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Bartonella quintana is a louse-borne intracellular bacterium that remains a neglected cause of bacteremia, bacillary angiomatosis, and infective endocarditis among individuals experiencing poverty. In October 2023, Health Canada notified Canadian organ transplantation programs of an outbreak of donor-derived B quintana infection. From March to August 2023, 5 cases of donor-derived B quintana disease were acquired in Alberta, Canada, from 3 deceased donors who had experienced homelessness. Similar cases recently occurred in the United States. In this article, we discuss strategies to screen organ donors and monitor transplant recipients for B quintana infection using epidemiologic risk factors, physical examination signs, and laboratory diagnostic tests. We review the limitations of existing diagnostic tests for B quintana and describe how these problems may be magnified in the organ transplantation context. [ABSTRACT FROM AUTHOR]

Background People with human immunodeficiency virus (PWH) with recurrent visceral leishmaniasis (VL) could potentially drive Leishmania transmission in areas with anthroponotic transmission such as East Africa, but studies are lacking. Leishmania parasitemia has been used as proxy for infectiousness. Methods This study is nested within the Predicting Visceral Leishmaniasis in HIV-InfectedPatients (PreLeisH) prospective cohort study, following 490 PWH free of VL at enrollment for up to 24–37 months in northwest Ethiopia. Blood Leishmania polymerase chain reaction (PCR) was done systematically. This case series reports on 10 PWH with chronic VL (≥3 VL episodes during follow-up) for up to 37 months, and 3 individuals with asymptomatic Leishmania infection for up to 24 months. Results All 10 chronic VL cases were male, on antiretroviral treatment, with 0–11 relapses before enrollment. Median baseline CD4 count was 82 cells/µL. They displayed 3–6 VL treatment episodes over a period up to 37 months. Leishmania blood PCR levels were strongly positive for almost the entire follow-up (median cycle threshold value, 26 [interquartile range, 23–30]), including during periods between VL treatment. Additionally, we describe 3 PWH with asymptomatic Leishmania infection and without VL history, with equally strong Leishmania parasitemia over a period of up to 24 months without developing VL. All were on antiretroviral treatment at enrollment, with baseline CD4 counts ranging from 78 to 350 cells/µL. Conclusions These are the first data on chronic parasitemia in PWH from Leishmania donovani –endemic areas. PWH with asymptomatic and symptomatic Leishmania infection could potentially be highly infectious and constitute Leishmania superspreaders. Xenodiagnosis studies are required to confirm infectiousness. [ABSTRACT FROM AUTHOR]

Accurate detection of viable Leishmania parasites is critical for evaluating visceral leishmaniasis (VL) treatment response at an early timepoint. We compared the decay of kinetoplast DNA (kDNA) and spliced-leader RNA (SL-RNA) in vitro, in vivo, and in a VL patient cohort. An optimized combination of blood preservation and nucleic acid extraction improved efficiency for both targets. SL-RNA degraded more rapidly during treatment than kDNA, and correlated better with microscopic examination. SL-RNA quantitative polymerase chain reaction emerges as a superior method for dynamic monitoring of viable Leishmania parasites. It enables individualized treatment monitoring for improved prognoses and has potential as an early surrogate endpoint in clinical trials. [ABSTRACT FROM AUTHOR]

Background Diagnosis of cutaneous leishmaniasis (CL) usually relies on invasive samples, but it is unclear whether more patient-friendly tools are good alternatives for diverse lesions when used with polymerase chain reaction (PCR). Methods Patients with suspected CL were enrolled consecutively in a prospective diagnostic accuracy study. We compared dental broach, tape disc, and microbiopsy samples with PCR as index tests, using PCR with skin slit samples as reference test. Subsequently, we constructed a composite reference test including microscopy, the 3 index tests and skin slit PCR, and we compared these same tests with the composite reference test. We assessed diagnostic accuracy parameters with 95% confidence intervals for all comparisons. Results Among 344 included patients, 282 (82.0%) had CL diagnosed, and 62 (18.0%) CL absence, by skin slit PCR. The sensitivity and specificity by PCR were 89.0% (95% confidence interval, 84.8%–92.1%) and 58.1% (45.7%–69.5%), respectively, for dental broach, 96.1% (93.2%–97.8%) and 27.4% (17.9%–39.6%) for tape disc, and 74.8% (66.3%–81.7%) and 72.7% (51.8%–86.8%) for microbiopsy. Several reference test–negative patients were consistently positive with the index tests. Using the composite reference test, dental broach, and skin slit had similar diagnostic performance. Discussion Dental broach seems a less invasive but similarly accurate alternative to skin slit for diagnosing CL when using PCR. Tape discs lack specificity and seem unsuitable for CL diagnosis without cutoff. Reference tests for CL are problematic, since using a single reference test is likely to miss true cases, while composite reference tests are often biased and impractical as they require multiple tests. [ABSTRACT FROM AUTHOR]

