Sepsis is currently a major problem and challenge facing the medical community. With rapid development and progress of modern medicine, researchers have put more and more attention on sepsis; meanwhile, the morbidity and mortality of sepsis remains high despite great efforts from experts in various fields. According to updated guidelines, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Infection is the initial step of sepsis progression, and development from infection to sepsis is a complex pathophysiological process, including pathogen invasion, cytokine release, capillary leakage, microcirculation dysfunction, etc. which finally leads to organ metabolic disorders and functional failure. According to the latest recommended international guidelines of Sepsis 3.0, the presence of infection and SOFA score ≥ 2 are considered as the diagnostic criteria for sepsis, and the “rescue” measures mainly focus on reversal of organ dysfunction. However, despite nearly two decades of efforts, the “Save Sepsis Campaign” has not achieved satisfactory results. Emergency medicine is the frontier subject of acute and severe illness which treats patients with acute infections at the earliest. If at this stage, physicians can predict the possibility of sepsis progression from demographic characteristics, localize the pathogen and infection, detect the inflammatory storms by tests of cytokines and evaluate the severity of the infection with more effective clinical scoring system, and then take effective measures to prevent infection from developing into sepsis in high-risk patients, the morbidity and mortality of sepsis in patients with acute infection will be greatly reduced. Based on this situation, Chinese emergency medicine experts proposed the concept of “preventing and blocking” sepsis, and launched the nationwide “Preventing Sepsis Campaign in China (PSCC)” nationwide. The main concept is summarized as “three early and two reduces” which includes early detection, early diagnosis and early intervention during the “pre-symptomatic” and “peri-septic” stage in order to reduce the incidence of sepsis and it proposed a new approach for diagnosis and treatment of acute severe infection. This consensus is jointly advocated, discussed and written by four academic associations in the field of emergency medicine and five scholarly publishing organizations. More than 40 experts from fields of emergency medicine, critical care medicine, infectious diseases, pharmacy and laboratory medicine have participated in several rounds of deliberation and finally reached consensus on the criteria of identifying patients with acute infection, taking anti-infective treatments, screening of high-risk patients with sepsis, detection and treatment of inflammatory storm, protection of vascular endothelial cells and the regulation of coagulation function, as well as strategies of liquid support and organ function protection etc. The consensus summarizes the commonly used clinical diagnosis criteria and treatment measures of sepsis both in Western medicine and traditional Chinese medicine for clinicians in order to provide evidence for the diagnosis and treatment of the disease.

Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial (artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span.

Objective: To determine the relationship between C-reactive protein (CRP) level and the severity of dengue and the potential use of CRP in predicting acute dengue infection. Methods: A prospective observational study was performed on dengue patients admitted to a tertiary care hospital in southern India. All patients of age above 18 years, diagnosed with dengue were included in the study. The detailed laboratory parameters pertaining to dengue were recorded. CRP levels were estimated and compared between groups i.e. severe and non-severe dengue. CRP cut-off value was detected using the receiver-operator curve. Results: Totally 98 patients with a mean age of 40 years were included. Among them, 11.2% of the patients suffered from severe dengue, 54.1% of the cases had non-severe dengue without warning signs, and 34.7% had non-severe dengue with warning signs. The median CRP was significantly higher in patients with severe dengue compared to patients with non-severe dengue (96.2 mg/dL vs. 5.3 mg/dL). Univariate logistic regression analysis showed that the odd’s ratio (OR) of CRP was 1.053 (P≤0.001, 95% CI=1.029-1.078). CRP at a cutoff value of 21.6 mg/L (0.929 AUC) had excellent sensitivity (100%) and specificity (81.6%) in predicting severe dengue infection. Multivariate logistic regression analysis showed that CRP (OR=1.089, P=0.013) and ALT (OR=1.010, P=0.034) were statistically significant independent predictors of dengue severity. Conclusions: CRP level could be used as a potential biomarker to predict severity of dengue in adults.

Objective: To explore the efficacy of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine and pyrimethamine (SP) against sensitive parasites. Methods: A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen, currently recommended three-dose regimen and 4, 6, 8-weekly regimens with specific focus on the impact of various non-adherence patterns in multiple transmission settings. Results: The effectiveness of the recommended three-dose regimen is high in all the transmission intensities, i.e. >99%, 98% and 92% in low, moderate and high transmission intensities respectively. The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women (>99%) regardless of transmission intensity. However, 8 weekly interval dose schedules were found to have 71% and 86% protective efficacies in high and moderate transmission areas, respectively. It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed. Conclusions: The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions. However, it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed. Adherence to the recommended IPTp-SP schedules is recommended.

Rationale: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recognized as highly pathogenic. The current pandemic of SARS-CoV-2 has been spread globally and infected more than 200 countries. Patient concerns: We report the first confirmed fatal case of COVID-19 in Pakistan. A 50-year-old man returned from Saudi Arabia on March 09, 2020 and presented with cough, fever, malaise, poor appetite and difficulty in breathing to the Pulmonologist at District Headquarter Hospital Mardan. Diagnosis: The patient was initially diagnosed as COVID-19 suspected case. A oropharyngeal swab sample was positive by realtime RT-PCR tests. Lessons: This report highlights the importance of close coordination between clinicians and public health authorities as well as the importance of early laboratory-based confirmation of COVID-19 cases.