What’s New in ID? May 2019 / Svibanj 2019.

Video observed therapy for the treatment of tuberculosis

Directly observed therapy (DOT) for treatment of tuberculosis (TB) involves observation by a health care provider as a patient swallows each dose of antituberculous medication; it is a longstanding standard of care for TB treatment but is inconvenient for patients and health care workers. In a randomized trial including more than 220 patients with TB in England, more patients managed with video observed therapy (VOT; daily observation via mobile phone) completed >80 percent of scheduled observations over two months than patients managed with DOT three to five times per week in home, community, or clinic settings (70 versus 31 percent). In settings where feasible, VOT is a reasonable alternative to DOT; further study is needed to evaluate feasibility in low- and middle-income settings.

Story A, Aldridge RW, Smith CM, Garber E, Hall J, Ferenando G, Possas L, Hemming S, Wurie F, Luchenski S, Abubakar I, McHugh TD, White PJ, Watson JM,Lipman M, Garfein R, Hayward AC. Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomized, controlled superiority trial. Lancet. 2019 Mar 23;393(10177):1216-1224.

One-month regimen for prevention of tuberculosis in patients with HIV infection

Available regimens for treatment of latent tuberculosis (LTBI) require several months of treatment. In a randomized trial including 3000 patients with HIV infection and either a positive test for LTBI or residence in an area with TB prevalence at least 60 cases per 100,000 population, patients were treated with a one-month regimen of daily isoniazid (INH) and rifapentine (RPT) or a nine-month regimen of daily INH [33]. The one-month regimen was noninferior to the nine-month regimen for preventing TB (median follow-up 3.3 years); the rate of serious adverse events was comparable. Study limitations include the relatively small proportion of patients with CD4 <250 cells/microL and low rate of positive tests for LTBI. The one-month regimen requires further study; in the meantime, we continue to suggest a nine-month regimen of daily INH for patients with HIV infection and risk for LTBI.

Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011.

Dihydroartemisinin-piperaquine for intermittent preventive treatment of pregnant women in malaria-endemic areas

For pregnant women in malaria-endemic areas, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent malaria and reduce the risk of adverse birth outcomes. However, SP resistance is emerging; dihydroartemisinin-piperaquine (DP) may be a reasonable alternative agent. In a randomized trial including more than 780 pregnant women from Uganda who received monthly IPTp with DP versus SP starting early in the second trimester, the risk of a composite adverse birth outcome (low birth weight, preterm birth, or small for gestational age) was comparable (16 versus 18 percent). However, the rate of symptomatic malaria was ≥90 percent lower among patients who received DP. DP was well tolerated but associated with asymptomatic QTc prolongation in some patients. Pending further study to evaluate whether DP results in improved maternal and fetal outcomes beyond reducing malaria infection, SP remains the preferred agent for IPTp.

Kajubi R, Ochieng T, Kakuru A, Jagannathan P, Nakalembe M, Ruel T, Opira B, Ochokoru H, Ategeka J, Nayebare P, Clark TD, Havlir DV, Kamya MR, Dorsey G. Monthly sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomized, controlled, superiority trial. Lancet. 2019 Apr 6;393(10179):1428-1439.

STI incidence among MSM using PrEP

Men who have sex with men (MSM), particularly those who have indications for pre-exposure prophylaxis against HIV (PrEP), are at high risk for sexually transmitted infections (STI). In a study of nearly 3000 MSM in Australia who were initiating PrEP, the incidence of new chlamydia, gonorrhea, or syphilis over the subsequent year was 92 cases per 100 person-years. Nearly half of the participants were diagnosed with an STI during the study period, with 25 percent accounting for 75 percent of all STIs diagnosed; the risk of STI was proportional to the number of sexual partners and frequency of group sex. These data highlight the importance of frequent STI screening for MSM using PrEP.

