Tropical Medicine
RCT: Albendazole–Ivermectin Co-Formulation Achieves Higher Cure Rates for T. trichiura and Hookworms
22 Jan, 2025 | 12:41h | UTCBackground: Soil-transmitted helminthiases (STH) affect an estimated 1.5 billion people worldwide, with Trichuris trichiura and hookworms remaining particularly challenging to treat. Although single-dose albendazole or mebendazole is standard in mass deworming programs, these agents show limited efficacy against T. trichiura and often leave Strongyloides stercoralis under-treated. Ivermectin has demonstrated broad activity against multiple parasites, suggesting that a combined albendazole–ivermectin regimen might enhance treatment outcomes, simplify protocols, and potentially curb emerging drug resistance.
Objective: This trial aimed to evaluate the safety, efficacy, and acceptability of a novel fixed-dose co-formulation (FDC) tablet containing albendazole (400 mg) plus a higher-than-standard, fixed dose of ivermectin (9 mg or 18 mg), administered once daily (FDC×1) or for three consecutive days (FDC×3). Investigators compared these regimens against single-dose albendazole alone for the treatment of T. trichiura, hookworms, and S. stercoralis in children and adolescents.
Methods: In this adaptive, randomized, parallel-group, phase 2/3 trial, 1001 participants aged 5–18 years were recruited from schools in Ethiopia, Kenya, and Mozambique. All were infected with at least one of T. trichiura, hookworms, or S. stercoralis. Eligible participants were allocated (by computer-generated block randomization) to either a single dose of albendazole 400 mg (control), a single-dose FDC of albendazole–ivermectin (FDC×1), or a three-day FDC regimen (FDC×3). Primary endpoints included safety (phase 2) and efficacy (phase 3), determined by cure rates at day 21 using the Kato–Katz and Baermann methods. Laboratory staff were blinded to treatment assignment.
Results: No serious adverse events were reported; mild-to-moderate gastrointestinal symptoms were the most frequent treatment-related events, resolving spontaneously within 48 hours. Cure rates for T. trichiura were 35.9% (95% CI 27.7–44.1) in the albendazole group, 82.9% (78.2–87.5) in FDC×1, and 97.2% (95.2–99.3) in FDC×3. For hookworms, cure rates were 65.1% (56.0–74.2) with albendazole, 79.8% (72.8–86.9) with FDC×1, and 95.0% (91.1–98.9) with FDC×3. Egg reduction rates in FDC arms consistently surpassed those of albendazole alone, especially for multi-day dosing. The sample size for S. stercoralis was insufficient to power a definitive efficacy conclusion, though ivermectin-containing arms trended toward favorable results. Palatability questionnaires indicated the orodispersible FDC was well accepted in taste, texture, and overall ease of administration.
Conclusions: A new co-formulation of albendazole plus ivermectin delivered at higher, fixed doses demonstrated an excellent safety profile and superior efficacy against T. trichiura and hookworms compared with albendazole monotherapy. This approach may streamline programmatic control of multiple STH species, including S. stercoralis, while contributing to reduced transmission in endemic communities.
Implications for Practice: For mass deworming initiatives, a single-dose FDC offers improved cure rates over albendazole alone while preserving simplicity. Where higher efficacy is critical—such as programs targeting near-elimination goals or in clinical settings—the three-day regimen may be preferable. Nonetheless, implementation feasibility, cost considerations, and further confirmation of efficacy against S. stercoralis and other co-endemic parasites remain important next steps.
Study Strengths and Limitations: Strengths include a multicenter design across three countries and a rigorous adaptive protocol that assessed both safety and efficacy. Limitations include the lack of blinding for participants and care providers (though outcome assessors were blinded), the underpowered sample size for S. stercoralis, and reliance on single-stool diagnostics, which may underestimate residual infections.
Future Research: Additional large-scale studies should confirm these findings in varied geographic regions and evaluate the cost-effectiveness of both single-dose and multi-day FDC strategies. Integrating albendazole–ivermectin with treatment programs for other neglected tropical diseases (e.g., onchocerciasis) could further amplify public health benefits. Genomic and pharmacokinetic analyses will clarify resistance patterns and optimize dosing regimens for broader implementation.
