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Le Infezioni in Medicina 2023cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and...
BACKGROUND
cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/μL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed.
RESULTS
the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for , while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement.
CONCLUSIONS
despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).
PubMed: 37701378
DOI: 10.53854/liim-3103-15 -
SAGE Open Medicine 2023Malaria in pregnancy is associated with adverse pregnancy outcomes including maternal anaemia and low birthweight. Uptake of preventive interventions is sub-optimal in...
Interventions for malaria prevention in pregnancy; factors influencing uptake and their effect on pregnancy outcomes among post-natal women in a tertiary facility in the Volta Region of Ghana.
OBJECTIVES
Malaria in pregnancy is associated with adverse pregnancy outcomes including maternal anaemia and low birthweight. Uptake of preventive interventions is sub-optimal in sub-Saharan Africa including Ghana. Understanding local-level factors that influence uptake of these interventions can enhance control. The study assessed uptake of intermittent preventive treatment of malaria during pregnancy using sulphadoxine-pyrimethamine (IPTp-SP) and insecticide-treated net (ITN) use, their determinants and effects on pregnancy outcomes.
METHODS
A cross-sectional study involving 349 post-partum women was conducted from 25 August 2022 to 9 October 2022 at the Ho Teaching Hospital. A structured questionnaire was used to collect data on participant socio-demographics, ITN use, number of doses of sulphadoxine-pyrimethamine received, knowledge of malaria in pregnancy, haemoglobin levels and birth weight among others. Summary statistics were reported as frequencies, percentages and means. Associations between exposure and outcome variables were assessed using logistic regression methods and odds ratios reported with 95% confidence intervals. Statistical significance was concluded at < 0.05.
RESULTS
More than 80% (291) of respondents received ⩾3 doses of intermittent preventive treatment using sulphadoxine-pyrimethamine and 64.8% (226) slept under ITNs the night before the survey. Age >25 years, employment, good knowledge of malaria in pregnancy, parity ⩾2 and initiating antenatal care visits in the first trimester facilitated the uptake of these interventions. Receiving ⩾3 doses of sulphadoxine-pyrimethamine was associated with having normal-weight babies (adjusted odds ratio 2.80, 95% CI: 1.07, 7.34; = 0.036) while ITN use was associated with having term babies (adjusted odds ratio 2.72, 95% CI: 1.24, 5.90; = 0.013) and normal maternal haemoglobin concentration at term (adjusted odds ratio 1.57, 95% CI: 1.01, 2.47; = 0.044).
CONCLUSIONS
The interventions were beneficial against low birthweight and preterm births which predispose to neonatal deaths and poor cognitive function in children. Malaria in pregnancy health campaigns should be intensified, especially among younger-aged primigravidae, to increase their knowledge of the condition as a way to further improve uptake of these preventive interventions.
PubMed: 37719169
DOI: 10.1177/20503121231199653 -
PloS One 2023Malaria in pregnancy is a global public health problem with the majority of its impact seen in sub-Saharan Africa. Pregnant women with malaria infection are at risk of...
INTRODUCTION
Malaria in pregnancy is a global public health problem with the majority of its impact seen in sub-Saharan Africa. Pregnant women with malaria infection are at risk of adverse maternal outcomes. In Ghana, malaria in pregnancy accounts for about 17.6% of outpatient department attendance. Ashanti region is among the three regions with the highest malaria prevalence in pregnancy, particularly in the Ejisu Municipality. The study, therefore, assessed the prevalence and determinants of malaria infection among pregnant women seeking antenatal care at the Ejisu Government Hospital in Ghana.
METHODS
A cross-sectional study design with a convenience sampling technique was used to select 140 respondents for the study. Primary data such as age and residence of respondents were collected using a questionnaire and secondary data such as gestational age and Sulphadoxine Pyrimethamine (SP) administration were collected from clients' maternal health record booklet. Bivariate and multivariate logistic regression analysis were used to assess the association between the malaria infection and the independent variables, and a p-value of < 0.05 was considered statistically significant.
RESULTS
The overall prevalence of malaria in pregnancy was 24 (17.1%). Most of the respondents had received counselling and health education 126 (90%), two or more doses of SP 95 (87.2%), Insecticide Treated Net (ITN) 99 (70.7%) and were sleeping under ITN 104 (74.3%). Multivariate logistic regression analysis showed a statistically significant association between malaria infection and sleeping under ITN (AOR = 0.05; 95% CI = 0.01-0.28, p< .001), the use of insecticide mosquito spray (AOR = 0.27; 95% CI = 0.09-0.84, p = .045) and reason for not using ITN due to the use of other preventive measures (AOR = 0.06; 95% CI = 0.01-0.61, p = .017).
