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[00:00:07] Emily: Hello and welcome back to Communicable, the podcast brought to you by CMI communications ESCMID's, open access journal, covering infectious diseases and clinical microbiology.

[00:00:16] Emily: I'm Emily McDonald. I'm a physician in general internal medicine and infectious disease, trialist and scientist at McGill University in Montreal, Canada, and associate editor at CMI Communications. The new WHO Meningitis guideline is featured on today's podcast, and we are excited to welcome three global leaders in the field.

[00:00:34] Emily: We'll be discussing how the WHO Meningitis guideline came about, what went into making the guideline behind the scenes, why it was needed, and some of the key take home messages for clinicians in both developed and developing countries who treat patients with meningitis. I'm delighted to be co-hosting this episode with Mark Bonton, fellow editor at CMI Comms.

[00:00:53] Marc: Hello and besides, editor at CMI Comms. I'm a clinical microbiologist and epidemiologist at the University Medical Center in Utrecht

[00:01:00] Marc: we're. Thrilled to have as our guest, Lorenzo Pezzoli and Nicolo Binello, both from the WHO Lorenzo Pezzoli is a field epidemiologist and the team lead for meningitis and epidemic bacterial diseases at the WHO Headquarters Lorenzo is passionate about public health and has spent the past two decades working in diverse settings on outbreak preparedness, vaccination strategies, and epidemic response.

[00:01:24] Marc: His experience encompasses a wide range of outbreak prone diseases, including meningitis, cholera, and other diseases affecting vulnerable populations. He currently leads WHO's efforts on defeating meningitis by 2030 roadmap, the W'S emergency program, supporting countries in strengthening preparedness, and response to bacterial meningitis outbreaks.

Nicolo Belo is a medical doctor and internal medicine specialist. He currently serves as a technical officer within the Epidemic bacterial diseases team at the WHO Headquarters, before moving to Geneva, we work as a clinician in resource limited and emergency settings.

[00:02:06] Emily: We're also joined today by Jacob, Bodilsen. Jacob, is a clinical associate professor medical doctor and researcher from

[00:02:12] Emily: the Alberg University in Denmark. His research focuses on CNS infections, and he's the chair of the ESCMID study group for infections of the brain.

[00:02:19] Jacob: Thanks for having me. Great to be here.

[00:02:21] Emily: As our regular listeners know, we always start the podcast with an icebreaker. Today's icebreaker what kind of activity do you regularly engage in for brain health? I'll go first.

[00:02:31] Emily: So I'm convinced that, fatty fish, like, the fatty belly of the tuna, salmon, mackerel, that all of these fishes make me smarter. so I regularly consume them. Hopefully not to the point. Where I get too much mercury to undo the smart fish fat. So that is me. Mark, you can go next.

Yes. I also have a, daily brain health activity, and that is my Sudoku in our national newspaper. It's kind of a well-known Sudoku. It seems not to be so easy. So I record my time and I can clearly see that during the weekdays it's easier than on the Saturday, but each time that I finish it, I think, well, not so bad.

[00:03:16] Marc: Still no dementia yet. So that's what I do from my brain health. So now Lorenzo, you're up next.

[00:03:23] Lorenzo: Thank you. Yeah. For me that's. A moving target. I would say if you would've asked me a few years ago, I would've said, photography,

[00:03:31] Lorenzo: but, anything that really takes you away from day-to-day distractions, especially these digital distractions I think is the key , I really appreciated going for walks with my family without taking the phone or even just reading paper books.

[00:03:47] Lorenzo: Actually, speaking of meningitis, I'm reading this book, by Andrea Lanfri, who is a meningitis survivor, who is the first Double Amputee who climbed Everest. And it's really an inspiring book.

[00:03:58] Marc: Thank you, Lorenzo. Ola,

[00:04:01] Nicolo': on my end.

[00:04:02] Nicolo': I'm a big, wildlife enthusiast, so, I unwind by watching animal documentaries or written books on nature. And as funny as it may sound, I find there's something, soothing about watching lions on the hunt or sharks, cruising for the next meal.

[00:04:18] Nicolo': The only catch is that while watching all of these animals and how the interact with humans, I try not to think too hard about species spill over because if I did, basically it would defeat the purpose of detaching from work and relaxing.

And Jacob.

[00:04:33] Jacob: I really like sports, so I play football or soccer every Tuesday night and I feel like I'm 15 years old again. Although it's somewhat humiliating, I'm not that good. And then Wednesday morning I feel like I'm 90 years old and then I slowly recover during the week and next Tuesday I'm off again.

So that's my moment of zen, I guess.

[00:04:53] Emily: Great activities, everyone with that settled? Let's get into the new WHO Meningitis guideline.

[00:04:59] Marc: Let's start with a little history about the guideline. For those of us who don't know Lorenzo , can you tell us what made the WHO want to craft a meningitis guideline and what did the process look like?

[00:05:10] Lorenzo: We work in the WHO Emergency Program, so I. from a, medical emergency point of view, I don't think there's any disease that is scarier than bacterial meningitis. it is a disease that can strike anyone anywhere in the world. the recent estimates say that it causes at least 1.6 million cases every year, including 240,000 deaths so one out of six patients die.

[00:05:36] Lorenzo: And, one in five survivors live with long-term disabilities. , It's a disease that, literally affects all countries in the world. And so all WHO regions, if we wanna speak in WHO terms, but, highest burden is in the area, , of Africa known as the meningitis belt.

[00:05:54] Lorenzo: This is an area of, Sub-Saharan Africa, that stretches between Senegal, to Ethiopia where, especially environmental climatic conditions. also, socioeconomic conditions, are, risk factors for the spread of bacterial meningitis. We're talking especially, the climate conditions that, cause, regular sandstorms,

[00:06:16] Lorenzo: , which.

[00:06:17] Lorenzo: Can damage upper airways and, facilitate the, spread of, bacteria meningitis. And in those areas, especially in, some core countries, we have been seeing, regular epidemics that, often coincide with, the dry season. a period that starts, roughly, from January, to until, may, June.

So we're at the, tail end of the meningitis season, and we see this very large scale, epidemics that, when they occur, they, have the capacity to disrupt, the healthcare system, it is with this goal in mind, especially to eliminate bacterial meningitis epidemics that, WHO in 2021 has, launched the defeating meningitis by 2030 roadmap. the goals are, three first one is eliminate bacterial meningitis epidemics, which, as I said regularly affect, the meningitis belt, but not only, reduce cases by 50% and death by 70% from vaccine preventable bacterial meningitis and reduce disability and improve quality of life after meningitis due to any cause.

