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Background: Recent studies have shown a shift in the traditional aetiologies commonly associated with tropical acute kidney injury (AKI) in some parts of Africa. In many low-income regions limited access to dialysis increases the risk of AKI-associated adverse outcomes. The goal of this study was to evaluate the aetiology, predictors of the need for dialysis, and outcomes of AKI among children evaluated by the renal service in Lusaka, Zambia. Methods: This retrospective study included children less than 16 years old, who were diagnosed with AKI between 2016 and 2021 and followed up by the renal service at the University Teaching Hospitals- Children’s hospital (UTH-CH). AKI was defined and staged using the KDIGO 2012 criteria. Data were extracted from patient folders using a pre-designed tool and then analysed using SPSS version 25. Categorical data were expressed as simple proportions while continuous variables were expressed as either means or median after determination of normality. Correlations were determined using the chi-square test, otherwise Fischer’s exact test in the case of categorical variables, and the independent t-test for continuous variables. The significance level was set at a p-value < 0.05. The predictors of need for dialysis, poor patient outcome, and malaria-associated AKI (MAKI) were identified by using binary logistic regression. Results: The 126 (37.7%) children diagnosed with AKI had a median age of 7.5 (interquartile range 0.3-16) yearsand a male-to-female ratio of 1.4. Of these, a total of 94(74.6%) underwent dialysis with 65(82.1%) receiving peritoneal dialysis (PD), 8(8.5%) receiving haemodialysis (HD), and 4(4.3%) undergoing both modalities. Predictors of need for dialysis were oliguria (OR 10.4, p= 0.002) and anuria (OR 8.7, p, 0.006) while the leading aetiologies of AKI were malaria (77, 60%) and glomerular disease (21, 16.6%). Twenty-three (18.3 %) children developed chronic kidney disease (CKD), 7(5.6 %) died and a year later 97 (77%) were lost to follow-up. Conclusion: Malaria is the leading cause of AKI and children from areas of medium malaria transmission intensity are at increased risk. Three-quarters of children in the cohort required dialysis. CKD and mortality rates may be underestimated due to the high loss to follow- up rate.

People living with HIV have been known to have a higher risk and threat of kidney disease. Globally, the prevalence of kidney disease for PLWH is postulated to be 6.4%. This prevalence is different for many different parts of the world, with 7.9% in Africa, 7.1% in North America, 5.7% in Asia and 3.7% in Europe. This systematic review set out to review and collect evidence from literature source and to provide a summary about factors influencing kidney disease for PLWH in Africa. We hypothesized that TDF containing ART is significantly associated with kidney disease. A systematic review and search of data was performed and all articles included were English articles from the following electronic databases: PubMed, Google Scholar and Embase. We carried out the selection of titles in three distinct phases: titles alone, abstracts, and then full text articles. 7 papers were included. While TDF was included in the ART regimens in all the studies, there was wide variation in ART combinations and concurrent medications and durations thereof.All studies except one included only adult patients of both men and women. Majority of the studies highlighted kidney disease and mostly these were hospital-based data. the findings establish a significant association between kidney disease and TDF use, but in terms of the clinical significance and weighting the risks against the benefits, we cannot discourage the continual use of the drug.

Kaposi's sarcoma (KS) is an AIDS-defining malignancy that can improve or worsen with antiretroviral therapy (ART). We aimed at identifying clinical, HIV-related, and sociodemographic factors associated with either progression or nonprogression (regression or stable disease) of ART-treated HIV-associated KS in patients with limited cutaneous disease. We conducted a prospective cohort study of ART-treated HIV-associated KS cases. Clinical, HIV-related, and sociodemographic variables were collected at baseline, and patients were followed up to determine treatment outcomes. Cox regression, linear mixed effects model, and Spearman's rank correlation were used for analysis. Half (50%) of the study participants had KS regression or stable disease, whereas the other half (50%) had disease progression during the treatment and follow-up period. Among the data analyzed, presence of KS nodules at baseline (hazard ratio = 5.47; 95% confidence interval = 1.32–22.65; p = .02) was an independent predictor of poor treatment outcome. Progressors and nonprogressors were indistinguishable in the changes they experienced in the HIV plasma viral load and CD4 counts as a result of ART. Even when cutaneous presentation is limited, the presence of nodular morphotype KS lesions should be considered an indicator for combined ART plus chemotherapy. Temporal trends in CD4 counts and HIV viral loads did not correlate with treatment outcome in ART-treated HIV-associated KS.

