Re-emergence of polio in Pakistan: Can the nation achieve the WPV1 eradication goal?

Background and Aims: Poliomyelitis is an acute neurologic condition that causes muscle weakness, permanent flaccid paralysis, and even death. The world has seen a drastic fall in the number of poliovirus cases owing to effective immunization programs and preventive measures. Pakistan and Afghanistan still remain the two endemic countries for poliovirus, particularly, the WPV1 strain. Global Polio Eradication Initiative (GPEI) has set a target to eradicate all WPV1 cases by the end of 2023. However, the re-emergence of WPV1 cases has posed a serious setback for the achievement of this target. This article aims to discuss the public health challenges that contribute to resurgence of poliovirus cases. Methods: A comprehensive literature search was conducted using various databases including Cochrane, Google Scholar, PubMed, Science Direct, MEDLINE. Only articles written in English were considered. All the articles reporting the incidence of poliovirus and WPV1 cases in Pakistan, surveillance data and global context of poliovirus outbreak were evaluated to write this correspondence. In addition, references from the selected articles were also examined to ensure a comprehensive review of the literature. Results: This article highlights the factors contributing to the re-emergence of WPV1 cases in Pakistan. Low vaccine coverage, attacks on frontline polio health workers, misinformation, and reluctance to vaccine acceptance pose a daunting challenge for polio eradication. Further, gaps in AFP surveillance and sensitivity may underestimate the true extent of the emerging genetic clusters. The Covid-19 pandemic and subsequent flooding in the affected area have further worsened the underdeveloped public health infrastructure. Conclusion: Despite the challenges, the country has observed a significant decline in the number of cases in the past 2 years. It is high time to capitalize on the decrease in WPV1 cases by intensifying the efforts to mitigate and limit the spread of the disease.

The effect of race on clinical presentation and outcomes in neurosarcoidosis.

BACKGROUND: Nervous system is affected in 25% of patients with sarcoidosis. Current literature is largely limited to case reports with disproportionate Caucasian population. We aim to evaluate differences in presentation, management and outcomes by race in neurosarcoidosis. METHODS: Clinical and demographic data on consecutive patients fulfilling Zajicek criteria for neurosarcoidosis from 1995 to 2016 at Henry Ford Hospital were extracted. Disparities in clinical presentation, laboratory values, radiological features, treatment and outcomes, were compared between two groups: African Americans (AA) and non-AA using chi-squared tests, two sample t-test for age and Wilcoxon two sample tests. RESULTS: A total of 118 patients were included, of which 58% were female and 73% were AA. The diagnosis of neurosarcoidosis was noted to be definite (25%), probable (64%) and possible (11%). AA patients had a significantly higher rate of elevated erythrocyte sedimentation rate (62% vs 24%, P = .005) and had lower resolution of abnormalities on follow-up imaging (14% vs 41%, P = .017). There was no difference in disability on follow-up (25% vs 33%, P = .43) or mortality (13% vs 9%, P = .6). CONCLUSIONS: There were no differences in presentation, management and outcomes by race. Discordance in the clinical and radiological data by race has clinical implications and needs further investigation.

Cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians. CASE DESCRIPTION: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed tomography scan revealed multiple cerebral abscesses. These abscesses were excised. The microbiological specimen was determined to be positive for Aspergillus fumigatus. His tracheal aspirate was positive for Mycobacterium tuberculosis polymerase chain reaction assay. Further work-up confirmed the diagnosis of CGD in the child. CONCLUSION: This report describes the course of the patient's illness in order to highlight the challenges associated with the management of these infections. We also aim to stress on the importance of pathological diagnosis before starting a therapy.

Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines.

In patients with malignancy, the major barrier to achieving complete response is emergence of resistance to current chemotherapeutic agents. One of the major mechanisms by which tumour cells become resistant to therapies is by altering cellular drug targets through mutations and/or deletions. Resistance by this mechanism is achieved more easily if the drug has limited cellular targets and/or processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) targets six proteins that are required for cancer cell survival and proliferation, it is highly unlikely for cancer cells to develop resistance to this toxin. We assessed ExoT's cytotoxicity against multiple invasive and highly resistant tumour cell lines in order to evaluate its potential as a chemotherapeutic agent. Our data demonstrated that ExoT induced potent cytotoxicity in all tumour cell lines that we examined. Collectively, our data highlighted the potential of ExoT as a possible chemotherapeutic candidate for the treatment of cancer.

Chronic alcohol exposure renders epithelial cells vulnerable to bacterial infection.

Despite two centuries of reports linking alcohol consumption with enhanced susceptibility to bacterial infections and in particular gut-derived bacteria, there have been no studies or model systems to assess the impact of long-term alcohol exposure on the ability of the epithelial barrier to withstand bacterial infection. It is well established that acute alcohol exposure leads to reduction in tight and adherens junctions, which in turn leads to increases in epithelial cellular permeability to bacterial products, leading to endotoxemia and a variety of deleterious effects in both rodents and human. We hypothesized that reduced fortification at junctional structures should also reduce the epithelial barrier's capacity to maintain its integrity in the face of bacterial challenge thus rendering epithelial cells more vulnerable to infection. In this study, we established a cell-culture based model system for long-term alcohol exposure to assess the impact of chronic alcohol exposure on the ability of Caco-2 intestinal epithelial cells to withstand infection when facing pathogenic bacteria under the intact or wounded conditions. We report that daily treatment with 0.2% ethanol for two months rendered Caco-2 cells far more susceptible to wound damage and cytotoxicity caused by most but not all bacterial pathogens tested in our studies. Consistent with acute alcohol exposure, long-term ethanol exposure also adversely impacted tight junction structures, but in contrast, it did not affect the adherens junction. Finally, alcohol-treated cells partially regained their ability to withstand infection when ethanol treatment was ceased for two weeks, indicating that alcohol's deleterious effects on cells may be reversible.

A novel human antimicrobial factor targets Pseudomonas aeruginosa through its type III secretion system.

Pseudomonas aeruginosa is an important opportunistic bacterial pathogen. Despite its metabolic and virulence versatility, it has not been shown to infect articular joints, which are areas that are rarely infected with bacteria in general. We hypothesized that articular joints possess antimicrobial activity that limits bacterial survival in these environments. We report that cartilages secrete a novel antimicrobial factor, henceforth referred to as the cartilage-associated antimicrobial factor (CA-AMF), with potent antimicrobial activity. Importantly, CA-AMF exhibited significantly more antimicrobial activity against P. aeruginosa strains with a functional type III secretion system (T3SS). We propose that CA-AMF represents a new class of human antimicrobial factors in innate immunity, one which has evolved to selectively target pathogenic bacteria among the beneficial and commensal microflora. The T3SS is the first example, to the best of our knowledge, of a pathogen-specific molecular target in this antimicrobial defence system.