Incident infection during the first year of treatment – A comparison of clozapine and paliperidone palmitate long-acting injection

Background: To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI). Method: A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services. Results: The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; p = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15–15.76, p = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related. Conclusion: Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.

Exhaled Mycobacterium tuberculosis predicts incident infection in household contacts

Background Halting transmission of Mycobacterium tuberculosis (Mtb) by identifying infectious individuals early is key to eradicating Tuberculosis (TB). Here we evaluate face mask sampling as a tool for stratifying infection risk in household contacts of pulmonary TB (pTB). Methods Forty-six sputum positive pTB patients in The Gambia (Aug 2016-Nov 2017) consented to mask sampling prior to commencing treatment. Incident Mtb infection was defined in their 181 household contacts as QuantiFERON (QFT) conversion or an increase in Interferon-ƴ release of ≥ 1IU/ml, 6 months after index diagnosis. Multilevel mixed-effects logistical regression analysis with cluster adjustment by household was used to identify predictors of incident infection. Findings Mtb was detected in 91% of pTB mask samples with high variation in IS6110 copies (5.3 x102 to 1.2 x107). A high mask Mtb level (≥20,000 IS6110 copies) was observed in 45% of cases and independently associated with increased likelihood of incident Mtb infection in contacts (AOR (95%CI) 3.20 (1.26 - 8.12), p=0.01), compared with cases having low/negative mask Mtb levels. Mask Mtb level was a better predictor of incident Mtb infection than sputum bacillary load, chest radiographic characteristics or sleeping proximity. Interpretation Mask sampling offers a highly sensitive and non-invasive tool to support both diagnosis of pTB and stratification of individuals who are most infectious. Our findings have the potential to revolutionise contact screening strategies and outbreak management in high TB burden settings and is of urgent public health importance.

Reduced Endometrial Ascension and Enhanced Reinfection Associated with IgG Antibodies to Specific Chlamydia trachomatis Proteins in Women at Risk for Chlamydia

Background Previous research revealed antibodies targeting Chlamydia trachomatis (CT) elementary bodies was not associated with reduced endometrial or incident infection in CT-exposed women. However, data on the role of CT protein-specific antibodies in protection are limited. Methods A whole-proteome CT array screening serum pools from CT-exposed women identified 121 immunoprevalent proteins. Individual sera were probed using a focused array. IgG antibody frequencies and endometrial or incident infection relationships were examined using Wilcoxon Rank sum test. The impact of breadth and magnitude of protein-specific IgGs on ascension and incident infection were examined using multivariable stepwise logistic regression. Complementary RNA-sequencing quantified CT gene transcripts in cervical swabs from infected women. Results IgG to Pgp3 and CT005 were associated with reduced endometrial infection; anti-CT443, -CT486 and -CT123 were associated with increased incident infection. Increased breadth of protein recognition did not however predict protection from endometrial or incident infection. mRNAs for immunoprevalent CT proteins were highly abundant in the cervix. Conclusions Protein-specific CT antibodies are not sufficient to protect against ascending or incident infection but broad recognition of CT proteins by IgG correlates with cervical CT gene transcript abundance, suggesting CT protein abundance correlates with immunogenicity and signifies their potential as vaccine candidates.

Characteristics of SARS-CoV-2 Positive Individuals in California From Two Periods During Notable Decline in Incident Infection

Despite declining SARS-CoV-2 incidence, continued epidemic monitoring is warranted. We collected SARS-CoV-2 test results from 150 drive-through testing centers across California from two observation periods: February 23rd-March 3rd 2021 and April 15th-April 30th 2021. We assessed SARS-CoV-2 positivity, stratified by Hispanic heritage among sociodemographic characteristics and potential exposures. We analyzed 114,789 test results (5.1% and 2.6% positive during the respective observation periods). Nearly half of all positive tests were among testers reporting a recent exposure (48.8% and 45.3% during the respective observation periods). Those findings may provide insight into evolving local transmission dynamics and support targeted public health strategies.

HIV incidence and associated risk factors in female spouses of men who inject drugs in Pakistan

Introduction Female sexual partners of men who inject drugs (MWID) living with HIV are at risk of HIV transmission. HIV prevalence estimates among non-drug using female sex partners of MWID are scarce, with no studies documenting HIV incidence. We investigated HIV prevalence and incidence among female spouses of MWID registered at Nai Zindagi Trust (NZT), Pakistan, between 2012 and 2019. Methods NZT registration and service provision data for female spouses who participated in HIV testing and counselling calculated HIV prevalence and incidence using the person years (PY) method. Cox proportional hazards models identified factors associated with incident infection. Results Overall HIV prevalence among female spouses of MWID was 8.5%. Among 3478 HIV-negative female spouses, 109 incident infections were observed, yielding an incidence rate of 1.5/100PY (95% CI 1.2–1.8). Independent predictors of incident infection were registration in Punjab province (AHR 1.73 95% CI 1.13–2.68, p = 0.012) and 1–5 years of education (AHR 1.89 95% CI 1.22–2.93, p = 0.004). Knowledge of HIV at registration was protective against infection (AHR 0.51, 95% CI 0.26–0.99, p = 0.047), along with a MWID spouse who had initiated antiretroviral therapy (ART) (AHR 0.25, 95% CI 0.16–0.38, p < 0.001), while incident infection was inversely associated with number of children (≥ 5 children AHR 0.44 95% CI 0.22–0.88, p = 0.022). Conclusions Additional efforts are needed to reduce HIV transmission among female spouses of MWID, including targeted provision of HIV education and access to HIV screening. Interventions that target MWID are also required, including evidence-based drug treatment and access to ART, including support to maximize adherence. Finally, consideration should be given to making HIV pre-exposure prophylaxis available to female spouses at high risk of HIV transmission, particularly young women and those whose husbands are not receiving, or have difficulty adhering to, ART.

Effective Human Immunodeficiency Virus Molecular Surveillance Requires Identification of Incident Cases of Infection

Background Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. Methods Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance–based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. Results Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09–113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. Conclusions Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.

Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

Objective: Clostridioides difficile infection (CDI) is the leading cause of infectious nosocomial diarrhea. Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists varied recommendations for first-episode non-severe CDI. Given the discrepancy in current treatment guidelines, we sought to evaluate the use of initial vancomycin versus metronidazole for first-episode non-severe CDI. Methods: We conducted a retrospective cohort study of all adult inpatients with first-episode CDI at our institution from January 2013 to May 2018. The initial vancomycin versus initial metronidazole cohorts were examined using a multivariate logistic regression model. Results: The study cohort of 737 patients had a median age of 72.3 years, and 357 of these patients (48.4%) had hospital-acquired infection. Among 326 patients with non-severe CDI, recurrence, new incident infection, and 30-day mortality rates were 16.2%, 10.9%, and 5.3%, respectively, when treated with initial metronidazole, compared to 20.0%, 1.4%, and 10.0%, respectively, when treated with initial vancomycin. In an adjusted multivariable analysis, the use of initial vancomycin for the treatment of non-severe CDI was associated with a reduction in new incident infection (adjusted odds ratio [ORadj], 0.11; 95% confidence interval [CI], 0.02–0.86; P = .035), compared to initial metronidazole. Conclusions: Initial vancomycin was associated with a reduced rate of new incident infection in the treatment of adult inpatients with first-episode non-severe CDI. These findings support the use of initial vancomycin for all inpatients with CDI, when fidaxomicin is unavailable.