Invasive Diseases Research Articles

Differential Transcriptional Responses of Human Granulocytes to Fungal Infection with Candida albicans and Aspergillus fumigatus.

Neutrophils are critical phagocytic cells in innate immunity, playing a significant role in defending against invasive fungal pathogens. This study aimed to explore the transcriptional activation of human neutrophils in response to different fungal pathogens, including Candida albicans and Aspergillus fumigatus, compared to the bacterial pathogen Escherichia coli. We identified distinct transcriptional profiles and stress-related pathways in neutrophils during fungal infections, highlighting their functional diversity and adaptability. The transcriptional response was largely redundant across all pathogens in immune-relevant categories and cytokine pathway activation. However, differences in the magnitude of differentially expressed genes (DEGs) were observed, with A. fumigatus inducing a lower transcriptional effect compared to C. albicans and E. coli. Notably, specific gene signatures associated with cell death were differentially regulated by fungal pathogens, potentially increasing neutrophil susceptibility to autophagy, pyroptosis, and neutrophil extracellular trap (NET) formation. These findings provide valuable insights into the complex immunological responses of neutrophils during fungal infections, offering new avenues for diagnostic and therapeutic strategies, particularly in the management of invasive fungal diseases.

Food and Drug Administration Public Workshop Summary-Addressing Challenges in Inhaled Antifungal Drug Development.

Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On 25 September 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.

Different Group A Streptococcus pili lead to varying proinflammatory cytokine responses and virulence.

The human pathogen Streptococcus pyogenes, or Group A Streptococcus (GAS), is associated with a variety of diseases ranging from mild skin and soft tissue infections to invasive diseases and immune sequelae such as rheumatic heart disease. We have recently reported that one of the virulence factors of this pathogen, the pilus, has inflammatory properties and strongly stimulates the innate immune system. Here we used a range of nonpathogenic Lactococcus lactis gain-of-function mutants, each expressing one of the major pilus types of GAS, to compare the immune responses generated by various types of fully assembled pili. In vitro assays indicated variability in the inflammatory response induced by different pili, with the fibronectin-binding, collagen-binding, T antigen (FCT)-1-type pilus from GAS serotype M6/T6 inducing significantly stronger cytokine secretion than other pili. Furthermore, we established that the same trend of pili-mediated immune response could be modeled in Galleria mellonella larvae, which possess a similar innate immune system to vertebrates. Counterintuitively, across the panel of pili types examined in this study, we observed a negative correlation between the intensity of the immune response demonstrated in our experiments and the disease severity observed clinically in the GAS strains associated with each pilus type. This observation suggests that pili-mediated inflammation is more likely to promote bacterial clearance instead of causing disruptive damages that intensify pathogenesis. This also indicates that pili may not be the main contributor to the inflammatory symptoms seen in GAS diseases. Rather, the immune-potentiating properties of the pilus components could potentially be exploited as a vaccine adjuvant.

New and emerging options for management of invasive fungal diseases in paediatric patients.

Invasive fungal diseases (IFDs) play an important role in the supportive care of paediatric patients with acute leukaemia and those undergoing allogeneic haematopoietic cell transplantation, and they are associated with significantly decreased overall survival rates in affected individuals. Relative to adults, children and adolescents are distinct in terms of host biology, predisposing conditions, presentation and epidemiology of fungal diseases, and in the pharmacology of antifungal agents. The paediatric development of antifungal agents has moved forward in a coordinated manner, and major advances have been made regarding concepts and recommendations for the prevention and treatment of IFDs. However, antifungal therapy is increasingly complex, and a solid knowledge of the available options is needed more than ever for successful management. This narrative review provides a summary of the paediatric development of agents that have been recently approved (anidulafungin, posaconazole) or are in advanced stages of development (isavuconazole). It also reviews the emerging evidence for the efficacy of echinocandins for prophylaxis of invasive aspergillosis, presents new data on alternative dosing regimens of echinocandins and voriconazole, and provides a brief overview of new antifungal agents in clinical development that are expected to be developed for paediatric patients.

