Completion of 6-mo isoniazid preventive treatment among eligible under six children:A cross-sectional study,Lagos,Nigeria

BACKGROUND Nigeria is one of the thirty high burden countries with significant contribution to the global childhood tuberculosis epidemic.Tuberculosis annual risk for children could be as high as 4%particularly in high tuberculosis(TB)prevalent communities.Isoniazid(INH)Preventive Therapy has been shown to prevent TB incidence but data on its implementation among children are scarce.AIM To determine the completion of INH among under six children that were exposed to adults with smear positive pulmonary TB in Lagos,Nigeria.METHODS This was a hospital-based retrospective cross-sectional review of 265 medical records of eligible children<6 years old enrolled for INH across 32 private hospitals in Lagos,Nigeria.The study took place between July and September 2020.Data was collected on independent variables(age,gender,type of facility,TB screening,dose and weight)and outcome variables(INH outcome and proportion lost to follow up across months 1-6 of INH treatment).RESULTS About 53.8%of the participants were female,95.4%were screened for TB and none was diagnosed of having TB.The participants’age ranged from 1 to 72 mo with a mean of 36.01±19.67 mo,and 40.2%were between the ages of 1-24 mo.Only 155(59.2%)of the 262 participants initiated on INH completed the six-month treatment.Cumulatively,107(41.0%)children were lost to follow-up at the end of the sixth month.Of the cumulative 107 loss to follow-up while on INH,largest drop-offs were reported at the end of month 2,52(49%)followed by 20(19%),17(16%),11(10.2%)and 7(6.5%)at months 3,4,5 and 6 respectively.The analysis showed that there was no significant association between age,gender,type of facility and completion of INH treatment(P>0.005).CONCLUSION This study demonstrated suboptimal INH completion rate among children with only 6 out of 10 children initiated on INH who completed a 6-mo treatment in Lagos,Nigeria.The huge drop-offs in the first 2 mo of INH calls for innovative strategies such as the use of 60-d INH calendar that would facilitate reminder and early engagement of children on INH and their caregivers in care and across the entire period of treatment.

Preferences for oral-vs blood-based human immunodeficiency virus self-testing:A scoping review of the literature

BACKGROUND The evidence on preferences for oral-vs blood-based human immunodeficiency virus self-testing(HIVST)has been heterogenous and inconclusive.In addition,most evaluations have relied on hypothetical or stated use cases using discreet choice experiments rather than actual preferences among experienced users,which are more objective and critical for the understanding of product uptake.Direct head-to-head comparison of consumer preferences for oral-versus bloodbased HIVST is lacking.AIM To examine the existing literature on preferences for oral-vs blood-based HIVST,determine the factors that impact these preferences,and assess the potential implications for HIVST programs.METHODS Databases such as PubMed,Medline,Google Scholar,and Web of Science were searched for articles published between January 2011 to October 2022.Articles must address preferences for oral-vs blood-based HIVST.The study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist to ensure the quality of the study.RESULTS The initial search revealed 2424 records,of which 8 studies were finally included in the scoping review.Pooled preference for blood-based HIVST was 48.8%(9%-78.6%),whereas pooled preference for oral HIVST was 59.8%(34.2%-91%)across all studies.However,for male-specific studies,the preference for blood-based HIVST(58%-65.6%)was higher than that for oral(34.2%-41%).The four studies that reported a higher preference for blood-based HIVST were in men.Participants considered blood-based HIVST to be more accurate and rapid,while those with a higher preference for oral HIVST did so because these were considered non-invasive and easy to use.CONCLUSION Consistently in the literature,men preferred blood-based HIVST over oral HIVST due to higher risk perception and desire for a test that provides higher accuracy coupled with rapidity,autonomy,privacy,and confidentiality,whereas those with a higher preference for oral HIVST did so because these were considered non-invasive and easy to use.Misinformation and distrust need to be addressed through promotional messaging to maximize the diversity of this new biomedical technology.

