Human Immunodeficiency Virus Coinfection Research Articles

ChimLeish, a new recombinant chimeric protein evaluated as a diagnostic and prognostic marker for visceral leishmaniasis and human immunodeficiency virus coinfection.

Visceral leishmaniasis (VL) is a neglected tropical disease of global importance caused by parasites of the genus Leishmania, and coinfection with human immunodeficiency virus (HIV) is common in countries where both diseases are endemic. In particular, widely used immunological tests for VL diagnosis have impaired sensitivity (Se) and specificity (Sp) in VL/HIV coinfected patients and there is also cross-reactivity with other endemic diseases, e.g., Chagas disease, malaria, and tuberculosis. To develop new antigens to improve the diagnosis of VL and VL/HIV coinfection, we predicted eight specific B-cell epitopes of four Leishmania infantum antigens and constructed a recombinant polypeptide chimera antigen called ChimLeish. A serological panel of 195 serum samples was used to compare the diagnostic capabilities of ChimLeish alongside the individual synthetic peptides. ChimLeish reacted with sera from all VL and VL/HIV coinfected patients [Se = 100%; Sp = 100%; area under the curve (AUC) = 1.0]. Peptides showed lower reactivities (Se = 76.8 to 99.2%; Sp = 67.1 to 95.7%; AUC between 0.87 and 0.98) as did a L. infantum antigenic preparation used as an antigen control (Se = 56.8%; Sp = 69.5%: AUC = 0.45). Notably, ChimLeish demonstrated a significant reduction (p < 0.05) of anti-ChimLeish antibodies after treatment and cure of a small number of patients. Although only a limited serological panel was tested, preliminary data suggest that ChimLeish should be evaluated in larger sample studies for the diagnosis of VL and VL/HIV coinfection.

Experience of our first-ever living donor liver transplantation in HIV-positive patient: Report from developing country with literature review

Human Immunodeficiency Virus (HIV) is one of the gravest health challenges worldwide in the present era as it has been for the past 4 decades. HIV has always been a sort of stigma and most clinicians are reluctant to perform liver transplantation for chronic liver disease patients with HIV co-infection. Patients with CD4+ cell count &gt;100/ml along with suppressed mRNA levels on PCR, stable HAART regimen, and absence of any AIDS-specific illness or opportunistic infections are the requirements for selecting HIV-positive recipients for liver transplantation.

Magnitude of Multidrug Resistance and Associated Factors of Pulmonary Tuberculosis Among Adult Smear Positive Patients in Eastern Ethiopia.

BackgroundIn Ethiopia, multidrug resistant tuberculosis is a major public health problem. However, information is scarce regarding MDR-TB and associated factors. ObjectiveThe study was aimed to assess the magnitude of multidrug resistance and associated factors of pulmonary tuberculosis among adult smear-positive patients in Harari regional state health facilities, eastern Ethiopia.MethodsA cross-sectional study was conducted among 395 adult smear-positive pulmonary tuberculosis patients attending health facilities from March to October 2019. Smear-positive sputum samples were collected from health facilities, and transported to Harari Health Research and Regional Laboratory, and tested for drug susceptibility using a line probe assay. Data were analyzed using Statistical Package for Social Sciences version 20. Bivariate and multivariable logistic regression analyses with 95% confidence intervals were carried out to identify factors associated with multidrug-resistant tuberculosis.ResultsThe overall magnitude of multidrug-resistant tuberculosis was 3.8% (15/395) (95% CI: 2.0–5.8%). Being male (AOR = 4.9; 95% CI: 1.16, 20.5), patients with a previous history of tuberculosis (AOR = 4.9; 95% CI: 1.5, 29.6), treatment failure (AOR = 8.5; 95% CI: 1.61, 45.3), treatment default (AOR = 10.38; 95% CI: 1.86, 58.0), human immunodeficiency virus co-infection (AOR = 9.83.95% CI: 3, 21, 30.1) and a previous history of contact with multidrug-resistant tuberculosis patients (AOR = 14.4; 95% CI: 3.1, 67.6) had higher odds of multidrug-resistant tuberculosis.ConclusionThe overall magnitude of multidrug-resistant tuberculosis was high. Strengthening the tuberculosis control program by giving special attention to HIV co-infected patients, treatment failure and default, previously infected patients as well as to those individuals who have a history of contact with multidrug-resistant tuberculosis infected patients .

