Immunological Criteria Research Articles

Identification of misdiagnosed HIV clients in an Early Access to ART for All implementation study in Swaziland.

Introduction: Rapid diagnostic testing has made HIV diagnosis and subsequent treatment more accessible. However, multiple factors, including improper implementation of testing strategies and clerical errors, have been reported to lead to HIV misdiagnosis. The World Health Organization has recommended HIV retesting prior to antiretroviral therapy (ART) initiation which has become pertinent with scaling up of Early Access to ART for All (EAAA). In this analysis, misdiagnosed clients are identified from a subgroup of clients enrolled in EAAA implementation study in Swaziland. Methods: The subgroup to assess misdiagnosis was identified from enrolled EAAA study clients, who had an undetectable viral load prior to ART initiation between September 1, 2014 and May 31, 2016. One hundred and five of 2533 (4%) clients had an undetectable viral load prior to initiation to ART (pre-ART). The HIV status of clients was confirmed using the Determine HIV 1/2 and Uni-Gold HIV 1/2 rapid tests performed serially as recommended by the national testing algorithm. The status of clients on ART was additionally confirmed by fourth-generation HIV Ag/Ab combo tests, Architect and Genscreen Ultra. Results: Fourteen of the 105 (13%) clients were false positive (HIV negative) on confirmation testing, of whom five (36%) were still in pre-ART care, while nine (64%) were in ART care. Overall, proportion of false positive was 0.6% (14/2533). The false-positive clients had a median CD4 of 791 cells/ml (interquartile range (IQR): 628, 967) compared to 549 cells/ml (IQR: 387, 791) for true positives (HIV positive) (p = 0.0081) and were nearly 20 years older (p = 0.0008). Conclusions: Overall 0.6% of all enrolled EAAA clients were misdiagnosed, and 64% of misdiagnosed clients were initiated on ART. With adoption of EAAA guidelines by national governments, ART initiation regardless of immunological criteria, strengthening of proficiency testing and adoption of retesting prior to ART initiation would allow identification of misdiagnosed clients and further reduce potential of initiating misdiagnosed clients on ART.

Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy.

IntroductionAntiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered. If failure on first-line ART occurs, a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and boosted lopinavir or atazanavir is recommended.Materials and methodsPlasma was obtained from subjects with first (n = 174) or second-line (n = 99) treatment failure, as defined by clinical or immunological criteria, as well as from a control group of ART naïve subjects (n = 17) in Dar es Salaam, Tanzania. Amplification of the pol region was performed locally and the amplified DNA fragment was sent to Sweden for sequencing (split genotyping procedure). The therapeutic options after failure were assessed by the genotypic sensitivity score and the EuResist predictive engine. Viral load was quantified in a subset of subjects with second-line failure (n = 52).ResultsThe HIV-1 pol region was successfully amplified from 55/174 (32%) and 28/99 (28%) subjects with first- or second-line failure, respectively, and 14/17 (82%) ART-naïve individuals. HIV-1 pol sequence was obtained in 82 of these 97 cases (84.5%). Undetectable or very low (<2.6 log10 copies/10−3 L) viral load explained 19 out of 25 (76%) amplification failures in subjects at second-line ART failure. At first and second line failure, extensive accumulation of NRTI (88% and 73%, respectively) and NNRTI (93% and 73%, respectively) DRMs but a limited number of PI DRMs (11% at second line failure) was observed. First line failure subjects displayed a high degree of cross-resistance to second-generation NNRTIs etravirine (ETR; 51% intermediate and 9% resistant) and rilpivirine (RPV; 12% intermediate and 58% resistant), and to abacavir (ABC; 49% resistant) which is reserved for second line therapy in Tanzania. The predicted probability of success with the best salvage regimen at second-line failure decreased from 93.9% to 78.7% when restricting access to the NRTIs, NNRTIs and PIs currently available in Tanzania compared to when including all approved drugs.DiscussionThe split genotyping procedure is potential tool to analyse drug resistance in Tanzania but the sensitivity should be evaluated further. The lack of viral load monitoring likely results in a high false positive rate of treatment failures, unnecessary therapy switches and massive accumulation of NRTI and NNRTI mutations. The introduction of regular virological monitoring should be prioritized and integrated with drug resistance studies in resource limited settings.

