Power-law population heterogeneity governs epidemic waves

We generalize the Susceptible-Infected-Removed (SIR) model for epidemics to take into account generic effects of heterogeneity in the degree of susceptibility to infection in the population. We introduce a single new parameter corresponding to a power-law exponent of the susceptibility distribution at small susceptibilities. We find that for this class of distributions the gamma distribution is the attractor of the dynamics. This allows us to identify generic effects of population heterogeneity in a model as simple as the original SIR model which is contained as a limiting case. Because of this simplicity, numerical solutions can be generated easily and key properties of the epidemic wave can still be obtained exactly. In particular, we present exact expressions for the herd immunity level, the final size of the epidemic, as well as for the shape of the wave and for observables that can be quantified during an epidemic. In strongly heterogeneous populations, the herd immunity level can be much lower than in models with homogeneous populations as commonly used for example to discuss effects of mitigation. Using our model to analyze data for the SARS-CoV-2 epidemic in Germany shows that the reported time course is consistent with several scenarios characterized by different levels of immunity. These scenarios differ in population heterogeneity and in the time course of the infection rate, for example due to mitigation efforts or seasonality. Our analysis reveals that quantifying the effects of mitigation requires knowledge on the degree of heterogeneity in the population. Our work shows that key effects of population heterogeneity can be captured without increasing the complexity of the model. We show that information about population heterogeneity will be key to understand how far an epidemic has progressed and what can be expected for its future course

Kaposi's sarcoma of the hand mimicking squamous cell carcinoma in a woman with no evidence of HIV infection: a case report

<p>Abstract</p> <p>Introduction</p> <p>Kaposi's sarcoma is a vascular neoplasm mainly affecting the skin of the lower extremities. Although it is the most common neoplasm affecting patients with AIDS, sporadic cases in HIV-negative people have been reported. It is a lesion mainly affecting men and its clinical presentation presents a challenge, as it can resemble other benign or malignant skin lesions.</p> <p>Case presentation</p> <p>We report a rare case of Kaposi's sarcoma presenting in a 68-year-old Mediterranean woman with no evidence of HIV infection. The patient had a 6-month history of a slowly progressing pigmented lesion on the dorsum of her left hand. The lesion clinically resembled a squamous cell carcinoma. The patient was treated with a wide excision of the lesion and primary reconstruction with a full thickness skin graft. Histopathological and immunohistochemical analysis of the excised lesion revealed the presence of Kaposi's sarcoma. Serologic investigation for HIV was negative but polymerase chain reaction for human herpes virus type 8 infection was positive. Thorough clinical and imaging investigation of the abdomen and chest were both negative for loci of disease.</p> <p>Conclusion</p> <p>Kaposi's sarcoma, although rare in its sporadic form, should be considered in the differential diagnosis of indeterminate skin lesions, especially those affecting the extremities.</p

Development of real-time NASBA assays with molecular beacon detection to quantify mRNA coding for HHV-8 lytic and latent genes

BACKGROUND: Human herpesvirus-8 (HHV-8) is linked to the pathogenesis of Kaposi's sarcoma (KS), and the HHV-8 DNA load in peripheral blood mononuclear cells (PBMC) is associated with the clinical stage of KS. To examine the expression of HHV-8 in PBMC, four HHV-8 mRNA specific NASBA assays were developed METHODS: We have developed four quantitative nucleic acid sequence-based amplification assays (NASBA-QT) specifically to detect mRNA coding for ORF 73 (latency-associated nuclear antigen, LANA), vGCR (a membrane receptor), vBcl-2 (a viral inhibitor of apoptosis) and vIL-6 (a viral growth factor). The NASBA technique amplifies nucleic acids without thermocycling and mRNA can be amplified in a dsDNA background. A molecular beacon is used during amplification to enable real-time detection of the product. The assays were tested on PBMC samples of two AIDS-KS patients from the Amsterdam Cohort. RESULTS: For all four assays, the limit of detection (LOD) of 50 molecules and the limit of quantification (LOQ) of 100 molecules were determined using in vitro transcribed RNA. The linear dynamic range was 50 to 10(7) molecules of HHV-8 mRNA. We found HHV-8 mRNA expression in 9 out of the 10 tested samples. CONCLUSION: These real-time NASBA assays with beacon detection provide tools for further study of HHV-8 expression in patient material

Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion

Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS

Herpesvirus type 6 in patients undergoing bone marrow transplantation: serologic features and detection by polymerase chain reaction

To evaluate the potential role of human herpesvirus type 6 (HHV-6) infection in patients after bone marrow transplantation (BMT) we sequentially analyzed buffy coat leukocytes, oral lavage fluid, and urine from 57 patients for the presence of HHV-6 DNA by polymerase chain reaction (PCR) before and after 60 BMTs. Twenty-four patients undergoing autologous BMT and 36 with allogeneic BMT were studied. Thirty-six patients (60%) were PCR positive in one or more tests. The majority of PCR-positive patients had positive results only sporadically, in 1 (n = 23) or 2 weeks (n = 5). Six patients were positive in 3 to 5 weeks. In 2 patients, we found a high frequency of positive tests, in 7 of 7 and 10 of 10 weeks analyzed. Twenty-four patients (40%) remained PCR negative throughout the post-BMT period. There was a significant correlation between the results of HHV-6 PCR and the occurrence of acute graft-versus-host disease (aGVHD). In grade II-IV, 6 of 8 (75%) patients had 2 or more positive PCR tests, compared with 5 of 25 (20%) patients without or with grade I aGVHD (P = .01). There was no difference in the outcome of PCR tests with respect to the type of BMT or pre-BMT HHV-6 enzyme-linked immunosorbent assay titers. Restriction enzyme analysis of PCR amplificates from 18 patients showed HHV-6 variant B in 16 (88.9%) and variant A in 2 cases (11.1%). We conclude that HHV-6 DNA can be detected in 60% of the patients after BMT. HHV-6 DNA can be detected more frequently in patients with moderate and severe aGVHD than in patients without aGVHD or with mild aGVHD

Development of recombinant diagnostic reagents based on pp85(U14) and p86(U11) proteins to detect the human immune response to human herpesvirus 7 infection.

infected cell proteins with apparent molecular masses of about 85 to 89 kDa. The genes that encode these proteins are unknown. However, several HHH-7 genes that possibly encode proteins in this molecular mass range have been identified. Thus, the proteins encoded by open reading frame U14 (85 kDa) and U11 (86 kDa) were expressed as recombinant proteins in bacteria. Of 13 human serum specimens that recognized the 85- to 89-kDa protein(s) of HHV-7-infected cells by immunoblotting, 12 were also reactive with recombinant pp85(U14) and 8 were reactive with p86(U11). It is concluded that (i) the HHV-7 immunodominant protein is pp85(U14) and (ii) the lack of posttranslational modifications in procaryotically expressed pp85 does not adversely affect the reactivity of human sera. Monoclonal antibody (MAb) 5E1 is an HHV-7-specific MAb directed to pp85(U14). Here, the HHV-7-specific epitope in pp85(U14) was finely mapped to the C' terminal region between amino acid residues 484 and 502. However, as indicated by the low level of reactivity of human sera with the HHV-7-specific epitope recognized by MAb 5E1, human sera recognize additional epitopes of pp85(U14) that are required for their full reactivity