Disentangling Microbial Mediators of Malnutrition: Modeling Environmental Enteric Dysfunction

Environmental enteric dysfunction (EED) (also referred to as environmental enteropathy) is a subclinical chronic intestinal disorder that is an emerging contributor to early childhood malnutrition. EED is common in resource-limited settings, and is postulated to consist of small intestinal injury, dysfunctional nutrient absorption, and chronic inflammation that results in impaired early child growth attainment. Although there is emerging interest in the hypothetical potential for chemical toxins in the environmental exposome to contribute to EED, the propensity of published data, and hence the focus of this review, implicates a critical role of environmental microbes. Early childhood malnutrition and EED are most prevalent in resource-limited settings where food is limited, and inadequate access to clean water and sanitation results in frequent gastrointestinal pathogen exposures. Even as overt diarrhea rates in these settings decline, silent enteric infections and faltering growth persist. Furthermore, beyond restricted physical growth, EED and/or enteric pathogens also associate with impaired oral vaccine responses, impaired cognitive development, and may even accelerate metabolic syndrome and its cardiovascular consequences. As these potentially costly long-term consequences of early childhood enteric infections increasingly are appreciated, novel therapeutic strategies that reverse damage resulting from nutritional deficiencies and microbial insults in the developing small intestine are needed. Given the inherent limitations in investigating how specific intestinal pathogens directly injure the small intestine in children, animal models provide an affordable and controlled opportunity to elucidate causal sequelae of specific enteric infections, to differentiate consequences of defined nutrient deprivation alone from co-incident enteropathogen insults, and to correlate the resulting gut pathologies with their functional impact during vulnerable early life windows

Impact of childhood malnutrition and intestinal microbiota on MDR infections

The global burden of infection from MDR organisms (MDROs) disproportionately affects children residing in low- and middle-income countries and those with increased healthcare exposure. These populations have high rates of malnutrition making them increasingly vulnerable to infection with intestinal-derived pathogens. Malnourished children experience increased incidence of intestinal carriage and invasive infection with intestinal-derived MDROs including ESBL- and carbapenemase-producing Enterobacterales. However, the relationship between malnutrition and MDRO infection remains to be clearly defined. Impairment in intestinal barrier function and innate and adaptive immunity in malnutrition increases the risk for infection with intestinal-derived pathogens, and there is an increasing appreciation of the role of the intestinal microbiota in this process. Current evidence from human studies and animal models suggests that diet and the intestinal microbiota influence each other to determine nutritional status, with important implications for infectious outcomes. These insights are crucial to developing microbiota-targeted strategies aimed at reversing the growing burden of MDRO infections in malnourished populations worldwide

Endemic Mycoses in Solid Organ Transplant Recipients

The endemic mycoses are a group of thermally dimorphic fungal pathogens occupying a specific geographic range. In North America, the chief endemic mycoses are histoplasmosis, coccidioidomycosis, and blastomycosis. Endemic fungi can cause serious infections in solid organ transplant recipients from primary infection, reactivation of latent disease, or donor-derived infection

Case report: Calcified neurocysticercus, perilesional edema, and histologic inflammation

Here, we present the second report of the histopathology of a Taenia solium calcification giving rise to perilesional edema. This has important implications, because if perilesional edema lesions are inflammatory in character, immunosuppressive or anti-inflammatory medications, not just antiepileptic drugs alone, may be useful to prevent or treat recurring episodes in such patients

Remote system for detection of low-levels of methane based on photonic crystal fibres and wavelength modulation spectroscopy

In this work we described an optical fibre sensing system for detecting low levels of methane. The properties of hollow-core photonic crystal fibres are explored to have a sensing head with favourable characteristics for gas sensing, particularly in what concerns intrinsic readout sensitivity and gas diffusion time in the sensing structure. The sensor interrogation was performed applying the Wavelength Modulation Spectroscopy technique, and a portable measurement unit was developed with performance suitable for remote detection of low levels of methane. This portable system has the capacity to simultaneously interrogate four remote photonic crystal fibre sensing heads. Copyright © 2009 J. P. Carvalho et al