Background Bartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical manifestations, and treatment of B. quintana endocarditis are biased by older studies from high-income countries. Methods We searched Pubmed Central, Medline, Scopus, Embase, EBSCO (CABI) Global Health, Web of Science and international trial registers for articles published before March 2023 with terms related to Bartonella quintana endocarditis. We included articles containing case-level information on B. quintana endocarditis and extracted data related to patient demographics, clinical features, diagnostic testing, treatment, and outcome. Results A total of 975 records were identified, of which 569 duplicates were removed prior to screening. In total, 84 articles were eligible for inclusion, describing a total of 167 cases. Infections were acquired in 40 different countries; 62 cases (37.1%) were acquired in low- and middle-income countries (LMICs). Disproportionately more female and pediatric patients were from LMICs. More patients presented with heart failure (n = 70/167 [41.9%]) than fever (n = 65/167 [38.9%]). Mean time from symptom onset to presentation was 5.1 months. Also, 25.7% of cases (n = 43/167) were associated with embolization, most commonly to the spleen and brain; 65.5% of antimicrobial regimens included doxycycline. The vast majority of cases underwent valve replacement surgery (n = 154/167, [98.0%]). Overall case fatality rate was 9.6% (n = 16/167). Conclusions B. quintana endocarditis has a global distribution, and long delays between symptom onset and presentation frequently occur. Improved clinician education and diagnostic capacity are needed to screen at-risk populations and identify infection before endocarditis develops. [ABSTRACT FROM AUTHOR]

Bartonella quintana is a louse-borne gram-negative bacillus that remains a poorly characterized cause of bacteremia, fever, and infective endocarditis. Due to the link with pediculosis, B quintana transmission is tied to poverty, conflict, overcrowding, and inadequate water access to maintain personal hygiene. Although these risk factors may be present globally, we argue that a substantial burden of undocumented B quintana infection occurs in Africa due to the high prevalence of these risk factors. Here, we describe the neglected burden of B quintana infection, endocarditis, and vector positivity in Africa and evaluate whether B quintana meets criteria to be considered a neglected tropical disease according to the World Health Organization. [ABSTRACT FROM AUTHOR]

The seventh author's name is spelled incorrectly. The correct name is: Johan van Griensven.By Workagegnehu Hailu; Rezika Mohamed; Helina Fikre; Saba Atnafu; Azeb Tadesse; Ermias Diro and Johan van GriensvenReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Background Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation, and outcome of these infections in a reference travel clinic over the past decades. Methods We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within 3–12 months. Results A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6, Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130, unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year on average in the 1990s to 6.3/year in the past decade, when loiasis became predominant. Cases reported symptoms in >80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively). Conclusions The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis. [ABSTRACT FROM AUTHOR]

Background Hepatosplenic schistosomiasis (HSS) is an important chronic complication of Schistosoma infection. However, its diagnosis and management are complicated due to lack of evidence and uniform guidance. In this study, we described the clinical profile and management of HSS in one of Ethiopia's referral hospitals. Methods A hospital-based, cross-sectional study was conducted using the medical records of patients diagnosed with HSS based on clinical symptoms and typical ultrasound findings observed at the gastroenterology clinic of Dessie referral hospital from September 2018 to December 2019. Results A total of 55 patient files were evaluated. Most patients (n=39; 70%) presented with upper gastrointestinal bleeding and severe anaemia. Nearly three-quarters of patients were admitted and 31 (56%) received a blood transfusion. Hepatitis B coinfection was documented in 11 patients (20%). Upper gastrointestinal endoscopy was performed in 31 patients (56%), in whom large oesophageal varices with red signs were the most common finding. Among patients who had endoscopy, band ligation was carried out in 21 cases (68%). Praziquantel was administered to 11 patients (20%). Conclusion HSS causes severe complications of portal hypertension, like variceal bleeding, which are currently not adequately treated. In addition to already existing preventive efforts, we advise control programmes to also address acute management and rehabilitation of these patients. [ABSTRACT FROM AUTHOR]

