Journal Article > ReviewFull Text
Clin Microbiol Infect. 1 March 2025; Volume 31 (Issue 3); 339-344.; DOI:10.1016/j.cmi.2024.06.015
Cohn J, Balasegaram M, Srinivasan H, Menghaney L, Mpundu M, et al.
Clin Microbiol Infect. 1 March 2025; Volume 31 (Issue 3); 339-344.; DOI:10.1016/j.cmi.2024.06.015
BACKGROUND
Antibiotics are indispensable to modern healthcare, yet their equitable access remains a pressing global challenge. Factors contributing to inequities include insufficient evidence for optimal clinical use, limited registration, pricing for Reserve antibiotics, and supply chain challenges. These issues disproportionately affect low- and middle-income countries, exacerbating antimicrobial resistance burdens.
OBJECTIVES
This paper explores the multifaceted dimensions of inequitable antibiotic access and proposes a comprehensive framework to address the crisis.
SOURCES
Published articles, grey literature analysis, and the authors' own expertise contributed to this article.
CONTENT
While much attention has been paid to push-and-pull incentives for antibiotic development, these interventions are inadequate to reach sustainable and equitable access to antibiotics. Improving equitable antibiotic access requires an ecosystem approach, involving multiple stakeholders and including public–private partnerships. The paper advocates for initiatives spanning research and development, regulatory pathways, procurement strategies, and financing mechanisms and suggests concrete interventions in each of these areas. The specific interventions and mix of public and private actors may vary according to antibiotic, market, and health system context, but must be designed to meet public health needs while also supporting a market that will sustain quality-assured production and delivery of antibiotics.
IMPLICATIONS
Addressing the challenge of equitable antibiotic access requires coordinated efforts across sectors and regions. By embracing an ecosystem approach centred on public health priorities, stakeholders can pave the way for a sustainable supply of antibiotics, and equitable access, safeguarding the future of global healthcare amidst the growing threat of antimicrobial resistance.
Journal Article > ReviewFull Text
Clin Microbiol Infect. 21 July 2023; Volume S1198-743X (Issue 23); 00339-7.; DOI:10.1016/j.cmi.2023.07.013
Motta I, Boeree M, Chesov D, Dheda K, Günther G, et al.
Clin Microbiol Infect. 21 July 2023; Volume S1198-743X (Issue 23); 00339-7.; DOI:10.1016/j.cmi.2023.07.013
BACKGROUND
Tuberculosis is a global health challenge and one of the leading causes of death worldwide. In the last decade, the tuberculosis treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, SHINE) and drug-resistant tuberculosis (STREAM, NiX-TB, ZeNix, TB-PRACTECAL). Dose optimization of rifamycins and repurposed drugs have also brought hopes of further development of safe and effective regimens. Consequently, international and World Health Organization clinical guidelines have been updated multiple times in the last years to keep pace with these advances.
OBJECTIVES
This narrative review aims to summarize the state-of-the-art on treatment of drug-susceptible and drug-resistant tuberculosis, as well as recent trials results and an overview of ongoing clinical trials.
SOURCES
A non-systematic literature review was conducted in PubMed and MEDLINE, focusing on the treatment of tuberculosis. Ongoing clinical trials were listed according to the authors' knowledge, and completed consulting clinicaltrials.gov and other publicly available websites (www.resisttb.org/clinical-trials-progress-report, www.newtbdrugs.org/pipeline/trials).
CONTENT
This review summarizes the recent, major changes in the landscape for drug-susceptible and drug-resistant treatment, with a specific focus on their potential impact on patient outcomes and programmatic TB management. Moreover, insights in host-directed therapies, and advances in pharmacokinetic and pharmacogenomics are discussed. A thorough outline of ongoing therapeutic clinical trials is presented, highlighting different approaches and goals in current TB clinical research.
IMPLICATIONS
Future research should be directed to individualize regimens and protect these recent breakthroughs by preventing and identifying the selection of drug resistance and providing widespread, affordable, patient-centered access to new treatment options for all people affected by tuberculosis.
