One of the greatest achievements of health sciences is the eradication of infectious diseases such as smallpox that in the past imposed a severe burden on humankind, through global vaccination campaigns. Moreover, progress towards the eradication of others such as poliomyelitis, dracunculiasis, and yaws is being made.

In contrast, other infections that were previously contained are reemerging, due to several factors, including lack of access to vaccines due to geopolitical reasons, the rise of anti-vaccine movements, and the constant mobility of infected persons from the endemic sites.

One of such disease is diphtheria, caused by Corynebacterium diphtheriae and a few other related species such as C. ulcerans and C. pseudotuberculosis. Importantly, in France, diphtheria cases reported in 2022 increased 7-fold from the average of previously recorded cases per year in the previous 4 years and the situation in other European countries is similar.

Hence, as reported here, Hennart et al. (2023) developed DIPHTOSCAN, a free access bioinformatics tool with user-friendly interphase, aimed to easily identify, extract and interpret important genomic features such as the sublineage of the strain, the presence of the tox gene (as a string predictor for toxigenic disease) as well as genes coding other virulence factors such as fimbriae, and the presence of know resistant mechanisms towards antibiotics like penicillin and erythromycin currently used in the clinic to treat this infection.

The authors validated the performance of their tool with a large collection of genomes, including those obtained from the isolates of the 2022 outbreak in France, more than 1,200 other genomes isolated from France, Algeria, and Yemen, and more than 500 genomes from several countries from Europe, America, Africa, Asia, and Oceania that are available through the NCBI site.

DIPHTOSCAN will allow the rapid identification and surveillance of potentially dangerous strains such as those being tox-positive isolates and resistant to multiple drugs and/or first-line treatments and a better understanding of the epidemiology and evolution of this important reemerging disease.

Reference

Hennart M., Crestani C., Bridel S., Armatys N., Brémont S., Carmi-Leroy A., Landier A., Passet V., Fonteneau L., Vaux S., Toubiana J., Badell E. and Brisse S. (2023). A global Corynebacterium diphtheriae genomic framework sheds light on current diphtheria reemergence. bioRxiv, 2023.02.20.529124, ver 3 peer-reviewed and recommended by PCI Infections. https://doi.org/10.1101/2023.02.20.529124

As recently reported by the world organisation for animal health, 60% of infectious diseases are zoonotic with a significant part associated to ticks. Ticks can transmit various pathogens such as bacteria, viruses and parasites. Among pathogens known to be transmitted by ticks, Ehrlichia ruminantium is an obligate intracellular Gram-negative bacterium responsible for the fatal heartwater disease of domestic and wild ruminants (Allsopp, 2010). E. ruminantium is transmitted by ticks of the genus Amblyomma in the tropical and sub-Saharan areas, as well as in the Caribbean islands. It constitutes a major threat for the American livestock industries since a suitable tick vector is already present in the American mainland and potential introduction of infected A. variegatum through migratory birds or uncontrolled movement of animals from Caribbean could occur (i.e. Deem, 1998 ; Kasari et al 2010). The disease is also a major obstacle to the introduction of animals from heartwater-free to heartwater-infected areas into sub-Saharan Africa and thus restrains breeding programs aiming at upgrading local stocks (Allsopp, 2010).

In this context, it is essential to develop control strategies against heartwater, as developing effective vaccines, for instance. Such an objective requires a better understanding of the early interaction of E. ruminantium and its host cells and of the mechanisms associated with bacterial adhesion to the host-cell. In this study, the authors. studied the role of E. ruminantium membrane protein ERGA_CDS_01230 in the adhesion process to host bovine aortic endothelial cells (BAEC).

After successfully producing the recombinant version of the protein, Pinarello et al (2022) followed the in vitro culture of E. ruminantium in BAEC and observed that the expression of the protein peaked at the extracellular infectious elementary body stages. This result would suggest the likely involvement of the protein in the early interaction of E. ruminantium with its host cells. The authors then showed using flow cytometry, and scanning electron microscopy, that beads coated with the recombinant protein adhered to BAEC. In addition, they also observed that the adhesion protein of E. ruminantium interacted with proteins of the cell's lysate, membrane and organelle fractions. Additionally, enzymatic treatment, degrading dermatan and chondroitin sulfates on the surface of BAEC, was associated with a 50% reduction in the number of bacteria in the host cell after a development cycle, indicating that glycosaminoglycans might play a role in the adhesion of E. ruminantium to the host-cell. Finally, the authors observed that the adhesion protein of E. ruminantium induced a humoral response in vaccinated animals, making this protein a possible vaccine candidate.

As rightly pointed out by both reviewers, the results of this study represent a significant advance (i) in the understanding of the role of the E. ruminantium membrane protein ERGA_CDS_01230 in the adhesion process to the host-cell and (ii) in the development of new control strategies against heartwater as this protein might potentially be used as an immunogen for the development of future vaccines.

