A randomised, open-label, phase 4 clinical trial

[Posted 22/Jan/2026]]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.

BACKGROUND: Anti-malarial artemisinin-based combination therapies (ACTs) might be losing efficacy in east Africa, with the spread of artemisinin partial resistance and reduced partner drug activity. Our trial aimed to measure the efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine in three sites in Uganda.

DETAILS: This randomised, open-label, phase 4 clinical trial was carried out at three sites in the Agago, Arua, and Busia districts of Uganda. Children aged 6 months to 10 years with uncomplicated Plasmodium falciparum malaria were randomly assigned to receive either artemether-lumefantrine (20 mg artemether; 120 mg lumefantrine; twice a day for 3 days) in all sites or dihydroartemisinin-piperaquine (40 mg dihydroartemisinin and 320 mg piperaquine, once a day for 3 days) in Agago, artesunate-amodiaquine (25 mg artesunate and 67.5 mg amodiaquine for children <9 kg or 50 mg artesunate and 135 mg amodiaquine for children >=9 kg, once a day for 3 days) in Busia; and artesunate-pyronaridine (60 mg artesunate and 180 mg pyronaridine for children >15 kg or 20 mg artesunate and 60 mg pyronaridine for children <15 kg, once a day for 3 days) in Arua, with follow-up to 42 days. Participants were not blinded to group assignments; however, investigators and those assessing outcome were masked. The primary outcome was parasitaemia, assessed by microscopy, either uncorrected or PCR-corrected to distinguish recrudescence from new infection. All participants who received the treatment per protocol and were not lost to follow-up were included in the primary outcome. All participants who were randomly allocated to treatment groups were included in the safety analyses. This study is registered with the Pan African Clinical Trials Registry, number PACTR202301796134887, and is complete. Between Nov 7, 2022, and March 24, 2023, 808 participants (437 [54%] female) were enrolled and assigned to treatment groups; 15 (2%) were lost to follow-up and 793 (98%) completed follow-up. The uncorrected adequate clinical and parasitological response for artemether-lumefantrine was 87 (51.8%; 95% CI 44.0-59.5) of 168 participants in Arua, 88 (51.8%; 44.0-59.4) of 170 and Busia, and 131 (79.4%; 72.3-85.1) of 165 in Agago. This response for artemether-lumefantrine was lower than that of the other ACTs at all sites: 97 (98.0%; 92.2-99.6) of 99 for dihydroartemisinin-piperaquine in Agago, 95 (99.0%; 93.5-99.9) of 96 for artesunate-amodiaquine in Busia, and 73 (73.7%; 63.8-81.8) of 99 for artesunate-pyronaridine in Arua. PCR-corrected 28-day efficacies were 88 (81.5%; 72.6-88.1) of 108 for artemether-lumefantrine and 95 (100%; 95.2-100.0) of 95 for artesunate-amodiaquine in Busia; 131 (97.0%; 92.1-99.0) of 135 for artemether-lumefantrine and 97 (100%; 95.3-100.0) of 97 for dihydroartemisinin-piperaquine in Agago; and 87 (82.1%; 73.2-88.6) of 106 for artemether-lumefantrine and 73 (92.4%; 83.6-96.9) of 79 for artesunate-pyronaridine in Arua. All regimens were well tolerated. The most common adverse events were upper respiratory tract infection, diarrhoea, and anaemia. None of the reported adverse events were attributed to the study drugs. There were two serious adverse events, both cases of severe malaria in Arua, one in each of the treatment groups. Parasite clearance half-lives were prolonged with parasites carrying the PfK13 Cys469Tyr (median 4.2 h; IQR 3.4-4.9) and Ala675Val (4.9 h; 3.4-5.7) mutations compared with wild-type parasites (2.8 h; 2.3-3.6; p<0.0001).

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Source: Kamya, M. R., Nankabirwa, J. I., Ebong, C., et al. Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial. The Lancet Infectious Diseases. 2026; 26(1): 67-68. Published: January, 2026. DOI: 10.1016/S1473-3099(25)00407-4.

[Posted 14/Sep/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: The analysis suggests that excluding long-term illness, mortality, and healthcare costs after TB treatment can substantially underestimate the health value of TB prevention. In the modeled Canadian immigrant population, incorporating these consequences more than doubled the estimated QALY benefit of postarrival TB infection screening and preventive treatment and reduced the estimated cost per QALY by more than half. However, the findings depend on assumptions about the long-term effects of TB, and the investigators noted that some underlying associations may include residual confounding and that post-TB illness estimates are less certain.

BACKGROUND: Tuberculosis prevention strategies are commonly evaluated by considering acute TB disease and death, while longer-term consequences after successful treatment may be overlooked. These consequences can include persistent illness, increased mortality, and additional healthcare utilization. This study assessed how incorporating these longer-term effects would change estimates of the health benefits and cost-effectiveness of postarrival TB infection screening and preventive treatment among people newly immigrating to Canada.

