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Indoor and outdoor ovitraps were placed in 15 randomly selected houses in two rural villages in Chiapas, southern Mexico. In addition, ovitraps were placed in five transects surrounding each village, with three traps per transect, one at the edge, one at 50 m, and another at 100 m from the edge of the village. All traps were inspected weekly. A transect with eight traps along a road between the two villages was also included. Population fluctuations of Aedes aegypti and Ae. albopictus were examined during 2016-2018 by counting egg numbers. A higher number of Aedes spp. eggs was recorded at Hidalgo village with 257,712 eggs (60.9%), of which 58.1% were present in outdoor ovitraps and 41.9% in indoor ovitraps, compared with 165,623 eggs (39.1%) collected in the village of Río Florido, 49.0% in outdoor and 51.0% in indoor ovitraps. A total of 84,047 eggs was collected from ovitraps placed along transects around Río Florido, compared to 67,542 eggs recorded from transects around Hidalgo. Fluctuations in egg counts were associated with annual variation in precipitation, with 2.3 to 3.2-fold more eggs collected from ovitraps placed in houses and 4.8 to 5.1-fold more eggs in ovitraps from the surrounding transects during the rainy season than in the dry season, respectively. Aedes aegypti was the dominant species during the dry season and at the start of the rainy season in both villages. Aedes albopictus populations were lower for most of the dry season, but increased during the rainy season and predominated at the end of the rainy season in both villages. Aedes albopictus was also the dominant species in the zones surrounding both villages. The numbers of eggs collected from intradomiciliary ovitraps were strongly correlated with the numbers of eggs in peridomiciliary ovitraps in both Río Florido (R 2 adj = 0.92) and Hidalgo (R 2 adj = 0.94), suggesting that peridomiciliary sampling could provide an accurate estimate of intradomiciliary oviposition by Aedes spp. in future studies in these villages. We conclude that the feasibility of sterile insect technique (SIT)-based program of vector control could be evaluated in the isolated Ae. aegypti populations in the rural villages of our baseline study., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

BB-94 (batimastat) is a broad- spectrum hydroxamic acid-based zinc metalloproteinase inhibitor that inhibits both the matrix metalloproteinases (MMP) and members of the ADAM family of enzymes such as Tumour Necrosis Factor-alpha Cleaving Enzyme (TACE). These enzymes are involved in the regulation of inflammatory processes in tuberculosis. Balb/c mice infected with M. tuberculosis via the intratracheal route were treated with BB-94 for 1 month, starting on the day of infection. Immunohistochemistry, semiquantitative RT-PCR and ELISA assays for cytokines revealed a deficit in IL-1 and IL-2 expression and a premature bias towards IL-4 expression, accompanied by a delay in granuloma formation and more rapid progression of disease in BB-94-treated animals. This situation corrected itself after the drug was withdrawn at 28 days. In contrast, when BB-94 was administered only after 1 month there were no significant changes apart from the presence of amyloid, and a paradoxically increased expression of IL-1alpha. These results cast light on mechanisms of immunity in tuberculosis and also indicate that in patients treated with similar broad-spectrum MMP inhibitors there may be a risk of inappropriate deviation of some immune responses towards a Type-2 cytokine profile.

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.