Natural ventilation reduces high TB transmission risk in traditional homes in rural KwaZulu-Natal, South Africa.

BACKGROUND: Transmission of drug susceptible and drug resistant TB occurs in health care facilities, and community and households settings, particularly in highly prevalent TB and HIV areas. There is a paucity of data regarding factors that may affect TB transmission risk in household settings. We evaluated air exchange and the impact of natural ventilation on estimated TB transmission risk in traditional Zulu homes in rural South Africa. METHODS: We utilized a carbon dioxide decay technique to measure ventilation in air changes per hour (ACH). We evaluated predominant home types to determine factors affecting ACH and used the Wells-Riley equation to estimate TB transmission risk. RESULTS: Two hundred eighteen ventilation measurements were taken in 24 traditional homes. All had low ventilation at baseline when windows were closed (mean ACH = 3, SD = 3.0), with estimated TB transmission risk of 55.4% over a ten hour period of exposure to an infectious TB patient. There was significant improvement with opening windows and door, reaching a mean ACH of 20 (SD = 13.1, p < 0.0001) resulting in significant decrease in estimated TB transmission risk to 9.6% (p < 0.0001). Multivariate analysis identified factors predicting ACH, including ventilation conditions (windows/doors open) and window to volume ratio. Expanding ventilation increased the odds of achieving ≥12 ACH by 60-fold. CONCLUSIONS: There is high estimated risk of TB transmission in traditional homes of infectious TB patients in rural South Africa. Improving natural ventilation may decrease household TB transmission risk and, combined with other strategies, may enhance TB control efforts.

Drug-resistant tuberculosis and pregnancy: treatment outcomes of 38 cases in Lima, Peru.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) disproportionately affects young adults, including women of childbearing age; however, treatment of MDR-TB during pregnancy is still controversial. This study looks at the treatment and pregnancy outcomes in a cohort of women who were treated for MDR-TB during pregnancy during a period of 10 years. METHODS: A retrospective case study was performed using a standardized data collection form and data from 3 ranked sources of patient records. All 38 participants were treated during pregnancy with individualized regimens that included second-line TB medications. We examined the frequency of favorable and adverse outcomes with regard to disease and pregnancy. RESULTS: After completion of MDR-TB treatment, 61% of the women were cured, 13% had died, 13% had defaulted, 5% remained in treatment, and 5% had experienced treatment failure. Four of the women experienced clinical deterioration of TB during pregnancy. Five of the pregnancies terminated in spontaneous abortions, and 1 child was stillborn. Among the living newborns, 3 were born with low birth weight, 1 was born prematurely, and 1 had fetal distress. CONCLUSIONS: The rates of success in treating MDR-TB in our cohort are comparable to those of other MDR-TB treatment programs in Peru. The birth outcomes of our cohort are similar to those among the general Peru population. Therefore, we advocate that a woman should be given the option to continue treatment of MDR-TB rather than terminating pregnancy or discontinuing MDR-TB treatment.

ERP correlates of Remember/Know decisions: association with the late posterior negativity.

A number of studies have utilized the Remember/Know paradigm to determine event-related potential (ERP) correlates of recollection and familiarity. However, no prior work has been specifically directed at examining the processing involved in making the Remember/Know distinction. The following study employed a two-step recognition memory test in which participants first decided whether they recognized a word from a prior study list (Old/New decision); if they did, they then determined whether it was recognized on the basis of recollection ('Remember' responses) or familiarity ('Know' responses). By time-locking ERPs to the initial Old/New decision, processing related to making the introspective Remember/Know judgment was isolated. This methodology revealed a posterior negativity that was largest for 'Remember' responses. Previous work has described a late posterior negativity which appears to be related to the search for and recapitulation of study details. Such processing may be critical in making Remember/Know determinations.

ERP correlates of recognition memory: effects of retention interval and false alarms.