Whether the human brain is a robust reservoir for HIV-1 subtype C has yet to be established. We aimed to determine whether HIV-1 subtype C infection can be detected in the brain tissue of a viremic individual at post-mortem and whether the viral burden was differential between different brain regions. This study reports a 38-year-old Zambian female decedent with severe wasting who was on Atripla for antiretroviral therapy. The cause of death was determined to be HIV/AIDS end-stage disease. The QuantStudio 3 Real-Time PCR System analyzed formalin-fixed paraffin-embedded tissue DNA from a systematic sampling of the entire left-brain hemisphere. Plasma and cerebral spinal fluid HIV-1 RNA loads were 576,123 and 14,962 copies/mL, respectively. The lymph node DNA viral load was 2316 copies per 10

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or Coronavirus was initially detected in Wuhan China in December 2019 and has subsequently resulted in the COVID-19 pandemic. The disease presents asymptomatically in some of individuals yet also causes symptoms ranging from those associated with influenza and pneumonia, acute respiratory distress syndrome (ARDS) and even death. The world is currently relying on physical (social) distancing, hygiene and repurposed medicines; however, it was predicted that an effective vaccine will be necessary to ensure comprehensive protection against COVID-19. There was a global effort to develop an effective vaccine against SARS-CoV-2 with approximately 300 vaccines in clinical trials, and over 200 more in different stages of development and anticipated that their success will change research clinical trials processes. Although every one of these vaccines comes with its own particular set of characteristics and difficulties, they were all developed as a direct result of research and development efforts that were carried out on a scale that had never been seen before. It is the first time in the history of vaccination that a worldwide immunization campaign has begun during a time of severe pandemic activity that is defined by high virus transmission. This achievement marks an important milestone in the history of vaccination. More than anything else, the most important aspect of the new game change in drug design is that the traditional drug discovery rules have been rewritten. This is especially significant for the development of vaccines, as it is possible for all clinical trials to be accelerated, which would bring a vaccine or drug molecule to market within a year rather than the traditional fifteen years for each phase of drug clinical trials. This review provides insight in respect to first generation COVID-19 vaccines, which were in clinical use as of December 2020 and focused on the Pfizer/ BioNTech/Fosun, Moderna mRNA-1273, Johnson and Johnson and AstraZeneca/Oxford AZD1222 vaccines.

Background Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored. Objectives To study the spectrum of lymphoma subtypes prevalent within the Zambian population. Methods Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher’s exact test was used for significance testing. Results During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin’s lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin’s lymphoma (CHL) was seen in 39 (16.3%). Burkitt’s lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002). Conclusion Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.

Background: Several vaccines have been developed and administered since coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. In April 2021, the authorities in Zambia administered the first doses of the Oxford-AstraZeneca® COVID-19 vaccine. However, little is known about the awareness and acceptability of the vaccines among the Zambian population. This study was undertaken to address this starting with undergraduate pharmacy students in Zambia. Materials and methods: A descriptive cross-sectional survey was conducted among 326 undergraduate pharmacy students in Zambia using an online semi-structured questionnaire from 12th to 25th April 2021 and analysed using Stata version 16. Test of associations were undertaken using Pearson chi-square test or Fisher's exact test as appropriate. The multivariable logistic regression was used to investigate the determinants of awareness and acceptability. All statistical tests were performed at a 5% significance level and 95% confidence level. Results: Among 326 participants, 98.8% were aware of the COVID-19 vaccination programme but only 24.5% would accept the vaccine should it be made available to them. Awareness of the COVID-19 vaccine was influenced by religious beliefs (aOR=0.01, 95% CI: 0.01 to 0.20, p=0.004). Being male (aOR=1.78, 95% CI: 1.05 to 3.02, p=0.034) and single (aOR=2.61, 95% CI: 1.04 to 6.55, p=0.041) was associated with higher odds of accepting the vaccine. Being unemployed (aOR=0.31, 95% CI: 0.15 to 0.66, p=0.002) was associated with lower odds of vaccine acceptancy. Barriers to acceptance of the vaccine were possible side effects (78.5%) and scepticism about its effectiveness to prevent COVID-19 (10.2%). Conclusion: There was significant vaccine hesitancy towards COVID-19 vaccines among Zambian pharmacy students despite their awareness about the vaccines. Health authorities must work collaboratively with the Universities and other institutions to mitigate vaccine hesitancy, especially with pharmacy students a key part of the future healthcare workforce overseeing disease prevention strategies. These findings can help guide future interventions to address vaccine hesitancy to reduce future transmission rates of this virus.

Background: Persons with HIV (PWH) are more likely to develop hypertension and cardiovascular disease than the HIV-negative population. The new hypertension guidelines by the American Heart Association (AHA) and the American College of Cardiology (ACC) lowered the definition of hypertension from a systolic and diastolic blood pressure (BP) of ≥140/90mmHg to ≥130/80, respectively. This study was aimed at determining the prevalence and factors associated with hypertension in PWH using the new hypertension diagnostic criteria.Methods: This was a cross-sectional study. We recruited 226 antiretroviral treated PWH attending routine visits. Socio-demographic, health, and clinical data including BP readings were collected. Interviewer-structured questionnaires adapted from the World Health Organization Stepwise approach to Surveillance (WHO STEPs) and the international physical activity questionnaire (IPAQ) were used to collect data. Statistical evaluations were employed to elucidate relationships between hypertension and all response variables.Results: The prevalence of hypertension using the old and new guidelines was 16% and 42%, respectively. Factors significantly associated with increased and reduced odds for developing hypertension after adjustments in multivariate logistic regression were age, body mass index (BMI), employment status, fasting blood sugar (FBS) and table salt consumption, respectively (pConclusion: The major risk factors associated with hypertension in PWH were increasing age, BMI and FBS. We recommend inclusion of FBS in routine measurements in PWH. The AHA/ACC new guidelines should be re-enforced in low-cost settings to increase the treatment of hypertension among PWH.

