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1.
Article in English | MEDLINE | ID: mdl-35490317

ABSTRACT

Neglected Tropical Diseases (NTDs) are a group of twenty (20) chronic, communicable, infectious diseases endemic to the tropics and sub-tropics climate countries which are intimately associated with poverty, poor sanitation, limited clean water, and healthcare delivery; and dwellers live in proximity to pathogens and diseases vectors. The pathogens are protozoans, bacteria, helminths, fungi, and viruses. NTDs currently affects about one billion people globally, out of which 500 million are Africans living in rural settlements with low political voice and support. In recent years, NTDs have received little research recognition, development, and funding because more research efforts by global health stakeholders are focused on recognized diseases like Cancers, Hepatitis, Tuberculosis, Acquired Immune-Deficiency Syndrome (AIDS), and Malaria that affects most developed countries. The emergence of the viral novel COVID-19 will exacerbate the burden of NTDs on disadvantaged communities as global health efforts are again focused on COVID-19 clearance in terms of research and development to find a drug/vaccine amidst other investigations on recognized infections. This development can result in high death tolls due to NTDs if control measures aren't prioritized now. This perspective piece addresses the need for NTDs control amidst COVID-19 clearance efforts to mitigate another viral health crisis in Africa.

3.
Brain Behav Immun ; 103: 243-245, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35550853

ABSTRACT

Conflicts are inevitable, and so are refugees. Due to conflicts in Ukraine, the global refugee population has reached new highs. As people continue to flee Ukraine amid the ongoing pandemic in droves, their exposure to COVID-19 and infectious diseases that are common among the refugee population, such as tuberculosis, is on the rise as well. Also factoring in the fact that Ukraine has a large population living with communicable diseases like HIV and hepatitis C, along with other non-communicable conditions like diabetes and cancer, there is a pronounced need to protect these refugees and local residents from potential public health crises. In this paper, we investigate the challenges that health and government officials face in addressing refugees' health needs and preferences. Furthermore, we discuss the imperative to provide timely and effective health services to refugees, such as psychoneuroimmunology-based interventions that could help address refugees' multifactorial and multifaceted health needs and requirements. While conflicts are inevitable, public health crises are not. In light of the renewed imperative to safeguard shared humanity and solidify global solidarity, collaborative actions are needed to ensure fair, kind, and true public health environments are available to refugees of the current conflict and beyond.

4.
FASEB J ; 36 Suppl 12022 May.
Article in English | MEDLINE | ID: mdl-35552769

ABSTRACT

BACKGROUND: Tuberculosis is the 13th leading cause of death and the second leading infectious killer after COVID-19 (above HIV/AIDS) around the world. In 2020, an estimated 10 million people fell ill with tuberculosis (TB) worldwide. Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (CDC). To avoid another pandemic from happening after covid-19 we must work on drug discovery and vaccines to prevent TB from spreading. OBJECTIVE: This work is done on mycobacterium tuberculosis, the causative agent of tuberculosis, using laboratory experiments and computational biological tools to characterize methyltransferase proteins of Mtb. This study is targeted to find out any potential drug or vaccine target in Mtb. METHOD: With the help of bioinformatic tools a hypothetical methyltransferse protein was selected from previously reported variety of 121 methyltransferses according to the domain configuration. The protein was verified by the thermal stability, Protein conformational changes, localization, signal peptide chain, structure prediction and function, mutational analysis and molecular docking. RESULTS: Rv3366 gene was selected based on its secretory characteristic and localisation in mitochondria among 121 methyltransferases. SignalP4.1 and Mitoprot ll were used for the cleavage site prediction. Protein modelled by online server has 95.6% allowed region and validated by Ramachandran Plot Statistics from Richardson's lab. The biophysical characteristics of the gene were also identified using methyltransferase assay, thermal denaturation assay, spectrophotometry, fluorescence assay. Alarm assay was done for quantitation of viable cell number in proliferation and cytotoxicity in the presence of the target protein. MitoTracker Red CMXRos kit was used to verify the localisation of the protein in mitochondria. CONCLUSION: This study covers essential identification of hypothetical methyltransferase that will help in targeting dataset for future studies leading to drug target and TB control of MTB or probably even MDRTB.

