Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells

Background Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation. Methodology/Principal findings Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DR(pos)CD38(pos) CD4 T cells and effector memory cells CD4 T cells (CD45RO(pos)CD27(neg)) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections. Conclusions/Significance W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection

Ascaris lumbricoides Infection and Its Relation to Environmental Factors in the Mbeya Region of Tanzania, a Cross-Sectional, Population-Based Study

Background: With one quarter of the world population infected, the intestinal nematode Ascaris lumbricoides is one of the most common infectious agents, especially in the tropics and sub-tropics. Infection is caused by oral intake of eggs and can cause respiratory and gastrointestinal problems. To identify high risk areas for intervention, it is necessary to understand the effects of climatic, environmental and socio-demographic conditions on A. lumbricoides infection. Methodology: Cross-sectional survey data of 6, 366 study participants in the Mbeya region of South-Western Tanzania were used to analyze associations between remotely sensed environmental data and A. lumbricoides infection. Non-linear associations were accounted for by using fractional polynomial regression, and socio-demographic and sanitary data were included as potential confounders. Principal Findings: The overall prevalence of A. lumbricoides infection was 6.8%. Our final multivariable model revealed a significant non-linear association between rainfall and A. lumbricoides infection with peak prevalences at 1740 mm of mean annual rainfall. Mean annual land surface temperature during the day was linearly modeled and negatively associated with A. lumbricoides infection (odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.78-0.97). Furthermore, age, which also showed a significant non-linear association (infection maximum at 7.7 years),socio-economic status (OR = 0.82, CI = 0.68-0.97),and latrine coverage around the house (OR = 0.80, CI = 0.67-0.96) remained in the final model. Conclusions: A. lumbricoides infection was associated with environmental, socio-demographic and sanitary factors both in uni-and multivariable analysis. Non-linear analysis with fractional polynomials can improve model fit, resulting in a better understanding of the relationship between environmental conditions and helminth infection, and more precise predictions of high prevalence areas. However, socio-demographic determinants and sanitary conditions should also be considered, especially when planning public health interventions on a smaller scale, such as the community level

The Mbeya Antimicrobial Stewardship Team: Implementing Antimicrobial Stewardship at a Zonal-Level Hospital in Southern Tanzania

In 2017, Mbeya Zonal Referral Hospital (MZRH) and the University of South Carolina (UofSC) agreed to collaboratively strengthen antimicrobial prescribing in the southern highlands of Tanzania and train a new generation of clinicians in responsible antimicrobial use. Key stakeholders and participants were identified and the Mbeya Antimicrobial Stewardship Team (MAST) was created. The team identified assets brought by the collaborators, and four investigations of baseline needs were developed. These investigations included (a) a baseline clinician survey regarding antimicrobial resistance and stewardship, (b) a serial chart review of inpatient antimicrobial prescribing practices, (c) an investigation of antimicrobial resistance rates using existing isolates at the MZRH laboratory, and (d) a survey of antimicrobial availability at community pharmacies in the city. 91% of physicians believe antimicrobial resistance is problem in Tanzania, although only 29% of physicians were familiar with the term antimicrobial stewardship . isolates had resistance rates of over 60% to the commonly used agents ciprofloxacin, trimethoprim-sulfamethoxazole, and ceftriaxone. Thirteen out of 14 community pharmacies offered over-the-counter antibiotics for upper respiratory symptoms. International antimicrobial stewardship collaborations can successfully identify opportunities and needs. Evaluating the team\u27s efforts to improve patient outcomes will be essential

Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-sectional, Population-based study.

Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care

Helminth-Associated Systemic Immune Activation and HIV Co-receptor Expression: Response to Albendazole/Praziquantel Treatment

Background: It has been hypothesized that helminth infections increase HIV susceptibility by enhancing systemic immune activation and hence contribute to elevated HIV-1 transmission in sub-Saharan Africa. Objective: To study systemic immune activation and HIV-1 co-receptor expression in relation to different helminth infections and in response to helminth treatment. Methods: HIV-negative adults with (n = 189) or without (n = 57) different helminth infections, as diagnosed by Kato-Katz, were enrolled in Mbeya, Tanzania. Blinded to helminth infection status, T cell differentiation (CD45RO, CD27),activation (HLA-DR, CD38) and CCR5 expression was determined at baseline and 3 months after Albendazole/Praziquantel treatment. Plasma cytokine levels were compared using a cytometric bead array. Results: Trichuris and Ascaris infections were linked to increased frequencies of "activated'' CD4 and/or CD8 T cells (p< 0.05),whereas Hookworm infection was associated with a trend towards decreased HLA-DR+ CD8 T cell frequencies (p = 0.222). In Trichuris infected subjects, there was a linear correlation between HLA-DR+ CD4 T cell frequencies and the cytokines IL-1 beta and IL-10 (p<0.05). Helminth treatment with Albendazole and Praziquantel significantly decreased eosinophilia for S. mansoni and Hookworm infections (p<0.005) but not for Trichuris infection and only moderately modulated T cell activation. CCR5 surface density on memory CD4 T cells was increased by 1.2-fold during Trichuris infection (p-value: 0.053) and reduced after treatment (p = 0.003). Conclusions: Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment

Comparative evaluation of Amplicor HIV-1 DNA test, version 1.5, by manual and automated DNA extraction methods using venous blood and dried blood spots for HIV-1 DNA PCR testing

Human immunodeficiency virus (HIV) DNA polymerase chain reaction (PCR) test using venous blood sample has been used for many years in low resource settings for early infant diagnosis of HIV infection in children less than 18 months. The aim of this study was to evaluate and compare the performance characteristics of Amplicor HIV-1 DNA assay version 1.5 following processing of venous blood and dried blood spot (DBS) samples by Roche manual DNA extraction and automated Roche MagNA Pure LC instrument (MP) for HIV-1 DNA PCR testing in Dar es Salaam, Tanzania, in order to scale up early infant diagnosis of HIV infection in routine practice. Venous blood samples from children under 18 months born to HIV-infected mothers between January and April 2008 were collected. Venous blood was used to prepare cell pellet and DBS samples. DNA extractions by manual procedure and MP were performed each on cell pellet, venous blood and DBS samples and tested by Amplicor HIV-1 DNA assay. Of 325 samples included, 60 (18.5%) were confirmed HIV-infected by manual extraction performed on cell pellets. Sensitivity of the assay following MP processing of venous blood was 95% (95% CI; 86.1-99.0%) and 98.3% (95% CI; 91.1 to 99.9%) for the manual extraction and processing by MP performed on DBS samples. Specificity of the assay with all DNA extraction methods was 99.6% (95% CI; 97.9 to 100%). Performance of the assay with Roche manual extraction and processing by MP on DBS samples compared well with Roche manual extraction performed on cell pellet samples. The choice of DNA extraction method needs to be individualized based on the level of laboratory facility, volume of testing and cost benefit analysis before it is adopted for use

Comparative evaluation of Amplicor HIV-1 DNA test, version 1.5, by manual and automated DNA extraction methods using venous blood and dried blood spots for HIV-1 DNA PCR testing

Human immunodeficiency virus (HIV) DNA polymerase chain reaction (PCR) test using venous blood sample has been used for many years in low resource settings for early infant diagnosis of HIV infection in children less than 18 months. The aim of this study was to evaluate and compare the performance characteristics of Amplicor HIV-1 DNA assay version 1.5 following processing of venous blood and dried blood spot (DBS) samples by Roche manual DNA extraction and automated Roche MagNA Pure LC instrument (MP) for HIV-1 DNA PCR testing in Dar es Salaam, Tanzania, in order to scale up early infant diagnosis of HIV infection in routine practice. Venous blood samples from children under 18 months born to HIV-infected mothers between January and April 2008 were collected. Venous blood was used to prepare cell pellet and DBS samples. DNA extractions by manual procedure and MP were performed each on cell pellet, venous blood and DBS samples and tested by Amplicor HIV-1 DNA assay. Of 325 samples included, 60 (18.5%) were confirmed HIV-infected by manual extraction performed on cell pellets. Sensitivity of the assay following MP processing of venous blood was 95% (95% CI; 86.1-99.0%) and 98.3% (95% CI; 91.1 to 99.9%) for the manual extraction and processing by MP performed on DBS samples. Specificity of the assay with all DNA extraction methods was 99.6% (95% CI; 97.9 to 100%). Performance of the assay with Roche manual extraction and processing by MP on DBS samples compared well with Roche manual extraction performed on cell pellet samples. The choice of DNA extraction method needs to be individualized based on the level of laboratory facility, volume of testing and cost benefit analysis before it is adopted for use

