Dengue virus, measles, TBI and TB disease: Are they being overlooked because of the pandemic?

The COVID-19 pandemic has taught health care providers a lot: how quickly a virus can spread globally, how unprepared we were to respond to a pandemic, and how rapidly science and technology could evolve to make a safe and effective vaccine, as well as that many people are vaccine hesitant or re- fusers and that individuals and groups resisting public health safety measures (eg, masking, social distancing) could prolong a pandemic with repetitive surges. Most importantly, we have learned that it is critical to be more than a step ahead of future infectious diseases by analyzing and responding to emerging data both in the United States and globally. This article reviews infectious diseases that may have taken a back seat in the news since March 2020 and how they affect the daily lives of children and adolescents all around the world.

Dengue virus

The Dengue virus (DENV) is a major public health problem in the tropics and subtropics and is endemic in the US territories of Puerto Rico, the US Virgin Islands, and American Samoa.¹ As Americans begin to travel and the United States welcomes global visitors, pediatric providers must consider who may be exposed to 1 of the 4 known DENVs and the presenting symptoms (Table^1,2). An individual can be infected with the 4 serotypes over time. Long- term immunity is achieved for an individual who contracted a homologous DENV, but this protection does not last more than 3 months if an individual is infected with a different serotype. Evidence has shown that a person who sustains a second infection is more likely to develop severe dengue compared with those experiencing the first or a third or fourth illness.² DENV is most often transmitted to a human through the bite of an infected mosquito (Aedes aegypti).¹ The incubation period is 3 to 14 days before symptom onset. Infected individuals can transmit DENV to mosquitoes 1 to 2 days before symptoms develop and during the 7-day viral illness.¹

Table

During the Ebola outbreak, it was critical when taking a patient’s history to ask anyone presenting with fever about recent travel. To diagnose a DENV illness, providers must continue the practice of asking about recent travel globally and within the endemic areas in the US territories. Dengvaxia, a Dengue vaccine, is now approved by the US Food and Drug Administration and is listed on the 2022 US immunization schedule for individuals aged 9 to 16 years. However, the vaccine can be administered only if prevaccination laboratory testing reveals confirmed evidence of a previous DENV infection.³ It is contraindicated to administer the Dengvaxia vaccine to children who are seronegative because that action would place them at high risk of hospitalization and severe dengue illness.³

Measles

In 2019, there were 1282 confirmed cases of measles in 31 states.⁴ There were 2 primary reasons for US outbreaks: In 2019, the number of people who contracted measles abroad increased; then, upon their return to the United States, these individuals spread the virus in communities that had low measles vaccination rates.⁴ In 2020 and 2021, the number of reported measles cases in the United States dropped significantly to 13 and 49, respectively; thus far, in 2022, 3 cases have been reported.⁴

Two factors may account for the 2020 and 2021 decreases. These data may represent the effect of the COVID-19 pandemic on measles transmission in the United States—fewer families traveled overseas as the pan- demic surged throughout this country. Also, many elementary and secondary schools were closed in 2020; when they reopened in 2021, masks and social distancing were in place. Thus, these factors may have significantly reduced children and unvaccinated families from contracting and spreading the measles virus.

These data provide evidence that pediatric providers should reach out to parents whose children need the measles-mumps-rubella (MMR) vaccine, citing 2 influential factors: (1) Many states have removed school mask mandates, putting unvaccinated children at risk of contracting measles. Parents should be reminded that measles spreads through direct contact with an infected person or airborne transmission (via coughing or sneezing) up to 4 days before rash onset and for 4 days after the rash erupts.⁵ (2) Timely measles vaccination will protect children who may be traveling to parts of the world where measles is endemic.

The World Health Organization (WHO) reported that measles remains a problem in developing countries, especially in parts of Africa and Asia. The WHO also reported that in 2018, more than 140,000 people—mostly children less than 5 years old—died from measles, with more than 95% of these deaths occurring in countries that have low-income populations and weak health care systems.⁶ The MMR vaccine saves lives. All health care providers should proactively encourage parents to vaccinate their children.