Acceptability and strategies for enhancing uptake of human immunodeficiency virus self-testing in Nigeria

BACKGROUND In 2019,the Nigerian Ministry of Health published the first operational guidelines for human immunodeficiency virus self-testing(HIVST)to improve access to human immunodeficiency virus(HIV)testing services among undertested populations in the country.Also,as part of the campaign to increase HIV testing services in Nigeria,the Nigerian Ministry of Health developed standard operating procedures for using HIVST kits.AIM To systematically review the acceptability and strategies for enhancing the uptake of HIVST in Nigeria.METHODS The systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Different databases were searched to get the necessary materials needed for this review.Standardized forms developed by the authors were used for data extraction to minimize the risk of bias and ensure that the articles used for the study were properly screened.Identified articles were first screened using the titles and their abstracts.The full papers were screened,and the similarities of the documents were determined.Qualitative,quantitative,and mixed-method studies were evaluated using the Critical Appraisal Skills Programme and Critical Appraisal Framework criteria.RESULTS All the publications reviewed were published between 2015 and 2022,with 33.3%published in 2021.Most(77.8%)of the studies were cross-sectional,43.3%were conducted in Lagos State,and 26.3%were conducted among young people.The study revealed a high level of acceptability of HIVST.Certain factors,such as gender,sexual activity,and previous testing experience,influence the acceptability of HIV self-testing,with some individuals more likely to opt-out.The cost of the kit was reported as the strongest factor for choosing HIVST services,and this ranged from 200 to 4000 Naira(approximately United States Dollar 0.55-11.07),with the majority willing to pay 500 Naira(approximately United States Dollar 1.38).Privately-owned,registered pharmacies,youthfriendly centres,supermarkets,and online stores were the most cited access locations for HIVST.The least influential attribute was the type of specimen needed for HIVST.Strategies addressing cost and preferred access points and diverse needs for social media promotion,local translation of product use instructions,and HIVST distribution led by key opinion leaders for key populations were found to significantly enhance HIVST uptake and linkage to care.CONCLUSION HIVST acceptability is generally high from an intention-to-use perspective.Targeted strategies are required to improve the acceptability of HIV self-testing,especially among males,sexually active individuals,and first-time testers.Identified and proposed uptake-enhancing strategies need to be investigated in controlled settings and among different populations and distribution models in Nigeria.

Lecanemab Unveiled:Exploring Alzheimer’s Treatment Advancements,Assessing Strengths,Limitations,and Its Therapeutic Landscape Position

In the ever-evolving landscape of Alzheimer’s treatment,lecanemab(Leqembi)has emerged as a promising drug.Unlike conventional therapies that merely alleviate symptoms,lecanemab is a humanized monoclonal antibody with a distinct focus.It targets protofibrils,insoluble fibrils,amyloid oligomers,and soluble amyloid-beta protofibrils,which are known to be especially damaging to neurons,with high accuracy.

Drug Resistance to HIV-1 Integrase Inhibitors among Treatment-naive Patients in Jiangsu, China

Integrase strand transfer inhibitors (In STIs) have been widely used in recent years because of their high genetic barrier to resistance.The World Health Organization (WHO) has recommended dolutegravir(DTG)-containing regimens as the preferred first-and second-line antiretroviral therapy (ART) regimens for people living with human immunodeficiency virus(HIV)[1].

Evaluation of HBsAg Quantification as Surrogate to HBV DNA Viral Load in Hepatitis B Infected Patients in Anambra State, Nigeria

Hepatitis B is an infectious disease of great public health importance. Nigeria is one of the countries with the highest incidence of Hepatitis B Virus (HBV) infection worldwide. However, the accessibility and affordability of HBV DNA quantification (viral load) assay is the key laboratory test for therapy initiation, and monitoring is a challenge to HBV management. This study aimed at determining the relationship between HBV DNA quantification and routine haemato-serological parameters in order to develop a more cost-effective diagnostic algorithm for Hepatitis B management. Cross sectional study design was used with a total of 264 subjects comprising of 88 HBsAg seropositive treatment naïve subjects, 88 HBsAg seropositive subjects on antiviral therapy as case subjects and 88 age-matched apparently healthy HBsAg seronegative individuals were recruited as control subjects. Hepatitis B Virus DNA assay was performed using real time PCR technique while ELISA technique was used for Hepatitis B surface antigen quantification. HBsAg quantification showed strong positive correlation with HBV DNA viral load both in treatment and non-treatment groups (r = 0.673;p < 0.001). However, the Receiver Operation Characteristics curve indicated a very poor performance characteristics (AUC = 0.537, p = 0.002). The non-treatment group has higher viral load (M = 805.50 IU/ml) compared with treatment group (M = 65.50 IU/ml) (p < 0.001). There was a significant difference in HBV DNA levels among the four serological patterns observed in the study (p < 0.001). This study has revealed that HBsAg quantification has strong correlation with HBV viral load but might not be efficient in clinical practice as a predictor of serum HBV viral load due to its poor performance characteristics in identifying high positive viral load.

