Methods used in preclinical assessment of anti-Buruli ulcer agents: A global perspective

Abstract

Buruli ulcer (BU) caused by Mycobacterium ulcerans is the third most common chronic mycobacterial infection in humans. Approximately 5000 cases are reported annually from at least 33 countries around the globe, especially in rural African communities. Even though anti-mycobacterial therapy is often effective for early nodular or ulcerative lesions, surgery is sometimes employed for aiding wound healing and correction of deformities. The usefulness of the antibiotherapy nonetheless is challenged by huge restrictive factors such as high cost, surgical scars and loss of income due to loss of man-hours, and in some instances employment. For these reasons, more effective and safer drugs are urgently needed, and research programs into alternative therapeutics including investigation of natural products should be encouraged. There is the need for appropriate susceptibility testing methods for the evaluation of potency. A number of biological assay methodologies are in current use, ranging from the classical agar and broth dilution assay formats, to radiorespirometric, dye-based, and fluorescent/luminescence reporter assays. Mice, rats, armadillo, guinea pigs, monkeys, grass cutters and lizards have been suggested as animal models for Buruli ulcer. This review presents an overview of in vitro and in vivo susceptibility testing methods developed so far for the determination of anti-Buruli ulcer activity of natural products and derivatives.

In Silico Screening of Isocitrate Lyase for Novel Anti-Buruli Ulcer Natural Products Originating from Africa

“…In its severe form, the sole recourse is surgery. The procedure can be performed only at facilities with adequate medical infrastructure and are not affordable for most patients [ 17 ].…”

“…The current treatment options are very limited. However, there are a few studies being conducted to mitigate it including amikacin administered in combination with rifampicin and azithromycin, which has been found to have antimicrobial activity against M. ulcerans in-vitro [ 17 ]. Results from a 2017 controlled pilot-study to access the efficacy of a combination of rifampicin and streptomycin or rifampicin and clarithromycin highlighted no significant difference in their curative rates [ 18 ].…”

Buruli ulcer in Africa: Geographical distribution, ecology, risk factors, diagnosis, and indigenous plant treatment options – A comprehensive review

“…& Perr. ), Brenan] seeds evergreen tree stem barks decoction and powder topical [ 91 ] Stemonocoleus micranthus [Harms]) seeds evergreen tree stem barks powder topical [ 91 ] Holarrhena floribunda (G. Don) T. Durand and Schinz seeds shrub or tree stem bark, leaf powder topical [ 21 , 93 ] Annona senegalensis subsp. oulotricha Le Thomas [Annonaceae] seeds, cuttings evergreen shrub leaf, stem decoction or powder topical, poultice [ 21 , 94 ] …”

“…Although the use of antibiotic medication has significantly improved BU management and produced superior results, streptomycin injections are associated with significant nephrotoxicity and ototoxicity [ 21 ]. Also, rifampicin has been implicated in drug-drug interactions [ 21 ]. Surgical treatments are only practicable in a small number of medical facilities with appropriate technology, and are neither economical nor available to a substantial portion of the population, particularly in Africa [ 6 , 22 ].…”

Skin in the Game: An Assay to Monitor Leukocyte Infiltration in Dermal Lesions of a Guinea Pig Model for Tick-Borne Rickettsiosis

“…Further, a suitable animal model is required to study host-tick-pathogen interactions effectively. The diseases already mentioned, including spotted fever rickettsiosis, and infectious diseases caused by agents not transmitted by vectors, can be appropriately modeled in a guinea pig [7][8][9]. Rickettsia parkeri, a tick-borne agent of spotted fever rickettsiosis, is transmitted by the Gulf Coast tick, Amblyomma maculatum, in the eastern and primarily Gulf Coast states of the United States.…”