Search

The palynological composition of the Karoo-equivalent strata in the Tanga Basin, coastal Tanzania, is presented. Two boreholes (Kakindu-1 and Vunde-1) through the basin were palynostratigraphically studied. According to the findings, gymnosperm pollen and a few fern spores dominate the palynological assemblages. The absence of marine palynomorphs in the studied strata of the Tanga Basin attests to deposition in terrestrial environments, which is consistent with the common geologic reconstruction of the Karoo Supergroup across Africa. Two palynological intervals, the Klausipollenites schaubergeri and Jugasporites vellicoites, are recognized in the Kakindu-1 borehole; and two others, the Klausipollenites schaubergeri–Scheuringipollenites circularis and Alisporites minutosaccus–Faunipollenites gopadensis intervals, are identified in the Vunde-1 borehole. The present palynological data suggest the Permian to Triassic age for the Karoo strata in the Tanga Basin. The composition of the reported assemblage implies a single phytogeographic province across the Gondwana Supercontinent during the Permian to Triassic. Based on depositional ages determined herein, the Karoo strata in the Tanga Basin are correlated with second–fourth depositional sequences in the inland Karoo type-section of the Ruhuhu Basin of Tanzania, as well as to Ecca and Beaufort groups of the original Karoo type-section in South Africa. [ABSTRACT FROM AUTHOR]

Background: Prospective studies of interferon-gamma release assays (IGRA) on healthy subjects in tuberculosis-endemic regions have not examined the long-term variability of serial assays. This issue is relevant to the interpretation of tuberculosis (TB) vaccine trials based on prevention of infection. Methods: T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. Results: 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (≥2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). Conclusions: Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease. [ABSTRACT FROM AUTHOR]

We present findings from a blast movement monitoring research conducted as a part of mine to mill campaign at the Geita Gold Mine—and additional data from blast monitoring practices at North Mara Gold Mine. These include measurement of the blast-induced rock movement and perimeter translation after blast derived from a blast shot at Nyankanga pit (Geita Gold Mine) and three other shots at the Nyabirama pit (North Mara Gold Mine). Using Blast Movement Technology, 34 movement-monitoring balls installed in 13 blast-monitoring boreholes made possible estimation of the average vertical and horizontal ore movements in the studied blast shots. Recorded ore movement estimates average horizontal and vertical movements of 3.69 and 1.56 m, respectively, at the Nyabirama pit and average horizontal and vertical movements of 4.5 and 2.48 m, respectively, at the Nyankanga pit. Based on the estimated material movements, zones of ore losses and dilution are established and new dig lines are proposed from successful ore block translation in all blast shots. [ABSTRACT FROM AUTHOR]

Children living with HIV can experience cognitive difficulties. Most neuropsychological tests have been constructed in Western languages, meaning they may not be appropriate for use in non-Western settings. To address this, we used an entirely nonverbal measure of cognitive ability in a sub-Saharan African sample. For this cross-sectional analysis, 316 children (162 HIV+ and 154 HIV-, ages 3–9) completed the Leiter-3 as part of a larger study in Dar es Salaam, Tanzania. Statistical tests included analysis of covariance and multiple linear regression to account for environmental variables. HIV+ children performed worse than HIV – controls on two composite scores: Nonverbal IQ (p <.001) and Processing Speed (p < 0.001). Similar trends were observed on core subtests. Multiple linear regression models revealed that age, socioeconomic status, and school attendance predicted all Leiter-3 test composites. Critically, the addition of HIV status to the models improved prediction of Nonverbal IQ (∆R2 = 0.03, p =.001) and Processing Speed (∆R2 = 0.06, p <.001). Children living with HIV performed worse than HIV- controls on most Leiter-3 measures. While age, SES, and school attendance predicted Leiter-3 performance, HIV status improved prediction capabilities when added to the model. The Leiter-3 may offer a viable measure of cognitive ability in non-Western settings that can be used in its original form without translation. [ABSTRACT FROM AUTHOR]