低收入高结核病负担国家的成人HIV/AIDS,特别是合并结核病者的处置

由于在低收入国家获得HIV抗逆转录病毒(antiretroviralARV)制剂可能性的提高,目前,许多临床医生需要ARV应用方面的培训。现在临床医生在治疗结核病(TB)时,还要进一步考虑到HIV/AIDS的情况。本文概要介绍医生处置HIV感染者时需要解决的关键问题,尤其是HIV/TB双重感染者。初级卫生保健医生要对所有提示HIV感染的症状、体征者和所有结核病患者进行HIV快速检测诊断。本文主要内容为:对HIV检测前和检测后的咨询问题进行探讨。对HIV感染者进行评估,确定临床分期;通过某些实验室检查判断免疫抑制的程度,以便确定应用ARV治疗和结核病预防性治疗的最佳时机。ARV治疗需要良好的依从性,建议劝导和加强依从性。介绍ARV治疗方案和患者随访要求。优先治疗结核病。不管是否合并HIV感染,治疗结核病的原则是相同的。对合并结核病的患者应用ARV提出了建议。必须建立标准化和不断充实的信息系统,以便监控HIV与结核病双重感染者的处置及结核病和HIV联合防治的执行情况。通过对结核病患者进行HIV感染的筛查,发现HIV感染病例,并对其进行诊断和处置,医生能为减少HIV负担做出贡献,同样也为减少结核病负担做出贡献。

Associated factors of self-reported psychopathology and health related quality of life among men who have sex with men (MSM) with HIV/AIDS in Dalian, China: a pilot study

Background:Despite the availability of Anti-Retroviral Therapy(ART),the health-related quality of life(HRQoL)among HIV-positive men who have sex with men(HIVMSM)in China remains poor.This study aimed to explore the relationship between self-reported psychopathology and HRQoL among HIVMSM in Dalian,China.Methods:A cross-sectional study was conducted in 112 HIVMSM.Symptom check list 90(SCL 90):a measure of psychopathology and World Health Organization quality of life in HIV infection(WHOQOL-HIV-Bref):a measure of HRQoL were used.Correlation and multiple regression analysis were employed to explore the association between self-reported psychopathology and HRQoL in HIVMSM.Results:Out of the total 112 HIVMSM cases,9(8%)cases were homosexuals and 103(92%)ones were bisexuals.The participants who had low family income(P=0.001),perceived discrimination(P=0.001)and lack of regular attendance in medical follow-ups(P=0.014)reported poorer HRQoL than their counterparts.Somatization,obsession,depression,phobia and overall SCL 90 scores in self-reported psycholpathology had a negative impact on the domains of HRQoL among HIVMSM.Conclusions:Total quality of life was predicted by family income,perceived discrimination,and medical follow-up attendance.Self-reported psychopathology was negatively correlated with HRQoL in HIVMSM.The Strategies that target MSM focusing on linking and engaging HIV-positive patients in medical care is the key step to improve their HRQoL.More emphasis is needed on the newly diagnosed HIVMSM in Dalian in order to develop a more targeted intervention to prevent perceived discrimination and lack of proper medical follow-up services.Trial registration:The trial registration number does not require for this manuscript.The study is cross-sectional design that do not involve intervention at all,it is not a clinical trial.