References

Allsopp, B.A. (2010). Natural history of Ehrlichia ruminantium. Vet Parasitol 167, 123-135. https://doi.org/10.1016/j.vetpar.2009.09.014

Deem, S.L. (1998). A review of heartwater and the threat of introduction of Cowdria ruminantium and Amblyomma spp. ticks to the American mainland. J Zoo Wildl Med 29, 109-113.

Kasari, T.R. et al (2010). Recognition of the threat of Ehrlichia ruminantium infection in domestic and wild ruminants in the continental United States. J Am Vet Med Assoc. 237:520-30. https://doi.org/10.2460/javma.237.5.520

Pinarello V, Bencurova E, Marcelino I, Gros O, Puech C, Bhide M, Vachiery N, Meyer DF (2022) Ehrlichia ruminantium uses its transmembrane protein Ape to adhere to host bovine aortic endothelial cells. bioRxiv, 2021.06.15.447525, ver. 3 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2021.06.15.447525

Understanding the ecological and evolutionary factors underlying the spread of new fungal pathogen populations can inform the development of more effective management strategies. In plant pathology, pathogenicity is generally presented as having two components: ‘virulence’ (qualitative pathogenicity) and aggressiveness (quantitative pathogenicity). Changes in virulence in response to the deployment of new resistant varieties are a major driver of the spread of new populations (called pathotypes, or races) in modern agrosystems, and the genomic (i.e. proximal) and eco-evolutionary (i.e. ultimate) factors underlying these changes are well-documented [1,2,3]. By contrast, the role of changes in aggressiveness in the spread of pathotypes remains little known [4].

The study by Cécilia Fontyn and collaborators [5] set out to characterize changes in aggressiveness for isolates of two pathotypes of the wheat leaf rust (Puccinia triticina) that have been dominant in France during the 2005-2016 period. Isolates were genetically characterized using multilocus microsatellite typing and phenotypically characterized for three components of aggressiveness on wheat varieties: infection efficiency, latency period, and sporulation capacity. Using experiments that represent quite a remarkable amount of work and effort, Fontyn et al. showed that each dominant pathotype consisted of several genotypes, including common genotypes whose frequency changed over time. For each pathotype, the genotypes that were more common initially were replaced by a more aggressive genotype. Together, these results show that changes in the genetic composition of populations of fungal plant pathogens can be associated with, and may be caused by, changes in the quantitative components of pathogenicity. This study also illustrates how extensive, decade-long monitoring of fungal pathogen populations, such as the one conducted for wheat leaf rust in France, represents a very valuable resource for research.

REFERENCES

[1] Brown, J. K. (1994). Chance and selection in the evolution of barley mildew. Trends in Microbiology, 2(12), 470-475. https://doi.org/10.1016/0966-842x(94)90650-5

[2] Daverdin, G., Rouxel, T., Gout, L., Aubertot, J. N., Fudal, I., Meyer, M., Parlange, F., Carpezat, J., & Balesdent, M. H. (2012). Genome structure and reproductive behaviour influence the evolutionary potential of a fungal phytopathogen. PLoS Pathogens, 8(11), e1003020. https://doi.org/10.1371/journal.ppat.1003020

[3] Gladieux, P., Feurtey, A., Hood, M. E., Snirc, A., Clavel, J., Dutech, C., Roy, M., & Giraud, T. (2015). The population biology of fungal invasions.Molecular Ecology, 24(9), 1969-86. https://doi.org/10.1111/mec.13028

[4] Fontyn, C., Zippert, A. C., Delestre, G., Marcel, T. C., Suffert, F., & Goyeau, H. (2022). Is virulence phenotype evolution driven exclusively by Lr gene deployment in French Puccinia triticina populations?. Plant Pathology, 71(7), 1511-1524. https://doi.org/10.1111/ppa.13599

[5] Fontyn, C., Meyer, K. J., Boixel, A. L., Delestre, G., Piaget, E., Picard, C., Suffer, F., Marcel, T.C., & Goyeau, H. (2022). Evolution within a given virulence phenotype (pathotype) is driven by changes in aggressiveness: a case study of French wheat leaf rust populations. bioRxiv, 2022.08.29.505401, ver. 3 peer-reviewed and recommended by Peer Community in Infections.  https://doi.org/10.1101/2022.08.29.505401

Despite decades of advances and understanding of the indiscriminate nature of human immunodeficiency virus (HIV), it remains shrouded in stigma that makes it difficult to reach some key populations at risk of transmission. The advent of self-testing technology for HIV (HIVST) has opened much-needed potential for bringing privacy to prevention that is crucial for curtailing its continued spread (Johnson et al., 2014). The HIV Self-Testing in Africa (STAR) Initiative (https://www.psi.org/fr/project/star/), carried out in Eastern and Southern Africa between 2015 and 2020 (Simwinga et al., 2022), demonstrated the market and public health operational potential of HIVST of different distribution methods. From 2019 to 2022, the “AutoTest de dépistage du VIH : Libre d’Accéder à la connaissance de son Statut" (ATLAS, translating to “HIVST: Freedom to know your status”) program built on these findings to quantify the public health value of HIVST for reaching key populations in West Africa (specifically, Mali, Senegal and Côte d’Ivoire) (Ky-Zerbo et al., 2022).

