Of note was the identification of a novel flavi-like virus most closely related to those found in marine vertebrates and invertebrates. Notably, the sampling procedure had the strongest association with virome composition, with greater RNA virome diversity in libraries prepared from whole termite bodies than those that only sampled heads.
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http://dx.doi.org/10.3390/v12101145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650761PMC
October 2020

Comparison of World Health Organization and Demographic and Health Surveys data to estimate sub-national deworming coverage in pre-school aged children.

PLoS Negl Trop Dis 2020 08 17;14(8):e0008551. Epub 2020 Aug 17.

Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background: The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation.

Methodology: We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses.

Principal Findings: We compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries.

Conclusions And Significance: Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.
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http://dx.doi.org/10.1371/journal.pntd.0008551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462292PMC
August 2020

Corrigendum to "A global molecular phylogeny and timescale of evolution for Cryptocercus woodroaches" [Mol. Phylogenet. Evol. 98 (2016) 201-209].

Mol Phylogenet Evol 2020 Nov 7;152:106907. Epub 2020 Aug 7.

College of Plant Protection, Southwest University, Beibei, Chongqing 400716, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.ympev.2020.106907DOI Listing
November 2020

Increased Mutation Rate Is Linked to Genome Reduction in Prokaryotes.

Curr Biol 2020 10 6;30(19):3848-3855.e4. Epub 2020 Aug 6.

School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia. Electronic address:

The evolutionary processes that drive variation in genome size across the tree of life remain unresolved. Effective population size (N) is thought to play an important role in shaping genome size [1-3]-a key example being the reduced genomes of insect endosymbionts, which undergo population bottlenecks during transmission [4]. However, the existence of reduced genomes in marine and terrestrial prokaryote species with large N indicate that genome reduction is influenced by multiple processes [3]. One candidate process is enhanced mutation rate, which can increase adaptive capacity but can also promote gene loss. To investigate evolutionary forces associated with prokaryotic genome reduction, we performed molecular evolutionary and phylogenomic analyses of nine lineages from five bacterial and archaeal phyla. We found that gene-loss rate strongly correlated with synonymous substitution rate (a proxy for mutation rate) in seven of the nine lineages. However, gene-loss rate showed weak or no correlation with the ratio of nonsynonymous/synonymous substitution rate (d/d). These results indicate that genome reduction is largely associated with increased mutation rate, while the association between gene loss and changes in N is less well defined. Lineages with relatively high d and d, as well as smaller genomes, lacked multiple DNA repair genes, providing a proximate cause for increased mutation rates. Our findings suggest that similar mechanisms drive genome reduction in both intracellular and free-living prokaryotes, with implications for developing a comprehensive theory of prokaryote genome size evolution.
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http://dx.doi.org/10.1016/j.cub.2020.07.034DOI Listing
October 2020

Angels in disguise: sympatric hybridization in the marine angelfishes is widespread and occurs between deeply divergent lineages.

Proc Biol Sci 2020 08 5;287(1932):20201459. Epub 2020 Aug 5.

School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.

Hybridization events are not uncommon in marine environments where physical barriers are attenuated. Studies of coral reef taxa have suggested that hybridization predominantly occurs between parapatric species distributed along biogeographic suture zones. By contrast, little is known about the extent of sympatric hybridization on coral reefs, despite the large amount of biogeographic overlap shared by many coral reef species. Here, we investigate if the propensity for hybridization along suture zones represents a general phenomenon among coral reef fishes, by focusing on the marine angelfishes (family Pomacanthidae). Although hybridization has been reported for this family, it has not been thoroughly surveyed, with more recent hybridization studies focusing instead on closely related species from a population genetics perspective. We provide a comprehensive survey of hybridization among the Pomacanthidae, characterize the upper limits of genetic divergences between hybridizing species and investigate the occurrence of sympatric hybridization within this group. We report the occurrence of hybridization involving 42 species (48% of the family) from all but one genus of the Pomacanthidae. Our results indicate that the marine angelfishes are among the groups of coral reef fishes with the highest incidences of hybridization, not only between sympatric species, but also between deeply divergent lineages.
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http://dx.doi.org/10.1098/rspb.2020.1459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575528PMC
August 2020

Correction: Phylogeography of the iconic Australian red-tailed black-cockatoo (Calyptorhynchus banksii) and implications for its conservation.