Unlatching of the stem domains in the Staphylococcus aureus pore-forming leukocidin LukAB influences toxin oligomerization

Staphylococcus aureus (S.aureus) is a serious global pathogen that causes a diverse range of invasive diseases. S.aureus utilizes a family of pore-forming toxins, known as bi-component leukocidins, to evade the host immune response and promote infection. Among these is LukAB (leukocidin A/leukocidin B), a toxin that assembles into an octameric β-barrel pore in the target cell membrane, resulting in host cell death. The established cellular receptor for LukAB is CD11b of the Mac-1 complex. Here, we show that hydrogen voltage-gated channel 1 is also required for the cytotoxicity of all major LukAB variants. We demonstrate that while each receptor is sufficient to recruit LukAB to the plasma membrane, both receptors are required for maximal lytic activity. Why LukAB requires two receptors, and how each of these receptors contributes to pore-formation remains unknown. To begin to resolve this, we performed an alanine scanning mutagenesis screen to identify mutations that allow LukAB to maintain cytotoxicity without CD11b. We discovered 30 mutations primarily localized in the stem domains of LukA and LukB that enable LukAB to exhibit full cytotoxicity in the absence of CD11b. Using crosslinking, electron microscopy, and hydroxyl radical protein footprinting, we show these mutations increase the solvent accessibility of the stem domain, priming LukAB for oligomerization. Together, our data support a model in which CD11b binding unlatches the membrane penetrating stem domains of LukAB, and this change in flexibility promotes toxin oligomerization.

Vaccination anti-infectieuse : pour qui ? Quand ? Comment ?: Anti-infectious vaccination: For whom? When? How?

Patients with solid tumors such as bronchopulmonary cancer have an increased susceptibility to infections, some of which are vaccine-preventable. Vaccines against invasive pneumococcal diseases, seasonal influenza and COVID-19 are specifically recommended in this population. Also, with the exception of live attenuated vaccines, which are contraindicated, the vaccines otherwise recommended in this population are those of the vaccination schedule in force. As in the general population and in all immunocompromised patients, improving vaccination coverage in patients with solid tumors is a public health issue.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Influenza enhances host susceptibility to non-pulmonary invasive Streptococcus pyogenes infections

ABSTRACT Streptococcus pyogenes (group A streptococcus; GAS) causes a variety of invasive diseases (iGAS) such as bacteremia, toxic shock syndrome, and pneumonia, which are associated with high mortality despite the susceptibility of the bacteria to penicillin ex vivo. Epidemiologic studies indicate that respiratory influenza virus infection is associated with an increase in the frequency of iGAS diseases, including those not directly involving the lung. We modified a murine model of influenza A (IAV)-GAS superinfection to determine if viral pneumonia increased the susceptibility of mice subsequently infected with GAS in the peritoneum. The results showed that respiratory IAV infection increased the morbidity (weight loss) of mice infected intraperitoneally (i.p.) with GAS 3, 5, and 10 d after the initial viral infection. Mortality was also significantly increased when mice were infected with GAS 3 and 5 d after pulmonary IAV infection. Increased mortality among mice infected with virus 5 d prior to bacterial infection correlated with increased dissemination of GAS from the peritoneum to the blood, spleen, and lungs. The interval was also associated with a significant increase in the pro-inflammatory cytokines IFN-γ, IL-12, TNF-α, MCP-1 and IL-27 in sera. We conclude, using a murine model, that respiratory influenza virus infection increases the likelihood and severity of systemic iGAS disease, even when GAS infection does not originate in the respiratory tract.

Біологічні особливості та перспективи штучного відтворення вирезуба (Rutilus frisii frisii Nordman, 1840) в Україні (огляд)

