RESUMO
BACKGROUND: Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. METHODS: NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50-199 copies/mL on <25% of measurements), pLLV (VL of 50-199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200-1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. RESULTS: Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42-4.93]), and hLV (2.29 [1.78-2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06-1.68]) and antiretroviral use prior to ART (1.79 [1.34-2.38]). Older age at ART initiation (0.71 [0.61-0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51-0.90]) or integrase strand transfer inhibitor use (0.26 [0.13-0.53]) were protective. CONCLUSION: Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1 , Carga Viral , Viremia , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/diagnóstico , Humanos , Masculino , Fatores de Risco , Falha de Tratamento , Adulto JovemRESUMO
Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.
Assuntos
Injúria Renal Aguda/etiologia , Oxalato de Cálcio/química , Nefrite Intersticial/etiologia , Escleroderma Sistêmico/complicações , Injúria Renal Aguda/metabolismo , Idoso , Feminino , Motilidade Gastrointestinal/fisiologia , Trânsito Gastrointestinal/fisiologia , Humanos , Absorção Intestinal/efeitos dos fármacos , Enteropatias/etiologia , Pseudo-Obstrução Intestinal/etiologia , Intestino Delgado/microbiologia , Nefrite Intersticial/metabolismo , Inibidores da Síntese de Ácido Nucleico/efeitos adversos , Rifamicinas/efeitos adversos , RifaximinaRESUMO
Background: The consequences of low-level viremia in people with HIV are unclear. We used data from the US Military HIV Natural History Study to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs). Methods: Included participants initiated antiretroviral therapy after 1996 and had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50â copies/mL, ≥6 months after antiretroviral therapy initiation. VLs were categorized as lower levels of LLV (51-199â copies/mL), higher level of low-level viremia (HLLV; 200-999â copies/mL), and (VF; ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS; ie, VL <50â copies/mL). Viral blips (ie, VLs between 50 and 999â copies/mL that are preceded and succeeded by VL <50â copies/mL) were analyzed in the VS category. Cox proportional hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% confidence intervals are presented. Results: A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3 [1.2-1.4]), HLLV (1.6 [1.5-1.7]), and virologic failure (1.7 [1.7-1.8]). Conclusions: The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study.
RESUMO
BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected disease and a public health problem in Latin America. The diagnosis of CL in poor hyperendemic regions relies to large extent on the identification of amastigotes in Giemsa-stained smears. There is an urgent need for a rapid, sensitive and low cost diagnostic method for use in field conditions for CL as current modalities are not readily available. The primary objective of this study was to determine the sensitivity and specificity of the FDA-cleared CL Detect Rapid Test in Peru, using modified test procedures rather than the instructions-for-use, by 1) increasing the extraction time and 2) increasing the volume of the sample added to the test strip. CL Detect Rapid Test results were compared against microscopy and kDNA-PCR, for the diagnosis of CL in ulcerated lesions. In addition, we compared two collection methods the dental broach used and mentioned in the CL Detect insert and the standard less invasive and easier to conduct scrapping method. METHODOLOGY: Participants were patients who presented for medical consultation due to a suspected CL lesion. Four samples from the index lesion were collected using a dental broach, per package insert, and lancet scraping and tested by the modified CL Detect Rapid Test, microscopy, and PCR. PRINCIPAL FINDINGS: A total of 156 subjects were eligible and evaluated. The modified CL Detect sensitivity was higher in specimens obtained by scraping (83.3%) than those from dental broach (64.2%). The specificity was lower in scrapings (77.8%) with a false positive rate of 22.2% compared with dental broach samples (91.7%) with a false positive rate of 8.3%. However, molecular analysis showed that all 8 false negative microscopy scrapings (those positive by modified CL Detect and negative by microscopy) were positive by kDNA-PCR, meaning that the modified CL Detect was more sensitive than microscopy. CONCLUSIONS: These modifications to the package insert that resulted in a diagnostic sensitivity (83.3%) comparable to microscopy for species found in Peru may enable earlier anti-leishmanial drug treatment decisions based on a positive result from the CL Detect Rapid Test alone until further diagnostic tests like microscopy and PCR can be performed. TRIAL REGISTRATION: NCT03762070; Clinicaltrials.gov.