Reference: Krolewiecki A, Kepha S, Fleitas PE, van Lieshout L, Gelaye W, Messa A Jr, et al. “Albendazole–ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.” The Lancet Infectious Diseases. Published January 10, 2025. DOI: https://doi.org/10.1016/S1473-3099(24)00669-8
Cluster-Randomized Trial: Twice-Yearly Azithromycin Reduces Mortality in Children Aged 1 to 59 Months in Niger – New England Journal of Medicine
24 Aug, 2024 | 19:44h | UTCStudy Design and Population: This adaptive cluster-randomized trial evaluated the impact of twice-yearly azithromycin distribution on childhood mortality in rural communities in Niger. A total of 1273 communities were assigned to three groups: children aged 1 to 59 months receiving azithromycin, infants aged 1 to 11 months receiving azithromycin and placebo for older children, and a placebo group. The study included 382,586 children and followed mortality over 419,440 person-years.
Main Findings: The study found a significant 14% reduction in mortality among children aged 1 to 59 months in the azithromycin group compared to placebo (11.9 vs. 13.9 deaths per 1000 person-years; P<0.001). However, azithromycin did not significantly reduce mortality in infants aged 1 to 11 months when compared to placebo (22.3 vs. 23.9 deaths per 1000 person-years).
Implications for Practice: Azithromycin distribution to children aged 1 to 59 months effectively reduces mortality in rural sub-Saharan Africa. However, targeting only infants may not yield significant benefits. Continuous monitoring for antimicrobial resistance is essential.
Phase 2 RCT: Preventive subcutaneous L9LS monoclonal antibody reduces malaria incidence by 66-70% in Malian children – N Engl J Med
7 May, 2024 | 15:31h | UTCThis phase 2 randomized clinical trial investigated the safety and efficacy of the monoclonal antibody L9LS in preventing Plasmodium falciparum infection and clinical malaria in children aged 6 to 10 years in Mali. The trial was structured in two parts: initial dose assessment in adults followed by a randomized, placebo-controlled test in children over a 6-month malaria season. A total of 225 children participated, divided equally among three groups to receive either 150 mg of L9LS, 300 mg of L9LS, or a placebo. Results demonstrated a significant reduction in the rate of P. falciparum infection—66% efficacy with the 150-mg dose and 70% efficacy with the 300-mg dose. Similarly, efficacy against clinical malaria was 67% with the 150-mg dose and 77% with the 300-mg dose. Both doses were well-tolerated with no safety concerns reported, underscoring the potential of L9LS as a preventative treatment against malaria in endemic regions.
Reference (link to abstract – $ for full-text):
M-A | Most dengue infections are asymptomatic and could significantly contribute to the transmission of the disease
9 Aug, 2023 | 15:21h | UTC
M-A | The global prevalence of human fascioliasis
8 Aug, 2023 | 13:10h | UTC
Global Burden of Disease Study | Understanding global trends of infectious diseases in younger population, 1990-2019
10 Jul, 2023 | 13:54h | UTCNews Release: Global efforts to reduce infectious diseases must extend beyond early childhood – Murdoch Children’s Research Institute
Commentary: Global infectious disease burden shifting from younger to older youth – CIDRAP
RCT | Single-Dose VLA1553 Chikungunya vaccine shows high immunogenicity and seems safe
23 Jun, 2023 | 13:38h | UTCNews Release: First phase 3 trial of a chikungunya vaccine candidate finds it is generally safe and provokes an immune response – The Lancet
Commentary on Twitter
New: First phase 3 trial of a chikungunya vaccine candidate finds it is generally safe and provokes an immune response. https://t.co/YSzV5oxXRc pic.twitter.com/rGL7A5eLAr
— The Lancet (@TheLancet) June 13, 2023
Cohort Study | Dengue patients at high risk of cholecystitis and pancreatitis within 30 days
21 Jun, 2023 | 13:34h | UTC
RCT | NmCV-5 pentavalent meningococcal vaccine shows non-inferiority to quadrivalent MenACWY-D in Mali and Gambia
30 May, 2023 | 11:46h | UTC
Commentary on Twitter
