Xpert HIV-1 qual point-of-care testing for HIV early infant diagnosis in Tanzania: experiences and perceptions of health care workers in a 2016 study.

BACKGROUND: HIV early infant diagnosis (HEID) at the centralized laboratory faces many challenges that impact the cascade of timely HEID. Point of Care (PoC) HEID has shown to reduce test turnaround times, allow for task shifting and has the potential to reduce infant mortality. We aimed at assessing the feasibility of nurse based PoC-HEID in five facilities of Mbeya region. METHODS: We analysed data from healthcare workers at five obstetric health facilities that participated in the BABY study which enrolled mothers living with HIV and their HIV exposed infants who were followed up until 6 weeks post-delivery. Nurses and laboratory personnel were trained and performed HEID procedures using the Xpert HIV-1 Qual PoC systems. Involved personnel were interviewed on feasibility, knowledge and competency of procedures and overall impression of the use of HIV-1 Qual PoC system in clinical settings. RESULTS: A total of 28 health care workers (HCWs) who participated in the study between 2014 and 2016 were interviewed, 23 being nurses, 1 clinical officer, 1 lab scientist and 3 lab technicians The median age was 39.5 years. Majority of the nurses (22/24) and all lab staff were confident using Gene Xpert PoC test after being trained. None of them rated Gene Xpert handling as too complicated despite minor challenges. Five HCWs (5/24) reported power cut as the most often occurring problem. As an overall impression, all interviewees agreed on PoC HEID to be used in clinical settings however, about half of them (11/24) indicated that the PoC-HEID procedures add a burden onto their routine workload. CONCLUSION: Overall, health care workers in our study demonstrated very good perceptions and experiences of using PoC HEID. Efforts should be invested on quality training, targeted task distribution at the clinics, continual supportive supervision and power back up mechanisms to make the wide-scale adoption of nurse based PoC HEID testing a possibility.

Tuberculosis Molecular Bacterial Load Assay Reveals Early Delayed Bacterial Killing in Patients With Relapse.

Bacterial killing in patients with tuberculosis (TB) relapse was compared to that in patients achieving cure, measured by TB molecular bacterial load assay (TB-MBLA) or mycobacteria growth indicator tube (MGIT) time to positivity (TTP). TB-MBLA in 4 relapsed patients was significantly different compared to 132 cured patients after 2 weeks of treatment; MGIT TTP showed a significant difference from week 8.

"Honestly, this problem has affected me a lot": a qualitative exploration of the lived experiences of people with chronic respiratory disease in Sudan and Tanzania.

BACKGROUND: Over 500 million people live with chronic respiratory diseases globally and approximately 4 million of these, mostly from the low- and middle-income countries including sub-Saharan Africa, die prematurely every year. Despite high CRD morbidity and mortality, only very few studies describe CRDs and little is known about the economic, social and psychological dimensions of living with CRDs in sub-Saharan Africa. We aimed to gain an in-depth understanding of the social, livelihood and psychological dimensions of living with CRD to inform management of CRDs in Sudan and Tanzania. METHOD: We conducted 12 in-depth interviews in 2019 with people with known or suspected CRD and 14 focus group discussions with community members in Gezira state, Sudan and Dodoma region, Tanzania, to share their understanding and experience with CRD. The data was analysed using thematic framework analysis. RESULTS: People with CRD in both contexts reported experiences under two broad themes: impact on economic wellbeing and impact on social and psychological wellbeing. Capacity to do hard physical work was significantly diminished, resulting in direct and indirect economic impacts for them and their families. Direct costs were incurred while seeking healthcare, including expenditures on transportation to health facility and procurement of diagnostic tests and treatments, whilst loss of working hours and jobs resulted in substantial indirect costs. Enacted and internalised stigma leading to withdrawal and social exclusion was described by participants and resulted partly from association of chronic cough with tuberculosis and HIV/AIDS. In Sudan, asthma was described as having negative impact on marital prospects for young women and non-disclosure related to stigma was a particular issue for young people. Impaired community participation and restrictions on social activity led to psychological stress for both people with CRD and their families. CONCLUSION: Chronic respiratory diseases have substantial social and economic impacts among people with CRD and their families in Sudan and Tanzania. Stigma is particularly strong and appears to be driven partly by association of chronic cough with infectiousness. Context-appropriate measures to address economic impacts and chronic cough stigma are urgently needed as part of interventions for chronic respiratory diseases in these sub-Saharan African contexts.

Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections.

Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30-41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman's rank correction coefficient (r) between TB-MBLA and MGIT was -0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics.

Phylogenetic lineages of tuberculosis isolates and their association with patient demographics in Tanzania.

BACKGROUND: Mycobacterium tuberculosis presents several lineages each with distinct characteristics of evolutionary status, transmissibility, drug resistance, host interaction, latency, and vaccine efficacy. Whole genome sequencing (WGS) has emerged as a new diagnostic tool to reliably inform the occurrence of phylogenetic lineages of Mycobacterium tuberculosis and examine their relationship with patient demographic characteristics and multidrug-resistance development. METHODS: 191 Mycobacterium tuberculosis isolates obtained from a 2017/2018 Tanzanian drug resistance survey were sequenced on the Illumina Miseq platform at Supranational Tuberculosis Reference Laboratory in Uganda. Obtained fast-q files were imported into tools for resistance profiling and lineage inference (Kvarq v0.12.2, Mykrobe v0.8.1 and TBprofiler v3.0.5). Additionally for phylogenetic tree construction, RaxML-NG v1.0.3(25) was used to generate a maximum likelihood phylogeny with 800 bootstrap replicates. The resulting trees were plotted, annotated and visualized using ggtree v2.0.4 RESULTS: Most [172(90.0%)] of the isolates were from newly treated Pulmonary TB patients. Coinfection with HIV was observed in 33(17.3%) TB patients. Of the 191 isolates, 22(11.5%) were resistant to one or more commonly used first line anti-TB drugs (FLD), 9(4.7%) isolates were MDR-TB while 3(1.6%) were resistant to all the drugs. Of the 24 isolates with any resistance conferring mutations, 13(54.2%) and 10(41.6%) had mutations in genes associated with resistance to INH and RIF respectively. The findings also show four major lineages i.e. Lineage 3[81 (42.4%)], followed by Lineage 4 [74 (38.7%)], the Lineage 1 [23 (12.0%)] and Lineages 2 [13 (6.8%)] circulaing in Tanzania. CONCLUSION: The findings in this study show that Lineage 3 is the most prevalent lineage in Tanzania whereas drug resistant mutations were more frequent among isolates that belonged to Lineage 4.

The second national anti-tuberculosis drug resistance survey in Tanzania, 2017-2018.

OBJECTIVE: To determine the levels and patterns of resistance to first- and second-line anti-tuberculosis (TB) drugs among new and previously treated sputum smear positive pulmonary TB (PTB) patients. METHODS: We conducted a nationally representative cross-sectional facility-based survey in June 2017-July 2018 involving 45 clusters selected based on probability proportional to size. The survey aimed to determine the prevalence of anti-TB drug resistance and associated risk factors among smear positive PTB patients in Tanzania. Sputum samples were examined using smear microscopy, Xpert MTB/RIF, culture and drug susceptibility testing (DST). Logistic regression was used to account for missing data and sampling design effects on the estimates and their standard errors. RESULTS: We enrolled 1557 TB patients, including 1408 (90.4%) newly diagnosed and 149 (9.6%) previously treated patients. The prevalence of multidrug-resistant TB (MDR-TB) was 0.85% [95% confidence interval (CI): 0.4-1.3] among new cases and 4.6% (95% CI: 1.1-8.2) among previously treated cases. The prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) was 1.7% among new TB patients and 6.5% among those previously treated. Drug resistance to all first-line drugs was similar (0.1%) in new and previously treated patients. None of the isolates displayed poly-resistance or extensively drug-resistant TB (XDR-TB). The only risk factor for MDR-TB was history of previous TB treatment (odds ratio = 5.7, 95% CI: 1.9-17.2). CONCLUSION: The burden of MDR-TB in the country was relatively low with no evidence of XDR-TB. Given the overall small number of MDR-TB cases in this survey, it will be beneficial focusing efforts on intensified case detection including universal DST.

Clinical-demographic markers for improving diabetes mellitus diagnosis in people with tuberculosis in Tanzania.