Within the framework of the dual process model of recognition memory, prior work with event-related potentials (ERPs) has suggested that an early component, the FN400, is a correlate of familiarity while a later component, the Late Positive Complex (LPC), is a correlate of recollection. However, other work has questioned the validity of these correlations, suggesting that the FN400 effect is too short-lived to reflect an explicit memory phenomenon and that the LPC may be influenced by decision-related factors. Using a Remember/Know paradigm we addressed these issues by (1) examining the effect of study-test delay on correctly recognized items associated with familiarity ('Know' responses) and recollection ('Remember' responses) and by (2) examining FN400 and LPC modulation associated with false alarms. Supporting the relationship of the FN400 with familiarity, attenuation of this component was present for 'Know' responses relative to correct rejections after both the short (39 min) and long (24 h) delay conditions. Attenuation of the FN400 also occurred for false alarms (responses largely driven by familiarity) relative to correct rejections. Although an increased LPC amplitude was found associated with 'Remember' responses at both delays, a decreased LPC amplitude was observed with false alarms relative to correct rejections. This latter result is discussed with regard to the possibility of an overlapping posterior negativity.

Heparanase mediates renal dysfunction during early sepsis in mice.

Heparanase, a heparan sulfate-specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced polymicrobial sepsis in mice using cecal ligation and puncture (CLP) in the presence or absence of competitive heparanase inhibitors (heparin or nonanticoagulant N-desulfated re-N-acetylated heparin [NAH]). Four hours after surgery, we collected serum and urine for measurement of renal function and systemic inflammation, invasively determined systemic hemodynamics, harvested kidneys for histology/protein/mRNA, and/or measured glomerular filtration by inulin clearance. CLP-treated mice demonstrated early activation of glomerular heparanase with coincident loss of glomerular filtration, as indicated by a >twofold increase in blood urea nitrogen (BUN) and a >50% decrease in inulin clearance (P < 0.05) in comparison to sham mice. Administration of heparanase inhibitors 2 h prior to CLP attenuated sepsis-induced loss of glomerular filtration rate, demonstrating that heparanase activation contributes to early septic renal dysfunction. Glomerular heparanase activation was not associated with renal neutrophil influx or altered vascular permeability, in marked contrast to previously described effects of pulmonary heparanase on neutrophilic lung injury during sepsis. CLP induction of renal inflammatory gene (IL-6, TNF-α, IL-1ß) expression was attenuated by NAH pretreatment. While serum inflammatory indices (KC, IL-6, TNF-α, IL-1ß) were not impacted by NAH pretreatment, heparanase inhibition attenuated the CLP-induced increase in serum IL-10. These findings demonstrate that glomerular heparanase is active during sepsis and contributes to septic renal dysfunction via mechanisms disparate from heparanase-mediated lung injury.

Culture conversion among HIV co-infected multidrug-resistant tuberculosis patients in Tugela Ferry, South Africa.

BACKGROUND: Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting. METHODS: Patients with culture-proven MDR-TB were treated with a standardized second-line regimen. Sputum cultures were taken monthly and conversion was defined as two negative cultures taken at least one month apart. Time-to-conversion was measured from the day of initiation of MDR-TB therapy. Subjects with HIV received antiretroviral therapy (ART) regardless of CD4 count. RESULTS: Among 45 MDR-TB patients, 36 (80%) were HIV-co-infected. Overall, 40 (89%) of the 45 patients culture-converted within the first six months and there was no difference in the proportion who converted based on HIV status. Median time-to-conversion was 62 days (IQR 48-111). Among the five patients who did not culture convert, three died, one was transferred to another facility, and one refused further treatment before completing 6 months of therapy. Thus, no patients remained persistently culture-positive at 6 months of therapy. CONCLUSIONS: With concurrent second-line TB and ART medications, MDR-TB/HIV co-infected patients can achieve culture conversion rates and times similar to those reported from HIV-negative patients worldwide. Future studies are needed to examine whether similar cure rates are achieved at the end of MDR-TB treatment and to determine the optimal use and timing of ART in the setting of MDR-TB treatment.