Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial.

BACKGROUND: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. METHODS: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. FINDINGS: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. INTERPRETATION: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. FUNDING: Belgian Health Care Knowledge Centre.

Rapid detection of S. pyogenes and S. pneumoniae in pleural fluid for diagnosis of parapneumonic empyema.

The aim of this study was to assess the reliability of rapid antigen detection tests (RADT) for Streptococcus pyogenes (GAS) and Streptococcus pneumoniae on pleural fluid samples for diagnosis of parapneumonic effusion/empyema (PPE) and their potential for improving pathogen identification rates. Sixty-three pleural samples were included from 54 patients on which GAS and S. pneumoniae RADT (BinaxNOW), culture, 16S rRNA PCR, and S. pneumoniae-specific PCR were performed. GAS RADT showed a sensitivity of 95.2% and a specificity of 100%. Pneumococcal RADT showed a sensitivity of 100% and specificity of 88.6%. Both RADT increased the pathogen identification rate in PPE compared to culture.

Risk factors for surgical site infection following cardiac surgery in a region endemic for multidrug resistant organisms.

OBJECTIVES: To identify risk factors for surgical site infections following cardiosurgery in an area endemic for multidrug resistant organisms. DESIGN: Single-center, historical cohort study including patients who underwent cardiosurgery during a 6-year period (2014-2020). SETTING: Joint Commission International accredited, multiorgan transplant center in Palermo, Italy. MAIN OUTCOME MEASURES: Surgical site infection was the main outcome. RESULTS: On a total of 3609 cardiosurgery patients, 184 developed surgical site infection (5.1 %). Intestinal colonization with multidrug resistant organisms was more frequent in patients with surgical site infections (69.6 % vs. 33.3 %; p < 0.001). About half of surgical site infections were caused by Gram-negative bacteria (n = 97; 52.7 %). Fifty surgical site infections were caused by multidrug resistant organisms (27.1 %), with extended-spectrum Beta-lactamase-producing Enterobacterales (n = 16; 8.7 %) and carbapenem-resistant Enterobacterales (n = 26; 14.1 %) being the predominant resistance problem. However, in only 24 of surgical site infections caused by multidrug resistant organisms (48 %), mostly carbapenem-resistant Enterobacterales (n = 22), a pathogen match between the rectal surveillance culture and surgical site infections clinical culture was demonstrated. Nevertheless, multivariate logistic regression analysis identified a rectal swab culture positive for multidrug resistant organisms as an independent risk factor for SSI (odds ratio 3.95, 95 % confidence interval 2.79-5.60). Other independent risk factors were female sex, chronic dialysis, diabetes mellitus, previous cardiosurgery, previous myocardial infarction, being overweight/obese, and longer intubation time. CONCLUSION: In an area endemic for carbapenem-resistant Enterobacterales, intestinal colonization with multidrug resistant organisms was recognized as independent risk factor for surgical site infections. IMPLICATIONS FOR CLINICAL PRACTICE: No causal relationship between colonization with resistant pathogens and subsequent infection could be demonstrated. However, from a broader epidemiological perspective, having a positive multidrug resistant organisms colonization status appeared a risk factor for surgical site infections. Therefore, strict infection control measures to prevent cross-transmission remain pivotal (e.g., nasal decolonization, hand hygiene, and skin antisepsis).

Development of quality indicators for antimicrobial stewardship in Belgian hospitals: a RAND - modified Delphi procedure.

INTRODUCTION: Inappropriate antibiotic use is a major cause of antibiotic resistance. Therefore, optimizing antibiotic usage is essential. In Belgium, optimization of antimicrobials for the fight against multidrug resistant organisms (MDROs) is followed up by national surveillance by public health authorities. To improve appropriate antimicrobial use in hospitals, an effective national Antimicrobial Stewardship (AMS) program should include indicators for measuring both the quantity and quality of antibiotic use. OBJECTIVES: The aim of this study was to develop a set of process quality indicators (QIs) to evaluate and improve AMS in hospitals. METHODS: A RAND-modified Delphi procedure was used. The procedure consisted of a structured narrative literature review to select the QIs, followed by two online questionnaires and an intermediate multidisciplinary panel discussion with experts in infectious diseases from general and teaching hospitals in Belgium. RESULTS: A total of 38 QIs were selected after the RAND-modified Delphi procedure, from which 11 QIs were selected unanimously. These QIs address compliancy of antibiotic therapy and prophylaxis with local guidelines, documentation of the rationale for antibiotic treatment in the medical record, the availability of AMS Programs and Outpatient Parenteral Antibiotic Therapy, resistance patterns and antimicrobial prescribing during focused ward rounds. CONCLUSION: Our study selected 38 relevant process QIs, from which 11 were unanimously selected. The QIs can contribute to the improvement of quality of antibiotic use by stimulating hospitals to present better outcomes and by providing a focus on how to intervene and to improve prescribing of antimicrobials.