Background High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. Methods We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. Results The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p Conclusions The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.

Cervical cancer has remained the most prevalent and lethal malignancy among women worldwide and accounted for over 250,000 deaths in 2019. Nearly ninety-five per cent of cervical cancer cases are associated with persistent infection with high-risk Human Papillomavirus (HPV), and seventy per cent of these are associated with viral integration in the host genome. HPV-infection imparts specific changes in the regulatory network of infected cancer cells that are of diagnostic, prognostic and importance. Here, we conducted a systems-level analysis of the regulatory network changes, and the associated regulatory proteins thereof, in HPV-positive cervical cancer. We applied functional pathway analysis to show that HPV-positive cancers are characterised by perturbations of numerous cellular processes, predominantly in those linked to the cell cycle, mitosis, cytokine and immune cell signalling. Using computational predictions, we revealed that HPV-positive cervical cancers are regulated by transcription factors including, SOX2, E2F, NANOG, OCT4, and MYC, which control various processes such as the renewal of cancer stem cells, and the proliferation and differentiation of tumour cells. Through the analysis of upstream regulatory kinases, we identified the mitogen-activated protein kinases; among others, MAPK1, MAPK3 and MAPK8, and the cyclin-dependent kinases; among others, CDK1, CDK2 and CDK4, as the key kinases that control the biological processes in HPV-positive cervical cancers. Taken together, we uncover a landscape of the key regulatory pathways and proteins in HPV-positive cervical cancers, all of which may provide attractive drug targets for future therapeutics.

Background:Greater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA). Objective:To determine the association between immune activation and arterial stiffness in lean PLWH in SSA. Method:Forty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) >5 years and 26 HIV-negative adults, all with BMI < 25 kg/m2and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status. Results:Increased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively;p< 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV;p= 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV;p= 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%;p< 0.05) in comparison to their HIV controls. Conclusion:Our population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation.

