Seasonality of cryptosporidiosis: A meta-analysis approach

Objectives

We developed methodology for and conducted a meta-analysis to examine how seasonal patterns of cryptosporidiosis, a primarily waterborne diarrheal illness, relate to precipitation and temperature fluctuations worldwide.

Methods

Monthly cryptosporidiosis data were abstracted from 61 published epidemiological studies that cover various climate regions based on the Köppen Climate Classification. Outcome data were supplemented with monthly aggregated ambient temperature and precipitation for each study location. We applied a linear mixed-effect model to relate the monthly normalized cryptosporidiosis incidence with normalized location-specific temperature and precipitation data. We also conducted a sub-analysis of associations between the Normalized Difference Vegetation Index (NDVI), a remote sensing measure for the combined effect of temperature and precipitation on vegetation, and cryptosporidiosis in Sub-Saharan Africa.

Results

Overall, and after adjusting for distance from the equator, increases in temperature and precipitation predict an increase in cryptosporidiosis; the strengths of relationship vary by climate subcategory. In moist tropical locations, precipitation is a strong seasonal driver for cryptosporidiosis whereas temperature is in mid-latitude and temperate climates. When assessing lagged relationships, temperature and precipitation remain strong predictors. In Sub-Saharan Africa, after adjusting for distance from the equator, low NDVI values are predictive of an increase in cryptosporidiosis in the following month.

Discussion

In this study we propose novel methodology to assess relationships between disease outcomes and meteorological data on a global scale. Our findings demonstrate that while climatic conditions typically define a pathogen habitat area, meteorological factors affect timing and intensity of seasonal outbreaks. Therefore, meteorological forecasts can be utilized to develop focused prevention programs for waterborne cryptosporidiosis.     

The effect of altitude on dosing and response to erythropoietin in ESRD

For poorly understood reasons, patients with end-stage renal disease (ESRD) differ substantially in their response to treatment with recombinant erythropoietin (EPO). Because hypoxia influences many of the biologic pathways involved in erythropoiesis, the altitude at which a patient lives may affect the dose-response relationship of EPO. In this retrospective cohort study, clinical data from 341,737 incident hemodialysis patients registered in the U.S. Renal Data System were combined with elevation data from the U.S. Geological Survey to address this question. Higher altitude was associated with smaller EPO doses and higher hematocrit levels. For example, compared with patients at sea level, patients living above 6000 ft received 19% less EPO (12.9 versus 15.9 thousand units/wk) but had hematocrit levels 1.1 points higher (35.7% versus 34.6%). These associations were found within subgroups defined by sex, race, age, calendar time, cause of ESRD, and dialysis center profit status, and persisted after adjustment for various potential confounding factors. Furthermore, resistance to EPO decreased with elevation. Our results suggest that ESRD patients living at high altitude either increase endogenous EPO production or respond better to endogenous and exogenous EPO.     

Visceral and post-Kala-Azar dermal leishmaniasis isolates show significant difference in their in vitro drug susceptibility pattern

Visceral leishmaniasis (VL) remains a major health problem in old world, and India accounts for half of the world burden. The widespread emergence of resistance to standard drug in India poses a major obstacle in the control of leishmaniasis. Post-Kala-Azar dermal leishmaniasis (PKDL) is considered as main source of drug resistance. Experimental data indicate that resistance against newer drugs is also imminent. Therefore, in vitro studies were carried out to test minimum parasiticidal concentration of five conventional and newly introduced anti-leishmanial drugs against 20 field isolates of Leishmania donovani obtained from visceral and post-Kala-Azar dermal leishmaniasis patients of India. Study revealed wide range of variation in minimum inhibitory concentration of sodium antimony gluconate (SAG). PKDL isolates displayed significantly lower susceptibility to SAG and miltefosine than VL isolates with P value of 0.0006 and 0.0243, respectively. All clinical isolates had higher IC₅₀ value for paromomycin and miltefosine as compared to reference strain indicating their vulnerability to develop unresponsiveness. However, isolates were uniformly susceptible to pentamidine and amphotericin B. The results of gene expression analysis of AQP1 were largely in agreement with phenotypic drug sensitivity results. Interestingly, significant down-regulation of AQP1 was observed in PKDL isolates as compared to VL isolates indicating their increased propensity for drug unresponsiveness. However, no significant difference in mRNA expression of LdMT and LdRos3 gene was found for two groups. The present study unravels valuable baseline scientific data showing variation in the drug susceptibility pattern in the L. donovani isolates. The information might have impact on the management and control of Indian visceral leishmaniasis.     

Can dehydroepiandrostenedione (DHEA) target PRL-3 to prevent colon cancer metastasis?

Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients. Metastasis caused by CRC is mainly responsible for this cancer-related deaths. Despite recent advancements in the treatment methods, prognosis remains poor. Therefore, effective treatment strategies need to be designed for successful management of this disease. Dehydroepiandrostenedione (DHEA), a 17-ketosteroid hormone produced by adrenal glands, gonads and including gastrointestinal tract is required for several physiological processes. Deregulation of DHEA levels leads to various disease conditions including cancer. In fact, several experimental studies strongly suggest that DHEA could be used as a chemopreventive agent against colon cancer. Prenlyation of certain membrane proteins such as phosphatase of regenerating liver-3 (PRL-3) is crucial for metastatic progression of colon cancer cells. The ability of DHEA to target prenylation pathway could be utilized to inhibit PRL-3 prenylation for successful prevention of CRC metastases. As DHEA is a widely consumed drug for various ailments, incorporation of DHEA in the treatment regimen may be beneficial to prevent or delay the occurrence of metastasis resulting from CRC.     

Symptoms of psychological distress reported by women from indigenous communities in South India: implications for methodology and future studies

Archives of Women's Mental Health - ‘Indigenous peoples’ across the globe suffer a disproportionate burden of mental illness. However, this burden is not fully explored in India...