Tuberculosis is a global health challenge and one of the leading causes of death worldwide. In the last decade, the tuberculosis treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, SHINE) and drug-resistant tuberculosis (STREAM, NiX-TB, ZeNix, TB-PRACTECAL). Dose optimization of rifamycins and repurposed drugs have also brought hopes of further development of safe and effective regimens. Consequently, international and World Health Organization clinical guidelines have been updated multiple times in the last years to keep pace with these advances.
OBJECTIVES
This narrative review aims to summarize the state-of-the-art on treatment of drug-susceptible and drug-resistant tuberculosis, as well as recent trials results and an overview of ongoing clinical trials.
SOURCES
A non-systematic literature review was conducted in PubMed and MEDLINE, focusing on the treatment of tuberculosis. Ongoing clinical trials were listed according to the authors' knowledge, and completed consulting clinicaltrials.gov and other publicly available websites (www.resisttb.org/clinical-trials-progress-report, www.newtbdrugs.org/pipeline/trials).
CONTENT
This review summarizes the recent, major changes in the landscape for drug-susceptible and drug-resistant treatment, with a specific focus on their potential impact on patient outcomes and programmatic TB management. Moreover, insights in host-directed therapies, and advances in pharmacokinetic and pharmacogenomics are discussed. A thorough outline of ongoing therapeutic clinical trials is presented, highlighting different approaches and goals in current TB clinical research.
IMPLICATIONS
Future research should be directed to individualize regimens and protect these recent breakthroughs by preventing and identifying the selection of drug resistance and providing widespread, affordable, patient-centered access to new treatment options for all people affected by tuberculosis.
Journal Article > ReviewFull Text
Clin Microbiol Infect. 1 October 2021; Volume 27 (Issue 10); 1414-1421.; DOI:10.1016/j.cmi.2021.04.015
Ronat JB, Natale A, Kesteman T, Andremont A, Elamin W, et al.
Clin Microbiol Infect. 1 October 2021; Volume 27 (Issue 10); 1414-1421.; DOI:10.1016/j.cmi.2021.04.015
BACKGROUND
In low- and middle-income countries (LMICs), data related to antimicrobial resistance (AMR) are often inconsistently collected. Humanitarian, private and non-governmental medical organizations (NGOs), working with or in parallel to public medical systems, are sometimes present in these contexts. Yet, what is the role of NGOs in the fight against AMR, and how can they contribute to AMR data collection in contexts where reporting is scarce? How can context-adapted, high-quality clinical bacteriology be implemented in remote, challenging and underserved areas of the world?
OBJECTIVES
The aim was to provide an overview of AMR data collection challenges in LMICs and describe one initiative, the Mini-Lab project developed by Médecins Sans Frontières (MSF), that attempts to partially address them.
SOURCES
We conducted a literature review using PubMed and Google scholar databases to identify peer-reviewed research and grey literature from publicly available reports and websites.
CONTENT
We address the necessity of and difficulties related to obtaining AMR data in LMICs, as well as the role that actors outside of public medical systems can play in the collection of this information. We then describe how the Mini-Lab can provide simplified bacteriological diagnosis and AMR surveillance in challenging settings.
IMPLICATIONS
NGOs are responsible for a large amount of healthcare provision in some very low-resourced contexts. As a result, they also have a role in AMR control, including bacteriological diagnosis and the collection of AMR-related data. Actors outside the public medical system can actively contribute to implementing and adapting clinical bacteriology in LMICs and can help improve AMR surveillance and data collection.
In low- and middle-income countries (LMICs), data related to antimicrobial resistance (AMR) are often inconsistently collected. Humanitarian, private and non-governmental medical organizations (NGOs), working with or in parallel to public medical systems, are sometimes present in these contexts. Yet, what is the role of NGOs in the fight against AMR, and how can they contribute to AMR data collection in contexts where reporting is scarce? How can context-adapted, high-quality clinical bacteriology be implemented in remote, challenging and underserved areas of the world?