Heredity (Edinb) 2020 Sep;125(3):167

School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41437-020-0343-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426908PMC
September 2020

Projected geographic disparities in healthcare worker absenteeism from COVID-19 school closures and the economic feasibility of child care subsidies: a simulation study.

BMC Med 2020 07 15;18(1):218. Epub 2020 Jul 15.

Center for Primary Care, Harvard Medical School, Boston, MA, USA.

Background: School closures have been enacted as a measure of mitigation during the ongoing coronavirus disease 2019 (COVID-19) pandemic. It has been shown that school closures could cause absenteeism among healthcare workers with dependent children, but there remains a need for spatially granular analyses of the relationship between school closures and healthcare worker absenteeism to inform local community preparedness.

Methods: We provide national- and county-level simulations of school closures and unmet child care needs across the USA. We develop individual simulations using county-level demographic and occupational data, and model school closure effectiveness with age-structured compartmental models. We perform multivariate quasi-Poisson ecological regressions to find associations between unmet child care needs and COVID-19 vulnerability factors.

Results: At the national level, we estimate the projected rate of unmet child care needs for healthcare worker households to range from 7.4 to 8.7%, and the effectiveness of school closures as a 7.6% and 8.4% reduction in fewer hospital and intensive care unit (ICU) beds, respectively, at peak demand when varying across initial reproduction number estimates by state. At the county level, we find substantial variations of projected unmet child care needs and school closure effects, 9.5% (interquartile range (IQR) 8.2-10.9%) of healthcare worker households and 5.2% (IQR 4.1-6.5%) and 6.8% (IQR 4.8-8.8%) reduction in fewer hospital and ICU beds, respectively, at peak demand. We find significant positive associations between estimated levels of unmet child care needs and diabetes prevalence, county rurality, and race (p<0.05). We estimate costs of absenteeism and child care and observe from our models that an estimated 76.3 to 96.8% of counties would find it less expensive to provide child care to all healthcare workers with children than to bear the costs of healthcare worker absenteeism during school closures.

Conclusions: School closures are projected to reduce peak ICU and hospital demand, but could disrupt healthcare systems through absenteeism, especially in counties that are already particularly vulnerable to COVID-19. Child care subsidies could help circumvent the ostensible trade-off between school closures and healthcare worker absenteeism.
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http://dx.doi.org/10.1186/s12916-020-01692-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360472PMC
July 2020

Frequency of routine testing for SARS-CoV-2 to reduce transmission among workers.

medRxiv 2020 May 6. Epub 2020 May 6.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Shelter-in-place policies have been considered effective in mitigating the transmission of the virus SARS-CoV-2. To end such policies, routine testing and self-quarantine of those testing positive for active infection have been proposed, yet it remains unclear how often routine testing would need to be performed among workers returning to workplaces, and how effective this strategy would be to meaningfully prevent continued transmission of the virus. We simulated SARS-CoV-2 polymerase chain reaction testing to estimate the frequency of testing needed to avert continued epidemic propagation as shelter-in-place orders are relaxed. We find that testing strategies less frequent than twice weekly (e.g. weekly testing or testing once prior to returning to work) are unlikely to prevent workforce outbreaks. Even given unlimited testing capacity, the impact of frequent testing may not be sufficient to reliably relax shelter-in-place policies without risking continued epidemic propagation, unless other measures are instituted to complement testing and self-isolation.
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http://dx.doi.org/10.1101/2020.04.30.20087015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273291PMC
May 2020

Projected geographic disparities in healthcare worker absenteeism from COVID-19 school closures and the economic feasibility of child care subsidies: a simulation study.

medRxiv 2020 Apr 16. Epub 2020 Apr 16.

Center for Primary Care, Harvard Medical School.

Background: School closures have been enacted as a measure of mitigation during the ongoing COVID-19 pandemic. It has been shown that school closures could cause absenteeism amongst healthcare workers with dependent children, but there remains a need for spatially granular analyses of the relationship between school closures and healthcare worker absenteeism to inform local community preparedness.

Methods: We provide national- and county-level simulations of school closures and unmet child care needs across the United States. We develop individual simulations using county-level demographic and occupational data, and model school closure effectiveness with age-structured compartmental models. We perform multivariate quasi-Poisson ecological regressions to find associations between unmet child care needs and COVID-19 vulnerability factors.

