Silent Circulation of Rift Valley Fever in Humans, Botswana, 2013-2014.

We evaluated the prevalence of Rift Valley fever virus IgG and IgM in human serum samples (n = 1,276) collected in 2013-2014 in northern Botswana. Our findings provide evidence of active circulation of this virus in humans in the absence of clinical disease in this region.

Unchartered waters: Climate change likely to intensify infectious disease outbreaks causing mass mortality events in marine mammals.

Infectious disease emergence has increased significantly over the last 30 years, with mass mortality events (MMEs) associated with epizootics becoming increasingly common. Factors influencing these events have been widely studied in terrestrial systems, but remain relatively unexplored in marine mammals. Infectious disease-induced MMEs (ID MMEs) have not been reported ubiquitously among marine mammal species, indicating that intrinsic (host) and/or extrinsic (environmental) ecological factors may influence this heterogeneity. We assess the occurrence of ID MMEs (1955-2018) across extant marine mammals (n = 129) in relation to key life-history characteristics (sociality, trophic level, habitat breadth) and environmental variables (season, sea surface temperature [SST] anomalies, El Niño occurrence). Our results show that ID MMEs have been reported in 14% of marine mammal species (95% CI 9%-21%), with 72% (n = 36; 95% CI 56%-84%) of these events caused predominantly by viruses, primarily morbillivirus and influenza A. Bacterial pathogens caused 25% (95% CI 14%-41%) of MMEs, with only one being the result of a protozoan pathogen. Overall, virus-induced MMEs involved a greater number of fatalities per event compared to other pathogens. No association was detected between the occurrence of ID MMEs and host characteristics, such as sociality or trophic level, but ID MMEs did occur more frequently in semiaquatic species (pinnipeds) compared to obligate ocean dwellers (cetaceans; χ2  = 9.6, p = .002). In contrast, extrinsic factors significantly influenced ID MMEs, with seasonality linked to frequency (χ2  = 19.85, p = .0002) and severity of these events, and global yearly SST anomalies positively correlated with their temporal occurrence (Z = 3.43, p = 2.7e-04). No significant association was identified between El Niño and ID MME occurrence (Z = 0.28, p = .81). With climate change forecasted to increase SSTs and the frequency of extreme seasonal weather events, epizootics causing MMEs are likely to intensify with significant consequences for marine mammal survival.

Effect of food limitation and reproductive activity on fecal glucocorticoid metabolite levels in banded mongooses.

BACKGROUND: Glucocorticoids mediate responses to perceived stressors, thereby restoring homeostasis. However, prolonged glucocorticoid elevation may cause homeostatic overload. Using extensive field investigations of banded mongoose (Mungos mungo) groups in northern Botswana, we assessed the influence of reproduction, predation risk, and food limitation on apparent homeostatic overload (n=13 groups, 1542 samples from 268 animals). We experimentally manipulated reproduction and regulated food supply in captive mongooses, and compared their glucocorticoid responses to those obtained from free-living groups. RESULTS: At the population level, variation in glucocorticoid levels in free-living mongooses was explained by food limitation: fecal organic matter, recent rainfall, and access to concentrated anthropogenic food resources. Soil macrofauna density and reproductive events explained less and predation risk very little variation in glucocorticoid levels. Reproduction and its associated challenges alone (under regulated feeding conditions) increased glucocorticoid levels 19-fold in a captive group. Among free-living groups, glucocorticoid elevation was seasonal (occurring in late dry season or early wet season when natural food resources were less available), but the timing of peak glucocorticoid production was moderated by access to anthropogenic resources (groups with fewer anthropogenic food sources had peaks earlier in dry seasons). Peak months represented 12- and 16-fold increases in glucocorticoids relative to nadir months with some animals exhibiting 100-fold increases. Relative to the captive group nadir, some free-living groups exhibited 60-fold increases in peak glucocorticoid levels with some animals exhibiting up to 800-fold increases. Most of these animals exhibited 1- to 10-fold increases relative to the captive animal peak. CONCLUSIONS: Banded mongooses exhibit seasonal chronic glucocorticoid elevation, associated primarily with food limitation and secondarily with reproduction. Magnitude and duration of this elevation suggests that this may be maladaptive for some animals, with possible fitness consequences. In late dry season, this population may face a convergence of stressors (food limitation, agonistic encounters at concentrated food resources, evictions, estrus, mate competition, parturition, and predation pressure on pups), which may induce homeostatic overload.