S2957 Visceral Leishmaniasis Diagnosed by Endoscopy in an Anemic Patient With HIV/AIDS

Introduction: Vicseral Leishmaniasis (VL) is a parasitic disease transmitted by sand fly vectors. It is far less common than cutaneous Leishmaniasis. Human immunodeficiency virus (HIV) co-infection is one of the major risk factors. Incubation period is 2 to 6 months but can last several years. We report a rare case of VL discovered by esophagogastroduodenoscopy (EGD) for anemia workup in a patient recently diagnosed with HIV. Case Description/Methods: A 43-year-old man from Guatemala with past medical history of HIV diagnosed one year prior and on antiretroviral therapy was admitted to the hospital for worsening anemia. He was seen by his primary care physician one week prior to presentation due to subjective fever and chest pain, and was subsequently found to have a hemoglobin drop from 10 g/dl to 7 g/dl within months. The patient reported bleeding from his gums and nose, as well as intermittent mild abdominal pain. On physical exam, he had hyperpigmented papules on the abdomen and extremities. At the time of admission, CD4 was 54, and the viral load was undetectable. On hospital day 3, the patient underwent EGD and colonoscopy for anemia workup, which showed atrophic mucosa and nodularity in the stomach body; and erythema in the gastric antrum, duodenal bulb, and rectum. Pathology on EGD biopsies showed active gastritis and duodenitis with presence of organisms measuring 3 to 5 microns morphologically consistent with Leishmania species. The patient also underwent punch biopsy of a right leg papule by dermatology, and pathology reported suppurative granulomatous dermatitis with many amastigotes within histiocytes, compatible with Leishmaniasis. Subsequent bone marrow biopsy further confirmed the diagnosis. He was started on amphotericin B, but then developed acute kidney injury after two doses. He was then switched to miltefosine and completed the treatment. Discussion: Both HIV and VL infections target cellular immune response and have synergistically detrimental effects. Infection of atypical sites may occur when CD4 < 50, including gastrointestinal (GI) tract, peritoneal space, lung, pleural space, and skin. GI symptoms of VL are nonspecific, and EGD frequently leads to unexpected diagnosis from pathology results. 3.2% of HIV patients undergoing EGD for undiagnosed digestive symptoms were found to have amastigotes. As in our case, VL was not anticipated as the cause of the patient’s anemia. Without treatment, the fatality of VL is more than 90% in patients co-infected with HIV.Figure 1.: Histopathology of duodenal biopsy. A. Hematoxylin-eosin staining at low magnification, 1x. B. Prominent lymphocytes with an infiltrate of small oval organisms, 20x. C. Multiple Leishmania organisms with small round nucleus, 60x. D. Arrow showing prominent nucleus and kinetoplast of Leishmania protozoa, 100x.

Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

ObjectiveChagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates.MethodsThis is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions.ResultsOut of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/μL and median viral load was 17,000 copies/μL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms.ConclusionThis study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements.

"Predictors of Mortality Among Children Co-Infected with Tuberculosis and Human Immunodeficiency Virus in Region, North Ethiopia, Retrospective Follow- Up Study"

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection remain a major global and national health problem that requires substantial action to achieve the Sustainable Development Goals (SDG) and the END-TB strategies..

Epidemiology of hepatitis b virus, hepatitis C virus and human immunodeficiency virus co-infection among assymptomatic persons resident in Alex Ekwueme federal university Ndufu-alike

Based on their epidemiology, Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV), share the same routes of transmission and risk factors for infection. This study was conducted to determine the epidemiology of HBV, HCV, HIV co-infection among residents of Alex Ekwueme Federal University Ndufu- Alike, Ebonyi State Nigeria who are mostly young adults. Three Hundred and Eighty-Four participants were enlisted for this study. Blood samples were collected and tested for presence of Hepatitis B surface antigen (HBsAg), Anti-HCV antibodies and HIV antibodies using first response antigen detection kits for HBV and HCV as well as Determine and StatPak kits for HIV. Data was analyzed using descriptive statistics, Chisquare was used to test the associations. Statistical significance was taken at P ˂ 0.05. Data was analyzed using SPSS version 20.0. Results obtained from this study showed that the mean age of the participants was 24 years (SD: 5.343). The prevalence for HCV and HBV was 8.85% and 10.86% respectively. The occurrence of HBV and HCV co-infection was statistically non- significant (p 0.50). However, the prevalence of HBV was statistically significant (p = 0.012) The prevalence of HIV was 5.99%. A total of 5 (1.30%) had concomitant HBV, HCV and HIV infections. Also, 11 (2.86%) had HBV/HIV co-infection, 8(2.08%) had HCV/HIV co-infection while 5(1.30%) had HBV/HCV co-infections. All the participants were asymptomatic. This study demonstrated high prevalence of HBV, HCV and HIV and provides the first epidemiologic data on the prevalence of these viral infections among the population within the geographic region studied. To reduce the prevalence of the viral infections among the populations, preventive strategies should be developed and implemented. Also, further studies should be conducted to elucidate the epidemiological pattern of HIV, HCV and HBV concomitant infections in other States within south-eastern Nigeria.

