Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022.

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Indicator-condition-guided HIV testing in rural DRC.

BACKGROUND: HIV testing services are a key component of the 95-95-95-0 goals. In many parts of the Democratic Republic of the Congo the availability of test kits is limited for multiple reasons. Targeted testing of patients with HIV indicator conditions is therefore the only feasible option in these settings. METHODS: We introduced an indicator condition-guided HIV testing project in the Emergency Room of the Hôpital Géneral de Référence de Kikwit, DRC. RESULTS: We screened 1274 patients for indicator condition. In 94 (7.4%) patients, the treating physician diagnosed at least one HIV indicator. 34 (36.2%) tested HIV-positive (2.7% of screened patients). 52% of the newly diagnosed patients were lost to follow-up two months after the first diagnosis of HIV. CONCLUSION: In a resource-limited setting with insufficient availability of HIV-Tests, indicator-triggered testing is a useful tool to find a high number of HIV-positive patients. Loss to follow-up is one of the major challenges.

A case of occupational transmission of mpox.

INTRODUCTION: Between May 2022 and January 2023, a global mpox outbreak affected more than 84,000 patients across all continents. Transmission of mpox occurs through large respiratory droplets and direct contact with skin lesions. CASE PRESENTATION: We present the case of a 31-year-old previously healthy male with mpox-Infection following occupational exposure to mpox from a needle stick injury with a sterile needle through a contaminated glove. The patient presented with a three-day history of fever, malaise, and an increasing erythema and swelling of one fingertip. The patient works as a medical doctor with regular exposure to patients infected with mpox. Mpox-PCR from a swab of the lesion and an oro-pharyngeal swab were positive. The lesion on his finger evolved into a necrotic skin lesion finally healing, leaving a scar. He did not develop any secondary pox on his skin and recovered fully. DISCUSSION: Only a minority of patients with mpox infection develop illness with pronounced local complications as in this case. CONCLUSION: Mpox can potentially be transmitted in an occupational context. Medical personnel should be informed about this possible route of transmission.

Hemophagocytic lymphohistiocytosis in HIV-associated lymphoproliferative disorders.

Compared to the general population the incidence of lymphoproliferative disorders (LPDs) is significantly elevated among people living with HIV (PLHIV). In high-income countries LPDs have become the most common HIV-associated cause of death among PLHIV. Lymphomas are one of the most frequent triggers of Hemophagocytic Lymphohistiocytosis (HLH), a life-threatening inflammatory syndrome that manifests as a sepsis-like syndrome thus obscuring the underlying condition and delaying its diagnosis and therapy. We performed this retrospective cohort study comprising all adult HIV-infected patients who started treatment for histologically proven LPDs between October 2013 and July 2019, to analyse risk factors, frequency and outcome of HLH among HIV-infected patients with LPDs. Of 75 patients, six (8%) presented with or developed HLH. Three patients had Hodgkin lymphoma and three had HHV-8 associated diseases. There was a significant correlation (p<0.01) between bone marrow involvement and the development of HLH. HLH was associated with lower overall survival (HR: 5.09; 95%CI: 1.53 - 16.91 p=0.008). In conclusion HLH appears to be more frequent in HIV-associated lymphomas than in HIV-negative lymphomas. The probability of developing HLH was particularly high in patients with Hodgkin lymphoma, lymphoma with bone marrow infiltration and HHV-8 associated lymphoma. Mortality was significantly increased in the presence of HLH.

Combined effects of different interleukin-28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 infection.

UNLABELLED: In patients with chronic hepatitis C virus (HCV) infection, several variants of the interleukin-28B (IL28B) gene have been shown to correlate significantly with a sustained virologic response (SVR). Recent evidence shows that determination of one single IL28B polymorphism, rs12979860, is sufficient for predicting treatment outcome. We examined whether the combined determination of the IL28B single-nucleotide polymorphisms (SNPs), rs12979860, rs8099917, rs12980275, and rs8103142, might improve the prediction of SVR in patients with HCV. In the study cohort, 54% of 942 patients with chronic HCV type 1 infection had SVR. The IL28B SNPs, rs12979860CC and rs8099917TT, correlated significantly with SVR (68% and 62%). The SNPs, rs12980275 and rs8103142, were in strong linkage disequilibrium with rs12979860 and were not included in further analysis. In homozygous carriers of the rs12979860 responder allele C, additional genotyping of the rs8099917 SNP had no effect on response prediction, whereas in carriers of the rs12979860 nonresponder allele, the rs8099917 SNP improved the response prediction. In heterozygous carriers of the rs12979860 nonresponder T allele, SVR rates were 55% in the presence of the rs8099917TT genotype and 40% in patients carrying the rs8099917 TG or GG genotype. Analysis of an independent confirmation cohort of 377 HCV type 1-infected patients verified the significant difference in SVR rates between the combined genotypes, rs12979860CT/rs8099917TT and rs12979860CT/rs8099917TG (38% versus 21%; P = 0.018). CONCLUSION: Treatment outcome prediction could not be improved in homozygous carriers of the IL28B rs12979860 C responder allele by the additional determination of the rs8099917 SNP. There is evidence that a significant proportion of heterozygous carriers of the rs12979860 T nonresponder allele can profit with respect to SVR prediction by further determination of the rs8099917 SNP. (HEPATOLOGY 2012;55:1700-1710).