BACKGROUND: Tuberculosis (TB) control is threatened by an increasing prevalence of diabetes mellitus (DM), particularly in endemic countries. Screening for DM is not routinely implemented in Tanzania; therefore, we aimed to screen for DM at TB diagnosis using clinical-demographic markers. METHODS: Our cross-sectional study recruited TB patients who received anti-TB treatment between October 2019 and September 2020 at health care facilities in three regions from Tanzania. Patients were screened for DM using DM symptoms (polydipsia, polyphagia and polyuria) and random blood glucose (RBG) testing. Patients with a history of DM and those with no history of DM but an RBG ≥ 7.8 mmol/L had point-of-care glycated haemoglobin (HbA1c) testing, and were considered to have DM if HbA1c was ≥ 48 mmol/mol. RESULTS: Of 1344 TB patients, the mean age was 41.0 (± 17.0) years, and 64.7% were male. A total of 1011 (75.2%) had pulmonary TB, and 133 (10.4%) had at least one DM symptom. Overall, the prevalence of DM was 7.8%, of which 36 (2.8%) TB patients with no history of DM were newly diagnosed with DM by RBG testing. TB/DM patients were older than those with only TB (50.0 ± 14.0 years vs 40.0 ± 17.0 years, p < 0.001). Patients with RBG ≥ 7.8 mmol/L were more likely to have pulmonary TB (p = 0.003), age ≥ 35 years (p = 0.018), and have at least one DM symptom (p < 0.001). There was a substantial agreement (Kappa = 0.74) between the on-site glucometer and point-of-care HbA1c tests in detecting DM range of hyperglycemia. CONCLUSION: The implementation of clinical-demographic markers and blood glucose screening identified the overall prevalence of DM and those at risk of DM in TB patients. Clinical-demographic markers are independent predictors for DM range hyperglycemia and highlight the importance of further diagnostic testing and early co-management of TB and DM.

Seroprevalence of herpes simplex virus type 1 among people living with HIV in Mbeya, Tanzania.

BACKGROUND: Despite the significant decline in the prevalence of HIV in Tanzania, the prevalence rates in Mbeya, Iringa, and Njombe regions are higher than the national average and have remained stable for years. The current stable HIV prevalence may be driven by factors such as a high incidence of sexually transmitted infections (STIs) and high-risk behaviours. In sub-Saharan Africa, it has previously been observed that up to 50% of HIV cases were attributed to herpes simplex type 2 (HSV-2) among low-risk populations. Because the proportion of sexually transmitted HSV-1 is rising, it is essential to study the interaction between HSV-1 and HIV infections. METHODS: We conducted a study in Mbeya region using the archived blood sera of participants from the recently completed EU-funded EMINI project. A specially designed questionnaire was used to obtain the social and demographic characteristics of the study participants in the database. We tested archived participants' sera for herpes simplex virus type 1 using Virotech HSV-1 (gG1) IgG ELISA (Enzygnost, Behring, Germany). Univariate and multivariate Poisson regression models were used to identify factors associated with HSV-1. RESULTS: A total of 640 adults were randomly recruited after stratification by HIV status (318 were HIV positive), age, and sex. The overall seroprevalence of HSV-1 in the study population was 92.1%. The extrapolated seroprevalence estimate of herpes simplex virus type 1 in the general population was 95.0% (96.0% in males versus 94.0% in females). Males and females were equally affected by HSV-1. HSV-1 was less prevalent in HIV-positive individuals than in HIV-negative individuals. CONCLUSION: People living with HIV were less likely to be HSV-1 seropositive. Further prospective studies are necessary to conclude a causal association.

Accuracy and Operational Characteristics of Xpert Human Immunodeficiency Virus Point-of-Care Testing at Birth and Until Week 6 in Human Immunodeficiency Virus-exposed Neonates in Tanzania.