Immunogenicities of Env glycoproteins from circulating HIV-1 isolates in China focusing on the strategy of ＂DNA prime plus protein boost＂

Background The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus on the induction of neutralizing antibodies. A major challenge in developing an HIV-1 vaccine is to identify immunogens and adopt delivery methods that can elicit broadly neutralizing antibodies against primary isolates of different genetic subtypes. Methods Most circulating HIV-1 isolates in China are composed of clades Thai-B, CRF_BC and CRF01_AE. In order to construct DNA vaccines against these 3 HIV-1 subtypes, DNA vaccines carrying the gp120 regions from HIV-1 isolates of GX48（AE）, GX79（AE）, NX22（BC）, GS22（BC）, HN24（Thai-B） were constructed. Expression of gp120 from these DNA vaccines was detected by Western blotting in transiently transfected 293T cells. Pilot immunizations of New Zealand white rabbits were performed using the strategy of ＂DNA prime plus protein boost＂ and the neutralizing antibody response was detected in a Tzm-bl cell based assay against different HIV-1 strains. Results Response of gp120-specific antibody was relatively low after DNA primes （mean titer=10^4.72）; however, the titer of gp120-specific antibody went up with 2 protein boosts （mean titer=10^6.81）. Above all, neutralizing antibody （Nab） titers induced by this combined approach were much better than those elicited by DNA or protein used alone （P 〈0.01）. Neutralizing activities of immunized rabbit sera against several pseudoviruses and laboratorial strains were evaluated, most rabbit sera primed with monovalent vaccine were capable of neutralizing only 1 of 5 viruses, however, sera primed with the polyvalent DNA vaccines were able to neutralize at least 2 of 5 viruses. Conclusion Polyvalent DNA prime plus protein boost is an effective immunization strategy to broaden the neutralization breadth and further research should be performed on the basis of this pilot study.

Are monitoring and evaluation systems adequate to report the programmatic coverage of HIV services among key populations in countries?

There was no global guidance or agreement regarding when a country has an adequate system to report on the service packages among human immunodeficiency virus(HIV)key populations.This article describes an approach to categorizing the system in a country for reporting the service package among HIV key populations.The approach consists of four dimensions,namely the epidemiological significance,comprehensiveness of the service packages,geographic coverage of services,and adequacy of the monitoring system.The proposed categorization approach utilizes available information and can inform the improvement of the service delivery and monitoring systems among HIV key populations.

Prostate Cancer’s Molecular Imaging by Targeting Based Nanoparticles: An Overview

Today nanoparticles based drug delivery or imaging agents are extremely being investigated as a very powerful tool in early diagnostics or treatment of different kinds of cancers including prostate malignancies. Among the diverse developing nanomaterials, biocompatible biodegradable dendrimers and chitosan or PLGA (Poly Lactic-co-Glycolic Acid) derivatives are more considered due to their safer profiles. As a result, finding novel prostate imaging agents based on nano sized structures would be of high global interest which will be further discussed in this review.

Identifying the Key Nodes of HIV Molecular Transmission Network Among Men Who Have Sex with Men—Guangzhou,Guangdong Province,China,2015–2017

Summary What is already known about this topic?Identifying the most influential spreaders in human immunodeficiency virus(HIV)transmission networks is crucial for developing effective prevention strategies.What is added by this report?This study identified key nodes of the HIV molecular transmission network among men who have sex with men(MSM)by utilizing linkages between sequences to reconstruct the transmission network at the molecular level.

Chimeric antigen receptors:On the road to realising their full potential

Chimeric antigen receptors （CARs） are fusion molecules that may be genetically delivered ex-vivo to T-cells and other immune cell populations, thereby conferring specifcity for native target antigens found on the surface of tumour and other target cell types. Antigen recognition by CARs is neither restricted by nor dependent upon human leukocyte antigen antigen expression, favouring widespread use of this technology across transplantation barriers. Signalling is delivered by a designer endodomain that provides a tailored and target-dependent activation signal to polyclonal circulating T-cells. Recent clinical data emphasise the enormous promise of this emer-ging immunotherapeutic strategy for B-cell malignancy, notably acute lymphoblastic leukaemia. In that context, CARs are generally targeted against the ubiquitous B-cell antigen, CD19. However, CAR T-cell immunotherapy is limited by potential for severe ontarget toxicity, notably due to cytokine release syndrome. Furthermore, effcacy in the context of solid tumours remains unproven, owing in part to lack of availability of safe tumourspecific targets, inadequate CAR T-cell homing and hostility of the tumour microenvironment to immune effector deployment. Manufacture and commercial development encountered with more traditional drug products. Finally, there is increasing interest in the application of this technology to the treatment of non-malignant disease states, such as autoimmunity, chronic infection and in the suppression of allograft rejection. Here, we consider the background and direction of travel of this emerging and highly promising treatment for malignant and other disease types.