The innovative secondary distribution methods these studies employed, where the primary targeted populations were also encouraged to take and provide tests to their contacts, helped widen the reach of HIVST within key population networks beyond those relying on access to HIV testing facilities.

The tricky part of the self-testing model lies in assessing its reach and impact while maintaining the privacy of self-testers that is central to its success. Following voluntary phone survey methods that previously were able to show expanded reach of HIVST to first-time testers in key populations in West Africa and high rates of confirmatory testing and treatment seeking (Kra et al., 2022), Kra et al. (Kra et al., 2024) quantified how many of these self-tests led to a positive result – allowing wider assessment of follow-up behaviors and positivity rates among the hard-to-reach populations the program had targeted. 

While the numbers were low, the results were informative. Among respondents who reported a positive (“reactive”) HIVST, just 44% proceeded to confirmatory testing. This is lower than in other populations where HIVST follow-up has been assessed (Thirumurthy et al., 2016). The main reasons given for not confirming a reactive self-test was misinterpretation of HIVST results and not understanding that confirmatory testing was needed. The result thus highlighted a need for improved communication on how to correctly interpret HIVST results, and the authors provided ranges for how this misinterpretation could have affected their positivity estimates. However, the majority of those who sought confirmatory testing did so within 3 months, and nearly all of those with confirmed infection started on treatment. HIV positivity rates in the three countries were all higher than other published HIV positivity estimates (Giguère et al., 2021; Maheu-Giroux et al., 2019), suggesting that HIVST methods were highly effective at reaching the targeted communities. 

Finally, while the authors demonstrated their methods as an effective way of assessing the utility of HIVST campaigns and identifying ways to improve them, the follow-up surveys are likely too costly to replace current passive surveillance methods for assessing community disease burden. That said, these precious data should be taken as validation of the public health value of HIV self-testing in key populations across communities in West Africa. With improvements in communicating instructions for use and follow-up, there is little doubt that the innovation of HIVST primary and secondary distribution could become a widely useful addition to the fight against HIV. 

References

Giguère, K., Eaton, J. W., Marsh, K., Johnson, L. F., Johnson, C. C., Ehui, E., Jahn, A., Wanyeki, I., Mbofana, F., Bakiono, F., Mahy, M., & Maheu-Giroux, M. (2021). Trends in knowledge of HIV status and efficiency of HIV testing services in sub-Saharan Africa, 2000–20: a modelling study using survey and HIV testing programme data. The Lancet HIV, 8(5), e284–e293. https://doi.org/10.1016/S2352-3018(20)30315-5

Johnson, C., Baggaley, R., Forsythe, S., Van Rooyen, H., Ford, N., Napierala Mavedzenge, S., Corbett, E., Natarajan, P., & Taegtmeyer, M. (2014). Realizing the potential for HIV self-testing. In AIDS and Behavior (Vol. 18, Issue SUPPL. 4). Springer New York LLC. https://doi.org/10.1007/s10461-014-0832-x

Kra, A. K., Fosto, A. S., N’guessan, K. N., Geoffroy, O., Younoussa, S., Kabemba, O. K., Gueye, P. A., Ndeye, P. D., Rouveau, N., Boily, M. C., Silhol, R., d’Elbée, M., Maheu-Giroux, M., Vautier, A., & Larmarange, J. (2022). Can HIV self-testing reach first-time testers? A telephone survey among self-test end users in Côte d’Ivoire, Mali, and Senegal. BMC Infectious Diseases, 22. https://doi.org/10.1186/s12879-023-08626-w

Kra, A. K., Fotso, A. S., Rouveau, N., Maheu-Giroux, M., Boily, M.-C., Silhol, R., d’Elbée, M., Vautier, A., Lamarange, J., & the Atlas team. (2024). HIV self-testing positivity rate and linkage to confirmatory testing and care: a telephone survey in Côte d’Ivoire, Mali, and Senegal. MedRxiv, Ver. 4 Peer-Reviewed and Recommended by Peer Community in Infections, 2023.06.10.23291206. https://doi.org/https://doi.org/10.1101/2023.06.10.23291206

