To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.
HIV-1 pol sequence data were analyzed to infer the ...local transmission network.
We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.
HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05).
Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine if arterial oxygen and carbon dioxide abnormalities in the first 24h after return of spontaneous circulation (ROSC) are associated with increased mortality in adult out-of-hospital ...cardiac arrest (OHCA).
We used data from the Resuscitation Outcomes Consortium (ROC), including adult OHCA with sustained ROSC ≥1h after Emergency Department arrival and at least one arterial blood gas (ABG) measurement. Among ABGs measured during the first 24h of hospitalization, we identified the presence of hyperoxemia (PaO2≥300mmHg), hypoxemia (PaO2<60mmHg), hypercarbia (PaCO2>50mmHg) and hypocarbia (PaCO2<30mmHg). We evaluated the associations between oxygen and carbon dioxide abnormalities and hospital mortality, adjusting for confounders.
Among 9186 OHCA included in the analysis, hospital mortality was 67.3%. Hyperoxemia, hypoxemia, hypercarbia, and hypocarbia occurred in 26.5%, 19.0%, 51.0% and 30.6%, respectively. Initial hyperoxemia only was not associated with hospital mortality (adjusted OR 1.10; 95% CI: 0.97–1.26). However, final and any hyperoxemia (1.25; 1.11–1.41) were associated with increased hospital mortality. Initial (1.58; 1.30–1.92), final (3.06; 2.42–3.86) and any (1.76; 1.54–2.02) hypoxemia (PaO2<60mmHg) were associated with increased hospital mortality. Initial (1.89; 1.70–2.10); final (2.57; 2.18–3.04) and any (1.85; 1.67–2.05) hypercarbia (PaCO2>50mmHg) were associated with increased hospital mortality. Initial (1.13; 0.90–1.41), final (1.19; 1.04–1.37) and any (1.01; 0.91–1.12) hypocarbia (PaCO2<30mmHg) were not associated with hospital mortality.
In the first 24h after ROSC, abnormal post-arrest oxygen and carbon dioxide tensions are associated with increased out of-hospital cardiac arrest mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background Previous research has demonstrated significant relationships between peri-shock pause and survival to discharge from out-of-hospital shockable cardiac arrest (OHCA). Objective To ...determine the impact of peri-shock pause on survival from OHCA during the ROC PRIMED randomized controlled trial. Methods We included patients in the ROC PRIMED trial who suffered OHCA between June 2007 and November 2009, presented with a shockable rhythm and had CPR process data for at least one shock. We used multivariable logistic regression to determine the association between peri-shock pause duration and survival to hospital discharge. Results Among 2006 patients studied, the median (IQR) shock pause duration was: pre-shock pause 15 s (8, 22); post-shock pause 6 s (4, 9); and peri-shock pause 22.0 s (14, 31). After adjusting for Utstein predictors of survival as well as CPR quality measures, the odds of survival to hospital discharge were significantly higher for patients with pre-shock pause <10 s (OR: 1.52, 95% CI: 1.09, 2.11) and peri-shock pause <20 s (OR: 1.82, 95% CI: 1.17, 2.85) when compared to patients with pre-shock pause ≥20 s and peri-shock pause ≥40 s. Post-shock pause was not significantly associated with survival to hospital discharge. Results for neurologically intact survival (Modified Rankin Score ≤ 3) were similar to our primary outcome. Conclusions In patients with cardiac arrest presenting in a shockable rhythm during the ROC PRIMED trial, shorter pre- and peri-shock pauses were significantly associated with higher odds of survival. Future cardiopulmonary education and technology should focus on minimizing all peri-shock pauses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The ITIP project was conducted at Kamuzu Central Hospital and Bwaila District Hospital in Lilongwe, Malawi between June 2016 and April 2019 and included two prospective, double-blind, randomized ...controlled clinical trials evaluating the duration of amoxicillin dispersible tablet (DT) treatment for non-severe community-acquired pneumonia among children 2–59 months of age. Only 14 (1.2%) and 44 (1.5%) children had any non-adherence reported in ITIP1 and ITIP2, respectively. Because adherence was so high, we were not able to identify any substantive differences in the level of adherence between any of the subgroups and did not perform any regression analysis. ITIP1 Average percent adherencea ITIP2 Average percent adherencea n = 1123 99.5 n = 2980 99.7% Age (months) 2–11, n (%) 392 (34.9%) 99.5 1728 (58.0%) 99.6 12–35, n (%) 507 (45.1%) 99.5 1015 (34.1%) 99.8 36–59, n (%) 224 (19.9%) 99.4 237 (8.0%) 99.7 Mean (SD) 21.3 (15.0) 13.5 (12.2) Gender Male, n (%) 524 (46.7%) 99.5 1642 (55.1%) 99.7 Female, n (%) 599 (53.3%) 99.5 1338 (44.9%) 99.6 Mother’s highest level of education None, n (%) 22 (2.0%) 100 100 (3.4%) 99.4 Primary, n (%) 497 (44.3%) 99.4 1698 (57.0%) 99.6 Secondary, n (%) 568 (50.6%) 99.5 1143 (38.4%) 99.8 Tertiary, n (%) 36 (3.2%) 100 39 (1.3%) 99.5 Any other children aged 0–10 years in same household Yes 660 (58.8%) 99.3 1718 (57.7%) 99.7 No 463 (41.2%) 99.7 1262 (42.3%) 99.6 Ill for more than 24 h before entering study, n (%) Yes 1061 (94.5%) 99.6 2610 (87.6%) 99.7 No 62 (5.5%) 98.4 370 (12.4%) 99.8 Axillary temperature ≥ 38 °C, n (%) Yes 335 (29.8%) 99.8 920 (30.9%) 99.6 No 788 (70.2%) 99.4 2060 (69.1%) 99.7 Any concurrent diagnosis Yes 374 (33.3%) 99.1 969 (32.5%) 99.5 No 749 (66.7%) 99.7 2011 (67.5%) 99.8 Any concomitant medication Yes 744 (66.3%) 99.3 1935 (64.9%) 99.6 No 379 (33.7%) 99.8 1045 (35.1%) 99.8 Any concomitant antibiotic Yes 33 (2.9%) 100 66 (2.2%) 99.7 No 1090 (97.1%) 99.5 2914 (97.8%) 99.7 Malaria, n (%) Yes 141 (12.6%) 98.8 267 (9.0%) 99.4 No 982 (87.4%) 99.6 2713 (91.0%) 99.7 Moderate acute malnutrition, n (%) Yes 18 (1.6%) 100 91 (3.1%) 99.6 No 1105 (98.4%) 99.5 2889 (96.9%) 99.7 Diarrhea, n (%) Yes 104 (9.3%) 99.4 410 (13.8%) 99.1 No 1019 (90.7%) 99.5 2570 (86.2%) 99.8 1. n number, SD Standard deviation 2. a Average adherence = Caregiver reported percent of study drug doses taken of the possible doses provided prior to treatment failure In a sub-analysis of a prospective cohort study also conducted in Malawi, non-adherence to cotrimoxazole was not uncommon among children aged 2–59 months with fast-breathing pneumonia diagnosed by community health workers at rural village clinics 5. The World Health Organization recommends oral amoxicillin DT as first-line treatment for non-severe pneumonia in children 2–59 months of age.
Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals.
Longitudinal cohort study of individuals enrolled during primary infection.
Eligible individuals were ...antiretroviral naïve participants enrolled in the cohort from December 1997-December 2005 and having at least two blood samples available with the first one collected within a year of their estimated date of infection. Population-based pol sequences were generated from collected blood samples and analyzed for genetic divergence over time in respect to dual infection status, HLA, CD4 count and viral load.
93 participants were observed for a median of 1.8 years (Mean = 2.2 years, SD =1.9 years). All participants classified as mono-infected had less than 0.7% divergence between any two of their pol sequences using the Tamura-Nei model (TN93), while individuals with dual infection had up to 7.0% divergence. The global substitution rates (substitutions/nucleotide/year) for mono and dually infected individuals were significantly different (p<0.001); however, substitution rates were not associated with HLA haplotype, CD4 or viral load.
Even after a maximum of almost 9 years of follow-up, all mono-infected participants had less than 1% divergence between baseline and longitudinal sequences, while participants with dual infection had 10 times greater divergence. These data support the use of HIV-1 pol sequence data to evaluate transmission events, networks and HIV-1 dual infection.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Antiretroviral (ARV) medications differentially penetrate across the blood-brain barrier into central nervous system (CNS) tissues, potentially influencing their effectiveness in treating ...brain infection. Methods. This randomized controlled clinical trial (RCT) called for 120 participants at 5 study sites to be randomized 1:1 to CNS-targeted (CNS-T) or non–CNS-T ART. Entry clinical factors such as ARV experience were balanced across arms using an adaptive randomization approach. The primary outcome, change in neurocognitive performance, was measured as the difference in global deficit score (GDS) from baseline to week 16. Results. The study was terminated early on the recommendation of its data safety monitoring board on the basis of slow accrual and a low likelihood of detecting a difference in the primary outcome. No safety concerns were identified. Of 326 participants screened, 59 met entry criteria and were randomized. The primary intent-to-treat analysis included 49 participants who completed week 16. These comprised 39 men and 10 women with a mean age of 44 years (SD, 10 years), and median nadir and current CD4 + T-cell counts of 175 cells/μL and 242 cells/μL, respectively. The proportional improvement in GDS from baseline was nonsignificantly larger (7%; 95% confidence interval CI, -31% to 62%) in the CNS-T arm than in the non-CNS-T arm, representing a treatment effect size of 0.09 (95% CI, -.48 to .65). Prespecified secondary analysis showed a trend interaction (P = .087), indicating that participants who had baseline plasma virologic suppression may have benefited from CNS-T. Conclusions. This study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV-associated neurocognitive disorders. A benefit for a subgroup or small overall benefits could not be excluded. Clinical Trials Registration. NCT00624195.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to ...appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia.
This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study will enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the study will be hospitalized for 48 h after enrollment and will have scheduled study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary outcome. We hypothesize that the rates of treatment failure will be similar in both arms and that 3 days of treatment will be non-inferior to 5 days of amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority margin of 1.5. This trial was approved by the Western Institutional Review Board and Malawi College of Medicine Research and Ethics Committee.
Given the paucity of data from Africa, African-based research is necessary to establish appropriate duration of treatment with amoxicillin DT for chest indrawing childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base will contribute to future iterations of World Health Organization Integrated Management of Childhood Illness guidelines.
NCT02678195 : Pre-results. Date registered February 9, 2016.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current public health efforts often use molecular technologies to identify and contain communicable disease networks, but not for HIV. Here, we investigate how molecular epidemiology can be used to ...identify highly related HIV networks within a population and how voluntary contact tracing of sexual partners can be used to selectively target these networks.
We evaluated the use of HIV-1 pol sequences obtained from participants of a community-recruited cohort (n = 268) and a primary infection research cohort (n = 369) to define highly related transmission clusters and the use of contact tracing to link other individuals (n = 36) within these clusters. The presence of transmitted drug resistance was interpreted from the pol sequences (Calibrated Population Resistance v3.0).
Phylogenetic clustering was conservatively defined when the genetic distance between any two pol sequences was less than 1%, which identified 34 distinct transmission clusters within the combined community-recruited and primary infection research cohorts containing 160 individuals. Although sequences from the epidemiologically linked partners represented approximately 5% of the total sequences, they clustered with 60% of the sequences that clustered from the combined cohorts (odds ratio 21.7; P < or = 0.01). Major resistance to at least one class of antiretroviral medication was found in 19% of clustering sequences.
Phylogenetic methods can be used to identify individuals who are within highly related transmission groups, and contact tracing of epidemiologically linked partners of recently infected individuals can be used to link into previously defined transmission groups. These methods could be used to implement selectively targeted prevention interventions.
Livestock ownership has the potential to improve child nutrition through various mechanisms, although direct evaluations of household livestock and child stunting status are uncommon. We conducted an ...analysis of Demographic and Health Survey (DHS) datasets from Ethiopia (2011), Kenya (2008-2009), and Uganda (2010) among rural children under 5 years of age to compare stunting status across levels of livestock ownership. We classified livestock ownership by summing reported household numbers of goats, sheep, cattle and chickens, as well as calculating a weighted score to combine multiple species. The primary association was assessed separately by country using a log-binomial model adjusted for wealth and region, which was then stratified by child diarrheal illness, animal-source foods intake, sub-region, and wealth index. This analysis included n = 8079 children from Ethiopia, n = 3903 children from Kenya, and n = 1645 from Uganda. A ten-fold increase in household livestock ownership had significant association with lower stunting prevalence in Ethiopia (Prevalence Ratio PR 0.95, 95% CI 0.92-0.98) and Uganda (PR 0.87, 95% CI 0.79-0.97), but not Kenya (PR 1.01, 95% CI 0.96-1.07). The weighted livestock score was only marginally associated with stunting status. The findings varied slightly by region, but not by wealth, diarrheal disease, or animal-source food intake. This analysis suggested a slightly beneficial effect of household livestock ownership on child stunting prevalence. The small effect size observed may be related to limitations of the DHS dataset or the potentially complicated relationship between malnutrition and livestock ownership, including livestock health and productivity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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