Purpose. The main goal of the thematic review was the analysis and generalization of literary sources on the peculiarities of its biology, technological aspects of artificial reproduction and growing of vyrezub (Rutilus frisii frisii Nordman, 1840) for the restoration of its natural population in water bodies of Ukraine. To evaluate the perspectives of artificial reproduction and growing of vyrezub in aquaculture of Ukraine. Findings. As a result of human impact on river networks of Ukraine, the abundance of vyrezub significantly decreased, it has become a rare and at the same time an endangered species. According to retrospective data, vyrezub previously belonged to the widespread commercial species of the Dnipro and Southern Bug rivers. The biological features of this species have been analyzed, the observance of which can allow obtaining viable fish seeds in aquaculture conditions. The adaptive possibilities of vyrezub to artificial conditions of reproduction have been reviewed. Historical information on the reproduction of this species over the last century has been analyzed. On the territory of Ukraine, first attempts to artificially reproduce vyrezub were carried out by specialists of Ukrcherrybvod. According to the results of studies of Ukrainian scientists, several stages of artificial reproduction of vyrezub have been identified, namely: taking spawners from natural water bodies, obtaining eggs and sperm, incubation of eggs in incubation devices, obtaining 6 g fish seeds, release of viable juveniles into natural water bodies. However, the works on artificial reproduction of vyrezub were not successful, which was the reason for their complete cessation. In particular, this species is promising for growing in polyculture, as it does not create intense trophic competition with most objects of freshwater aquaculture, and as a result of the consumption of mollusks will reduce the likelihood of the spread of some invasive fish diseases. Practical value. The review of information sources on various aspects of the use of vyrezub in aquaculture will contribute to the development of a system of separate links of the technology of its cultivation for the needs of rearing in the conditions of aquaculture enterprises and stocking of internal water bodies with viable juveniles. Key words: vyrezub (Rutilus frisii frisii Nord­man, 1840), aquaculture, biocontrol effect, artificial reproduction, viable juveniles, stocking, restoration of population abundance.

Invasive bacterial disease in young infants in rural Gambia: Population-based surveillance.

Invasive bacterial diseases (IBD) cause significant mortality in young infants. There are limited population-based data on IBD in young infants in Sub-Saharan Africa. We conducted population-based surveillance for IBD among infants aged 0-90 days in a demographic surveillance area in rural Gambia between 1 March 2011 and 31 December 2017. Infants admitted to health facilities within the study area had standardised clinical evaluation plus conventional microbiological investigation. We defined IBD as isolation of pathogenic bacteria from blood, cerebrospinal fluid, lung, or pleural aspirate. We determined incidence, aetiology and case-fatality of IBD. A total of 3794 infants were admitted and 3605 (95%) had at least one sample collected for culture. We detected 254 (8.0%) episodes of IBD (bacteraemia 241; meningitis 14; pneumonia seven). The incidence of IBD in infants aged 0-90 days was 25 episodes/1000 person-years (95% confidence interval (CI) = 22-28), the incidence in neonates was 50 episodes/1000 person-years (95% CI = 43-58) and the incidence in infants aged 29-90 days was 12 episodes/1000 person-years (95% CI = 9-15). The most common pathogens causing IBD were Staphylococcus aureus (n = 102, 40%), Escherichia coli (n = 37, 15%), Streptococcus pneumoniae (n = 24, 9%) and Klebsiella pneumoniae (n = 12, 5%). Case-fatality was 29% (95% CI = 23-37) in neonates and 19% (95% CI = 11-29) in infants aged 29-90 days. A minimum of 7.3% of all young infant deaths in the population were caused by IBD. IBD are common in young infants in rural Gambia and have a high case-fatality. Strategies are needed to prevent IBD in young infants. Overcoming barriers to widespread implementation of existing vaccines and developing new vaccines against the most common pathogens causing IBD should be among top priorities for reducing the high mortality rate in young infants.

Atypical imaging patterns during lung invasive mould diseases: lessons for clinicians.

Imaging of pulmonary invasive mould diseases (IMDs), which represents a cornerstone in their work-up, is mainly based on computed tomography (CT). The purpose of this review is to discuss their CT features, mainly those related to aspergillosis and mucormycosis. We will especially focus on atypical radiological presentations that are increasingly observed among non-neutropenic emerging populations of patients at risk, such as those receiving novel anticancer therapies or those in the intensive care unit. We will also discuss the interest of other available imaging techniques, mainly positron emission tomography/CT, that may play a role in the diagnosis as well as evaluation of disease extent and follow-up. We will show that any new airway-centred abnormality or caveated lesion should evoke IMDs in mildly immunocompromised hosts. Limitations in their recognition may be due to potential underlying abnormalities that increase the complexity of interpretation of lung imaging, as well as the non-specificity of imaging features. In this way, the differentials of all morphological/metabolic aspects must be kept in mind for the optimal management of patients, as well as the benefit of evaluation of the vascular status.