Factors that Affect the Frequency of HIV Testing in College Men Who Have Sex with Men--Northeast China,2017-2018

Summary What is already known about this topic?Human immunodeficiency virus(HIV)testing is a critical tool in reducing HIV transmission among men who have sex with men(MSM);young MSM frequently use mobile phone applications and participate in social hook-ups.

高效抗逆转录病毒治疗期间AIDS相关Kaposi肉瘤的预后指数

Background: AIDS-associated Kaposi’ s sarcoma remains common in individuals with HIV-1 infection in the era of highly active antiretroviral therapy (HAART). We developed a simple model for predicting mortality on the basis of clinical characteristics present at the time of diagnosis of Kaposi’ s sarcoma. Methods: Of 5873 individuals with HIV-1 infection, 326 (6% ) developed Kaposi’ s sarcoma; for 262 (80% ) this was their first AIDS-defining illness. We did univariate and multivariate Cox regression analyses to identify covariates predictive of overall survival and validated our model with an independent data set of 446 patients with Kaposi’ s sarcoma. Results: In the primary model, we developed a prognostic score from 0 to 15 starting at 10. Having Kaposi’ s sarcoma as the AIDSdefining illness (- 3 points) and increasing CD4 count (- 1 point for every complete 100 cells per mm3) improved prognosis; age of 50 years or older (2 points) and having another AIDS-associated illness at the same time (3 points) conveyed a poorer prognosis. In individuals with prognostic scores of 0, 5, 10, and 15, probability of survival at 1-year was 0.993, 0.967, 0.834, and 0.378, and at 5 years was 0.984, 0.918, 0.631, and 0.084, respectively. Increasing prognostic score by 1 increased 1-year death hazard ratio by 40% (95% CI 28- 53% ; bootstrapped hazard ratio 1.39, 1.25- 1.51). The index had concordance of 76.8% (71.7- 82.3). Interpretation: We identified four prognostic factors that can be used to obtain an accurate prognostic index at diagnosis of AIDS- associated Kaposi’ s sarcoma. This index is widely applicable and can be used to guide therapeutic options.

Challenges in the control of COVID-19 outbreaks caused by the delta variant during periods of low humidity:an observational study in Sydney,Australia

Background: Since the appearance of severe acute respiratory coronavirus 2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) pandemic, a growing body of evidence has suggested that weather factors, particularly temperature and humidity, influence transmission. This relationship might differ for the recently emerged B.1.617.2 (delta) variant of SARS-CoV-2. Here we use data from an outbreak in Sydney, Australia that commenced in winter and time-series analysis to investigate the association between reported cases and temperature and relative humidity.Methods: Between 16 June and 10 September 2021, the peak of the outbreak, there were 31,662 locally-acquired cases reported in five local health districts of Sydney, Australia. The associations between daily 9:00 am and 3:00 pm temperature (°C), relative humidity (%) and their difference, and a time series of reported daily cases were assessed using univariable and multivariable generalized additive models and a 14-day exponential moving average. Akaike information criterion (AIC) and the likelihood ratio statistic were used to compare different models and determine the best fitting model. A sensitivity analysis was performed by modifying the exponential moving average.Results: During the 87-day time-series, relative humidity ranged widely (< 30-98%) and temperatures were mild (approximately 11-17℃). The best-fitting (AIC: 1,119.64) generalized additive model included 14-day exponential moving averages of 9:00 am temperature (P < 0.001) and 9:00 am relative humidity (P < 0.001), and the interaction between these two weather variables (P < 0.001). Humidity was negatively associated with cases no matter whether temperature was high or low. The effect of lower relative humidity on increased cases was more pronounced below relative humidity of about 70%;below this threshold, not only were the effects of humidity pronounced but also the relationship between temperature and cases of the delta variant becomes apparent.Conclusions: We suggest that the control of COVID-19 outbreaks, specifically those due to the delta variant, is particularly challenging during periods of the year with lower relative humidity and warmer temperatures. In addition to vaccination, stronger implementation of other interventions such as mask-wearing and social distancing might need to be considered during these higher risk periods.

