Shweta Bansal

When individual behaviour matters: homogeneous and network models in epidemiology

Heterogeneity in host contact patterns profoundly shapes population-level disease dynamics. Many epidemiological models make simplifying assumptions about the patterns of disease-causing interactions among hosts. In particular, homogeneous-mixing models assume that all hosts have identical rates of disease-causing contacts. In recent years, several network-based approaches have been developed to explicitly model heterogeneity in host contact patterns. Here, we use a network perspective to quantify the extent to which real populations depart from the homogeneous-mixing assumption, in terms of both the underlying network structure and the resulting epidemiological dynamics. We find that human contact patterns are indeed more heterogeneous than assumed by homogeneous-mixing models, but are not as variable as some have speculated. We then evaluate a variety of methodologies for incorporating contact heterogeneity, including network-based models and several modifications to the simple SIR compartmental model. We conclude that the homogeneous-mixing compartmental model is appropriate when host populations are nearly homogeneous, and can be modified effectively for a few classes of non-homogeneous networks. In general, however, network models are more intuitive and accurate for predicting disease spread through heterogeneous host populations.

A Comparative Analysis of Influenza Vaccination Programs

Background The threat of avian influenza and the 2004–2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. Methods and Findings We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. Conclusions If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities.

Sodium Retention in Heart Failure and Cirrhosis Potential Role of Natriuretic Doses of Mineralocorticoid Antagonist

Patients with cirrhosis and heart failure (HF) share the pathophysiology of decreased effective arterial blood volume because of splanchnic vasodilatation in cirrhosis and decreased cardiac output in HF, with resultant stimulation of the renin-angiotensin-aldosterone system. Hyperaldosteronism plays a major role in the pathogenesis of ascites and contributes to resistance to loop diuretics. Therefore, the use of high doses of aldosterone antagonist (spironolactone up to 400 mg/day) is the main therapy to produce a negative sodium balance in cirrhotic patients with ascites. Hyperaldosteronism also has increasingly been recognized as a risk factor for myocardial and vascular fibrosis. Therefore, low-dose aldosterone antagonists are being used in patients with HF for cardioprotective action. However, the doses (25 to 50 mg/day) at which they are being used in cardiac patients as reported in the Randomized Aldactone Evaluation Study are not natriuretic. It is likely, therefore, that the mortality benefit relates primarily from their effect on cardiac and vascular fibrosis. Resistance to commonly used loop diuretics is frequently present in patients with advanced HF. In patients with decompensated HF with volume overload who are loop diuretic resistant, ultrafiltration may be the only available option. This is, however, an invasive procedure. For these patients, natriuretic doses of aldosterone antagonists (spironolactone >50 mg/day) may be a potential option. The competitive natriuretic response of aldosterone antagonists is related to activity of the renin-angiotensin-aldosterone system: the higher the renin-angiotensin-aldosterone system activity, the higher the dose of aldosterone antagonist required to produce natriuresis. This article will discuss the potential use of natriuretic doses of aldosterone antagonists in patients with HF, including the potential side effect of hyperkalemia.

Network frailty and the geometry of herd immunity

The spread of infectious disease through communities depends fundamentally on the underlying patterns of contacts between individuals. Generally, the more contacts one individual has, the more vulnerable they are to infection during an epidemic. Thus, outbreaks disproportionately impact the most highly connected demographics. Epidemics can then lead, through immunization or removal of individuals, to sparser networks that are more resistant to future transmission of a given disease. Using several classes of contact networks—Poisson, scale-free and small-world—we characterize the structural evolution of a network due to an epidemic in terms of frailty (the degree to which highly connected individuals are more vulnerable to infection) and interference (the extent to which the epidemic cuts off connectivity among the susceptible population that remains following an epidemic). The evolution of the susceptible network over the course of an epidemic differs among the classes of networks; frailty, relative to interference, accounts for an increasing component of network evolution on networks with greater variance in contacts. The result is that immunization due to prior epidemics can provide greater community protection than random vaccination on networks with heterogeneous contact patterns, while the reverse is true for highly structured populations.

