Each and every one of us will recall the severe acute respiratory syndrome (SARS) coronavirus (CoV-2) pandemic, and the national and international political hesitations in its management. Fall 2019, in the city of Wuhan, Hubei province, China, an outbreak of unusual viral pneumonia due to a new emerging coronavirus named as SARS-CoV-2 started, generating late February a modern pandemic called COVID-19, posing very serious threat to global public health and the world economy (Hu et al. 2021). As we are getting out from this pandemic, and even if viral variants are still circulating, what have we learned and retained from this difficult period, shaking our certainties and reminding us of past images of devastating plagues? The COVID-19 pandemic highlighted the importance of early action, widespread testing, open data sharing, and strong public responses (The Lancet Infectious Diseases 2024). It has also highlighted that the animal origin of SARS-CoV-2 was still unknown and the existence of a reservoir host not really demonstrated (Cohen 2021). Beyond this, the COVID-19 pandemic has also revealed the importance of early and continuous surveillance, also raised questions about the role of meteorological conditions on the dispersion and viability of this virus, and highlighted the devastating effects of social inequality. We all remember some medical doctors who became modern preachers announcing the end of the pandemic because of unfavorable weather conditions coming for viral spread!

However, epidemiological studies analyzing the role of different parameters, and effects of national and regional restrictions at local or regional scales on COVID-19 are still rare. In this investigation entitled “Spatial and temporal epidemiology of SARS-3 CoV-2 virus lineages in Teesside, UK, in 2020: effects of socio-economic deprivation, weather, and lockdown on lineage dynamics”, Moss and collaborators’ aim is to analyze how a range of parameters, using both generalized linear mixed- and Bayesian spatial modeling, affected positive cases in the Teesside subregion of North East England during 2020 (Moss et al. 2024). Also, the authors wanted to understand the impacts of national and local government interventions introduced this year affected disease conditions in this subregion showing high levels of deprivation due to deindustrialisation in the latter half of the 20th century. 

According to Moss et al. (2024), the UK government decided for a heterogenous ”tier” system of local restrictions in England during the second wave associated with a more stringent national lockdown. The intention was to be more responsive and appropriate to the different English local contexts. The authors take us through a detailed statistical analysis to show that disease patterns in Teesside were associated with demographic parameters, social deprivation, weather conditions (essentially temperature) and governmental health interventions. Interestingly, findings lead to the conclusion that local tier interventions by public authorities was less effective at reducing COVID-19 cases in Teesside than a strict, long-term national lockdown.  A closer look at the spatio-temporal dynamics of the eight most common SARS-CoV-2 lineages circulating in Teesside in 2020 reveals complex dynamic behaviours differing to those of the total positive cases, certainly due to environmental and demographic stochasticity, and sublocal heterogenous social and economic conditions.

Overall, we recommend reading this study, which reveals the complexity of dealing with epidemics and pandemics, and highlights the importance of sound national political decisions and difficulties to proceed to local adjustments, i.e. tier system, in epidemic and pandemic control. 

The present recommendation is resulting from thorough reviews produced by Samuel Alizon and two anonymous reviewers, and which I thank very much for their review works here. 

References

Jon COHEN. 2021. Prophet in purgatory. Science 374, 1040-1045. https://www.science.org/doi/epdf/10.1126/science.acx9661

Ben HU, Hua GUO, Peng ZHOU, Zheng-Li SHI. 2021. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 19, 141-54. https://doi.org/10.1038/s41579-020-00459-7 

The Lancet Infectious Diseases. 2024. Have we learned anything? Editorial. The Lancet Infectious Diseases 24, 793. https://doi.org/10.1016/S1473-3099(24)00439-0

E.D. Moss, S.P. Rushton, P. Baker, M. Bashton, M.R. Crown, R.N. dos Santos, A. Nelson, S.J. O’Brien, Z. Richards, R.A. Sanderson, W.C. Yew, G.R. Young, C.M. McCann, D.L. Smith (2024) Spatial and temporal epidemiology of SARS-CoV-2 virus lineages in Teesside, UK, in 2020: effects of socio-economic deprivation, weather, and lockdown on lineage dynamics. medRxiv, ver.5 peer-reviewed and recommended by PCI Infections. https://doi.org/10.1101/2022.02.05.22269279

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

According to the international animal health authority, i.e., the World Organization on Animal Health (WOAH, former OIE), circoviruses are part of the Circoviridae family, which only includes 2 genera Circovirus and Cyclovirus, and infect swine, canine, ursid, viverrid, felid, pinniped, herpestid, mustelid, and several avian species (WOAH 2021). They are small (12–27 nm), non-enveloped, circular, single-stranded DNA viruses, viral replication is nuclear, and wild and domestic birds and mammals could serve as natural hosts. If most infections caused by circoviruses are subclinical in both wild and domestic species, they can be responsible for severe diseases in the commercial pig industry due to the Porcine circovirus-2 (PCV-2). These viruses can constitute a threat to wildlife, and cause their hosts to become immunocompromised, and animals often present with secondary coinfections. 

