Summary Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated ...global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.
The protozoan parasite Cryptosporidium infects all major vertebrate groups and causes significant diarrhea in humans, with a spectrum of diseases ranging from asymptomatic to life-threatening. ...Children and immunodeficient individuals are disproportionately affected, especially in developing countries, where cryptosporidiosis contributes substantially to morbidity and mortality in preschool-age children. Despite the enormous disease burden from cryptosporidiosis, no antiprotozoal agent or vaccine exists for effective treatment or prevention. Cryptosporidiosis involving the respiratory tract has been described for avian species and mammals, including immunocompromised humans. Recent evidence indicates that respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions, in addition to the more recognized fecal-oral route. It is postulated that transmission of Cryptosporidium oocysts may occur by inhalation of aerosolized droplets or by contact with fomites contaminated by coughing. Delineating the role of the respiratory tract in disease transmission may provide necessary evidence to establish further guidelines for prevention of cryptosporidiosis.
Some agricultural practices, such as irrigation, have the potential to buffer seasonal dietary gaps and through increased production and consumption improve diets, particularly of the rural poor ...relying on subsistence farming but also for rural and urban households purchasing irrigated produce on local markets. The study aimed to evaluate the effect of seasonality and irrigation on women's diet in rural Ethiopia. Using a longitudinal study design, three rounds of surveys were conducted among women of reproductive age (15–49 years). Data on socioeconomic status, food consumption and haemoglobin concentration was collected. Energy and nutrient intakes were estimated using an interviewer‐administered multiple‐pass 24‐h recall. Women's dietary diversity score (WDDS), the proportion of women meeting the minimum dietary diversity for women (MDDW), haemoglobin concentration, the prevalence of anaemia and energy and nutrients intakes were compared between irrigators and nonirrigators and by season. Associations between MDDW/WDDS and irrigation status were assessed using fixed‐effect models, after adjusting for covariates. WDDS was low (3–4 out of 10 food groups) and exhibited high seasonal variability (p < 0.05). Diets were predominantly cereal‐based, with little consumption of nutrient‐dense foods like fruits and animal source foods. High seasonal variability in energy, protein, vitamin C, calcium, iron and zinc intakes were observed (p < 0.01). Irrigators were more likely to meet the MDDW than women from non‐irrigating households (p < 0.05). No cases of malaria were reported from the three rounds of screening. There is a high seasonal variation in women's diet, but this could be partly offset by irrigation practices.
Key message
Women's dietary diversity was low and exhibited high seasonal variation.
The associations between season and diets were mediated by irrigation.
Higher energy intakes were observed among women from households practising irrigation.
High seasonal variability in energy, protein, vitamin C, calcium, iron and zinc intakes were observed. The high seasonal variation in women's diet could be partly offset by irrigation practices.
Poor nutritional status in pregnancy expressed as low mid-upper arm circumference (MUAC) is associated with low birth weight. The study aims were to assess the nutritional status of pregnant ...Ethiopian women using MUAC and examine association with nutrition-specific and nutrition-sensitive factors, using baseline data of a prospective longitudinal observational birth cohort study conducted in three rural districts in the Oromia region of Ethiopia. Recruitment into the cohort was rolling over a period of nine months, and the data used for this analysis were collected while the women were between 12-32 weeks of gestation. Detailed household socio-demographics, agricultural production, women's health, morbidity and diets, with weights, heights and MUAC, and anemia prevalence (HemoCue) were collected. The prevalence of low MUAC (< 23 cm) was 41%. Controlling for location and clustering, wealth quintile (OR = 0.88, CI = 0.82 to 0.96, p<0.01) was associated with decreased risk of low MUAC, while trimester (OR = 1.31, CI = 1.16 to 1.48, p<0.001) was associated with increased risk of low MUAC. The only significant factor amenable to nutrition-specific interventions was altitude-adjusted anemia, which was associated with increased risk of low MUAC (OR = 1.28, CI = 1.09 to 1.49, p<0.01). Significant factors amenable to nutrition-sensitive factors and associated with higher odds of low MUAC were household food insecurity (OR = 1.04, CI = 1.02 to 1.06, p<0.001), distance to the clinic in minutes (OR = 1.01, CI = 1.0 to 1.01, p<0.0001) and season of recruitment (lean versus non lean) (OR = 1.30, CI = 1.10 to 1.54, p<0.01). Literacy (OR = 0.85, CI = 0.74 to 0.98, p<0.05) and numeracy (OR = 0.75, CI = 0.62 to 0.91, p<0.01) were also significantly associated with lower odds of low MUAC. Poor nutritional status in pregnancy expressed as percent with low MUAC was high in Ethiopian women. It was associated with several nutrition-specific and -sensitive factors indicating the importance of multisectoral actions in improving outcomes within the first 1000 days.