Objective: Rapid automatized naming (RAN) assesses pre-literacy and could be useful for assessing the effects of HIV infection on the development of literacy. Many children with HIV live in sub-Saharan Africa, but the RAN has not been well-studied there. Cultural differences in when children learn color names and in how they prioritize between accuracy and speed can affect RAN results. Typically, RAN and other cognitive functions (e.g., general intelligence, processing speed, working memory, attention) are strongly related. Our goal is to examine how RAN performance relates to neurocognitive function in sub-Saharan Africa and whether RAN performance could reveal the effect of HIV on pre-literacy. The current study examines the relationship between RAN performance and cognitive variables in both children living with HIV (CLWH) and healthy controls in Tanzania. Participants and Methods: 486 children (ages 3-8) were administered RAN Color and Object tasks as part of a larger longitudinal study in Dar es Salaam, Tanzania. All participants were also administered the Leiter International Performance Scale - 3rd Edition (Leiter-3), a test of nonverbal intelligence and general cognitive function. Binomial logistic regression examined the likelihood of completing a RAN task and included age, Leiter-3 composite standard scores, and HIV status. Multiple linear regression using the same predictors assessed factors associated with RAN completion time in children who completed the tests. SES and education were not included in the model specifications because they were not correlated with any RAN measures. Results: Only 40% of children could complete the RAN Color task, while 88% completed the Object task. Logistic regression models showed that age (p<0.001), Leiter-3 Nonverbal IQ (p<0.01), and Processing Speed (p<0.001) composite scores were all unique predictors of whether children would complete the RAN Color task. Age (p <0.001) and Nonverbal IQ (p<0.001) were predictors of completing of the RAN Object task. Of those who could complete the RAN Color task, multiple linear regression demonstrated that age (p<0.01), Leiter-3 Nonverbal IQ (p=0.01) and Processing Speed (p=0.001) composites predicted completion time, with the model accounting for 25% of the variance. For the RAN Object task, multiple linear regression indicated age (p<0.001), Leiter-3 Processing Speed (p=0.01) and Nonverbal Memory (p=0.01) composites, and living with HIV (p=0.01), predicted completion time, with the model accounting for 42% of the variance. Conclusions: Completion rates for RAN Color and Object tasks were low but improved with age. Consistent with brain maturation, increasing age and processing speed improved completion time, regardless of the RAN task. General cognitive ability predicted RAN Color performance, and Nonverbal Memory (encompassing attention, working memory, and retrieval) and HIV status additionally predicted RAN Object performance. Results extend research indicating RAN is distinct yet multifactorial, relying on various neurocognitive functions working together. Additionally, the relationship of HIV to RAN Object performance implies an overlap between the neurocognitive functions inherent in RAN and the neurocognitive weaknesses often reported in CLWH. These findings suggest cognitive vulnerabilities in CLWH may extend to literacy skills in sub-Saharan Africa, which requires further study. [ABSTRACT FROM AUTHOR]

The Ruvu Basin in northeastern coastal Tanzania is one of the least studied basins in the country. It likely contains a record of the pre-and post-breakup sequences of the Gondwana supercontinent. In this study, the first comprehensive palynological investigation on drill-cuttings samples from the Makarawe-1 well in the Ruvu Basin was conducted. In the lower section of this well, four distinct palynologic intervals are recorded: Aratrisporites spp.-Klausipollenites schaubergeri interval (Upper Permian); Reduviasporonites spp. interval (Permo-Triassic transition); Extinction Interval (Permo-Triassic extinction) and Alisporites-Falcisporites Interval (Upper Triassic). This implies that the Ruvu Basin heralds a succession across the Permian-Triassic boundary and its associated extinction. We also record substantial palynological change across the transition to the upper portion of the Makarawe-1 well, where marine dinoflagellate cysts and abundant Classopollis pollen dominate the assemblage. Based on the ranges of dinoflagellate cysts supplemented by pollen-spore ranges, two main palynological intervals (the Classopollis-Nannoceratopsis interval and the Wanaea clathrata interval) are here established. These intervals are of late Middle Jurassic and Late Jurassic (Bajocian - Kimmeridgian) age. This suggests possible correlations with the Lugoba, Msata, Msolwa, Magindu and Malivundo formations of the Ruvu Basin. The findings presented herein suggest a downhole extension of the Wanaea clathrata interval (Oxfordian-Kimmeridgian) sensu [Msaky 2007] to 1215–1235 m. In addition, the Nannoceratopsis- dominated assemblage is indicative of an Early Jurassic association that developed during immediate post-break-up phase, with low-salinities and basinal restriction. With similarity to the Ngerengere dinocyst assemblage reported in previous studies, these results further suggest that the Ngerengere beds are not a so-called Karoo equivalent, but rather a syn- or post-breakup sequence. The recorded intervals are highly similar to other palynostratigraphic units of Africa, Australia, Europe and South America. The data collected in this study add important insights for the general stratigraphic framework within this poorly constrained coastal basin, while also providing a perspective on more distant correlations using palynology. • We present Late Permian to Late Jurassic palynology of the Ruvu Basin in Tanzania. • Six palynologic intervals are used to refine Late Permian-Late Jurassic stratigraphy. • Immediate post-break-up of Gondwana is marked by low salinity in a restricted basin. • Ngerengere Beds are not Karoo equivalent but rather late syn- or post-breakup strata. [ABSTRACT FROM AUTHOR]

