Molds and More: Rare Fungal Infections in Preterm Infants <24 Weeks of Gestation.

BACKGROUND: Extreme immature infants are at an increased risk of fungal infection due to immaturity of the skin barrier and the immune system. Besides Candida infections, in particular, Aspergillus may cause life-threatening diseases in preterm infants. Frequently, Aspergillus primarily affects the skin and may cause extensive damage. METHODS: We searched our hospital database for fungal infections other than Candida in preterm infants treated between 2015 and 2020 at our level III neonatal intensive care unit of the University Hospital of Cologne. RESULTS: In total, 13 preterm infants were identified. Of these, 11 had cutaneous Aspergillosis, one infant had severe enterocolitis caused by Aspergillus and Rhizopus and one had invasive intraabdominal Trichosporon mucoides infection. All infants were born <24 weeks of gestation, were delivered due to premature labor or chorioamnionitis, and had received prenatal steroids and/or hydrocortisone. Voriconazole and liposomal Amphotericin B were first-line treatments and the length of treatment varied between 3 and 148 days. Two infants died associated with severe infection. Liver toxicity was observed in six infants treated with Voriconazole. Therapeutic drug management for Voriconazole was performed in four infants. Target levels were not achieved by the doses that are recommended. CONCLUSIONS: Rare fungal infections, predominantly cutaneous Aspergillosis affects the most immature preterm infants and may cause severe disease. Treatment with Voriconazole has a high rate of liver toxicity and target levels are difficult to achieve in extremely immature infants.

Pharmacokinetics of antitubercular drugs in patients hospitalized with HIV-associated tuberculosis: a population modeling analysis.

BACKGROUND: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups. METHODS: Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM ® was used to analyze the data. RESULTS: Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin's absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid's clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide's clearance was more variable among hospitalized patients. The variability in clearance among patients  was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients.   Conclusion. We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts.

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis.

AIMS: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). METHODS: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. RESULTS: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax ]: 7.4 vs 8.3 µg mL-1 , P = .223; 3.6 vs 3.5 µg mL-1 , P = .569; 50.1 vs 46.8 µg mL-1 , P = .081; area under the concentration-time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L-1 , P = 0.290; 13.5 vs 12.4 mg h L-1 , P = .630; 316.5 vs 292.2 mg h L-1 , P = .164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L-1 . CONCLUSION: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.

Clinical, microbiologic, and immunologic determinants of mortality in hospitalized patients with HIV-associated tuberculosis: A prospective cohort study.

BACKGROUND: In high-burden settings, case fatality rates are reported to be between 11% and 32% in hospitalized patients with HIV-associated tuberculosis, yet the underlying causes of mortality remain poorly characterized. Understanding causes of mortality could inform the development of novel management strategies to improve survival. We aimed to assess clinical and microbiologic determinants of mortality and to characterize the pathophysiological processes underlying death by evaluating host soluble inflammatory mediators and determined the relationship between these mediators and death as well as biomarkers of disseminated tuberculosis. METHODS AND FINDINGS: Adult patients with HIV hospitalized with a new diagnosis of HIV-associated tuberculosis were enrolled in Cape Town between 2014 and 2016. Detailed tuberculosis diagnostic testing was performed. Biomarkers of tuberculosis dissemination and host soluble inflammatory mediators at baseline were assessed. Of 682 enrolled participants, 576 with tuberculosis (487/576, 84.5% microbiologically confirmed) were included in analyses. The median age was 37 years (IQR = 31-43), 51.2% were female, and the patients had advanced HIV with a median cluster of differentiation 4 (CD4) count of 58 cells/L (IQR = 21-120) and a median HIV viral load of 5.1 log10 copies/mL (IQR = 3.3-5.7). Antituberculosis therapy was initiated in 566/576 (98.3%) and 487/576 (84.5%) started therapy within 48 hours of enrolment. Twelve-week mortality was 124/576 (21.5%), with 46/124 (37.1%) deaths occurring within 7 days of enrolment. Clinical and microbiologic determinants of mortality included disseminated tuberculosis (positive urine lipoarabinomannan [LAM], urine Xpert MTB/RIF, or tuberculosis blood culture in 79.6% of deaths versus 60.7% of survivors, p = 0.001), sepsis syndrome (high lactate in 50.8% of deaths versus 28.9% of survivors, p < 0.001), and rifampicin-resistant tuberculosis (16.9% of deaths versus 7.2% of survivors, p = 0.002). Using non-supervised two-way hierarchical cluster and principal components analyses, we describe an immune profile dominated by mediators of the innate immune system and chemotactic signaling (interleukin-1 receptor antagonist [IL-1Ra], IL-6, IL-8, macrophage inflammatory protein-1 beta [MIP-1ß]/C-C motif chemokine ligand 4 [CCL4], interferon gamma-induced protein-10 [IP-10]/C-X-C motif chemokine ligand 10 [CXCL10], MIP-1 alpha [MIP-1α]/CCL3), which segregated participants who died from those who survived. This immune profile was associated with mortality in a Cox proportional hazards model (adjusted hazard ratio [aHR] = 2.2, 95%CI = 1.9-2.7, p < 0.001) and with detection of biomarkers of disseminated tuberculosis. Clinicians attributing causes of death identified tuberculosis as a cause or one of the major causes of death in 89.5% of cases. We did not perform longitudinal sampling and did not have autopsy-confirmed causes of death. CONCLUSIONS: In this study, we did not identify a major contribution from coinfections to these deaths. Disseminated tuberculosis, sepsis syndrome, and rifampicin resistance were associated with mortality. An immune profile dominated by mediators of the innate immune system and chemotactic signaling was associated with both tuberculosis dissemination and mortality. These findings provide pathophysiologic insights into underlying causes of mortality and could be used to inform the development of novel treatment strategies and to develop methods to risk stratify patients to appropriately target novel interventions. Causal relationships cannot be established from this study.