To determine the clinical manifestations and outcome of shigellosis among children infected with different species of Shigella.
We identified all patients <15 years infected with Shigella admitted to ...the icddr, b Dhaka hospital during one year. Study staff reviewed admission records and repeated the physical examinations and history of patients daily.
Of 792 children with shigellosis 63% were infected with S. flexneri, 20% with S. dysenteriae type 1, 10% with S. boydii, 4% with S. sonnei, and 3% with S. dysenteriae types 2-10. Children infected with S. dysenteriae type 1, when compared to children infected with other species, were significantly (P<0.05) more likely to have severe gastrointestinal manifestations: grossly bloody stools (78% vs. 33%), more stools in the 24 h before admission (median 25 vs. 11), and rectal prolapse (52% vs. 15%)--and extra-intestinal manifestations--leukemoid reaction (22% vs. 2%), hemolytic-uremic syndrome (8% vs. 1%), severe hyponatremia (58% vs. 26%) and neurologic abnormalities (24% vs. 16%). The overall fatality rate was 10% and did not differ significantly by species. In a multiple regression analysis young age, malnutrition, hyponatremia, lesser stool frequency, documented seizure, and unconsciousness were predictive of death.
Both severe intestinal disease and extra-intestinal manifestations of shigellosis occur with infection by any of the four species of Shigella, but are most common with S. dysenteriae type 1. Among these inpatient children, the risk of death was high with infection of any of the four Shigella species.
Respiratory cryptosporidiosis is thought to be a rare, end-stage complication of HIV. Few studies have systematically examined the frequency of such infection in adults. Sputum specimens submitted ...for tuberculosis (TB) testing at Mulago Hospital, Uganda, were anonymously retested for
using real-time polymerase chain reaction (PCR). Visual confirmation using immunofluorescence confocal microscopy was performed for a subset of PCR-positive samples. Of 824 sputum samples tested, 24 (2.9%) were
positive. Prevalence in sputum ranged between 0% and 10% in each month of the study and exceeded TB prevalence in some months. In this referral population, respiratory
prevalence was lower in people with HIV (1.3% versus 4.4% without HIV,
= 0.028) and higher in those with TB (6.8% versus 2.6% without TB,
= 0.086). The weak association between respiratory
infection and TB persisted after controlling for HIV (odds ratio = 3.2, 95% confidence interval: 0.9, 11.8;
= 0.080). This is the first study to document adult respiratory tract cryptosporidiosis in a referral population with presumed TB. These findings 1) confirm that
respiratory infection occurs in HIV-negative and -positive adults; 2) suggest there is potential for
to be disseminated or transmitted by coughing or expectoration; and 3) identify possible synergy between
and TB in the respiratory tract.
The role of dogs and cats in human cryptosporidiosis has been the focus of much attention. Studies in which genotyping of Cryptospiridium oocysts in feces of dogs and cats have been successful and ...have demonstrated that most infections in these animals are caused by host-specific C. canis and C. felis , respectively. Most human cases of cryptosporidiosis are associated with C. hominis and C. parvum ; C. canis and C. felis are responsible for only a small number of cases. Thus, molecular epidemiologic studies support the contention that the risk of zoonotic transmission of Cryptosporidium spp. from pet cats and dogs is low. Veterinarians can inform their clients of this minimal risk, but nevertheless advise them to minimize contact with pet cat and dog feces.
KEAP1 is the key regulator of the NRF2-mediated cytoprotective response, and increasingly recognized as a target for diseases involving oxidative stress. Pharmacological intervention has focused on ...molecules that decrease NRF2-ubiquitination through covalent modification of KEAP1 cysteine residues, but such electrophilic compounds lack selectivity and may be associated with off-target toxicity. We report here the first use of a fragment-based approach to directly target the KEAP1 Kelch–NRF2 interaction. X-ray crystallographic screening identified three distinct “hot-spots” for fragment binding within the NRF2 binding pocket of KEAP1, allowing progression of a weak fragment hit to molecules with nanomolar affinity for KEAP1 while maintaining drug-like properties. This work resulted in a promising lead compound which exhibits tight and selective binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in vivo models, thereby providing a high quality chemical probe to explore the therapeutic potential of disrupting the KEAP1–NRF2 interaction.
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