Hepatitis and tuberculosis testing are much less common than HIV testing among adults in Kisumu, Kenya: results from a cross-sectional assessment

Background Kenya has a high burden of HIV, viral hepatitis, and tuberculosis. Screening is necessary for early diagnosis and treatment, which reduces morbidity and mortality across all three illnesses. We evaluated testing uptake for HIV, viral hepatitis, and tuberculosis in Kisumu, Kenya. Methods Cross-sectional data from adults aged 18–35 years who enrolled in a prospective HIV incidence cohort study from February 2017 to May 2018 were analyzed. A questionnaire was administered to each participant at screening for study eligibility to collect behavioral characteristics and to assess prior testing practices. Among participants without a history of previously-diagnosed HIV, multivariable robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV testing in the 12 months prior to enrollment. A hierarchical model was used to test for differential access to testing due to spatial location. Results Of 671 participants, 52 (7.7%) were living with HIV, 308 (45.9%) were female, and the median age was 24 (interquartile range 21–28) years. Among 651 (97.0%) who had ever been tested for HIV, 400 (61.2%) reported HIV testing in the past 6 months, 129 (19.7%) in the past 6–12 months, and 125 (19.1%) more than one year prior to enrollment. Any prior testing for viral hepatitis was reported by 8 (1.2%) participants and for tuberculosis by 51 (7.6%). In unadjusted models, HIV testing in the past year was more common among females (PR 1.08 [95% CI 1.01, 1.17]) and participants with secondary education or higher (PR 1.10 [95% CI 1.02, 1.19]). In the multivariable model, only secondary education or higher was associated with recent HIV testing (adjusted PR 1.10 [95% CI 1.02, 1.20]). Hierarchical models showed no geographic differences in HIV testing across Kisumu subcounties. Conclusions Prior HIV testing was common among study participants and most had been tested within the past year but testing for tuberculosis and viral hepatitis was far less common. HIV testing gaps exist for males and those with lower levels of education. HIV testing infrastructure could be leveraged to increase access to testing for other endemic infectious diseases.

Fizzle Testing: An Equation Utilizing Random Surveillance to Help Reduce COVID-19 Risks

A closed-form equation, the Fizzle Equation, was derived from a mathematical model predicting Severe Acute Respiratory Virus-2 dynamics, optimized for a 4000-student university cohort. This equation sought to determine the frequency and percentage of random surveillance testing required to prevent an outbreak, enabling an institution to develop scientifically sound public health policies to bring the effective reproduction number of the virus below one, halting virus progression. Model permutations evaluated the potential spread of the virus based on the level of random surveillance testing, increased viral infectivity and implementing additional safety measures. The model outcomes included: required level of surveillance testing, the number of infected individuals, and the number of quarantined individuals. Using the derived equations, this study illustrates expected infection load and how testing policy can prevent outbreaks in an institution. Furthermore, this process is iterative, making it possible to develop responsive policies scaling the amount of surveillance testing based on prior testing results, further conserving resources.