[00:07:24] Lorenzo: so the roadmap really focuses on meningitis of any cause, but the core is really , the bacterial meningitis epidemics, but not only also more broadly any vaccine preventable bacterial meningitis. When we are talking outbreaks, we especially think of, three pathogens that, cause this epidemics, first and foremost, meningococcus.

[00:07:45] Lorenzo: So Neisseria meningitidis. This is really the main cause of epidemic meningitis. But then we have also streptococcus pneumonia, which causes, epidemics, streptococcus pneumonia, causes also, epidemic meningitis or to a lower extent. And, hemophilus influenza, especially hemophilus influenza type B.

[00:08:05] Lorenzo: Although this, last one is, not really. Luckily, a big focus of our work because thanks to an excellent, immunization program. We rarely see epidemics of, hemophilic influenza. One other vaccine preventable bacterial meningitis cause is, group B streptococcus. This is not an epidemic prone disease, but, it is, a pathogen that causes meningitis, especially in, uh, mother to child transmission in infants and pre-born.

[00:08:33] Lorenzo: also for this one, WHO is, in the final stages of launching, a vaccination program. So those are the vaccine preventable bacterial meningitis causes. and, it is part the roadmap , that, we have developed, this new guidelines, because the roadmap focuses on, five pillars.

[00:08:50] Lorenzo: the first one is prevention and epidemic control. the second is diagnosis and treatment. Then we have disease surveillance, support and care for people affected women, meningitis and, advocacy and engagement. So these five, very interconnected pillar. And as part of the, pillar on diagnosis and treatment, WHO and partners wanted to have a solid, guideline, to, support countries, in tackling, bacterial meningitis and starting of course with, the patients and how we diagnose the meningitis, how we treat it, which are the first things to do when it comes to epidemic meningitis.

[00:09:27] Marc: Thank you, Lorenzo. and Nicola, can you tell us something about what went into the development of the guideline?

[00:09:31] Marc: Who was involved, what type of specialist? How long to finalize the guideline?

[00:09:36] Nicolo': So these are the very first, comprehensive WHO clinical guidelines, on meningitis. They were finally published two months ago, after nearly three years in development.

[00:09:46] Nicolo': So it's a long time coming. The guidelines, include 37 recommendations as well as, hundreds of clinical remarks and implementation considerations.

But before we dive in, I think it's important to, clarify the scope of the document.

[00:09:58] Nicolo': So, these guidelines [00:10:00] address acute onset community acquired meningitis in adults, adolescents, and children over one month of age. So they do not cover meningitis in neonates. They do not cover hospital acquired meningitis. They do not address subacute or chronic forms of meningitis, nor do they address, non-infectious forms of meningitis.

in the context of acute onset of meningitis, they do. Provide recommendations for both bacterial and viral meningitis. In terms of target audience, the guidelines are intended for global use, including in resource limited and emergency settings. They're primarily aimed at healthcare professionals and frontline, clinicians, but they're also relevant for policy makers, national public health authorities, international organizations, and academic institutions.

The document is structured around three main chapters, diagnosis covering lab investigations, and cranial imaging, treatment: Antibiotic therapy, adjunctive treatment and supportive care. And finally, management of sequalae addressing long-term physical, neurological, and psychological complications of meningitis.

Now to the question of why this took so long, the timeline is largely due to the, rigorous nature of the WHO Guide development process, which is a methodological approach involving several stages of development and a wide range of contributors, both internal and external to WHO. the process began with the establishment of a WHO steering group, which including technical experts from across headquarters and regional offices, which coordinated the entire process and determined the composition of the guideline development group, which is a multidisciplinary team of experts.

[00:11:28] Nicolo': including clinicians, infectious disease, internal medicine, neurologist, specialists, but also researchers, policy experts, and individuals with lived experience from all over the world. 20 guideline questions were proposed by WHO, validated by the Guideline Development Group, and they subsequently informed the systematic review process so.

[00:11:45] Nicolo': These reviews, 20 quantitative and one qualitative reviews, were conducted by five academic institutions over the following month. As you can see, this is a massive, undertaking and once all the evidence was retrieved and synthesized, the GDG was reconvened by WHO and presented with the evidence.

[00:12:03] Nicolo': Using the grade approach, the group of experts then formulated the recommendations and good practice statements, which form the core, of the document. After that, the draft was circulated to an external review group, an additional body of experts serving as peer reviewers, and to the guideline review committee, which is the WHO's internal body that ensures that the guidelines are aligned with established procedures and meet the highest standards.

[00:12:26] Nicolo': Only after passing all of these steps was the document ready for publication. So, yes, it was a lengthy process, but, necessary one given the breadth of the topic and the potential, impact hopefully, of these guidelines.

[00:12:38] Emily: Thanks Nicolo, and thanks Lorenzo. It's really interesting to hear, how the guideline was put together and everyone who was involved.

[00:12:45] Emily: Given this is a guideline to help clinicians, fundamentally better diagnose and treat meningitis, we're really pleased that, Jacob, is able to join us today to give us a clinical perspective and also a research perspective. Jacob, can you tell us some of the challenges that you faced personally in the diagnosis and treatment of meningitis?

[00:13:05] Jacob: Sure. like Nicolo and Lorenzo nicely alluded to this is a really rare but challenging infection, it has bacteria surrounding your brain, which It makes you uneasy as a doctor, right? First of all, we know that we have to be really attentive towards getting the diagnostic and treatment algorithm right for managing the patients, you don't want to overlook this diagnosis and you don't want to be the boy who cried wolf all the time either.

[00:13:30] Jacob: so you have to get that kind of balance right when to suspect this

[00:13:33] Jacob: so I think working as a clinician and having conversations with colleagues and younger colleagues, especially, I think the old saying, if, you thought meningitis, you should almost always exclude it. Right? I think that still holds true.

[00:13:47] Emily: Classic. Yep. Yep.

[00:13:49] Jacob: So I think as a clinician you get a very focused initial history if it's possible what's been going on just prior to hospitalization.

[00:13:57] Jacob: Check for the classic signs like fever, neck, stiffness, also mental status. If there are petechiae you check every inch of the skin, the nail beds, the conjunctiva, the oral mucosa to see if there are any petechiae, and then you decide really fast, do I need to go, on with a lumbar puncture or can it be clearly ruled out?

[00:14:15] Jacob: And then it differs a little bit from setting to setting. There are different contra indications to doing LPs with, or without having brain imaging. First, do we get all the right microbiological specimens for diagnostics? Do we start antibiotics immediately and dexamethasone, or is the suspicion very low and the patient is clinically stable?

[00:14:33] Jacob: You want to see what's going on with the diagnostics. What are the initial results? what about monitoring afterwards, searching for additional foci of infection. An important aspect is talking to family explaining, what's going on and what is the foreseeable future.