Misdiagnosis of HIV treatment failure based on clinical and immunological criteria in Eastern and Central Kenya

BackgroundRoutine laboratory monitoring is part of the basic care package offered to people living with the Human Immunodeficiency Virus (PLHIV). This paper aims to identify the proportion of PLHIVs with clinical and immunological failure who are virologically suppressed and risk being misclassified as treatment failures.MethodsA retrospective analysis of patient viral load data collected between January 2013 and June 2014 was conducted. Of the patients classified as experiencing either clinical or immunological failure, we evaluated the proportion of true (virological) failure, and estimated the sensitivity and specificity of the immunological and clinical criteria in diagnosing true treatment failure.ResultsOf the 27,418 PLHIVs aged 2–80 years on ART in the study period, 6.8% (n = 1859) were suspected of treatment failure and their viral loads analysed. 40% (n = 737) demonstrated viral suppression (VL < 1000 copies/ml). The median viral load (VL) was 3317 copies/ml (IQR 0–47,547). Among the 799 (2.9%) PLHIVs on ART classified as having clinical failure, 41.1% (n = 328) of them had confirmed viral suppression. Of the 463 (1.7%) classified as having immunological failure, 36.9% (n = 171) had confirmed viral suppression. The sensitivity of the clinical criteria in diagnosing true failure was 61% (CI 58%–65%) while that of the immunological criteria 38% (CI 35%–42%). The specificity of the clinical criteria was 34% (CI 30%–39%) while that of the immunological criteria 66% (61%–70%). Age below 20 years was associated with a high viral load (p < .001). Sex and ART regimen were not associated with the viral load.ConclusionClinical and immunological criteria alone are not sufficient to identify true treatment failure. There is need for accurate treatment failure diagnosis through viral load testing to avoid incorrect early or delayed switching of patients to second-line regimens. This study recommends increased viral load testing in line with the Kenya’s ART guidelines.

Subclinical Antibody-Mediated Rejection

Subclinical Antibody-Mediated Rejection

A case of stiff dog syndrome associated with anti-glutamic acid decarboxylase antibodies

BackgroundThe stiff person syndrome (SPS) is a rare and debilitating autoimmune disorder with an unknown pathogenesis and variable clinical presentation that can present a diagnostic challenge. Although entities that clinically mimic stiff-person spectrum disorders (SPSD) have manifested in horses, they have not been reported in dogs.Case presentationWe describe a 2-year-old beagle dog presented for progressive attacks of muscular rigidity and lordosis with superimposed spasms of the appendicular muscles triggered by tactile stimulation which resulted in marked gait impairment. Resting electromyography revealed continuous motor unit activity in the axial musculature. Compared to age-matched healthy beagle dogs, this patient had elevated glutamic acid decarboxylase antibody concentrations in serum and cerebrospinal fluid.ConclusionThis dog presented with phenotypic, electrodiagnostic, and immunologic criterion consistent with an SPSD, including elevated anti-GAD antibody titers, which we have termed the “stiff dog syndrome (SDS)”. Durable clinical improvement was achieved with symptomatic and immunosuppressive treatments including baclofen, gabapentin, prednisone, and intravenous immunoglobulin.

Atovaquone/proguanil-induced autoimmune-like hepatitis.