Hydrometeorology and flood pulse dynamics drive diarrheal disease outbreaks and increase vulnerability to climate change in surface-water-dependent populations: A retrospective analysis.

BACKGROUND: The impacts of climate change on surface water, waterborne disease, and human health remain a growing area of concern, particularly in Africa, where diarrheal disease is one of the most important health threats to children under 5 years of age. Little is known about the role of surface water and annual flood dynamics (flood pulse) on waterborne disease and human health nor about the expected impact of climate change on surface-water-dependent populations. METHODS AND FINDINGS: Using the Chobe River in northern Botswana, a flood pulse river-floodplain system, we applied multimodel inference approaches assessing the influence of river height, water quality (bimonthly counts of Escherichia coli and total suspended solids [TSS], 2011-2017), and meteorological variability on weekly diarrheal case reports among children under 5 presenting to health facilities (n = 10 health facilities, January 2007-June 2017). We assessed diarrheal cases by clinical characteristics and season across age groups using monthly outpatient data (January 1998-June 2017). A strong seasonal pattern was identified, with 2 outbreaks occurring regularly in the wet and dry seasons. The timing of outbreaks diverged from that at the level of the country, where surface water is largely absent. Across age groups, the number of diarrheal cases was greater, on average, during the dry season. Demographic and clinical characteristics varied by season, underscoring the importance of environmental drivers. In the wet season, rainfall (8-week lag) had a significant influence on under-5 diarrhea, with a 10-mm increase in rainfall associated with an estimated 6.5% rise in the number of cases. Rainfall, minimum temperature, and river height were predictive of E. coli concentration, and increases in E. coli in the river were positively associated with diarrheal cases. In the dry season, river height (1-week lag) and maximum temperature (1- and 4-week lag) were significantly associated with diarrheal cases. During this period, a 1-meter drop in river height corresponded to an estimated 16.7% and 16.1% increase in reported diarrhea with a 1- and 4-week lag, respectively. In this region, as floodwaters receded from the surrounding floodplains, TSS levels increased and were positively associated with diarrheal cases (0- and 3-week lag). Populations living in this region utilized improved water sources, suggesting that hydrological variability and rapid water quality shifts in surface waters may compromise water treatment processes. Limitations include the potential influence of health beliefs and health seeking behaviors on data obtained through passive surveillance. CONCLUSIONS: In flood pulse river-floodplain systems, hydrology and water quality dynamics can be highly variable, potentially impacting conventional water treatment facilities and the production of safe drinking water. In Southern Africa, climate change is predicted to intensify hydrological variability and the frequency of extreme weather events, amplifying the public health threat of waterborne disease in surface-water-dependent populations. Water sector development should be prioritized with urgency, incorporating technologies that are robust to local environmental conditions and expected climate-driven impacts. In populations with high HIV burdens, expansion of diarrheal disease surveillance and intervention strategies may also be needed. As annual flood pulse processes are predominantly influenced by climate controls in distant regions, country-level data may be inadequate to refine predictions of climate-health interactions in these systems.

Pathology of the Emerging Mycobacterium tuberculosis Complex Pathogen, Mycobacterium mungi, in the Banded Mongoose ( Mungos mungo).

Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion. Similar inflammatory cell infiltrates expanded the dermis of the nasal planum with frequent ulceration. However, even in cases with intact epidermis, acid-fast bacilli were present in variable numbers among dermal infiltrates and on the epidermal surface among desquamated cells and debris, most commonly in small crevices or folds. In general, tissue involvement varied among cases but was highest in lymph nodes (50/54, 93%), liver (39/53, 74%), spleen (37/51, 73%), and anal glands/sacs (6/8, 75%). Pulmonary lesions were present in 67% of sampled mongooses (35/52) but only in advanced disseminated disease. The pathological presentation of M. mungi in the banded mongoose is consistent with pathogen shedding occurring through scent-marking behaviors (urine and anal gland secretions) with new infections arising from contact with these contaminated olfactory secretions and percutaneous movement of the pathogen through breaks in the skin, nasal planum, and/or skin of the snout. Given the character and distribution of lesions and the presence of intracellular acid-fast bacilli, we hypothesize that pathogen spread occurs within the body through a hematogenous and/or lymphatic route. Features of prototypical granulomas such as multinucleated giant cells and peripheral fibrosis were rarely present in affected mongooses. Acid-fast bacilli were consistently found intracellularly, even in regions of necrosis. The mongoose genome has a unique deletion (RD1mon) that includes part of the encoding region for PPE68 (Rv3873), a gene co-operonic with PE35. These proteins can influence the host's cellular immune response to mycobacterial infections, and it remains uncertain how this deletion might contribute to observed patterns of pathology. M. mungi infection in banded mongooses is characterized by both a unique transmission and exposure route, as well as accompanying pathological features, providing an opportunity to increase our understanding of MTC pathogenesis across host-pathogen systems.