Empiric malaria treatment in Sub-Saharan Africa has significantly decreased with the scaling-up of malaria rapid diagnostic tests; this coincided with a pronounced increase in empiric antibiotic prescriptions. In high-income countries, guidance for antibiotic prescriptions using biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) has reduced antibiotic use while safe-guarding patient safety. Importantly, several low-cost point-of-care CRP/PCT tests are currently available. However, only a few studies on the role of CRP/PCT in differentiating bacterial vs viral infections in acute febrile illness have been conducted in Sub-Saharan Africa. Studies from Central and West Africa (most of which is malaria-endemic) are particularly scarce, and only 1 has included adults. The evidence base for point-of-care use of CRP/PCT biomarkers in acute fever in Sub-Saharan Africa should be urgently built. Before engaging in clinical trials to assess clinical impact, pilot studies should be conducted to address key knowledge gaps including recommended CRP/PCT cutoff values and the effect of malaria coinfection. [ABSTRACT FROM AUTHOR]

Countries around the world are facing an enormous challenge due to the COVID-19 pandemic. The pressure that the pandemic inflicts on health systems could certainly impact on the care, control, and elimination of neglected tropical diseases (NTDs). From mid-January 2020, Ethiopia started to prepare for the prevention and treatment of COVID-19. The Federal Ministry of Health pledged to continue essential healthcare, including NTD care, during this pandemic. However, some hospitals have been closed for other healthcare services and have been turned into isolation and treatment centers for COVID-19. In addition to the healthcare facility measures, all community-based health promotion and disease prevention services have been stopped. The current shift in attention towards COVID-19 is expected to have a negative impact on NTD prevention and care. [ABSTRACT FROM AUTHOR]

Current sampling methods to diagnose cutaneous leishmaniasis are invasive and painful. An alternative and minimally invasive microbiopsy device was evaluated in a diverse range of cutaneous leishmaniasis lesions in Ethiopia. Using polymerase chain reaction–based diagnosis, the microbiopsy outperformed the routine skin slit sample by detecting more patients while pain scores were significantly lower. [ABSTRACT FROM AUTHOR]

Background: Over the last decade, the availability and use of mobile phones have grown exponentially globally and in Cambodia. In the Sihanouk Hospital Centre of Hope(SHCH) in Cambodia about half of all tuberculosis patients referred out to peripheral health facilities for TB treatment initiation or continuation were lost to contact after referral ranging from 19 to 69% between 2008 and 2013. To address this, we implemented a mobile phone-based patient tracking intervention. Here, we report the number and proportion of referred TB patients who could be contacted through a mobile phone and retained in care after the introduction of mobile phone tracking.Methods: A descriptive study involving follow-up of TB patients referred out from SHCH to peripheral health facilities during May-October 2014. Standard operating procedures were used to contact individual patients and/or health facilities using a mobile phone.Results: Among 109 TB patients referred to peripheral health facilities, 107(98%) had access to a mobile phone of whom, 103(97%) could be contacted directly while 5(2%) were contacted through their health care providers. A total of 108(99%) of 109 referred TB patients in intervention period were thus placed on TB treatment.Conclusions: This study provides preliminary, but promising evidence that using mobile phones was accompanied with improved retention of referred TB patients compared to historical cohorts. Given the limitations associated with historical controls, we need better designed studies with larger sample size to strengthen the evidence before national scale-up. [ABSTRACT FROM AUTHOR]

Background: Although stavudine (D4T) remains frequently used in low-income countries in Asia, associated long-term toxicity data are scarce. The aim of this study was to determine the long-term incidence of severe D4T-toxicity (requiring drug substitution) and associated risk factors in HIV-infected Cambodians up to six years on antiretroviral treatment (ART). Methodology/Principal Findings: This is a retrospective analysis of an observational cohort, using data from an ART program with systematic monitoring for D4T-toxicity. Probabilities of time to D4T substitution due to suspected D4T toxicity (treatment-limiting D4T toxicity) were calculated, a risk factor analysis was performed using multivariate Cox regression modelling. Out of 2581 adults initiating a D4T-containing regimen, D4T was replaced in 276 (10.7%) patients for neuropathy, 14 (0.5%) for lactic acidosis and 957 (37.1%) for lipoatrophy. The main early side effect was peripheral neuropathy (7.0% by 1 year). After the first year, lipoatrophy became predominant, with a cumulative incidence of 56.1% and 72.4% by 3 and 6 years respectively. Older age (aHR 1.8; 95%CI: 1.4-2.3) and lower baseline haemoglobin (aHR 1.7; 95%CI: 1.4-2.2) were associated with the occurrence of neuropathy. Being female (aHR 3.8; 95%CI: 1.1-12.5), a higher baseline BMI (aHR 12.6; 95%CI: 3.7-43.1), and TB treatment at ART initiation (aHR 8.6; 95%CI: 2.7-27.5) increased the likelihood of lactic acidosis. Lipoatrophy was positively associated with female gender (aHR 2.3; 95%CI: 2.0-2.6), an older age (aHR 1.3; 95%CI: 1.1-1.4), and a CD4 count <200 cells/μL (aHR 1.3; 95%CI: 1.1-1.5). Conclusions: Stavudine-based treatment regimens in low-income countries are associated with significant long-term toxicities, predominantly lipoatrophy. Close clinical monitoring for toxicity with timely D4T substitution is recommended. Phasing-out of stavudine should be implemented, as costs allows. [ABSTRACT FROM AUTHOR]