Results: At the national level, we estimate the projected rate of unmet child care needs for healthcare worker households to range from 7.5% to 8.6%, and the effectiveness of school closures to range from 3.2% ( = 4) to 7.2% ( = 2) reduction in fewer ICU beds at peak demand. At the county-level, we find substantial variations of projected unmet child care needs and school closure effects, ranging from 1.9% to 18.3% of healthcare worker households and 5.7% to 8.8% reduction in fewer ICU beds at peak demand ( = 2). We find significant positive associations between estimated levels of unmet child care needs and diabetes prevalence, county rurality, and race ( < 0.05). We estimate costs of absenteeism and child care and observe from our models that an estimated 71.1% to 98.8% of counties would find it less expensive to provide child care to all healthcare workers with children than to bear the costs of healthcare worker absenteeism during school closures.

Conclusions: School closures are projected to reduce peak ICU bed demand, but could disrupt healthcare systems through absenteeism, especially in counties that are already particularly vulnerable to COVID-19. Child care subsidies could help circumvent the ostensible tradeoff between school closures and healthcare worker absenteeism.
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http://dx.doi.org/10.1101/2020.03.19.20039404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239083PMC
April 2020

Application of Schistosomiasis Consortium for Operational Research and Evaluation Study Findings to Refine Predictive Modeling of and Control in Sub-Saharan Africa.

Am J Trop Med Hyg 2020 07;103(1_Suppl):97-104

Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, Cleveland, Ohio.

An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control and elimination of schistosomiasis. To provide more accurate, evidence-based projections of the most likely impact of different control interventions, whether implemented alone or in combination, SCORE supported mathematical modeling teams to provide simulations of community-level infection outcomes in the setting of real or hypothetical programs implementing multiyear mass drug administration (MDA) for parasite control. These models were calibrated using SCORE experience with and gaining and sustaining control studies, and with data from comparable programs that used community-based or school-based praziquantel MDA in other parts of sub-Saharan Africa. From 2010 to 2019, models were developed and refined, first to project the likely SCORE control outcomes, and later to more accurately reflect impact of MDA across different transmission settings, including the role of snail ecology and the impact of seasonal rainfall on snail abundance. Starting in 2014, SCORE modeling projections were also compared with the models of colleagues in the Neglected Tropical Diseases Modelling Consortium. To explore further possible improvement to program-based control, later simulations examined the cost-effectiveness of combining MDA with environmental snail control, and the utility of early impact assessment to more quickly identify persistent hot spots of transmission. This article provides a nontechnical summary of the 11 SCORE-related modeling projects and provides links to the original open-access articles describing model development and projections relevant to schistosomiasis control policy.
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http://dx.doi.org/10.4269/ajtmh.19-0852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351296PMC
July 2020

Phylogeography of the iconic Australian red-tailed black-cockatoo (Calyptorhynchus banksii) and implications for its conservation.

Heredity (Edinb) 2020 09 12;125(3):85-100. Epub 2020 May 12.

School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.

Advances in sequencing technologies have revolutionized wildlife conservation genetics. Analysis of genomic data sets can provide high-resolution estimates of genetic structure, genetic diversity, gene flow, and evolutionary history. These data can be used to characterize conservation units and to effectively manage the genetic health of species in a broad evolutionary context. Here we utilize thousands of genome-wide single-nucleotide polymorphisms (SNPs) and mitochondrial DNA to provide the first genetic assessment of the Australian red-tailed black-cockatoo (Calyptorhynchus banksii), a widespread bird species comprising populations of varying conservation concern. We identified five evolutionarily significant units, which are estimated to have diverged during the Pleistocene. These units are only partially congruent with the existing morphology-based subspecies taxonomy. Genetic clusters inferred from mitochondrial DNA differed from those based on SNPs and were less resolved. Our study has a range of conservation and taxonomic implications for this species. In particular, we provide advice on the potential genetic rescue of the Endangered and restricted-range subspecies C. b. graptogyne, and propose that the western C. b. samueli population is diagnosable as a separate subspecies. The results of our study highlight the utility of considering the phylogeographic relationships inferred from genome-wide SNPs when characterizing conservation units and management priorities, which is particularly relevant as genomic data sets become increasingly accessible.
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http://dx.doi.org/10.1038/s41437-020-0315-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426920PMC
September 2020

Childhood vaccines and antibiotic use in low- and middle-income countries.

