Therapeutic Advances in Infectious Disease最新文献

Background: Pre-exposure prophylaxis (PrEP) is a safe and effective HIV prevention strategy. However, in countries such as India where PrEP is driven by the private healthcare system and there is no centralized reporting, it is unknown which populations benefit from PrEP and which populations are being left behind.

Objectives: We examined and characterized PrEP use and awareness among the sexual and gender minorities using smartphones in India and found measures of association of PrEP use.

Design: This is a cross-sectional study design.

Methods: We used Grindr-a widely used geosocial mobile application-to conduct a national cross-sectional survey in India, including respondents who were 18 years or older and reported sex with men (those who identified as cis-gender females were excluded). We examined overall PrEP awareness and PrEP use, then calculated adjusted prevalence odds ratio and 95% confidence intervals to understand PrEP use correlation with socio-behavioral factors.

Results: Out of the total of 3116 eligible participants, 30.3% (N = 947) were aware of PrEP and 3.1% (N = 97) reported current PrEP use. Our multivariate regression model found that there was a statistically significant association of PrEP use with higher income, being employed, preferred language as English for survey, relationship status as single, and use of party drugs. At the same time, there was a statistically significant association of PrEP awareness with age group, having higher education as a graduate or above, higher income, use of party drugs, and multiple sexual partners.

Conclusion: We found overall low awareness and low PrEP use in our cross-sectional sample. PrEP use and awareness were higher among those who belonged to higher-income groups. Including PrEP in existing programmatic interventions by government and NGOs may contribute to PrEP scale-up, which is urgent to stop the HIV epidemic in India.

We describe a group of four travelers returning to the United States and Canada who acquired Leishmania braziliensis infection in the Peruvian Amazon. Pentavalent antimonials are the preferred treatment option for cutaneous leishmaniasis (CL) in most endemic countries in Central and South America. However, we initially treated our patients with liposomal amphotericin B (LAB) and miltefosine since these are the only two available Food and Drug Administration approved drugs in the United States. Refractory disease was common as three of the four travelers required repeated courses of miltefosine and two also received LAB. One patient required intravenous therapy with meglumine antimoniate (NMG), and one received intralesional NMG. Given the increasing number of cases of CL identified in the United States, there is an urgent need for expanded access to pentavalent antimonials for treating leishmaniasis acquired in Central and South America.

Fungal pathogens cause a wide range of infections in humans, from superficial to disfiguring, allergic syndromes, and life-threatening invasive infections, affecting over a billion individuals globally. With an estimated 1.5 million deaths annually attributable to them, fungal pathogens are a major cause of mortality in humans, especially people with underlying immunosuppression. The continuous increase in the population of individuals at risk of fungal infections in sub-Saharan Africa, such as HIV patients, tuberculosis patients, intensive care patients, patients with haematological malignancies, transplant (haematopoietic stem cell and organ) recipients and the growing global threat of multidrug-resistant fungal strains, raise the need for an appreciation of the region's perspective on antifungal usage and resistance. In addition, the unavailability of recently introduced novel antifungal drugs in sub-Saharan Africa further calls for regular evaluation of resistance to antifungal agents in these settings. This is critical for ensuring appropriate and optimal use of the limited available arsenal to minimise antifungal resistance. This review, therefore, elaborates on the multifaceted nature of fungal resistance to the available antifungal drugs on the market and further provides insights into the prevalence of fungal infections and the use of antifungal agents in sub-Saharan Africa.

International spread of polio continues to be a Public Health Emergency of International Concern since its declaration by the World Health Organization in 2014 and its reiteration in 2024. In 2023 and 2024, two countries remained endemic for wild poliovirus (WPV) but 20 countries reported polio outbreaks due to vaccine-derived polioviruses (VDPVs) in 2023 and 10 countries in 2024 (up to mid-June). Guidelines from various agencies recommend polio vaccination before travelling to or from polio-affected countries, or attending mass gatherings anywhere in the world, particularly if the crowd is international. Immunity protects against polio paralysis but not against poliovirus re-infection, irrespective of which vaccine was involved - live attenuated oral polio vaccine (OPV) or inactivated poliovirus vaccine (IPV). Infection with WPV or circulating VDPV in the vast majority of non-immune individuals (first infection) is asymptomatic, while they are efficient virus transmitters. Re-infections in immune individuals are always asymptomatic, but they are also infectious and may act as source for further transmission, although less efficiently than the former. Thus, travellers can become transmission vectors, illustrated by many episodes of importations of WPV or VDPVs into polio-free countries in recent years. The route of poliovirus transmission remains controversial, with many believing it to be faecal-oral, but epidemiological analysis is consistent with respiratory route and not faecal-oral. Transmission occurs person-to-person during social contact. Travellers must ensure they are adequately immunised to avoid polio, and becoming vectors of virus importation. The vaccine efficacy (VE) of OPV is highly variable - high in temperate climate countries, particularly rich countries, but low or very low in tropical low-income countries. On the other hand, VE of IPV is excellent everywhere irrespective of geography.