[00:14:47] Jacob: but also, leaving some hope for them because there is good grounds for having hope , so those are some of the issues that are pressing during initial management, I think.

[00:14:56] Emily: Absolutely. It's such a challenging, diagnosis to make. the test to diagnose it can be quite frightening, both for the patient and for healthcare workers to perform. I think this really provides important perspective, for the clinical need for this guideline.

[00:15:14] Emily: I work in a tertiary care academic hospital, and so cases of meningitis are, pretty rare. I have resources like interventional radiology who could perform a lumbar puncture if it's challenging or have neurology on call. where I work, lumbar punctures can be performed quickly and safely.

[00:15:31] Emily: When CNS imaging is needed, we obtain it rapidly. We've got access to a broad range of antibiotics and resistance is relatively rare. And you know, this is certainly not the case. The world over. for a number of years I would travel and work in Haiti, and it was an entirely different story. you know, at that time we had cases of, suspected cryptococcus among young people with newly diagnosed or untreated HIV.

[00:15:58] Emily: And to get a CT scan, the patient would've had to travel, by car. For over an hour. And, the CT scan didn't always work. we were often troubled by whether it was safe to perform a lumbar puncture in the absence of readily available diagnostics. We frequently had to initiate therapy without a firm diagnosis, which isn't great for stewardship.

And it was really one of the most challenging diagnosis that we had to make and manage, at a. Nicolo, can you tell us what, some of the key recommendations are with respect to the diagnosis of meningitis that are presented in the WHO guideline?

[00:16:40] Nicolo': Probably should start off by saying that the guidelines do indicate in individuals with suspected acute meningitis, lumbar puncture should be performed as soon as possible, preferably before starting antibiotics, unless there are specific contraindications or reasons for deferral, and I'm gonna get to those reasons in a moment. But once CSF is collected, lumbar puncture is performed.

[00:17:00] Nicolo': Microscopic appearance of the CSF should be inspected, and a number of initial tests are all strongly recommended by the guidelines, including glucose and total protein concentration, white blood cell count, and gram staining. All of these investigations have been shown to have varying sensitivity and specificity.

[00:17:16] Nicolo': We already knew that actually, but none can, confirm or rule out a diagnosis of meningitis when taken alone. So we did emphasize in the guidelines that an integrated approach to interpreting these CSF findings is indeed essential to reduce the risks associated with relying on individual tests for false positives, false negatives.

[00:17:35] Nicolo': The guidelines also indicated in resource limited settings. These initial CSF investigations should be widely accessible, including in peripheral health facilities and where this is not possible, CSF samples should be collected and properly transported, to higher level labs, as in the need for sample referral should not be used to defer CSF collection and lumbar puncture in the first place.

The guidelines also highlighted That CSF culture remains the gold standard for diagnosing bacterial meningitis and should always be associated with antibiotic susceptibility testing to identify resistance profiles and tailor antibiotic therapy. CSF molecular testing is also strongly recommended for all suspected cases.

[00:18:14] Nicolo': However, because of the risk of false positives, PCR results, should always be interpreted in the broader context of the clinical presentation, as Jacob mentioned, and other, laboratory findings. Importantly, PCR is not meant to replace culture and antimicrobial sustainability testing, but it needs to be performed in addition to them. Culture remains the gold standard for diagnosis.

Now, we all know very well that lumbar puncture can be performed safely in most cases, That said, there are certain conditions that increase the risk of complications. The guidelines have identified certain absolute contraindications to the procedure, which include a skin or soft tissue infection close to the lumbar puncture site, hemodynamic or respiratory instability and bleeding disorders Also.

lumbar puncture can increase the risk of brain herniation in selected patients with increased intercranial pressure, such as those with severe diffuse brain swelling or space occupying lesions causing midline shift. To minimize the risk and the incidence of brain herniation, it's important to identify those patients where lumbar puncture should be deferred.

these are the so-called relative contraindications to the procedure. Identified based on very limited evidence, only one prospective study and the. knowledge and expertise. And these include, patients with a coma or a Glasgow coma scale, less than 10 focal neurological signs, cranial, nerve deficits, pap edema, neuro onset seizures as far as adults are concerned, and patients with a severe immunocompromised state.

this is exactly where cranial imaging comes in , the guidelines make it very clear that cranial imaging should not be performed routinely in all suspected cases of acute meningitis. But at the same time, in settings where it is available and readily accessible, it should be performed and conducted prior to lumbar puncture.

How about [00:20:00] those settings where a cranial imaging is not available or readily accessible, which is often the case in resource limited environments? in these cases, the groups strongly recommended the clinicians.

[00:20:09] Nicolo': Deferral lumbar puncture until the reasons for deferral have fully resolved. if the reason for deferral cannot be resolved, then lumbar puncture should not be performed. The only exception is in people with advanced HIV disease and cryptococcal meningitis is suspected. In that case, lumbar puncture should still be performed Finally, blood testing. I think this is really important because we often forget that the bacterial pathogens that are most commonly associated with meningitis are often responsible for bacteremia and or sepsis. Therefore, the guidelines recommend obtaining blood cultures in all suspected cases of acute meningitis as soon as possible, preferably again before starting antibiotics.

[00:20:47] Nicolo': And similarly to CSF, blood culture and antibiotic susceptibility testing should, then be used to tailor antibiotic therapy based on the isolated pathogen and its resistance profiles. the guidelines also try to address, the differential diagnosis with cerebral malaria in malaria endemic areas.

In these areas, a parasitology test should always be performed for any suspected case of cerebral malaria slash acute meningitis, either microscopy or an RDTA positive malaria test confirms malaria infection and requires anti malaria treatment, but does not rule out the possibility of concurrent meningitis, especially in areas of stable transmission of malaria, where malaria may be asymptomatic or present with non-severe manifestations, including, especially in older children and adults.

any delay in diagnostic investigations including lumbar puncture deferral, cranial imaging should not delay treatment initiation. that was made very clear in the guidelines. And even though the diagnostic yield domain of these CSF and blood tests is reduced after the initiation of antibiotics, they should still be performed.

[00:21:50] Nicolo': and again. A diagnostic test, including lumbar puncture, should be performed unless there are specific contraindications.

[00:21:57] Marc: Now nicolo, do we have any quantitative analysis of how frequently there truly is a contraindication for lumbar puncture?

My experiences, although some time ago that once the CT scanning availability came in, that the standard of doing lumbar puncture changed in standard of not doing a lumbar puncture until after the CT scanning. And, I don't have, any quantitative evidence, but in my impression that has led to a delay in diagnosis.

So even though the guideline strictly defines the contra indicators, They may be taken liberal in daily practice leading to, a delay in diagnostic procedures. Is there any quantitative data on how frequently this happens and how frequently that is inappropriate?

