Search

Background Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective. Methods A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021. Results Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database. Conclusions HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218. [ABSTRACT FROM AUTHOR]

Background We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. Methods We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. Results We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens. Conclusions Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential. [ABSTRACT FROM AUTHOR]

Background Infectious diseases and ophthalmology professional societies have disagreed regarding ocular screening in patients with candidemia. We aimed to summarize the current evidence on the prevalence of ocular candidiasis (OC) and Candida endophthalmitis (CE) according to the standardized definitions. Methods A literature search was conducted from the inception date through 16 October 2022 using PubMed, Embase, and SCOPUS. Pooled prevalence of ocular complications was derived from generalized linear mixed models (PROSPERO CRD42022326610). Results A total of 70 and 35 studies were included in the meta-analysis for OC and concordant CE (chorioretinitis with vitreous involvement), respectively. This study represented 8599 patients with candidemia who underwent ophthalmologic examination. Pooled prevalences (95% CI) of OC, overall CE, concordant CE, and discordant CE were 10.7% (8.4–13.5%), 3.1% (2.1–4.5%), 1.8% (1.3–2.6%), and 7.4% (4.5–12%) of patients screened, respectively. Studies from Asian countries had significantly higher concordant CE prevalence (95% CI) of patients screened (3.6%; 2.9–4.6%) compared with studies from European countries (1.4%;.4–5%) and American countries (1.4%;.9–2.2%) (P <.01). Presence of total parenteral nutrition and Candida albicans was associated with CE, with pooled odds ratios (95% CI) of 6.92 (3.58–13.36) and 3.02 (1.67–5.46), respectively. Conclusions Prevalence of concordant CE overall and among Asian countries was 2 and 4 times higher than the prevalence previously reported by the American Academy of Ophthalmology (AAO) of <0.9%, respectively. There is an urgent need to study optimal screening protocols and to establish joint recommendations by the Infectious Diseases Society of America and AAO. [ABSTRACT FROM AUTHOR]

The duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis. Studies on the duration of protection after 1 and ≥2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models. We identified 36 studies from 20 countries, comprising more than 17 000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2 years, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning. The extent of waning of seroprotection after yellow fever vaccination depends on age and immune status at primary vaccination. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI,.66 to.94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients. [ABSTRACT FROM AUTHOR]

Background Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. Methods We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. Results We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis , effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. Conclusions These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment. [ABSTRACT FROM AUTHOR]

Background Scabies is a neglected tropical disease of the skin that can lead to impetigo, serious secondary bacterial infections and immune-mediated diseases. Mass drug administration (MDA) has been reported in several studies to reduce the prevalence of scabies and impetigo. We aimed to assess the efficacy of MDA for scabies on scabies and impetigo. Methods We conducted a systematic review and meta-analysis of reports on the impact of MDA on scabies and impetigo. We included randomized control trials and observational evaluations reported from January 1970 to April 2021 and involving human participants. We searched PubMed, Ovid Medline, Embase, and Cochrane. We considered MDA as treatment intended for the whole population, regardless of individual infection status or symptoms. The main outcome assessed was the change in scabies and impetigo prevalence following MDA. This review is registered with PROSPERO (CRD42020169839). Results We identified 1110 records, of which 11 met inclusion criteria for the review and 9 were deemed suitable for meta-analysis for scabies and 4 for impetigo. Most studies were in small populations. There was a high degree of heterogeneity between studies (I2 value 96.19%). The overall relative reduction of the impact of MDA on scabies prevalence was 79%. The effect size was comparable for MDA based on ivermectin and permethrin. MDA for scabies also led to a reduction in impetigo prevalence with a relative reduction of 66%. Conclusions MDA for scabies is highly effective in reducing the prevalence of scabies and impetigo. Further research is needed to determine the durability of impact, and the effectiveness of MDA regimens in larger populations. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin. Methods Relevant databases were queried and study outcomes extracted using a standardized method and summarized. Results Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0–3%), but CLAD progression 180–360 days postinfection was substantial (pooled incidences 19–24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27–1.18]), although results were highly variable between studies. Conclusions RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections. [ABSTRACT FROM AUTHOR]