Diagnosis and management of hyponatremia in acute illness.

Purpose of reviewHyponatremia is the most common electrolyte disorder present in hospitalized patients. Acute and severe hyponatremia can cause significant morbidity and mortality. The present review discusses the epidemiology, causes, and a practical approach to the diagnosis and management of acute and chronic hyponatremia, including the appropriate use of hypertonic saline and potential future use of the new V2 vasopressin receptor antagonists in critically ill patients. Recent findingsThe increasing knowledge of aquaporin water channels and the role of vasopressin in water homeostasis have enhanced our understanding of hyponatremic disorders. Increased vasopressin secretion due to nonosmotic stimuli leads to decreased electrolyte-free water excretion with resulting water retention and hyponatremia. Vasopressin receptor antagonists induce electrolyte-free water diuresis without natriuresis and kaliuresis. Phase three trials indicate that these agents predictably reduce urine osmolality, increase electrolyte-free water excretion, and raise serum sodium concentration. They are likely to become a mainstay of treatment of euvolemic and hypervolemic hyponatremia. SummaryThe correct diagnosis and management of hyponatremia is complex and requires a systematic approach. Vasopressin receptor antagonists are potential tools in the management of hyponatremia. Further studies are needed to determine their role in the treatment of acute, severe, life-threatening hyponatremia as well as chronic hyponatremia.

Ghrelin protects mice against endotoxemia-induced acute kidney injury

Acute kidney injury (AKI) in septic patients drastically increases the mortality to 50-80%. Sepsis is characterized by hemodynamic perturbations as well as overwhelming induction of proinflammatory cytokines. Since ghrelin has been shown to have anti-inflammatory properties, we hypothesized that ghrelin may afford renal protection during endotoxemia-induced AKI. Studies were conducted in a normotensive endotoxemia-induced AKI model in mice by intraperitoneal injection of 3.5 mg/kg LPS. Serum ghrelin levels were increased during endotoxemia accompanied by increased ghrelin receptor (GHSR-1a) protein expression in the kidney. Ghrelin administration (1.0 mg/kg sc 6 h and 30 min before and 14 h after LPS) significantly decreased serum cytokine levels (TNF-alpha, IL-1beta, and IL-6) and serum endothelin-1 levels which had been induced by LPS. The elevated serum nitric oxide (NO) levels and renal inducible NO synthase expression were also decreased by ghrelin. Renal TNF-alpha levels were also increased significantly in response to LPS and ghrelin significantly attenuated this increase. When administrated before LPS, ghrelin protected against the fall in glomerular filtration rate at 16 h (172.9 +/- 14.7 vs. 90.6 +/- 15.2 microl/min, P < 0.001) and 24 h (147.2 +/- 20.3 vs. 59.4 +/- 20.7 microl/min, P < 0.05) as well as renal blood flow at 16 h (1.65 +/- 0.07 vs. 1.47 +/- 0.04 ml/min, P < 0.01) and 24 h (1.56 +/- 0.08 vs. 1.22 +/- 0.03 ml/min, P < 0.05) after LPS administration without affecting mean arterial pressure. Ghrelin remained renal protective even when it was given after LPS. In summary, ghrelin offered significant protection against endotoxemia-induced AKI. The renal protective effect of ghrelin was associated with an inhibition of the proinflammatory cytokines. Of particular importance was the suppression of TNF-alpha both in the circulation and kidney tissues. Thus, ghrelin may be a promising peptide in managing endotoxemia-induced AKI.

Pulmonary Hypertension, Right Ventricular Failure, and Kidney: Different from Left Ventricular Failure?

In this article, the pathophysiology of left ventricular failure is reviewed. By contrast, the paucity of information about pulmonary arterial hypertension and right ventricular failure is acknowledged. The potential mechanisms whereby renal sodium and water retention in right ventricular failure secondary to pulmonary arterial hypertension can occur, despite normal left ventricular function, are discussed. With right ventricular failure as the primary cause of death in patients with pulmonary hypertension, more information about the mechanisms of renal sodium and water retention in these patients is direly needed. Specifically, studies to examine the activation of the neurohumoral axis at various stages of pulmonary arterial hypertension and right ventricular failure, including inhibition of mineralocorticoid and V2 vasopressin receptors, are indicated.