Potential of recombinant LiHyQ, a novel Leishmania infantum protein, for the diagnosis of canine visceral leishmaniasis and as a diagnostic and prognostic marker for human leishmaniasis and human immunodeficiency virus co-infection: A preliminary study

Laboratory diagnosis of leishmaniasis shows variable efficacy in detecting infected mammalian hosts and there is a need to identify suitable antigens to improve the accuracy of diagnostic tests. In the present study, a L. infantum hypothetical protein called LiHyQ was evaluated for the diagnosis of tegumentary (TL) and visceral (VL) leishmaniasis using canine and human samples. A collection of dog sera (n=155) were tested and contained samples from asymptomatic (n=20) and symptomatic (n=25) VL animals, from healthy dogs living in endemic (n=25) or non-endemic (n=25) areas of disease, from Leish-Tec® vaccinated dogs (n=20) or from dogs infected with Ehrlichia canis (n=15), Babesia canis (n=10) and Trypanosoma cruzi (n=15). Sensitivity (Se), Specificity (Sp), Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 100% were observed for rLiHyQ with these samples, whereas the Se, Sp, PPV and NPV values with L. infantum Soluble Leishmania Antigen (SLA) preparation were 60.0%, 99.0%, 96.0% and 86.0%, respectively. A collection of human sera (n=305) were tested and contained samples from TL (n=50) and VL (n=40) patients, from VL/HIV co-infected patients (n=35), from patients infected with HIV alone (n=30), Chagas Disease (n=30), malaria (n=10), tuberculosis (n=10), paracoccidioidomycosis (n=15), leprosy (n=30) or aspergillosis (n=15); and from healthy subjects (n=40). Se, Sp, PPV and NPV values of 100% were observed for rLiHyQ with these samples, whereas the Se, Sp, PPV and NPV values with SLA were 58.0%, 76.0%, 50.0% and 82.0%, respectively. The antibody reactivity against the protein was compared with commercial kits, and the kappa index varied from 0.95 to 1.00 for rLiHyQ, and of 0.55 to 0.82 for the kits. In addition, the serological follow-up of treated patients showed a significant reduction in rLiHyQ-specific IgG antibody levels. All canine and human samples were tested at the same time using the same reagents, in order to reduce experimental variation and interference in data interpretation. In conclusion, our preliminary data suggest a diagnostic and prognostic role for rLiHyQ against leishmaniasis.

Causes of death in patients with tuberculosis and human immunodeficiency virus co-infection

Objectives. The aim of the study was to investigate the cause of death of tuberculosis patients infected with the human immunodeficiency virus (HIV). Many researchers and experts note the urgency of the problem of tuberculosis combined with HIV infection in the world and in Russia. One of the main criteria for assessing the effectiveness of medical care for tuberculosis patients infected with the human immunodeficiency virus is the mortality rate.Materials and methods. For a detailed study of the causes of death of patients with tuberculosis in combination with HIV infection, we analyzed the causes of death of this contingent of patients in 5 regions of the Russian Federation.Results. The social characteristics of patients, the forms and course of the disease, the main and immediate causes of death of 223 patients with co-infection with HIV and tuberculosis were studied.Conclusion. Half of the deaths of tuberculosis patients infected with human im­munodeficiency virus were not associated with tuberculosis. Among these cases, there was either the presence of several infections at the same time, equally leading to death, or separate opportunistic infections (candidiasis, Pneumocystis pneumonia, toxoplasmosis), or cancer. In addition, the lifestyle of patients often became the cause of deaths, namely: drug poisoning and accidents, or cirrhosis of the liver, which develops as a result of alcoholism or hepatitis C infection which occurred during intravenous administration of drugs.

