Background. Group A Beta-hemolytic Streptococcal (GAS) pharyngitis is the precipitating cause of rheumatic fever (RF) and rheumatic heart disease (RHD). Primary prevention of RF/RHD is accomplished ...via identification of and subsequent treatment of the organism that causes GAS, Streptococcus pyogenes, to eradicate it from the nasopharynx. However, without laboratory facilities for diagnosis, as is often the case in developing (middle and low income) nations, clinicians must rely on a non-laboratory diagnosis, thus making a determination of GAS positivity based on signs, symptoms, and other patient characteristics. Clinical prediction rules (CPRs) are used to make such clinical diagnoses. Unfortunately, due to the widely overlapping clinical presentations of GAS and non-GAS pharyngitides, good CPRs have been difficult to create, and though some function well in one setting, they often do not in other settings. Here we describe the variation in clinical presentation of GAS and non-GAS pharyngitis, conduct a multi-country evaluation of a promising rapid test for GAS diagnosis, and develop clinical prediction rules for use in various settings. Methods. The present study had two parts, a diagnostic study (Group A Beta-hemolytic Streptococcus Pharyngitis (GRASP)) and a treatment study (Treatment of Pharyngitis Study (TOPS)). Data from the GRASP study are used for the analyses described in this dissertation. The GRASP study was a prospective, descriptive, study of enrolled children in Brazil, Croatia, Egypt, and Latvia (and a pilot phase in India). Overall, 2,456 children were enrolled in the GRASP Study. Results. This dissertation consists of a literature review and three papers. The literature review provides a background on GAS related epidemiology, diagnostic tests, and clinical prediction. The first paper describes the variation in clinical presentation of GAS and non-GAS pharyngitis in children in developing nations. We found that the signs and symptoms vary across countries, for GAS and non-GAS cases. The relationship between a sign/symptom and GAS status is not steady across countries for most signs/symptoms. And, though the clinical presentation varies across countries, it is slightly less variable for cases of GAS pharyngitis. The second paper evaluates the diagnostic accuracy of a rapid antigen test for detecting GAS in children in the same countries. The test performed well in all countries, with diagnostic accuracy ranging from 84% to 91%; sensitivity ranging from 74.7% in Egypt to 91.8% in Croatia; and specificity of the test ranging from 88.3% in Latvia to 96.4% in Brazil. The third and final paper details the development of a novel clinical prediction rule for GAS, with the goal of replacing the currently used WHO recommended rule. (Abstract shortened by UMI.)
After the declaration of eradication of wild poliovirus type 2 in 2015, all countries using oral poliovirus vaccine (OPV) switched from using trivalent OPV (tOPV) (containing vaccine virus types 1, ...2, and 3) to bivalent OPV (bOPV) (containing types 1 and 3) in April 2016. Vaccine-derived polioviruses (VDPVs), strains that have diverged from the live vaccine virus during prolonged circulation, can emerge rarely in areas with inadequate OPV coverage and can cause outbreaks of paralysis. Before the global switch from tOPV to bOPV, many circulating VDPV (cVDPV) outbreaks identified globally were caused by type 2 cVDPV (cVDPV2). In October 2017, a VDPV2 isolate was detected from a sewage sample collected from one of four environmental surveillance sites in Banadir, Somalia.
With more than 5 million fatalities and close to 300 million reported cases, COVID-19 is the first documented pandemic due to a coronavirus that continues to be a major health challenge. Despite ...being rapid, uncontrollable, and highly infectious in its spread, it also created incentives for technology development and redefined public health needs and research agendas to fast-track innovations to be translated. Breakthroughs in computational biology peaked during the pandemic with renewed attention to making all cutting-edge technology deliver agents to combat the disease. The demand to develop effective treatments yielded surprising collaborations from previously segregated fields of science and technology. The long-standing pharmaceutical industry's aversion to repurposing existing drugs due to a lack of exponential financial gain was overrun by the health crisis and pressures created by front-line researchers and providers. Effective vaccine development even at an unprecedented pace took more than a year to develop and commence trials. Now the emergence of variants and waning protections during the booster shots is resulting in breakthrough infections that continue to strain health care systems. As of now, every protein of SARS-CoV-2 has been structurally characterized and related host pathways have been extensively mapped out. The research community has addressed the druggability of a multitude of possible targets. This has been made possible due to existing technology for virtual computer-assisted drug development as well as new tools and technologies such as artificial intelligence to deliver new leads. Here in this article, we are discussing advances in the drug discovery field related to target-based drug discovery and exploring the implications of known target-specific agents on COVID-19 therapeutic management. The current scenario calls for more personalized medicine efforts and stratifying patient populations early on for their need for different combinations of prognosis-specific therapeutics. We intend to highlight target hotspots and their potential agents, with the ultimate goal of using rational design of new therapeutics to not only end this pandemic but also uncover a generalizable platform for use in future pandemics.