Source attribution of community-acquired cases of Legionnaires' disease-results from the German LeTriWa study; Berlin, 2016-2019.

INTRODUCTION: Sources of infection of most cases of community-acquired Legionnaires' disease (CALD) are unknown. OBJECTIVE: Identification of sources of infection of CALD. SETTING: Berlin; December 2016-May 2019. PARTICIPANTS: Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls. MAIN OUTCOME MEASURE: Percentage of cases of CALD with attributed source of infection. METHODS: Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls)). RESULTS: Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25-93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed. CONCLUSION: Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation.

HIV status and mortality of surgical inpatients in rural Zimbabwe: A retrospective chart review.

BACKGROUND: People living with HIV treated with antiretroviral therapy (ART) are now living longer and thus many are requiring surgical procedures. For healthcare resource planning, it would be helpful to better understand the prevalence of HIV in surgical patients, the types of surgery HIV-positive patients are undergoing and whether HIV status impacts mortality. OBJECTIVE: The goal of this study was to determine the prevalence of HIV in surgical inpatients and the extent of ART coverage, as well as to assess any differences between HIV-positive and HIV-negative patients in type of surgery undergone and in-hospital mortality at Karanda Mission Hospital, Mount Darwin, Zimbabwe. METHOD: A 1-year retrospective chart review was undertaken to collect clinical and demographic data for adult (excluding maternity cases) and paediatric surgical inpatients including age, sex, type of surgery, HIV status, CD4+ counts and, if patient was HIV-positive, whether he or she was taking ART.Results and conclusion: Charts for 1510 surgical inpatient stays were reviewed. HIV prevalence among the adults was higher than that in the general population in Zimbabwe in 2016 (23.2% vs. 14.7%). There was no significant difference in inpatient mortality between the HIV-negative group and the HIV-positive group. Within the group of patients with malignancies, people living with HIV were significantly younger than uninfected patients (mean age 50.5 vs. 64.4 years; p < 0.01). There were correlations between HIV and certain malignancies. Thus, in addition to AIDS-defining illnesses, clinicians must be alert to squamous cell carcinoma and oesophageal, anal and penile cancers in HIV-positive patients.

Association of IFNL3 rs12979860 and rs8099917 with biochemical predictors of interferon responsiveness in chronic hepatitis C virus infection.

BACKGROUND & AIMS: Genetic variations near the interferon lambda 3 gene (IFNL3, IL28B) are the most powerful predictors for sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, compared to other biochemical or histological baseline parameters. We evaluated whether the interplay of both IFNL3 polymorphisms rs12979860 and rs8099917 together with non-genetic clinical factors contributes to the predictive role of these genetic variants. METHODS: The cohort comprised 1,402 patients of European descent with chronic HCV type 1 infection. 1,298 patients received interferon-based antiviral therapy, and 719 (55%) achieved SVR. The IFNL3 polymorphisms were genotyped by polymerase chain reaction and melting curve analysis. RESULTS: A significant correlation was found between the IFNL3 polymorphisms and biochemical as well as virologic predictors of treatment outcome such as ALT, GGT, cholesterol, and HCV RNA levels. In multivariate regression analysis, IFLN3 SNPs, HCV RNA levels, and the GGT/ALT ratio were independent predictors of SVR. Dependent on the GGT/ALT ratio and on the HCV RNA concentration, significant variations in the likelihood for achieving SVR were observed in both, carriers of the responder as well as non-responder alleles. CONCLUSIONS: Our data support a clear association between IFNL3 genotypes and baseline parameters known to impact interferon responsiveness. Improved treatment outcome prediction was achieved when these predictors were considered in combination with the IFNL3 genotype.