CONCLUSION
There was a high prevalence of malaria infection among study respondents despite the high usage of preventive measures for malaria in this study. It is therefore crucial that stakeholders in malaria control identify effective strategies to curb malaria transmission globally.
Topics: Female; Pregnancy; Humans; Pregnant Women; Antimalarials; Cross-Sectional Studies; Ghana; Prevalence; Insecticides; Pregnancy Complications, Parasitic; Malaria; Drug Combinations; Government; Hospitals
PubMed: 37903177
DOI: 10.1371/journal.pone.0293420 -
Acta Tropica Dec 2023The 2022 malaria WHO reported around 4000 P. knowlesi infections in the South-East Asia region. In the same period, 72 positive cases were reported by the Department of...
BACKGROUND
The 2022 malaria WHO reported around 4000 P. knowlesi infections in the South-East Asia region. In the same period, 72 positive cases were reported by the Department of Disease Control in Thailand, suggesting a persistent infection. Little is known about dihydrofolate reductase (pkdhfr) and dihydropteroate synthase (pkdhps), putative antimalarial resistance markers for P. knowlesi. The relevant amplification and sequencing protocol are presently unavailable. In this study, we developed a protocol for amplifying and evaluating pkdhps mutations. The haplotype pattern of pkdhfr-pkdhps in Thai isolates was analyzed, and the effects of these pkdhps mutations were predicted by using a computer program.
METHODS
Pkdhps were amplified and sequenced from 28 P. knowlesi samples collected in 2008 and 2020 from nine provinces across Thailand. Combining pkdhfr sequencing data from previous work with pkdhps data to analyze polymorphisms of pkdhfr and pkdhps haplotype. Protein modeling and molecular docking were constructed using two inhibitors, sulfadoxine and sulfamethoxazole, and further details were obtained through analyses of protein-ligand interactions by using the Genetic Optimisation for Ligand Docking program. A phylogenetic tree cluster analysis was reconstructed to compare the P. knowlesi Malaysia isolates.
RESULTS
Five nonsynonymous mutations in the pkdhps were detected outside the equivalence of the binding pocket sites to sulfadoxine and sulfamethoxazole, which are at N391S, E421G, I425R, A449S, and N517S. Based on the modeling and molecular docking analyses, the N391S and N517S mutations located close to the enzyme-binding pocket demonstrated a different docking score and protein-ligand interaction in loop 2 of the enzyme. These findings indicated that it was less likely to induce drug resistance. Of the four haplotypes of pkdhfr-pkdhps, the most common one is the R34L pkdhfr mutation and the pkdhps quadruple mutation (GRSS) at E421G, I425R, A449S, and N517S, which were observed in P. knowlesi in southern Thailand (53.57%). Based on the results of neighbor-joining analysis for pkdhfr and pkdhps, the samples isolated from eastern Thailand displayed a close relationship with Cambodia isolates, while southern Thailand isolates showed a long branch separated from the Malaysian isolates.
CONCLUSIONS
A new PCR protocol amplification and evaluation of dihydropteroate synthase mutations in Knowlesi (pkdhps) has been developed. The most prevalent pkdhfr-pkdhps haplotypes (53.57%) in southern Thailand are R34L pkdhfr mutation and pkdhps quadruple mutation. Further investigation requires additional phenotypic data from clinical isolates, transgenic lines expressing mutant alleles, or recombinant proteins.
Topics: Sulfadoxine; Pyrimethamine; Tetrahydrofolate Dehydrogenase; Dihydropteroate Synthase; Plasmodium knowlesi; Thailand; Molecular Docking Simulation; Ligands; Phylogeny; Antimalarials; Drug Resistance; Sulfamethoxazole; Plasmodium falciparum
PubMed: 37683820
DOI: 10.1016/j.actatropica.2023.107016 -
Pathogens and Global Health Jul 2023Malaria in Pregnancy (MiP) leading to morbidity and mortality is a major public health problem that poses significant risk to pregnant women and their fetus. To cope... (Review)
Review
Malaria in Pregnancy (MiP) leading to morbidity and mortality is a major public health problem that poses significant risk to pregnant women and their fetus. To cope with this alarming situation, administration of Sulfadoxine-pyrimethamine (SP) drugs to pregnant women as an intermittent preventive treatment (IPT) from 16 weeks of gestation is recommended by the World Health Organization (WHO) guidelines. We conducted a comprehensive search of published articles related to MiP in last 10 years with predefined keywords or their synonyms. The mapping of malaria in pregnant women showed a prevalence rate up to 35% in many countries. Although IPTp-SP has been implemented in endemic regions since several years but the IPTp-SP coverage percentage vary from country to country and continue to remain below the target of 80%. Major reasons for low IPTp-SP involve gestational age at first prenatal visit, level of education, place of residence, knowledge of IPTp-SP benefits, and use of antenatal services. Several challenges including the emergence of septuple and octuple SP-resistant parasites is reported from many countries which make the prophylactic use of IPTp-SP currently debatable. This narrative review addresses the barriers for optimal use of IPTp-SP and discusses alternative approaches to increase the use and effectiveness of SP intervention for preventing MiP. The COVID pandemic has drastically affected the public health disrupting the management of diseases worldwide. In view of this, a brief summary of COVID impact on MiP situation is also included.
