Duration of Fever in Patients with Dengue: A Systematic Review and Meta-Analysis.

Dengue is an acute febrile illness endemic to tropical countries and associated with high mortality rates. Despite being a viral infection, there is rampant misuse of antibiotics in patients with dengue because of perceived delay in defervescence and fear of secondary bacterial infections. Therefore, there is a need to establish the average fever duration with a confidence interval among patients with dengue. Studies up to October 21, 2022 from two databases (PubMed and Embase) were included using the search terms related to dengue and duration of fever. All retrieved articles were screened for eligibility by two independent reviewers. Studies where the average duration of fever was available were included for systematic review. Articles with at least more than 20 patients where a mean and standard deviation for the total duration of fever was available were included for meta-analysis. A total of 643 articles were included from the two databases after duplicate deletion. After two rounds of screening, 31 articles (n = 7,905) were finally included. The mean duration of fever in the 20 articles included for meta-analysis was 5.1 (95% CI: 4.7-5.5) days. Longer duration of fever was seen in those with a higher grade of fever, those with higher disease severity, and those with concurrent bacterial infections. In the absence of risk factors for concurrent bacteremia, antimicrobials may be unnecessary in those with dengue fever duration of less than 5.5 days.

Development of a clinical scoring system to make a presumptive diagnosis of Kyasanur Forest Disease: a case-control study from South India.

Introduction: Kyasanur Forest Disease (KFD) is a viral haemorrhagic fever endemic in South India. Based on clinical presentation alone, it is challenging to distinguish KFD from other febrile illnesses in the region. The study aimed to develop a clinical scoring system for early presumptive diagnosis of KFD. Patients and methods: This retrospective case-control study included microbiologically diagnosed KFD patients (n=186) with other undifferentiated febrile illnesses as controls (n=203). The clinical and laboratory features between cases and controls were compared. A logistic regression analysis included those variables found to be significantly associated with KFD on univariate analysis. The adjusted odds ratio for the significant variables was calculated and converted into logarithmic scales. These numbers were rounded off to the nearest integer to find the score assigned to each variable. A receiver operating characteristics curve was created to find the best cut-off for the scoring system that predicted the diagnosis of KFD. Results: A total of 186 anonymised cases and 203 anonymised controls were recruited from the records for this study. Myalgia, headache, lymphadenopathy, bleeding manifestations, Central Nervous System (CNS) involvement, raised haematocrit, leukopenia, and raised transaminases were more common in patients with KFD. Except for lymphadenopathy and raised transaminases, all the other variables were independent predictors of making a diagnosis of KFD. Since raised transaminases tended towards significance, it was included in the scoring system with other independent predictors. A scoring system was created with a maximum score of 12. The receiver operating characteristic curve showed an Area Under Curve of 0.912 (95%CI: 0.88-0.94). A score of 4 or more was found to have a sensitivity and specificity of 83% and 87%, respectively. Conclusion: The presence of specific features should alert primary care physicians working in endemic areas about the possibility of KFD. This diagnostic scoring system can be used to make a presumptive diagnosis of KFD after undergoing a prospective validation study.

Hidden Burden of Bartonella quintana on the African Continent: Should the Bacterial Infection Be Considered a Neglected Tropical Disease?

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.

Ceftazidime-avibactam and aztreonam combination for Carbapenem-resistant Enterobacterales bloodstream infections with presumed Metallo-ß-lactamase production: a systematic review and meta-analysis.

INTRODUCTION: Carbapenem-resistant Enterobacterales (CRE) due to Metallo-ß-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections. METHODOLOGY: In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like 'CRE', 'MBL', 'AA' and 'polymyxins'. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval. RESULTS: After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p < 0.001. There was no significant heterogeneity. CONCLUSION: The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.

Bartonella quintana Endocarditis: A Systematic Review of Individual Cases.

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.

Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis.