A Belgian student with black eschars.

BACKGROUND: Human cowpox virus infection is a rare zoonotic disease. Cowpox virus is a member of the Orthopoxvirus genus, like smallpox. Over the last years records of cowpox virus transmission from pet cats and pet rats to humans in Europe have increased. This observation may result from the loss of cross-immunity against orthopoxviruses after discontinuation of routine smallpox vaccination in the 1980s. CASE PRESENTATION: We report the first case of a human cowpox infection in an unvaccinated Belgian citizen. This 19-year-old student presented with multiple necrotic skin lesions on the chin, the scalp and the pubic region, and with cervical lymphadenopathy and flu-like symptoms. The diagnosis of human cowpox was based on electron microscopic findings and PCR examination performed on a skin biopsy of the pubic lesion. Close contact with cats (her domestic cats or cats from a local shelter) was probably the source of transmission. Spreading of the lesions was likely the result of autoinoculation. After six months all lesions spontaneously healed with atrophic scars. DISCUSSION: To enhance awareness of this rare viral zoonosis and to verify the suspected increase in incidence and symptom severity after cessation of smallpox vaccination, one could argue whether human cowpox should become a notifiable disease.

Management Challenges of Extrapulmonary Nontuberculous Mycobacterial Infection: A Single-Center Case Series and Literature Review.

Extrapulmonary nontuberculous mycobacterial (NTM) disease remains largely enigmatic, yet these mycobacteria are increasingly acknowledged as important opportunistic pathogens in humans. Traditionally, NTM infections have been identified across various anatomical locations, with the respiratory system being the most affected and best understood. Historically, extrapulmonary NTM infection was predominantly associated with HIV/AIDS, with Mycobacterium avium lymphadenopathy being the most commonly reported. Today, however, because of the expanding utilization of immunosuppressive therapies and the demographic shift towards an aging population, an increasing number of NTM infections are expected and seen. Hence, a heightened index of suspicion is essential, necessitating a multifaceted approach to identification and drug sensitivity testing to improve treatment outcomes. In extrapulmonary NTM management, expert consultation is strongly recommended to determine the most efficacious treatment regimen, as individualized, patient-tailored therapies are often required. Furthermore, the economic burden of NTM disease is considerable, accompanied by high rates of hospitalization. To optimize the management of these intricate infections, there is an urgent need for comprehensive data on incidence, prevalence, and outcomes. This case-based series delves into the intricate nature of extrapulmonary NTM infections, focusing on both rapid and slow-growing NTM species, and explores therapeutic options, resistance mechanisms, and host-related immunological factors.

The Role of Abdominal Drain Cultures in Managing Abdominal Infections.

Intra-abdominal infections (IAI) are common in hospitalized patients, both in and outside of the intensive care unit. Management principles include antimicrobial therapy and source control. Typically, these infections are polymicrobial, and intra-operative samples will guide the targeted antimicrobial therapy. Although the use of prophylactic abdominal drains in patients undergoing abdominal surgery is decreasing, the use of drains to treat IAI, both in surgical and non-surgical strategies for abdominal infection, is increasing. In this context, samples from abdominal drains are often used to assist in antimicrobial decision making. In this narrative review, we provide an overview of the current role of abdominal drains in surgery, discuss the importance of biofilm formation in abdominal drains and the mechanisms involved, and review the clinical data on the use of sampling these drains for diagnostic purposes. We conclude that biofilm formation and the colonization of abdominal drains is common, which precludes the use of abdominal fluid to reliably diagnose IAI and identify the pathogens involved. We recommend limiting the use of drains and, when present, avoiding routine microbiological sampling.

PS-SiZer map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration.

OBJECTIVES: We extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy. METHODS: We propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain. RESULTS: Through simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38-62 weeks versus 55-93 weeks in those receiving non-d4T-based regimens. DISCUSSION: PS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves.