Topics: Female; Pregnancy; Humans; Pyrimethamine; Sulfadoxine; Antimalarials; Pregnant Women; Pharmaceutical Preparations; COVID-19; Malaria; Drug Combinations; Pregnancy Complications, Parasitic
PubMed: 36177658
DOI: 10.1080/20477724.2022.2128563 -
Parasites & Vectors Aug 2023Quercetin (QUE) is a natural polyphenol known to have numerous pharmacological properties against infectious and non-infectious diseases. Azithromycin (AZ) is an...
Quercetin (QUE) is a natural polyphenol known to have numerous pharmacological properties against infectious and non-infectious diseases. Azithromycin (AZ) is an antibiotic that belongs to the azalide class of antimicrobials and an antiparasitic that is known to be effective in combination with clindamycin against pyrimethamine/sulfadiazine-resistant Toxoplasma gondii tachyzoites in clinical settings. Both compounds are known to target protein synthesis and have anti-inflammatory properties. However, little is known about QUE and AZ synergistic interaction against T. gondii growth. Here, we report for the first time the effects of the combination of QUE and AZ on T. gondii growth. The 50% inhibitory concentration (IC) for QUE at 72 h of interaction was determined to be 0.50 µM, whereas AZ gave an IC value of 0.66 µM at 72 h of interaction with parasites. Combination testing of QUE and AZ in a ratio of 2:1 (QUE:AZ) showed an IC value of 0.081 µM. Interestingly, a fractional inhibitory index value of 0.28 was observed, indicating a strong synergy. QUE was also found to upregulate the generation of reactive oxygen species and cause dysfunction of the mitochondria membrane of both intracellular and extracellular T. gondii tachyzoites. Overall, the results indicate that QUE is a novel lead capable of synergizing with AZ for inhibiting T. gondii growth and may merit future investigation in vivo for possible combination drug development.
Topics: Animals; Toxoplasma; Azithromycin; Quercetin; Parasites; Anti-Infective Agents; Cell Proliferation
PubMed: 37537675
DOI: 10.1186/s13071-023-05849-3 -
Outcomes of trimethoprim/ sulfamethoxazole treatment for ocular toxoplasmosis in Congolese patients.BMC Ophthalmology Oct 2023Ocular toxoplasmosis (OT) is the leading cause of infectious posterior uveitis in several areas worldwide. The combination of Trimethoprim/Sulfamethoxazole (TMP/SMX) has...
BACKGROUND
Ocular toxoplasmosis (OT) is the leading cause of infectious posterior uveitis in several areas worldwide. The combination of Trimethoprim/Sulfamethoxazole (TMP/SMX) has been presented as an attractive alternative to the "classic' treatment therapy (Pyrimethamine/Sulfadiazine).
METHODS
A prospective study was carried out between February 2020 and September 2021 in 2 ophthalmic centers in Kinshasa. This study aimed to describe TMP/SMX treatment outcomes for OT in a cohort of immunocompetent Congolese patients.
RESULTS
54 patients were included, with a mean age at presentation of 37.5 ± 13.6 years old and a Male-Female ratio of 1.45:1. Three patients (5.6%) presented a recurrence during the follow-up period. At the end of the follow-up, improvement in VA and resolution of inflammation concerned 75.9% and 77.5% of patients, respectively. Cataracts (3.7%), macular scars (3.7%), and vitreous opacities (3.7%) were the principal causes of non-improvement in VA. Treatment-related adverse events were present in 10 patients (18.5%); gastrointestinal (14.8%) and dermatological (3.7%) adverse events were the most frequent. Dermatological adverse events led to discontinuation of treatment.
CONCLUSION
TMP/SMX regimen appears to be a safe and effective treatment for OT in Congolese patients. The low cost and the accessibility of the molecules make this regimen an option for treating OT in resource-limited countries.