5.
FASEB J ; 36 Suppl 12022 May.
Article in English | MEDLINE | ID: mdl-35554659

ABSTRACT

Tuberculosis (TB) is a disease of the lung caused by the bacterium, Mycobacterium tuberculosis (Mtb), and is the second leading cause of mortality from an infectious agent after SARS-CoV-2. Mtb is an opportunistic pathogen that benefits from a compromised immune system and is particularly deadly in HIV patients. New therapies targeting TB are necessary due to an increase in multi-drug resistant strains. Our collaborators at Texas Southern University identified novel bacterial methionine aminopeptidase (MtMetAP1) inhibitors. Genetic knockout studies support the lethality of the deletion of MtMetAP1 in Mtb. Further studies support the existence of an ortholog in Homo sapiens (HsMetAP1) that performs similar essential functions. Although these novel inhibitors are known to be effective against Mtb, their cytotoxicity in mammalian cells has yet to be established. We hypothesize that there will be low levels of cytotoxicity in cancerous and primary lung cell lines at varying concentrations of the MetAP novel inhibitor, UST-001. Using flow cytometry via a MUSE® Cell Count and Viability Kit, the cytotoxicity of UST-001 was assayed in H1299 cancer cells. The H1299 cells were exposed to concentrations of UST-001 ranging from 0.1µM to 750µM for 48 hours at 37℃and 5% CO2. Three negative controls were included in each replicate: DMSO (carrier), pure media, and Isoniazid (INH). INH is a common clinically effective TB treatment. The viability of H1299 cells was still over 60% at the highest inhibitor concentration tested. Trypan Blue Assays were performed on the same H1299 cells at each concentration and the controls, which corroborated flow cytometry results. In establishment of a dose-response curve, our data showed that at UST-001 concentrations below 100 µM, induced little to no cell death and cell viability of 90% or higher. Since cancerous cells have higher mitotic rates and more repair pathways, we hypothesize that we will be able to establish an IC50 curve in non-cancerous Mlg-2908 lung fibroblast cells at higher concentrations. Current flow cytometry testing on Mlg-2908 cells, using the same protocol as the H1299 cells, shows cell viability of 89% or higher in 0.1 µM to 10 µM UST-001 concentrations. Since cancerous cells have higher mitotic rates and more repair pathways, we hypothesize that we will be able to establish an IC50 curve in Mlg-2908 cells at higher concentrations. Further studies using a Muse Annexin V apoptosis assay will focus on the UST-001 mechanism of cell death. Our ultimate goal is to characterize the toxicity of this drug in mammalian systems, with hopes of potentially identifying a new class of antibiotics and pharmaceutical targets.

6.
Front Pediatr ; 10: 897803, 2022.
Article in English | MEDLINE | ID: mdl-35558376

ABSTRACT

This joint statement by the European Society for Emergency Paediatrics and European Academy of Paediatrics aims to highlight recommendations for dealing with refugee children and young people fleeing the Ukrainian war when presenting to emergency departments (EDs) across Europe. Children and young people might present, sometimes unaccompanied, with either ongoing complex health needs or illnesses, mental health issues, and injuries related to the war itself and the flight from it. Obstacles to providing urgent and emergency care include lack of clinical guidelines, language barriers, and lack of insight in previous medical history. Children with complex health needs are at high risk for complications and their continued access to specialist healthcare should be prioritized in resettlements programs. Ukraine has one of the lowest vaccination coverages in the Europe, and outbreaks of cholera, measles, diphtheria, poliomyelitis, and COVID-19 should be anticipated. In Ukraine, rates of multidrug resistant tuberculosis are high, making screening for this important. Urgent and emergency care facilities should also prepare for dealing with children with war-related injuries and mental health issues. Ukrainian refugee children and young people should be included in local educational systems and social activities at the earliest opportunity.

7.
Lancet HIV ; 2022 May 10.
Article in English | MEDLINE | ID: mdl-35561704

ABSTRACT

BACKGROUND: WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors. METHODS: Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors. FINDINGS: Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status. INTERPRETATION: In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

8.
Cell Rep Methods ; : 100224, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35571764

ABSTRACT

The B cell "help" function of CD4+ T cells is an important mechanism of adaptive immunity. Here, we describe improved antigen-specific T-B co-cultures for quantitative measurement of T cell-dependent B cell responses, with as few as ∼90 T cells. Utilizing Mtb, we show that early priming and activation of CD4+ T cells is important for productive interaction between T and B cells, and that similar effects are achieved by supplementing co-cultures with monocytes. We find that monocytes promote survivability of B cells via BAFF and SCGF/CLEC11A, but this alone does not fully recapitulate the effects of monocyte-supplementation. Importantly, we demonstrate improved activation and immunological output of SARS-CoV-2 specific memory CD4+ T - B cell co-cultures with the inclusion of monocytes. This method may therefore provide a more sensitive assay to evaluate the B cell help quality of memory CD4+ T cells, for example after vaccination or natural infection.