INTRODUCTION: Scrub typhus is a bacterial mite-borne disease associated with poor clinical outcomes if not treated adequately. The study aimed to compare the time to defervescence, clinical failure, mortality and treatment-related adverse effects of two common drugs (doxycycline and azithromycin) used for its treatment. METHODOLOGY: This was a systematic review and meta-analysis. All studies up to 20.03.2023 were screened for eligibility in Pubmed and Embase using a search string containing terms related to scrub typhus, doxycycline and azithromycin. After two phases of screening, all comparative studies where doxycycline and azithromycin were used to treat scrub typhus were included. The studies were critically appraised using standardised tools, and a meta-analysis was performed for time to defervescence (primary outcome), clinical failure, mortality and treatment-related adverse effects. RESULTS: Of 744 articles from two databases, ten were included in the meta-analysis. All but two studies had a high risk of bias. The meta-analysis for time to defervescence had a high heterogeneity and did not show any significant difference between doxycycline and azithromycin arms [Mean difference of -3.37 hours (95%CI: -10.31 to 3.57), p=0.34]. When the analysis was restricted to studies that included only severe scrub typhus, doxycycline was found to have a shorter time to defervescence [mean difference of -10.15 (95%CI: -19.83 to -0.46) hours, p=0.04]. Additionally, there was no difference between the two arms concerning clinical failure, mortality and treatment-related adverse effects. CONCLUSION: The current data from studies with a high risk of bias did not find statistically significant differences in clinical outcomes between doxycycline and azithromycin for scrub typhus.

Fosfomycin for Non-Urinary Tract Infections: a systematic review.

Introduction: Although fosfomycin is currently approved for treating urinary tract infections, it is increasingly being used as salvage therapy for various infectious syndromes outside the urinary tract. This systematic review evaluates clinical and microbiological cure rates in patients with bacterial infections not restricted to the urinary tract where fosfomycin was used off-label. Materials and Methods: Articles from two databases (Pubmed and Scopus) were reviewed. The dosage, route, and duration of fosfomycin therapy along with the details of adjunctive antimicrobial agents were noted. The final outcomes captured were clinical or microbiological cures. Results: A total of 649 articles, not including duplicates, were selected for the title and abstract screening. After title and abstract screening, 102 articles were kept for full-text screening. Of the 102 articles, 23 studies (n=1227 patients) were kept in the final analysis. Of the 1227 patients, 301 (25%) received fosfomycin as monotherapy, and the remaining 926 75%) received fosfomycin in combination with at least one other antimicrobial agent. Most of the patients received intravenous fosfomycin (n=1046, 85%). Staphylococcus spp and Enterobacteriaceae were the most common organisms. The pooled clinical and microbiological cure rates were 75% and 84%, respectively. Conclusion: Fosfomycin has moderate clinical success in patients with non-urinary tract infections, especially when used with other antimicrobials. Due to the paucity of randomized controlled trials, fosfomycin's use should be limited to situations where no alternatives are supported by better clinical evidence.

Using Serum Specimens for Real-Time PCR-Based Diagnosis of Human Granulocytic Anaplasmosis, Canada.

Whole blood is the optimal specimen for anaplasmosis diagnosis but might not be available in all cases. We PCR tested serum samples collected in Canada for Anaplasma serology and found 84.8%-95.8% sensitivity and 2.8 average cycle threshold elevation. Serum can be acceptable for detecting Anaplasma spp. when whole blood is unavailable.

Expanded prenatal syphilis screening in Manitoba, Canada: a direct short-term cost-avoidance analysis in an outbreak context.

OBJECTIVE: The objective of this study is to provide a direct short-term cost-avoidance analysis of expanded three-time prenatal syphilis screening in the context of Manitoba's ongoing outbreak. METHODS: A conservative modelling approach increased all financial costs of prenatal screening and minimized the direct costs of congenital syphilis treatment. The cost of syphilis screening was calculated using instrument, reagent and consumable costs as well as laboratory overhead and labour costs as documented by Cadham Provincial Laboratory. The short-term direct costs of treating congenital syphilis were calculated using hospital costs and doctor's billing fees. All costs were calculated in 2021 Canadian dollars. These numbers were applied to Manitoba's 2021 congenital syphilis statistics to provide a pragmatic cost-avoidance analysis. RESULTS: The cost of applying three-time prenatal syphilis screening to all 16,800 yearly pregnancies in Manitoba equalled CAD $139,608.00 per year. The direct short-term cost of treating one uncomplicated case of congenital syphilis was $18,151.40. As 81 cases of congenital syphilis were treated in Manitoba in 2021, the short-term direct cost of treating congenital syphilis in Manitoba in 2021 was $1,470,263.40. Applying screening costs to the 125 adequately prevented cases of congenital syphilis in 2021, the screening program is associated with a cost-avoidance ratio of 16.25. If no prenatal syphilis program existed in Manitoba, an expanded screening program would be associated with a cost-avoidance ratio of 26.8. CONCLUSION: Expanding prenatal syphilis screening is highly cost-avoidant in Manitoba. The 81 cases of congenital syphilis treated in Manitoba in 2021 highlight the need for novel community-based approaches to increase accessibility and engagement with prenatal care.