Background: Point-of-care (PoC) systems for early infant diagnosis (EID) may improve timely infant human immunodeficiency virus (HIV) management. Experiences within African public health settings are limited. Methods: We evaluated the accuracy and operational feasibility of the Xpert HIV-1 Qual for PoC-EID testing, using fresh blood and dried blood spots (DBS) samples at obstetric health facilities in Tanzania at birth and at postpartum weeks 1, 2, 3, and 6 in HIV-exposed infants. Test results were confirmed using TaqMan DBS HIV-deoxyribonucleic acid and/or plasma HIV-ribonucleic acid (RNA) testing. Results: At week 6, 15 (2.5%) out of 614 infants were diagnosed with HIV; 10 (66.7%) of them at birth (median HIV-RNA 4570 copies/mL). At birth, the Xpert-PoC and Xpert-DBS were 100% sensitive (95% confidence intervals: PoC, 69.2-100%; DBS, 66.4-100%) and 100% specific (PoC, 92.1-100%; DBS, 88.4-100%). By week 3, 5 infants with intra/postpartum HIV-infection (median HIV-RNA 1 160 000 copies/mL) were all correctly diagnosed by Xpert. In 2 cases, Xpert-PoC testing correctly identified HIV-infection when DBS tests (Xpert and TaqMan) were negative, suggesting a greater sensitivity. In 2 infants with confirmed HIV at birth, all tests were negative at week 6, possibly because of viral suppression under nevirapine prophylaxis. Problems were reported in 183/2736 (6.7%) of Xpert-PoC tests, mostly related to power cuts (57.9%). Conclusions: We demonstrated excellent Xpert HIV-1 Qual performance and good operational feasibility for PoC-EID testing at obstetric health facilities. Week 6 sensitivity issues were possibly related to nevirapine prophylaxis, supporting additional birth PoC-EID testing to avoid underdiagnosis. Clinical Trials Registration: NCT02545296.

Quantifying Viable M. tuberculosis Safely Obviating the Need for High Containment Facilities.

Mycobacterium tuberculosis is an infectious pathogen that requires biosafety level-3 laboratory for handling. The risk of transmission is high to laboratory staff, and to manage the organism safely, it is necessary to construct high containment laboratory facilities at great expense. This limits the application of tuberculosis diagnostics to areas where there is insufficient capital to invest in laboratory infrastructure. In this method, we describe a process of inactivating sputum samples by either heat or guanidine thiocyanate (GTC) that renders them safe without affecting the quantification of viable bacteria. This method eliminates the need for level 3 containment laboratory for the tuberculosis molecular bacterial load assay (TB-MBLA) and is applicable in low- and middle-income countries.

Improved Diagnosis and Treatment Monitoring of Tuberculosis Using Stool and the Tuberculosis Bacterial Load Assay (TB-MBLA).

The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment. We have shown that stool is a potential alternative sample type for diagnosis of tuberculosis. Currently, available protocols like the Xpert MTB/RIF use DNA as a target to detect Mycobacterium tuberculosis in stool but DNA survives long after the organism is dead so it is not certain whether a positive test is from an old or a partially treated infection. The TB MBLA only detects live organisms and thus, can be used to follow the response to treatment. In this chapter, we describe a protocol for TB-MBLA, an RNA-based assay, and apply it to quantify TB bacteria in stool.

Performance of a stool-based quantitative PCR assay for the diagnosis of tuberculosis in adolescents and adults: a multinational, prospective diagnostic accuracy study.

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens. METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR test with the current diagnostic standard for Mycobacterium tuberculosis DNA detection from sputum and stool, Xpert-MTB/RIF Ultra (Xpert Ultra). Sputum, stool, and urine samples were provided by a cohort of participants, aged 10 years or older, diagnosed with tuberculosis. Participants with tuberculosis (cases) were enrolled within 72 h of treatment initiation for tuberculosis diagnosed clinically or following laboratory confirmation. Participants without tuberculosis (controls) consisted of household contacts of the cases who did not develop tuberculosis during a 6-month follow-up. The performance was compared with a robust composite microbiological reference standard (CMRS). FINDINGS: The cohort of adolescents and adults (n=408) included 268 participants with confirmed or clinical tuberculosis (cases), 147 (55%) of whom were living with HIV, and 140 participants (controls) without tuberculosis. The sensitivity of the novel stool qPCR was 93·7% (95% CI 87·4-97·4) compared with participants with detectable growth on M tuberculosis culture, and 88·1% (81·3-93·0) compared with sputum Xpert Ultra. The stool qPCR had an equivalent sensitivity as sputum Xpert Ultra (94·8%, 89·1-98·1) compared with culture. Compared with the CMRS, the sensitivity of the stool qPCR was higher than the current standard for tuberculosis diagnostics on stool, Xpert Ultra (80·4%, 73·4-86·2 vs 73·5%, 66·0-80·1; p=0·025 on paired comparison). The qPCR also identified 17-21% additional tuberculosis cases compared to sputum Xpert Ultra or sputum culture. In controls without tuberculosis, the specificity of the stool qPCR was 96·9% (92·2-99·1). INTERPRETATION: In this study, a novel qPCR for the diagnosis of tuberculosis from stool specimens had a higher accuracy in adolescents and adults than the current diagnostic PCR gold standard on stool, Xpert-MTB/RIF Ultra, and equivalent sensitivity to Xpert-MTB/RIF Ultra on sputum. FUNDING: National Institutes of Health (NIH) Allergy and Infectious Diseases, and NIH Fogarty International Center.