This is a very interesting topic. I think that for the purposes of the guideline development, this was not, reviewed systematically. it was not part of the 20, guideline questions but I am aware of a couple of studies at least that, do investigate prospectively, how frequently lumbar puncture are deferred in favor of cranial imaging and whether or not they meet, clinical guidelines.

best of my knowledge, these studies have been performed in Europe and, even though we cannot necessarily generalize the findings from European countries to the rest of the world, cranial imaging is, often performed prior to lumbar puncture, despite the fact there may not be absolute or relative contraindications, to lumbar puncture.

[00:23:21] Nicolo': What the guidelines say, again, , is that it should not be performed routinely only in selected cases. as part of the next, steps of the guideline development process, which includes developing clinical tools and, job aids that clinicians can refer to, we'll try to make it, it as accurate as possible.

[00:23:37] Nicolo': Try to emphasize the role of lumbar puncture and limit the role of cranial imaging in selected settings.

[00:23:42] Marc: Thank you. Okay.

[00:23:43] Marc: That's very clear. Second question was for Jacob. as he was involved in a recently published study in which the role of CRP, not PCR, but CRP measurement in cerebrospinal fluid was evaluated. I looked at the guideline. It was not included in the guideline because there's probably not that many studies that looked at it before, but maybe Jacob could comment on that aspect for the diagnosis.

[00:24:05] Jacob: Well, thanks. I must pay tribute to Matthijs Brouwer and Sabine Olie, who really did, most of the work in that. We just provided some control samples, I think it was ingenious, because it was just so simple. they looked for all these biomarkers, very advanced biomarkers, and the one that paid out was the very old and well-known, CRP and just measured in the CSF, and it had some incremental value.

[00:24:26] Jacob: On top of CSF leukocytes because it should always be when we do these diagnostic accuracy studies, it should be, is there any incremental value, diagnostic value that is clinically relevant if we increase the AUC by one or 2% or, percentage points? it's unlikely to pay out much in clinical, practice.

but here, there seems to be some added, benefit. I think especially for that more troublesome group with a CSF leukocyte count of around a hundred to a thousand, which are the ones where we may be in doubt sometimes. Is this bacteria, meningitis or some other condition?

[00:24:58] Emily: And, sorry, I'm not familiar with this study.

[00:25:00] Emily: Was it that an elevated CRP was more specific for meningitis or when the CRP was low, it helped to rule out

[00:25:07] Jacob: both sensitive and specific. it was very close to a hundred on, both parameters. could I maybe circle back a little bit to the contraindications, to lumbar puncture, I really appreciate the WHO guideline having this global perspective, because, I mean, , all countries have their own guidelines and versions of this, and I think it's mostly because the association between each of these proxies for a mass lesion with brain shift or severe generalized edema are just proxies.

[00:25:36] Jacob: And they're, really not well established in terms of predicting subsequent risks of herniation. And I think this is really important to talk about the lack of robust data to support this. It's mostly based on case reports and case series expert opinion and, clinical reasoning. but at times it may lead to some unnecessary delays in treatment and it's been shown countries that have the most, contraindications to doing, LP just straight away are the ones that have the longest time to LP and sometimes also antibiotics. . At least in Europe, when you think about bacterial meningitis in these patients, we only write in about one out 13 to one out 17. And the other mimics they require the same kind of timely diagnosis and treatment as bacteria meningitis does.

But I did wonder about, allowing clinicians to proceed with the lumbar puncture eventually if brain imaging is not available .

Yes, obviously this is a very complicated topic to address through a guideline. both because of the limited evidence available and, because, providing global guidance that is applicable to all settings is extremely complicated.

what we try to do is outline a set of criteria that clinicians can use, but we also established the one very important exception, in that people with advanced HIV disease, where crypto meningitis, for example, is, suspected or sometimes even the most likely diagnosis.

In those cases, lumbar puncture should still be performed. And that's a recommendation applicable, where the prevalence of advanced HIV disease is particularly high. also, the remark on coma or gla coma scale less than 10, that one should be interpreted in the broader context, as in when bacterial meningitis is suspected.

if a patient. has Glasgow Co scale and fever in a malaria endemic area the most likely diagnosis is malaria. for example, coma may, resolve after, a couple of days of IV or testate. And in that case, navigating those clinical challenges, by deferring lumbar puncture, establishing a diagnosis of malaria, and then take it from there as to the next steps, might also be something that is feasible in a lower source setting.

again, going back to the main point, yes, we provided a list to facilitate. the clinical work, on the frontline, but there are exceptions. and, it will obviously be up to the clinician treating the patient to make those decisions. by the way, one of the reasons why we listed, these criteria is because sometimes in the field, in resource limited settings, clinicians treating patients with meningitis do not have specialized skills.

[00:28:09] Nicolo': They're not infectious disease, specialists. they may be just general practitioners, may not have, been exposed to a lot of meningitis patients so far, or the, adequate skills. So by doing this, we hope to provide some kind of reference that they can go to, as needed.

[00:28:25] Emily: Yeah, I think we, completely appreciate that. One thing that, some listeners might be thinking is, you know. you can do the lumbar puncture if you suspect crypto cocal meningitis. That would be an exception. If you're not able to get CNS imaging. Maybe we could, mention now that some places that have access to cryptococcal antigen in the serum, that could be quite helpful.

[00:28:47] Emily: 'cause that's fairly sensitive and, specific because for those who were wondering, well, how do I know if they have cryptococcal meningitis if I can't do the lumbar puncture? this is one of the cases where the serum testing

[00:28:58] Emily: could be quite helpful and, is, fairly accessible.

[00:29:01] Emily: I'd love to move on to treatment now. unless there's any other thoughts about diagnostics, anything that we missed that you wanna cover?

[00:29:10] Jacob: I was wondering about the advice against doing a lumbar puncture for diagnosis of bacterial meningitis in patients with suspected bleeding disorder. But lumbar puncture in patients with coagulopathy does carry a theoretical risk of spinal hematoma. That may, in a worst case scenario, lead to inferior paraparesis.

[00:29:29] Jacob: However, observational studies suggest that this risk is very low, likely below 0.2% or so. Could you please comment on what you mean about bleeding disorder and how it should be managed in this context?

[00:29:40] Nicolo': sure. Sure. That's another very interesting topic. So, by way of background, the absolute contraindications for lumbar puncture procedure were not, provided after a systematic review of the evidence. but they were based upon, clinical and expert opinion.

They're not part of the recommendations, of the guideline. That said, the reason [00:30:00] why, it's not specified, it's on purpose. this is one of the scenarios where we leave it up to the clinician sometimes. while this may not be an absent contraindication, in highend income settings, A completely different scenario can be seen in low resource settings where, patients with bacterial meningitis often access healthcare facilities at a very late stage. , They may already have, signs and symptoms of septic shock or, disseminated intravascular coagulation, without the possibility of.

[00:30:29] Nicolo': being properly managing that context, where again, frontline clinicians may not even, be properly trained to perform lumbar puncture. Again, we did not want to specify a list of bleeding disorders, to give some flexibility, to the treating clinician to make their own decisions, at the point of care.

[00:30:48] Nicolo': but again, as soon as. evidence will be gathered on this topic, more than currently available. We'll be happy to revisit, this list, which was developed with a global perspective, trying to take into consideration differently resource settings and how can lumbar puncture fit in these different settings.

[00:31:06] Emily: Yeah, it is why it's so interesting for us to talk about a guideline made by the WHO that does have a global perspective. We're very used to country level or region specific guidelines, and, considering how technically proficient the person is, who's performing the lumbar puncture, and, whether they have the right equipment, smaller needle versus a larger needle, is entirely relevant.

[00:31:32] Emily: Let's move on to treatment. I think we should divide it up into treatment and adjunctive therapy. So let's start off with regular treatment. Are there some main, updates to this guideline? new things that clinicians should be aware of?

[00:31:46] Nicolo': We have tried to provide some guidance. As to where meningitis patients should be managed, considering that bacterial meningitis is a medical emergency that requires prompt diagnosis. referral comes with several logistical challenges in resource limited settings. So, the guidelines indicate that all suspected cases should be immediately admitted or urgently transferred to an appropriate healthcare facility. defined as, a healthcare facility where lumbar puncture can be performed in the absence of contraindications and adequate monitoring and management of severe illness can be ensured. So this is the first, broad management recommendation that, we have. Sometimes we do have queries from countries as to where meningitis patients should be admitted. , The answer is it depends. It on the capacity of that facility to manage that patient. Regarding antibiotics, again, considering meningitis and medical emergency, obviously IV and empiric antibiotic, therapy is recommended.

when should antibiotics start? Simple answer is as early as possible, ideally within one hour of admission. And as mentioned earlier, delays in diagnostic tests should never delay the start of treatment. the approach is very straightforward so far. But what about those patients admitted to healthcare facilities that are not equipped for lumbar puncture, performance, or adequate management of severe illness?

[00:33:03] Nicolo': And this may be likely the case of a rural health center in a low income country, for example. And during the epidemic season in the meningitis belt, a substantial proportion of these patients, are seen. In this type of facilities, these patients should be referred to an appropriate healthcare facility as soon as possible, and especially when a clinically significant delay in transfer is expected.

[00:33:25] Nicolo': Pre-referral antibiotics should be considered. This is a conditional recommendation based on very low certainty of evidence. However, this is a huge change compared to previous practice. It's very similar to what's being used for severe malaria and was specifically designed to address operational challenges, feasibility concerns in resource limited settings.

[00:33:46] Nicolo': Where referral systems may be suboptimal and a clinically significant delay in transfer may be expected by default. So in other words, empiric, parenteral treatment is given before transfer, as it may be beneficial, as long as acute bacterial meningitis is strongly suspected on epidemiological and clinical grounds in these situations, both IV and when an IV line cannot be secured.

[00:34:11] Nicolo': IM administration. Of antibiotics are acceptable. when it comes to antibiotic regimens, obviously IV suboxone or cefotaxime should form the backbone treatment. If there are risk factors for listeria age over 60 pregnancy immunocompromised state, then IV ampicillin or amoxicillin should be added to the initial regimen.

[00:34:29] Nicolo': And in areas with a high prevalence of strep pneumo, resistant to penicillin or third generation cephalosporin, IV vancomycin should also be considered as part of the initial treatment. Finally, this guidelines strongly highlighted. Antibiotic regimens should always be reviewed and adjusted based on culture, based on antibiotic susceptibility, testing results.

[00:34:50] Nicolo': And the goal here is to minimize the inappropriate use of broad spectrum antibiotics and the emergence of drug resistance strains. In terms of how long to treat, duration, depends partly on the specific pathogen, and the document provides some guidance in that regard. , but What happens when the pathogen is not identified and remains unknown?

this may be the case in resource limited environments, and we wanted to address this through, a, recommendation in non epidemic settings. Stopping empiric antibiotics may be considered after seven days, provided the person has fully recovered and has been stable for at least 48 hours. Final bit on outbreaks.

[00:35:25] Nicolo': How does treatment differ from non epidemic settings? Well, during meningococcal and pneumococcal disease epidemics, IV axone should be preferred over cefotaxime Mainly because it's more widely available and has a longer half-life allows for 12 hourly administration in meningococcal disease epidemics, suspected and probable case of meningitis should receive such action for five days In pneumococcal disease epidemics, recommended duration is longer, 10 days.

[00:35:54] Nicolo': The guidelines, address potential operational challenges that may occur during outbreaks. For example, in the context of large scale meningococcal disease epidemics, , when a full five day regimen is not practical at all and health services are stretched, the capacity, , single dose treatment protocols may still be used.

[00:36:11] Nicolo': But this should only happen when there's lab confirmation that the outbreak is actually caused by Neisseria meningitidis, and the person can be reviewed after 24 and 48 hours, which might be problematic in some settings. So this is, a summary of all the recommendations regarding antibiotics.

[00:36:27] Marc: Yes. But also it, it's extremely challenging , in, western hospitals, you have everything available, but what, if not, and if a patient needs to go and transfer for a lumbar. puncture, you give the antibiotics, you can take a blood culture, but it'll reduce your diagnostic yield.

[00:36:44] Marc: So the likelihood of identifying the correct pathogen and having the correct epidemiological information for your other measures reduces if you, increase your therapeutic strategy by having antibiotics in, or the corticosteroids.

[00:37:00] Marc: How do you say to all physicians in the lower middle income countries. Get these antibiotics in first and then start thinking about sending a patient for a, lumbar puncture, or send your patient for lumbar puncture first and wait with your antibiotics.

[00:37:15] Nicolo': Well, I think that's a very complicated, question to answer but this is exactly what we have been trying to do very recently in Ghana this year and, in Nigeria last year where, during the course of, two different bacterial meningitis epidemics, one pneumococcal disease outbreak, and one in Chicago disease outbreak.

[00:37:34] Nicolo': But basically we traveled across all these very rural primary healthcare facilities, where you have, very limited, capacity to perform lumbar puncture and, referral or transfer to a first or second level hospital is likely to take. hours, if not days. in these cases, we develop job aids pasted onto the walls of various healthcare facilities.

[00:37:57] Nicolo': If the patient meets certain criteria, sort of a case definition, then, consider giving one shot of, Ceftriaxone and send the patient for further management. we, we, are, we aware that this practice has tremendous implications in terms of AMR and this is something that, we're always very cognizant of, but the alternative for the individual management of this patient might be worse. This approach, is very well known to frontline healthcare workers in lower resource settings because they do exactly the same for malaria. You see a, suspected or confirmed case of severe malaria, you give our testate and then you send the patient to a hospital or a high level healthcare facility.

[00:38:35] Nicolo': Then same approach should be followed for meningitis. whereby if the delay in transporting referral is expected to be substantial, then in that case you give antibiotics and you send the patient for lumbar puncture. once referred to a an appropriate facility, physicians should still try their best to perform all sorts of CSF and blood investigations based on available resources, despite the diagnostic yield is reduced.

[00:39:01] Nicolo': this is a, another very common. situation in resource-limited settings where patients may have received oral antibiotics before being seen, in a healthcare facility. I think that developing very simplified, clinical algorithms for managing these patients in peripheral health facilities is the way to go.

We set the example in, the meningitis belt, but it is also, hopefully applicable in other resource limited settings and even in humanitarian emergencies, by the way.

[00:39:29] Marc: yeah. And you mentioned the rule of AMR and the consequences of using Ceftriaxone.

That's always the moment that I want to quote Bruce Levin, who said, well, antibiotics do more than causing resistance. So should the fear of AMR be a consideration in the acute phase of this disease? I don't think so.

[00:39:49] Emily (2): it's an interesting question mark. one other thing to consider is the reduced accuracy of the diagnosis isn't necessarily the same for molecular testing as it [00:40:00] is for bacterial culture. so it is possible for the molecular tests to stay positive longer, than the bacterial culture after the receipt of antibiotics.

[00:40:10] Emily (2): And so maybe as more people have access to molecular testing will become less afraid, we can give antibiotics because we know we could still make the diagnosis.

[00:40:19] Marc: Yes. And the c reactive protein will still be increased.

[00:40:23] Nicolo': and if I can add, that we don't want to encourage at all is to use antibiotics for those patients that present with non-severe clinical manifestations.

[00:40:33] Nicolo': And, they may be considered suspected case of meningitis while in fact they're not. And this is another very common challenging across the meningitis belt, where antibiotics are often used for patients and many of these patients are just uncomplicated malaria patients, or, they might just have a viral self-limiting, infection. So that's why I mentioned providing criteria because even though you cannot encapsulate all the differences and all the nuances of meningitis by developing a list of criteria, at least, that provides a reference for clinicians, when it comes to deciding whether or not.

[00:41:06] Nicolo': A third generation cephalosporin should be given.

[00:41:08] Emily: I guess that also brings us to, the fact that it's, not just antibiotics that we're giving people, before we've made the diagnosis. we're also now sometimes giving adjunctive therapies like dexamethasone. So I was wondering if you could speak a little bit about that.

[00:41:22] Nicolo': in selected settings, adjuvant steroids can be given to individuals with acute bacterial meningitis in addition to antibiotics. dexamethasone is the corticosteroid of choice. it might not be available in some resource limited environments.

in that case, hydrocortisone or methylprednisolone can be used instead at equivalent. Doses. So far, several guidelines have recommended steroids only in high income countries or in high income settings, leaving a gap for low and middle income countries, which these guidelines have tried to address through a systematic review that including 26 randomized control trials performed in high resource and low resource settings.

In non epidemic settings when lumbar puncture can be performed, IV steroids should be started alongside the first dose of antibiotics. In all suspected cases, this is a strong recommendation from the But if CSF results are not consistent with bacterial meningitis, then steroids should be discontinued. When lumbar puncture cannot be done for whatever reason, either because it's contraindicated or because it's not possible to perform lumbar puncture, corticosteroids may still be given with the first antibiotic dose provided that bacterial meningitis is strongly suspected and there are no contraindications to the reuse, and this is a conditional recommendation.

[00:42:37] Nicolo': In malaria endemic areas, one. Strong contraindication to the use of steroids is confirmed cases of cerebral malaria. So in those patients with a confirmed diagnosis of cerebral malaria, then steroids should not be used.

I want to emphasize that these recommendations apply to both high income and low-middle income, countries, primarily based on the fact that there was no evidence in our systematic review of a difference in mortality between high income countries and low middle income, countries. There was some differences in terms of neurological complications.

but in terms of mortality, there was no evidence in the subgroup analysis. During outbreaks the situation changes during meningococcal disease epidemics, which are the most common. IV steroids should not be routinely used in suspected or probable cases of meningococcal meningitis.

[00:43:22] Nicolo': Primarily due to the lack of evidence suggesting a beneficial effect of steroids in individuals with confirmed meningococcal meningitis in terms of mortality and neurological complications. By contrast, during pneumococcal disease epidemics, steroids should be started with the first dose of antibiotics in all suspected and probable cases of pneumococcal meningitis.

you can see that, the recommendation on steroids changes based on epidemiological considerations. there are also recommendations on, fluid management therapy, treatment of seizures and management of sequela, maybe I just provide a very brief summary.

fluid management, the guidelines provide a conditional recommendation against fluid restriction. So for maintenance fluids, prefer route is oral or through an enteric tube. if this is not possible, then isotonic IV solutions should be routinely used for maintenance purposes. Meaning ringers, lactate, or normal saline.

we wanted to make this very clear because of the widespread use of hypotonic or glucose based solutions in lower resource settings, which are, not indicated unless hypoglycemia is a concurrent concern. Increased intracranial pressure, is a well-known, life-threatening complication of meningitis and the true medical emergency, which may require osmotic therapy.

[00:44:33] Nicolo': it's important to note that the glycerol, should not be used routinely as adjunctive therapy. In patients with bacterial meningitis, the guidelines indicate that mannitol or sometimes hypertonic saline may be used as a temporary measure to lower intracranial pressure alongside all the other treatments regarding seizures in someone with meningitis..

Decision to start anti-seizure medication Depends on a variety of clinical considerations. the person's overall clinical stability and the risk of having another seizure. What the guidelines say in this regard is that, the length of antiseizure medication, Should not be prolonged for more than three months, as long as no further seizures occur during that period of time. finally, there are several recommendations on, sequalae, which set the standards for the first time, for the management of long-term complications.

And they're very obvious in a way. but important to have in mind when developing. Control plans of meningitis. individual with acute meningitis from any cause, should be reviewed for sequela by a healthcare provider prior to discharge and at follow up within four weeks.

[00:45:36] Nicolo': Same goes for audiological screening before discharge or after four weeks. Second, in those where one or more these complications are diagnosed, rehabilitation services should be provided as early as possible. And this includes hearing rehabilitation as needed. these are very obvious clinical considerations, but having them framed as recommendations, hopefully will engage countries in providing those services, as part of the package, to manage, patients with meningitis, including in resource limited, settings,

[00:46:06] Emily: Thank you. it's a lot to consider it is helpful to put it down in writing as recommendations because that can help, hospitals set quality metrics, set some targets to attain. It must have been very humbling, writing these guidelines, especially, we see exactly where there is and also where there isn't evidence, to support our practice.

[00:46:28] Emily: I was wondering if you could speak a little bit about, was missing in terms of the level of evidence and, and maybe particularly as it pertains to Chemoprophylaxis, is that was a, a newer recommendation in the guideline.

[00:46:40] Nicolo': So I think that strong and conditional recommendations in this guideline, as any other guideline from WHO are based on variable levels of evidence, right?

[00:46:51] Nicolo': So under the grade approach, that, , that informs the guideline development process at WHO evidence certainty is, rated as high, moderate, low, or very low. Randomized control trials start off as high certainty observational studies and non-randomized trials begin as low From there, ratings can be further downgraded for factors like indirectness in precision inconsistency, publication bias and study limitations. So it's very difficult to actually have high certainty evidence for these recommendations. However, recommendations are formulated by taking into consideration other key domains such as resource requirements, cost effectiveness, equity, visibility, acceptability, all of these domains are incorporated , into this decision making. even in the presence of very low certainty evidence, the Guideline Development Group decided on issuing strong recommendations.

this is the case for chemoprophylaxis. Chemoprophylaxis for a close contacts of cases of meningococcal disease with or without meningitis, is well known, the guidelines recommend. That the choice of the first line antibiotic, either single dose, ceftriaxone, or single dose ciprofloxacin, be based on locally known resistance patterns and adjusted as needed.

[00:48:03] Nicolo': Especially if the index case, shows resistance on susceptibility testing. this is a crucial part of the recommendation as we're seeing increasing reports of, Ciprofloxacin resistant strains in several parts of the world. in the presence of sporadic disease, antibiotic prophylaxis is strongly recommended for close contact of laboratory confirmed cases, and during large scale epidemics of meningococcal disease where lab confirmation can be resource intensive and suboptimal.

It is still strongly recommended to close contact this time of clinically suspected cases. And this marks a substantial shift from previous WHO recommendations, which advised against chemoprophylaxis during outbreaks in the meningitis belt. what changed here? . The main supporting evidence came from a cluster randomized controlled trial conducted in rural Niger during a meningococcal disease outbreak.

[00:48:52] Nicolo': The trial showed that the effect of household level prophylaxis with single dose  ciprofloxin on preventing secondary cases was uncertain. But when cipro was administered village wide, a protective effect was observed. And in addition to all of this individual level protective effectiveness of 82% was demonstrated when comparing all people who received ciprofloxin in both household and village wide arms to those who did not.

[00:49:20] Nicolo': but this was the only study and the group definitely did not want to formulate a recommendation for village wide prophylaxis, for global use. So. The evidence was rated as very low. but despite this, the Guideline development group still agreed to make a strong recommendation that applies across both outbreak and non-outbreak settings within and outside of Meningitis Belt.

[00:49:40] Nicolo': Not just based on data, but also by taking into consideration, feasibility and equity concerns, especially in low settings. during meningococcal disease outbreak, the primary control measure is a reactive vaccination campaign, but we all know that these campaigns can take several weeks to roll out, and that's why the guidelines highlight the need for additional control measures such [00:50:00] as Chemoprophylaxis to help bridge that gap.

Can I just comment on that? And I have a question. comes the AMR guy again. So there was, over concern of antimicrobial resistance with the treatment of individual patients with a very strong recommendation that you can prevent mortality or sequela at the cost of a lower diagnostic yield.

[00:50:20] Marc: But here the recommendation is to give ciprofloxacin to whole communities based on low evidence, based on feasibility and equity. and ciprofloxacin for a population definitely has consequences for AMR. So how is this, AMR aspect, incorporated in this recommendation.

this was the most important concern that was raised while formulating the recommendations The middle ground that we found is to recommend chemoprophylaxis across settings. , To close contacts, not to, entire communities. one may say that close contact in a rural village in Niger is indeed an entire community.

[00:50:59] Nicolo': but the definition of close contacts remains up to the country or to the local health authorities because there is no way that we can provide a, one for all definition of close contacts. That being said, the guidelines try to address AMR concerns, saying that the antibiotic should be based on whatever is known in terms of antibiotic resistance in that area, either in the community or at the individual level. In the index case, if that is not known, which is often the case in some resource limited settings, the guidelines are not too explicit because, other considerations may be taken into account.

[00:51:38] Nicolo': We do our best to provide a recommendation that, allows for implementation of chemoprophylaxis, to control infection, transmission across settings. But, without necessarily promoting the indiscriminate use of ciprofloxacin or ceftriaxone so basing public health decisions, on known antibiotic resistance data is key here.

[00:52:01] Nicolo': And if they're not available, WHO encourages and strongly recommends generating that evidence in order to inform better public health response and mitigate the risk of antimicrobial resistance. If, new evidence is generated regarding, ciprofloxacin resistance among the Neisseria meningitidis strains And they probably will, WHO I think is able to reconsider these recommendations moving forward.

And it's not the worry for the susceptibility of the Neisseria meningitidis for ciprofloxacin, it's more the whole gram-negative flora of the population being exposed to ciprofloxacin, what that will do for treatment of, subsequent UTIs and urosepsis.

[00:52:40] Marc: And this is, of course, a very, very difficult thing. it really, marks out the research agenda to answer that question.

[00:52:49] Nicolo': Absolutely. And if yes, AMR is really a horizontal topic, and when you have a vertical guideline, it becomes really difficult to use other, considerations coming from other diseases, other infections, or even, addressing the problem with, microbiota while formulating recommendations.

[00:53:06] Nicolo': so I think in this regard, all guidelines, are not very fit for that. but we tried our best to, address this, while emphasizing the importance of generating evidence on antimicrobial resistance within the community.

[00:53:21] Emily: . I think what you mentioned, Nikola about how the WHO is, open to new evidence on the topic is so important because sometimes when you try to prove that there is equipoise, it can be hard if there's a guideline that strongly recommends something. So I think the fact that, you've come out and very clearly stated that we made the strong recommendation, but it was based on a low level of evidence and we are open to new evidence and we could reverse this decision with new evidence is, really, really important.

[00:53:48] Emily: Lorenzo, I think you were gonna talk about, the impact of this on infection control and controlling outbreaks. so, I think , the aim of WHO is to bring any population, any person, wherever they live, to the highest standard of health. And, in that respect, we were facing a landscape before where we had, very, clear recommendations of what to do in a meningitis case happens in a, high income setting.