Pit Latrines: A Noninvasive Sampling Strategy to Assess Fecal Pathogen Occurrence in Low Resource Communities.

Limited understanding of disease in low resource communities continues to hamper improvements in health. We evaluated household pit latrine sampling as a non-invasive approach to investigate important fecal pathogens such as Giardia lamblia and Cryptosporidium spp. in impoverished communities where health-seeking behavior limits the sensitivity of health facility-based surveillance. Fecal samples were collected from pit latrines in randomly selected households and from patients presenting to the only hospital in the region during the same time periods. Samples were tested with a commercially available ELISA. Giardia household prevalence was 28.7% in 2016 and 48.4% in 2017, while individual samples from hospital submission had a Giardia prevalence of 2.4% in 2016 and 8.0% in 2017. Cryptosporidium was only found in one household. Results suggest that pit latrine surveillance for fecal-borne infections provide course estimates of community infection levels that are unbiased by health seeking behaviors and allow surveillance of vulnerable sectors of a population.

Household-level spatiotemporal patterns of incidence of cholera, Haiti, 2011.

A cholera outbreak began in Haiti during October, 2010. Spatiotemporal patterns of household-level cholera in Ouest Department showed that the initial clusters tended to follow major roadways; subsequent clusters occurred further inland. Our data highlight transmission pathway complexities and the need for case and household-level analysis to understand disease spread and optimize interventions.

Characterization of Diarrheagenic Escherichia coli and Salmonella enterica from produce in the Chobe District of Botswana.

Diarrheal disease is a leading cause of death in children in low- and moderate-income countries. Fresh produce, including fruits and vegetables, may harbor diarrheal disease-causing bacteria including strains of Salmonella enterica and Escherichia coli. This study aimed to determine prevalence and antibiotic resistance profiles of S. enterica and E. coli isolated from produce samples (n=207) obtained from retail markets northern Botswana in Chobe District of Botswana in 2022. Samples were enriched in the appropriate selective media: Brilliant Green Bile Broth for E. coli and Rappaport Vassiliadis Broth for S. enterica. E. coli were confirmed by PCR detecting the phoA gene, and classified as potentially pathogenic through screening for the eae, stx, and stx2 and estIb genes. S. enterica isolates were confirmed using invA primers. Isolates were evaluated for resistance to ampicillin, amoxicillin-clavulanic acid, chloramphenicol, cefotaxime, doxycycline, streptomycin, sulfamethoxazole and tetracycline antibiotic using the Kirby-Bauer Disk Diffusion method. E. coli was isolated from 15.5% of produce samples (n=207). The gene eae was detected from 1.5% of samples, while stx1, stx2, and estIb were not detected. Resistance to one or more antibiotics was common (72%) with the majority of the resistant E. coli (n=32) isolated from fruits (22%) and greens (18%) compared to other types of vegetables. Multidrug resistance (MDR, resistant to 3 or more antibiotics) was identified in 18% of samples. S. enterica was isolated from 3.4% of produce samples (7, n=207). Resistance was uncommon among the S. enterica isolates (1/7). Overall prevalence of diarrheagenic S. enterica and E. coli was low, however their presence and that of MDR E. coli in foods commonly consumed raw increases the risk to vulnerable populations. Strategies to reduce contamination of fresh produce and public education on washing and cooking some types of produce may be useful to reduce disease.

Long-term stability of clinical-grade lentiviral vectors for cell therapy.