We report a novel association between the commonly used antimalarial medication atovaquone/proguanil and drug‐induced autoimmune‐like hepatitis. The patient developed severe liver disease fulfilling biochemical, immunologic, and histologic criteria for the diagnosis of autoimmune hepatitis after the inadvertent rechallenge with the offending drug, which had caused self‐limited hepatitic symptoms a year previously. Over a period of 18 months, the patient underwent two follow‐up liver biopsies showing progressive resolution of the liver inflammation and achieved complete biochemical and immunologic remission on steroids. This remission persisted for 20 months following treatment withdrawal. Conclusion: This well documented case raises awareness of the potential hepatotoxicity of atovaquone/proguanil. (Hepatology Communications 2017;1:293–298)

Clinicohistopathological correlation of leprosy

BACKGROUND: Leprosy is a chronic infectious granulomatous disease caused by Mycobacterium leprae. It is a spectral disease which is classified into five groups according to Ridley and Jopling based on clinical, histological, microbiological and immunological criteria. Adequate clinical information combined with bacilloscopy and histopathology is helpful not only in classification of different types of leprosy but also useful for management of the cases.METHOD: 50 cases of leprosy were examined and clinical data was recorded. Slit skin smears were stained with Ziehl Neelsen stain. Skin biopsy was stained with Hematoxylin-Eosin stain and Fite Farraco stain was performed to demonstrate acid fast bacilli. All patients were classified according to Ridley &amp; Jopling classification. Clinico-histopathological correlation was done. Statistical analysis was done using SPSS (Statistical Package for the Social Sciences) 16.0.RESULTS: Most common histological type of leprosy was tuberculoid leprosy seen in 19(38%) cases followed by indeterminate leprosy. Overall clinico-histopathological correlation was seen in 39.58%. The correlation was highest in indeterminate and histoid leprosy (100%) followed by lepromatous leprosy (66.66 %%) and tuberculoid leprosy (50%). Slit skin smear showed bacilli in 12 out of 48 cases (25%) while biopsy showed bacilli in 16 out of 48 cases (33.3%).CONCLUSION: In the present study, clinical diagnosis did not correlate with histopathological diagnosis significantly (p value=0.04159). The study emphasizes the role of histopathological and bacilloscopic examination to aid the clinical diagnosis for accurate typing of leprosy cases then better management of the patient.

Effects of carbon sources and plant protein levels in a biofloc system on growth performance, and the immune and antioxidant status of Nile tilapia (Oreochromis niloticus)

The efficacy of different biofloc treatments (BFTs) to compensate for a reduction in dietary protein level under zero-water exchange systems was studied during a 10 weeks experiment, assessing the effect on water quality, growth, immune and antioxidant status of Nile tilapia (Oreochromis niloticus) fingerlings. Six groups were established and fed the same plant-based feed containing 20 or 30% crude protein: two groups in clear water conditions with no added carbon source, two biofloc groups given a wheat milling by-product (WMB) as additional carbon source and two biofloc groups given rice bran (RB). The results showed that biofloc volume was higher when WMB was used as carbon source. The highest growth performance were obtained with the biofloc system and the higher dietary protein level. Fish fed 20% crude protein and stocked in WMB biofloc significantly outperformed the fish fed 30% crude protein and stocked in clear water. Significant improvements in hematocrit, white blood cells, lymphocytes, plasma proteins, and humoral (immunoglobulin, lysozyme, myeloperoxidase and ACH50) and cellular (phagocytosis activity and respiratory burst) immune parameters were observed in all BFT fish. BFT also increased superoxide dismutase and catalase activities. Moreover, the fish fed 20% dietary protein and reared in both biofloc conditions showed equal or superior levels of the immunological criteria to fish fed 30% protein in clear water conditions. In conclusion, using WMB as carbon source could make up for a reduction in dietary protein levels of 10% and improve growth performance, and the immune and antioxidant status of O. niloticus.

P-E1 Immunologic Criteria are Poor Predictors of Virologic Out-comes

P-E1 Immunologic Criteria are Poor Predictors of Virologic Out-comes

Клинико-иммунологические критерии внутриматочной инфекции

Клинико-иммунологические критерии внутриматочной инфекции

Molecular identification and phylogenetic analysis of Wuchereria bancrofti from human blood samples in Egypt.