The efficacy of a brief intervention to reduce alcohol use in persons with HIV in South Africa, a randomized clinical trial.

BACKGROUND: Since there is a high prevalence of high risk alcohol use in patients with HIV in Africa, with negative health effects, there is a need for short interventions to reduce alcohol use. METHODS: We studied the efficacy of a short intervention aiming to reduce alcohol use based on the Information-Motivation-Behavioural Skills Model in patients with HIV with high alcohol use (measured by AUDIT). The study was performed in three outpatient clinics in South Africa. The intervention group received in one-session intervention a personalized feedback on AUDIT results trying to make people aware that they are in the medium- or high-risk drinking category. Both the intervention and the control group received a health education leaflet. RESULTS: A total of 560 patients participated in the study with a follow up of 1 year. There was a significant decrease in total AUDIT scores between baseline and follow up points 1 (5 months) and 2 (1 year) in both groups. There was no significant decrease between time points 1 and 2. However, between the intervention and control groups there was no difference in reduction of alcohol use to abstinence or low risk alcohol use over time as there was no difference in absolute decrease in AUDIT-score or percentage of change in AUDIT score. The intervention had no influence on the quality of life outcomes, depression scores, stigma, tobacco use, viral load and therapy adherence at both time points. In all secondary outcomes, there was no significant interaction between intervention and time. CONCLUSION: The brief intervention was not successful at reducing alcohol use both 5 and 12 months after the intervention. However, there was a beneficial effect on reported hazardous or harmful alcohol use at least over a short term follow up period in both study groups. It might be that only an interview and/or the distribution of a health leaflet can be successful in reducing alcohol use but this needs to be investigated with more objective measures of alcohol use. To sustain an effect, most likely repetitive contacts with hazardous or harmful alcohol drinkers will be needed during a long follow up period.

Body Mass Index and Waist Circumference in Patients with HIV in South Africa and Associated Socio-demographic, Health Related and Psychosocial Factors.

A high body mass index (BMI) and high waist circumference are important health risk factors predisposing for cardiovascular and metabolic diseases and certain cancers. Historically, underweight was a diagnostic criterion of HIV-infection. In a cross-sectional study the prevalence of BMI-categories and high waist circumference and its associated factors in patients visiting three outpatient HIV clinics in South Africa were measured with anthropometric measurements and structured questionnaires regarding socio-demographic information, quality of life (QoL), AIDS-related stigma, symptoms of depression, alcohol use, HIV related information and level of adherence to ART. The median age of the 2230 included patients was 37 years, 66.5% were women and 88.6% received antiretroviral therapy. The prevalences of overweight, obesity and high waist circumference were 29.2, 21.9 and 44.6% respectively in women and 12.4, 4.0 and 3.9% respectively in men. Underweight was found in 18.2% of men and 6.3% of women. In multinomial regression analysis compared to a normal BMI, both overweight and obesity were associated with female gender, with being married or cohabiting and with a higher QoL score. Underweight was associated with male gender and tobacco use and negatively associated with being married or cohabiting and the physical domain of the QoL measure. A high waist circumference in men was associated with higher age and negatively associated with tobacco use and stigma score. In women it was negatively associated with never being married. A high prevalence of overweight and obesity was observed in HIV-clinics in South Africa, mainly in women. Since overweight and obesity are important health risk factors, effective weight reduction interventions are desirable.

National guidelines not always followed when diagnosing smear-negative pulmonary tuberculosis in patients with HIV in Botswana.