Assuntos
Leishmania , Leishmaniose Cutânea , Humanos , DNA de Cinetoplasto , Peru , Leishmaniose Cutânea/diagnóstico , Leishmania/genética , Reação em Cadeia da Polimerase/métodos , Sensibilidade e EspecificidadeRESUMO
Malaria is a major health problem in Peru despite substantial progress achieved by the ongoing malaria elimination program. This study explored the population genetics of 63 Plasmodium falciparum and 170 P. vivax cases collected in the Peruvian Amazon Basin between 2015 and 2019. Microscopy and PCR were used for malaria detection and positive samples were genotyped at neutral and drug resistance-associated regions. The P. falciparum population exhibited a low nucleotide diversity (π = 0.02) whereas the P. vivax population presented a higher genetic diversity (π = 0.34). All P. falciparum samples (n = 63) carried chloroquine (CQ) resistant mutations on Pfcrt. Most P. falciparum samples (53 out of 54) carried sulfadoxine (SD) resistant mutations on Pfdhfr and Pfdhps. No evidence was found of artemisinin resistance mutations on kelch13. Population structure showed that a single cluster accounted for 93.4% of the P. falciparum samples whereas three clusters were found for P. vivax. Our study shows a low genetic diversity for both species with significant differences in genetic sub-structuring. The high prevalence of CQ-resistance mutations could be a result of indirect selection pressures driven by the P. vivax treatment scheme. These results could be useful for public health authorities to safeguard the progress that Peru has achieved towards malaria elimination.
Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária Vivax , Malária , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Resistência a Medicamentos/genética , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Nucleotídeos/uso terapêutico , Peru/epidemiologia , Plasmodium falciparum/genética , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Sulfadoxina/uso terapêuticoRESUMO
Peru was the first country where pfhrp2 and pfhrp3 gene deletions were detected despite the fact that rapid diagnostics tests are not commonly used for confirmatory malaria diagnosis. This context provides a unique scenario to study the dynamics of pfhrp2 and pfhrp3 gene deletions without apparent RDTs selection pressure. In this study we characterized the presence of pfhrp2 and pfhrp3 genes on 325 P. falciparum samples collected in Iquitos and surrounding communities between 2011 and 2018 in order to understand the dynamics of gene deletion prevalence, potential associations with clinical symptomatology and parasite genetic background. P. falciparum presence was confirmed by microscopy and PCR of 18 s rRNA, pfmsp1 and pfmsp2. Gene deletions were assessed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCRs. Confirmation of absence of HRP2 expression was assessed by ELISA of HRP2 and pLDH. Genotyping of 254 samples were performed using a panel of seven neutral microsatellite markers. Overall, pfhrp2 and pfhrp3 dual gene deletions were detected in 67% (217/324) parasite samples. Concordance between pfhrp2 deletion and negligible HRP2 protein levels was observed (Cohen's Kappa = 0.842). Prevalence of gene deletions was heterogeneous across study sites (adjusted p < 0.005) but there is an overall tendency towards increase through time in the prevalence of dual pfhrp2/3-deleted parasites between 2011 (14.3%) and 2016 (88.39%) stabilizing around 65% in 2018. Dual deletions increase was associated with dominance of a single new parasite haplotype (H8) which rapidly spread to all study sites during the 8 study years. Interestingly, participants infected with dual pfhrp2/3-deleted parasites had a significantly lower parasitemias than those without gene deletions in this cohort. Our study showed the increase of pfhrp2/3 deletions in the absence of RDTs pressure and a clonal replacement of circulating lines in the Peruvian Amazon basin. These results suggest that other factors linked to the pfhrp2/3 deletion provide a selective advantage over non-deleted strains and highlight the need for additional studies and continuing surveillance.
Assuntos
Malária Falciparum , Plasmodium falciparum , Humanos , Plasmodium falciparum/genética , Peru/epidemiologia , Histidina/genética , Deleção de Genes , Malária Falciparum/parasitologiaRESUMO
A 40-year-old woman was referred to infectious disease specialists for a Mycobacterium mageritense skin infection following mastectomy and bilateral reconstruction with deep inferior epigastric perforator flap. Her case demonstrates the difficulty in treating non-tuberculosis mycobacterial infections, especially the rarely seen species. She failed to respond to dual antibiotic therapy containing imipenem-cilastin despite reported sensitivity. Additionally, her course was complicated by intolerance to various regimens, including gastrointestinal distress, a drug rash with eosinophilia and systemic symptoms, and tendinopathy. With few published data, no treatment guidelines, and limited medications from which to choose for M. mageritense, her treatment posed a challenge. She ultimately required aggressive surgical intervention and a triple therapy antibiotic regimen. The duration of our patient's treatment and the extent of her complications suggest a potential need for early surgical intervention in postsurgical wounds infected with M. mageritense that do not respond to conventional treatment.
