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Cureus May 2024Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology...
Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology can be categorized as physiologic, reactive, neoplastic, idiopathic, or indicative of systemic illness. Several systemic drugs have been linked to the development of oral and/or cutaneous pigmentation, either by stimulating the production of melanin or by the accumulation of the drug or its byproducts. The medications most commonly associated with this condition include antimalarials, hormones, oral contraceptives, phenothiazines, chemotherapeutics, amiodarone, minocycline, zidovudine, clofazimine, and ketoconazole. The aim of this case report is to illustrate the drug-induced appearance of multiple melanotic macules in an 89-year-old female patient. The patient was referred to the Department of Oral Medicine and Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining of the recent and constant appearance of black spots in her oral cavity. Her medical history revealed a multitude of prescribed drugs, with citalopram being the most recently prescribed one, approximately one year prior to the examination. The clinical examination revealed multiple melanotic macules, on the upper and lower lip as well as on the hard and soft palate. Based on these findings, a biopsy of a melanotic macule of the lip was carried out. The histopathological examination showed that the basal layer of the stratified squamous epithelium exhibited hyperpigmentation (melanin-pigmented basal cells). In addition, scattered melaninophages were noted in lamina propria. Psychotropic drugs associated with cutaneous hyperpigmentation include citalopram. Therefore, our case constitutes an exception since citalopram induced intraoral and perioral, instead of cutaneous, hyperpigmentation.
PubMed: 38910786
DOI: 10.7759/cureus.60889 -
European Journal of Medicinal Chemistry Jun 2024The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput...
The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates.
PubMed: 38909569
DOI: 10.1016/j.ejmech.2024.116599 -
Diagnostic Microbiology and Infectious... Jun 2024Drug resistance surveillance is a major integral part of malaria control programs. Molecular methods play a pivotal role in drug resistance detection and related...
Drug resistance surveillance is a major integral part of malaria control programs. Molecular methods play a pivotal role in drug resistance detection and related molecular research. This study aimed to develop a rapid and accurate detection method for drug resistance of Plasmodium falciparum (P. falciparum). A quantitative real-time PCR (qPCR) assay has been developed that identifies the mutation at locus A256T in the P.falciparum multi-drug resistance(pfmdr1) gene producing amino acid change at position 86. The results of 198 samples detected by qPCR were consistent with nested PCR and sequencing, giving an accuracy of 94.3%. The sensitivity, specificity, positive and negative predictive value of qPCR were 85.7%, 97.6%, 90.0% and 96.4%, respectively. The results of qPCR are basically consistent with the nested PCR, which is expected to replace the nested PCR as a new molecular biological method for drug resistance detection, providing reliable technical support for global malaria prevention and control.
PubMed: 38909426
DOI: 10.1016/j.diagmicrobio.2024.116400 -
Supportive Care in Cancer : Official... Jun 2024
Topics: Humans; Pleural Effusion, Malignant; Pleurodesis; Povidone-Iodine; Doxycycline; Chest Tubes; Randomized Controlled Trials as Topic; Anti-Bacterial Agents
PubMed: 38909347
DOI: 10.1007/s00520-024-08670-5 -
The National Medical Journal of India 2023Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal...
Burden of malaria during pregnancy in perennial transmission settings of two densely forested and remote blocks (Baihar and Birsa) of district Balaghat, Madhya Pradesh, central India.
Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal outcomes in endemic areas. Methods We did a field-based study to assess the burden of MIP (prevalence at the time of enrolment and follow-up) and to identify risk factors for MIP in the Birsa and Baihar blocks of district Balaghat in Madhya Pradesh, which have perennial malaria transmission. Malaria screening (during 2015-2017) was done by microscopy and bivalent rapid diagnostic test (SD Bioline RDT, malaria antigen Plasmodium falciparum/Plasmodium vivax Pf/Pv). Dried blood spots were used for haemoglobin estimation. Sociodemographic details with past and present pregnancy status were obtained. A subset of pregnant women were followed up for malaria during pregnancy. Women were also screened for malaria post delivery. Malaria treatment was given as per the National Guidelines of 2013. Multivariate analysis was done to assess independent risk factors for malaria. Results A total of 1728 pregnant women were screened, of which 1651 were included in the final analysis. Malaria prevalence at first screening was 23.4% (Pf 88%). Prevalence and Pf parasitaemia both were significantly higher among primigravid (G1) compared to multigravid (G>2; p value 0.012 and 0.019, respectively). Pregnant women of the Baiga ethnic group were more likely to have malaria compared to those belonging to the Gond group (OR [95% CI]; 2.4 [1.7-3.4]; p<0.00001) and non-indigenous group (OR [95% CI]; 8.3 [3.9-19.7]; p<0.00001). Primigravid status of women, first and second trimester of pregnancy, women belonging to indigenous ethnic tribal group and cash crop insufficiency for whole year (a socioeconomic indicator) in the family were the independent risk factors for malaria. Conclusion MIP is a major public health problem in forested tribal settlements of Birsa and Baihar blocks of Balaghat district in Madhya Pradesh and requires immediate intervention.
Topics: Humans; Female; Pregnancy; India; Adult; Pregnancy Complications, Parasitic; Prevalence; Risk Factors; Malaria, Falciparum; Young Adult; Malaria, Vivax; Forests; Adolescent; Antimalarials; Plasmodium falciparum
PubMed: 38909309
DOI: 10.25259/NMJI_535_21 -
International Ophthalmology Jun 2024To assess the quality of hydroxychloroquine (HCQ)-induced retinopathy screening at a Canadian tertiary center, we concentrate on risk factor documentation within the...