An update on the global treatment of invasive fungal infections.

Fungal infections are a serious problem affecting many people worldwide, creating critical economic and medical consequences. Fungi are ubiquitous and can cause invasive diseases in individuals mostly living in developing countries or with weakened immune systems, and antifungal drugs currently available have important limitations in tolerability and efficacy. In an effort to counteract the high morbidity and mortality rates associated with invasive fungal infections, various approaches are being utilized to discover and develop new antifungal agents. This review discusses the challenges posed by fungal infections, outlines different methods for developing antifungal drugsand reports on the status of drugs currently in clinical trials, which offer hope for combating this serious global problem.

Epidemiological Features of Purulent Bacterial Meningitis in the Russian Federation at the Present Stage

Relevance. The decrease in the number of cases of invasive diseases caused by N. meningitidis, S. pneumoniae, H. influenzae and in the world has been associated with measures against the spread of the 2019 coronavirus disease (COVID-19).Aim. Presentation of the epidemiological features of purulent bacterial meningitis (PBM) in the Russian Federation at the present stage.Materials and methods. On the basis of the Russian Reference Center for Monitoring Bacterial Meningitis (RCMC), an in-depth personalized system for recording PBM cases has been established. Since 2010, all territories of the Russian Federation have been included in the monitoring system. In 2022, the RCMC received information on 1596 cases of PBM. The descriptive-evaluative epidemiological method was used in the work: a retrospective analysis.Results. The increase in the incidence of a generalized form of meningococcal infection (GFMI), which began in 2017, was recorded in 2018 and 2019, but in 2020–2021 growth was interrupted: the indicator dropped sharply, amounting to 0.26–0.21 per 100 thousand of the population, which is most likely due to the disunity of the population as a result of measures aimed at combating the new coronavirus infection. Measures to combat COVID-19 were canceled in 2021, and already in 2022 the incidence rate of GBM increased by 1.4 times, while the GFMI by 2 times, amounting to 0.44 per 100 thousand of the population. A sharp decrease in the incidence of PBM caused by S. pneumoniae and H. influenzae in 2020-2021 was replaced in 2022 by an increase in the incidence of pneumococcal meningitis, however, the incidence of meningitis caused by H. influenzae remained at the same level.Conclusion. Continued monitoring of the incidence of PBM and the properties of the pathogen are extremely important tasks in order to identify risk groups and areas for the timely optimization of vaccination measures, given that the three infections that cause bacterial meningitis are vaccine-controlled, and vaccination is recognized as the most effective measure to combat meningococcal, pneumococcal and hemophilic infections.

Pulmonary Invasive Fungal Disease: Ultrasound and Computed Tomography Scan Findings.

The importance of ultrasound in diagnosing pulmonary invasive fungal diseases (IFD) has yet to be assessed. Thus, this study aimed to evaluate the frequency of sonographic findings in patients suspected of an invasive pulmonary fungal infection. This prospective longitudinal study examined all patients with lung lesions in imaging modalities and suspected IFDs referred to Dr. Sheikh and Akbar pediatric hospitals from 2019 to 2022. Considered variables were the halo sign in the computed tomography (CT) scan; the target sign in the ultrasound and contrast-enhanced CT scan; the cavity; wedge-shaped consoli- dation; and pleuritis and extrapulmonary invasion to the chest wall or subdiaphragmatic invasion in both modalities. All patients who underwent lung CT scans and ultrasounds until the final diagnosis were followed up. The degree of agreement between ultrasound and CT scan findings and the sensitivity, specificity, and diagnostic accuracy of these signs were assessed. This study involved 40 patients with an average age of 7.16 ± 4.23 years. Acute leukemia was the commonest underlying dis- ease detected in 17 (42.5%) cases. The target sign in ultrasound (61.9%) and the halo sign in CT scan (71.4%) had the highest frequency among the variables in patients with IFD. Cohen's kappa coefficient agreement in both modalities was 0.5 for the cavity, with significant relation (P = .02). The Cohen's kappa was less than .17 for other findings (P > .05). The diagnostic criteria in the simultaneous examina- tion of the fungus target in ultrasound and halo in CT scan showed a sensitivity of 82.4% and specificity of 76.5%, respectively. Combining the characteristic findings of ultrasound and CT-scan provides a higher value in diagnosing pulmonary invasive fungal disease.

