By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Lyme Carditis: Any AV Block of Concern

SOURCE: Marx GE, Leikauskas J, Lindstrom K, et al. Fatal Lyme carditis in New England: Two case reports. Ann Intern Med 2019; Oct. 22. doi: 10.7326/L19-0483. [Epub ahead of print].

In the United States, Lyme carditis is uncommon, occurring in ~1.5% to 5% of all patients with untreated acute Lyme disease, although pathologic studies suggest that cardiac involvement may be more common. Lyme disease should be included in the differential in anyone presenting with a new atrioventricular (AV) block. Ninety percent of patients with Lyme carditis present with various degrees of AV block, and 60% have some component of perimyocarditis. In one study, 44% of those who presented with first-degree AV block developed, at least temporarily, complete AV block. Generally, AV conduction abnormalities are reversible with treatment, although temporary pacing may be required. Permanent pacer placement seldom is necessary. Prolonged QT is uncommon, although it has been documented in a few pediatric cases. Congestive failure and dilated cardiomyopathy usually is a later manifestation of untreated Lyme carditis.

These two case reports document the fairly rapid progression of conduction defects in untreated Lyme carditis. A 49-year-old woman from Massachusetts developed a flu-like illness with a headache and required parenteral fluids. Two weeks later, she developed syncope, and an electrocardiogram (ECG) showed AV dissociation. Laboratory studies and cardiac home event monitoring were ordered. She was presumptively prescribed doxycycline, but before she could take her first dose, she died of ventricular tachycardia, detected on the home monitor.

Another case involved a 57-year-old man from Vermont with erythema migrans consistent with disseminated Lyme. An ECG showed first-degree AV block with a PR interval of 220 msec. Laboratory studies were ordered, which were positive for Borrelia burgdorferi by ELISA and Western blot. Twelve days later, before treatment was initiated, the man was found unresponsive and died. Postmortem examination in both cases revealed pancarditis with immunohistochemical evidence of Borrelia, and spirochetes were visualized in cardiac tissue from the first case.

Lyme carditis should be considered in anyone presenting with new AV conduction disorder, regardless of age, but especially if a young person presents with AV block. If cardiac Lyme is suspected, laboratory testing for Lyme, an ECG, chest radiograph, and echocardiogram are appropriate next steps. Close monitoring with telemetry is recommended for those with PR interval > 300 msec, as progression to complete AV block or dissociative rhythm is common and may occur quickly.

Syphilis Screening in Pregnancy a Must

SOURCE: Umapathi KK, Thavamani A, Chotikanatis K. Incidence trends, risk factors, mortality and healthcare utilization in congenital syphilis-related hospitalizations in the United States: A nationwide population analysis. Ped Infect Dis J 2019;38:1126-1130.

Cases of congenital syphilis (CS) in the United States continue to escalate, precipitated by our evolving syphilis epidemic. CS results in significant neonatal morbidity and mortality, and frequent permanent disability in survivors. Untreated CS results in a 40% risk of intrauterine demise, miscarriage, or neonatal death. According to Centers for Disease Control and Prevention (CDC) data, CS cases have increased steadily since 2013, when 362 cases were reported, to 918 cases in 2017, and to a whopping 1,306 cases in 2018. Of these, 70% were reported from five states: Florida, California, Arizona, Texas, and Louisiana.

This survey examined national trends in hospital-ization and healthcare utilization related to CS from 2009 to 2016, based on data abstracted from the Agency for Healthcare Research and Quality for hospital stays for patients younger than 21 years of age, as well as the National Inpatient Sample (NIS). During the seven-year study period, a total of 5,912 CS-related hospitalizations in infants < 12 months of age were examined. Of these, 47% were African-American and 29% were Hispanic. A higher number of CS-related hospitalizations was associated with public insurance or no insurance (88%), and low median income. The majority were hospitalized in the South (59%) or the Western United States (21%). Excluding stillbirths, the mortality rate among hospitalizations was 0.54%, with 32 deaths.

The mean length of hospital stay was 12 days. Hospital charges, adjusted for inflation, significantly increased over the years, reaching in $58,500 per hospitalization in 2016, which is significantly higher compared with other hospitalizations for the same age group. This means that more than $120 million was spent on CS-related hospitalizations in the United States in 2016. Note that the number of CS-related hospitalizations is significantly higher than the number of CS cases reported by the CDC. This could result from more frequent hospitalization in affected cases, although more likely it includes CS cases not reported to the public health system.