9.
J Thorac Dis ; 14(4): 1282-1295, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35572880

ABSTRACT

General thoracic surgery operations in Egypt are performed mainly by cardiothoracic surgeons and less oftenly by dedicated thoracic surgeons and general surgeons. This is mainly due to the relatively small number of thoracic surgeons in relation to population as only 210 cardiothoracic surgery specialists and 458 consultants are registered with the Egyptian Medical Syndicate (EMS) in a country with a population of more than 100 million people. Thoracic surgeons in Egypt are faced with a number of burdens, including the need to propagate the service to advanced technology infront of the obstacle of limited resources. Other burdens include higher incidence of TB, trauma and foreign body inhalation related to cultural backgrounds. More centres now are major video-assisted thoracic surgery (VATS) providing centres and others are specialized in more complex surgeries like complicated airway procedures and radical surgery for mesothelioma. As part of the international community, the COVID-19 pandemic has put more burdens on the thoracic surgery service as most centres have reduced their elective surgery workload to less than half of usual. Interestingly, the pandemic has allowed a self-referral screening programme with widespread Computed Tomography (CT) chest being performed among the population allowing thoracic surgeons to operate more on early stage lung cancer. The academic challenges for thoracic surgeons are even more with need for developing national databases. Nevertheless, thoracic surgeons in Egypt are optimistic regarding the future. The rising interest among the younger population will push training programs to meet the interests of enthusiastic junior surgeons. While the ancient history of thoracic surgery in Egypt seems to be extraordinary, the future perspectives promise to be more rewarding.

10.
Pediatric Health Med Ther ; 13: 165-174, 2022.
Article in English | MEDLINE | ID: mdl-35573390

ABSTRACT

Introduction: Most previous pediatric COVID-19 studies reported milder disease in children. However, there are limited pediatric data from low-income settings. We aimed to assess the characteristics and outcomes of pediatric COVID-19 in Ethiopia. Setting: St. Paul's COVID-19 treatment center; a tertiary COVID-19 center. Pediatric care was provided in a dedicated ward but with a common ICU. Methods: St. Paul's Hospital COVID-19 cohort (SPC-19) included inpatient COVID-19 RT-PCR confirmed cases from August 2020 to January 2021. Data were extracted from case report forms attached to patient charts and completed by the clinicians. Data were uploaded into the Redcap database and exported to SPSS 20 for analysis. Binary logistic regression and chi-square test were used in the analysis. Results: Seventy-nine patients 0-19 years were included from the SPC-19 cohort over 6 months. Pediatric admissions accounted for 11% of cases in the cohort. The mean age (SD) was 6.9 (±6.36) years and 40 (50.6%) were female. The disease was asymptomatic or mild in 57 (72.2%), moderate in 15 (19%), and severe or critical in 7 (8.8%). The commonest presentations in symptomatic children were prostration (26.6%) followed by vomiting (12.7%), fever and cough (11.4% each), and dyspnea (10%). About 53 (67%) children had multimorbidity, and 14 (17.7%) children died. All deaths were in children with comorbidities with tuberculosis and malignancy being associated with 43% of deaths. Nearly 5% of children reported long-COVID symptoms highlighting the need for prolonged follow-up in those children. Conclusion: Despite lower admissions and severity, high mortality and morbidity was documented in our pediatric cohort. The presence of comorbidity and inadequate care organization likely contributed to high mortality. COVID-19 centers of low-income settings should emphasize optimizing the care of children with COVID-19 and multimorbidity, and vaccination should be considered in those children to prevent high morbidity and mortality.