Objective: To determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants. Design: Randomized, controlled trial. Setting: Dar es Salaam, Tanzania Subjects, participants: Pregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months. Intervention: Randomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding. Main outcome measure(s): Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months. Results: PCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388–719 Kcal); and increases in daily protein intake (range of differences: +22–33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03). Conclusions: In comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed. Trial registration: Clinical Trials.Gov . [ABSTRACT FROM AUTHOR]

SRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13–15 years in Tanzania. Adolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). Among 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted. Trial Registration. The trial is registered at ClinicalTrials.gov as NCT02712424. [ABSTRACT FROM AUTHOR]

Importance: Predicting neurocognitive deficits using complex auditory assessments could change how cognitive dysfunction is identified, and monitored over time. Detecting cognitive impairment in people living with HIV (PLWH) is important for early intervention, especially in low- to middle-income countries where most cases exist. Auditory tests relate to neurocognitive test results, but the incremental predictive capability beyond demographic factors is unknown., Objective: Use machine learning to predict neurocognitive deficits, using auditory tests and demographic factors., Setting: The Infectious Disease Center in Dar es Salaam, Tanzania., Participants: Participants were 939 Tanzanian individuals from Dar es Salaam living with and without HIV who were part of a longitudinal study. Patients who had only one visit, a positive history of ear drainage, concussion, significant noise or chemical exposure, neurological disease, mental illness, or exposure to ototoxic antibiotics (e.g., gentamycin), or chemotherapy were excluded. This provided 478 participants (349 PLWH, 129 HIV-negative). Participant data were randomized to training and test sets for machine learning., Main Outcome(s) and Measure(s): The main outcome was whether auditory variables combined with relevant demographic variables could predict neurocognitive dysfunction (defined as a score of <26 on the Kiswahili Montreal Cognitive Assessment) better than demographic factors alone. The performance of predictive machine learning algorithms was primarily evaluated using the area under the receiver operational characteristic curve. Secondary metrics for evaluation included F1 scores, accuracies, and the Youden's indices for the algorithms., Results: The percentage of individuals with cognitive deficits was 36.2% (139 PLWH and 34 HIV-negative). The Gaussian and kernel naïve Bayes classifiers were the most predictive algorithms for neurocognitive impairment. Algorithms trained with auditory variables had average area under the curve values of 0.91 and 0.87, F1 scores (metric for precision and recall) of 0.81 and 0.76, and average accuracies of 86.3% and 81.9% respectively. Algorithms trained without auditory variables as features were statistically worse (p < .001) in both the primary measure of area under the curve (0.82/0.78) and the secondary measure of accuracy (72.3%/74.5%) for the Gaussian and kernel algorithms respectively., Conclusions and Relevance: Auditory variables improved the prediction of cognitive function. Since auditory tests are easy-to-administer and often naturalistic tasks, they may offer objective measures or predictors of neurocognitive performance suitable for many global settings. Further research and development into using machine learning algorithms for predicting cognitive outcomes should be pursued., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Niemczak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Central nervous system (CNS) damage from HIV infection or treatment can lead to developmental delays and poor educational outcomes in children living with HIV (CLWH). Early markers of central nervous system dysfunction are needed to target interventions and prevent life-long disability. The frequency following response (FFR) is an auditory electrophysiology test that can reflect the health of the central nervous system. In this study, we explore whether the FFR reveals auditory central nervous system dysfunction in CLWH., Study Design: Cross-sectional analysis of an ongoing cohort study. Data were from the child's first visit in the study., Setting: The infectious disease center in Dar es Salaam, Tanzania., Methods: We collected the FFR from 151 CLWH and 151 HIV-negative children. To evoke the FFR, three speech syllabi (/da/, /ba/, /ga/) were played monaurally to the child's right ear. Response measures included neural timing (peak latencies), strength of frequency encoding (fundamental frequency and first