Nature 2020 05 29;581(7806):94-99. Epub 2020 Apr 29.

Center for Disease Dynamics, Economics & Policy, New Delhi, India.

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance.
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http://dx.doi.org/10.1038/s41586-020-2238-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332418PMC
May 2020

Invasive rabbits host immature Ixodes ticks at the urban-forest interface.

Ticks Tick Borne Dis 2020 07 9;11(4):101439. Epub 2020 Apr 9.

School of Life and Environmental Sciences, The University of Sydney, Camperdown, Australia.

Introduced wildlife may be important alternative hosts for generalist ticks that cause health issues for humans and companion animals in urban areas, but to date are rarely considered as part of the tick-host community compared to native wildlife. In Australia, European rabbits, Oryctolagus cuniculus, are a widespread and abundant invasive species common to a range of human-modified ecosystems. To understand the potential role of rabbits in the life cycle of Australian ticks, we investigated the seasonal abundance of all tick life stages (larva, nymph, and adult) on rabbits collected from pest control programs in two urban forest remnants in Sydney, Australia. We also recorded whether larvae, nymphs, and adults were attached to the head, body, or limbs of rabbits to reveal patterns of tick attachment. Of the 2426 Ixodes ticks collected from 42 rabbits, larvae were by far the most abundant life stage (2360), peaking in abundance in autumn, while small numbers of nymphs (62) and adults (4) were present in winter and summer respectively. Larvae were found all over the body, whereas adults and nymphs were predominantly attached to the head, suggesting that the mature life stages use the host landscape differently, or that adults or nymphs may be groomed off the body. The most abundant tick species, as determined by morphology and DNA sequencing, was Ixodes holocyclus, a generalist tick responsible for significant human and companion animal health concerns in Australia. Our findings highlight the importance of understanding the role of introduced wildlife in tick dynamics particularly in novel ecosystems where non-native hosts may be more abundant than native hosts.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101439DOI Listing
July 2020

Scientific and ethical basis for social-distancing interventions against COVID-19.

Lancet Infect Dis 2020 06 23;20(6):631-633. Epub 2020 Mar 23.

Department of Medicine, University of California, San Francisco, CA, USA.

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http://dx.doi.org/10.1016/S1473-3099(20)30190-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118670PMC
June 2020

Evolutionary rates are correlated between cockroach symbionts and mitochondrial genomes.

Biol Lett 2020 01 8;16(1):20190702. Epub 2020 Jan 8.

School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.

Bacterial endosymbionts evolve under strong host-driven selection. Factors influencing host evolution might affect symbionts in similar ways, potentially leading to correlations between the molecular evolutionary rates of hosts and symbionts. Although there is evidence of rate correlations between mitochondrial and nuclear genes, similar investigations of hosts and symbionts are lacking. Here, we demonstrate a correlation in molecular rates between the genomes of an endosymbiont () and the mitochondrial genomes of their hosts (cockroaches). We used partial genome data for multiple strains of to compare phylogenetic relationships and evolutionary rates for 55 cockroach/symbiont pairs. The phylogenies inferred for and the mitochondrial genomes of their hosts were largely congruent, as expected from their identical maternal and cytoplasmic mode of inheritance. We found a correlation between evolutionary rates of the two genomes, based on comparisons of root-to-tip distances and on comparisons of the branch lengths of phylogenetically independent species pairs. Our results underscore the profound effects that long-term symbiosis can have on the biology of each symbiotic partner.
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http://dx.doi.org/10.1098/rsbl.2019.0702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013487PMC
January 2020

The 2016 California policy to eliminate nonmedical vaccine exemptions and changes in vaccine coverage: An empirical policy analysis.

PLoS Med 2019 12 23;16(12):e1002994. Epub 2019 Dec 23.

Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.

Background: Vaccine hesitancy, the reluctance or refusal to receive vaccination, is a growing public health problem in the United States and globally. State policies that eliminate nonmedical ("personal belief") exemptions to childhood vaccination requirements are controversial, and their effectiveness to improve vaccination coverage remains unclear given limited rigorous policy analysis. In 2016, a California policy (Senate Bill 277) eliminated nonmedical exemptions from school entry requirements. The objective of this study was to estimate the association between California's 2016 policy and changes in vaccine coverage.

