Study of Serum Creatine Phosphokinase (CPK) as A Prognostic Indicator in Patients with Organophosphorus Compound Poisoning

Organophosphorus (OP) is an easily accessible pesticide which has a high morbidity and mortality on human exposure. Serum cholinesterase (SChE) is usually used for assessing the severity of poisoning, in this study we assess the role of serum creatine phosphokinase (CPK) as an alternative prognostic marker. This was a single centred, hospital-based, prospective and observational study, conducted on 88 patients with a history of OP compound consumption who were admitted to the ICU of tertiary care hospital, from the time period October 2019 to March 2021.  The patients were clinically categorized into mild, moderate and severe categories according to Peradeniya Organophosphorus Poisoning (POP) scale and before initiation of treatment, the samples were sent for estimation of SChE and serum CPK.  Out of the 88 patients, OP poisoning was more common in the age group of 21-30 years and males had a higher incidence. Chlorpyriphos (62.5%) was the most common compound. A higher POP score, marked reduction in SChE levels, and increased serum CPK levels were observed to have increased the duration of hospital stay, increased the severity of poisoning, increased the need for ventilator support and also increased the mortality

Immune Escape via a Transient Gene Expression Program Enables Productive Replication of a Latent Pathogen

How type I and II interferons prevent periodic reemergence of latent pathogens in tissues of diverse cell types remains unknown. Using homogeneous neuron cultures latently infected with herpes simplex virus 1, we show that extrinsic type I or II interferon acts directly on neurons to induce unique gene expression signatures and inhibit the reactivation-specific burst of viral genome-wide transcription called phase I. Surprisingly, interferons suppressed reactivation only during a limited period early in phase I preceding productive virus growth. Sensitivity to type II interferon was selectively lost if viral ICP0, which normally accumulates later in phase I, was expressed before reactivation. Thus, interferons suppress reactivation by preventing initial expression of latent genomes but are ineffective once phase I viral proteins accumulate, limiting interferon action. This demonstrates that inducible reactivation from latency is only transiently sensitive to interferon. Moreover, it illustrates how latent pathogens escape host immune control to periodically replicate by rapidly deploying an interferon-resistant state

Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention