Ruimei Zhang, Xiangyu Xi, Chunying Wang, Yong Pan, Changhua Ge, Liying Zhang, Shuo Zhang, Huimei Liu

by Ruimei Zhang, Xiangyu Xi, Chunying Wang, Yong Pan, Changhua Ge, Liying Zhang, Shuo Zhang, Huimei Liu Background Interleukin 2 (IL-2) is a cytokine secreted by activated T cells. Studies exploring recombinant human interleukin 2 (rhuIL-2) as an adjunctive immunotherapeutic agent to treat tuberculosis (TB) have shown variable results; however, the true therapeutic efficacy of rhuIL-2 administration in TB patients has not been determined. Methods A systematic review to identify publications exploring the association between rhuIL-2-based immunotherapy for TB and outcomes (sputum culture conversion, sputum smear conversion, radiographic changes, and leukocyte phenotype changes) in patients with pulmonary TB published before June 8, 2018 was performed. Data were extracted and analyzed by two investigators independently. Results A total of 2,272 records were screened. Four randomized controlled trials (RCTs) comprising 656 pulmonary TB patients were finally included. The rhuIL-2 treatment could significantly improve the sputum culture conversion of TB (RR, 1.18; 95%CI: 1.03–1.36; I2 < 0.01; P = 0.019) after at least 3 months of anti-TB therapy and the sputum smear conversion of TB during anti-TB therapy. Treating multidrug-resistant tuberculosis (MDR-TB) with rhuIL-2 could improve the sputum culture conversion (RR, 1.28; 95%CI: 1.05–1.57; I2 < 0.01; P = 0.016) and smear conversion (RR, 1.28; 95%CI: 1.09–1.51; I2 < 0.01; P = 0.003) at the end of anti-TB treatment. Meanwhile, rhuIL-2-based adjunctive immunotherapy could expand the proliferation and conversion of CD4+ and natural killer (NK) cells. Three of the included studies suggested that radiographic changes could not be improved by the use of rhuIL-2 as adjunctive immunotherapy. Publication bias did not exist. Conclusions Based on this first meta-analysis, rhuIL-2-based adjunctive immunotherapy appears to expand the proliferation and conversion of CD4+ and NK cells, as well as improve the sputum culture (at 3 months and later) and smear conversion of TB patients.

Mrittika Barua, Francien Van Driel, Willy Jansen

by Mrittika Barua, Francien Van Driel, Willy Jansen When they do not meet norms related to sexuality and reproduction, Bangladeshi women often face abandonment and are thus deprived of an active sexual life, a marital relationship, and motherhood. Little is known about how a stigmatised disease such as tuberculosis (TB) may constrain the reproductive health and sexual lives of women. This article, derived from a larger study on the impact of TB on women’s sexual and reproductive health and rights in Narsingdi district and Dhaka, Bangladesh, aims to fill this gap. Based on interviews with nine married women who have or had TB, four husbands, and two mothers-in-law, this article highlights that the ways in which TB impedes on the sexual and reproductive lives of women depends on the stigma within their family and community, their relationships with their husbands, motherhood, their living arrangements, their economic contribution to the family and/or their disclosure of their TB diagnosis. Women with children and supportive husbands retain a stronger position among their in-laws and are less likely to be isolated or rejected. The patients’ narratives revealed that the instructions of health workers influenced their decisions about intercourse or abstinence. Future studies should examine the instructions patients receive from health workers regarding their living and sleeping arrangements, sexual intercourse, and pregnancy, as well as policy documents on TB treatment and prevention.

Jarvis J, Harrison T.

Siedner M, Triant V.

Dennis A, Zhou S, Sellers C, et al.

AbstractIntra-host viral sequence diversity can be evaluated over multiple genomic regions using next generation sequencing (NGS) and scaled to population level diversity to identify recent HIV-1 infection. Using Primer-ID NGS we sequenced the RT and env V1-V3 regions from persons with known infection dates, and assessed the mean (π) and first quintile of pairwise diversity distributions over time. ROC area under the curve (AUC) of RT and V1-V3 combined showed excellent discrimination of recent infection

Henry Dilonga Meriki, Kukwah Anthony Tufon, Damian Nota Anong, Nyeke James Tony, Tebit Emmanuel Kwenti, Ayah Flora Bolimo, Youmbi Sylvain Kouanou, Theresa Nkuo-Akenji

by Henry Dilonga Meriki, Kukwah Anthony Tufon, Damian Nota Anong, Nyeke James Tony, Tebit Emmanuel Kwenti, Ayah Flora Bolimo, Youmbi Sylvain Kouanou, Theresa Nkuo-Akenji Background HBV infection affects about 257 million people globally and Sub-Saharan Africa has the highest burden. The disease still constitutes a major public health problem despite the advent of preventive measures like the HBV vaccine. This study was aimed at identifying factors that influence vaccine uptake and the efficacy of administered vaccines among people at high risk of HBV infection. Methods This was a cross-sectional study conducted between January 2016 and December 2017. A pretested semi-structured questionnaire was used to capture information on sociodemographic and vaccination status from healthcare workers, household and sexual contacts to HBV infected people. HBV serological panel as well as quantitative anti-HBs ELISA test was done for all participants. Additional information was obtained from the institutions that administered the vaccines. Results A total of 265 participants with a mean age of 32.1±8.7 were enrolled. Eighty (30.2%) of them had received at least 1 dose of the HBV vaccine while 185 (69.8%) were unvaccinated. Healthcare workers were the most vaccinated (37%). Ignorance, negligence, fear of injection and the cost of the vaccine all contributed to poor vaccine uptake in the study population. Natural immunity was seen in 9 (3.4%) of the participants. Only 64.9% of the vaccinated participants attained the desirable level of anti-HBs (≥10mIU/ml) 1–2 months after ≥ 3 doses of the vaccine. Age, gender, obesity, alcohol and smoking were not significantly associated with poor immune responses. No standardized protocol was followed by the institutions administering the vaccine. Conclusion This study revealed very poor vaccine uptake and poor immune responses to the HBV vaccine in the study population and this should urge the health sector in Cameroon to intensify their sensitization on HBV vaccine, standardize the protocol for storing and administering the vaccine, subsidize the cost of the vaccine especially amongst healthcare workers and encourage anti-HBs post vaccination testing.

Mukap, M., Sprod, C., Tefuarani, N., Laman, M., Page-Sharp, M., Salman, S., Moore, B. R., Batty, K. T., Davis, T. M. E., Manning, L.

Background: Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) studies in situations where venous blood sampling is logistically and/or ethically challenging. In this study we aimed to demonstrate the validity of a DBS ceftriaxone assay in a PK study of children from Papua New Guinea (PNG) with severe illness, a setting in which healthcare resources are limited and anemia is common.Methods: Using a previously validated liquid chromatography-mass spectroscopy (LC-MS/MS) assay, serial plasma and DBS ceftriaxone concentrations were measured in PNG children aged 5-10 years with acute bacterial meningitis or severe pneumonia. The concentration-time data were incorporated into population PK models.Results: Ten children were recruited with an admission hematocrit of 0.22-0.52. Raw data demonstrated good correlation between plasma and DBS concentrations (Spearman rs =0.94 [95% confidence interval 0.91-0.97], P

Auriti, C., Goffredo, B. M., Ronchetti, M. P., Piersigilli, F., Cairoli, S., Bersani, I., Dotta, A., Pai, M. P.

Major gaps exist in our knowledge of antimicrobial pharmacokinetics in critically ill neonates and infants that require validated microsampling and bioanalysis methods to support therapeutic drug monitoring. We compared serially collected intravenous (IV) and heel-stick capillary (HSC) sampled plasma concentrations of micafungin (8 mg/kg) in eight infants born preterm, with systemic candidiasis. The mean (SD) micafungin AUCinf was 316 (65.0) h·mg/L based on HSC concentrations that strongly correlated (R2= 0.92) with IV values to support dose adjustment.

Abstract Background Globally, 40% of all tuberculosis (TB) cases, 65% paediatric cases and 75% multi-drug resistant TB (MDR-TB) cases are missed due to underreporting and/or under diagnosis. A recent Kenyan TB prevalence survey found that a significant number of TB cases are being missed here. Understanding spatial distribution and patterns of use of TB diagnostic tests as per the guidelines could potentially help improve TB case detection by identifying diagnostic gaps. Methods We used 2015 Kenya National TB programme data to map TB case notification rates (CNR) in different counties, linked with their capacity to perform diagnostic tests (chest x-rays, smear microscopy, Xpert MTB/RIF®, culture and line probe assay). We then ran hierarchical regression models for adults and children to specifically establish determinants of use of Xpert® (as per Kenyan guidelines) with county and facility as random effects. Results In 2015, 82,313 TB cases were notified and 7.8% were children. The median CNR/100,000 amongst 0-14yr olds was 37.2 (IQR 20.6, 41.0) and 267.4 (IQR 202.6, 338.1) for ≥15yr olds respectively. 4.8% of child TB cases and 12.2% of adult TB cases had an Xpert® test done, with gaps in guideline adherence. There were 2,072 microscopy sites (mean microscopy density 4.46/100,000); 129 Xpert® sites (mean 0.31/100,000); two TB culture laboratories and 304 chest X-ray facilities (mean 0.74/100,000) with variability in spatial distribution across the 47 counties. Retreatment cases (i.e. failures, relapses/recurrences, defaulters) had the highest odds of getting an Xpert® test compared to new/transfer-in patients (AOR 7.81, 95% CI 7.33-8.33). Children had reduced odds of getting an Xpert® (AOR 0.41, CI 0.36-0.47). HIV-positive individuals had nearly twice the odds of getting an Xpert® test (AOR 1.82, CI 1.73-1.92). Private sector and higher-level hospitals had a tendency towards lower odds of use of Xpert®. Conclusions We noted under-use and gaps in guideline adherence for Xpert® especially in children. The under-use despite considerable investment undermines cost-effectiveness of Xpert®. Further research is needed to develop strategies enhancing use of diagnostics, including innovations to improve access (e.g. specimen referral) and overcoming local barriers to adoption of guidelines and technologies.

Andrea Parriott, Mohsen Malekinejad, Amanda P. Miller, Hacsi Horvath, Suzanne M. Marks, James G. Kahn

by Andrea Parriott, Mohsen Malekinejad, Amanda P. Miller, Hacsi Horvath, Suzanne M. Marks, James G. Kahn Background Contact investigation is an important strategy for maintaining control of tuberculosis (TB) in the United States. However, testing and treatment outcomes specifically to foreign-born populations are poorly understood. We reviewed literature on testing and LTBI identified during contact investigations in foreign-born populations living in the US. Methods We conducted a comprehensive search of peer-reviewed and grey literature using Cochrane systematic review methods. We included studies with adult and adolescent populations that were at least 50% foreign-born. Pooled proportions and 95% confidence intervals (CIs) were calculated via inverse-variance weighted meta-analysis, and cumulative proportions were calculated as products of adjacent step proportions. Results We identified 22 studies published between 1997 and 2014 that included at least 50% foreign-born participants. From studies of predominantly (>90%) foreign-born populations, almost all identified contacts were recruited and had valid test results, and 54.8% (95% CI 45.1–62.5%) of contacts with valid test results tested positive. From studies of majority (50% to 90%) foreign-born populations, 78.4% (95% CI 78.0–78.9%) of identified contacts were recruited, 92.0% (95% CI 91.6–92.3%) of recruited contacts had valid test results, and 38.5% (95% CI 31.9%-44.2%) of persons with valid results tested positive. These proportions varied by test type in studies of predominantly foreign-born populations. For every 1000 contacts identified in predominantly foreign-born populations, we estimate that 535 (95% CI 438 to 625) will test positive, and 354 (95% CI 244 to 453) will complete LTBI treatment. For every 1000 contacts identified in majority foreign-born populations, these estimates are 276 (95% CI 230 to 318), and 134 (95% CI 44 to 264), respectively. Conclusions Contact investigation is a high yield activity for identifying and treating foreign-born persons with LTBI, but must be complemented by other tuberculosis control activities in order to achieve continued progress toward TB elimination.