DETAILS: The investigators developed a Markov microsimulation model representing a hypothetical cohort of 400,000 people immigrating permanently to Canada in 2025. The analysis compared the existing postarrival TB infection screening level of 0.5% with a modeled screening strategy reaching 68% of eligible new immigrants. The intervention targeted new permanent residents from countries with annual TB incidence >50/100,000 persons; individuals testing positive for TB infection were assumed to receive 4 months of daily rifampin as preventive treatment. Outcomes were projected over 25 years and included TB episodes, TB deaths, quality-adjusted life-years (QALYs), and TB-related healthcare costs. The model incorporated three post-TB consequences: increased mortality after TB treatment, persistent illness or disability, and excess healthcare costs. A total of 2,000 probabilistic simulations were performed to account for uncertainty in model parameters.

When only acute TB consequences were considered under the current screening scenario, the model projected 927 (95% UR 764-1,123) TB cases, 30 (95% UR 24-36) TB deaths, and 312 (95% UR 241-386) QALYs lost over 25 years. Adding post-TB death increased estimated QALYs lost by 1.6-fold, while including post-TB illness increased them by 1.5-fold. When all three long-term consequences were incorporated, TB was projected to account for 657 (95% UR 479-876) QALYs lost, a 2.1-fold increase compared with considering acute consequences alone.

The expanded screening and preventive-treatment strategy produced 2.4-fold greater estimated QALY gains (95% UR 1.6-4.4-fold) and 2.2-fold more TB deaths averted (95% UR 1.6-3.0-fold) when all post-TB consequences were included. The estimated incremental cost-effectiveness ratio decreased from $235,088 to $100,742 CAD per QALY gained. In the model incorporating all post-TB consequences, 53% of simulations fell below a willingness-to-pay threshold of $100,000 per QALY, compared with 8% when only acute TB consequences were considered.

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Source: Ainiwaer, A., Uppal, A., Schwartzman, K., et al. Posttuberculosis Consequences on Tuberculosis Prevention Effectiveness and Cost-effectiveness among New Immigrants, Canada. Emerging Infectious Diseases. 2026; 32(9): 1421-1429. Published: September, 2026. DOI: 10.3201/eid3209.260473.

A Nationwide Analysis

[Posted 26/Aug/2026]

AUDIENCE: Hospice & Palliative Nursing, Oncologys

KEY FINDINGS: Among adults with cancer approaching death, hospice utilization was associated with less frequent and lower-intensity broad-spectrum antibiotic exposure, particularly during the final days of life. The findings are consistent with a transition toward comfort-focused care, although they do not establish that hospice care itself caused the reduction. Hospice initiation occurred relatively close to death, with a mean interval of 39.9 days and a median of 22.0 days, and some antibiotic treatment may have preceded hospice enrollment. In addition, cancer stage, treatment status, infection severity, microbiological findings, functional status, symptom burden, and treatment intent were unavailable in the claims data.

BACKGROUND: Antibiotic treatment remains common during end-of-life care for patients with cancer, despite uncertain benefits for survival and potential burdens including drug toxicity, intravenous administration, adverse effects, and antimicrobial resistance. This retrospective cohort study evaluated whether hospice involvement was associated with differences in broad-spectrum antibiotic use among adults with cancer during the final 3 months of life.

DETAILS: Investigators analyzed Korean National Health Insurance Service claims data for adults aged ≥18 years who died between January 1, 2018, and December 31, 2021, with one of the 10 leading cancer-related causes of death. Hospice users had received inpatient, home-based, or consultation-based hospice care before death. Broad-spectrum antibiotic exposure included anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides. The final 90 days of life were divided into four intervals: 1–3 months before death, 1 week to 1 month before death, the final week, and the final 3 days. Antibiotic exposure was assessed by the proportion of patients receiving antibiotics and by days of therapy (DOT) per 1,000 patient-days. Propensity score matching was performed at a 1:2 ratio.

After matching, 38,102 hospice users and 75,736 non-hospice users were analyzed. During the final 3 months of life, 74.6% of hospice users and 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P0.001). Antibiotic use was initially slightly higher among hospice users during the period 1–3 months before death, at 34.0% versus 32.2% (P0.001), but became consistently lower among hospice users thereafter. From 1 week to 1 month before death, use was 31.1% versus 32.8%; during the final week, 11.3% versus 18.5%; and during the final 3 days, 4.8% versus 10.3% among hospice and non-hospice users, respectively (all P0.001).