11.
Int J Pept Res Ther ; 28(3): 99, 2022.
Article in English | MEDLINE | ID: mdl-35573911

ABSTRACT

Mycobacterium tuberculosis causes a life-threatening disease known as tuberculosis (TB). In 2021, tuberculosis was the second cause of death after COVID-19 among infectious diseases. Latent life cycle and development of multidrug resistance in one hand and lack of an effective vaccine in another hand have made TB a global health issue. Here, a multi-epitope vaccine have been designed against TB using five new antigenic protein and immunoinformatic tools. To do so, immunodominant MHC-I/MHC-II binding epitopes of Rv2346, Rv2347, Rv3614, Rv3615 and Rv2031 antigenic proteins have been selected using advanced computational procedures. The vaccine was designed by linking ten epitopes from the antigenic proteins and flagellin and TpD as adjuvant. Three-dimensional (3D) structure of the vaccine was modeled, was refined and was evaluated using bioinformatics tools. The 3D structure of the vaccine was docked into the toll-like-receptors (TLR3, 4, 8) to evaluate potential interaction between the vaccine and TLRs. Evaluation of immunological and physicochemical properties of the constructed vaccine have demonstrated the vaccine construct can induce significant humoral and cellular immune responses, the vaccine is non-allergenic and can be recognized by TLR proteins. The immunoinformatic results reported in the present study demonstrates that it is worth following the designed vaccine by experimental investigations.

12.
Immunobiology ; 227(3): 152224, 2022 May 05.
Article in English | MEDLINE | ID: mdl-35533535

ABSTRACT

The COVID-19 pandemic has set back progress made on antimicrobial resistance (AMR). Without urgent re-focus, we risk slowing down drug discovery and providing treatment for drug resistant Mycobacterium tuberculosis. Unique in its immune evasion, dormancy and resuscitation, the causal pathogens of tuberculosis (TB) have demonstrated resistance to antibiotics with efflux pumps and the ability to form biofilms. Repurposing drugs is a prospective avenue for finding new anti-TB drugs. There are many advantages to discovering novel targets of an existing drug, as the pharmacokinetic and pharmacodynamic properties have already been established, they are cost-efficient and can be commercially accelerated for the new development. One such group of drugs are non-steroidal anti-inflammatory drugs (NSAIDs) that are originally known for their ability to supress the host proinflammatory responses. In addition to their anti-inflammatory properties, some NSAIDs have been discovered to have antimicrobial modes of action. Of particular interest is Carprofen, identified to inhibit the efflux mechanism and disrupt biofilm formation in mycobacteria. Due to the complexities of host-pathogens interactions in the lung microbiome, inflammatory responses must carefully be controlled alongside the in vivo actions of the prospective anti-infectives. This critical review explores the potential dual role of a selection of NSAIDs, as an anti-inflammatory and anti-tubercular adjunct to reverse the tide of antimicrobial resistance in existing treatments.

13.
Lancet Microbe ; 3(5): e357-e365, 2022 May.
Article in English | MEDLINE | ID: mdl-35544096

ABSTRACT

BACKGROUND: Pneumonia is a leading cause of death worldwide and is a major health-care challenge in people living with HIV. Despite this, the causes of pneumonia in this population remain poorly understood. We aimed to assess the feasibility of metatranscriptomics for epidemiological surveillance of pneumonia in patients with HIV in Uganda. METHODS: We performed a retrospective observational study in patients with HIV who were admitted to Mulago Hospital, Kampala, Uganda between Oct 1, 2009, and Dec 31, 2011. Inclusion criteria were age 18 years or older, HIV-positivity, and clinically diagnosed pneumonia. Exclusion criteria were contraindication to bronchoscopy or an existing diagnosis of tuberculosis. Bronchoalveolar lavage fluid was collected within 72 h of admission and a combination of RNA sequencing and Mycobacterium tuberculosis culture plus PCR were performed. The primary outcome was detection of an established or possible respiratory pathogen in the total study population. FINDINGS: We consecutively enrolled 217 patients during the study period. A potential microbial cause for pneumonia was identified in 211 (97%) patients. At least one microorganism of established respiratory pathogenicity was identified in 113 (52%) patients, and a microbe of possible pathogenicity was identified in an additional 98 (45%). M tuberculosis was the most commonly identified established pathogen (35 [16%] patients; in whom bacterial or viral co-infections were identified in 13 [37%]). Streptococcus mitis, although not previously reported as a cause of pneumonia in patients with HIV, was the most commonly identified bacterial organism (37 [17%] patients). Haemophilus influenzae was the most commonly identified established bacterial pathogen (20 [9%] patients). Pneumocystis jirovecii was only identified in patients with a CD4 count of less than 200 cells per mL. INTERPRETATION: We show the feasibility of using metatranscriptomics for epidemiologic surveillance of pneumonia by describing the spectrum of respiratory pathogens in adults with HIV in Uganda. Applying these methods to a contemporary cohort could enable broad assessment of changes in pneumonia aetiology following the emergence of SARS-CoV-2. FUNDING: US National Institutes of Health, Chan Zuckerberg Biohub.