Restrictive measures imposed because of the coronavirus disease 2019 (COVID-19) pandemic have resulted in severe social, economic and health effects. Some countries have considered the use of immunity certification as a strategy to relax these measures for people who have recovered from the infection by issuing these individuals a document, commonly called an immunity passport. This document certifies them as having protective immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19. The World Health Organization has advised against the implementation of immunity certification at present because of uncertainty about whether long-term immunity truly exists for those who have recovered from COVID-19 and concerns over the reliability of the proposed serological test method for determining immunity. Immunity certification can only be considered if scientific thresholds for assuring immunity are met, whether based on antibodies or other criteria. However, even if immunity certification became well supported by science, it has many ethical issues in terms of different restrictions on individual liberties and its implementation process. We examine the main considerations for the ethical acceptability of immunity certification to exempt individuals from restrictive measures during the COVID-19 pandemic. As well as needing to meet robust scientific criteria, the ethical acceptability of immunity certification depends on its uses and policy objectives and the measures in place to reduce potential harms, and prevent disproportionate burdens on non-certified individuals and violation of individual liberties and rights.Les restrictions imposées dans le cadre de la lutte contre la pandémie de maladie à coronavirus 2019 (COVID-19) ont eu de lourdes conséquences économiques, sociales et sanitaires. Certains pays ont envisagé la mise en place d'une stratégie visant à alléger ces restrictions pour les individus guéris en leur octroyant un document communément appelé «passeport d'immunité». Ce document atteste qu'ils ont développé une immunité protectrice contre le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2), le virus à l'origine de la COVID-19. L'Organisation mondiale de la Santé a déconseillé l'usage du certificat d'immunité pour l'instant, car l'incertitude demeure quant à l'existence réelle d'une immunité à long terme pour ceux qui se sont remis de la COVID-19. En outre, la fiabilité des tests sérologiques censés déterminer si l'individu est immunisé n'est pas avérée. Un tel certificat ne peut être instauré que si les seuils scientifiques en matière d'immunité sont respectés, qu'ils soient fondés sur les anticorps ou sur d'autres critères. Néanmoins, même si le certificat d'immunité est désormais bien accepté par la science, il s'accompagne de nombreuses questions d'ordre éthique en ce qui concerne la limitation des libertés individuelles et la mise en œuvre. Dans le présent document, nous examinons les principales considérations à prendre en compte pour garantir l'acceptabilité éthique du certificat d'immunité visant à lever les mesures de restriction pour certaines personnes durant la pandémie de COVID-19. Cette acceptabilité éthique dépend non seulement de son degré de conformité à des critères scientifiques stricts, mais aussi de son usage, des objectifs politiques ainsi que des mesures mises en place pour atténuer les préjudices potentiels et éviter d'imposer une charge disproportionnée sur les individus dépourvus de certificat, ou de bafouer les droits et libertés de tout un chacun.Las medidas restrictivas impuestas a causa de la pandemia de la enfermedad coronavirus de 2019 (COVID-19) han tenido graves efectos sociales, económicos y sanitarios. Algunos países han considerado la posibilidad de utilizar la certificación de inmunidad como estrategia para flexibilizar dichas medidas para las personas que se han recuperado de la infección mediante la expedición a dichas personas de un documento, comúnmente denominado pasaporte de inmunidad. Este documento certifica que han desarrollado inmunidad protectora contra el coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2), el virus que causa la COVID-19. La Organización Mundial de la Salud ha desaconsejado la aplicación de la certificación de la inmunidad en la actualidad debido a la incertidumbre sobre si existe realmente una inmunidad a largo plazo para quienes se han recuperado de la COVID-19 y a las preocupaciones sobre la fiabilidad del método de prueba serológica propuesto para determinar la inmunidad. La certificación de la inmunidad solo puede considerarse si se cumplen los umbrales científicos para asegurar la inmunidad, ya sea que se basen en anticuerpos o en otros criterios. Sin embargo, incluso si la certificación de la inmunidad llegara a estar bien respaldada por la ciencia, tiene muchas cuestiones éticas en cuanto a las diferentes restricciones de las libertades individuales y su proceso de aplicación. Examinamos las principales consideraciones sobre la aceptabilidad ética de la certificación de la inmunidad para eximir a los individuos de las medidas restrictivas durante la pandemia de la COVID-19. Además de necesitar cumplir criterios científicos sólidos, la aceptabilidad ética de la certificación de inmunidad depende de sus usos y objetivos de política y de las medidas que se apliquen para reducir los posibles daños y evitar que se impongan cargas desproporcionadas a las personas que no cuenten con dicha certificación y se violen las libertades y derechos individuales.الإجراءات التقييدية المفروضة نظراً لأن جائحة مرض فيروس كورونا 19 (كوفيد 19) قد أدت إلى آثار اجتماعية واقتصادية وصحية وخيمة. اعتبرت بعض الدول استخدام شهادة المناعة كاستراتيجية لتخفيف هذه الإجراءات للأشخاص الذين تعافوا من الإصابة، وذلك بإصدار مستند لهؤلاء الأفراد، يُطلق عليها بصورة شائعة مصطلح: جواز المناعة. يشهد هذا المستند على أنهم يتمتعون بمناعة وقائية ضد المتلازمة التنفسية الحادة الوخيمة لفيروس كورونا 2 (SARS-CoV-2)، الفيروس المسبب لكوفيد 19. وقد نصحت منظمة الصحة العالمية بعدم تطبيق شهادة المناعة في الوقت الحالي بسبب عدم اليقين بشأن ما إذا كانت المناعة طويلة المدى موجودة بالفعل لدى هؤلاء الذين تعافوا من كوفيد 19، فضلاً عن المخاوف بشأن موثوقية طريقة الاختبار المصلي المقترحة لتحديد المناعة. لا يمكن النظر لشهادة المناعة بعين الاعتبار إلا إذا تم تلبية الشروط العلمية لضمان المناعة، سواء بناءً على الأجسام المضادة أو معايير أخرى. ومع ذلك، حتى إذا أصبحت شهادة المناعة مدعومة جيدًا من جانب العلم، فإنها تواجه العديد من القضايا الأخلاقية فيما يتعلق بالقيود المختلفة على الحريات الفردية وعملية تنفيذها. نحن ندرس الاعتبارات الرئيسية للقبول الأخلاقي لشهادة المناعة لإعفاء الأفراد من الإجراءات التقييدية أثناء جائحة كوفيد 19. وفضلاً عن الحاجة إلى تلبية معايير علمية صارمة، فإن القبول الأخلاقي لشهادة المناعة يعتمد على استخداماتها وأهدافها السياسة، والتدابير المتبعة لتقليل الأضرار المحتملة، ومنع الأعباء غير المتناسبة على الأفراد غير الحاصلين على الشهادة، وانتهاك الحريات والحقوق الفردية.因新型冠状病毒肺炎（新冠肺炎）大流行而强制实施的限制性措施已造成严重的社会、经济和健康影响。有些国家已考虑采用免疫认证策略来放松这些限制性措施，即，向感染后康复的人员发放一份通常被称为免疫通行证的证件。该证件证明此类人员对引起新冠肺炎的病毒——严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)——具有保护性免疫力。世界卫生组织建议目前不要实施免疫认证，因为尚不确定感染新冠肺炎后康复的人员是否切实存在长期免疫力，且对计划用于测定免疫力的血清学检测方法的可靠性尚存疑虑。仅当达到确保免疫的科学阈值（无论是基于抗体还是其他标准）时，才可以考虑采取免疫认证。然而，即使免疫认证得到了科学的充分支持，也仍存在许多伦理问题，包括对个人自由的不同限制及其实施过程。对于在新冠肺炎大流行期间准许某些人员无需遵守限制性措施的免疫认证，我们研究了这种认证在伦理上予以接受的主要考虑因素。免疫认证不仅需要满足严格的科学标准，而且在伦理上是否予以接受还取决于免疫认证的用法、实施对象以及是否采取措施以降低对未获得认证的人员造成的潜在伤害，防止对其产生过重的压力以及违反个人自由和权利方面的规定。.Ограничительные меры, введенные с началом пандемии коронавирусного заболевания 2019 года (COVID-19), привели к серьезным социальным и экономическим последствиям, а также неблагоприятно отразились на здоровье населения. Некоторые страны рассматривают возможность использования сертификации иммунитета в качестве стратегии по ослаблению таких мер для людей, перенесших заболевание, посредством выдачи этим лицам документа, именуемого «паспорт иммунитета». Данный документ подтверждает, что эти лица обладают защитным иммунитетом к тяжелому острому респираторному синдрому коронавируса-2 (SARS-CoV-2) — вирусу, вызывающему COVID-19. Всемирная организация здравоохранения не рекомендует внедрять сертификацию иммунитета в настоящее время по причине неуверенности в формировании длительного иммунитета у лиц, переболевших COVID-19, а также ввиду опасений в отношении надежности предлагаемого метода серологического тестирования для определения иммунитета. Сертификацию иммунитета можно рассматривать только при условии соблюдения научных пороговых значений для обеспечения иммунитета, основанных на антителах или других критериях. Однако, даже если сертификация иммунитета получит широкую поддержку со стороны науки, она имеет массу этических проблем с точки зрения различных ограничений индивидуальных свобод и процесса реализации этих ограничений. Авторы исследуют основные соображения этической приемлемости сертификации иммунитета для освобождения людей от ограничительных мер во время пандемии COVID-19. Этическая приемлемость сертификации иммунитета зависит не только от необходимости соответствовать строгим научным критериям, но и от ее использования, целей политики и принимаемых мер по снижению потенциального вреда и предотвращению непропорционального бремени для не имеющих сертификата лиц и нарушений личных свобод и прав.