OBJECTIVES
The aim was to provide an overview of AMR data collection challenges in LMICs and describe one initiative, the Mini-Lab project developed by Médecins Sans Frontières (MSF), that attempts to partially address them.
SOURCES
We conducted a literature review using PubMed and Google scholar databases to identify peer-reviewed research and grey literature from publicly available reports and websites.
CONTENT
We address the necessity of and difficulties related to obtaining AMR data in LMICs, as well as the role that actors outside of public medical systems can play in the collection of this information. We then describe how the Mini-Lab can provide simplified bacteriological diagnosis and AMR surveillance in challenging settings.
IMPLICATIONS
NGOs are responsible for a large amount of healthcare provision in some very low-resourced contexts. As a result, they also have a role in AMR control, including bacteriological diagnosis and the collection of AMR-related data. Actors outside the public medical system can actively contribute to implementing and adapting clinical bacteriology in LMICs and can help improve AMR surveillance and data collection.
Journal Article > CommentaryFull Text
Clin Microbiol Infect. 29 June 2016; Volume 22 (Issue 8); DOI:10.1016/j.cmi.2016.06.012
Reid J, Balasegaram M
Clin Microbiol Infect. 29 June 2016; Volume 22 (Issue 8); DOI:10.1016/j.cmi.2016.06.012
Earlier this year a series of advertisements appeared in London's Westminster tube stations asking viewers to consider a seemingly simple question, 'what does it take to make one medicine?' But as it turns out, this question is not so simple to answer. In this commentary we highlight some key considerations and questions on what it takes to make one medicine, and what it could take to develop medicines that meet people's health needs and are accessible and affordable for all who need them.
Journal Article > ReviewFull Text
Clin Microbiol Infect. 18 May 2021; Volume 27 (Issue 10); 1400-1408.; DOI: 10.1016/j.cmi.2021.05.016
Orekan J, Barbe B, Oeng S, Ronat JB, Letchford J, et al.
Clin Microbiol Infect. 18 May 2021; Volume 27 (Issue 10); 1400-1408.; DOI: 10.1016/j.cmi.2021.05.016
BACKGROUND
Culture media are fundamental in clinical microbiology. In laboratories in low- and middle-income countries (LMICs), they are mostly prepared in-house, which is challenging.
OBJECTIVES
This narrative review describes challenges related to culture media in LMICs, compiles best practices for in-house media preparation, gives recommendations to improve access to quality-assured culture media products in LMICs and formulates outstanding questions for further research.
SOURCES
Scientific literature was searched using PubMed and predefined MeSH terms. In addition, grey literature was screened, including manufacturer's websites and manuals as well as microbiology textbooks.
CONTENT
Bacteriology laboratories in LMICs often face challenges at multiple levels: lack of clean water and uninterrupted power supply, high environmental temperatures and humidity, dust, inexperienced and poorly trained staff, and a variable supply of consumables (often of poor quality). To deal with this at a base level, one should be very careful in selecting culture media. It is recommended to look for products supported by the national reference laboratory that are being distributed by an in-country supplier. Correct storage is key, as is appropriate preparation and waste management. Centralized media acquisition has been advocated for LMICs, a role that can be taken up by the national reference laboratories, next to guidance and support of the local laboratories. In addition, there is an important role in tropicalization and customization of culture media formulations for private in vitro diagnostic manufacturers, who are often still unfamiliar with the LMIC market and the plethora of bacteriology products.
IMPLICATION
The present narrative review will assist clinical microbiology laboratories in LMICs to establish best practices for handling culture media by defining quality, regulatory and research paths.
Culture media are fundamental in clinical microbiology. In laboratories in low- and middle-income countries (LMICs), they are mostly prepared in-house, which is challenging.
OBJECTIVES
This narrative review describes challenges related to culture media in LMICs, compiles best practices for in-house media preparation, gives recommendations to improve access to quality-assured culture media products in LMICs and formulates outstanding questions for further research.
SOURCES
Scientific literature was searched using PubMed and predefined MeSH terms. In addition, grey literature was screened, including manufacturer's websites and manuals as well as microbiology textbooks.