Experience of our First-Ever Living Donor Liver Transplantation In Hiv-Positive Patient-Report From Developing Country with Literature Review

Human Immunodeficiency Virus (HIV) is one of the gravest health challenges worldwide in the present era as it has been for the past 4 decades. HIV has always been a sort of stigma and most clinicians are reluctant to perform liver transplantation for chronic liver disease patients with HIV co-infection. Patients with CD4+ cell count &gt;100/ml along with suppressed mRNA levels on PCR, stable HAART regimen, and absence of any AIDS-specific illness or opportunistic infectionsare the requirements for selecting HIV-positive recipients for liver transplantation. We report the first living donor liver transplant in an HIV-positive recipient in a developing country. Here are the details of the case. Keywords: HIV, living donor, Liver transplantation, developing country

Diagnostic application of sensitive and specific phage-exposed epitopes for visceral leishmaniasis and human immunodeficiency virus coinfection.

The diagnosis of visceral leishmaniasis (VL) has improved with the search of novel antigens; however, their performance is limited when samples from VL/human immunodeficiency virus (HIV)-coinfected patients are tested. In this context, studies conducted to identify more suitable antigens to detect both VL and VL/HIC coinfection cases should be performed. In the current study, phage display was performed using serum samples from healthy subjects and VL, HIV-infected and VL/HIV-coinfected patients; aiming to identify novel phage-exposed epitopes to be evaluated with this diagnostic purpose. Nine non-repetitive and valid sequences were identified, synthetized and tested as peptides in enzyme-linked immunosorbent assay experiments. Results showed that three (Pep2, Pep3 and Pep4) peptides showed excellent performance to diagnose VL and VL/HIV coinfection, with 100% sensitivity and specificity values. The other peptides showed sensitivity varying from 50.9 to 80.0%, as well as specificity ranging from 60.0 to 95.6%. Pep2, Pep3 and Pep4 also showed a potential prognostic effect, since specific serological reactivity was significantly decreased after patient treatment. Bioinformatics assays indicated that Leishmania trypanothione reductase protein was predicted to contain these three conformational epitopes. In conclusion, data suggest that Pep2, Pep3 and Pep4 could be tested for the diagnosis of VL and VL/HIV coinfection.

A meta-analysis on the prevalence and characteristics of severe malaria in patients with Plasmodium spp. and HIV co-infection

Co-infection with malaria and human immunodeficiency virus (HIV) increases the severity and mortality rates of both diseases. A better understanding of the effects of co-infections could help in the diagnosis, prompt treatment, prevention, and control of malarial parasites among HIV-infected patients. In this systematic review and meta-analysis, we estimated the prevalence and characteristics of severe malaria (SM) caused by co-infection with HIV. We included relevant studies that were conducted between the years 1991 and 2018 and reporting on SM. We pooled the prevalence of SM in patients with co-infection, pooled odds ratios of SM in patients with co-infection and Plasmodium mono-infection, and differences in laboratory parameters such as parasite density and leucocyte counts, between co-infected and Plasmodium mono-infected patients. The meta-analysis included 29 studies (1126 SM cases). The pooled prevalence of SM in co-infected patients using the data of 23 studies (SM = 795 cases, all co-infection cases = 2534 cases) was 43.0% (95% confidence interval [CI] 31.0–56.0%; I2, 98.0%). Overall, the odds of SM from 18 studies were pooled. The odds of SM were significantly higher in co-infected patients than in Plasmodium mono-infected patients (OR 2.41; 95% CI 1.43–4.08; I2 = 85%; P = 0.001) and also significantly higher in children (OR 9.69; 95% CI 5.14–18.3; I2, 0%; P < 0.0001; two studies) than in adults (OR 2.68; 95% CI 1.52–4.73; I2, 79.0%; P = 0.0007; 12 studies). Co-infected patients with SM had a higher parasite density than those with Plasmodium mono-infection when the data of seven studies were analysed (SMD, 1.25; 95% CI 0.14–2.36; I2, 98.0%; P = 0.03) and higher leukocyte counts when the data of four studies were analysed (MD, 1570 cells/µL; 95% CI 850–2300 cells/µL; I2, 21.0%; P < 0.0001). Thus, the prevalence of SM among patients co-infected with Plasmodium spp. and HIV is high. Because co-infections could lead to SM, patients with Plasmodium spp. and HIV co-infection should be identified and treated to reduce the prevalence of SM and the number of deaths.