Anaemia is a condition in which either the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiologic needs, which vary by age, sex, altitude, smoking and pregnancy status. The global estimate of childhood anaemia indicates that 293.1 million children are anaemic, and 28.5% of these children reside in sub-Sahara Africa. Also, anaemia is a significant public health problem with a high age-standardised death rate of 11.18 per 100,000 in Zambia.We conducted a cross-sectional study involving 392 anaemic children aged one year to 14 years. The study was conducted at the Children Hospital, University Teaching Hospitals, which is a third-level referral Hospital in Lusaka, Zambia. The aim was to determine the most common type of anaemia, it’s severity, and the most affected age groups among children aged 1–14 years.Out of 392 participants, 219 (56%) were female. Maximum haemoglobin recorded was 10.9g/dl, a minimum of 2.0 g/dl, a mean of 7.8g/dl and a standard deviation of 1.86g/dl. 200 (51%) participants had severe anaemia, and 192 (49%) had moderate anaemia with none having mild anaemia. Microcytic hypochromic anaemia was the commonest (60%), followed by normochromic normocytic anaemia (26%) and the least was macrocytic anaemia in 14% of the participants. An analysis of variance (ANOVA) showed that the difference in mean haemoglobin concentration between age groups was not significant, F (7.94) = 0.83, p > 0.57. A Chi-squared test was used to determine the relationship between anaemia types (microcytic, hypochromic) and age groups. The interaction was not significant (Chi-Square (1) = 1.28, p-value = 0.73. Microcytic hypochromic anaemia was the most prevalent and all age groups were equally affected. We recommend the country’s National Food and Nutrition Commission to revisit the Zambian National Strategy and Plan of Action for the Prevention and Control of Vitamin A Deficiency and Anaemia of 1999 to 2004 and implement the measures stated in the strategic plan.