PURPOSE
To assess the quality of hydroxychloroquine (HCQ)-induced retinopathy screening at a Canadian tertiary center, we concentrate on risk factor documentation within the electronic health record, in accordance with the 2016 AAO guidelines.
METHODS
We performed a retrospective quality assessment study based on chart review of patients who underwent screening for HCQ-induced retinopathy at the Centre Hospitalier de l'Université de Montréal (CHUM) from 2016 to 2019. We evaluated four key risk factors for HCQ-induced retinopathy: daily dose, duration of use, renal disease, and tamoxifen use, using a three-tier grading system (ideal, adequate, inadequate) for documentation assessment. Pareto and root cause analyses were conducted to identify potential improvement solutions.
RESULTS
Documentation quality varied in our study: daily dosage was 33% ideal, 31% appropriate, and 36% inappropriate. Duration of use documentation was 75% ideal, 2% adequate, and 24% inadequate. Renal disease documentation was only 6% ideal, with 62% adequate and 32% of charts lacking any past medical history. Among women's charts, tamoxifen use wasn't documented at all, with 65% adequately documenting medication lists. Pareto analysis indicated that improving renal disease and tamoxifen documentation could reduce 64% of non-ideal records, and enhancing daily dose documentation could decrease this by up to 90%.
CONCLUSION
Accurate documentation of key risk factors is critical for HCQ-induced retinopathy screening, impacting both exam initiation and frequency. Our study identifies potential improvements in the screening process at the hospital, referring physician, and ophthalmologist levels. Implementing integrated pathways could enhance patient experience and screening effectiveness.
Topics: Humans; Hydroxychloroquine; Retrospective Studies; Female; Retinal Diseases; Male; Middle Aged; Antirheumatic Agents; Hospitals, Teaching; Canada; Aged; Risk Factors; Mass Screening; Adult
PubMed: 38909150
DOI: 10.1007/s10792-024-03194-7 -
The American Journal of Clinical... Jun 2024In Senegal, anemia prevalence among women of reproductive age (WRA) decreased from 59% in 2005 to 54% in 2017. However, determinants of reduction in disease burden under...
BACKGROUND
In Senegal, anemia prevalence among women of reproductive age (WRA) decreased from 59% in 2005 to 54% in 2017. However, determinants of reduction in disease burden under challenging public health conditions have not been studied.
OBJECTIVE
To conduct a systematic in-depth assessment of the quantitative and qualitative determinants of anemia reduction among WRA in Senegal between 2005 and 2017.
METHODS
Standard Exemplars in Global Health methodology was used for quantitative analyses using Senegal's Demographic and Health Surveys. Qualitative analyses included a systematic literature review, program/policy analysis, and interviews with key stakeholders. A final Oaxaca-Blinder decomposition analysis (OBDA) evaluated the relative contribution of direct and indirect factors.
RESULTS
Among non-pregnant women (NPW), mean hemoglobin (Hb) increased from 11.4 g/dL in 2005 to 11.7 g/dL in 2017 (p<0.0001), corresponding to a 5%-point decline in anemia prevalence (58% to 53%). However, inequities by geographical region, household wealth, women's educational attainment, urban compared to rural residence, and antenatal care (ANC) during last pregnancy continue to persist. During this time period, several indirect nutrition programs were implemented, with stakeholders acknowledging the importance of these programs, but agreeing there needs to be more consistency, evaluation, and oversight for them to be effective. Our OBDA explained 59% of the observed change in mean Hb, with family planning (25%), malaria prevention programs (17%), use of iron and folic acid (IFA) during last pregnancy (17%), and improvement in women's empowerment (12%) emerging as drivers of anemia decline, corroborating our qualitative and policy analyses.
CONCLUSIONS
Despite a reduction in anemia prevalence, anemia remains a severe public health problem in Senegal. To protect the gains achieved to date, as well as accelerate reduction in WRA anemia burden, focused efforts to reduce gender and social disparities, and improve coverage of health services, such as family planning, IFA, and antimalarial programs, are needed.
PubMed: 38908516
DOI: 10.1016/j.ajcnut.2024.05.031 -
BMC Infectious Diseases Jun 2024Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the... (Review)
Review
BACKGROUND
Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis.
CASE PRESENTATION
We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis.
CONCLUSIONS
To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.
Topics: Humans; Male; Nocardia Infections; Aged; Anti-Bacterial Agents; Nocardia; Fever of Unknown Origin; Immunocompromised Host; Trimethoprim, Sulfamethoxazole Drug Combination; Testis; Orchitis
PubMed: 38907186
DOI: 10.1186/s12879-024-09521-8 -
Drug Safety Jun 2024Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude... (Review)
Review
INTRODUCTION
Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs.
METHODS
We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources.
RESULTS
We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries.
CONCLUSION
The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.
PubMed: 38907172
DOI: 10.1007/s40264-024-01445-1 -
Medicine Jun 2024Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system... (Review)
Review
RATIONALE
Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon.
PATIENT CONCERNS
A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation.
DIAGNOSES
The patient was diagnosed with a central nervous system infection.
INTERVENTIONS
Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders.
OUTCOMES
Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided.
CONCLUSIONS
The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective.
LESSION
Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.
Topics: Humans; Scrub Typhus; Male; Adolescent; Anti-Bacterial Agents; Doxycycline; Orientia tsutsugamushi; Meningitis, Bacterial
PubMed: 38905360
DOI: 10.1097/MD.0000000000038613