Don’t underestimate these common diseases

By Naveed Saleh, MD, MS
Published October 21, 2020

Key Takeaways

The United States had an estimated 8.3 million COVID-19 cases as of October 22, 2020, with 222,200 deaths, according to Johns Hopkins’ COVID-19 Dashboard. However large this number sounds, it’s likely an underestimate.

In fact, the number of COVID-19 infections is likely more than 10 times higher than reported, per a cross-sectional study published in JAMA. These findings were based on SARS-CoV-2 antibody testing of 16,025 residual clinical specimens from several US sites. 

Unfortunately, COVID-19 is not the only disease experts have underestimated. Here are five others.

Lyme disease

If left untreated, Lyme disease can lead to a gamut of symptoms depending on the stage of infection, including rash, fever, facial paralysis, and arthritis.

The number of cases of Lyme disease reported each year by state health departments nationwide is 30,000, but the actual number may be 10 times higher, or 300,000, according to the CDC. This higher estimate is based on studies assessing medical claims from insurance companies and test results from clinical laboratories.  

“Surveillance systems provide vital information but they do not capture every illness,” the CDC noted. “Because only a fraction of illnesses are reported, researchers need to estimate the total burden of illness to set public health goals, allocate resources, and measure the economic impact of disease.”

They added, “CDC uses the best data available and makes reasonable adjustments—based on related data, previous study results, and common assumptions—to account for missing pieces of information.”

Importantly, 96% of Lyme disease cases that are reported to the CDC come from 14 states—mostly the Northeast and upper Midwest—with new estimates reflecting this geographic distribution shown by national surveillance.

Venous thromboembolism

Venous thromboembolism—including pulmonary embolism and deep vein thrombosis—is a preventable but insidious public health issue in the United States.

The number of Americans beset with venous thromboembolism (VTE) is unknown, with estimates ranging from 350,000–900,000 incidents per year, and leading to 100,000–300,000 deaths. “Current estimates are not precise because they are based on studies in counties that are not representative of the US population and they may underestimate the true occurrence of VTE,” noted the CDC.

In a study published in the American Heart Journal, researchers leveraged multiple sources to assess the number of inpatient, outpatient, and death-related VTE events in a nationally-representative population-based surveillance system in Oklahoma County between 2012 and 2014.

The researchers identified 2,725 cases of VTE based on 54,494 records of imaging studies, including x-ray, MRI, and special ultrasound. Notably, 8.4% of cases identified were outpatient, meaning that clinic providers can play an essential role in diagnosis and treatment. 

“Currently, there is no national monitoring system for VTE, making it difficult to understand the true burden of VTE in the United States. The methods and results of this project will help inform future efforts to develop valid US estimates of VTE burden and will help guide VTE prevention efforts,” noted the CDC, commenting on the study. 


Glaucoma is a progressive optic neuropathy and the leading cause of irreversible blindness worldwide. This condition is challenging to diagnose even among specialists, who may disagree about whether an eye exhibits signs of glaucoma.

In a prospective, observational study published in JAMA Ophthalmology, researchers had 197 ophthalmologists and ophthalmology trainees evaluate images of glaucomatous and healthy optic discs.

“Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood,” the authors reported. 

“Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2,” they concluded. 

Alzheimer disease

Alzheimer disease and related disorders greatly contribute to disease burden and healthcare costs in the United States, with an estimated 5.6 million Americans aged 65 years and older living with dementia in 2019. In total, Alzheimer disease accounts for 80% of dementia diagnoses. 

Per the results of a nationally-representative cohort study involving 7,342 adults, routine mortality statistics may underestimate the mortality burden associated with dementia by a factor of 2.7.

“These results suggest that the mortality burden of dementia may be greater than recognized and highlight the importance of expanding access to population-based interventions focused on dementia prevention and care,” wrote the authors of the JAMA Neurology study.

“Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” they added. 

Early-onset colorectal cancer

Incidence rates of early-onset colorectal cancer (CRC) are on the rise, but debate clouds the issue of whether to start screening at 45 or at 50 years of age. In 2018, the American Cancer Society recommended that screening begin at 45 years, but other authorities recommend starting at 50 years.

In a cross-sectional study of CRC incidence rates published in JAMA Network Open, researchers investigated how colorectal cancer incidence rates increased from age 49 to age 50, when large segments of the population begin average-risk screening. 

The researchers mined the Surveillance, Epidemiology, and End Results (SEER) registries from 2000-2015, and found a 46.1% increase in the CRC incidence rate in the one year between age 49 and age 50, and 92.9% of these cases were invasive.

“The findings of this study indicate that the burden of early-onset of colorectal cancer incidence for 45-49-year olds has been underestimated because asymptomatic colorectal cancers were not detected due to lack of screening,” noted one of the study’s authors, Xiao-Cheng Wu, MD, professor and director of the Louisiana Tumor Registry at LSU Health New Orleans School of Public Health.

In the article, the authors concluded: “These cancers were not reflected in observed SEER rates among individuals younger than 50 years; therefore, relying on SEER incidence rates among individuals aged 45 to 49 years alone to estimate potential outcomes of earlier screening at 45 years may underestimate the number of CRCs that can be prevented or diagnosed at earlier stages.”

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