Background. Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India. Methods. The study included all patients with newly diagnosed VL-HIV coinfection and initiating treatment with liposomal amphotericin B (20-25 mg/kg in 4-15 days) between July 2007 and September 2010. Kaplan-Meier estimates of the cumulative incidence of death/treatment failure were calculated. Results. Fifty-five patients were included (83.6% male; median age, 35 years; 62% migrant laborers; median follow-up, 1 year). The median CD4 cell count at VL diagnosis was 66 cells/μL (interquartile range, 38-112). Twentyseven patients (49.1%) presented with VL relapse of VL. The overall tolerance of liposomal amphotericin B was excellent, with no interrupted treatment. Survival by 1 and 2 years after VL treatment was estimated at 85.5%. Nopatients had initial treatment failure. The probabilities of VL relapse were 0%, 8.1%, and 26.5% at 0.5, 1, and 2 years after VL treatment, respectively; relapse rates were similar for primary VL and VL relapse. CD4 counts<200 cells/μL at 6 months after cART initiation were predictive of subsequent relapse. The mean CD4 cell counts at 6 and 24 months after cART initiation were 187 and 261 cells/μL, respectively. The rate for retention in HIV care was 83.6%. Conclusions. Good long-term survival and retention rates were obtained for VL-HIV-coinfected patients treated with liposomal amphotericin B and cART. Although the initial VL treatment response was excellent, VL relapse within 2 years remained frequent. [ABSTRACT FROM AUTHOR]

Background Visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection remains a major problem in Ethiopia, India, and Brazil. Tuberculosis (TB), a treatable factor, could contribute to high mortality (up to 25%) in VL-HIV coinfection. However, the current evidence on the prevalence and clinical impact of TB in VL-HIV coinfection is very limited. In previous reports on routine care, TB prevalence ranged from 5.7% to 29.7%, but information on how and when TB was diagnosed was lacking. Methods Field observations suggest that TB work-up is often not done systematically, and it is only done in patients who do not respond well to VL treatment. Here, we advocate high-quality diagnostic studies in VL-HIV-coinfected patients, during which all patients are systematically screened for TB, including a comprehensive work-up, to obtain reliable estimates. Results Cost-effective and feasible diagnostic algorithms can be developed for field use, and this can be integrated in VL clinical guidelines. Conclusions An accurate diagnosis of TB can allow clinicians to assess its clinical impact and evaluate the impact of early TB diagnosis. [ABSTRACT FROM AUTHOR]

Background: We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian human immunodeficiency virus-infected patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of up to 2.5 years after initiating PSP, including 1-year follow-up after PSP discontinuation., Methods: The trial had 3 phases: (1) 12 months of PSP; (2) a 6-month PSP extension period if CD4 count was ≤200 cells/μL at month 12; and (3) 12-month follow-up after stopping PSP. The probability of relapse and risk factors were calculated using Kaplan-Meier methods and Cox regression analysis., Results: For the 74 patients included, final study outcomes were as follows: 39 (53%) relapse-free, 20 (27%) relapsed, 5 (7%) deaths, 10 (14%) lost to follow-up. The 2-year risk of relapse was 36.9% (95% confidence interval, 23.4%-55.0%) and was highest for those with a history of VL relapse and low baseline CD4 count. Forty-five patients were relapse-free and in follow-up at month 12 of PSP. This included 28 patients with month 12 CD4 counts >200 cells/µL, remaining relapse-free after PSP discontinuation. Among the 17 with month 12 CD4 count <200 cells/µL, 1 relapsed and 3 were lost during the PSP extension period. During 1-year post-PSP follow-up, 2 patients relapsed and 1 was lost to follow-up. No PSP-related serious adverse events were reported during the PSP-extension/post-PSP follow-up period., Conclusions: It seems safe to discontinue PSP at month 12 CD4 counts of >200 cells/µL. The management of those failing to reach this level remains to be defined., Clinical Trials Registration: NCT01360762., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

The process of double ethical review involves the ethics committees (ECs) in the country(ies) of the research site(s) and of the sponsor. This paper aims to assess the experience of the double ethical review in the Ebola-Tx trial, and to make general recommendations for research conducted during public health emergencies.