Effectiveness of service models and organisational structures supporting tuberculosis identification and management in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review.

OBJECTIVE: To determine which service models and organisational structures are effective and cost-effective for delivering tuberculosis (TB) services to hard-to-reach populations. DESIGN: Embase and MEDLINE (1990-2017) were searched in order to update and extend the 2011 systematic review commissioned by National Institute for Health and Care Excellence (NICE), discussing interventions targeting service models and organisational structures for the identification and management of TB in hard-to-reach populations. The NICE and Cochrane Collaboration standards were followed. SETTING: European Union, European Economic Area, European Union candidate countries and Organisation for Economic Co-operation and Development countries. PARTICIPANTS: Hard-to-reach populations, including migrants, homeless people, drug users, prisoners, sex workers, people living with HIV and children within vulnerable and hard-to-reach populations. PRIMARY AND SECONDARY OUTCOME MEASURES: Effectiveness and cost-effectiveness of the interventions. RESULTS: From the 19 720 citations found, five new studies were identified, in addition to the six discussed in the NICE review. Community health workers from the same migrant community, street teams and peers improved TB screening uptake by providing health education, promoting TB screening and organising contact tracing. Mobile TB clinics, specialised TB clinics and improved cooperation between healthcare services can be effective at identifying and treating active TB cases and are likely to be cost-effective. No difference in treatment outcome was detected when directly observed therapy was delivered at a health clinic or at a convenient location in the community. CONCLUSIONS: Although evidence is limited due to the lack of high-quality studies, interventions using peers and community health workers, mobile TB services, specialised TB clinics and improved cooperation between health services can be effective to control TB in hard-to-reach populations. Future studies should evaluate the (cost-)effectiveness of interventions on TB identification and management in hard-to-reach populations and countries should be urged to publish the outcomes of their TB control systems. PROSPERO REGISTRATION NUMBER: CRD42015017865.

Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes.

Background: Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population. Methods: This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalized HIV-infected tuberculosis patients with CD4 counts <350 cells/µL were included; tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without active tuberculosis were recruited as controls. Whole blood was stimulated with Escherichia coli derived lipopolysaccharide, heat-killed Streptococcus pneumoniae, and Mycobacterium tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex), were assessed for associations with 12-week mortality using Cox proportional hazard models. Second, we investigated associations of these immune markers with tuberculosis mycobacteremia. Results: Sixty patients were included (median CD4 count 53 cells/µL (interquartile range [IQR], 22-132); 16 (27%) died after a median of 12 (IQR, 0-24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony-stimulating factor 3), and antiinflammatory markers (increased interleukin-1 receptor antagonist and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis. Conclusions: Twelve-week mortality was associated with greater pro- and antiinflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis.

Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study.

BACKGROUND: Mortality rates remain high for human immunodeficiency virus (HIV)-associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. METHODS: We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates. RESULTS: Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0-24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality. CONCLUSIONS: Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality.

Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature.

Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes.

Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review.

Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality.

HIV infection rather than concurrent opportunistic infections drives most systemic procoagulant, vascular and damage responses - a prospective cohort study in central Africa.

