News Scan for Apr 28, 2020

News brief

Studies analyze effects of mass azithromycin distribution in Malawi

A new analysis of data from a randomized clinical trial that found that mass distribution of the antibiotic azithromycin to children under 5 years old was associated with reduced childhood mortality in three African countries suggests mortality reduction may be linked to effects on pneumonia, diarrhea, or HIV/AIDS mortality. The findings were published yesterday in the American Journal of Tropical Hygiene and Medicine.

The secondary analysis of results from the MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial looked specifically at causes of deaths during the trial in Malawi (Niger and Tanzania were the other trial sites). Although the trial was not powered to investigate mortality effects at individual trial sites, investigators used verbal autopsy (VA)—a structured interview with relatives of the deceased to ascertain cause of death—and two different methods of automated VA analysis (InterVA and SmartVA) to assess the major causes of death during the trial and develop a hypothesis about how azithromycin may effect childhood mortality.

A total of 334 communities in Malawi were randomized to receive azithromycin or placebo during the trial, and 1,184 deaths were recorded, of which 1,131 were followed up with VA. Mortality was 9% lower in the azithromycin-treated communities than in communities that received placebo. An intention-to-treat analysis using IntervA suggested fewer HIV/AIDS deaths in azithromycin-treated communities (rate ratio, 0.70; 95% confidence interval [CI], 0.50 to 0.97; P = 0.03) and fewer pneumonia deaths (rate ratio, 0.82; 95% CI, 0.60 to 1.12; P = 0.22). The use of the SmartVA algorithm suggested fewer diarrhea deaths (rate ratio, 0.71; 95% CI, 0.51 to 1.00; P = 0.05) and fewer pneumonia deaths (rate ratio, 0.58; 95% CI, 0.33 to 1.00; P = 0.05).

"Although this study is not able to provide strong evidence on the causes of death in the MORDOR trial, the data have been presented fully to enable generation of hypotheses regarding mechanisms of effect of azithromycin on childhood mortality," the authors wrote. "Larger studies will be required to clearly define the effects of azithromycin on cause-specific childhood mortality."

Another MORDOR analysis published in the same journal found that mass distribution of azithromycin has the potential to be a highly cost-effective intervention for reducing childhood mortality in some settings in Malawi, while a third analysis found that mass distribution of the drug in Malawi had no effect on malaria parasitemia at the community or individual levels.
Apr 27 Am J Trop Med Hyg abstract 1
Apr 27 Am J Trop Med Hyg abstract 2
Apr 27 Am J Trop Med Hyg abstract 3

Rapid MDR-TB susceptibility test tied to faster diagnosis, better outcomes

The use of rapid molecular drug susceptibility testing (DST) in patients with multidrug-resistant tuberculosis (MDR-TB) significantly reduced time to diagnosis and was associated with decreased time to culture conversion and improved treatment outcomes, Chinese and Swedish researchers reported yesterday in the International Journal of Infectious Diseases.

In a study that included 242 MDR-TB patients admitted to two Chinese hospitals from 2012 through 2015, the researchers compared time to diagnosis and treatment outcomes in patients before and after implementation of commercially available rapid molecular DST tools (Genotype MTBDRsI and MTBDRplus Assay) for MDR-TB diagnosis. They assessed clinical improvement by looking at time to sputum culture conversion and final treatment outcomes after 2 years of treatment. A total of 114 patients belonged to the pre-implementation group and 128 to the post-implementation group.

The analysis found that post-implementation patients had a significantly reduced time to MDR-TB diagnosis compared with patients in the pre-implementation group (median: 16 vs 62 days), along with shorter treatment with first-line drugs (median: 11 days vs 59 days) and earlier initiation with second-line drugs (median: 19 vs 69 days). In addition, patients in the post-implementation group had a more rapid culture conversion (median: 12 months vs 24 months) and a higher rate of treatment success (68% vs 47%, P < 0.01).

Multivariate analysis showed that the effect of molecular DST implementation was significantly positively correlated with early sputum culture conversion (adjusted hazard ratio, 1.94; 95% CI, 1.37 to 2.73) and treatment success (adjusted odds ratio, 2.47; 95% CI, 1.38 to 4.42).

The authors says the findings are important because MDR-TB poses a major threat to TB control programs, and conventional phenotypic DST methods are time consuming, prolong the time to effective treatment, and require a TB-containment laboratory, which is not always available in low-income settings.

"Our findings highlight the importance of rapid diagnostic testing for the improvement of MDR-TB treatment outcome," they concluded.
Apr 27 Int J Infect Dis study

WHO: Flu low in most of world, COVID-19 complicates data interpretation

Flu activity in the Northern Hemisphere is low in most countries and is still at interseasonal levels in the Southern Hemisphere, the World Health Organization (WHO) said today in its latest update. The agency warned, however, that flu reports should be interpreted cautiously, because the COVID-19 pandemic could be influencing healthcare-seeking behaviors and distancing measures could be interrupting flu transmission.

In Europe, flulike activity was still elevated in Estonia and the Netherlands and severe respiratory illness markers are still high in Russia, but flu detections are low in most reporting countries. Pooled mortality estimates from Europe show an overall increase led by substantial excesses in some countries, likely due to the COVID-19 pandemic.