Lymphatic filariasis (LF) is a serious vector-borne health problem, and Wuchereria bancrofti (W.b) is the major cause of LF worldwide and is focally endemic in Egypt. Identification of filarial infection using traditional morphologic and immunological criteria can be difficult and lead to misdiagnosis. The aim of the present study was molecular detection of W.b in residents in endemic areas in Egypt, sequence variance analysis, and phylogenetic analysis of W.b DNA. Collected blood samples from residents in filariasis endemic areas in five governorates were subjected to semi-nested PCR targeting repeated DNA sequence, for detection of W.b DNA. PCR products were sequenced; subsequently, a phylogenetic analysis of the obtained sequences was performed. Out of 300 blood samples, W.b DNA was identified in 48 (16%). Sequencing analysis confirmed PCR results identifying only W.b species. Sequence alignment and phylogenetic analysis indicated genetically distinct clusters of W.b among the study population. Study results demonstrated that the semi-nested PCR proved to be an effective diagnostic tool for accurate and rapid detection of W.b infections in nano-epidemics and is applicable for samples collected in the daytime as well as the night time. PCR products sequencing and phylogenitic analysis revealed three different nucleotide sequences variants. Further genetic studies of W.b in Egypt and other endemic areas are needed to distinguish related strains and the various ecological as well as drug effects exerted on them to support W.b elimination.

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

BackgroundOptimal HIV treatment monitoring remains a big challenge in resource limited settings. Guidelines recommend the use of clinical and immunological criteria in resource limited settings due to unavailability of viral load monitoring; however their utility is questionable. This study aimed at assessing the accuracy of immunological criteria in detecting treatment failure among HIV infected Tanzanian adults receiving first line ART.MethodsA clinic based cross sectional study was conducted between February and July 2011 at Bugando Medical centre (BMC) HIV care and treatment clinic (CTC) involving HIV infected patients aged 18 years and above, receiving first line ART; followed up for at least 1 year. Viral load was tested for every enrolled patient. Standard WHO criteria were used to define immunological failure. Virological failure was defined as one viral load measurement of >5000 copies/ml and was used as a gold standard. A 2 × 2 table was used to assess the accuracy of immunological criteria in detecting treatment failure.ResultsA total of 274 HIV-infected adults were enrolled into the study. Out of these, 65.7% were females, the median age was 39 years (IQR 33–45), the median BMI 21.9 kg/m2 (IQR 19.7–24.0). Out of the 274 study participants 156 (56.9%) had immunological failure. Only 60 of the study participants (21.9%) had viral load >5000. Only 42 patients (70%) were found to have both immunological failure and virological failure. The sensitivity of immunological criteria in detecting treatment failure was 70%, specificity 46.7%, positive predictive and negative predictive values of 26.9 and 84.7% respectively.ConclusionWHO immunological criteria have low sensitivity and positive predictive value for detecting treatment failure. Relying on CD4 counts for treatment monitoring would therefore lead to misclassifications of treatment failure that could result into unnecessary or delayed switch to second line ART. Access to viral load monitoring is important to avoid these misclassifications.

Myocarditis in children: problems and solutions

Myocarditis defined by the World Health Organization (WHO), International Society and Federation of Cardiology as an inflammatory disease of the heart muscle confirmed by histological, immunological and immunohistochemical criteria continues to challenge clinicians due to the significant heterogeneity of clinical presentations, specific problems in relation to diagnostic and therapeutic options [1, 2].

Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized by the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, fever and neurologic abnormalities. It is associated with infections, malignancy, drugs and autoimmune diseases. TTP and systemic lupus erythematosus (SLE) rarely present simultaneously and generally constitute a diagnostic dilemma. We present a case of a 42-year-old patient with overlapping features of SLE and TTP, who was admitted to our hospital with complaints of generalized fatigue, epistaxis and bruises. The workup revealed microangiopathic hemolytic anemia (negative Coomb’s test with schistocytes), and thrombocytopenia. The presence of clinical and immunological criteria made the diagnosis of SLE possible. Recognition of TTP in the setting of SLE is important, because the combination of both conditions carries a worse prognosis than SLE alone. Prompt treatment with plasmapheresis and aggressive immunosuppressive therapy is life saving. J Med Cases. 2017;8(1):5-7 doi: https://doi.org/10.14740/jmc2692w