Scedosporium, a widespread filamentous fungus found in diverse environments, has experienced a rise in cases due to escalating malignancies and chronic immunosuppression. Clinical manifestations span ...mycetoma, airway involvement, and various infections, with osteomyelitis being a notable complication. We present a case of a 77-year-old female initially displaying cutaneous Scedosporium signs, which progressed to osteomyelitis. The patient, with a history of trauma, chronic low dose steroid use, and underlying conditions, presented with a foot injury caused by her dog. Despite initial management, worsening symptoms led to the identification of Scedosporium. A comprehensive approach involving debridement, antimicrobial therapy, and reduction of immunosuppression resulted in clinical improvement. The rarity of zoonotic transmission, diagnostic challenges, and antifungal efficacy are also discussed. The patient's positive trajectory emphasizes early diagnosis, targeted treatment, and vigilance in managing immunosuppression. An adaptable treatment protocol is proposed based on risk factors. Considering the rising opportunistic fungal infections and delayed culture results, initiating empirical antifungals based on clinical judgment and regional prevalence is vital for favorable outcomes.
Mycobacterium nebraskense is a rare, slow growing nontuberculous mycobacterium species with limited documented cases. This systematic review aims to comprehensively analyze the clinical ...characteristics, presentation, and management of M. nebraskense infections by analyzing the available literature, including a newly reported case that we present in this article.
A comprehensive search was conducted using PubMed and Google Scholar to identify relevant cases up to October 2023. Only seven reported cases were found, highlighting the scarcity of information on this pathogen.
Our analysis revealed several key findings. First, gender disparities were observed, with females being more susceptible to M. nebraskense infections. Additionally, a significant portion of patients presented with asymptomatic infections. Most affected individuals were over the age of 60, emphasizing potential age-related susceptibility. Comorbidity profiles varied widely among cases, and patients with preexisting lung comorbidities were at an increased risk of infection. The decision to treat or observe depended on clinical presentation, with even immunosuppressed individuals not always requiring treatment. Regarding treatment, we proposed an empirical approach with amikacin, clarithromycin, or rifabutin, considering the reported resistance to doxycycline and minocycline. Combination therapy was commonly employed to minimize resistance development, consistent with mycobacterial infection management.
This study underscores the need for further research to validate these findings and enhance our understanding of M. nebraskense infections. As limited data are available, this review aims to provide valuable insights into a rare and emerging pathogen to guide clinical practice and future research endeavors.
The last confirmed wild poliovirus (WPV) case in Democratic Republic of the Congo (DRC) had paralysis onset in December 2011 (1). DRC has had cases of vaccine-derived polioviruses (VDPVs) documented ...since 2004 (Table 1) (1-6). After an outbreak of 30 circulating VDPV type 2 (cVDPV2) cases during 2011-2012, only five VDPV2 cases were reported during 2013-2016 (Table 1) (1-6). VDPVs can emerge from oral poliovirus vaccine (OPV types 1, 2, or 3; Sabin) polioviruses that have genetically mutated resulting in reversion to neurovirulence. This process occurs during extensive person-to-person transmission in populations with low immunity or after extended replication in the intestines of immune-deficient persons following vaccination (1-6). During 2017 (as of March 8, 2018), 25 VDPV cases were reported in three provinces in DRC: in Tanganyika province, an emergence with one VDPV2 case (pending final classification) in Kabalo health zone and an emergence with one ambiguous VDPV type 1 (aVDPV1) case in Ankoro health zone; in Maniema province, an emergence with two cVDPV2 cases; and in Haut Lomami province, an emergence with 20 cVDPV2 cases that originated in Haut Lomami province and later spread to Tanganyika province (hereafter referred to as the Haut Lomami outbreak area) and an emergence with one aVDPV type 2 (aVDPV2) case in Lwamba health zone (Table 1) (Figure) (6). Outbreak response supplementary immunization activities (SIAs) were conducted during June-December 2017 (Table 2) (6). Because of limitations in surveillance and suboptimal SIA quality and geographic scope, cVDPV2 circulation is likely continuing in 2018, requiring additional SIAs. DRC health officials and Global Polio Eradication Initiative (GPEI) partners are increasing human and financial resources to improve all aspects of outbreak response.
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