Canine circoviruses (CanineCV) harbour a worldwide distribution in dogs, and is the sole member of the viral genus to infect canines. They can be detected in wild carnivores, such as wolves, badgers, foxes and jackals, which indicates an ability for cross-species transmission between wildlife and domestic dogs. However, fox circovirus (FoCV), a distinct lineage of CanineCV, has been identified exclusively in wild canids (foxes and wolves) and not in dogs in Europe and North America, where it can cause in red foxes meningoencephalitis and other central nervous system signs. 

In their article, Canuti et al. (2024) investigate the presence, distribution and ecology of CanineCV in grey wolf specimens from the Northwest Territories, Canada. CanineCV occurrence appears to be relatively high with 45.3% positive specimens and parvoviral superinfections observed. The authors identify a high CanineCV genetic diversity among the investigated grey wolf specimens, and exacerbated by viral recombination. Phylogenetic analysis reveals the existence of 4 lineages, within each of them strains segregate by geography and not by host origin. This observed geographic segregation is interpreted as being due to the absence of exchange flows between grey wolf host subpopulations.  Due to the paucity of knowledge on these circoviruses in wildlife and at the interface between wild and domestic animals, the authors discuss the plausible role of wolves as natural host reservoirs for disease transmission due to long-lasting virus-host coevolution. They are also conscious that additional maintenance hosts could exist in the wild, claiming for further studies to decipher fox circovirus disease ecology and transmission dynamics.

This study underlines the importance of better understanding the transmission ecology and evolution of these Canine circoviruses, and I can only agree. Xiao et al. (2023), a research not referred to in the present work, evidenced CanineCV infection in cats in China, and obtained the first whole genome of cat-derived CanineCV. This emphasizes the importance of monitoring additional animal species and locations in the world to clarify disease ecology and transmission dynamics. A broader sampling of a wide range of animal species in different parts of the world using a species community-based approach is the key to understanding these CanineCV infections.

References

Marta CANUTI, Abigail V.L. KING, Giovanni FRANZO, H. Dean CLUFF, Lars E. LARSEN, Heather FENTON, Suzanne C. DUFOUR, Andrew S. LANG. 2024. Diverse fox circovirus (Circovirus canine) variants circulate at high prevalence in grey wolves (Canis lupus) from the Northwest Territories, Canada. bioRxiv, ver. 2 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2024.03.08.584028

World Organization on Animal Health. 2021. Circoviruses.  https://www.woah.org/app/uploads/2021/05/circoviruses-infection-with.pdf [consulted on July 9th, 2024].

Xiangyu XIAO, Yan CHAO LI, Feng PEI XU, Xiangpi HAO, Shoujun LI, Pei ZHOU. 2023. Canine circovirus among dogs and cats in China: first identification in cats. Front. Microbiol. 14. https://doi.org/10.3389/fmicb.2023.1252272

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

Thanks to the coordinated and sustained efforts of national control programs, the World Health Organization (WHO), bilateral cooperation and nongovernmental organizations, the incidence of Human African Trypanosomiasis (HAT), better known as sleeping sickness, has drastically decreased during the last two decades (WHO, 2023a). Indeed, between 1999 and 2022, the reported number of new cases of the chronic form of sleeping sickness (Trypanosoma brucei gambiense) fell by 97% (from 27 862 to 799), and the number of newly reported cases of the acute form of HAT (Trypanosoma brucei rhodesiense) fell by 94% (from 619 to 38) (WHO, 2023b). These encouraging trends led the WHO to target this debilitating and highly fatal (if untreated) vector-borne parasitic disease for elimination as a public health problem by 2020, and for interruption of transmission (zero case) by 2030 (WHO, 2021, WHO, 2023a). However, the disease is persisting in many foci, and even some cases of resurgence have been documented after unfortunate events such as war or pandemics (Moore et al., 1999; Sah et al., 2023. Simarro et al). Although effective control measures, diagnosis and treatment are complex and require specific skills (WHO, 2023), especially in a context which animal reservoirs, including hidden reservoirs, can contribute to the maintenance/persistence of infection (Welburn and Maudlin, 2012; Camara et al., 2021). Vector control therefore appears as a viable alternative to accelerate sleeping sickness transmission interruption, and WHO has identified some critical actions for HAT elimination, including the coordination of vector control and animal trypanosomiasis management among countries, stakeholders and other sectors (e.g. tourism and wildlife) through multisectoral national bodies to maximize synergies (WHO, 2021).