Methods And Findings: We used a quasi-experimental state-level synthetic control analysis and a county-level difference-in-differences analysis to estimate the impact of the 2016 California policy on vaccination coverage and prevalence of exemptions to vaccine requirements (nonmedical and medical). We used publicly available state-level data from the US Centers for Disease Control and Prevention on coverage of measles, mumps, and rubella (MMR) vaccination, nonmedical exemption, and medical exemption in children entering kindergarten. We used county-level data individually requested from state departments of public health on overall vaccine coverage and exemptions. Based on data availability, we included state-level data for 45 states, including California, from 2011 to 2017 and county-level data for 17 states from 2010 to 2017. The prespecified primary study outcome was MMR vaccination in the state analysis and overall vaccine coverage in the county analysis. In the state-level synthetic control analysis, MMR coverage in California increased by 3.3% relative to its synthetic control in the postpolicy period (top 2 of 43 states evaluated in the placebo tests, top 5%), nonmedical exemptions decreased by 2.4% (top 2 of 43 states evaluated in the placebo tests, top 5%), and medical exemptions increased by 0.4% (top 1 of 44 states evaluated in the placebo tests, top 2%). In the county-level analysis, overall vaccination coverage increased by 4.3% (95% confidence interval [CI] 2.9%-5.8%, p < 0.001), nonmedical exemptions decreased by 3.9% (95% CI 2.4%-5.4%, p < 0.001), and medical exemptions increased by 2.4% (95% CI 2.0%-2.9%, p < 0.001). Changes in vaccination coverage across counties after the policy implementation from 2015 to 2017 ranged from -6% to 26%, with larger increases in coverage in counties with lower prepolicy vaccine coverage. Results were robust to alternative model specifications. The limitations of the study were the exclusion of a subset of US states from the analysis and the use of only 2 years of postpolicy data based on data availability.

Conclusions: In this study, implementation of the California policy that eliminated nonmedical childhood vaccine exemptions was associated with an estimated increase in vaccination coverage and a reduction in nonmedical exemptions at state and county levels. The observed increase in medical exemptions was offset by the larger reduction in nonmedical exemptions. The largest increases in vaccine coverage were observed in the most "high-risk" counties, meaning those with the lowest prepolicy vaccine coverage. Our findings suggest that government policies removing nonmedical exemptions can be effective at increasing vaccination coverage.
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http://dx.doi.org/10.1371/journal.pmed.1002994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927583PMC
December 2019

Novel Lineages of Oxymonad Flagellates from the Termite Porotermes adamsoni (Stolotermitidae): the Genera Oxynympha and Termitimonas.

Protist 2019 12 21;170(6):125683. Epub 2019 Oct 21.

Research Group Insect Gut Microbiology and Symbiosis, Max Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany. Electronic address:

The symbiotic gut flagellates of lower termites form host-specific consortia composed of Parabasalia and Oxymonadida. The analysis of their coevolution with termites is hampered by a lack of information, particularly on the flagellates colonizing the basal host lineages. To date, there are no reports on the presence of oxymonads in termites of the family Stolotermitidae. We discovered three novel, deep-branching lineages of oxymonads in a member of this family, the damp-wood termite Porotermes adamsoni. One tiny species (6-10μm), Termitimonas travisi, morphologically resembles members of the genus Monocercomonoides, but its SSU rRNA genes are highly dissimilar to recently published sequences of Polymastigidae from cockroaches and vertebrates. A second small species (9-13μm), Oxynympha loricata, has a slight phylogenetic affinity to members of the Saccinobaculidae, which are found exclusively in wood-feeding cockroaches of the genus Cryptocercus, the closest relatives of termites, but shows a combination of morphological features that is unprecedented in any oxymonad family. The third, very rare species is larger and possesses a contractile axostyle; it represents a phylogenetic sister group to the Oxymonadidae. These findings significantly advance our understanding of the diversity of oxymonads in termite guts and the evolutionary history of symbiotic digestion.
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http://dx.doi.org/10.1016/j.protis.2019.125683DOI Listing
December 2019

Evolution of Termite Symbiosis Informed by Transcriptome-Based Phylogenies.

