Spatiotemporal trends of cutaneous leishmaniasis in Costa Rica.

BACKGROUND: Cutaneous leishmaniasis (CL) remains an important neglected tropical disease in Costa Rica, which has one of the largest burdens of this disease in Latin America. METHODS: We identified district-level hotspots of CL from 2006 to 2017 and conducted temporal analysis to identify where hotspots were increasing across the country. RESULTS: Clear patterns of CL risk were detected, with persistent hotspots located in the Caribbean region, where risk was also found to be increasing over time in some areas. CONCLUSIONS: We identify spatiotemporal hotspots, which may be used in support of the leishmaniasis plan of action for the Americas

Spatiotemporal dynamics of vector-borne disease risk across human land-use gradients: examining the role of agriculture, indigenous territories, and protected areas in Costa Rica

Background Costa Rica has undergone significant changes to its forest ecosystems due, in part, to the proliferation of palm oil and other industrial agriculture operations. However, the country also boasts conservation programmes that are among the most robust in the neotropics. Consequently, gradients of anthropogenic to intact ecosystems are found throughout the country. Forest ecosystems may decrease vector-borne disease (VBD) risk by maintaining insect populations in a state of relative equilibrium; however, evidence suggests that intact forests foster biodiversity and may also amplify VBD risk in some circumstances. As a result, focal points of human-vector contact are likely idiosyncratic. This may be particularly true in indigenous territories, which have been shown to play a vital role in maintaining the ecological integrity of conservation areas. Here, we investigate the relationships between anthropogenic landscapes, indigenous territories, protected areas, and risk of VBD. Methods We quantified spatial dynamics of risk across three distinct categories of VBD in Costa Rica: emerging flaviviruses (Zika virus disease and dengue); neglected tropical diseases (cutaneous leishmaniasis and Chagas disease); and a disease nearing eradication (malaria). We collected district-level incidence data from between 2006 and 2017 and used spatial statistics to identify hotspots of elevated risk. We then quantified the associations between anthropogenic landscapes, intact forest ecosystems, and indigenous territories with both the presence and persistence of elevated transmission risk over time using multivariate hurdle models. Findings We detected clear patterns of non-random disease risk across each of the three categories of VBD. Compared with protected areas, districts with higher proportions of human-altered landscapes, particularly agricultural intensification, were at higher risk for VBD across all categories. Districts with the highest proportion of crop cover, compared with the lowest proportion, were significantly associated with the presence of hotspots for Zika virus disease (OR 15·19 [95% CI 6·19–37·26]), dengue (13·00 [7·24–23·35]), leishmaniasis (4·46 [1·18–16·84]), Chagas disease (3·09 [1·47–6·49]), and malaria (8·40 [3·56–19·83]). Interpretation A set of spatial epidemiology tools within a planetary health framework allowed for a refined understanding of the risk of VBD of global public health significance in a biodiversity hotspot. Our findings may be used to better guide targeted public health disease surveillance, control, and prevention programmes. Additional research to understand the role that socioeconomic factors play in the variating VBD risk would contribute additional context to these findings, as these factors are often also spatially associated

Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study

Background: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The aim of this study was to characterise antimalarial drug susceptibility of Plasmodium falciparum isolates from Tororo and Busia districts in Uganda. Methods: In this prospective longitudinal study, P falciparum isolates were collected from patients aged 6 months or older presenting at the Tororo District Hospital (Tororo district, a site with relatively low malaria incidence) or Masafu General Hospital (Busia district, a high-incidence site) in eastern Uganda with clinical symptoms of malaria, a positive Giemsa-stained blood film for P falciparum, and no signs of severe disease. Ex-vivo susceptibilities to ten antimalarial drugs were measured using a 72-h microplate growth inhibition assay with SYBR Green detection. Relevant P falciparum genetic polymorphisms were characterised by molecular methods. We compared results with those from earlier studies in this region and searched for associations between drug susceptibility and parasite genotypes. Findings: From June 10, 2016, to July 29, 2019, 361 P falciparum isolates were collected in the Busia district and 79 in the Tororo district from 440 participants. Of 440 total isolates, 392 (89%) successfully grew in culture and showed excellent drug susceptibility for chloroquine (median half-maximal inhibitory concentration [IC50] 20·0 nM [IQR 12·0-26·0]), monodesethylamodiaquine (7·1 nM [4·3-8·9]), pyronaridine (1·1 nM [0·7-2·3]), piperaquine (5·6 nM [3·3-8·6]), ferroquine (1·8 nM [1·5-3·3]), AQ-13 (24·0 nM [17·0-32·0]), lumefantrine (5·1 nM [3·2-7·7]), mefloquine (9·5 nM [6·6-13·0]), dihydroartemisinin (1·5 nM [1·0-2·0]), and atovaquone (0·3 nM [0·2-0·4]). Compared with results from our study in 2010-13, significant improvements in susceptibility were seen for chloroquine (median IC50 288·0 nM [IQR 122·0-607·0]; p\u3c0·0001), monodesethylamodiaquine (76·0 nM [44·0-137]; p\u3c0·0001), and piperaquine (21·0 nM [7·6-43·0]; p\u3c0·0001), a small but significant decrease in susceptibility was seen for lumefantrine (3·0 nM [1·1-7·6]; p\u3c0·0001), and no change in susceptibility was seen with dihydroartemisinin (1·3 nM [0·8-2·5]; p=0·64). Chloroquine resistance (IC50\u3e100 nM) was more common in isolates from the Tororo district (11 [15%] of 71), compared with those from the Busia district (12 [4%] of 320; p=0·0017). We showed significant increases between 2010-12 and 2016-19 in the prevalences of wild-type P falciparum multidrug resistance protein 1 (PfMDR1) Asn86Tyr from 60% (391 of 653) to 99% (418 of 422; p\u3c0·0001), PfMDR1 Asp1246Tyr from 60% (390 of 650) to 90% (371 of 419; p\u3c0·0001), and P falciparum chloroquine resistance transporter (PfCRT) Lys76Thr from 7% (44 of 675) to 87% (364 of 417; p\u3c0·0001). Interpretation: Our results show marked changes in P falciparum drug susceptibility phenotypes and genotypes in Uganda during the past decade. These results suggest that additional changes will be seen over time and continued surveillance of susceptibility to key ACT components is warranted. Funding: National Institutes of Health and Medicines for Malaria Venture

Associations between Varied Susceptibilities to PfATP4 Inhibitors and Genotypes in Ugandan Plasmodium falciparum Isolates.

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda, from 2016 to 2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many nonsynonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%), and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92, and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild-type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated the presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites

Spatiotemporal dynamics of the Southern California Asian citrus psyllid (<i>Diaphorina citri</i>) invasion

<div><p>Biological invasions are governed by spatial processes that tend to be distributed in non-random ways across landscapes. Characterizing the spatial and temporal heterogeneities of the introduction, establishment, and spread of non-native insect species is a key aspect of effectively managing their geographic expansion. The Asian citrus psyllid (<i>Diaphorina citri</i>), a vector of the bacterium associated with huanglongbing (HLB), poses a serious threat to commercial and residential citrus trees. In 2008, <i>D</i>. <i>citri</i> first began expanding northward from Mexico into parts of Southern California. Using georeferenced <i>D</i>. <i>citri</i> occurrence data from 2008–2014, we sought to better understand the extent of the geographic expansion of this invasive vector species. Our objectives were to: 1) describe the spatial and temporal distribution of <i>D</i>. <i>citri</i> in Southern California, 2) identify the locations of statistically significant <i>D</i>. <i>citri</i> hotspots, and 3) quantify the dynamics of anisotropic spread. We found clear evidence that the spatial and temporal distribution of <i>D</i>. <i>citri</i> in Southern California is non-random. Further, we identified the existence of statistically significant hotspots of <i>D</i>. <i>citri</i> occurrence and described the anisotropic dispersion across the Southern California landscape. For example, the dominant hotspot surrounding Los Angeles showed rapid and strongly asymmetric spread to the south and east. Our study demonstrates the feasibility of quantitative invasive insect risk assessment with the application of a spatial epidemiology framework.</p></div

Proportion of annual urban <i>D</i>. <i>citri</i> occurrences in a given month.

<p>Only those years shown for which there were adequate occurrences each month of the year (2010–2014 for urban, 2013–2014 for commercial citrus).</p

Standard deviational ellipses depicting anisotropic spread of <i>D</i>. <i>citri</i> hotspots.

<p>Standard deviational ellipses depicting anisotropic spread of <i>D</i>. <i>citri</i> hotspots.</p

Local Moran’s <i>I</i> clusters of <i>D</i>. <i>citri</i> abundance, 2008–2014.

<p>Local Moran’s <i>I</i> clusters of <i>D</i>. <i>citri</i> abundance, 2008–2014.</p

Cumulative annual <i>D</i>. <i>citri</i> occurrences in urban areas versus commercial citrus.

<p>Cumulative annual <i>D</i>. <i>citri</i> occurrences in urban areas versus commercial citrus.</p

Spider plot of the anisotropic spread of the Los Angeles <i>D</i>. <i>citri</i> hotspot from 2009 to 2014.

<p>Concentric rings indicate the rate of spread in increments of 5 km per year.</p