Original Article: Meningococcal ACWYX Conjugate Vaccine in 2-to-29-Year-Olds in Mali and Gambia https://t.co/RScQOr5IWS#InfectiousDisease pic.twitter.com/jA6d92QlK2
— NEJM (@NEJM) May 26, 2023
Phase 2a RCT | Emodepside demonstrates superior efficacy to albendazole in treating Trichuris trichiura and Hookworm Infection
25 May, 2023 | 11:33h | UTCEmodepside for Trichuris trichiura and Hookworm Infection – New England Journal of Medicine (link to abstract – $ for full-text)
Liver cystic echinococcosis: a parasitic review
25 May, 2023 | 11:19h | UTCLiver cystic echinococcosis: a parasitic review – Therapeutic Advances in Infectious Disease
RCT | Safety of integrated MDA of azithromycin, albendazole and ivermectin vs. standard treatment regimens
10 May, 2023 | 15:24h | UTC
Burden of typhoid and paratyphoid fever in India
25 Apr, 2023 | 14:32h | UTCBurden of Typhoid and Paratyphoid Fever in India – New England Journal of Medicine
Commentary on Twitter
From 2017 through 2020 in India, weekly surveillance for blood-confirmed typhoid and paratyphoid among children showed an incidence of 576 to 1173 cases of typhoid fever per 100,000 child-years in urban sites. Full NSSEFI study: https://t.co/BbweY5hVcQ#InfectiousDisease pic.twitter.com/S2D3bM29f5
— NEJM (@NEJM) April 19, 2023
Cluster RCT | Long-lasting insecticidal nets compared for malaria control
12 Apr, 2023 | 13:04h | UTCInvited Commentary: Getting ahead of insecticide-resistant malaria vector mosquitoes – The Lancet (free registration required)
WHO Report | Dengue & Chikungunya cases spreading beyond known transmission zones in the Americas
10 Apr, 2023 | 14:04h | UTCCommentary: WHO: Concerning Spread of Dengue, Chikungunya in Latin America – JAMA
RCT | Sulfadoxine-pyrimethamine vs. dihydroartemisinin-piperaquine for preventive treatment of malaria in pregnant women in Africa
13 Mar, 2023 | 14:43h | UTC
RCT | Combination of intravenous doxycycline and azithromycin better than either drug alone for severe scrub typhus
8 Mar, 2023 | 14:36h | UTCSummary:
The study aimed to compare the efficacy of intravenous doxycycline, azithromycin, or a combination of both drugs in treating severe scrub typhus. The study randomized 794 patients with severe scrub typhus and at least one organ involvement to receive a 7-day course of intravenous doxycycline, azithromycin, or both.
The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. The study found that combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for treating severe scrub typhus than monotherapy with either drug alone.
Article: Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: A combination therapy is found to be more effective on severe scrub typhus – University of Oxford
Commentary on Twitter
Original Article: Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus https://t.co/uZ4Y51zoZ2#InfectiousDisease pic.twitter.com/xzmeAV8Tyi
— NEJM (@NEJM) March 4, 2023
Early diagnostic indicators of dengue vs. other febrile illnesses in Asia and Latin America: a multicenter, prospective, observational study
8 Mar, 2023 | 14:16h | UTCSummary:
The IDAMS study is a large, prospective, observational study conducted in eight countries in Asia and Latin America to investigate early diagnostic indicators of dengue compared to other febrile illnesses. The study included 7428 patients with undifferentiated fever, of whom 2694 were diagnosed with laboratory-confirmed dengue and 2495 with other febrile illnesses.
Platelet count, white blood cell count, and their changes over time were strongly associated with dengue, while cough and rhinitis were strongly associated with other febrile illnesses. The study found that a set of 14 clinical and three laboratory predictors can distinguish between dengue and other febrile illnesses during the early phase of symptoms, with sensitivities of 80-87% and specificities of 80-91%. The study also found that models that include laboratory markers outperform those based solely on clinical variables.
The study’s results provide important information for updating guidelines on the management of febrile illnesses, particularly in resource-limited settings where distinguishing between dengue and other febrile illnesses is crucial for patient management.
