Diagnosis Based on History, Not Examination

Cat scratch disease (CSD), caused by the bacterium Bartonella henselae, is usually self-limiting, presenting with low-grade fever and tender lymphadenopathy. With delayed diagnosis or reactivation of latent disease, CSD is associated with severe debilitating symptoms. We are presenting a patient who proved adiagnostic challenge, before being found to have reactivation of Bartonella henselae, requiring three-months IV Trimethoprim-Sulfamethoxazole andHydrocortisone.

Non-bullous pemphigoid associated with immune checkpoint inhibitor treatment

Though a variety of immune-related adverse events of immune checkpoint inhibitors (ICIs) including bullous pemphigoid have been reported, non-bullous pemphigoid (NBP) associated with ICI therapy was scarcely reported. We present a case of NBP with a long latent disease course without diagnosis during nivolumab, an ICI therapy.

Tuberculosis

The failure to control tuberculosis (TB) in recent times stems, at least in part, from complacency towards TB control in the 1970s and 1980s and the subsequent devastating impact of the HIV-1 pandemic, the rising emergence of drug resistance as well as the growing disparity in disease burden between developed and developing countries. Progress has also been hindered by the slow development of more effective tools such as point-of-care diagnostics and treatments for active and latent disease, preventive vaccines, and laboratory assays of disease progression, immune protection, and cure. This lack of progress is, in turn, related to a poor understanding of the fundamental relationship between Mycobacterium tuberculosis and the human host and especially the nature of what is referred to as ‘latent TB infection’. An increased focus on understanding the mechanics and drivers of transmission together with a concerted effort to translate research findings into policy and practice contextualized to local needs and resources is required. This chapter reviews recent advances in tackling tuberculosis, highlighting key unmet needs and strategies for an accelerated effort to achieve control.

Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening

Estrogen receptor α-positive (ER+) breast cancers (BCs) represent more than 70% of all breast cancers and pose a particular clinical challenge because they recur up to decades after initial diagnosis and treatment. The mechanisms governing tumor cell dormancy and latent disease remain elusive due to a lack of adequate models. Here, we compare tumor progression of ER+ and triple-negative (TN) BC subtypes with a clinically relevant mouse intraductal xenografting approach (MIND). Both ER+ and TN BC cells disseminate already during the in situstage. However, TN disseminated tumor cells (DTCs) proliferate at the same rate as cells at the primary site and give rise to macro-metastases. ER+ DTCs have low proliferative indices, form only micro-metastases and lose epithelial characteristics. Expression of CDH1 is decreased whereas the mesenchymal marker VIM and the transcription factors, ZEB1/ZEB2, which control epithelial-mesenchymal plasticity (EMP) are increased. EMP is not detected earlier during ER+ BC development and not required for invasion or metastasis. In vivo, forced transition to the epithelial state through ectopic E-cadherin expression overcomes dormancy with increased growth of lung metastases. We conclude that EMP is essential for the generation of a dormant cell state and the development of latent disease. Targeting exit from EMP is of therapeutic potential.

OBSERVATION OF MORPHOLOGICAL CHANGES IN THE FETUS AND PLACENTA OF PREGNANT WOMEN INFECTED WITH CYTOMEGALOVIRUS THROUGH ULTRASOUND EXAMINATION

In 2008-2018, 89 pregnant women registered at the Beaumonde Clinic were observed with only cytomegalovirus activity. Laboratory tests for cytomegalovirus were performed 4 times in total, and ultrasound examination was performed 3 times during pregnancy. The results were distributed as follows: (1) We could have assumed with high probability that we had reinfection processes and not a primary infection. (2) During the ultrasound examinations, no significant organic disturbances in the development of the fetus were detected. (3) In all cases, various morphological changes were observed in the placenta, which are not specific for CMV and are found during any infectious process: premature aging of the placenta, increase in thickness and enhanced calcification. Degenerative changes in placental tissues increase the risk of perinatal loss. (4) As a result of childbirth, all newborns were born without visible pathology. However, this did not rule out latent disease and later detected pathologies.

Latent leprosy infection identified by dual RLEP and anti-PGL-I positivity: Implications for new control strategies

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.

A Latent Disease Model to Reduce Detection Bias in Cancer Risk Prediction Studies

In studies of cancer risk, detection bias arises when risk factors are associated with screening patterns, affecting the likelihood and timing of diagnosis. To eliminate detection bias in a screened cohort, we propose modeling the latent onset of cancer and estimating the association between risk factors and onset rather than diagnosis. We apply this framework to estimate the increase in prostate cancer risk associated with black race and family history using data from the SELECT prostate cancer prevention trial, in which men were screened and biopsied according to community practices. A positive family history was associated with a hazard ratio (HR) of prostate cancer onset of 1.8, lower than the corresponding HR of prostate cancer diagnosis (HR = 2.2). This result comports with a finding that men in SELECT with a family history were more likely to be biopsied following a positive PSA test than men with no family history. For black race, the HRs for onset and diagnosis were similar, consistent with similar patterns of screening and biopsy by race. If individual screening and diagnosis histories are available, latent disease modeling can be used to decouple risk of disease from risk of disease diagnosis and reduce detection bias.