14.
J Mol Biol ; : 167610, 2022 Apr 28.
Article in English | MEDLINE | ID: mdl-35490897

ABSTRACT

Drug research and development is a multidisciplinary field with its own successes. Yet, given the complexity of the process, it also faces challenges over the long development stages and even includes those that develop once a drug is marketed, i.e. drug toxicity and drug resistance. Better success can be achieved via well designed criteria in the early drug development stages. Here, we introduce the concepts of allostery and missense mutations, and argue that incorporation of these two intermittently linked biological phenomena into the early computational drug discovery stages would help to reduce the attrition risk in later stages of the process. We discuss the individual or in concert mechanisms of actions of mutations in allostery. Design of allosteric drugs is challenging compared to orthosteric drugs, yet they have been gaining popularity in recent years as alternative systems for the therapeutic regulation of proteins with an action-at-a-distance mode and non-invasive mechanisms. We propose an easy-to-apply computational allosteric drug discovery protocol which considers the mutation effect, and detail it with three case studies focusing on (1) analysis of effect of an allosteric mutation related to isoniazid drug resistance in tuberculosis; (2) identification of a cryptic pocket in the presence of an allosteric mutation of falcipain-2 as a malarial drug target; and (3) deciphering the effects of SARS-CoV-2 evolutionary mutations on a potential allosteric modulator with changes to allosteric communication paths.

15.
Malays J Med Sci ; 29(2): 1-7, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35528817

ABSTRACT

Cholera, a diarrheal disease caused by Vibrio cholerae (V. cholerae) O139 and O1 strains, remains a public health problem. The existing World Health Organization (WHO)-licenced, killed, multiple-dose oral cholera vaccines demand 'cold-chain supply' at 2 °C-8 °C. Therefore, a live, single-dose, cold-chain-free vaccine would relieve significant bottlenecks and costs of cholera vaccination campaigns. Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with isolation of the hemA gene from V. cholerae, followed by development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the 5-aminolaevulinic acid (ALA) prototrophic trait and excellent colonisation and immunological properties (100% protection to wild-type challenged rabbits). It was further refined in Asian Institute of Medicine, Science and Technology (AIMST University), with completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by development of a novel cold-chain-free VCUSM14P formulation in 2020. VCUSM14P is unique for its intact cholera toxin B, a known mucosal adjuvant. The built-in adjuvant makes VCUSM14P an ideal vaccine delivery platform for emerging diseases (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and tuberculosis). Our vaccine formulation mimics natural infection, remains non-reactogenic and immunogenic in vivo, and protects against infection and disease. It will also cost less and be less cumbersome to distribute due to its stability at room temperature. These features could revolutionise the outreach of this and other vaccines to meet global immunisation programmes, particularly in low-resourced areas. The next stage of our journey will be meeting the requisite regulatory requirements to produce the vaccine for rollout to countries where it is most needed.

16.
Radiol Clin North Am ; 60(3): 507-520, 2022 May.
Article in English | MEDLINE | ID: mdl-35534134

ABSTRACT

Despite the development of combination antiretroviral therapy (cART) infections continue to cause significant morbidity and mortality among people living with HIV (PLWH). Pulmonary infections with Streptococcus pneumoniae, Haemophilus influenza, and Staphylococcus aureus remain common. One-third of PLWH worldwide are infected with tuberculosis and the infection manifests at any stage of HIV infection. Fungal infection is usually confined to PLWH unaware of their HIV infection until immunosuppression is advanced or those choosing to discontinue cART. The importance of viral infections has diminished since wide availability of cART; however, mortality from COVID-19 in PLWH may remain greater than in the non-HIV population.