Social, spatial, and temporal organization in a complex insect society

High-density living is often associated with high disease risk due to density-dependent epidemic spread. Despite being paragons of high-density living, the social insects have largely decoupled the association with density-dependent epidemics. It is hypothesized that this is accomplished through prophylactic and inducible defenses termed ‘collective immunity’. Here we characterise segregation of carpenter ants that would be most likely to encounter infectious agents (i.e. foragers) using integrated social, spatial, and temporal analyses. Importantly, we do this in the absence of disease to establish baseline colony organization. Behavioural and social network analyses show that active foragers engage in more trophallaxis interactions than their nest worker and queen counterparts and occupy greater area within the nest. When the temporal ordering of social interactions is taken into account, active foragers and inactive foragers are not observed to interact with the queen in ways that could lead to the meaningful transfer of disease. Furthermore, theoretical resource spread analyses show that such temporal segregation does not appear to impact the colony-wide flow of food. This study provides an understanding of a complex society’s organization in the absence of disease that will serve as a null model for future studies in which disease is explicitly introduced.

A case of polyomavirus-associated nephropathy presenting late after transplantation

Background A 36-year-old white female, who had received a deceased-donor kidney transplant for end-stage renal disease secondary to reflux nephropathy 8 years previously, was referred to a transplant clinic for evaluation following an increase in her serum creatinine level from 123.8 µmol/l to 185.6 µmol/l (1.4 mg/dl to 2.1 mg/dl) over the preceding 9 months. Her immunosuppression regimen included mycophenolate mofetil, ciclosporin and prednisone, with ciclosporin trough levels ranging from 100 ng/ml to 150 ng/ml, as detected by fluorescence polarization immunoassay, over the preceding year. The following possible causes of subacute renal failure were ruled out: post-obstructive nephropathy, altered hemodynamics (hypotension and renal artery stenosis), and toxicity from medications other than calcineurin inhibitors. Potential etiologies such as acute T-cell-mediated rejection, acute and chronic antibody-mediated rejection, polyomavirus-associated nephropathy, and calcineurin inhibitor nephrotoxicity were considered.Investigations Physical examination, urine and blood analysis, analysis of human leukocyte antigen antibodies by flow cytometry (Luminex®, Luminex Corporation, Austin, TX), ultrasound of the transplanted kidney, polymerase chain reaction assay for the detection of BK virus in the serum, and biopsy of the transplanted kidney with staining for simian virus 40 antigen.Diagnosis Polyomavirus-associated nephropathy with advanced nephrosclerosis and moderate to marked hyaline arteriolosclerosis.Management Reduction of immunosuppression by discontinuation of mycophenolate mofetil, dose reduction of ciclosporin, and initiation of leflunomide.

Diabetic nephropathy among Mexican Americans

The incidence of diabetic nephropathy (DN) is growing rapidly worldwide as a consequence of the rising prevalence of Type 2 diabetes mellitus (T2DM). Among U.S. ethnic groups, Mexican Americans have a disproportionately high incidence and prevalence of DN and associated end-stage renal disease (ESRD). In communities bordering Mexico, as many as 90% of Mexican American patients with ESRD also suffer from T2DM compared to only 50% of non-Hispanic Whites (NHW). Both socio-economic factors and genetic predisposition appear to have a strong influence on this association. In addition, certain pathogenetic and clinical features of T2DM and DN are different in Mexican Americans compared to NHW, raising questions as to whether the diagnostic and treatment strategies that are standard practice in the NHW patient population may not be applicable in Mexican Americans. This article reviews the epidemiology of DN in Mexican Americans, describes the pathophysiology and associated risk factors, and identifies gaps in our knowledge and understanding that needs to be addressed by future investigations.