Evidence map›Paper›PMID 31254719›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2019

Screening the Medicines for Malaria Venture Pathogen Box against piroplasm parasites.

Arifin Budiman Nugraha, Bumduuren Tuvshintulga, Azirwan Guswanto, Dickson Stuart Tayebwa, Mohamed Abdo Rizk, Sambuu Gantuya, Gaber El-Saber Batiha, Amany Magdy Beshbishy, Thillaiampalam Sivakumar, Naoaki Yokoyama and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Tulathromycin and Diclazuril Lack Efficacy againstPathogens (Basel, Switzerland) · 2023
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  13. Treatment of Human Babesiosis: Then and Now.Pathogens (Basel, Switzerland) · 2021
    Review
  14. Discovering the Potent Inhibitors AgainstFrontiers in veterinary science · 2021
    Article
  15. Review
  16. Article
  17. Myrrh OilPathogens (Basel, Switzerland) · 2020
    Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Arifin Budiman NugrahaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan; Department of Animal Infectious Diseases and Veterinary Public Health, Faculty of Veterinary Medicine, IPB University, Jl. Agatis, Kampus IPB Dramaga, Bogor, Jawa Barat, 16680, Indonesia.
Bumduuren TuvshintulgaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Azirwan GuswantoBalai Veteriner Subang (DIC Subang), Jl. Terusan Garuda 33/11 Blok Werasari Dangdeur, Subang, Jawa Barat, 41212, Indonesia.
Dickson Stuart Tayebwa(f)Research Center for Tropical Diseases and Vector Control, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, 7062, Kampala, Uganda.
Mohamed Abdo RizkNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan; Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
Sambuu GantuyaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Gaber El-Saber BatihaDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Al-Beheira, 22511, Egypt.
Amany Magdy BeshbishyNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Thillaiampalam SivakumarNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Naoaki YokoyamaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Ikuo IgarashiNational Research Center for Protozoan Diseases, Obihiro University of Agriculture Veterinary Medicine, Nishi 2 Sen-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan. Electronic address: igarcpmi@obihiro.ac.jp.
Obihiro University of Agriculture and Veterinary Medicine · JPDamanhour University · EGIPB University · IDMansoura University · EG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diminazene aceturate (DA) and imidocarb dipropionate are commonly used in livestock as antipiroplasm agents. However, toxic side effects are common in animals treated with these two drugs. Therefore, evaluations of novel therapeutic agents with high efficacy against piroplasm parasites and low toxicity to host animals are of paramount importance. In this study, the 400 compounds in the Pathogen Box provided by the Medicines for Malaria Venture foundation were screened against Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi. A fluorescence-based method using SYBR Green 1 stain was used for initial in vitro screening and determination of the half maximal inhibitory concentration (IC50). The initial in vitro screening performed using a 1 μM concentration as baseline revealed nine effective compounds against four tested parasites. Two "hit" compounds, namely MMV021057 and MMV675968, that showed IC50 < 0.3 μM and a selectivity index (SI)> 100 were selected. The IC50s of MMV021057 and MMV675968 against B. bovis, B. bigemina, T. equi and B. caballi were 23, 39, 229, and 146 nM, and 2.9, 3, 25.7, and 2.9 nM, respectively. In addition, a combination of MMV021057 and DA showed additive or synergistic effects against four tested parasites, while combinations of MMV021057 with MMV675968 and of MMV675968 with DA showed antagonistic effects. In mice, treated with 50 mg/kg MMV021057 and 25 mg/kg MMV675968 inhibited the growth of Babesia microti by 54 and 64%, respectively, as compared to the untreated group on day 8. Interestingly, a combination treatment with 6.25 mg/kg DA and 25 mg/kg MMV021057 inhibited B. microti by 91.6%, which was a stronger inhibition than that by single treatments with 50 mg/kg MMV021057 and 25 mg/kg DA, which showed 54 and 83% inhibition, respectively. Our findings indicated that MMV021057, MMV675968, and the combination treatment with MMV021057 and DA are prospects for further development of antipiroplasm drugs.

Indexed as

Drug Evaluation, PreclinicalAnimalsAntipruriticsBabesiaBabesiosisCattleDrug SynergismDrug Therapy, CombinationErythrocytesFemaleHumansInhibitory Concentration 50MaleMiceMice, Inbred BALB CTheileriaAntipruriticsAntipiroplasm agentDrug screeningPathogen Box

Identifiers

PMID31254719
PMCPMC6603297
OpenAlexW2952793420

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.