Background Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes with radiologically/etiologically confirmed outcomes. Methods We performed a systematic review of efficacy trials for several vaccines (1997–2019) and report results for pneumococcal conjugate vaccines. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator). Results Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 (95% CI not calculable), 2.1 (1.5–3.0), and 3.7 (1.0–10.2); the VPDI ratios comparing clinically defined with radiologically confirmed pneumonia ranged from not calculable to 2.7 (1.2–10.4); the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) with laboratory-confirmed IPD was 3.8 (95% CI not calculable). Among adults, the ratio comparing clinically defined with radiologically confirmed pneumonia was 1.9 (−6.0 to 9.1) and with vaccine serotype–confirmed pneumonia was 2.9 (.5–7.8). Conclusions While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine's public health value. [ABSTRACT FROM AUTHOR]

Background Estimates of the serial interval distribution contribute to our understanding of the transmission dynamics of coronavirus disease 2019 (COVID-19). Here, we aimed to summarize the existing evidence on serial interval distributions and delays in case isolation for COVID-19. Methods We conducted a systematic review of the published literature and preprints in PubMed on 2 epidemiological parameters, namely, serial intervals and delay intervals relating to isolation of cases for COVID-19 from 1 January 2020 to 22 October 2020 following predefined eligibility criteria. We assessed the variation in these parameter estimates using correlation and regression analysis. Results Of 103 unique studies on serial intervals of COVID-19, 56 were included, providing 129 estimates. Of 451 unique studies on isolation delays, 18 were included, providing 74 estimates. Serial interval estimates from 56 included studies varied from 1.0 to 9.9 days, while case isolation delays from 18 included studies varied from 1.0 to 12.5 days, which were associated with spatial, methodological, and temporal factors. In mainland China, the pooled mean serial interval was 6.2 days (range, 5.1–7.8) before the epidemic peak and reduced to 4.9 days (range, 1.9–6.5) after the epidemic peak. Similarly, the pooled mean isolation delay related intervals were 6.0 days (range, 2.9–12.5) and 2.4 days (range, 2.0–2.7) before and after the epidemic peak, respectively. There was a positive association between serial interval and case isolation delay. Conclusions Temporal factors, such as different control measures and case isolation in particular, led to shorter serial interval estimates over time. Correcting transmissibility estimates for these time-varying distributions could aid mitigation efforts. [ABSTRACT FROM AUTHOR]

Background Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared with both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intrahost viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and 9 persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent coronavirus disease 2019 (COVID-19) demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution. [ABSTRACT FROM AUTHOR]

Background Prevention of surgical site infection (SSI) is a public health challenge. Our objective was to determine if prophylactic negative-pressure wound therapy (pNPWT) allows preventing SSI after laparotomy. Methods Medline, Embase, and Web of Science were searched on 6 October 2019 for original studies reporting the incidences of SSI in patients undergoing open abdominal surgery with and without pNPWT. Risk differences (RDs) between control and pNPWT patients and risk ratios (RRs) for SSI were obtained using random-effects models. Results Twenty-one studies (2930 patients, 5 randomized controlled trials [RCTs], 16 observational studies) were retained for the analysis. Pooled RD between patients with and without pNPWT was −12% (95% confidence interval [CI], −17% to −8%; I 2 = 57%; P  < .00001) in favor of pNPWT. That risk difference was −12% (95% CI, −22% to −1%; I 2 = 69%; P  = .03) when pooling only RCTs (792 patients). pNPWT was protective against the incidence of SSI with a RR of 0.53 (95% CI,.40–.71; I 2 = 56%; P  < .0001). The effect on pNPWT was more pronounced in studies with an incidence of SSI ≥20% in the control arm. The preventive effect of pNPWT on SSI remained after correction for potential publication bias. However, when pooling only high-quality observational studies (642 patients) or RCTs (527 patients), significance was lost. Conclusions Existing studies suggest that pNPWT on closed wounds is protective against the occurrence of SSI in abdominal surgery, but these findings need to be confirmed by more high-quality evidence, preferentially in subgroups of patients with an incidence of SSI ≥20% in the control arm. [ABSTRACT FROM AUTHOR]