formant amplitude), encoding consistency (inter-response consistency), and encoding precision (stimulus-to-response correlation)., Results: CLWH showed smaller first formant amplitudes ( P  < 0.0001), weaker inter-response consistencies ( P  < 0.0001) and smaller stimulus to response correlations ( P  < 0.0001) than FFRs from HIV-negative children. These findings generalized across the three speech stimuli with moderately strong effect sizes (partial η2 ranged from 0.061 to 0.094)., Conclusion: The FFR shows auditory central nervous system dysfunction in CLWH. Neural encoding of auditory stimuli was less robust, more variable, and less accurate. As the FFR is a passive and objective test, it may offer an effective way to assess and detect central nervous system function in CLWH., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Children with HIV (CWH) are at increased risk for cognitive and developmental delays. Whether HIV affects literacy development, however, remains unknown. Rapid automatized naming (RAN) tasks offer the simplest preliteracy assessment a child can perform that predicts future reading skills across languages., Design and Methods: RAN performance was analyzed cross-sectionally on 473 children (249 children without HIV and 217 CWH; ages 3-9) drawn from a longitudinal study in Tanzania. These data were compared to results from 341 normally developing children without HIV (ages 3-8) from the United States. Participants performed two RAN subtests: colors and objects., Results: RAN object completion was greater than for the RAN color in Tanzanian children. CWH were less likely to complete either subtest and performed worse on the object subtest compared to Tanzanian children without HIV. Compared to the US cohort, the Tanzanian cohort was less likely to complete both subtests - in particular the colors subtest - and showed more variability in responses at younger ages. After approximately age 6, however, the trajectory of improvement between the United States and Tanzania was similar., Conclusions: CWH performed worse on this per-literacy test, indicating literacy skill development in CWH needs further study. The differences between US and Tanzanian results likely reflect variability in when children learn to name colors and objects. The trajectory of improvement between countries became more similar as the children aged. This study motivates further longitudinal analyses aimed at assessing the developmental trajectory of the RAN, its predictive ability for reading skills, and its link with other preliteracy and cognitive skills., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Despite normal audiometry, adults living with HIV have lower distortion product otoacoustic emissions (DPOAEs) compared with HIV-negative controls, but the degree of these differences in children living with HIV is unknown. If subclinical auditory deficits are present, results could affect developmental outcomes in children living with HIV (CLWH)., Objective: To compare DPOAEs and auditory brainstem responses (ABR) between 2 age- and sex-matched groups of younger children with normal audiometry, 1 infected with HIV and the other uninfected., Design, Setting, and Participants: Cohort study in an infectious disease center in Dar es Salaam, Tanzania. Participants included 340 Tanzanian children aged 3 to 9 years with clinically normal hearing, type A tympanograms bilaterally, and air-conduction thresholds of 20 dB HL or less from 0.5 to 8 kHz. Participants in the cohort repeated testing approximately every 6 months (approximately 2.2 sessions per participant) for a total of 744 total observations. Data were analyzed from March 2020 to January 2022., Main Outcomes and Measures: DPOAE amplitudes from 1.5 to 8 kHz using an f2 to f1 ratio of 1.2 and L1/L2 values of 65/55 dB sound pressure level and click-evoked ABR using a slow (21.1/s) and fast (61.1/s) click rate., Results: A total of 141 CLWH (70 female participants [49.3%]; mean [SD] age, 7.24 [1.67] years) and 199 HIV-negative individuals (99 female participants [49.7%]; mean [SD] age, 7.26 [1.44] years) participated in the study. The groups did not differ significantly in age, static immittance, or air-conduction thresholds. HIV status was independently associated with approximately 1.4 dB (95% CI, -3.28 to 0.30 dB) to 3.8 dB (95% CI, 6.03 to -1.99 dB) lower DPOAE amplitudes at 6 and 8 kHz bilaterally and 0.28 μV (95% CI, 0.01 to 0.33 μV) lower ABR wave V amplitudes in the right ear., Conclusions and Relevance: Consistent with previous findings in young adults, CLWH had slightly, but reliably, lower DPOAEs and ABR wave V amplitudes than HIV-negative controls. The magnitude of these differences was small, but results suggest an early and consistent association between HIV infection or treatment and outer hair cell and auditory brainstem responses in children as young as 3 years. These subclinical changes suggest tracking both auditory function and development outcomes in CLWH is warranted.