Localization and phenotyping of tuberculosis bacteria using a combination of deep learning and SVMs.

Successful treatment of pulmonary tuberculosis (TB) depends on early diagnosis and careful monitoring of treatment response. Identification of acid-fast bacilli by fluorescence microscopy of sputum smears is a common tool for both tasks. Microscopy-based analysis of the intracellular lipid content and dimensions of individual Mycobacterium tuberculosis (Mtb) cells also describe phenotypic changes which may improve our biological understanding of antibiotic therapy for TB. However, fluorescence microscopy is a challenging, time-consuming and subjective procedure. In this work, we automate examination of fields of view (FOVs) from microscopy images to determine the lipid content and dimensions (length and width) of Mtb cells. We introduce an adapted variation of the UNet model to efficiently localising bacteria within FOVs stained by two fluorescence dyes; auramine O to identify Mtb and LipidTox Red to identify intracellular lipids. Thereafter, we propose a feature extractor in conjunction with feature descriptors to extract a representation into a support vector multi-regressor and estimate the length and width of each bacterium. Using a real-world data corpus from Tanzania, the proposed method i) outperformed previous methods for bacterial detection with a 8% improvement (Dice coefficient) and ii) estimated the cell length and width with a root mean square error of less than 0.01%. Our network can be used to examine phenotypic characteristics of Mtb cells visualised by fluorescence microscopy, improving consistency and time efficiency of this procedure compared to manual methods.

A practical approach to render tuberculosis samples safe for application of tuberculosis molecular bacterial load assay in clinical settings without a biosafety level 3 laboratory.

BACKGROUND: Mycobacterium tuberculosis is a category B infectious pathogen requiring level-3-containment laboratories for handling. We assessed the efficacy of heat and Guanidine thiocyanate (GTC) to inactivate M. tuberculosis prior to performance of tuberculosis Molecular Bacterial Load Assay (TB-MBLA). METHOD: We performed in vitro experiments using M.tb, H37Rv reference strain and replicated in sputum specimens. A 0.5 MacFarland standard of M. tuberculosis was serially diluted to 1x101 CFU/mL and pooled sputum was homogenised prior to serial dilutions and Xpert MTB/RIF Ultra. Three replicates for each containing 1 mL for M. tuberculosis and sputum were inactivated at 80 °C for 20 min and with GTC for 15 min. Inactivated samples were processed for culture and TB-MBLA. RESULTS: No M. tuberculosis growth was observed in MGIT for GTC or heat treated H37Rv cultures. All untreated H37Rv dilutions were MGIT positive except the most diluted specimens. Heat and GTC treatment of H37Rv reduced TB-MBLA load by 2.1log10 (P = 0.7) and 1.8log10 (P = 0.7) respectively, compared to controls. In contrast, heat treated sputum had TB-MBLA bacterial load of 3.47 ± 3.53 log10 compared to 5.4 ± 3.1 log10 eCFU/mL for GTC (p = 0.57). All heat and GTC treated sputum were culture negative. CONCLUSION: Heat or GTC renders M. tuberculosis non-viable and eliminates the need for BSL3 laboratory for performing TB-MBLA in routine healthcare settings.

Burden and associated phenotypic characteristics of tuberculosis infection in adult Africans with diabetes: a systematic review.

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I2 = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease.

Humoral Immune Responses following COVID-19 Vaccinations among Adults in Tanzania.

COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania. A total of 1048 randomly selected adults who received COVID-19 vaccines at different time points were enrolled and humoral immune responses (IR) were tested at baseline and three months later (960, 91.6%). The level of SARS-CoV-2 anti-spike/receptor binding domain (RBD) IgG, anti-nucleocapsid IgG, and IgM antibodies were determined using a commercially available chemiluminescent microparticle immunoassay. Descriptive data analysis was performed using STATA version 18 and R. At baseline, serum IgG against anti-spike/RBD was detected in 1010/1048 (96.4%) participants (95%CI: 94.9-97.5) and 98.3% (95%CI: 97.3-99) three months later. The IgG against the SARS-CoV-2 nucleocapsid proteins were detected in 40.8% and 45.3% of participants at baseline and follow-up, respectively. The proportion of seroconverters following vaccination and mean titers of anti-spike/RBD antibodies were significantly more among those who had past SARS-CoV-2 infection than in those with no evidence of past infection, (p < 0.001). Only 0.5% of those who had detectable anti-spike/RBD antibodies at baseline were negative after three months of follow-up and 1.5% had breakthrough infections. The majority of participants (99.5%) had detectable anti-spike/RBD antibodies beyond 6 months post-vaccination. The proportion of Tanzanians who mounted humoral IR following COVID-19 vaccination was very high. Seroconversions, as well as the mean titers and durability of humoral IR, were significantly enhanced by exposure to natural SARS-CoV-2 infection. In view of the limited availability of COVID-19 vaccines as well as challenges to completing subsequent doses, booster doses could only be suggested to high-risk groups.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl-1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response.

HIV testing and linkage to care-A case of a mobile diagnostic and counseling service in Mbeya, Tanzania; A quantitative study.

HIV-care programmes are faced with significant challenges in getting newly diagnosed People Living with Human Immunodeficiency Virus (PLHIV) linked to care despite massive investment in HIV prevention, treatment and care. This study assessed the performance of mobile HIV Testing and Counseling service (mHTC) in provision of HIV-testing and linkage to care of newly diagnosed PLHIV from Key and Vulnerable Populations (KVPs). A retrospective review of the records of 25,248 clients was extracted from the mHTC database from October-2016 to September-2018. Of 25,248 clients, 51.71% were in 25-45 years age group, 55.4% were males, 60.5% were married and 62.1% had primary level of education. The median age of clients was 31 (IQR: 23-42) years. Out of the clients tested, 800 (3.17%) were diagnosed HIV-positive. Positivity was high among females 450 (4%), age group 25-45 years 538 (4.12%), divorced 202 (7.41%) and clients with primary level of education 504 (3.21%). An association between HIV status and sex, age group, relationship status and level of education was observed (P<0001). Out of the 800 HIV-positive clients, 418 (52.30%) were successfully linked to care. Among the positive clients, 5/6 (83.33%) children below 15 years old, 238/450 (52.89%) females and 39/64 (60.94%) widows were successfully linked to care. In the multivariable log binomial regression model age of the clients was associated with successful linkage to care. The mHTC was able to reach KVP clients; overall linkage for both sexes was 52.30% below the recommended UNAIDS 90-90-90 target. Raising the need to address the challenges associated with linkage and specific care for KVPs as a subset of the general population. The mHTC has shown that it is feasible to improve the reach of KVP clients; however, further research is required to examine the quality of this service at the community level.

Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients-A Systematic Review.

Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH) neutralizes ROS, although it is consumed. NAC is a precursor of GSH synthesis, and administering an appropriate dose of NAC to patients with respiratory conditions may enhance lung recovery and replenish GSH. The present review searched for articles reporting on the effects of NAC in TB treatment from 1960 to 31 May 2022. The PICO search strategy was used in Google Scholar, PubMed, SciFinder, and Wiley online library databases. The COVIDENCE tool was used to delete inappropriate content. We eventually discovered five clinical trials, one case report, seven reviews, in vitro research, and four experimental animal studies from the twenty-four accepted articles. The use of NAC resulted in increased GSH levels, decreased treatment time, and was safe with minimal adverse events. However, the evidence is currently insufficient to estimate the overall effects of NAC, thus the study warrants more NAC clinical trials to demonstrate its effects in TB treatment.