[00:54:14] Lorenzo: where, You always provide chemoprophylaxis to interrupt transmissions. And in those settings, meningitis is a very rare disease. you may have one case, because of waning, immunization coverage or not.

[00:54:26] Lorenzo: All the sero groups are covered in the same way by vaccines. and it almost never escalates into an outbreak maximum. You have a cluster in a very close setting and then we had this other setting where we have this large scale epidemics, where the guidelines was a bit less prescriptive because we knew that it's not feasible. If you have this large scale outbreaks, everybody becomes a close contact and then you mass administer, antibiotics and, we have the problems of AMR, the problems of not targeting the right, people, and so on and so forth.

up to now there was this dichotomy, what is the gold standard happening in high income countries? And what was the, the reality in outbreak settings? as we move forward towards eliminating meningitis, first of all, these epidemics still happen, but they happen I. less and less in the meningitis belt. Since 2010, we have introduced a conjugate vaccine against meningococcal meningitis A, which has effectively wiped out the major cause of epidemic meningitis, which was serogroup a. Now, since 2023, we have pre-qualified a Pentavalent vaccine.

so A-C-W-Y-N-X, same technology conjugate vaccine. conjugate vaccines protect, not only the individuals, but also from carriage. So it has a, huge potential for herd immunity. By introducing that vaccine in the meningitis belt, we expect that, the epidemiology of meningitis will be more similar to what we see in, temperate climate settings or high income settings. And there is where we can take the chemoprophylaxis one step forward. with all the caveats, with all the interpretations, as we said, the need of evidence, we asked ourselves why should the recommendation be different If there is a possibility to, provide the, uh, chemoprophylaxis to the, close contacts.

[00:56:16] Lorenzo: it should be our, duty out of equity. that no matter where you live, you should have access to these, preventive tools. and that's our vision. It's the big difference from previous guidelines, and I feel a, a potentially game changer recommendation.

as we said, it's only the first step we will need to work and support countries, to adapt this guidelines to their context as much as possible. Reinforce holistically the AMR, surveillance, uh, systems, and the monitoring systems. But I think that, if we would have started with this very strong recommendation, we would've, not started in the right way.

[00:56:53] Lorenzo: So I'm very optimistic that, we are, in good track with the roadmap to defeat meningitis by 2030, by the way, now it's 2025 and we are exactly at the midway. of our roadmap, which was launched in 2021. and having this guidelines, to accompany us for the next five years is, something extremely exciting and really appreciate, the work that has gone into producing this, evidence-based guidelines together with, all the experts around the world.

[00:57:19] Emily: it's inspiring Lorenzo. I imagine too that one day we are living in a world where, vaccination, has eliminated the need for Chemoprophylaxis. And that would remain a last resort. if we can vaccinate enough of the population. To finish us up.

[00:57:34] Emily: Jacob, this is your bread and butter doing research in infections of the brain. what are your take homes from today in terms of what remains to be done? What are the next steps?

It was a joy and a real opportunity to listen to the discussion that was going on. I'd like to commend the WHO for performing this huge task and this comprehensive guideline. given all the lack of evidence and having to create a guideline that works for the entire world. I think to a large extent the WHO has succeeded and that I was really happy to hear that they would be willing to reevaluate the evidence of course, uh, during the next couple of years.

[00:58:10] Jacob: It's no secret that I think better studies on the diagnostic workflow is really important using patients with suspected bacterial meningitis and not just confirmed bacterial meningitis but better diagnostics, for those with an unknown etiology also, maybe implementation studies of different algorithms because different guidelines suggest different things about 10 years ago, the discussion on hyper-inflammatory versus hypo inflammatory meningitis , there's some animal studies suggesting to kill bacteria softly and then vice versa. So should we start slowly or should we give even higher doses, like a very high first initial dose to get that concentration in the CSF right away. What about continuous treatment versus bolus? And then finally, we need to know more about these adjunctive immunomodulatory treatments because we left with corticosteroids, which we've been using for 70 years.

I completely agree. and the work that is currently ongoing is, as Nicole already hinted, is the case definitions.

[00:59:08] Lorenzo: most of the time in those settings, the best you can do is, especially at the beginning, is have a strong, clinical case definition to decide if you have a suspected bacterial meningitis outbreak or not. there are derivative product of the guidelines and it's currently in publication.

[00:59:24] Lorenzo: We have already revised, the meningococcal disease, case definitions with a group that is partly a guidance development group, so the GDG, of our experts on the diagnosis in a separate group within our roadmap, which is the surveillance working group. So it's kind of a collaboration between the clinicians and the epidemiologists.

[00:59:44] Lorenzo: To define what are the best, suspected, case definitions, in order not to miss outbreaks and not to miss people who need the antibiotics, and at the same time not to overuse them. As we said, with a very generic, case definition, we may end up, using [01:00:00] antibiotics where they're not needed.

[01:00:01] Lorenzo: So it's a complex, exercise, and it's really our priority that, after the publication of the guidelines, so meningococcal case definitions are, in publication. I think Nicolo is leading that project. And the next one, he will think his teeth thin is, uh, the pneumococcal, disease, case definitions, which have additional complexities because of course, uh, pneumococcus, uh.

[01:00:23] Lorenzo: It's not necessarily typically only a meningitis type of disease, but has many other presentations. So this is our, work for the next month.

[01:00:32] Emily: It sounds exciting, and thanks for those final words. Lorenzo.

[01:00:36] Emily: So I really wanna thank Lorenzo and Nicolo for sitting in the hot seat and, answering our, tough clinical questions. on the new WHO meningitis guidelines. Jacob, it was really great to have you, round out the discussion with the clinical and the research perspective and Mark for bringing up the issues with AMR.

[01:00:57] Emily: Thank you to our listeners for listening to communicable the CMI Comms podcast. This episode was hosted by Mark Bonton and me, Emily McDonald, editors at CMI, comms ESCMID's Open Access Journal. It was edited by Katie Hostetler and peer reviewed by Dr. Ljiljana Lukić of University Hospital for Infectious Diseases in Zagreb Croatia.

[01:01:19] Emily: Theme music was composed and conducted by Joseph McDade, and the executive producer of Communicable is Angela Hutter.

[01:01:25] Angela: This episode will be citable with a written summary referenced by A DOI in the next eight weeks, and all the literature we've discussed today, can be found in the show notes.

You can subscribe to Communicable wherever you get your podcasts, or you can find it on ESCMID's website for the CMI COMMS Journal. Thanks for listening and helping CMI, comms and ESCMID move the conversation in ID and clinical microbiology further along.