A case study of rhino orbito cerebral Mucormycosis (ROCM) in a diabetic patient reported from a multispeciality hospital in Tamil Nadu

ROCM is the most common type of Mucormycosis and it can rapidly spread from the paranasal sinuses to orbit and brain which can be fatal in most patients. Diabetes mellitus is the most common risk factor in India. As invasive fungal diseases present with nonspecific clinical features, increasing awareness and education among clinicians about this deadly enemy is very crucial for early diagnosis and prompt initiation of appropriate therapy. We are reporting a case study on ROCM in a Diabetic patient caused by species along with a short review on the taxonomy, risk factors, pathogenesis, clinical forms, diagnosis and management of mucormycosis. We hope that this will help in expanding awareness among medical community about mucormycosis which is a lethal opponent of patients with Diabetes Mellitus.

Conference Report 33rd European Congress on Clinical Microbiology and Infectious Diseases (ECCMID): New developments in pediatric oncology infectious disease supportive care.

Infections continue to be major causes of morbidity and mortality in immunocompromised children and adolescents with cancer or undergoing allogeneic hematopoietic cell transplantation. This report summarizes new clinical research data presented at the 33rd European Congress on Clinical Microbiology and Infectious Diseases on infections in this vulnerable population, with a focus on the epidemiology, diagnosis, and prevention of invasive fungal diseases and de-escalation strategies in neutropenic patients with fever of unknown origin.

Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.

To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period. All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines. Overall, 1,516 S. pneumoniae isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years. PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.

Emerging Roles of (1→3)-β-D-Glucan in Cerebrospinal Fluid for Detection and Therapeutic Monitoring of Invasive Fungal Diseases of the Central Nervous System.

Emerging Roles of (1→3)-β-D-Glucan in Cerebrospinal Fluid for Detection and Therapeutic Monitoring of Invasive Fungal Diseases of the Central Nervous System.

Molecular Identification and Detection of Streptococcus pneumoniae Serotypes Isolated from the Cerebrospinal Fluid of Children with Suspected Meningitis: First Report From Alborz, Iran

Background: Pneumococcus causes various infections, some of which are life-threatening, including pneumonia, meningitis, otitis media, bacteremia, and sinusitis. Currently, more than 95 serotypes have been identified. Objectives: The purpose of this study was to isolate and determine Streptococcus pneumoniae serotypes from the cerebrospinal fluid (CSF) of children with suspected meningitis using the multiplex polymerase chain reaction (PCR) method. Materials and Methods: A total of 864 CSF samples were taken from children with suspected meningitis who were admitted to Imam Ali Hospital of Karaj for one year (January 2019 to January 2020). To collect positive S. pneumonia samples, the lytA gene was traced using specific primers and PCR techniques. Results: The results of this study indicated that only 16 patients have a pneumococcal infection (1.85%), of whom 50% have encapsulated pneumococci. Furthermore, serotypes 38 (12.5%), 7F (12.5%), 23F (25%), and 6A/B (50%) were the most common serotypes causing invasive pneumococcal infections in the included samples. Conclusion: Among the techniques for serotyping S. pneumoniae, the multiplex PCR technique is known as a fast, easy, and low-cost method that can serotype a large number of samples. The results also showed that the 13-valent pneumococcal conjugate vaccine can cover at least 50% of the strains that cause invasive pneumococcal diseases (IPDs), which are life-threatening, especially in children. Therefore, it is suggested that the healthcare administrators of Iran design and implement a public vaccination program.

Development of a bivalent protein-based vaccine candidate against invasive pneumococcal diseases based on novel pneumococcal surface protein A in combination with pneumococcal histidine triad protein D.