Assuntos
Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Desbridamento/efeitos adversos , Doxiciclina/uso terapêutico , Mamoplastia , Mastectomia , Mycobacteriaceae/isolamento & purificação , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Neoplasias da Mama/cirurgia , Feminino , Humanos , Retalho PerfuranteRESUMO
Previous studies have shown that P. falciparum parasites in South America have undergone population bottlenecks resulting in clonal lineages that are differentially distributed and that have been responsible for several outbreaks different endemic regions. In this study, we explored the genomic profile of 18 P. falciparum samples collected in the Peruvian Amazon Basin (Loreto) and 6 from the Peruvian North Coast (Tumbes). Our results showed the presence of three subpopulations that matched previously typed lineages in Peru: Bv1 (n = 17), Clonet D (n = 4) and Acre-Loreto type (n = 3). Gene coverage analysis showed that none of the Bv1 samples presented coverage for pfhrp2 and pfhrp3. Genotyping of drug resistance markers showed a high prevalence of Chloroquine resistance mutations S1034C/N1042D/D1246Y in pfmdr1 (62.5%) and K45T in pfcrt (87.5%). Mutations associated with sulfadoxine and pyrimethamine treatment failure were found on 88.8% of the Bv1 samples which were triple mutants for pfdhfr (50R/51I/108N) and pfdhps (437G/540E/581G). Analysis of the pfS47 gene that allows P. falciparum to evade mosquito immune responses showed that the Bv1 lineage presented one pfS47 haplotype exclusive to Loreto and another haplotype that was present in both Loreto and Tumbes. Furthermore, a possible expansion of Bv1 was detected since 2011 in Loreto. This replacement could be a result of the high prevalence of CQ resistance polymorphisms in Bv1, which could have provided a selective advantage to the indirect selection pressures driven by the use of CQ for P. vivax treatment.
Assuntos
Evolução Molecular , Plasmodium falciparum/genética , Polimorfismo de Nucleotídeo Único , Antiprotozoários/toxicidade , Cloroquina/toxicidade , Resistência a Medicamentos/genética , Frequência do Gene , Genoma de Protozoário , Mosquitos Vetores/parasitologia , Peru , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Pirimetamina/toxicidade , Sulfadoxina/toxicidadeRESUMO
A major challenge for malaria is the lack of tools for accurate and timely diagnosis in the field which are critical for case management and surveillance. Microscopy along with rapid diagnostic tests are the current mainstay for malaria diagnosis in most endemic regions. However, these methods present several limitations. This study assessed the accuracy of Gazelle, a novel rapid malaria diagnostic device, from samples collected from the Peruvian Amazon between 2019 and 2020. Diagnostic accuracy was compared against microscopy and two rapid diagnostic tests (SD Bioline and BinaxNOW) using 18ssr nested-PCR as reference test. In addition, a real-time PCR assay (PET-PCR) was used for parasite quantification. Out of 217 febrile patients enrolled and tested, 180 specimens (85 P. vivax and 95 negatives) were included in the final analysis. Using nested-PCR as the gold standard, the sensitivity and specificity of Gazelle was 88.2% and 97.9%, respectively. Using a cutoff of 200 parasites/µl, Gazelle's sensitivity for samples with more than 200 p/uL was 98.67% (95%CI: 92.79% to 99.97%) whereas the sensitivity for samples lower than 200 p/uL (n = 10) was 12.5% (95%CI: 0.32% to 52.65%). Gazelle's sensitivity and specificity were statistically similar to microscopy (sensitivity = 91.8, specificity = 100%, p = 0.983) and higher than both SD Bioline (sensitivity = 82.4, specificity = 100%, p = 0.016) and BinaxNOW (sensitivity = 71.8%, specificity = 97.9%, p = 0.002). The diagnostic accuracy of Gazelle for malaria detection in P. vivax infections was comparable to light microscopy and superior to both RDTs even in the presence of low parasitemia infections. The performance of Gazelle makes it a valuable tool for malaria diagnosis and active case detection that can be utilized in different malaria-endemic regions.