Days of therapy per 1,000 patient-days were also consistently lower among hospice users, with the greatest differences occurring during the final week and final 3 days of life. Carbapenems and glycopeptides demonstrated particularly pronounced differences between the groups. In cancer-specific analyses, patients with hematologic malignancies had the highest overall antibiotic exposure, followed by those with pancreatobiliary and gastric cancers, while exposure was comparatively lower among patients with breast and liver cancers.

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Source: Jeung, Y. S., Kim, H. J., Yu, J., et al. Comparison of Broad-Spectrum Antibiotic Use According to Hospice Utilization Among Patients with Cancer at the End of Life in South Korea: A Nationwide Analysis. Journal of Hospice and Palliative Care. 2026; 29(2): 41-50. Published: June 1, 2026. DOI: 10.14475/jhpc.2026.29.2.41.

[Posted 13/Aug/2026]

AUDIENCE: Pediatrics, Infectiouos Disease

KEY FINDINGS: As of August 6, 2026, the US had reported 2,465 confirmed measles cases and 38 new outbreaks, with 94% of cases outbreak-associated. The increase occurs alongside a decline in kindergarten MMR coverage to 92.5% in 2024-2025 from 95.2% in 2019-2020. CDC emphasizes that measles can spread rapidly in communities with lower vaccination coverage, while 2 doses of MMR vaccine provide 97% protection against measles.

BACKGROUND: Measles was officially eliminated in the United States in 2000 following widespread use of the measles, mumps, and rubella (MMR) vaccine. However, declining vaccination coverage and increasing global measles activity have increased opportunities for measles transmission following importation into the United States.

DETAILS: As of August 6, 2026, the Centers for Disease Control and Prevention (CDC) reported 2,465 confirmed measles cases in the United States in 2026. Of these, 2,449 cases were reported by 47 jurisdictions, while 16 cases occurred among international visitors to the United States. Thirty-eight new outbreaks had been reported during 2026.

Overall, 94% of confirmed cases in 2026 (2,309 of 2,465) were associated with outbreaks, including 936 cases from outbreaks beginning in 2026 and 1,373 from outbreaks that began in 2025. For comparison, 2,289 confirmed cases and 48 outbreaks were reported during the full year of 2025; 90% of cases (2,066 of 2,289) were outbreak-associated.

CDC reports confirmed measles cases notified by jurisdictions as of noon on Thursdays. An outbreak is defined as 3 or more related cases. State and CDC counts may differ because jurisdictions update and publicly report their data on different schedules.

MMR vaccination coverage among US kindergartners declined from 95.2% during the 2019-2020 school year to 92.5% during the 2024-2025 school year, leaving approximately 286,000 kindergartners at risk during the 2024-2025 school year. CDC notes that communities with vaccination coverage below the 95% level are more vulnerable to measles outbreaks. The 2026 measles case count reported by CDC as of August 6, 2026, had already exceeded the total number of confirmed cases reported during all of 2025 (2,465 vs 2,289). The high proportion of outbreak-associated cases indicates sustained transmission within affected communities.

The burden of measles remains closely associated with vaccination status. CDC reports that 2 doses of MMR vaccine are 97% effective at preventing measles, while 1 dose is 93% effective. Breakthrough infections can occur, particularly during outbreaks with high levels of circulating measles virus, and account for approximately 10% of all measles infections.

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Source: CDC: Measles Cases and Outbreaks. Centers for Disease Control and Prevention (CDC). 2026; Published: August 7, 2026.

[Posted 7/Aug/2026]

AUDIENCE: Pediatrics, Infectiouos Disease

KEY FINDINGS: This global pediatric surveillance study demonstrates a sustained increase in antimicrobial resistance among children, with the greatest concern involving Gram-negative pathogens, intensive care settings, sepsis cases, and resource-limited regions. Increasing resistance to Watch and Reserve antibiotics may compromise treatment options for severe childhood infections. Forecasted growth in carbapenem resistance among Klebsiella species and Acinetobacter baumannii highlights the need for strengthened antimicrobial stewardship, surveillance systems, and development of effective pediatric treatment strategies.

BACKGROUND: Antimicrobial resistance (AMR) threatens the effectiveness of antibiotic therapy for severe childhood infections, yet comprehensive pediatric AMR surveillance data across multiple regions remain limited. This study evaluated global and temporal patterns of antimicrobial resistance among children using the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) antibiotic classification framework and projected future resistance trends

DETAILS: This cross-sectional surveillance study analyzed pediatric bacterial isolates from the Antimicrobial Testing Leadership and Surveillance (ATLAS) database collected between January 2004 and December 2022. The study included 106 581 isolates from 106 581 children aged 0 to 18 years across 82 countries. Data were analyzed from February 2024 to April 2026. Resistance trends were assessed by geographic region, age group, clinical setting, infection syndrome, and pathogen type, with spatiotemporal models used to forecast resistance patterns through 2035.