Extensive efforts have been made toward improving effective strategies for pneumococcal vaccination, focusing on evaluating the potential of multivalent protein-based vaccines and overcoming the limitations of pneumococcal polysaccharide-based vaccines. In this study, we investigated the protective potential of mice co-immunization with the pneumococcal PhtD and novel rPspA proteins against pneumococcal sepsis infection. The formulations of each antigen alone or in combination were administered intraperitoneally with alum adjuvant into BALB/c mice three times at 14-day intervals. The production of antigen-specific IgG, IgG1 and IgG2a subclasses, and IL-4 and IFN-γ cytokines, were analyzed. Two in vitro complement- and opsonophagocytic-mediated killing activities of raised antibodies on day 42 were also assessed. Finally, the protection against an intraperitoneal challenge with 106 CFU/mouse of multi-drug resistance of Streptococcus pneumoniae ATCC49619 was investigated. Our findings showed a significant increase in the anti-PhtD and anti-rPspA sera IgG levels in the immunized group with the PhtD+rPspA formulation compared to each alone. Moreover, the results demonstrated a synergistic effect with a 6.7- and 1.3- fold increase in anti-PhtD and anti-rPspA IgG1, as well as a 5.59- and 1.08- fold increase in anti-PhtD and anti-rPspA IgG2a, respectively. Co-administration of rPspA+PhtD elicited a mixture of Th-2 and Th-1 immune responses, more towards Th-2. In addition, the highest complement-mediated killing activity was observed in the sera of the immunized group with PhtD+rPspA at 1/16 dilution, and the opsonophagocytic activity was increased from 74% to 86.3%. Finally, the survival rates showed that mice receiving the rPspA+PhtD formulation survived significantly longer (100%) than those receiving protein alone or PBS and exhibited the strongest clearance with a 2 log10 decrease in bacterial load in the blood 24h after challenge compared to the control group. In conclusion, the rPspA+PhtD formulation can be considered a promising bivalent serotype-independent vaccine candidate for protection against invasive pneumococcal infection in the future.

Epidemiology of Streptococcus pneumoniae Serotypes in Jordan Amongst Children Younger than the Age of 5: A National Cross-Sectional Study.

Streptococcus pneumoniae infections are a major cause of mortality and morbidity worldwide. In Jordan, pneumococcal conjugate vaccines (PCVs) are not included in the national vaccination program. Due to the current availability of several PCVs, including PCV-10, PCV-13, and PCV-15, along with PCV-20, currently undergoing pediatric approvals globally, the decision to introduce PCVs and their selection should be based on valid local data on the common serotypes of Streptococcus pneumoniae. This cross-sectional study aimed to identify the frequency of serotypes of Streptococcus pneumoniae in children aged below 5 years hospitalized with invasive pneumococcal diseases (IPDs), including pneumonia, septicemia, and meningitis, during the study's duration in representative areas of Jordan. Serotyping for culture-positive cases was based on the capsular reaction test, known as the Quellung reaction. qPCR was conducted on the blood samples of patients with lobar pneumonia identified via X-ray or on cerebrospinal fluid for those with a positive latex agglutination test for Streptococcus pneumoniae. This study was based on the analysis of the serotypes of 1015 Streptococcus pneumoniae cases among children younger than the age of 5: 1006 cases with pneumonia, 6 cases with meningitis, and 3 cases with septicemia. Only 23 culture-positive cases were identified in comparison to 992 lobar pneumonia cases, which were PCR-positive but culture-negative, with a PCR positivity rate of 92%. Serotypes 6B, 6A, 14, and 19F were the most common serotypes identified in this study, with prevalence rates of 16.45%, 13.60%, 12.12%, and 8.18%, respectively. PCV-10, PCV-13, PCV-15, and PCV-20 coverage rates were 45.32%, 61.87%, 64.14%, and 68.47%, respectively. To the best of our knowledge, this is the largest prospective study from the Middle East and one of the largest studies worldwide showing the serotypes of Streptococcus pneumoniae. It reveals the urgency for the introduction of a PCV vaccination in Jordan, utilizing recently developed vaccines with a broader serotype coverage.