RéSUMé: OBJECTIF: Dans le contexte de l'éclosion de syphilis qui sévit actuellement au Manitoba, notre étude vise à présenter une analyse des coûts directs à court terme qui pourraient être évités en étendant le dépistage de la syphilis au cours des trois trimestres de la grossesse. MéTHODE: En adoptant une approche de modélisation prudente, nous avons accru tous les coûts financiers du dépistage anténatal et réduit les coûts de traitement directs de la syphilis congénitale. Les coûts de dépistage de la syphilis ont été calculés en utilisant les coûts des instruments, des réactifs et des consommables, ainsi que les frais généraux et les coûts de main-d'œuvre des laboratoires selon le Laboratoire provincial Cadham. Les coûts directs à court terme du traitement de la syphilis congénitale ont été calculés en utilisant les frais hospitaliers et les frais facturés par les médecins. Tous les coûts ont été calculés en dollars canadiens de 2021. Ces chiffres ont été appliqués aux statistiques de 2021 du Manitoba sur la syphilis congénitale pour produire une analyse pragmatique de prévention des coûts. RéSULTATS: Le coût d'étendre le dépistage de la syphilis au cours des trois trimestres de la grossesse aux 16 800 grossesses annuelles au Manitoba représentait 139 608 $ CAN par année. Le coût direct à court terme du traitement d'un cas de syphilis congénitale sans complications était de 18 151,40 $. Étant donné que 81 cas de syphilis congénitale ont été traités au Manitoba en 2021, le coût direct à court terme du traitement de syphilis congénitale dans la province en 2021 s'est élevé à 1 470 263,40 $. En appliquant les coûts de dépistage aux 125 cas de syphilis congénitale que l'on a réussi à prévenir en 2021, le programme de dépistage est associé à un rapport de prévention des coûts de 16,25. S'il n'existait aucun programme de dépistage anténatal de la syphilis au Manitoba, un programme de dépistage élargi serait associé à un rapport de prévention des coûts de 26,8. CONCLUSION: L'expansion du dépistage anténatal de la syphilis serait une mesure de prévention des coûts très efficace au Manitoba. Les 81 cas de syphilis congénitale traités dans la province en 2021 montrent qu'il faut adopter de nouvelles approches de proximité pour améliorer l'accès et la participation aux soins anténatals.

Early Lyme neuroborreliosis manifesting as brachial plexopathy and meningitis in Northwestern Ontario, Canada: A case report.

RATIONALE: Lyme disease is a tick-borne disease caused by the spirochete B. burgdorferi, and patients often present with symptoms comparable to a viral-like illness. The diagnosis can be challenging given its wide range of manifestations and diagnostic testing can take days or longer. Here, we present a case of Lyme disease presenting as brachial plexopathy and meningitis. PATIENT CONCERNS: A 76-years-old male presented to a tertiary-care hospital with left arm weakness and neck pain. DIAGNOSIS: Our patient was diagnosed with Lyme neuroborreliosis and had positive serology, including enzyme immunoassay and Western blot. INTERVENTIONS: Our patient received 17 days of ceftriaxone (2g IV daily) followed by oral doxycycline (100mg bid). OUTCOMES: Over the subsequent year, our patient had eventual complete recovery in muscle strength and sensation, with slower improvement to the cervical neck and left arm pain. LESSONS: Incidence of Lyme disease is increasing in North America, and the disease has a wide range of symptoms. Lyme neuroborreliosis (LNB) is 1 presentation and can present with early or late manifestations; clinicians should maintain a high index of suspicion and begin empiric treatment in individuals with a clinical syndrome consistent with LNB. Early LNB manifestations have onset within 6 months of infection and include cranial and peripheral neuropathy, radiculitis, and aseptic meningitis; late LNB encompasses a chronic encephalomyelitis.

Leprosy chemoprophylaxis of household contacts: A survey of Canadian infectious disease and tropical medicine specialists.