IntroductionThe novel Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2), in Africa is characterised by a more substantial proportion of asymptomatic (or mildly symptomatic) individuals thought to be playing a role in the spread of the infection. The exact proportion and degree of infectiousness of asymptomatic individuals remains unclear. Studies however indicate that their management is crucial for control of SARS-CoV-2 transmission.MethodologyWe developed a simplified deterministic susceptible-exposed-infectious-removed (SEIR) mathematical model to assess the effect of active isolation of SARS-CoV-2 infected but asymptomatic individuals through blanket testing for control of the outbreak in Lusaka Province of Zambia. Here we modelled two scenarios; (1) assuming asymptomatic individuals comprised 70% of all COVID-19 cases and (2) asymptomatic individuals comprised only 50% of the cases. For contrast, the model was assessed first under the assumption that asymptomatic individuals are equally as infectious as symptomatic individuals and then secondly, and more likely, assuming asymptomatic individuals are only half as infectious as symptomatic individuals.ResultsFor the model assuming 70% asymptomatic cases, a minimum sustained blanket testing rate of ≥ 7911 tests/100000 population was sufficient to control the outbreak if asymptomatic individuals are only half as infectious while if equal infectiousness was assumed then a testing rate of ≥ 10028 tests/ 100000 population would be required. For 50% asymptomatic, minimum blanket testing rates of ≥ 4540 tests/ 100000 population was sufficient to control the outbreak at both assumed levels of infectiousness for asymptomatic individuals relative to symptomatic individuals.Discussion and conclusionOur model predicts that the current testing rates of ≈ 150/100,000 population are inadequate to control transmission of SARS-Cov-2 in Lusaka. Active isolation of COVID-19 cases including asymptomatic individuals through blanket testing can be used as a possible measure for control of the SARS-Cov-2 transmission in Lusaka, Zambia.

The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, which include some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes that occur in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the transcriptional variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using mRNA transcription data of ELF4 from the Cancer Genome Atlas pan-cancer project of 9,350 samples, we identify two groups of patient's tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we found that, besides being associated with comparatively worse disease outcomes, tumours that express high ELF4 mRNA transcript tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines from the Genomics of Drug Sensitivity in Cancer, we discover that cell lines that express high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment and prognostic strategies.

The Coronavirus disease 2019 (COVID-19) pandemic has killed over two hundred thousand people by end of April, 2020. America and Europe top in deaths from COVID-19 whereas the numbers are lower in Africa for unclear reasons. Emerging evidence suggests the role of hyperactive immune responses characterised by high pro-inflammatory cytokines in severe cases of COVID-19 and deaths. In this perspective, we explore the possible factors that may contribute to mild inflammatory responses in some cases of COVID-19 by focusing on immune education, parasites, sex hormones and chronic diseases, as well as genetic tolerance. To build our perspective, evidence is also extracted from wild rodents due to their multi-tasking immune responses as a result of constant exposure to pathogens.

IntroductionLifestyle-related diseases like type 2 diabetes mellitus, have emerged as a significant public health problem due to rapid urbanization and industrialization. In 2018, the prevalence of type 2 diabetes mellitus was estimated to be 500 million cases worldwide and was comparable between high- and low-income countries. Diabetes leads to multiple complications, including end-stage renal disease, cardiovascular disease, infection, and death. Anaemia in diabetic individuals has severe adverse effects on the quality of life and is associated with disease progression. A cross-sectional study was conducted that included 101 participants. The study aimed to determine the prevalence of anaemia and kidney disease and their interplay with medication and/or blood glucose levels in T2D patients.Resultsseventy-one per cent of participants were females. Majority of patients 62% were on Insulin, 30% on metformin, 7% on a combination of metformin and glimepiride and 1% on glimepiride. Ninety-five (94%) of the participants were HIV negative. The prevalence of anaemia among the participants was 23% out of which 56% had moderate anaemia, and 44% had mild anaemia. Twenty-one per cent (21%) of the participants had high creatinine levels signifying impaired kidney function or kidney disease. Anaemia was significantly associated with kidney function, fasting blood glucose and use of metformin; p = 0.042 beta = 2.5, p = 0.025 beta = 2.7 and p = 0.040 beta = −2.5 respectively.ConclusionThe study found the prevalence of anaemia of 23%, which was of moderate public health concern. Also, the prevalence of kidney disease was high in patients with Type 2 Diabetes Mellitus. It also found that kidney disease and high blood glucose levels increase the chances of developing anaemia. However, we found that metformin had a protective role against the development of anaemia in Type 2 Diabetes Mellitus patients.