This systematic review assesses the literature for estimates of influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalization in children. Studies of any design to June 8, 2020, were included if the outcome was hospitalization, participants were 17 years or younger and influenza infection was laboratory-confirmed. A random-effects meta-analysis of 37 studies that used a test-negative design gave a pooled seasonal IVE against hospitalization of 53.3% (47.2–58.8) for any influenza. IVE was higher against influenza A/H1N1pdm09 (68.7%, 56.9–77.2) and lowest against influenza A/H3N2 (35.8%, 23.4–46.3). Estimates by vaccine type ranged from 44.3% (30.1–55.7) for live-attenuated influenza vaccines to 68.9% (53.6–79.2) for inactivated vaccines. IVE estimates were higher in seasons when the circulating influenza strains were antigenically matched to vaccine strains (59.3%, 48.3–68.0). Influenza vaccination gives moderate overall protection against influenza-associated hospitalization in children supporting annual vaccination. IVE varies by influenza subtype and vaccine type. [ABSTRACT FROM AUTHOR]

Background There are large knowledge gaps on the transmission dynamics of Mycobacterium tuberculosis in settings where both tuberculosis and human immunodeficiency virus (HIV) are endemic. We aimed to assess the infectiousness of tuberculosis patients coinfected with HIV. Methods We systematically searched for studies of contacts of both HIV-positive and HIV-negative tuberculosis index cases. Our primary outcome was Mycobacterium tuberculosis infection in contacts. Data on sputum smear and lung cavitation status of index cases were extracted from each study to assess effect modification. Secondary outcomes included prevalent tuberculosis and HIV in contacts of HIV-positive and HIV-negative index cases. Results Of 5255 original citations identified, 32 studies met inclusion criteria, including 25 studies investigating M. tuberculosis infection (Nparticipants = 36 893), 13 on tuberculosis (Nparticipants = 18 853), and 12 on HIV positivity (Nparticipants = 18 424). Risk of M. tuberculosis infection was lower in contacts of HIV-positive index cases (odds ratio [OR], 0.67, 95% confidence interval [CI],.58–.77) but was heterogeneous (I 2 = 75.1%). Two factors modified this relationship: the lung cavitary status of the index case and immunosuppression (measured through CD4 counts or HIV or acquired immunodeficiency syndrome diagnoses) among index people living with HIV. Rates of HIV were consistently higher in contacts of coinfected index cases (OR, 4.9; 95% CI, 3.0–8.0). This was modified by whether the study was in sub-Saharan Africa (OR, 2.8; 95% CI, 1.6–4.9) or in another global region (OR, 9.8; 95% CI, 5.9–16.3). Conclusions Tuberculosis patients coinfected with HIV are less infectious than HIV-uninfected cases when they have severe immunosuppression or paucibacillary disease. Contacts of coinfected index cases are almost 5 times more likely to also have HIV. [ABSTRACT FROM AUTHOR]