Infusion therapy for cardiovascular diseases: the allowed limits

Background. Analysis of the mortality structure of patients with coronavirus disease (COVID-19) had found that 69.2 % of non-survivors had hypertension. Comorbid diabetes mellitus (31.8 %) and coronary heart disease (28.2 %) were also common. During pandemic, it is necessary to maintain optimal cardiovascular therapy by continuing to administer its main drugs (acetylsalicylic acid, statins, β-blockers, angiotensin-converting enzyme inhibitors – ACEI). Objective. To describe infusion therapy (IT) for cerebrovascular and cardiovascular diseases in settings of the COVID-19 pandemic. Materials and methods. Analysis of the literature on this topic. Results and discussion. Although the spike proteins of the new coronavirus have the tropism to ACE-2, discontinuation of ACEI is unwarranted and may worsen the course of cardiovascular disease (CVD). Particular attention should be paid to the diagnosis of acute coronary syndrome (ACS) in COVID-19. In myocardial infarction, myocarditis or cardiomyopathy on the background of COVID-19, there is a moderate increase in troponin, brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide. An increase in D-dimers is a prognostic marker of the unfavorable prognosis. The algorithm for the ACS diagnosis includes the detection of typical clinical symptoms, ECG analysis, detection of disorders of local contractility of the left ventricle. Determination of troponin in patients without clinical manifestations of ACS with nonspecific manifestations of COVID-19 is not recommended. As for reperfusion therapy strategies, it is indicated in patients with symptoms of ischemia lasting >12 hours and a persistent increase in ST in two adjacent leads. In the absence of prior testing for coronavirus infection, all patients should be managed according to the tactics for COVID-positive patients. In non-STEMI, patients should be stratified according to their risk level (very high, high, moderate, low). In case of high risk, the early (<24 hours) invasive strategy is reasonable, in case of intermediate risk it is reasonable to consider noninvasive treatment. It should be remembered that the use of certain drugs for the treatment of COVID-19 (azithromycin, chloroquine, hydroxychloroquine, lopinavir, ritonavir) is associated with a risk of cardiotoxicity and life-threatening arrhythmias. Cardiotoxicity monitoring (determination of the corrected QT interval) should be performed before the start of therapy and then once in 5 days, primarily in risk groups (men >55 years, women >65 years and people with the CVD history). Lopinavir and ritonavir may also decrease the levels of active metabolites of clopidogrel and increase – of ticagrelor, so prasugrel is the antiplatelet drug of choice for COVID-19. Amiodarone also interacts with a large number of antiviral drugs. In turn, statins have multiple immunomodulatory effects including increase of the innate antiviral immune response. It is recommended to continue taking those statins that were prescribed earlier. If co-administration with lopinavir and ritonavir is required, the minimum dose of rosuvastatin or atorvastatin should be started. These antivirals are able to interact with calcium channel blockers and increase their concentration, so the dose of amlodipine and diltiazem can be reduced by 50 %. Endothelial dysfunction (ED) caused by a viral infection leads to the excessive thrombin formation and inhibition of fibrinolysis, increasing the risk of thrombotic complications. Nitric oxide (NO) plays an important role in counteracting ED. NO also inhibits the replication of the acute severe respiratory syndrome coronavirus and improves the survival of infected cells. L-arginine (Tivortin, “Yuria-Pharm”) is the only substrate for NO synthase that catalyzes the formation of NO in endothelial cells. According to the results of the own study, Tivortin helped to reduce the content of fibrinogen and soluble fibrin-monomer complexes, as well as to increase the thromboplastin time. Endothelium-dependent vasodilation also improved after administration of Tivortin. Tivorel (“Yuria-Pharm”) contains L-arginine and L-carnitine, which allows this drug to increase the survival of cardiomyocytes and endothelial cells, to restore homeostasis in the affected areas of the myocardium, and to counteract the progression of atherogenesis and thrombosis. In case of COVID-19, it is also advisable to prescribe edaravone (Ksavron, “Yuria-Pharm”), which neutralizes the cytokine storm, inhibits lipid peroxidation, protects against endothelial damage and, penetrating the blood-brain barrier, counteracts cerebral edema. In case of the need in IT, it is advisable to choose Reosorbilact (“Yuria-Pharm”), which has anti-shock, rheological, detoxifying, alkalizing and osmodiuretic effects. In hypovolemic shock and intracranial hemorrhage, the use of isotonic low-molecular-weight gelatin preparations (Volutenz, “Yuria-Pharm”) has been shown. Conclusions. 1. In the absence of prior testing for coronavirus infection, all patients should be managed following the tactics for COVID-positive patients. 2. The use of azithromycin, chloroquine, hydroxychloroquine, lopinavir, ritonavir is associated with a risk of cardiotoxicity and life-threatening arrhythmias. 3. ED, caused by a viral infection, increases the risk of thrombotic complications. 4. It is reasonable to include the required solutions (Tivortin, Tivorel, Ksavron, Reosorbilact, Volutenz) into the combined IT of COVID-19 patients.

Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer?

Purpose To characterize the spectrum of BRCA1 and BRCA2 pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations. Methods Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation in BRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screened BRCA1 and BRCA2 in the germline DNA of 426 women in total. Results We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants in BRCA1 and BRCA2, respectively. We observed five BRCA1 and eight BRCA2 P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 in BRCA1 and 10 in BRCA2). Conclusions These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.

