METHODS: This is an extensive literature review of published articles on IPD in selected developing countries from East Asia, South Asia, Middle East, sub-Saharan Africa, and Latin America. We reviewed all the articles retrieved from the knowledge bases that were published between the years 2000 and 2010.
RESULTS: After applying the inclusion, exclusion, and quality criteria, the comprehensive review of the literature yielded 10 articles with data for pneumococcal meningitis, septicemia/bacteremia, and pneumonia. These selected articles were from 10 developing countries from five different regions. Out of the 10 selected articles, 8 have a detailed discussion on IPD, one of them has s detailed discussion on bacteremia and meningitis, and another one has discussed pneumococcal bacteremia. Out of these 10 articles, only 5 articles discussed the case-fatality ratio (CFR). In our article review, the incidence of IPD ranged from less than 5/100,000 to 416/100,000 population and the CFR ranged from 12.2% to 80% in the developing countries.
CONCLUSIONS: The review demonstrated that the clinical burden of IPD was high in the developing countries. The incidence of IPD and CFR varies from region to region and from country to country. The IPD burden was highest in sub-Saharan African countries followed by South Asian countries. The CFR was low in high-income countries than in low-income countries.
METHODS: We report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.
RESULTS: One intriguing disease phenotype of this new model is the development of characteristic "White-Jade" patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host's immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.
CONCLUSIONS: In this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.
OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.
RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.
CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.