BACKGROUND: Diagnosis of smear negative pulmonary tuberculosis (SNPTB) is challenging, especially in patients with HIV. The Botswana National Tuberculosis Program (BNTP) guidelines give guidance in diagnosing and treating SNPTB. Patients with chronic cough should be screened for TB by 3 sputum smear investigations. If negative, a chest x-ray (CXR) should be performed. If negative for TB, antimicrobial treatment for other infections should be started. We investigated the clinicians' use of the guidelines in clinical practice. METHODS: Data regarding the medical history (coughing period), requested and conducted investigations concerning tuberculosis diagnosis (sputum smear or culture or CXR) or alternative diagnoses (sputum microscopy or blood or sputum culture for diagnosis of other organisms), in SNPTB HIV-positive patients (outpatients and admitted patients) from 2006-2009 in a district hospital in Botswana were extracted from all available hospital medical records. Additionally, a survey was done in all doctors diagnosing SNPTB in this hospital using a self-administered questionnaire with questions regarding the application of the BNTP guidelines in practice. Descriptive analyses of collected data were performed to test the compliance to the guidelines. RESULTS: Data from medical records showed that in 47.0% (132/281) of patients, TB treatment was started without microbiological results from sputum smears. Other methods to rule out or confirm PTB were used in 2.1% (6/281); and 99.6% (280/281) of SNPTB patients had received a CXR. The survey in 7 clinicians found that all always used CXR, and all clinicians requested three sputum results only sometimes. Six out of 7 clinicians started antibiotics before starting TB treatment. Reasons clinicians gave for difficulties in following the guidelines included inability of patients to produce sputum; and laboratory delays in releasing sputum results. CONCLUSION: Between 2006 and 2009 a high proportion of SNPTB diagnoses in a district hospital in Botswana were not supported by laboratory investigation.

The efficacy of a brief intervention to reduce alcohol misuse in patients with HIV in South Africa: study protocol for a randomized controlled trial.

BACKGROUND: Alcohol abuse comes with risks for increased morbidity and mortality among patients with HIV. This study aims to determine the prevalence of alcohol use and other risk factors in a sample of primary care patients with HIV in South Africa and to assess a brief intervention to reduce the use of alcohol in this group. METHODS/DESIGN: A single-blinded randomized controlled trial is designed to determine the efficacy of a brief intervention to reduce hazardous alcohol use in patients with HIV. The study will be carried out on out-patients with HIV in two primary healthcare HIV clinics near Pretoria, South Africa. Alcohol use will be assessed with the Alcohol Use Disorder Identification Test questionnaire. Other data that will be collected relate to health-related quality of life, depression, sexual behavior, internalized AIDS stigma, HIV-related information and adherence to antiretroviral therapy (self-reported 7-day recall of missed doses, Visual Analog Scale and pill count). The intervention consists of a brief counseling session to reduce alcohol risk; the control group receives a health education leaflet. DISCUSSION: The findings will be important in the public health setting. If the intervention proves to be efficient, it could potentially be incorporated into the HIV care policy of the Ministry of Health. TRIAL REGISTRATION: Pan African Clinical trial Registry: PACTR201202000355384.

Interventions to reduce mortality in sub-Saharan Africa among HIV-infected adults not yet on antiretroviral therapy.

Where antiretroviral therapy is available, the primary source of mortality among HIV-infected people is the delay in starting treatment. Many of these delays occur in the context of care and are modifiable through changes in the protocols followed by healthcare providers for HIV testing, staging and preparation of patients for antiretroviral therapy. A number of potential evidence-based interventions are discussed in the context of sub-Saharan Africa. Included are decentralizing services, initiating counseling on antiretroviral therapy without delay, tracing patients that miss appointments, protecting patient confidentiality, reducing user fees, and providing point-of-care tests for CD4 cell counts, cryptococcal antigen, and for the diagnosis of TB.

Using giant African pouched rats to detect tuberculosis in human sputum samples: 2009 findings.

In 2009, giant African pouched rats trained to detect tuberculosis (TB) evaluated sputum samples from 10,523 patients whose sputum had previously been evaluated by smear microscopy. Microscopists found 13.3% of the patients to be TB-positive. Simulated second-line screening by the rats revealed 620 new TB-positive patients, increasing the case detection rate by 44%. These data suggest that the rats may be useful for TB detection in developing countries, although further research is needed.

The role and significance of sputum cultures in the diagnosis of melioidosis.

Pneumonia is a common manifestation of melioidosis, the disease caused by Burkholderia pseudomallei. In this study, we defined the prognostic significance of a positive sputum culture. A total of 712 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, Thailand, with melioidosis between January 1992 and December 2002 had a sputum culture performed during admission, which was positive for B. pseudomallei in 444 patients (62%). The median duration of sputum positivity was 9 days (range, 1 to 49 days). Sputum cultures were negative in 32% of patients with radiologic changes suggestive of pulmonary involvement. Overall in-hospital mortality was 48%. A positive sputum culture was associated with mortality (adjusted OR 2.8, 95% CI: 1.9, 4.0; P < 0.001). This was independent of renal disease, a prior history of melioidosis, positive blood cultures, and other potential confounders. The presence of B. pseudomallei in the sputum of patients with melioidosis is associated with a poorer prognosis.