Hepatitis D virus dual infection increased the risk of hepatocellular carcinoma compared with hepatitis B virus mono infection: A meta-analysis.

Hepatitis delta virus (HDV) is a defective virus that relies on the supply of hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV) to assemble HDV virions and infect hepatocytes. However, controversy remains in whether the presence of HDV increases the risk of hepatocellular carcinoma (HCC). Our aim is to evaluate the influence of HDV on the risk of HCC through a systematic review and meta-analysis. A review of all English-language literature was conducted in the major medical databases using the subject search terms "hepatocellular carcinoma," "liver cancer," "hepatic tumor," and "hepatitis delta." A meta-analysis of the qualifying publications was then performed. The meta-analysis included 21 studies, which revealed a significantly higher risk of HCC among patients with HDV/HBV dual infection (odds ratio [OR] = 2.08, 95% confidence interval [CI], 1.37-3.14, p < 0.01) compared with those with HBV monoinfection. Those with HDV/HBV dual infection remained at higher risk of HCC in the subgroup analysis, irrespective of the status of hepatitis C virus (HCV) or human immunodeficiency virus (HIV) coinfection and in different ethnicities. The HCC risk remained higher in patients with HDV/HBV dual infection with heterogeneous fibrosis stage (OR = 2.04, 95% CI, 1.31-3.17, p < 0.01). The difference in the risk of HCC between HDV/HBV dual infection and HBV monoinfection was not statistically significant in patients with cirrhosis or advanced fibrosis (OR = 1.84, 95% CI, 0.48-7.02, p = 0.37). However, this subgroup comprised only two studies. HDV and HBV dual infection significantly increase the risk of HCC development compared with HBV monoinfection.

A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection.

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.

The Effect of HBV/HCV in Response to HAART in HIV Patients after 12 Months in Kumba Health District in the South West Region of Cameroon.

Hepatitis B (HBV) and C (HCV) are two among the numerous forms of infections whose clinical degeneration, morbidity–mortality and low immune responsiveness in people living with human immunodeficiency virus (HIV) are highly evident. Co-infection of HIV with HBV and HCV has been associated with reduced survival, increased risk of progression to liver diseases and increased risk of hepatotoxicity associated with antiretroviral therapy (ARV). We carried out biochemical, immunological, virological and clinical analysis of hepatitis B and C positive HIV patients as well as some HIV positive individuals receiving antiretroviral therapy in Kumba Health District to evaluate the immune response to the ARV therapy and identified risk factors associated with the treatment outcomes. A total of 52 HIV patients, 36 HIV/HBV and 12 HIV/HCV patients were involved in this study. We performed CD4 counts, viral load test, analyzed ALAT/ASAT, albumin, bilirubin, and creatinine and measured the weights of HIV patients, HIV/HBV and HIV/HCV enrolled for not more than one year in Kumba Health District. The results were analyzed to evaluate the immune response and possible risk factors associated with the treatment outcomes. The mean increase in weight in participants of all groups over 12 months (17.12 kg) was greater than the mean increase in CD4 (8.92 cell/mm3). However, the mean decrease in viral loads over a 12 months was also very high (1035.17 copies/mL). There was a significant change in the mean values from baseline for all the three variables (p < 0.0001). HIV disease outcomes following HAART (high active antiretroviral therapy) do not appear to be adversely affected by HBV or HCV co-infection, except for slightly poorer CD4 count responses in HIV/HCV co-infected patients. Concerning the renal and liver functions, all the biomarkers witnessed a decrease in patients of all groups in response to HAART over time, with a more rapid decrease in mono-infected patients as compared with those co-infected with HBV but the case was contrary for those co-infected with HCV. Co-infection with HBV or HCV was relatively common among HIV infected participants in Kumba Health District. There were differences in response to HAART between the mono-infected compared with the co-infected, taking into consideration the weight, CD4 count, and viral load. In addition, there was also a variation in the different biomarkers of liver and renal function between mono-infected and co-infected patients.

Hepatitis C Virus Infection: What Are We Currently Doing in Latin America About WHO's Proposals for 2030?