The use of lentiviral vectors in cell and gene therapy is steadily increasing, both in commercial and investigational therapies. Although existing data increasingly support the usefulness and safety of clinical-grade lentiviral vectors used in cell manufacturing, comprehensive studies specifically addressing their long-term stability are currently lacking. This is significant considering the high cost of producing and testing GMP-grade vectors, the limited number of production facilities, and lengthy queue for production slots. Therefore, an extended shelf life is a critical attribute to justify the investment in large vector lots for investigational cell therapies. This study offers a thorough examination of essential stability attributes, including vector titer, transduction efficiency, and potency for a series of clinical-grade vector lots, each assessed at a minimum of 36 months following their date of manufacture. The 13 vector lots included in this study were used for cell product manufacturing in 16 different clinical trials, and at the time of the analysis had a maximum storage time at -80°C of up to 8 years. The results emphasize the long-term durability and efficacy of GMP-grade lentiviral vectors for use in ex vivo cell therapy manufacturing.

Survival of Inoculated Campylobacter jejuni and Escherichia coli O157:H7 on Kale During Refrigerated Storage.

Campylobacter and pathogenic Escherichia coliillnesses have been attributed to the consumption of fresh produce. The leafy green, kale, is increasingly consumed raw. In comparison to other leafy greens, kale has a longer shelf-life. Due to the extended shelf-life of kale, it is warranted to examine the survival of pathogenic Campylobacter jejuni and E. coli O157:H7 inoculated on the surface of kale stored in a controlled environment at 4 ± 1.4°C, and average humidity of 95 ± 1.9% over a 23-day period. At predetermined time points (days 0, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21), inoculated kale was destructively sampled and the surviving bacteria determined by serial dilution and plating onto Tryptic soy agar, Charcoal cefoperozone deoxycholate agar, and Eosin methylene blue for total aerobic bacteria, C. jejuni, and E. coli O157:H7, respectively. Enrichment and PCR were used for detection when pathogens were not detected using serial dilution and plating. Aerobic heterotrophic bacteria increased over the 23-day period, in contrast, significant declines in the inoculated pathogens were observed. Inoculated E. coli O157:H7 survived longer on kale (up to 19 d); in comparison, C. jejuni was undetectable by day 13 using enrichment and PCR or plating. In conclusion, C. jejuni and E. coli O157:H7 declined on fresh kale over time when held at refrigerated temperatures but were still detected during the majority of the time when the kale would likely still be considered edible by consumers.

Coursing hyenas and stalking lions: The potential for inter- and intraspecific interactions.

Resource partitioning promotes coexistence among guild members, and carnivores reduce interference competition through behavioral mechanisms that promote spatio-temporal separation. We analyzed sympatric lion and spotted hyena movements and activity patterns to ascertain the mechanisms facilitating their coexistence within semi-arid and wetland ecosystems. We identified recurrent high-use (revisitation) and extended stay (duration) areas within home ranges, as well as correlated movement-derived measures of inter- and intraspecific interactions with environmental variables. Spatial overlaps among lions and hyenas expanded during the wet season, and occurred at edges of home ranges, around water-points, along pathways between patches of high-use areas. Lions shared more of their home ranges with spotted hyenas in arid ecosystems, but shared more of their ranges with conspecifics in mesic environments. Despite shared space use, we found evidence for subtle temporal differences in the nocturnal movement and activity patterns between the two predators, suggesting a fine localized-scale avoidance strategy. Revisitation frequency and duration within home ranges were influenced by interspecific interactions, after land cover categories and diel cycles. Intraspecific interactions were also important for lions and, important for hyenas were moon illumination and ungulates attracted to former anthrax carcass sites in Etosha, with distance to water in Chobe/Linyanti. Recursion and duration according to locales of competitor probabilities were similar among female lions and both sexes of hyenas, but different for male lions. Our results suggest that lions and spotted hyenas mediate the potential for interference competition through subtle differences in temporal activity, fine-scale habitat use differentiation, and localized reactive-avoidance behaviors. These findings enhance our understanding of the potential effects of interspecific interactions among large carnivore space-use patterns within an apex predator system and show adaptability across heterogeneous and homogeneous environments. Future conservation plans should emphasize the importance of inter- and intraspecific competition within large carnivore communities, particularly moderating such effects within increasingly fragmented landscapes.

The Many Hosts of Mycobacteria 9 (MHM9): A conference report.

The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.

Non-invasive monitoring of glucocorticoid metabolites in banded mongooses (Mungos mungo) in response to physiological and biological challenges.