Background: Fungal infective endocarditis (IE) is a rare, yet increasingly recognised condition associated with substantial mortality rates. Candida and Histoplasma are among the notable causative agents, presenting diverse clinical manifestations and complexities in diagnosis and management.

Objectives: This study was undertaken to examine the clinical profiles, diagnostic challenges, treatment modalities, and outcomes of four compelling cases involving Candida and Histoplasma endocarditis.

Methods & design: This was a descriptive case series study conducted from July 2021 to July 2023. All patients with definite/possible endocarditis diagnosed based on modified Duke's criteria were reviewed in this study. Data on demographics, risk factors, clinical signs and symptoms, echocardiography findings, microbiological aetiology, complications, treatment, and outcomes were collected.

Results: Among 212 suspected IE cases reviewed, 54 met the modified Duke's criteria for possible or definite IE, with four instances identified as fungal endocarditis. Candida species accounted for three cases, while an uncommon instance of Histoplasma Endocarditis (HE) was also observed. Clinical presentations varied, with fever and dyspnoea being prominent symptoms. Risk factors included chronic kidney disease, prior surgeries, prosthetic valves, and immunocompromised states. Diagnosis posed challenges due to the resemblance to bacterial IE, low blood culture yields, and delayed suspicion. Various diagnostic approaches, including blood cultures, serological markers, and imaging, were employed. Therapeutic strategies involved antifungal agents and surgical intervention, where feasible. However, despite prompt treatment initiation, many patients faced rapid clinical deterioration, emphasising the severity and aggressive nature of fungal endocarditis. Mortality rates remained notably high across the cohort.

Conclusion: This study highlights the criticality of early suspicion, prompt diagnosis, and a multidisciplinary approach to managing fungal endocarditis. While recognising the limitations in current diagnostic tools and therapeutic options, the study underscores the urgent need for enhanced diagnostic modalities and novel treatment strategies to improve outcomes in these challenging cases.

Opportunistic central nervous system (CNS) infections are a significant cause of morbidity and mortality in immunocompromized patients, including those undergoing transplantation and receiving immunomodulatory therapy. Particularly in these individuals, the clinical presentation of these infections may have atypical patterns, emphasizing the need to consider various diagnostic possibilities, including noninfectious conditions. Quick and accurate identification, along with prompt treatment, is crucial for improving patient outcomes. Therefore, understanding which pathogens are likely to cause infection based on factors such as timing post-transplantation, specific organ transplant, and the mechanism of action of immunomodulatory medications is essential. This review will provide a detailed description of the types of infections that may arise in the context of transplantation and immunomodulatory therapy.

Cat scratch disease (CSD) is a zoonotic disease transmitted to humans, usually via scratches or bites. Bartonella henselae is the primary causative agent. It causes a mild, self-limiting disease. In immunocompromised patients, the course of the infection can be more serious because of the suppressed antibacterial response, causing a life-threatening disease. A 54-year-old male patient presented with ulcerative colitis. Five days after receiving the first dose of infliximab 400 mg intravenously and 0.5 mg/kg methylprednisolone, he presented with enlarged axillary lymph nodes and colliquation of the intraabdominal lymph node with intrahepatic colliquating areas caused by B. henselae after cat bites. Long-term treatment with multiple antibiotics and prednisolone resulted in clinical improvement and regression of the liver and intra-abdominal lymph nodes. After further treatment for ulcerative colitis, we assessed the possibility of reintroducing immunosuppressive therapy. Adalimumab was introduced after consulting an infectious disease specialist. At the follow-up visit, the patient was in remission of ulcerative colitis and without signs of reactivation of bartonellosis. Diseases such as CSD with a benign clinical appearance and prognosis can develop a severe and life-threatening course in immunocompromised patients. This requires a complex understanding of the immune processes in such patients, and the reintroduction of immunosuppressive therapy after successful treatment of CSD probably does not increase the risk of reactivation.

Background: Malaria during pregnancy contributes to significant perinatal morbidity and mortality, accounting for almost 25% of global maternal mortality. However, the epidemiology and risk factors for subclinical malaria among pregnant women living in refugee settlements is poorly understood.

Objective: To determine the prevalence and predictors of subclinical malaria among pregnant women in refugee settlements in Northern Uganda.

Design: We conducted a multi-center, cross-sectional study.