Pediatric tuberculosis

A diagnosis of pediatric tuberculosis (TB), for either latent TB (referred to as tuberculosis infection [TBI]⁷) or TB disease (active TB), is made for patients aged less than 15 years who have either a positive tuberculin skin test or a positive interferon- gamma release assay.^7,8 Both tests have a high positive predictive value when used for children who have had a direct contact exposure to an adult with TB disease.⁷ Infants and young children are at increased risk of developing life-threatening forms of the disease, including TB meningitis and disseminated TB, compared with older children and adults.⁸ The greatest numbers of TB cases occur in children under 5 years old, with 38% of pediatric cases occurring⁷ within this age range. In addition, in 2020, 28% of the 10- to 14-year- old population had a diagnosis of pediatric TB.⁸ Data from TB cases in children aged less than 18 years living in the United States from 2010 to 2017 revealed that 32% of children with TB disease were born in other countries.⁹

Adults who have the TB bacterium, Mycobacterium tuberculosis, spread the organism via airborne transmission by coughing, speaking, or singing. However, children with pediatric TB do not spread the organism as readily as adults, because pediatric TB is less infectious than the adult form.⁸ Children may present with a cough, weakness, weight loss, fever, change in playtime behaviors, and/or night sweats.⁸

Children younger than 4 years are at the highest risk of progressing from TBI to TB disease, with data showing a risk of 40% to 50% for infants less than 1 year old and 25% for 1- to 2-year-olds.⁸ However, children with a diagnosis of TBI who receive drug therapy and whose parents adhere to the regimen have a 90% reduced risk of developing TB disease.⁸ Adolescents older than 12 years have a risk of progression to adult-type TB disease. Children and adolescents who are immunocompromised also have a high risk of disease progression.

In 2021, the clinical practice guidance for treatment of latent TB and TB disease was revised.^7,8 Children older than 2 years may be treated with once-weekly isoniazid-rifapentine for 12 weeks. Additional regimens include 4 months of rifapentine or 9 months of daily isoniazid.^7,8 Parents often prefer shorter courses, resulting in more children completing a full course.

For TB disease, children can be treated with several anti-TB medications for 4, 6, or 9 months, based on the selection of the drug therapy believed to be most effective for the child and for parental administration. Providers need to be aware that the Centers for Disease Control and Prevention does not recommend the 4-month rifapentine-moxifloxacin TB regimen for children younger than 12 years.⁸ Best practices for pediatric providers include consulting a TB expert prior to beginning the treatment course, based on the available data showing that young children have a high risk of developing life-threatening TB disease.⁸

Conclusions

Pediatric health care providers are on the frontlines for identifying infectious diseases and, to prevent poor outcomes, must react quickly to diagnose and treat cases in children and adolescents. The COVID-19 pandemic public health measures— masking, social distancing, and limited social contact among children and adolescents—have reduced the prevalence of other infectious diseases. As public health policies begin to change and global travel resumes, pediatric providers must remain astutely aware of the potentially devasting effects of emerging infectious diseases and newer ones that may affect US and global pediatric populations.

References

1. Kimberline DW, Barnett ED, Lynfield R, Sawyer MH. Dengue. In: Kimberline DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021:301-304.

2. Paz-Bailey G, Adams L, Wong JM, et al. Dengue vaccine: recommendations of the Advisory Committee on Immunization Practices, United States, 2021. MMWR. 2021;70(6):1-16. doi:10.15585/mmwr.rr7006a1

3. Child and adolescent immunization schedule. Centers for Disease Control and Prevention. Updated February 17, 2022. Accessed March 25, 2022. https://www.cdc.gov/vaccines/schedules/hcp/imz/child- adolescent.html#note-dengue

4. Measles cases and outbreaks. Centers for Disease Control and Prevention. Updated April 6, 2022. Accessed March 26, 2022. https://www.cdc.gov/ measles/cases-outbreaks.html

5. Measles: key facts. World Health Organization. December 5, 2019. Accessed March 26, 2022. https:// www.who.int/news-room/fact-sheets/detail/ measles

6. Measles. World Health Organization. Accessed March 26, 2022. https://www.who.int/health-topics/ measles#tab=tab_1

7. TB and children. Centers for Disease Control and Prevention. October 19, 2021. Accessed March 26, 2022. https://www.cdc.gov/tb/topic/populations/

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8. Nolt D, Starke JR. Tuberculosis infection in children and adolescents: testing and treatment. Pediatrics. 2021;148(6):e20211054663. doi:10.1542/ peds.2021-054663

9. Cowger TL, Wortham JM, Burton DC. Epidemiology of tuberculosis among children and adolescents in the USA, 2007-17: an analysis of national surveillance data. The Lancet. 2019;4(10):e506-e516. doi:10.1016/S2468-2667(19)30134-3