Background Antibiotic noninferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic noninferiority RCTs. Methods We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and the Food and Drug Administration drug database from inception until November 22, 2019, for noninferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes, or durations were included. Methodological and reporting quality indicators were based on the Consolidated Standards of Reporting Trials reporting guidelines. Two independent reviewers extracted the data. Results The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the noninferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early because of logistical reasons (3.0% vs 19.1%; odds ratio [OR] = 0.13; 95% confidence interval [CI],.04–.37) and to show inconclusive results (11.1% vs 42.9%; OR = 0.17; 95% CI,.08–.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis, and having misleading conclusions. Conclusions There is room for improvement in the methodology and reporting of antibiotic noninferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process. There is room for improvement in the methodology and reporting of antibiotic noninferiority trials including justification of noninferiority margin, reporting of intention-to-treat analysis with per-protocol analysis, and having conclusions that are concordant with study results. Clinical Trials Registration PROSPERO registration number CRD42020165040. [ABSTRACT FROM AUTHOR]

Background Invasive meningococcal disease (IMD), caused by Neisseria meningitidis , leads to significant morbidity and mortality worldwide. This review aimed to establish the effectiveness of meningococcal vaccines at preventing IMD and N. meningitidis pharyngeal carriage. Methods A search within PubMed, Embase, Scopus, and unpublished studies up to 1 February 2020 was conducted. Results After removal of duplicates, 8565 studies were screened and 27 studies included. Protection was provided by meningococcal C vaccines for group C IMD (odds ratio [OR], 0.13 [95% confidence interval {CI},.07–.23]), outer membrane vesicle (OMV) vaccines against group B IMD (OR, 0.35 [95% CI,.25–.48]), and meningococcal A, C, W, Y (MenACWY) vaccines against group ACWY IMD (OR, 0.31 [95% CI,.20–.49]). A single time series analysis found a reduction following an infant 4CMenB program (incidence rate ratio, 0.25 [95% CI,.19–.36]). Multivalent MenACWY vaccines did not reduce carriage (relative risk [RR], 0.88 [95% CI,.66–1.18]), unlike monovalent C vaccines (RR, 0.50 [95% CI,.26–.97]). 4CMenB vaccine had no effect on group B carriage (RR, 1.12 [95% CI,.90–1.40]). There was also no reduction in group B carriage following MenB-FHbp vaccination (RR, 0.98 [95% CI,.53–1.79]). Conclusions Meningococcal conjugate C, ACWY, and OMV vaccines are effective at reducing IMD. A small number of studies demonstrate that monovalent C conjugate vaccines reduce pharyngeal N. meningitidis carriage. There is no evidence of carriage reduction for multivalent MenACWY, OMV, or recombinant MenB vaccines, which has implications for immunization strategies. Clinical Trials Registration CRD42018082085 (PROSPERO). [ABSTRACT FROM AUTHOR]

Background Histoplasmosis caused by Histoplasma capsulatum var. duboisii (Hcd) is a rare, but probably underestimated, endemic infection described in intertropical Africa. Therefore, the epidemiology of the infection remains unclear, and there is no consensus on therapeutic management. Methods Using a comprehensive search on different Internet databases, we collected case reports of Hcd infection published from 1993 to 2019. Epidemiological and clinical charts and therapeutic strategies were analyzed. Results We found 94 well-documented cases of Hcd infection, and 30.1% of the patients were under 18 years old. Symptoms occurred in some patients several decades after leaving the endemic area. Cutaneous/subcutaneous lesions, bone infections, and lymphadenopathies, both isolated and combined, were the most frequent presentations. The human immunodeficiency virus (HIV) coinfection rate was at 20.8%, with fever, lymphadenopathies, and an absence of bone infection being the differentiating elements from patients living without HIV. The rate of disseminated forms (60.6% in our review) significantly increased as compared to studies published before 1993, but without correlation with HIV infection. The global mortality rate was at 23.4% by the end of follow-up. The outcome was not correlated with the antifungal drug prescribed, nor with HIV serologic status, but was correlated with the initiation of an antifungal therapy. Conclusions Hcd histoplasmosis is a severe fungal infection for which the precise mode of acquisition remains to be determined. There is a need for affordable and more specific diagnostic tools. Itraconazole and amphotericin B are the best therapeutic alternatives and should be available in all low-income countries of the endemic area. [ABSTRACT FROM AUTHOR]