Hepatitis C Virus Infection: What Are We Currently Doing in Latin America About WHO's Proposals for 2030?

Neurologic Complications of Tuberculosis.

This article describes the current epidemiology, common clinical characteristics, and up-to-date evidence-based approaches to the diagnosis and management of the most common neurologic complications of tuberculosis (TB): tuberculous meningitis, intracranial tuberculoma, and spinal TB. Central nervous system (CNS) TB remains common and associated with significant mortality and neurologic sequelae worldwide. Human immunodeficiency virus (HIV) co-infection is strongly associated with both the development of and mortality due to CNS TB. Strongyloides co-infection is associated with reduced CNS inflammation and improved outcomes in the setting of tuberculous meningitis. Stroke remains a common complication of tuberculous meningitis, and emerging evidence suggests aspirin may be used in this context. Although a recent nucleic acid amplification test has demonstrated suboptimal sensitivity in the diagnosis of CNS TB, emerging diagnostic techniques include cell-free DNA, peripheral blood microRNA, metagenomic next-generation sequencing, and advanced imaging techniques, but these are not yet well validated. CNS TB is associated with high mortality even with current treatment regimens, although novel, promising strategies for treatment are under investigation, including a combination of IV isoniazid and ethambutol and high-dose rifampicin. TB can affect the nervous system in various ways and is associated with high mortality. Diagnosis remains challenging in endemic settings, with empiric treatment often initiated without a definitive diagnosis. Furthermore, optimal treatment regimens remain uncertain because current treatment for all forms of CNS TB is extrapolated from trials of tuberculous meningitis whereas the role of steroids in people with HIV and tuberculous meningitis remains controversial.

Use of prednisolone to prevent the development of immunity reconstitution syndrome in patients with multidrug-resistant tuberculosis

Inflammatory reconstitution of immune syndrome (IRIS) is an immunological reaction characterized by recurrent or new inflammatory signs of tuberculosis (TB) that occur shortly after antiretroviral therapy (ART) in 18 % of patients infected with human immunodeficiency virus (HIV). Features of the syndrome include recurrent symptoms: fever, lymphadenitis and the spread of pulmonary infiltrates on radiography. Low CD4 levels and a short interval between the onset of ART increase the risk of developing TB-associated immune system recovery syndrome. Clinical trials show that early onset of ART results in higher survival rates than ART initiated approximately 8 weeks after the start of TB treatment in patients with a CD4 count of 50 cells/μl. These findings are in line with the recommendations of the World Health Organization, which emphasize the acceleration of the onset of ART in patients with TB and low CD4 levels. However, despite the advantage of survival, early administration of ART more than increases the risk of developing IRIS associated with TB. There is no evidence-based strategy for the prevention of IRIS associated with TB. Studies evaluating adjuvant glucocorticoids for the treatment of various forms of TB have shown reduced mortality among TB patients and fewer complications among TB patients. The aim of the study was to evaluate the prophylactic use of prednisolone to safely reduce the incidence of TB-associated IRIS in patients with multidrug resistant TB (MDR TB) is at high risk of developing the syndrome. We observed HIV-infected patients who started ART (and had not previously received ART) and started TB treatment within 30 days before the start of ART and had a CD4 count of 50 cells/μl. Patients received either standard therapy with prednisolone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or only standard therapy without prednisolone. The main endpoint was the development of TB associated with TB within 12 weeks after the onset of ART. Among the 64 patients observed, the mean age was 36 years, 60 % were male, and 73 % had microbiologically confirmed TB; the median amount of CD4 was 49 cells/μl, and the median viral load was 5.5 log 10 copies/μl. Patients were divided into 2 groups. Each group included 32 patients with MDR TB / HIV co-infection. IRIS associated with TB was diagnosed in 10 patients (31.25 %) in the prednisolone group and in 17 (53.14 %) in the control group (p&lt;001). Thus, prednisolone treatment of co-infected patients with MDR TB for the first 4 weeks after the onset of HIV-related ART resulted in a lower incidence of TB-associated IRIS than in the control group, with no evidence of an increased risk of severe infections or cancer.

The Roles of Fibrosis Index Based on Four Factors and Aspartate Transaminase-to-Platelet Ratio Index Scoring Systems as an Alternative to Transient Elastography Liver Stiffness in Liver Fibrosis Staging in Human Immunodeficiency Virus and Hepatitis C Virus Co-Infected Patients.