BACKGROUND: Leprosy is uncommon in Canada. However, immigration from leprosy-endemic areas has introduced the infection to a Canadian context, in which most doctors have little knowledge of the disease. Although post-exposure chemoprophylaxis (PEP) is reported to decrease leprosy transmission, no Canadian guidelines advise clinical decision making about leprosy PEP. Here, we characterize the practice patterns of Canadian infectious disease specialists with respect to leprosy PEP and screening of household contacts by yearly physical examinations. METHODS: Canadian infectious disease specialists with known experience treating leprosy were identified using university faculty lists. An online anonymous survey was distributed. Certain questions allowed more than one response. RESULTS: The survey response rate was 46.5% (20/43). Thirty-five percent responded that PEP is needed for household contacts, 40.0% responded that PEP is not needed for household contacts, and 25.0% did not know whether PEP is needed (multinomial test p = 0.79). Twenty-five percent responded that PEP should be given to all household contacts, 62.5% responded that PEP should be given to contacts of multibacillary cases, and 25.0% responded that PEP should be given to contacts who are genetically related to the index case. For specialists who prescribe PEP, 57.1% use rifampicin, ofloxacin (levofloxacin), and minocycline; 14.3% prescribe single-dose rifampicin; and 28.6% prescribe multiple doses of rifampicin (multinomial test p = 0.11). In addition, 68.4% recommend yearly screening of household contacts, whereas 31.6% do not (multinomial test p = 0.17). CONCLUSION: Consensus among Canadian infectious diseases specialists is lacking regarding leprosy PEP and screening of household contacts.

HISTORIQUE: La lèpre est peu courante au Canada. Cependant, en raison de l'immigration de régions où la lèpre est endémique, cette infection existe, mais la plupart des médecins du Canada la connaissent peu. Même s'il est établi que la chimioprophylaxie post-exposition (PPE) réduit la transmission de la lèpre, il n'existe aucune directive canadienne pour éclairer les décisions cliniques sur la PPE de la lèpre. Les chercheurs caractérisent les schémas d'exercice des infectiologues canadiens au sujet de la PPE de la lèpre et du dépistage des contacts familiaux par des examens physiques annuels des aspects dermatologiques et nerveux périphériques. MÉTHODOLOGIE: Les chercheurs ont répertorié les infectiologues canadiens qui ont une expérience démontrée du traitement de la lèpre grâce aux listes des professeurs universitaires. Ils ont distribué un sondage anonyme en ligne. Pour certaines questions, les participants pouvaient fournir plus d'une réponse. Ils pouvaient aussi sauter certaines questions. RÉSULTATS: Le taux de réponse au sondage s'élevait à 46,5 % (20 cas sur 43). De cette proportion, 35,0 % ont répondu que les contacts familiaux avaient besoin d'une PPE, 40,0 %, qu'ils n'en avaient pas besoin, et 25,0 %, qu'ils ne le savaient pas (test multinomial, p = 0,79). Sur l'ensemble des répondants, 25,0 % ont répondu que tous les contacts familiaux devraient recevoir une PPE, 62,5 %, qu'elle devait être administrée aux contacts des cas multibacillaires, et 25,0 %, aux contacts génétiquement apparentés au cas de référence. Chez les spécialistes qui prescrivent une PPE, 57,1 % utilisent de la rifampicine, de l'ofloxacine (lévofloxacine) et de la minocycline, 14,3 %, une seule dose de rifampicine, et 28,6 %, de multiples doses de rifampicine (test multinomial p = 0,11). De plus, 68,4 % recommandent le dépistage annuel des contacts familiaux, et 31,6 % ne le recommandent pas (test multinomial p = 0,17). CONCLUSION: Il n'y a pas de consensus chez les infectiologues canadiens au sujet de la PPE de la lèpre et du dépistage des contacts familiaux.

Bartonella quintana endocarditis in a child from Northern Manitoba, Canada.

We describe a case of Bartonella quintana endocarditis in an 11-year-old child from Northern Manitoba, Canada. This case demonstrates the neglected endemicity of B. quintana in Northern Canada and highlights the need for improved case finding and elucidation of specific risk factors for B. quintana infection in the Canadian North. Considering B. quintana's predominant transmission via body lice ectoparasitosis, we hypothesize that B. quintana's endemicity in Northern Canada is linked to inadequate access to suitable housing and running water among remote communities in the Canadian North.

Serologic testing for Bartonella in Manitoba, Canada, 2010-2020: a retrospective case series.