Traeger MW, Cornelisse VJ, Asselin J, Price B, Roth NJ, Willcox J, Tee BK,Fairley CK, Chang CC, Armishaw J, Vujovic O, Penn M, Cundill P, Forgan-Smith G, Gall J, Pickett C, Lal L, Mak A, Spelman TD, Nguyen L, Murphy DA, Ryan KE, El-Hayek C, West M, Ruth S, Batrouney C, Lockwood JT, Hoy JF, Hellard ME, Stoové

MA, Wright EJ; PrEPX Study Team. Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection. JAMA. 2019 Apr 9;321(14):1380-1390.

Transplants from HCV-infected donors to uninfected recipients

Pre-emptive therapy with direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) offers the opportunity to expand the solid organ transplant pool by enabling organ transplantation from HCV-infected donors into uninfected recipients. In a prospective study of HCV-uninfected heart and/or lung transplant recipients who received an organ from an HCV-infected donor and received pre-emptive sofosbuvir-velpatasvir for four weeks, none of the 35 recipients who had >6 months of follow-up developed chronic HCV infection and all had graft survival. Similar results had been noted in previous case series of pre-emptive DAA treatment at the time of transplant. These studies suggest that organ transplantation from HCV-infected donors to uninfected recipients can be safely performed; the optimal pre-emptive regimen is yet to be determined.

Woolley AE, Singh SK, Goldberg HJ, Mallidi HR, Givertz MM, Mehra MR, Coppolino A, Kusztos AE, Johnson ME, Chen K, Haddad EA, Fanikos J, Harrington DP, Camp PC,Baden LR; DONATE HCV Trial Team; the DONATE HCV Trial Team. Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients. N Engl J Med. 2019 Apr 25;380(17):1606-1617.

Uveitis following Ebola virus disease

Outbreaks of Ebola virus disease due to the Zaire species continue to occur, with an ongoing outbreak in the eastern region of the Democratic Republic of the Congo. Patients who survive Ebola virus disease typically begin to improve during the second week of illness. However, survivors often suffer from a variety of disabling symptoms during the convalescent period (eg, weakness, fatigue, muscle and joint pain, uveitis, neurologic manifestations); some of these symptoms can develop months to years later. As an example, in a prospective longitudinal study of Ebola virus disease survivors enrolled a median of one year after infection, the prevalence of uveitis increased after an additional year of follow-up, at a rate higher than that observed among controls. These findings stress the importance of appropriate follow-up care for Ebola survivors, including vision care for those who develop ocular findings.

PREVAIL III Study Group, Sneller MC, Reilly C, Badio M, Bishop RJ, Eghrari AO, Moses SJ, Johnson KL, Gayedyu-Dennis D, Hensley LE, Higgs ES, Nath A, Tuznik K,Varughese J, Jensen KS, Dighero-Kemp B, Neaton JD, Lane HC, Fallah MP. A Longitudinal Study of Ebola Sequelae in Liberia. N Engl J Med. 2019 Mar 7;380(10):924-934.

Health advisory about H3N2 influenza A activity in the United States

In late March 2019, the Centers for Disease Control and Prevention (CDC) released a health advisory stating that influenza activity remains high in the United States, with an increasing proportion of influenza activity being due to the influenza A subtype, H3N2 . The increase in influenza A H3N2 cases is important because this subtype has been associated with an increase in hospitalizations and deaths in patients ≥65 years of age. In addition, influenza vaccines are frequently less effective against influenza A H3N2 viruses than against influenza A H1N1 and influenza B viruses. Influenza should be considered as a possible diagnosis for patients with respiratory illness while local influenza activity remains elevated, with early empiric antiviral therapy for hospitalized and high-risk patients. Additional details can be found on the CDC’s website.

Centers for Disease Control and Prevention. Health Alert Network. Influenza season continues with an increase in influenza A(H3N2) activity. https://emergency.cdc.gov/han/han00419.asp (Accessed on April 01, 2019). No abstract available

Source: UpToDate May 2019.