Methods: The study was conducted between April and June 2023 and involved pregnant women aged 18-45 years attending routine antenatal care (ANC) at three health facilities serving refugee communities in Adjumani district, Uganda. We collected sociodemographic, environmental, maternal, and obstetric factors using a structured questionnaire. Both CareStart Malaria HRP-2/pLDH (Pf/Pan) combo rapid diagnostic test (RDT) and blood smear microscopy with 3% Giemsa staining were simultaneously performed on samples from each patient. Logistic regression analysis identified factors independently associated with subclinical malaria, reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results: We enrolled 304 pregnant women, with a mean age of 25 years. In total, 68.8% (n = 209) had lived in the settlement for over 12 months, 25.7% (n = 78) were primigravida, and 1.0% (n = 3) were living with HIV. Malaria prevalence was 5.3% (n = 16) by RDT and 3.2% (n = 10; seven Plasmodium falciparum and three P. malariae) by microscopy. Only 4 (25.0%) of the RDT-positive cases were also positive by microscopy (Cohen's kappa: 0.278-Fair agreement). All participants were asymptomatic. Factors associated with higher odds of subclinical malaria included primiparity (aOR: 2.79, 95% CI: 1.25-6.25, p = 0.013), ⩾4 ANC visits (aOR: 2.41, 95% CI: 1.34-4.34, p = 0.003), and residence in the settlement for less than 12 months (aOR: 2.54, 95% CI: 2.0-3.22, p < 0.001). Living in the settlement for over 3 years, being primigravida, and being married were associated with 68%, 50%, and 68% lower odds of subclinical malaria, respectively (aOR: 0.32, 95% CI: 0.13-0.79, p = 0.014; aOR: 0.50, 95% CI: 1.22-5.52, p = 0.016; aOR: 0.32, 95% CI: 0.13-0.78, p = 0.012).

Conclusion: Our study reveals the high prevalence of subclinical malaria among pregnant women in refugee settlements, particularly among primiparous women and recent arrivals. The poor agreement between RDT and microscopy suggests the need for dual screening in asymptomatic pregnant women.

Background: The combined effect of the aging human immunodeficiency virus (HIV) population, HIV's natural progression, and HIV drugs have great implications for comorbidity burden and hypertension control among people living with HIV (PLHIV).

Objectives: This study assessed hypertension burden, treatment outcomes, and treatment outcome predictors among PLHIV in Nigeria.

Design: Cross-sectional design.

Methods: A cross-sectional study of 2613 adult PLHIV who initiated antiretroviral therapy (ART) between 2004 and 2020 in two HIV clinics in Northern and Southern Nigeria. Study outcomes were: (1) controlled blood pressure defined as two consecutive blood pressure (BP) measurements of <140/90 mmHg (Joint National Committee guideline (JNC) 7) on the interview day in previously diagnosed hypertensive participants; and (2) HIV viral suppression defined as recent viral load count of <1000 copies/ml in a hypertensive participant. Data were analyzed using Statistical Package of Social Sciences IBM version 23. Univariate and multivariate logistic regression was done to ascertain factors associated with the study outcomes at p < 0.05.

Result: The mean age of respondents at the point of the study was 45.3 ± 9.8 years. Most of the participants were female, 1940 (74.2%), on a dolutegravir-based therapy, 2433 (93.2%). About 452 (17.3%) of the participants had clinically diagnosed hypertension. Of those diagnosed hypertensives, 443 (98.0%) were on antihypertensive drugs. About 407 (90.0%) and 229 (51.7%) of the hypertensive PLHIV had HIV viral suppression and controlled hypertension respectively. Factors associated with controlled hypertension were age at ART initiation (adjusted odds ratio (AOR): 0.96, 95% CI: 0.94-0.98), use of thiazide only antihypertensive (AOR: 1.91, 95% CI: 1.73-3.24, Ref: calcium channel blocker only) and thiazide-calcium channel blocker combination (AOR: 2.19, 95% CI: 1.05-4.58). No hypertension comorbidity-related factors were found to be associated with HIV viral suppression.

Conclusion: There is suboptimal hypertension control among hypertensive PLHIV especially those on non-thiazide-based antihypertensive drugs. Close monitoring should be given to hypertension management in PLHIV.

Background: Urinary tract infections (UTIs) are the most common bacterial infections in children. The high variability in pathogen susceptibility rates leads to the lack of clear guidelines for empiric and targeted therapies. In this view, local microbiological surveillance and locally adapted stewardship interventions need to be implemented.

Objective: The study aims to describe the results of a pediatric antimicrobial stewardship program on antibiotic prescriptions for UTIs over 8 years in a pediatric general ward of a tertiary center.

Design: This quasi-experimental study was conducted between 2015 and 2022, with two different implementations, one in 2018 and one in 2021.

Methods: Demographic, clinical, microbiological, and therapeutic data were retrieved from the electronic clinical records of included patients. The primary outcomes were adherence to local guidelines for empiric therapies and the adequacy of targeted therapy. Secondary outcomes were evaluating antibiotic prescription patterns stratified by antibiotics during hospital stay and at discharge, and assessing the microbiological characteristics of UTI episodes.

Results: During the study period, 7038 patients were admitted to the pediatric acute care unit (PACU), and 264 (3.7%) were included in this study. Adherence to local guidelines was highest immediately after the interventions, and it slightly decreased thereafter. Use of cephalosporins remained high throughout the 8 years but the changing microbiological scenario observed led to changing recommendations within the study period. An increase in E. coli strains resistant to co-amoxiclav was observed in the last years. Oral second-line agent consumption remained high but was adequate considering the prevalence of resistant bacteria.

Conclusion: The variability of antimicrobial consumption reflects the changing resistance patterns for UTIs pathogens, underlying the importance of locally adapted, persevering antimicrobial stewardship interventions.