Validating Autoclave Cycles for Carcass Disposal in Animal Biosafety Level 2/3 Containment Laboratories

Introduction:Animal carcasses differ in composition from other types of solid waste, and through prior testing it was determined that cycle parameters applied to general, solid biohazardous waste did not ensure proper sterilization of ferret carcasses.Objectives:The goals of this study were to develop and validate an autoclave cycle that would ensure the decontamination of infectious animal carcasses before removal from an animal biosafety level 2/3 containment suite for downstream disposal and to test different ways to prepare and package animal carcasses for autoclaving.Methods:Intact ferret carcasses were implanted with biological indicators, and the carcasses were placed in biohazard bags, then into metal pans. To test the efficacy of the autoclave cycle on larger biomasses, 1, 2, or 4 ferret carcasses were placed in a biohazard bag. A total of 4 carcasses were placed in each pan. An autoclave cycle was created to begin the study. After initial tests, minor modifications to the initial test cycle parameters were made, and a new cycle was validated for ferret carcasses up to 2 kg each. Parameters for the validated cycle were as follows: sterilization time 240 minutes, temperature 125°C, 5 prevacuum pulses, and chamber pressure 15 psi.Results:The results of this study indicate that an extended sterilization time is required to successfully decontaminate animal carcasses compared with regular, solid, and biohazardous waste.Conclusions:This study demonstrates that it is possible to sterilize multiple intact ferret carcasses per load under validated autoclave cycle conditions.

The gendered experience of HIV testing: factors associated with prior testing differ among men and women in rural Tanzania

HIV testing remains below UNAIDS 90–90–90 goals in sub-Saharan Africa. The aim of this study was to understand gender-specific factors related to HIV testing in Kisarawe, Tanzania. Informed by Social Action Theory, we analyzed cross-sectional data from a population-based random sample using bivariate and multivariate logistic regression to identify the contextual, behavioral, and interpersonal factors associated with prior HIV testing – specifically, any prior testing and testing within the past year. Of 644 participants, 63.1% of men and 85.5% of women reported ever testing for HIV. Younger men and women (aged 18–25 years) had significantly lower odds of prior HIV testing compared with older participants. For men, low levels of anticipated stigma and having ever talked about HIV were both positively associated with any prior testing. Men who knew if a sexual partner had received an HIV test had almost three times the odds of receiving a recent HIV test compared to men with no knowledge of their partners’ testing status (aOR = 2.96, 95% CI: 1.22–7.17, p = 0.01). For women, knowing someone who is HIV-positive was associated with increased odds of any prior testing (aOR = 2.74, 95% CI: 1.24–6.07, p = 0.01). Gender-specific, proactive interventions are needed to increase testing uptake, especially for young people and men.

P.129 Worster-Drought syndrome caused by LINS mutations

Background: Worster-Drought syndrome (WDS) is a congenital, pseudobulbar paresis. Patients show oromotor apraxia causing impaired speech, drooling, dysphagia and varying degrees of cognitive impairment. Familial cases are reported although causative genes have not been identified. LINS mutations have recently been reported in patients with severe cognitive and language impairment. Methods: The proband was diagnosed with WDS at 8 years old because of longstanding drooling, dysphagia and impaired tongue movement. At 14 years old, he remains aphonic, using sign language and typing on a smart-tablet to communicate. Neurological examination including facial and extraocular movement was otherwise unremarkable. MRI brain revealed no heterotopia or atrophy. Results: An expanded intellectual disability panel at GeneDx identified nonsense mutations in LINS alleles: c.1096; p.Glu366X and c.1178 T>G, p.Lys393X. Neuropsychological testing at 14 years old noted nonverbal reasoning skills at 5 year old level with relative sparing of his receptive vocabulary and visual attention. Compared to prior testing at 9 years his receptive language improved from a 6 year old to an 8.5 year old level. Conclusions: Nonsense mutations of LINS have been identified in a patient with WDS. Despite his severe and persistent aphonia, improvements in receptive language were observed with global intellectual functioning better than expected.