Flu levels in the rest of the world are low, but Mozambique is reporting mainly 2009 H1N1 activity. In the Southern Hemisphere's temperate countries, emergency department visits for respiratory symptoms are higher than expected for this time of the year in Australia, though flu stayed at interseasonal levels, the WHO said.

At the global level, of specimens tested in the first half of April, 54.9% were influenza A and 45.1% were influenza B. Of subtyped influenza A viruses, 77.8% were 2009 H1N1 and 22.2% were H3N2. Of the characterized flu B viruses, 93.5% belonged to the Victoria lineage.
Apr 27 WHO global flu update

COVID-19 Scan for Apr 28, 2020

News brief

COVID-19 not linked to poor outcomes in pregnant women, study finds

Pregnant women hospitalized with COVID-19 had similar clinical illness and outcomes as nonpregnant women of reproductive age and did not pass the virus to their newborns, according to a retrospective study published yesterday in the International Journal of Infectious Diseases.

The researchers studied the electronic medical records of 28 infected pregnant women and 54 nonpregnant peers hospitalized in the Central Hospital of Wuhan, China, from Jan 15 to Mar 15.

They found no link between pregnancy and illness severity (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.08 to 5.15; P = 0.76), virus clearance time (OR, 1.16; 95% CI, 0.65 to 2.01; P = 0.62), or length of hospitalization (hazard ratio, 1.10; 95% CI, 0.66 to 1.84; P = 0.71).

Two pregnant women (7.1%) had mild illness, while 24 (85.7%) had moderate pneumonia, similar to nonpregnant women (53 women, 98.1%). Two pregnant women (7.1%) and one nonpregnant woman (1.9%) had severe pneumonia. Nonpregnant women were more likely to report fever and cough at hospital admission than pregnant women, some of whom reported abdominal pain.

Twenty-two women had 23 live births (one set of twins), 17 (60.7%) of them via cesarean section and five (17.9%) vaginally. None of the newborns were infected with the novel coronavirus. Four women had first- or second-trimester abortions over concerns about possible side effects from drugs, radiologic examinations, and the coronavirus on the fetus, and two were still pregnant when the study period ended.

Median age of the pregnant women was 30 years, versus 31 in non-pregnant women.
Apr 27 Int J Infect Dis study

Recommended PPE may not protect emergency department workers

A simulation showed contamination of healthcare workers' skin, hair, and shoes after performing endotracheal intubation, despite wearing recommended personal protective equipment (PPE), according to a research letter published yesterday in JAMA.

In the simulation, which took place in an emergency department in Israel, researchers aimed to determine personnel exposure to respiratory droplets generated during the provision of standard care for COVID-19 patients in respiratory distress. They used an atomizer and an invisible fluorescent compound as a marker of contamination to simulate adult and child scenarios involving respiratory droplet generation from coughing.

Personnel wore N95 respirators, eye protection, isolation gowns, and gloves, as recommended by the US Centers for Disease Control and Prevention (CDC) and the World Health Organization for aerosol-generating procedures.

One scenario involved a 74-year-old man with fever, shortness of breath, and declining oxygen levels who needed endotracheal intubation and an intravenous cannula. The pediatric scenario was similar. Two doctors and two nurses participated in each scenario. To avoid aerosol generation, bag-mask ventilation before intubation was allowed only when preoxygenation was inadequate.

Ultraviolet light revealed fluorescent markers on 7 of the 8 participants' skin, 6 on the neck, and 1 on an ear. All had fluorescent markers on their hair, and 4 on their shoes.

"The findings suggest that the current recommendations for personal protective equipment may not fully prevent exposures in emergency department settings," the authors said. "Clothing that covers all skin may further diminish exposure risk."

In an editorial in the same journal, David Weissman, MD, Marie de Perio, MD, and Lewis Radonovich, Jr, MD, of the CDC said that the findings highlight the importance of hand washing and using face shields during invasive procedures.

"Loose-fitting powered air-purifying respirators provide both high-level respiratory protection, as well as extensive facial and hair covering, and could be an effective and convenient alternative," they wrote.
Apr 27 JAMA research letter and editorial

COVID-19 restrictions tied to less flu activity in Taiwan, Singapore

Two new research letters in Emerging Infectious Diseases show decreased influenza activity in Taiwan and Singapore in light of restrictions placed in both countries to curb the spread of COVID-19.

Because of its previous experience with SARS (severe acute respiratory syndrome, also caused by a coronavirus), the government of Taiwan took early and swift action against COVID-19, with citizens avoiding gatherings, maintaining physical distance, wearing masks, practicing hand and respiratory hygiene, monitoring their temperatures, and quarantining when appropriate, the authors said.

"Although the success of these measures for limiting COVID-19 transmission remains to be determined, nationwide surveillance has shown the rapid decline of influenza activity during the first 12 weeks of 2020 (through March 21) in Taiwan," the authors said. Flu activity was significantly lower than during the same period in 2019.

In Singapore, influenza-like illness for 2020 before and after COVID-19 measures were taken was compared to three previous flu seasons.

"Percentage influenza positivity decreased by 64% (p = 0.001) and estimated daily number of influenza cases decreased by 76% (p = 0.002) in epidemiologic weeks 5–9 of 2020 compared with the preceding years," the authors wrote.
Apr 27 Emerg Infect Dis Taiwan letter
Apr 27 Emerg Infect Dis Singapore letter