Curr Biol 2019 11 17;29(21):3728-3734.e4. Epub 2019 Oct 17.

Okinawa Institute of Science & Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan; Faculty of Forestry and Wood Sciences, Czech University of Life Sciences, Kamycka 129, 16521 Prague, Czech Republic. Electronic address:

Termitidae comprises ∼80% of all termite species [1] that play dominant decomposer roles in tropical ecosystems [2, 3]. Two major events during termite evolution were the loss of cellulolytic gut protozoans in the ancestor of Termitidae and the subsequent gain in the termitid subfamily Macrotermitinae of fungal symbionts cultivated externally in "combs" constructed within the nest [4, 5]. How these symbiotic transitions occurred remains unresolved. Phylogenetic analyses of mitochondrial data previously suggested that Macrotermitinae is the earliest branching termitid lineage, followed soon after by Sphaerotermitinae [6], which cultivates bacterial symbionts on combs inside its nests [7]. This has led to the hypothesis that comb building was an important evolutionary step in the loss of gut protozoa in ancestral termitids [8]. We sequenced genomes and transcriptomes of 55 termite species and reconstructed phylogenetic trees from up to 4,065 orthologous genes of 68 species. We found strong support for a novel sister-group relationship between the bacterial comb-building Sphaerotermitinae and fungus comb-building Macrotermitinae. This key finding indicates that comb building is a derived trait within Termitidae and that the creation of a comb-like "external rumen" involving bacteria or fungi may not have driven the loss of protozoa from ancestral termitids, as previously hypothesized. Instead, associations with gut prokaryotic symbionts, combined with dietary shifts from wood to other plant-based substrates, may have played a more important role in this symbiotic transition. Our phylogenetic tree provides a platform for future studies of comparative termite evolution and the evolution of symbiosis in this taxon.
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http://dx.doi.org/10.1016/j.cub.2019.08.076DOI Listing
November 2019

Recalibration of the insect evolutionary time scale using Monte San Giorgio fossils suggests survival of key lineages through the End-Permian Extinction.

Proc Biol Sci 2019 10 9;286(1912):20191854. Epub 2019 Oct 9.

School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Sydney, Australia.

Insects are a highly diverse group of organisms and constitute more than half of all known animal species. They have evolved an extraordinary range of traits, from flight and complete metamorphosis to complex polyphenisms and advanced eusociality. Although the rich insect fossil record has helped to chart the appearance of many phenotypic innovations, data are scarce for a number of key periods. One such period is that following the End-Permian Extinction, recognized as the most catastrophic of all extinction events. We recently discovered several 240-million-year-old insect fossils in the Mount San Giorgio Lagerstätte (Switzerland-Italy) that are remarkable for their state of preservation (including internal organs and soft tissues), and because they extend the records of their respective taxa by up to 200 million years. By using these fossils as calibrations in a phylogenomic dating analysis, we present a revised time scale for insect evolution. Our date estimates for several major lineages, including the hyperdiverse crown groups of Lepidoptera, Hemiptera: Heteroptera and Diptera, are substantially older than their currently accepted post-Permian origins. We found that major evolutionary innovations, including flight and metamorphosis, appeared considerably earlier than previously thought. These results have numerous implications for understanding the evolution of insects and their resilience in the face of extreme events such as the End-Permian Extinction.
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http://dx.doi.org/10.1098/rspb.2019.1854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790769PMC
October 2019

State of deworming coverage and equity in low-income and middle-income countries using household health surveys: a spatiotemporal cross-sectional study.

Lancet Glob Health 2019 11 23;7(11):e1511-e1520. Epub 2019 Sep 23.

Focus Area for Compassion and Ethics, Task Force for Global Health, Decatur, GA, USA.

Background: Mass deworming against soil-transmitted helminthiasis, which affects 1 billion of the poorest people globally, is one of the largest public health programmes for neglected tropical diseases, and is intended to be equitable. However, the extent to which treatment programmes for deworming achieve equitable coverage across wealth class and sex is unclear and the public health metric of national deworming coverage does not include representation of equity. This study aims to measure both coverage and equity in global, national, and subnational deworming to guide future programmatic evaluation, investment, and metric design.