ЭФФЕКТИВНОСТЬ АНТИРЕТРОВИРУСНОЙ ТЕРАПИИ В ЗАВИСИМОСТИ ОТ ТРОПИЗМА ВИРУСА

Aim of study: to evaluate the effectiveness of antiretroviral therapy(ART) for HIV-infected patients depending on the tropism of the virus.Material and methods. The analysis of the effectiveness of ART was performed in 98 HIV-infected patients, of them there were 55 (56.1%) women, 43 (43.9%) men, the average age of patients was 36.4 +5.8 years. R5-tropic variant of HIV was in 63 (64.2%), non-R5 tropic variant - in 35 (35.8%) patients. HIV tropism was determined by using theAmpliSens HIV-Resist-Seq reagent kit (Russia).Results. Therapy were administered to 41 patients (65%) of the first group and 21 (60%) patients of the 2nd group (p&gt; 0, 05). There was no difference in the frequency of clinical and immunological indications for ART, the effectiveness of therapy on virological and immunological criteria depending on the tropism of the virus did not differ significantly.Conclusions. The presence of non-R5 tropic HIV in the patient is an indication for the first-time use of ART, since the absence of therapy in such patients is associated with disease progression, a reduction in FPR, a higher incidence of death compared to the patients infected with the R5-tropic virus.

Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized by the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, fever and neurologic abnormalities. It is associated with infections, malignancy, drugs and autoimmune diseases. TTP and systemic lupus erythematosus (SLE) rarely present simultaneously and generally constitute a diagnostic dilemma. We present a case of a 42-year-old patient with overlapping features of SLE and TTP, who was admitted to our hospital with complaints of generalized fatigue, epistaxis and bruises. The workup revealed microangiopathic hemolytic anemia (negative Coomb’s test with schistocytes), and thrombocytopenia. The presence of clinical and immunological criteria made the diagnosis of SLE possible. Recognition of TTP in the setting of SLE is important, because the combination of both conditions carries a worse prognosis than SLE alone. Prompt treatment with plasmapheresis and aggressive immunosuppressive therapy is life saving. J Med Cases. 2017;8(1):5-7 doi: https://doi.org/10.14740/jmc2692w

Evaluation of clinical and immunological criteria of the effectiveness of intravitreal injection of ranibizumab at macular edema due to retinal vein occlusion

Branch retinal vein occlusion (BRVO) leads to retinal ischemia, releases vascular endothelial growth factor (VEGF) and other cytokines that damage to the blood retinal barrier which causes to macular edema. The aim of the study was to determine the serum and the lacrimal fluid (LF) levels of VEGF-A and IL-6 in their association with clinical parameters in patients with BRVO on the background of ranibizumab treatment. Materials and methods: 32 patients (median age 58.9 years, women - 21) underwent a three month intravitreal ranibizumab injection (IRI) due to macular edema causes BRVO. Ophthalmological examination and spectral domain optical coherence tomography was performed every month. Serum and the LF levels of VEGF-A and IL-6 were measure by ELISA before and after 3 months of treatment with IRI. The control group consist of healthy volunteers in the same age. Results: The visual acuity was improved on the background of the three IRI to 0.3 (±0.1) by Snellen in nonischemic type and 0.15 (±0.04) in ischemic type BRVO. Reduction of the retinal thickness in the macula was obtained in both groups. The serum (714.6±311 pg/ml) and LF level (762.6±432 pg/ml) of VEGF-A were in 2 times higher than in a con-trol and significantly correlated (p=0.0001) with retinal thickness. The serum level of IL-6 was higher than in control in ischemic type BRVO. Ranibizumab treatment resulted to decrease serum and LF level of VEGF-A in all patients in correlation with clinical parameters. LF level of IL-6 was decreased in while non-ischemic type of occlusion. Conclusions: There were determined high serum and lacrimal fluid levels of VEGF-A correlated with retinal thickness in patients with macular edema due to BRVO. Intravitreal ranibizumab injections led to reduced VEGF-A in serum and tear, correlating with improvement in clinical parameters.