BackgroundDespite contributing to a significant reduction in rotavirus associated diarrhoea in highly burdened low- and middle-income countries, live attenuated, oral rotavirus vaccines have lower immunogenicity and efficacy in these settings in comparison to more developed countries. Breastmilk has been implicated among factors contributing to this lowered oral vaccine efficacy. We conductedin-vitroexperiments to investigate the inhibitory effects of maternal antibody and other non-antibody components in breastmilk on rotavirus vaccine strain (Rotarix) multiplication in MA104 cell culture system and assessed associations within-vivovaccine seroconversion in vaccinated infants.MethodsBreastmilk samples were collected from mothers before routine rotavirus vaccination of their infant at 6 weeks of age. For each sample, whole breastmilk, purified IgA, purified IgG and IgG and IgA depleted breastmilk samples were prepared as exposure preparations. A 96 well microtitre plate was set up for each sample including a control in which only MA104 cells were grown as well as a virus control with MA104 cells and virus only. The outcome of interest was 50% inhibition dilution of each of the exposure preparations calculated as the titer at which 50% of virus dilution was achieved. Samples from 30 women were tested and correlated to vaccine seroconversion status of the infant. HIV status was also correlated to antiviral breastmilk proteins.ResultsThe mean 50% inhibitory dilution titer when whole breastmilk was added to virus infected MA104 cells was 14.3 (95% CI: 7.1, 22.7). Incubation with purified IgG resulted in a mean 50% inhibitory dilution of 5 (95%CI -1.6, 11.6). Incubating with purified IgA resulted in a mean 50% inhibitory dilution of 6.5 (95% CI -0.7, 13.7) and IgG and IgA depleted breastmilk did not yield any inhibition with a titer of 1.06 (95%CI 0.9, 1.2). Higher milk IgA levels contributed to a failure of infants to seroconvert. HIV was also not associated with any antiviral breastmilk proteins.Discussion and conclusionWhole breastmilk and breastmilk purified IgG and IgA fractions showed inhibitory activity against the rotavirus vaccine Rotarix™ whilst IgA and IgG depleted breastmilk with non-antibody breastmilk fraction failed to show any inhibition activityin-vitro. These findings suggest that IgA and IgG may have functional inhibitory properties and indicates a possible mechanism of how mothers in rotavirus endemic areas with high titres of IgA and IgG may inhibit viral multiplication in the infant gut and would potentially contribute to the failure of their infants to serocovert. There was not association of HIV with either lactoferrin, lactadherin or tenascin-C concentrations.

Background People living with HIV ( PLWH ) are at increased risk of cardiovascular disease, including hypertension, which persists despite effective plasma viral suppression on antiretroviral therapy. HIV infection is characterized by long‐term alterations in immune function, but the contribution of immune factors to hypertension in PLWH is not fully understood. Prior studies have found that both innate and adaptive immune cell activation contributes to hypertension. Methods and Results We hypothesized that chronic inflammation may contribute to hypertension in PLWH . To test this hypothesis, we enrolled a cohort of 70 PLWH (44% hypertensive) on a long‐term single antiretroviral therapy regimen for broad phenotyping of inflammation biomarkers. We found that hypertensive PLWH had higher levels of inflammatory cytokines, including tumor necrosis factor‐α receptor 1, interleukin‐6, interleukin‐17, interleukin‐5, intercellular adhesion molecule 1 and macrophage inflammatory protein‐1α. After adjustment for age, sex, and fat mass index, the circulating eosinophils remained significantly associated with hypertension. On the basis of these results, we assessed the relationship of eosinophils and hypertension in 2 cohorts of 50 and 81 039 similar HIV ‐negative people; although eosinophil count was associated with prevalent hypertension, this relationship was abrogated by body mass index. Conclusions These findings may represent a unique linkage between immune status and cardiovascular physiological characteristics in HIV infection, which should be evaluated further.

Purpose of Review To systematically review recent findings on the role of immune cell activation in the pathogenesis of hypertension in people living with HIV (PLWH) and compare studies from Sub-Saharan Africa with what is reported in the USA and European literature according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Recent Findings PLWH have an increased risk for development of hypertension and cardiovascular disease. Chronic immune activation contributes to hypertension but the inflammatory milieu that predisposes PLWH to hypertension is poorly understood. We identified 45 relevant studies from 13 unique African countries. The prevalence of hypertension in PLWH on antiretroviral therapy (ART) and the ART-naive PLWH ranged from 6 to 50% and 2 to 41%, respectively. Interleukin (IL)-17A, interferon (IFN)-γ, and higher CD4+ T cell counts were associated with hypertension in ART-treated participants. Summary Targeting adaptive immune activation could provide improved care for hypertensive PLWH. Further research is needed to characterize the inflammatory milieu contributing to hypertension in PLWH especially in African populations where the global burden of HIV is the highest.

Objective The objective of this study is to quantify and compare the effect of excess dietary salt on immune cell activation and blood pressure in HIV versus HIV negative individuals. Results Salt-sensitivity is associated with increased immune cell activation in animal studies. This concept has not been tested in people living with HIV. This study will therefore add more information in elucidating the interaction between HIV infection and/or anti-retroviral therapy (ART), immune-activation/inflammation and hypertension. Electronic supplementary material The online version of this article (10.1186/s13104-019-4470-2) contains supplementary material, which is available to authorized users.