The paper by Kagbadouno and Collaborators (2024) uses microsatellite markers genotyping and population genetics tools to investigate the impact of 11 years of tiny target-based vector control on the population biology of Glossina palpalis gambiensis in Boffa, one of the three active sleeping sickness foci in Guinea (Kagbadouno et al., 2012). Although vector control significantly reduced the apparent densities of tsetse flies (and therefore the human exposure to the vector) as well as the prevalence and incidence of the disease in the Boffa HAT focus (Courtin et al., 2015), no genetic signature of vector control was observed as no difference in population size, before and after the onset of the control policy, was found. The authors then provided national programs and implementing partners with indications on the actions to be taken to (i) maintain the achievements of vector control (thus avoiding rebound/resurgence as was experienced in the past (Franco et al., 2014), and (ii) accelerate the momentum towards elimination by for example combining these vector control efforts with medical surveys for case detection and treatment, in line with WHO recommendations (WHO, 2021). 

References

Camara M, Soumah AM, Ilboudo H, Travaillé C, Clucas C, Cooper A, Kuispond Swar NR, Camara O, Sadissou I, Calvo Alvarez E, Crouzols A, Bart JM, Jamonneau V, Camara M, MacLeod A, Bucheton B, Rotureau B. Extravascular Dermal Trypanosomes in Suspected and Confirmed Cases of gambiense Human African Trypanosomiasis. Clin Infect Dis. 2021 Jul 1;73(1):12-20. https://doi.org/10.1093/cid/ciaa897

Courtin F, Camara M, Rayaisse JB, Kagbadouno M, Dama E, Camara O, Traore IS, Rouamba J, Peylhard M, Somda MB, Leno M, Lehane MJ, Torr SJ, Solano P, Jamonneau V, Bucheton B (2015) Reducing human-tsetse contact significantly enhances the efficacy of sleeping sickness active screening campaigns: a promising result in the context of elimination. PLoS Neglected Tropical Diseases, 9. https://doi.org/10.1371/journal.pntd.0003727

Franco JR, Simarro PP, Diarra A, Jannin JG. (2014) Epidemiology of human African trypanosomiasis. Clin Epidemiol. 6:257-75. https://doi.org/10.2147/CLEP.S39728

Kagbadouno, M. S., Séré, M., Ségard, A., Camara, A. D., Camara, M., Bucheton, B., ... & Ravel, S. (2023). Population genetics of Glossina palpalis gambiensis in the sleeping sickness focus of Boffa (Guinea) before and after eight years of vector control: no effect of control despite a significant decrease of human exposure to the disease. bioRxiv, ver. 2 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2023.07.25.550445

Kagbadouno MS, Camara M, Rouamba J, Rayaisse JB, Traoré IS, Camara O, Onikoyamou MF, Courtin F, Ravel S, De Meeûs T, Bucheton B, Jamonneau V, Solano P (2012) Epidemiology of sleeping sickness in boffa (Guinea): where are the trypanosomes? PLoS Neglected Tropical Diseases, 6, e1949. https://doi.org/10.1371/journal.pntd.0001949 

Moore A, Richer M, Enrile M, Losio E, Roberts J, Levy D. Resurgence of sleeping sickness in Tambura County, Sudan. Am J Trop Med Hyg. 1999 Aug;61(2):315-8. https://doi.org/10.4269/ajtmh.1999.61.315

Sah R, Mohanty A, Rohilla R, Padhi BK. A resurgence of Sleeping sickness amidst the COVID-19 pandemic: Correspondence. Int J Surg Open. 2023 Apr;53:100604. https://doi.org/10.1016/j.ijso.2023.100604

Welburn SC, Maudlin I. Priorities for the elimination of sleeping sickness. Adv Parasitol. 2012;79:299-337. https://doi.org/10.1016/B978-0-12-398457-9.00004-4

World Health Organization, 2021. Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021–2030. World Health Organization, Geneva, Switzerland. ISBN: 978 92 4 001035 2. 196p. 

World Health Organization, 2023a. Trypanosomiasis, human African (sleeping sickness): key facts. Accessed at https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness) on February 19, 2023.

World Health Organization, 2023b. Human African Trypanosomiasis, (sleeping sickness): the global health observatory. Accessed at https://www.who.int/data/gho/data/themes/topics/human-african-trypanosomiasis on February 19, 2023.