Subject(s)
COVID-19 , HIV Infections , HIV Infections/complications , HIV Infections/epidemiology , Humans
18.
Front Immunol ; 13: 856906, 2022.
Article in English | MEDLINE | ID: mdl-35514994

ABSTRACT

Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with Mycobacterium tuberculosis (Mtb), that results either in a latent or active form of disease, the latter associated with Mtb spread. In the absence of an effective vaccine, epidemiologic modeling suggests that aggressive treatment of individuals with active TB (ATB) may curb spread. Yet, clinical discrimination between latent (LTB) and ATB remains a challenge. While antibodies are widely used to diagnose many infections, the utility of antibody-based tests to diagnose ATB has only regained significant traction recently. Specifically, recent interest in the humoral immune response to TB has pointed to potential differences in both targeted antigens and antibody features that can discriminate latent and active TB. Here we aimed to integrate these observations and broadly profile the humoral immune response across individuals with LTB or ATB, with and without HIV co-infection, to define the most discriminatory humoral properties and diagnose TB disease more easily. Using 209 Mtb antigens, striking differences in antigen-recognition were observed across latently and actively infected individuals that was modulated by HIV serostatus. However, ATB and LTB could be discriminated, irrespective of HIV-status, based on a combination of both antibody levels and Fc receptor-binding characteristics targeting both well characterized (like lipoarabinomannan, 38 kDa or antigen 85) but also novel Mtb antigens (including Rv1792, Rv1528, Rv2435C or Rv1508). These data reveal new Mtb-specific immunologic markers that can improve the classification of ATB versus LTB.


Subject(s)
COVID-19 , HIV Infections , Latent Tuberculosis , Tuberculosis , Antibodies , HIV Infections/complications , Humans
19.
JMIR Form Res ; 6(5): e35994, 2022 May 06.
Article in English | MEDLINE | ID: mdl-35522469

ABSTRACT

BACKGROUND: In Thailand, the health care system has struggled to cope with COVID-19, resulting in directly observed therapy for tuberculosis being de-emphasized. A video-observed therapy (VOT) system, or more specifically, the Thai VOT (TH VOT) system, was developed to replace directly observed therapy. According to the pilot study, the system needed notifications to improve usability and user compliance. The updated version of the TH VOT system thus enabled LINE (Line Corporation) notifications. OBJECTIVE: This study aimed to reassess users' compliance with and the usability of the updated TH VOT system. METHODS: This study was conducted in the Hat Yai and Mueang Songkhla districts in Songkhla Province, Southern Thailand, from September 18 to December 1, 2021. The system was used by not only patients with tuberculosis but also tuberculosis staff, who acted as observers in primary health care settings. Some of the observers used the simulated VOT system instead of the actual system due to the lack of participating patients in their jurisdiction. After 30 days of using the system, VOT session records were analyzed to determine the compliance of the patients and observers. The User Experience Questionnaire was administered to reassess the usability of the system and compare the ratings of the participants with the general benchmark scores of the User Experience Questionnaire. The results were summarized to reveal the degree of user compliance and usability in the following three groups: the patients, actual VOT observers, and simulated VOT observers. RESULTS: Of the 19 observers, 10 used the actual VOT system, and the remaining 9 used the simulated VOT system; there were also 10 patients with tuberculosis. The patients, actual VOT observers, and simulated VOT observers exhibited about 70%, 65%, and 50% compliance, respectively, in terms of following the standard operating procedures every day. The scores of all groups on all dimensions were well above the average scores. There was no significant difference in any of the dimensional scores among the three groups. CONCLUSIONS: The updated version of the TH VOT system was deemed usable by both the patients and the health care staff. Compliance with the use of the system was high among the patients but moderate among the observers.

20.
Health Policy Plan ; 2022 May 09.
Article in English | MEDLINE | ID: mdl-35527232

ABSTRACT

Decentralised, person-centred models of care-delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high burden TB countries. The implementation of such models - made increasingly urgent by the COVID-19 pandemic - are key to addressing gaps in DR-TB care. We abstracted data of RR/MDR-TB patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan. We analysed trends in treatment outcomes relating to program expansion to peri-urban and rural areas and estimated driving distance from patient residence to treatment facility. Among the 5586 RR/MDR-TB patients in the analysis, overall treatment success decreased from 82% to 66% between 2010 and 2017, as the program expanded. The adjusted risk ratio for unfavourable outcomes was 1.013 (95% CI 1.005-1.021) for every 20 kilometres of driving distance. Our analysis suggests that expanding DR-TB care to centralised hubs added to increased unfavourable outcomes for people accessing care in peri-urban and rural districts. We propose that as enrolments increase, expanding DR-TB services close to or within affected communities is essential.

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