Invited Commentary: Differentiating dengue from other febrile illnesses: a dilemma faced by clinicians in dengue endemic countries – The Lancet Global Health
Commentary on Twitter
From the March Issue: Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study https://t.co/xyvYpoiyWM (1/2) pic.twitter.com/xgvkA39PV5
— The Lancet Global Health (@LancetGH) February 23, 2023
Mpox outbreak in advanced HIV cases | Global case series reveals higher mortality and clinical complications
23 Feb, 2023 | 13:44h | UTCSummary: This article discusses a case series investigating monkeypox (mpox) in people with HIV and low CD4 cell counts. The mpox outbreak in 2022 has affected a significant percentage of people living with HIV, and data suggest worse clinical outcomes and higher mortality in those with more advanced HIV. The case series includes data from 382 confirmed mpox cases in people living with HIV from 19 countries. The individuals included were predominantly cisgender men, with a median age of 35. Most individuals were adherent to antiretroviral therapy, and the median CD4 count was 211 cells per mm3. Severe complications were more common in those with lower CD4 cell counts, including necrotizing skin lesions, lung involvement, secondary infections, and sepsis. Approximately 28% of individuals were hospitalized, and 25% of those hospitalized died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. The study reinforces the importance of HIV and CD4 testing in mpox cases, prioritization of preventive mpox vaccination in people with HIV and a CD4 cell count of less than 200 cells per mm3, and the use of potential mpox antivirals where available. The authors suggest that a severe, disseminated, and necrotizing form of mpox should be considered an AIDS-defining condition in CDC and WHO HIV disease classifications. Clinicians should also be aware that starting antiretroviral therapy in people with advanced HIV and mpox could contribute to deterioration and possible death, possibly as part of an immune reconstitution syndrome.
Article: Mpox in people with advanced HIV infection: a global case series – The Lancet (free registration required)
News Release: Clinicians identify severe form of mpox with high mortality in people with advanced HIV – Queen Mary University of London
Commentaries:
Mpox: Clinicians identify severe form with high mortality in advanced HIV patients – The BMJ
Commentary from the author on Twitter (thread – click for more)
📣 📣 Our global case series on MPOX in people with advanced HIV infection is at #CROI2023 and in @TheLancet today: 382 cases of human MPOX infection in PLWH with CD4 counts <350 cells/mm3 in 19 countries
**We found MPOX is an opportunistic pathogen** /1https://t.co/WodDN4Ujoj pic.twitter.com/IlK7viABmy— @profchloeorkin.bsky.social (@profchloeorkin) February 21, 2023
M-A | Oral manifestation of the monkeypox virus
23 Feb, 2023 | 13:42h | UTCOral manifestation of the monkeypox virus: a systematic review and meta-analysis – eClinicalMedicine
Current pharmacotherapeutic strategies for Strongyloidiasis and the complications in its treatment
23 Feb, 2023 | 13:13h | UTC
Eight countries eliminated a neglected tropical disease in 2022
14 Feb, 2023 | 10:45h | UTCEight countries eliminated a neglected tropical disease in 2022 – Nature
Original report: WHO Global report on neglected tropical diseases 2023
Brief Review | Mpox — A rapidly evolving disease
10 Feb, 2023 | 13:56h | UTCMpox—A Rapidly Evolving Disease – JAMA Dermatology
Related:
Monkeypox (hMPXV infection): A practical review – American Journal of Medicine
WHO renames “monkeypox” as “mpox” to help destigmatize the disease.
Study shows there is substantial monkeypox transmission before symptoms appear.
Monkeypox – New England Journal of Medicine
Monkeypox: disease epidemiology, host immunity and clinical interventions.
Monkeypox: A clinical update for paediatricians – Journal of Pediatrics and Child Health
CDC Report | Epidemiologic and clinical characteristics of Monkeypox cases in the US.
Update on the Monkeypox Outbreak – JAMA
WHO Declares Global Public Health Emergency Over Monkeypox Virus Outbreak – Health Policy Watch
Monkeypox: A Contemporary Review for Healthcare Professionals – Open Forum Infectious Diseases
Video | Malaria — Epidemiology, treatment, and prevention
8 Feb, 2023 | 12:37h | UTCMalaria — Epidemiology, Treatment, and Prevention | NEJM
WHO Global report on neglected tropical diseases 2023
31 Jan, 2023 | 14:09h | UTCGlobal report on neglected tropical diseases 2023 – World Health Organization
News Release: More countries eliminate neglected tropical diseases but investments key to sustain progress – World Health Organization
Commentary on Twitter
It's World Neglected Tropical Diseases Day!
Chagas disease
Chikungunya
Dengue
Dracunculiasis
Leishmaniasis
Leprosy
Elephantiasis
Mycetoma
River blindness
Rabies
Sleeping sickness
Trachoma& other neglected tropical diseases affect 1 BILLION people 🌍!
➡️https://t.co/qni6m5CjiQ pic.twitter.com/N1sU1w6YWf
— World Health Organization (WHO) (@WHO) January 29, 2023