The analysis categorized antibiotics according to the WHO AWaRe framework: Access antibiotics used for first-line treatment, Watch antibiotics with higher resistance potential, and Reserve antibiotics intended for difficult-to-treat infections. The study evaluated WHO priority pathogens and examined resistance patterns among different pediatric populations, including children with sepsis and respiratory infections.

From 2004 to 2022, pediatric AMR increased across all regions, with higher resistance levels and faster increases observed in resource-limited settings. Resistance to Access-group antibiotics was highest overall, with a mean resistance of 36% (range, 2%-66%), compared with Watch-group antibiotics at a mean of 22% (range, 1%-47%) and Reserve-group antibiotics at a mean of 13% (range, 0%-30%).

Resistance to higher-tier antibiotics increased substantially in vulnerable clinical groups. In intensive care units, Watch-group resistance increased from 15% (517/3564) to 33% (2910/8748) (P < .001), particularly among children aged 0 to 2 years, where resistance increased from 12% (325/2649) to 32% (1257/3959) (P < .001). Among children with sepsis, Watch-group resistance increased from 15% (298/2030) to 30% (1409/4705) (P < .001), while Reserve-group resistance increased from 3% (16/474) to 26% (746/2824) (P < .001).

Among critical pathogens, Acinetobacter baumannii demonstrated the highest overall resistance, exceeding 55% in every AWaRe antibiotic category in 2022. Klebsiella species showed the fastest increases in resistance, particularly to third- or fourth-generation cephalosporins and carbapenems. Forecasts estimated that by 2035, carbapenem resistance would reach 35% (95% uncertainty interval [UI], 29%-40%) in Klebsiella species and 82% (95% UI, 77%-85%) in A baumannii.

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Source: Hu, Y. J., Qiu, H., Harwell, J. I., et al. Childhood Antimicrobial Resistance With Global Forecasts. JAMA Pediatrics. 2026; Published: July 20, 2026. DOI: 10.1001/jamapediatrics.2026.2808.

[Posted 3/Aug/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF for maintaining virologic suppression through week 48 in adults with previously suppressed HIV-1. No participants receiving ISL/LEN had HIV-1 RNA levels of 50 copies/mL or higher, and virologic suppression rates remained high in both treatment groups. CD4+ T-cell changes and safety outcomes were broadly comparable. The once-weekly oral regimen may provide a less frequent treatment option for patients who prefer oral therapy but may benefit from reduced dosing frequency.

BACKGROUND: Daily single-tablet antiretroviral regimens have substantially improved HIV-1 management; however, maintaining long-term adherence remains challenging for some patients. Less frequent oral treatment schedules may provide an alternative to daily therapy while avoiding the need for injectable regimens. This phase 3 trial evaluated the efficacy and safety of once-weekly oral islatravir-lenacapavir (ISL/LEN) in adults with virologically suppressed HIV-1.

DETAILS: This phase 3, double-blind, randomized, active-controlled, noninferiority trial was conducted in 12 countries. Adults with HIV-1 viral suppression for at least 6 months while receiving once-daily bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) were randomly assigned in a 1:1 ratio to switch to once-weekly oral ISL/LEN (2 mg/300 mg) or continue once-daily B/F/TAF for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA levels of 50 copies/mL or higher at week 48, assessed using the FDA-defined snapshot algorithm. The prespecified noninferiority margin was 4 percentage points. A total of 607 participants underwent randomization, including 304 assigned to ISL/LEN and 303 assigned to B/F/TAF. At week 48, no participants in the ISL/LEN group and 1 participant (0.3%) in the B/F/TAF group had HIV-1 RNA levels of 50 copies/mL or higher (difference, -0.3 percentage points; 95.002% CI, -1.4 to 0.8), meeting the criterion for noninferiority. HIV-1 RNA levels below 50 copies/mL were observed in 284 participants (93.4%) receiving ISL/LEN and 280 participants (92.4%) receiving B/F/TAF (difference, 1.0 percentage point; 95% CI, -3.2 to 5.2). The mean change in CD4+ T-cell count was -10 cells/µL with ISL/LEN and -18 cells/µL with B/F/TAF, with a least-squares mean difference of 12 cells/µL (95% CI, -16 to 39). Treatment discontinuation due to adverse events occurred in 6 participants (2.0%) receiving ISL/LEN and 5 participants (1.7%) receiving B/F/TAF; serious adverse events occurred in 16 participants (5.3%) and 14 participants (4.6%), respectively.

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Source: Rockstroh, J. K., Ramgopal, M. N., Curran Fabregas, A., et al. Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment. The New England Journal of Medicine. 2026; Published: July 29, 2026. DOI: 10.1056/NEJMoa2607973.