BACKGROUND: HIV infection is accompanied by various systemic host responses, including activation of coagulation and the vascular endothelium. We sought to determine the impact of opportunistic coinfections in a central African setting. METHODS: This prospective study included 98 HIV-infected individuals in Gabon initiating combination antiretroviral therapy (cART) and followed them up for 6 months. Patients were stratified according to the presence of active tuberculosis (TB; n=19), mucocutaneous opportunistic infection (n=9) or no opportunistic infection (n=70). HIV-uninfected subjects were included as controls (n=32). Plasma concentrations of 14 markers of coagulation, endothelial activation, extracellular matrix formation and tissue damage were measured with a multiplex assay at baseline and months 3 and 6 after cART initiation. RESULTS: HIV-infected patients showed elevated plasma levels of all biomarkers measured with exception of protein C, which was reduced. Concurrent TB was only associated with elevated concentrations of D-dimer, metallopeptidase inhibitor 1 and Tenascin-C. Mucocutaneous coinfection did not alter HIV-associated responses. Most markers measured declined but remained elevated despite response to cART. CONCLUSIONS: HIV infection is associated with systemic pro-coagulant, vascular and damage responses. In an ambulatory setting, concurrent opportunistic infections have little if any influence on these responses and normalization is incomplete after response to cART. This suggests that these responses are mainly driven by HIV-associated immune activation and less so by opportunistic infections.

Ultrasound for patients in a high HIV/tuberculosis prevalence setting: a needs assessment and review of focused applications for Sub-Saharan Africa.

Ultrasound is increasingly used in point-of-care applications and has great potential to support the diagnosis of infectious diseases, especially in resource-limited settings. A cross-sectional study was performed involving 100 Malawian patients with a clinical indication for ultrasound. Furthermore, the literature on point-of-care ultrasound (POCUS) in Sub-Saharan Africa was reviewed to establish its applicability, most frequent indications, findings, and implications for treatment, and therefore relevance in POCUS curricula, with a main focus on infectious diseases. In Malawi, the main indications for ultrasound were weight loss, abdominal pain, and shortness of breath. Abnormal findings were observed in 77% of patients, the most common being enlarged abdominal lymph nodes (n=17), pericardial effusion (n=15), splenic microabscesses (n=15), and pleural effusion (n=14). POCUS led to a change in treatment in 72% of patients. The literature on the various POCUS applications used in Malawi was reviewed, including focused assessment with sonography for HIV-associated TB (FASH), heart, liver, kidney, deep venous thrombosis (DVT), and gynaecology. Based on disease prevalence, impact of POCUS on treatment, and technical difficulty, it is proposed that FASH, heart, and DVT are the most relevant POCUS applications in comparable Sub-Saharan African settings and should be incorporated in POCUS curricula.

Tuberculosis Treatment Outcome and Drug Resistance in Lambaréné, Gabon: A Prospective Cohort Study.

Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action.

Chest ultrasonography in patients with HIV: a case series and review of the literature.

INTRODUCTION: Pulmonary disease is common in HIV-infected patients. Diagnostic means, however, are often scarce in areas where most HIV patients are living. Chest ultrasonography has recently evolved as a highly sensitive and specific imaging tool for diagnosing chest conditions such as pneumothorax, pneumonia and pulmonary edema in critically ill patients. This article addresses the issue of imaging and differentiating common pulmonary conditions in HIV-infected patients by chest ultrasonography. METHODS: We report chest ultrasound features of five different common pulmonary diseases in HIV-infected patients (bacterial pneumonia, Pneumocystis jirovecii pneumonia, tuberculosis, cytomegalovirus pneumonia and non-Hodgkin lymphoma) and review the respective literature. CONCLUSIONS: We observed characteristic ultrasound patterns especially in Pneumocystis jirovecii pneumonia and pulmonary lymphoma. Further exploration of chest ultrasonography in HIV-infected patients appears promising and may translate into new diagnostic approaches for pulmonary conditions in patients living with HIV.

Factors Associated with Retention to Care in an HIV Clinic in Gabon, Central Africa.

BACKGROUND: Retention to HIV care is vital for patients' survival, to prevent onward transmission and emergence of drug resistance. Travelling to receive care might influence adherence. Data on the functioning of and retention to HIV care in the Central African region are limited. METHODS: This retrospective study reports outcomes and factors associated with retention to HIV care at a primary HIV clinic in Lambaréné, Gabon. Adult patients who presented to this clinic between January 2010 and January 2012 were included. Outcomes were retention in care (defined as documented show-up for clinical visits, regardless of delay) or LTFU (defined as a patient not retained in care; on ART or ART naïve, not returning to care during the study period with a patient delay for scheduled visits of more than 6 months), and mortality. Cox regression analysis was used to assess factors associated with respective outcomes. Qualitative data on reasons for LTFU were obtained from focus-group discussions. RESULTS: Of 223 patients included, 67.3% were female. The mean age was 40.5 (standard deviation 11.4) years and the median CD4 count 275 (interquartile range 100.5-449.5) cells/µL. In total, 34.1% were lost to follow up and 8.1% died. Documented tuberculosis was associated with increased risk of being LTFU (adjusted hazard ratio (aHR) 1.80, 95% confidence interval (95% CI) 1.05-3.11, P = 0.03), whereas early starting anti-retroviral therapy (ART) was associated with a decreased risk of LTFU (aHR 0.43, 95%CI 0.24-0.76, P = 0.004), as was confirmed by qualitative data. CONCLUSIONS: Retention to HIV care in a primary clinic in Gabon is relatively poor and interventions to address this should be prioritized in the HIV program. Early initiation of ART might improve retention in care.

Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambaréné, Gabon.

BACKGROUND: Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections. METHODOLOGY AND PRINCIPAL FINDINGS: This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence. CONCLUSIONS/SIGNIFICANCE: CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established.

The impact of HIV on presentation and outcome of bacterial sepsis and other causes of acute febrile illness in Gabon.

PURPOSE: HIV, bacterial sepsis, malaria, and tuberculosis are important causes of disease in Africa. We aimed to determine the impact of HIV on the presentation, causes and outcome of bacterial sepsis and other acute febrile illnesses in Gabon, Central Africa. METHODS: We performed a prospective observational study in new adult admissions with fever or hypothermia (≥ 38 or <36 °C). Blood cultures, as well as HIV and malaria testing were performed in all patients. RESULTS: We enrolled 382 patients, including 77 (20.2%) with HIV infection. Malaria was the most frequent diagnosis (n = 130, 34%), and was associated with a more severe presentation in HIV patients. Sepsis was also common (n = 107, 28%), including 29 (7.6%) patients with culture confirmed bacterial bloodstream infection. Bacterial bloodstream infections were more frequent in HIV patients, in particular with S. pneumoniae. Tuberculosis was observed in 29 (7.6%) patients, and was also more common in HIV patients. The majority of HIV patients was newly diagnosed, and only 15 (19.5%) were using combination antiretroviral therapy. CONCLUSIONS: Our findings illustrate the impact of HIV co-infection on the burden of sepsis, malaria and tuberculosis in Gabon, as well as the need to scale up HIV counseling, testing and treatment.

Bedaquiline for the treatment of drug-resistant tuberculosis.

Bedaquiline is a much-needed novel drug which is highly effective against drug-resistant tuberculosis. While its clinical development has been laudably fast-tracked and the drug is now available for inclusion into treatment regimens when no suitable alternatives exist, clinical experience with bedaquiline is still limited. Phase III trial data and Phase IV studies are needed particularly to study different patient populations and to optimize treatment regimens. Drug resistance to bedaquiline needs to be monitored carefully, and full access to bedaquiline treatment where it is appropriate and needed must be promoted.

Effect of deworming on disease progression markers in HIV-1-infected pregnant women on antiretroviral therapy: a longitudinal observational study from Rwanda.

BACKGROUND: Deworming human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) may be beneficial, particularly during pregnancy. We determined the efficacy of targeted and nontargeted antihelminth therapy and its effects on Plasmodium falciparum infection status, hemoglobin levels, CD4 counts, and viral load in pregnant, HIV-positive women receiving ART. METHODS: Nine hundred eighty HIV-infected pregnant women receiving ART were examined at 2 visits during pregnancy and 2 postpartum visits within 12 weeks. Women were given antimalarials when malaria-positive whereas albendazole was given in a targeted (n = 467; treatment when helminth stool screening was positive) or nontargeted (n = 513; treatment at all time points, with stool screening) fashion. RESULTS: No significant differences were noted between targeted and nontargeted albendazole treatments for the variables measured at each study visit except for CD4 counts, which were lower (P < .05) in the latter group at the final visit. Albendazole therapy was associated with favorable changes in subjects' hemoglobin levels, CD4 counts, and viral loads, particularly with helminth infections. CONCLUSIONS: Antihelminthic therapy reduces detectable viral load, and increases CD4 counts and hemoglobin levels in pregnant HIV-infected women with helminth coinfections receiving ART.

Limited access to drugs for resistant tuberculosis: a call to action.

Although the rate of new tuberculosis (TB) cases has been falling worldwide, progress toward the targets for diagnosis and treatment of drug-resistant TB is far off-track. In countries with no reliable TB surveillance system, setbacks and progression of TB control is barely reflected and little is known on the situation in the field. Interviews with health professionals in Gabon revealed limited access to first- and second-line TB drugs and important deficiencies in basic TB control. National and international action needs to be taken to meet the global TB control targets.