Assuntos
Malária Vivax/diagnóstico , Plasmodium vivax , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
Malaria elimination efforts in Peru have dramatically reduced the incidence of cases in the Amazon Basin. To achieve the elimination, the detection of asymptomatic and submicroscopic carriers becomes a priority. Therefore, efforts should focus on tests sensitive enough to detect low-density parasitemia, deployable to resource-limited areas and affordable for large screening purposes. In this study, we assessed the performance of the Malachite-Green LAMP (MG-LAMP) using heat-treated DNA extraction (Boil & Spin; B&S MG-LAMP) on 283 whole blood samples collected from 9 different sites in Loreto, Peru and compared its performance to expert and field microscopy. A real-time PCR assay was used to quantify the parasite density. In addition, we explored a modified version of the B&S MG-LAMP for detection of submicroscopic infection in 500 samples and compared the turnaround time and cost of the MG-LAMP with microscopy. Compared to expert microscopy, the genus B&S MG-LAMP had a sensitivity of 99.4% (95%CI: 96.9%- 100%) and specificity of 97.1% (95%CI: 91.9%- 99.4%). The P. vivax specific B&S MG-LAMP had a sensitivity of 99.4% (96.6%- 100%) and specificity of 99.2% (95.5%- 100%) and the P. falciparum assay had a sensitivity of 100% (95%CI: 78.2%- 100%) and specificity of 99.3% (95%CI: 97.3%- 99.8%). The modified genus B&S MG-LAMP assay detected eight submicroscopic malaria cases (1.6%) which the species-specific assays did not identify. The turnaround time of B&S MG-LAMP was faster than expert microscopy with as many as 60 samples being processed per day by field technicians with limited training and utilizing a simple heat-block. The modified B&S MG-LAMP offers a simple and sensitive molecular test of choice for the detection of submicroscopic infections that can be used for mass screening in resources limited facilities in endemic settings nearing elimination and where a deployable test is required.
Assuntos
Malária Falciparum/diagnóstico , Microscopia/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Plasmodium falciparum/isolamento & purificação , Corantes de Rosanilina/química , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Peru/epidemiologiaRESUMO
BACKGROUND: Cutaneous leishmaniasis (CL) is an endemic disease in Brazil that is highly prevalent in the northern region of the country. Although there is a continuous and growing number of cases registered in the state of Roraima, there is limited information regarding the species of Leishmania that affect the human population. In this study, we aimed to characterize which Leishmania species cause human disease in those presenting with cutaneous leishmaniasis in endemic areas of the State of Roraima. METHODS: We conducted a prospective surveillance study between 2016 to 2018 in health centers located in the State of Roraima, Brazil. Participants with clinical suspicion of CL were enrolled and provided lesion samples for parasitological detection by microscopy. A subset of the samples was tested by polymerase chain reaction and sequencing of the internal transcribed spacer 1 (ITS-1 PCR) for molecular species identification. RESULTS: A total of 262 participants were enrolled in this study. Of those, 129 (49.27%) were positive by parasitological examination. Most positive subjects (81.58%) were male, and most cases presented a single lesion (80.26%). ITS-1 PCR and sequencing on a subset of 76 samples allowed us to detect nine different species of Leishmania: L. (V.) braziliensis, L (V.) panamensis, L. (V.) guyanensis, L. (V.) naiffi, L. (V.) shawi, L.(V.) utingensis, L. (V.) lindenbergi, L. (L.) amazonensis and L. (L.) mexicana. CONCLUSIONS: Our study provides the first assessment of circulating species of Leishmania in the State of Roraima, Brazil, and shows the high diversity in this region. This study opens the path for further research on the transmission of leishmaniasis in the northernmost Brazilian State including vector and reservoir surveillance as well as for intensification of investigation and control activities against CL in the region.
Assuntos
Leishmania/genética , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , DNA de Protozoário/genética , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Leishmania/classificação , Leishmania/isolamento & purificação , Leishmania/patogenicidade , Leishmania braziliensis/genética , Leishmania braziliensis/patogenicidade , Leishmania guyanensis/genética , Leishmania guyanensis/patogenicidade , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sequência de DNA , Adulto JovemRESUMO
Cutaneous leishmaniasis (CL) is a diverse human disease caused by more than 20 Leishmania species transmitted by the bite of an infected sand fly. Diagnostic testing is recommended to confirm infection and determine the infecting species. Treatment decisions are complex and providers should consider infecting species, patient comorbidities, extent and location of lesions, and previous treatments. There is no single universal treatment for CL and some treatment can have toxicity. Treatment should be individualized and factors, such as self-healing nature of this infection, risk of metastatic complications (ie, mucosal leishmaniasis), and patient wishes, need to be included in individual risk-benefit treatment decisions.
Assuntos
Antiprotozoários/uso terapêutico , Gerenciamento Clínico , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Anfotericina B/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Metanálise como Assunto , Técnicas de Diagnóstico MolecularRESUMO
International travel to the developing world is becoming more common in elderly patients (defined here as individuals greater than 65 years old). When providing pre-travel counseling, providers must appreciate the changing physiology, comorbidities, immunity and pharmacokinetics associated with the aging process to prepare elderly patients for the stressors of international travel. These guidelines present an evidence-based approach to pre-travel counseling, immunization, and pharmacology concerns unique to elderly patients seeking care in a travel clinic setting.