Free-ranging banded mongooses are infected by the novel pathogen, Mycobacterium mungi in northern Botswana. A reliable method for determining stress-related physiological responses in banded mongooses will increase our understanding of the stress response in M. mungi infection. Therefore, our aim was to examine the suitability of four enzyme immunoassays (EIAs) for monitoring adrenocortical endocrine function in captive and free-ranging banded mongooses based on fecal glucocorticoid metabolite (FGM) analysis. A conducted adrenocorticotropic hormone challenge revealed suitability of a valid measurement of FGM levels in banded mongoose feces for all four tested EIAs, with an 11-oxoetiocholanolone assay detecting 11,17-dioxoandrostanes (11,17-DOA) performing best. Subsequent analyses using only this EIA showed the expected decrease in FGM concentrations 48 h after administering dexamethasone sodium phosphate. Furthermore, captive mongooses showed higher FGM concentrations during reproductive activity, agonistic encounters and depredation events. Finally, a late-stage, tuberculosis-infected moribund mongoose in a free-ranging troop had a 54-fold elevation in FGM levels relative to the rest of the troop. Measurements of gastrointestinal transit times and FGM metabolism post-defecation indicate that the time delay of FGM excretion approximately corresponded with food transit time and that FGM metabolism is minimal up to 8h post-defecation. The ability to reliably assess adrenocortical endocrine function in banded mongoose now provides a solid basis for advancing our understanding of infectious disease and endocrinology in this species.

Urban landscapes increase dispersal, gene flow, and pathogen transmission potential in banded mongoose (Mungos mungo) in northern Botswana.

Disease transmission can be strongly influenced by the manner in which conspecifics are connected across a landscape and the effects of land use upon these dynamics. In northern Botswana, the territorial and group-living banded mongoose (Mungos mungo) lives across urban and natural landscapes and is infected with a novel Mycobacterium tuberculosis complex pathogen, M. mungi. Using microsatellite markers amplified from DNA derived from banded mongoose fecal and tissue samples (n = 168), we evaluated population genetic structure, individual dispersal, and gene flow for 12 troops. Genetic structure was detectable and moderately strong across groups (F ST = 0.086), with K = 7 being the best-supported number of genetic clusters. Indications of admixture in certain troops suggest formation of new groups through recent fusion events. Differentiation was higher for troops inhabiting natural areas (F ST = 0.102) than for troops in urban landscapes (F ST = 0.081). While this suggests increased levels of gene flow between urban-dwelling troops, the inclusion of a smaller number of study troops from natural land types may have influenced these findings. Of those individuals confirmed infected with M. mungi, the majority (73%, n = 11) were assigned to their natal group which is consistent with previous observations linking lower levels of dispersal with infection. Twenty-one probable dispersing individuals were identified, with all suspected migrants originating from troops within the urban landscape. Findings suggest that urbanized landscapes may increase gene flow and dispersal behavior with a concomitant increase in the risk of pathogen spread. As urban landscapes expand, there is an increasing need to understand how land use and pathogen infection may change wildlife behavior and disease transmission potential.

Novel Mycobacterium tuberculosis complex pathogen, M. mungi.

Seven outbreaks involving increasing numbers of banded mongoose troops and high death rates have been documented. We identified a Mycobacterium tuberculosis complex pathogen, M. mungi sp. nov., as the causative agent among banded mongooses that live near humans in Chobe District, Botswana. Host spectrum and transmission dynamics remain unknown.

Ensemble forecast and parameter inference of childhood diarrhea in Chobe District, Botswana.

Diarrheal disease is the second largest cause of mortality in children younger than 5, yet our ability to anticipate and prepare for outbreaks remains limited. Here, we develop and test an epidemiological forecast model for childhood diarrheal disease in Chobe District, Botswana. Our prediction system uses a compartmental susceptible-infected-recovered-susceptible (SIRS) model coupled with Bayesian data assimilation to infer relevant epidemiological parameter values and generate retrospective forecasts. Our model inferred two system parameters and accurately simulated weekly observed diarrhea cases from 2007-2017. Accurate retrospective forecasts for diarrhea outbreaks were generated up to six weeks before the predicted peak of the outbreak, and accuracy increased over the progression of the outbreak. Many forecasts generated by our model system were more accurate than predictions made using only historical data trends. Accurate real-time forecasts have the potential to increase local preparedness for coming outbreaks through improved resource allocation and healthcare worker distribution.

Anthropogenic landscapes increase Campylobacter jejuni infections in urbanizing banded mongoose (Mungos mungo): A one health approach.