Topics: Humans; Male; Female; Young Adult; Adult; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Toxoplasmosis, Ocular; Pyrimethamine; Prospective Studies; Democratic Republic of the Congo
PubMed: 37907920
DOI: 10.1186/s12886-023-03183-x -
Scientific Reports Jul 2023Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in...
Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing.
Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt, Pfmdr1, Pfdhps, Pfdhfr, and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (Pfdhfr/Pfdhps: N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.
Topics: Pregnancy; Female; Humans; Kenya; Malaria, Falciparum; Antimalarials; Pyrimethamine; Sulfadoxine; Malaria; Plasmodium falciparum; Drug Resistance; Drug Combinations; High-Throughput Nucleotide Sequencing
PubMed: 37452073
DOI: 10.1038/s41598-023-38481-3 -
Malaria Journal Jul 2023Artemisinin-based combinations therapy (ACT) is the current frontline curative therapy for uncomplicated malaria in Burkina Faso. Sulfadoxine-pyrimethamine (SP) is used...
BACKGROUND
Artemisinin-based combinations therapy (ACT) is the current frontline curative therapy for uncomplicated malaria in Burkina Faso. Sulfadoxine-pyrimethamine (SP) is used for the preventive treatment of pregnant women (IPTp), while SP plus amodiaquine (SP-AQ) is recommended for children under five in seasonal malaria chemoprevention (SMC). This study aimed to assess the proportions of mutations in the P. falciparum multidrug-resistance 1 (Pfmdr1), P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum dihydrofolate reductase (pfdhfr), and P. falciparum dihydropteroate synthase (pfdhps), genes from isolates collected during household surveys in Burkina Faso.
METHODS
Dried blood spots from Plasmodium falciparum-positive cases at three sites (Orodara, Gaoua, and Banfora) collected during the peak of transmission were analysed for mutations in Pfcrt (codons 72-76, 93, 97, 145, 218, 343, 350 and 353), Pfmdr-1 (codons 86, 184, 1034, 1042 and 1246) dhfr (codons 51, 59, 108, 164) and dhps (at codons 431, 436, 437, 540, 581, 613) genes using deep sequencing of multiplexed Polymerase chaine reaction (PCR) amplicons.
RESULTS
Of the 377 samples analysed, 346 (91.7%), 369 (97.9%), 368 (97.6%), and 374 (99.2%) were successfully sequenced for Pfcrt, Pfmdr-1, dhfr, and dhps, respectively. Most of the samples had a Pfcrt wild-type allele (89.3%). The 76T mutation was below 10%. The most frequent Pfmdr-1 mutation was detected at codon 184 (Y > F, 30.9%). The single mutant genotype (NFSND) predominated (66.7%), followed by the wild-type genotype (NYSND, 30.4%). The highest dhfr mutations were observed at codon 59R (69.8%), followed by codons 51I (66.6%) and 108 N (14.7%). The double mutant genotype (ACIRSI) predominated (52.4%). For mutation in the dhps gene, the highest frequency was observed at codon 437 K (89.3%), followed by codons 436 A (61.2%), and 613 S (14.4%). The double mutant genotype (IAKKAA) and the single mutant genotype (ISKKAA) were predominant (37.7% and 37.2%, respectively). The most frequent dhfr/dhps haplotypes were the triple mutant ACIRSI/IAKKAA (23%), the wild-type ACNCSI/ISKKAA (19%) and the double mutant ACIRSI/ISKKAA (14%). A septuple mutant ACIRNI/VAKKGA was observed in 2 isolates from Gaoua (0.5%).
CONCLUSION
The efficacy of ACT partner drugs and drugs used in IPTp and SMC does not appear to be affected by the low proportion of highly resistant mutants observed in this study. Continued monitoring, including molecular surveillance, is critical for decision-making on effective treatment policy in Burkina Faso.
Topics: Humans; Child; Female; Pregnancy; Plasmodium falciparum; Antimalarials; Burkina Faso; Pyrimethamine; Sulfadoxine; Malaria, Falciparum; Malaria; Mutation; Tetrahydrofolate Dehydrogenase; Drug Combinations; Drug Resistance; Codon
PubMed: 37474966
DOI: 10.1186/s12936-023-04645-9 -
The American Journal of Tropical... May 2024Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of...
Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of >15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with >15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate-sulfadoxine-pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.
Topics: Plasmodium falciparum; Pyrimethamine; Sulfadoxine; India; Drug Resistance; Antimalarials; Drug Combinations; Humans; Malaria, Falciparum; Artemisinins; Tetrahydrofolate Dehydrogenase; Genetic Markers; Dihydropteroate Synthase; Protozoan Proteins
PubMed: 38574550
DOI: 10.4269/ajtmh.23-0631