BackgroundLiver biopsy used to be the gold standard to assess liver fibrosis in patients infected with hepatitis C virus (HCV). Nonetheless, due to its invasive nature, techniques such as transient elastography liver stiffness (TE-LS), fibrosis index based on four factors (FIB-4) and aspartate transaminase-to-platelet ratio index (APRI) scores are currently being used. FIB-4 and APRI scores have the advantage of low cost and are readily available, compared with TE-LS. Herein, we evaluated the diagnostic performance of these scoring systems as compared to TE-LS in assessing liver fibrosis in patients with human immunodeficiency virus (HIV) and HCV co-infection.MethodsThe medical records of patients with HIV and HCV co-infection who had TE-LS done at our facility between August 1, 2013 and January 1, 2020 were extracted and analyzed. Exclusion criteria include: 1) patients co-infected with hepatitis B virus; 2) invalid TE-LS assessment; 3) have ≥ 10th upper limit of normal (ULN) alanine aminotransferase (ALT) levels; and 4) excessive alcohol use. Patient demographics, medical history, biochemical and clinical data were retrieved. For each patient, we calculated the FIB-4 and APRI score. Descriptive analysis was performed and correlation of FIB-4 and APRI with TE-LS was assessed with GraphPad Prism statistical software.ResultsFive hundred forty-seven patients underwent TE-LS during the study period. After excluding those without complete laboratory parameters, the total study population was 344. Their age was 56 ± 10.4 years and 234 (68%) were male. The average aspartate aminotransferase (AST) and ALT were 27.95 and 30.73. The average platelet count was 224 and the average TE-LS was 7.29. Fourteen patients (4.1%) had TE-LS values between 9 and 11.9 kPa and were classified as F3, while 29 (8.5%) had TE-LS ≥ 12 kPa and were classified as F4. With the correlation analysis, both APRI (correlation coefficient, r = 0.1097, 95% confidence interval (CI) 0.0403 - 0.2130; P = 0.042) and FIB-4 (r = 0.0424, 95% CI -0.0634 - 0.1474; P = 0.4335) were not correlated with TE-LS stages of fibrosis.ConclusionIn our cohort, we failed to demonstrate that APRI and FIB-4 are reliable alternatives for screening liver fibrosis in patients with HIV and HCV co-infection. Nonetheless, APRI score still has a potential role as a screening tool instead of TE-LS measurement, which is costly and not readily available. It will be important to corroborate these findings in another large cohort, since this may have an important impact on patient management.

A nutritional profile of patients with tuberculosis at Standerton Tuberculosis Specialised Hospital, Mpumalanga, South Africa.

BackgroundTuberculosis (TB) is strongly influenced by nutritional status, with nutrition interventions being likely to have an impact on the prevalence of disease, response to drugs and quality of life.AimThe aim of this research study was to determine the nutritional profile of patients with TB and TB and human immunodeficiency virus (HIV) co-infection.SettingThe study was conducted at Standerton TB Specialised Hospital, Mpumalanga.MethodsA cross-sectional study was undertaken. A structured interview was conducted by the researcher with each patient. The Malnutrition Universal Screening Tool (MUST) was used to determine the risk of malnutrition. Weight, height, mid-upper arm circumference (MUAC) and triceps skinfold were measured using standard techniques. Biochemical parameters that were part of the routine hospital procedure were noted.ResultsMore than two-thirds of the participants (68%) were found to be HIV positive. Food-related side effects included loss of appetite (59%) and dry mouth (48%). According to the MUST, 70% had a high risk of malnutrition. The median body mass index (BMI) was in the underweight category at 18.3 kg/m². About half of the participants had low MUAC measurements (51%) and triceps skinfold measurements below the 15th percentile (49.9%), indicating malnutrition. Most participants had low albumin and haemoglobin levels (79% and 92%, respectively).ConclusionsPatients with both TB and TB and HIV co-infection had a compromised nutritional status and an increased risk for developing malnutrition. Interventions aimed at addressing malnutrition could make a meaningful contribution to improving the quality of life in these patients.ContributionThis research provides evidence on the nutritional profile of patients with tuberculosis at Standerton TB Specialised Hospital, it gives opportunity to extend this research project to confirm these findings in other TB burdened areas.