Ky-Zerbo, O., Desclaux, A., Boye, S., Maheu-Giroux, M., Rouveau, N., Vautier, A., Camara, C. S., Kouadio, B. A., Sow, S., Doumenc-Aidara, C., Gueye, P. A., Geoffroy, O., Kamemba, O. K., Ehui, E., Ndour, C. T., Keita, A., & Larmarange, J. (2022). “I take it and give it to my partners who will give it to their partners”: Secondary distribution of HIV self-tests by key populations in Côte d’Ivoire, Mali, and Senegal. BMC Infectious Diseases, 22. https://doi.org/10.1186/s12879-023-08319-4

Maheu-Giroux, M., Marsh, K., Doyle, C. M., Godin, A., Lanièce Delaunay, C., Johnson, L. F., Jahn, A., Abo, K., Mbofana, F., Boily, M. C., Buckeridge, D. L., Hankins, C. A., & Eaton, J. W. (2019). National HIV testing and diagnosis coverage in sub-Saharan Africa: A new modeling tool for estimating the “first 90” from program and survey data. AIDS, 33, S255–S269. https://doi.org/10.1097/QAD.0000000000002386

Simwinga, M., Gwanu, L., Hensen, B., Sigande, L., Mainga, M., Phiri, T., Mwanza, E., Kabumbu, M., Mulubwa, C., Mwenge, L., Bwalya, C., Kumwenda, M., Mubanga, E., Mee, P., Johnson, C. C., Corbett, E. L., Hatzold, K., Neuman, M., Ayles, H., & Taegtmeyer, M. (2022). Lessons learned from implementation of four HIV self-testing (HIVST) distribution models in Zambia: applying the Consolidated Framework for Implementation Research to understand impact of contextual factors on implementation. BMC Infectious Diseases, 22(Suppl 1). https://doi.org/10.1186/s12879-024-09168-5

Thirumurthy, H., Masters, S. H., Mavedzenge, S. N., Maman, S., Omanga, E., & Agot, K. (2016). Promoting male partner HIV testing and safer sexual decision making through secondary distribution of self-tests by HIV-negative female sex workers and women receiving antenatal and post-partum care in Kenya: a cohort study. The Lancet HIV, 3(6), e266–e274. https://doi.org/10.1016/S2352-3018(16)00041-2

African trypanosomiasis is caused by to the infection of a protozoan parasite of the Trypanosoma genus. It is transmitted by the tsetse fly, and is largely affecting cattle in the sub-humid areas of Africa, causing a high economic impact. However, not all the bovine strains are equally susceptible to the infection (1). 

In order to dissect the mechanisms underlying susceptibility to African trypanosoma infection, Peylhard et al (2) performed blood transcriptional profiles of trypanotolerant, trypanosensitive and mixed cattle breeds, before and after experimental infection with T. congolense. 

First of all, the authors have characterized the basal transcriptional profiles in the blood of the different breeds under study, which could be classified in a wide array of functional pathways. Of note, after infection some pathways were consistently enriched in all the group tested. Among them, the immune system-related ones were again on the top functions reported. The search for specific canonical pathways pointed to a prominent role of lipid and cholesterol-related pathways, as well as mitochondrial function and B and T lymphocyte activation.

However, the analysis of infected animals demonstrated that trypanosusceptible animals showed a stronger transcriptomic reprogramming, highly enriched in specific metabolic and immunological pathways. It is worthy to highlight striking differences in genes involved in immune signal transduction, cytokines and markers of different leukocyte subpopulations.

This work represents undoubtedly a significant momentum in the field, since the authors explore in deep a wide panel of cattle breeds representing the majority of West-African taurine and zebu in a systematic way. Since the animals were studied at different timepoints after infection, future longitudinal analyses of these datasets will be providing a precious insight on the kinetics of immune and metabolic reprogramming associated with susceptibility and tolerance to African trypanosoma infection, widening the application of this interesting study into new therapeutic interventions.

References

1. Berthier D, Peylhard M, Dayo G-K, Flori L, Sylla S, Bolly S, Sakande H, Chantal I, Thevenon S (2015) A Comparison of Phenotypic Traits Related to Trypanotolerance in Five West African Cattle Breeds Highlights the Value of Shorthorn Taurine Breeds. PLOS ONE, 10, e0126498. https://doi.org/10.1371/journal.pone.0126498

2. Peylhard M, Berthier D, Dayo G-K, Chantal I, Sylla S, Nidelet S, Dubois E, Martin G, Sempéré G, Flori L, Thévenon S (2022) Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense. bioRxiv, 2022.06.10.495622, ver. 2 peer-reviewed and recommended by Peer Community Infections. https://doi.org/10.1101/2022.06.10.495622.