CONTENT
Bacteriology laboratories in LMICs often face challenges at multiple levels: lack of clean water and uninterrupted power supply, high environmental temperatures and humidity, dust, inexperienced and poorly trained staff, and a variable supply of consumables (often of poor quality). To deal with this at a base level, one should be very careful in selecting culture media. It is recommended to look for products supported by the national reference laboratory that are being distributed by an in-country supplier. Correct storage is key, as is appropriate preparation and waste management. Centralized media acquisition has been advocated for LMICs, a role that can be taken up by the national reference laboratories, next to guidance and support of the local laboratories. In addition, there is an important role in tropicalization and customization of culture media formulations for private in vitro diagnostic manufacturers, who are often still unfamiliar with the LMIC market and the plethora of bacteriology products.
IMPLICATION
The present narrative review will assist clinical microbiology laboratories in LMICs to establish best practices for handling culture media by defining quality, regulatory and research paths.
Journal Article > CommentaryFull Text
Clin Microbiol Infect. 29 October 2021; Volume S1198-743X (Issue 21); 00613-3.; DOI:10.1016/j.cmi.2021.10.012
Azman AS, Ciglenecki I, Luquero FJ
Clin Microbiol Infect. 29 October 2021; Volume S1198-743X (Issue 21); 00613-3.; DOI:10.1016/j.cmi.2021.10.012
Journal Article > ResearchFull Text
Clin Microbiol Infect. 16 March 2018; Volume 24 (Issue 12); DOI:10.1016/j.cmi.2018.03.017
Antinori S, Galimberti L, Grande R, Bianco R, Oreni L, et al.
Clin Microbiol Infect. 16 March 2018; Volume 24 (Issue 12); DOI:10.1016/j.cmi.2018.03.017
OBJECTIVES:
We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability.
METHODS:
A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information.
RESULTS:
Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%).
CONCLUSIONS:
CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.
We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability.
METHODS:
A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information.
RESULTS:
Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%).
CONCLUSIONS:
CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.
Journal Article > ReviewFull Text
Clin Microbiol Infect. 4 April 2011; Volume 17 (Issue 7); DOI:10.1111/j.1469-0691.2011.03536.x
Malvy D, Chappuis F
Clin Microbiol Infect. 4 April 2011; Volume 17 (Issue 7); DOI:10.1111/j.1469-0691.2011.03536.x
Human African trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease that flourishes in impoverished, rural parts of sub-Saharan Africa. It is caused by infection with the protozoan parasite Trypanosoma brucei and is transmitted by tsetse flies of the genus Glossina. The majority of cases are caused by T. b. gambiense, which gives rise to the chronic, anthroponotic endemic disease in Western and Central Africa. Infection with T. b. rhodesiense leads to the acute, zoonotic form of Eastern and Southern Africa. The parasites live and multiply extracellularly in the blood and tissue fluids of their human host. They have elaborated a variety of strategies for invading hosts, to escape the immune system and to take advantage of host growth factors. HAT is a challenging and deadly disease owing to its complex epidemiology and clinical presentation and, if left untreated, can result in high death rates. As one of the most neglected tropical diseases, HAT is characterized by the limited availability of safe and cost-effective control tools. No vaccine against HAT is available, and the toxicity of existing old and cumbersome drugs precludes the adoption of control strategies based on preventive chemotherapy. As a result, the keystones of interventions against sleeping sickness are active and passive case-finding for early detection of cases followed by treatment, vector control and animal reservoir management. New methods to diagnose and treat patients and to control transmission by the tsetse fly are needed to achieve the goal of global elimination of the disease.
Journal Article > ReviewFull Text
Clin Microbiol Infect. 1 May 2013; Volume 19 (Issue 5); 422-431.; DOI:10.1111/1469-0691.12154
Chappuis F, Alirol E, d'Acremont V, Bottieau E, Yansouni CP
Clin Microbiol Infect. 1 May 2013; Volume 19 (Issue 5); 422-431.; DOI:10.1111/1469-0691.12154
The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.