Objective: Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV., Study Design: Matched cohort study with repeated measures., Setting: Infectious disease center in Dar es Salaam, Tanzania., Methods: Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses., Results: HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear., Conclusion: Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.

Background: Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease., Methods: In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment., Results: At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 ×  10 6 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005)., Conclusions: In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity., Trial Registration: Clinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.

Objective: Evidence suggests damage to brain auditory pathways, rather than inner ear damage, underlies the hearing difficulties HIV+ individuals report. But, antiretroviral therapy (ART) may affect the hearing system and also lead to hearing complaints., Design: Longitudinal study of HIV+ and HIV- individuals in Dar es Salaam Tanzania. A subset of this cohort started ART while in the study allowing the effects of ART to be studied directly., Methods: The ability to hear quiet sounds (pure-tone audiometry), cochlear outer hair cell function [distortion-product otoacoustic emissions (DPOAEs)], and gaps-in-noise detection thresholds (a central auditory processing test) were assessed at each visit. Visits were scheduled for 6-month intervals, but the number and spacing of visits varied. In the group that started ART while in the study, 107 HIV+ individuals had audiometric thresholds, 98 had DPOAEs, and 98 had gap measurements suitable for analysis. Data were analyzed using a linear mixed model with time and starting ART as fixed effects and individual participant repeated measures as random effects., Results: Starting ART did not affect audiometric or gap detection thresholds. The slope of the DPOAE amplitude vs. time relationship was more negative after starting ART but did not differ from the HIV- group. Gap thresholds were higher in the HIV+ group., Conclusion: ART did not affect audiometric thresholds significantly suggesting common ART drugs are not major ototoxins. The gap detection results from the study show effects on central auditory processing in HIV+ individuals, supporting the origin of HIV-related hearing complaints in the central auditory system.

Immunosuppression resulting from HIV infection increases the risk of progression to active tuberculosis (TB) both in individuals newly exposed to Mycobacterium tuberculosis (MTB) and in those with latent infections. We hypothesized that HIV-positive individuals who do not develop TB, despite living in areas where it is hyperendemic, provide a model of natural resistance. We performed a genome-wide association study of TB resistance by using 581 HIV-positive Ugandans and Tanzanians enrolled in prospective cohort studies of TB; 267 of these individuals developed active TB, and 314 did not. A common variant, rs4921437 at 5q33.3, was significantly associated with TB (odds ratio = 0.37, p = 2.11 × 10(-8)). This variant lies within a genomic region that includes IL12B and is embedded in an H3K27Ac histone mark. The locus also displays consistent patterns of linkage disequilibrium across African populations and has signals of strong selection in populations from equatorial Africa. Along with prior studies demonstrating that therapy with IL-12 (the cytokine encoded in part by IL12B, associated with longer survival following MTB infection in mice deficient in CD4 T cells), our results suggest that this pathway might be an excellent target for the development of new modalities for treating TB, especially for HIV-positive individuals. Our results also indicate that studying extreme disease resistance in the face of extensive exposure can increase the power to detect associations in complex infectious disease., (Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)