BACKGROUND: Campylobacter is a common, but neglected foodborne-zoonotic pathogen, identified as a growing cause of foodborne disease worldwide. Wildlife and domestic animals are considered important reservoirs, but little is known about pathogen infection dynamics in free-ranging mammalian wildlife particularly in sub-Saharan Africa. In countries like Botswana, there is significant overlap between humans and wildlife, with the human population having one of the highest HIV infection rates in the world, increasing vulnerability to infection. METHODOLOGY/PRINCIPAL FINDINGS: We investigated Campylobacter occurrence in archived human fecal samples (children and adults, n = 122, 2011), feces from free-ranging banded mongooses (Mungos mungo, n = 201), surface water (n = 70), and river sediment samples (n = 81) collected in 2017 from the Chobe District, northern Botswana. Campylobacter spp. was widespread in humans (23.0%, 95% CI 13.9-35.4%), with infections dominantly associated with C. jejuni (82.1%, n = 28, 95% CI 55.1-94.5%). A small number of patients presented with asymptomatic infections (n = 6). While Campylobacter spp. was rare or absent in environmental samples, over half of sampled mongooses tested positive (56%, 95% CI 45.6-65.4%). Across the urban-wilderness continuum, we found significant differences in Campylobacter spp. detection associated with the type of den used by study mongooses. Mongooses utilizing man-made structures as den sites had significantly higher levels of C. jejuni infection (p = 0.019) than mongooses using natural dens. Conversely, mongooses using natural dens had overall higher levels of detection of Campylobacter at the genus level (p = 0.001). CONCLUSIONS: These results suggest that landscape features may have important influences on Campylobacter species exposure and transmission dynamics in wildlife. In particular, data suggest that human-modified landscapes may increase C. jejuni infection, a primarily human pathogen, in banded mongooses. Pathogen circulation and transmission in urbanizing wildlife reservoirs may increase human vulnerability to infection, findings that may have critical implications for both public and animal health in regions where people live in close proximity to wildlife.

Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats.

These experiments utilized an enzyme-based microelectrode selective for the second-by-second detection of extracellular glutamate to reveal the alpha 7-based nicotinic modulation of glutamate release in the prefrontal cortex (PFC) of freely moving rats. Rats received intracortical infusions of the nonselective nicotinic agonist nicotine (12.0 mM, 1.0 microg/0.4 microl) or the selective alpha 7 agonist choline (2.0 mM/0.4 microl). The selectivity of drug-induced glutamate release was assessed in subgroups of animals pretreated with the alpha 7 antagonist, alpha-bungarotoxin (alpha-BGT, 10 microM), or kynurenine (10 microM) the precursor of the astrocyte-derived, negative allosteric alpha 7 modulator kynurenic acid. Local administration of nicotine increased glutamate signals (maximum amplitude = 4.3 +/- 0.6 microM) that were cleared to baseline levels in 493 +/- 80 seconds. Pretreatment with alpha-BGT or kynurenine attenuated nicotine-induced glutamate by 61% and 60%, respectively. Local administration of choline also increased glutamate signals (maximum amplitude = 6.3 +/- 0.9 microM). In contrast to nicotine-evoked glutamate release, choline-evoked signals were cleared more quickly (28 +/- 6 seconds) and pretreatment with alpha-BGT or kynurenine completely blocked the stimulated glutamate release. Using a method that reveals the temporal dynamics of in vivo glutamate release and clearance, these data indicate a nicotinic modulation of cortical glutamate release that is both alpha 7- and non-alpha 7-mediated. Furthermore, these data may also provide a mechanism underlying the recent focus on alpha 7 full and partial agonists as therapeutic agents in the treatment of cortically mediated cognitive deficits in schizophrenia.

El Niño-Southern oscillation and under-5 diarrhea in Botswana.

Childhood diarrheal disease causes significant morbidity and mortality in low and middle-income countries, yet our ability to accurately predict diarrhea incidence remains limited. El Niño-Southern Oscillation (ENSO) has been shown to affect diarrhea dynamics in South America and Asia. However, understanding of its effects in sub-Saharan Africa, where the burden of under-5 diarrhea is high, remains inadequate. Here we investigate the connections between ENSO, local environmental conditions, and childhood diarrheal disease in Chobe District, Botswana. Our results demonstrate that La Niña conditions are associated with cooler temperatures, increased rainfall, and higher flooding in the Chobe region during the rainy season. In turn, La Niña conditions lagged 0-5 months are associated with higher than average incidence of under-5 diarrhea in the early rainy season. These findings demonstrate the potential use of ENSO as a long-lead prediction tool for childhood diarrhea in southern Africa.