All but six states mandate syphilis screening during pregnancy. While the requirements for screening vary among states, most recommend screening on presentation for the first prenatal exam (84%).1 The CDC and other advisory bodies recommend screening at 28 weeks gestation and again at delivery in higher-risk women. However, only eight states (15.7%) require screening at delivery, and five require it only if the woman is at “high risk.” Six states do not require screening for syphilis during pregnancy, including Iowa, Ohio, Minnesota, Mississippi, New Hampshire, and Wisconsin. Hawaii and Maine provide no specific requirements as to when testing should be done. Changing these laws to mandatory prenatal screening for all women at presentation and again in the third trimester, with mandatory public health reporting, would go a long way to limiting the end effects of this epidemic on neonates. Attempts to reduce spending for public health and STD treatment in the United States since 2003 have precipitated an even costlier public health crisis.

REFERENCE

  1. Warren HP, Cramer R, Kidd S, Leichliter JS. State requirements for prenatal syphilis screening in the United States, 2016. Matern Child Health J 2018;22:1227-1232.

Deferring INH Until Postpartum in HIV-Positive Women

SOURCE: Gupta A, Montepiedra G, Aaron L, et al. Isoniazid preventive therapy in HIV-infected pregnant and postpartum women. N Engl J Med 2019;381:1333-1346.

The World Health Organization (WHO) provides general recommendations for treatment with antiretroviral therapy and pre-emptive isoniazid (INH) therapy in HIV-positive pregnant women at risk for tuberculosis (TB). However, there has been a lack of information on the safety and tolerance of INH during pregnancy, and the optimal timing of INH in such women has not been established. These questions were examined in this large-scale, double-blind, placebo-controlled trial of INH chemoprophylaxis in HIV-positive pregnant women, most of whom were receiving antiretroviral therapy. The project was conducted at 13 clinical sites in eight different countries at risk for TB infection. Women were randomly assigned to standard INH treatment for 28 weeks, beginning during pregnancy, or to deferred treatment at 12 weeks following delivery. Eligible women included those between 14 and 34 weeks of gestation, who weighed at least 35 kg, who had fairly normal cell counts, and who had liver enzymes no more than 1.25 times the upper limit of normal within 30 days of entry, and with no recent known exposure to TB, no prior treatment for TB, and no diagnosis of hepatitis or neuropathy within the previous year. Evidence of latent TB at entry was not a requirement, although about 30% had a positive Interferon-Gamma Release Assay (IGRA) at entry. The primary outcome of the study was a composite safety outcome of grade 3 or higher adverse events or permanent discontinuation of therapy because of side effects. Patients were followed every four weeks through 48 weeks post-delivery.

A total of 956 pregnant women were recruited for study. The median age was 29 years, 90.5% were Black African, the median CD4 count was 493 cells/mL, and all but one were receiving highly active antiretroviral therapy (HAART); 85% were receiving a regimen containing efavirenz. Nearly one-fifth (17.9%) discontinued the trial prematurely, including 8.9% who were lost to follow-up and six who died. Before the study, primary outcomes were estimated to occur in about 5% of participants, but, in fact, were much higher than anticipated, occurring in 15.1% of the early treatment group and 15.2% of the deferred treatment group. The intent-to-treat analysis showed no significant differences in the incidence of grade 3 or higher adverse events between the early treatment group vs. the deferred group (incidence rate 34.95 vs. 31.26 per 100 person-years, P = NS). The incident rate of hepatotoxicity was similar between the two groups (incident rate 5.8 in the early treatment group vs. 6.7 per 100 person-years in the deferred treatment group, P = NS). Six women died, including two in the early treatment group and four in the deferred treatment group. All six deaths occurred postpartum, and four of the deaths were due to liver failure. All four were receiving combination efavirenz-tenofovir-emtricitabine at the time of death, and two women had received INH. Active TB developed in six women (three in each group).

There were 926 deliveries. Adverse pregnancy outcomes were significantly higher in the early treatment group than in the deferred treatment group (23.6% vs. 17%, P = 0.01). This included stillbirths, spontaneous abortion, low birth weight, preterm delivery, or congenital abnormalities in an infant. A composite score for severe adverse pregnancy events was similar between the groups.

This large-scale study of pregnant HIV-positive women shows that INH preventive therapy administered during pregnancy was non-inferior to deferred treatment three months post-delivery, although the risks of INH treatment when started during pregnancy (after the first trimester) appeared to be greater. Grade 3 or higher maternal adverse events were three times higher than anticipated (~15%), especially during the postpartum period in both treatment groups, regardless of whether INH was initiated during pregnancy or deferred until three months after delivery. There also was a higher than expected risk of adverse pregnancy outcomes in those receiving INH during pregnancy, although pregnant women in the early treatment group did not begin INH until at least week 14 of pregnancy. Although the study was conducted in countries endemic for TB, the number of cases of active TB occurring during study was low.