BACKGROUND: Bartonella are gram-negative bacilli not identified by routine bacterial culture. The objectives of this study were to review the results of all serologic testing for Bartonella ordered in Manitoba, Canada, and to review cases with positive test results among adults to assess species identification, risk factors, clinical manifestations and outcomes. METHODS: This retrospective study included all Bartonella serologic tests ordered in Manitoba and performed at the National Microbiology Laboratory, Winnipeg, from Jan. 1, 2010, until Dec. 31, 2020. We analyzed the aggregate data for all serologic tests for Bartonella for patients of all ages. We reviewed the charts of adult (age ≥ 18 yr) patients with serologic positivity for Bartonella who had a medical chart at 1 of Winnipeg's 2 largest hospitals (Health Sciences Centre and St. Boniface Hospital) to extract clinical and demographic data and create a case series. Descriptive statistics were performed. RESULTS: During the study period, 1014 Bartonella serologic tests were ordered in adult and pediatric patients, of which 24 (2.4%) gave a positive result. Sixteen adults (12 men and 4 women; mean age 48 yr) seen at a participating hospital had a positive result. Molecular species-level identification occurred on explanted cardiac valves in 5 (31%) of the 16 cases; B. quintana was identified in all 5. Six patients (38%) were diagnosed with probable B. quintana infection, for a total of 11 B. quintana cases (69%); 8 (73%) of the 11 had endocarditis. Four cases of B. quintana infection (36%) were associated with rural residence. Four cases (25%) of probable B. henselae were identified; 2 patients had fever and lymphadenopathy, and 2 had endocarditis. The remaining patient was deemed to have a false-positive result as his B. henselae titre was at the threshold for positivity, his B. quintana serologic test gave a negative result, and his clinical syndrome was not suggestive of Bartonella infection. Two patients died; both had multivalvular B. quintana endocarditis with ruptured intracranial mycotic aneurysms. INTERPRETATION: Bartonella quintana was a common cause of Bartonella serologic positivity among adults in Manitoba in 2010-2020 and was associated with endocarditis and systemic embolization. As B. quintana is transmitted by body lice, active case finding for people who lack suitable housing, both in urban and rural settings, should prioritize those with elevated Bartonella titres to receive echocardiography and detect endocarditis before systemic embolization occurs.

Trichosporon mucoides prosthetic valve endocarditis managed with antifungal suppression therapy.

A 63-year-old male with mechanical aortic valve replacement presents with Trichosporon mucoides endocarditis. Eosinophilia was noted, which has recently been described in invasive trichosporonosis. He was treated successfully with combination voriconazole and terbinafine therapy. He was deemed not to be a cardiac surgery candidate, due to excessive estimated procedural mortality.

Absence of transmission of NDM and OXA-48 carbapenemase genes in a chronic care unit of a long-term care facility.

Infection prevention and control measures are used to contain outbreaks of carbapenemase-producing Enterobacteriaceae. We report the absence of transmission of Klebsiella pneumoniae carrying New Delhi metallo-ß-lactamase and oxacillinase-48 genes among 19 screened contacts of an index case after 14 months of routine practices in a long-term care facility.

Mapping and size estimation of men who have sex with men in virtual platforms in Delhi, India.

INTRODUCTION: In India, the HIV epidemic is concentrated among Key Populations (KPs), such as men who have sex with men (MSM), who bear a disproportionate burden of HIV disease. Conventional targeted interventions (TI) mitigate HIV transmission among MSM by focusing on physical hotspots. As increasingly, there is a shift within India's MSM community to connect with sex partners online, novel approaches are needed to map virtual platforms where sexual networks are formed. The objective of this study was to estimate the number of MSM in Delhi using virtual platforms to connect for sex and to describe patterns of their use. METHODS: The study was conducted in the state of Delhi among MSM over 18 years of age who used virtual platforms to look for sexual partners. Virtual platforms were identified through community consultations. Size estimation was carried out by enumerating the number of online users, accounting for duplication across sites and time and based on interviews with 565 MSM. RESULTS: 28,058 MSM (95% CI: range 26,455-29,817) use virtual sites to find sexual partners. We listed 14 MSM specific virtual sites, 14 general virtual sites, 19 social networking pages and 112 messenger groups, all used by MSM. Five virtual sites met feasibility criteria to be included in the virtual mapping. Of the MSM on these sites, 81% used them at night and 94% used them on Sundays, making these the peak time and day of use. Only 16% of users were aware of organizations providing HIV services and 7% were contacted by peer educators in the preceding three months. Two-fifths (42%) also visited a physical location to connect with sexual partners in the month prior to the study. DISCUSSION: TI programs that focus on physical hotspots do not reach the majority of MSM who use virtual sites. MSM active on virtual sites have a low awareness of HIV services. Virtual mapping and programmatic interventions to include them must be incorporated into current public health interventions to reach MSM at risk of HIV.