Methods: We used nationally representative, geospatial, household data from Demographic and Health Surveys that measured mother-reported deworming in children of preschool age (12-59 months). Deworming was defined as children having received drugs for intestinal parasites in the previous 6 months before the survey. We estimated deworming coverage disaggregated by geography, wealth quintile, and sex, and computed an equity index. We examined trends in coverage and equity index across countries, within countries, and over time. We used a regression model to compute the household correlates of deworming and ecological correlates of equitable deworming.

Findings: Our study included 820 883 children living in 50 countries from Africa, the Americas, Asia, and Europe that are endemic for soil-transmitted helminthiasis using 77 Demographic and Health Surveys from December, 2003, to October, 2017. In these countries, the mean deworming coverage in preschool children was estimated at 33·0% (95% CI 32·9-33·1). The subnational coverage ranged from 0·5% to 87·5%, and within-country variation was greater than between-country variation. Of the 31 countries reporting that they reached the WHO goal of more than 75% national coverage, 30 had inequity in deworming, with treatment concentrated in wealthier populations. We did not detect systematic differences in deworming equity by sex.

Interpretation: Substantial inequities in mass deworming programmes are common as wealthier populations have consistently higher coverage than that of the poor, including in countries reporting to have reached the WHO goal of more than 75% national coverage. These inequities seem to be geographically heterogeneous, modestly improving over time, with no evidence of sex differences in inequity. Future reporting of deworming coverage should consider disaggregation by geography, wealth, and sex with incorporation of an equity index to complement the conventional public health metric of national deworming coverage.

Funding: Bill & Melinda Gates Foundation, Stanford University Medical Scientist Training Program.
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http://dx.doi.org/10.1016/S2214-109X(19)30413-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024997PMC
November 2019

Improving public health control of schistosomiasis with a modified WHO strategy: a model-based comparison study.

Lancet Glob Health 2019 10;7(10):e1414-e1422

School of Medicine, Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.

Background: Schistosomiasis is endemic in many low-income and middle-income countries. To reduce infection-associated morbidity, WHO has published guidelines for control of schistosomiasis based on targeted mass drug administration (MDA) and, in 2017, on supplemental snail control. We compared the current WHO guideline-based strategies from 2012 to an alternative, adaptive decision making framework for control in heterogeneous environments, to estimate their predicted relative effectiveness and time to achievement of defined public health goals.

Methods: In this model-based comparison study, we adapted an established transmission model for Schistosoma infection that couples local human and snail populations and includes aspects of snail ecology and parasite biology. We calibrated the model using data from high-risk, moderate-risk, and lower-risk rural villages in Kenya, and then simulated control via MDA. We compared 2012 WHO guidelines with a modified adaptive strategy that tested a lower-prevalence threshold for MDA and shorter intervals between implementation, evaluation, and modification. We also explored the addition of snail control to this modified strategy. The primary outcomes were the proportion of simulations that achieved the WHO targets in children aged 5-14 years of less than 5% (2020 morbidity control goal) and less than 1% (2025 elimination as a public health problem goal) heavy infection and the mean duration of treatment required to achieve these goals.

Findings: In high-risk communities (80% baseline prevalence), current WHO strategies for MDA were not predicted to achieve morbidity control (<5% prevalence of heavy infections) in 80% of simulations over a 10-year period, whereas the modified adaptive strategy was predicted to achieve this goal in over 50% of simulations within 5 years. In low-risk and moderate-risk communities, current WHO guidelines from 2012 were predicted to achieve morbidity control in most simulations (96% in low-risk and 41% for moderate-risk), although the proposed adaptive strategy reached this goal in a shorter period (mean reduction of 5 years). The model predicted that the addition of snail control to the proposed adaptive strategy would achieve morbidity control in all high-risk communities, and 54% of communities could reach the goal for elimination as a public health problem (<1% heavy infection) within 7 years.

Interpretation: The modified adaptive decision making framework is predicted to be more effective than the current WHO guidelines in reaching 2025 public health goals, especially for high-prevalence regions. Modifications in current guidelines could reduce the time and resources needed for countries who are currently working on achieving public health goals against schistosomiasis.

Funding: University of Georgia Research Foundation, The Bill & Melinda Gates Foundation, and the Medical Scientist Training Program at Stanford University School of Medicine.
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http://dx.doi.org/10.1016/S2214-109X(19)30346-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024988PMC
October 2019
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