Prescribing patterns of antimicrobials according to the WHO AWaRe classification at a tertiary referral hospital in the southern highlands of Tanzania

Summary: Background: Antimicrobial consumption continues to rise globally and contributes to the emergence and spread of antimicrobial resistance. This study aimed to evaluate antimicrobial prescribing patterns in a selected tertiary hospital in Tanzania. Methods: This cross-sectional study was conducted for one year (September 2021–September 2022) at Mbeya Zonal Referral Hospital, a public hospital in the southern highlands zone of Tanzania. Data on clinical diagnosis, laboratory tests, prescribed antimicrobials, and prescribers' designations were collected through a custom eMedical system, aligning antimicrobials with the WHO's 2021 AWaRe classification. Descriptive analysis was performed to assess the pattern of antimicrobial prescriptions. Results: Of 2,293 antimicrobial prescriptions, 62.41% were ACCESS, 37.42% were WATCH, and 0.17% fell in the RESERVE categories. Metronidazole, accounting for 23.8%, was the most commonly prescribed antimicrobial. More than 50% of the ACCESS and WATCH prescriptions were justified by laboratory diagnosis and were predominantly prescribed by clinicians. A very small proportion of prescriptions (<1%) were informed by culture and sensitivity (C/S) testing. The Paediatric department had the majority of WATCH prescriptions (72.2%). Conclusion: The prescribing patterns at the study hospital generally align with WHO AWaRe guidelines, potentially mitigating antimicrobial resistance. Nevertheless, the scarcity of culture and sensitivity testing is a concern that warrants targeted improvement

Reasons for false-positive lipoarabinomannan ELISA results in a Tanzanian population

Abstract Lipoarabinomannan (LAM), a cell wall component of mycobacteria, can be detected in the urine of tuberculosis (TB) patients. Advantages of this diagnostic include the ease of sample collection and test methods. However, as with most new TB diagnostics, LAM tests have been evaluated in well-controlled laboratory settings and subsequently need assessment under real working conditions. Our experience showed that the diagnosis of TB using the detection of LAM in urine under field conditions is prone to false-positive results due to contamination. Dust and soil, but also stool, seemed to lead to increased OD values and thus false-positive results of the enzyme-linked immunosorbent assay (ELISA) for LAM; however, contamination with blood, as well as bacterial or fungal organisms, had no influence. The collection of urine for the detection of LAM should therefore follow strict collection criteria in order to avoid contamination

Diagnostic accuracy of Kato-Katz, FLOTAC, Baermann, and PCR methods for the detection of light-intensity hookworm and Strongyloides stercoralis infections in Tanzania

Abstract. Sensitive diagnostic tools are crucial for an accurate assessment of helminth infections in low-endemicity areas. We examined stool samples from Tanzanian individuals and compared the diagnostic accuracy of a real-time polymerase chain reaction (PCR) with the FLOTAC technique and the Kato-Katz method for hookworm and the Baermann method for Strongyloides stercoralis detection. Only FLOTAC had a higher sensitivity than the Kato-Katz method for hookworm diagnosis; the sensitivities of PCR and the Kato-Katz method were equal. PCR had a very low sensitivity for S. stercoralis detection. The cycle threshold values of the PCR were negatively correlated with the logarithm of hookworm egg and S. stercoralis larvae counts. The median larvae count was significantly lower in PCR false negatives than true positives. All methods failed to detect very low-intensity infections. New diagnostic approaches are needed for monitoring of progressing helminth control programs, confirmation of elimination, or surveillance of disease recrudescence