Assessment of POC CD4 Detecting Mode in District or County Labs-Jiangsu Province, China, 2021

Objective:This study seeks to explore efficient and multiple-item detection modes in new-style HIV labs,as well as access the accuracy and reliability of CD4 cell count detected by point of care(POC)to analyze POC work feasibility in district or county labs.Methods:POC devices adopted in grassroots-level labs and flow cytometers adopted in prefecture-level labs were used to analyze the same group of blood samples.The individual results were collected and compared for parametric tests in correlation and consistency.Results:The Pearson correlation coefficients(r)between results detected by FACSPresto and those by FACSCalibur,FACSVia,FACSCantoII,and EPICSXL were 0.922,0.938,0.914,and 0.823,respectively;the average deviations were−25.64,24.68,3.05,and 70.97 cells/μL,respectively;the Pearson correlation coefficient(r)between results by Pima and FACSCalibur,FACSVia,FACSCantoII,and EPICSXL were 0.900,0.950,0.954,and 0.876,respectively;and the average deviations were−73.99,−40.78,−29.32,and−22.75 cells/μL,respectively.Discussion:Strong positive correlations and good consistency were observed between the CD4 count tested by POC and flow cytometers.These findings provide theoretical support for new-style HIV labs and one-stop services,which can provide shorter testing duration and simpler testing processes,so that the most comprehensive testing results can be obtained in the shortest amount of time.

HIV-Positive Men Are More Likely to Be Hyper Linked Within College Student Social Network-Northeast China,2017-2018

What is already known about this topic?Men who have sex with men(MSM)bear a disproportionate burden of new human immunodeficiency virus(HIV)infections and young MSM demonstrate parallel internet-driven HIV incident infection and dynamic social network.What is added by this report?The HIV positive prevalence and incidence among college MSM were 3.8%and 2.9 per 100 person-years,respectively,while these rates were 13.9%and 10.5 per 100 person-years,respectively,among their social contacts.The overall HIV positive prevalence was 7.2%in Northeast China.HIV-positive MSM have comparatively more social contacts than HIVseronegative MSM.What are the implications for public health practice?Hyper-linkages found in app-based social networks play an important role in HIV transmission via risky sexual behavior and suggest options for online intervention to promote HIV prevention.

Diabetes Is Not Associated with Increased 10-week Mortality Risk in Patients with Cryptococcal Meningitis

Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic CM patients and 98 non-diabetic CM patients from January 2008 to December 2018 in the First Affiliated Hospital of Zhejiang University were included by propensity score-matched method(1:2).Demographic characteristics,symptoms,and clinical assay parameters between the two groups were compared.Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality.Results:The mean age of diabetic patients was 58.2±13.8 years;71.4%(35/49)were more than 50 years old and 46.9%were male.No difference in symptoms was found between diabetic and non-diabetic CM patients.The Charlson comorbidity score was higher in the diabetic group(1.9 vs.0.7,P<0.001).CM patients with diabetes had higher white blood cells count(106/L,111.0(18.0–242.5)vs.50.0(10.0–140.0),P=0.034)in cerebrospinal fluid(CSF),lower CSF India ink positivity(40.8%vs.60.2%,P=0.039),and Cryptococcus culture positivity(42.9%vs.60.2%,P=0.047).The overall 10-week survival rate was 79.7%in diabetic patients vs.83.2%in non-diabetic patients(log-rank P=0.794).Conclusion:Diabetic CM patients have higher CSF glucose and Charlson comorbidity score,but lower CSF India ink and culture positivity than non-diabetic CM patients.No difference in 10-week mortality was found between patients with and without diabetes.Other comorbidities may have a greater effect on prognosis.