The aim of this study was to determine the nature and role of traditional forms of counselling and the scope of common problems presented to traditional counsellors in Lusaka province. It used a qualitative research methodology and deployed a holistic single-case study design with multiple embedded units of analysis. The sample consisted of 80 adult participants and one focus group interview with 8 discussants; and it was selected based on the purposive sampling method and snowball technique. Data collection was elicited through structured individual interviews and semi-structured group interview. The study revealed that traditional forms of counselling are rooted in traditional systems of knowledge and sociocultural values, customs, and practices; and they are essentially community-based and multicultural in nature.

Background: Introduction of rotavirus vaccines has resulted in a decrease in rotavirus related mortality and morbidity. We sought to conduct a meta-analysis to estimate the effect of rotavirus vaccine on incidence of diarrhoea. Methods: The MEDLINE database was searched through PubMed interface using both textword and subject headings (MeSH). The search strategies were [“rotavirus vaccine effectiveness” or “rotavirus vaccine efficacy” or “rotavirus vaccine eff*”]. The reference lists of the most recent studies identified by the search were checked for additional studies (if not already retrieved). We included both randomised trials and observational studies, which investigated the effect of rotavirus vaccine on incidence of diarrhoea. Results: There was strong evidence of vaccine efficacy (70%) on incidence of diarrhoea (Pooled risk ratio (pRR)=0.30; 95% confidence interval (CI)=(0.24,0.38); p

Both HIV infection and Methamphetamine (Meth) use disorders are associated with greater depressive symptoms and oxidative stress; whether the two conditions would show additive or interactive effects on the severity of depressive symptoms, and whether this is related to the level of oxidative stress in the CNS is unknown. 123 participants were evaluated, which included 41 HIV-seronegative subjects without substance use disorders (Control), 25 with recent (

Proton magnetic resonance spectroscopy ((1)H MRS) has been applied to numerous clinical studies, especially for neurological disorders. This technique can non-invasively evaluate brain metabolites and neurochemicals in selected brain regions and is particularly useful for assessing neuroinflammatory disorders. Neurometabolites assessed with MRS include the neuronal markers N-acetylaspartate (NAA) and glutamate (Glu), as well as the glial marker myo-inositol (MI). Therefore, the concentrations of these metabolites typically correspond to disease severity and often correlate well with clinical variables in the various brain disorders. Neuroinflammation with activated astrocytes and microglia in brain disorders are often associated with elevated MI, and to a lesser extent elevated total creatine (tCr) and choline containing compounds (Cho), which are found in higher concentrations in glia than neurons, while neuronal injury is indicated by lower than normal levels of NAA and Glu. This review summarizes the neurometabolite abnormalities found in MRS studies performed in patients with neuroinflammatory disorders or neuropathic pain, which also may be associated with neuroinflammation. These brain disorders include multiple sclerosis, neuroviral infections (including Human Immunodeficiency virus and Hepatitis C), degenerative brain disorders (including Alzheimer's disease and Parkinson's disease), stimulant abuse (including methamphetamine and cocaine) as well as several chronic pain syndromes.

The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE e 4 allele(s) in HIV-infected patients are unknown. However, APOE e 4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE e 4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (-19%, p= 0.03). While SN subjects with or without e 4 allele showed no difference in CSF APOE levels, e 4+ HIV+ subjects had similar levels to the SN subjects but higher levels than e 4- HIV+ subjects (+34%, p= 0.01). Furthermore, while HIV+ subjects with e 2 or e 3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r= +0.35, p= 0.05), e 4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r= -0.61, p= 0.02), had lower Global Cognitive Scores (r= -0.57, p= 0.03), and had poorer performance on tests involving learning (e 4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in e 4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the e 4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.

Background: Microbial translocation has been recognized as an important factor in monocyte activation and contributing to AIDS pathogenesis with elevated plasma lipopolysaccharide (LPS) levels, as a marker for microbial translocation, seen in advanced HIV disease. Therefore, the current study was undertaken to assess monocyte activation in vitro by LPS and to determine its impact on monocyte phenotype. Methods: Monocytes from non-HIV-infected donors were analyzed for CD14, CD16, CD69, TNFα, and CCR5 by flow cytometry pre- and post-stimulation with LPS. In-vitro cultures were then set up to expose non-activated and activated monocytes to R5-, X4-, and dual (R5/X4)-tropic viruses; and the amount of HIV present on the cells was assayed. Results: Non-HIV-infected monocytes, after LPS stimulation, were confirmed to have an activated phenotype with increase in CD16 and CD69 surface expressions (p 0.05). The activation phenotype was supported by increase in TNFα production, p 0.05. The activated monocytes had increased surface CCR5 (from 21% to 98%; p = 0.05); and were found to have more R5-tropic virus than non-activated monocytes (p 0.05). Conclusions: Following activation by LPS, non-HIV-infected monocytes were found to have increase in surface CCR5. These activated monocytes, when exposed to R5-tropic virus, were found to have more virus compared to non-activated monocytes. The significance of the findings could lie in explaining how microbial translocation plays a role in HIV progression; and possibly promoting CCR5-directed strategies in treating HIV.