Sulfonamides without trimethoprim in the treatment of Nocardia infections: A case report and literature review

Sulfonamides are recommended as part of first-line therapy for most Nocardia infections, with trimethoprim-sulfamethoxazole (TMP-SMX) considered the drug of choice for susceptible isolates. However, in the case of central nervous system, disseminated disease, and other serious Nocardia infections, TMP-SMX should not be used as monotherapy. The preferred treatment for a patient unable to take TMP-SMX because of allergy or intolerance remains uncertain. Prior to the availability of TMP-SMX in 1973, other sulfonamides were mainstays of treatment. We describe a Nocardia infection successfully treated with sulfadiazine in a lung transplant recipient who could not tolerate TMP-SMX. A review of similar cases reported in the literature provides insight into the successful treatment of Nocardia infections with sulfonamide regimens not containing trimethoprim in transplant recipients and other immunocompromised hosts

Amixicile reduces severity of cryptosporidiosis but does not have in vitro activity against Cryptosporidium

Cryptosporidium species cause significant morbidity in malnourished children. Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ has diminished effectiveness during malnutrition. Here, we show that amixicile, a highly selective water-soluble derivative of NTZ diminishes Cryptosporidium infection severity in a malnourished mouse model despite a lack of direct anticryptosporidial activity. We suggest that amixicile, by tamping down anaerobes associated with intestinal inflammation, reverses weight loss and indirectly mitigates infection-associated pathology

High anti-cryptosporidium parvum igg seroprevalence in hiv-infected adults in limpopo, south africa

A seroepidemiological study was performed to determine the seroprevalence of Cryptosporidium in human immunodeficiency virus (HIV)-infected adults and local university students in the Limpopo Province, South Africa. Using a custom anti-C. parvum immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), the seroprevalence of Cryptosporidium was found to be significantly higher (75.3%; 146 of 193) in HIV-infected individuals compared with student volunteers (32.8%; 19 of 58) (P < 0.001). A more recent diagnosis of HIV was associated with anti-C. parvum IgG seropositivity, as was lower weight among HIV-infected women. This is the first seroepidemiologic study of Cryptosporidium in rural South Africa, and it shows high endemicity among the HIV-infected population. In addition to raising the possibility of significant Cryptosporidium-related morbidities, this finding reveals that in Limpopo and perhaps in other low-income, rural populations, interrupting waterborne pathogen transmission will require strategies effective against environmentally hardy parasites such as Cryptosporidium

"Barriers" to Child Development and Human Potential: The Case for Including the "Neglected Enteric Protozoa" (NEP) and Other Enteropathy-Associated Pathogens in the NTDs

The World Health Organization (WHO) has set forth ambitious efforts to control, and where possible, eliminate the neglected tropical diseases (NTDs) that contribute to poverty and ‘‘impair the ability of those infected to achieve their full potential, both developmentally and socioeconomically’’ [1,2]. This neglected disease initiative’s (NDI) purpose has been to close the existing poverty gap between individuals living in low/middle-income and high-income countries, and thus facilitate the achievement of the 2000 Millennium Developmental Goals [3]. The gap is still large. Yet, some marked achievements of the NDI, including coordinated administration of preventive chemotherapy to nearly 670 million children globally and the imminent elimination of dracunculiasis, give hope that the WHO’s NTD paradigm, a ‘‘five-pronged’’ approach of 1) preventive chemotherapy, 2) intensified case-management, 3) vector control, 4) provision of safe water, sanitation, and hygiene, and 5) veterinary public health, are proving beneficia

Persistent G. lamblia impairs growth in a murine malnutrition model

Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia-specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a "stunting" pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia-potentiated growth decrements