Microbiological and immunological diagnostic criteria for initial degree of generalized periodontitis at the stage of pre X-ray manifestations.

The article presents the results of a comparative study of the microbial landscape and violations of local immunity in patients with generalized periodontitis at pre clinic al- radiological stage of development in 60 patients. It was revealed that appearance of representatives of the major periodontal bacteria in the gum tissue is a precursor of development of initial stage of generalized periodontitis in them . It has been established that the earl y objective indicators of bone resorptive process in periodontal tissues in patients with generalized catarrhal gingivitis is an overproduction of proinflammatory cytokines IL-1.beta and TNF-alpha and the lack of anti-inflammatory IL-4, which persists for a long time during the observation period.

Encefalitis límbica con fenotipo de encefalitis por anticuerpos contra receptores NMDA en paciente con diagnóstico de novo de lupus eritematoso sistémico. Reporte de caso

Malignancy-associated limbic encephalitis was first described in 1968. Since then, cases have been reported in association with the herpes simplex virus, Hashimoto's encephalopathy, lupus, Sjögren's syndrome and paraneoplasias.A syndrome with prominent psychiatric symptoms was described in 2005, consisting in memory loss, reduced level of consciousness and central hypoventilation in four young women with ovarian teratoma and antibodies against an antigen highly expressed in the hippocampus.Shortly afterwards, these patients were found to have autoantibodies against NMDA receptor NR1 (GluN1) subunit. This discovery has been of the greatest importance in clinical practice since it identifies a devastating, life-threatening neurological disorder that is treatable.In 2007, it was recognized as a nosologic entity and today it is the most common cause of autoimmune encephalitis after disseminated subacute encephalomyelitis.Case report presentation of a patient exhibiting almost all the clinical symptoms described in the syndrome characterised by NMDA receptor-associated encephalitis. Moreover, a neuroradiological correlation was found, with involvement of limbic structures seen on brain magnetic resonance imaging.Reasonable exclusion was made of the presence of neoplasia and neuroinfection, and clinical and immunological criteria of systemic lupus erythematosus were found, helping with the categorisation of lupus-associated limbic encephalitis.Mortality due to limbic encephalitis is 25%, and 75% of patients may have permanent sequelae.Given adequate response to immunosuppressive therapy, early and correct recognition are critically important.

Limbic encephalitis with phenotypic NMDA receptor antibodies in patients with de novo diagnosis of Systemic Lupus Erythematosus. Case report

Malignancy-associated limbic encephalitis was first described in 1968. Since then, cases have been reported in association with the Herpes Simplex virus, Hashimoto's encephalopathy, lupus, Sjögren's syndrome and paraneoplasias. A syndrome with prominent psychiatric symptoms was described in 2005: consisting of memory loss, reduced level of consciousness and central hypoventilation in four young women with ovarian teratoma and antibodies against an antigen highly expressed in the hippocampus.Shortly afterwards, these patients were found to have autoantibodies against NMDA receptor NR1 (GluN1) subunit. This discovery has been of the greatest importance in clinical practice since it identifies a devastating, life-threatening neurological disorder that is treatable. In 2007, it was recognised as a nosologic entity and today it is the most common cause of autoimmune encephalitis after disseminated subacute encephalomyelitis.Case report presentation of a patient exhibiting almost all the clinical symptoms described in the syndrome characterised by NMDA receptor-associated encephalitis. Moreover, a neuroradiological correlation was found, with involvement of limbic structures seen on brain magnetic resonance imaging.Reasonable exclusion was made of the presence of neoplasia and neuroinfection, and clinical and immunological criteria of systemic lupus erythemathosus were found, helping with the categorisation of lupus-associated limbic encephalitis.Mortality due to limbic encephalitis is 25%, and 75% of patients may have permanent sequelae.Given adequate response to immunosuppressive therapy, early and correct recognition are critically important.