Reduced Mortality among COVID-19 ICU Patients after Treatment with HemoClear Convalescent Plasma in Suriname.

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in low- and middle-income country settings such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as a treatment option in Suriname. Two hundred patients with severe SARS-CoV-2 infection requiring intensive care were recruited. Fifty eight patients (29%) received COVID-19 convalescent plasma (CCP) treatment in addition to standard of care (SOC). The CCP treatment and SOC groups were matched by age, sex, and disease severity scores. Mortality in the CCP treatment group was significantly lower than that in the SOC group (21% versus 39%; Fisher's exact test P = 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.18 to 0.66; P = 0.001), while complication of acute renal failure (creatinine levels, >110 mol/L; HR, 4.45; 95% CI, 2.54 to 7.80; P < 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, interquartile range [IQR] -4 to -1) was significantly greater than that in the SOC group (median -1 point, IQR -3 to 1, Mann-Whitney test P = 0.0004). Improvement in the PaO2/FiO2 ratio was also significantly greater in the CCP treatment group (median 83, IQR 8 to 140) than in the SOC group (median 35, IQR -3 to 92, Mann-Whitney P = 0.0234). Further research is needed for HemoClear-produced CCP as a therapy for SARS-CoV-2 infection together with adequately powered, randomized controlled trials. IMPORTANCE This study compares mortality and other endpoints between intensive care unit COVID-19 patients treated with convalescent plasma plus standard of care (CCP), and a control group of patients hospitalized in the same medical ICU facility treated with standard of care alone (SOC) in a low- and middle-income country (LMIC) setting using bedside donor whole blood separation by gravity (HemoClear) to produce the CCP. It demonstrates a significant 65% survival improvement in HemoClear-produced CCP recipients (HR, 0.35; 95% CI, 0.19 to 0.66; P = 0.001). Although this is an exploratory study, it clearly shows the benefit of using the HemoClear-produced CCP in ICU patients in the Suriname LMIC setting. Additional studies could further substantiate our findings and their applicability for both LMICs and high-income countries and the use of CCP as a prepared readiness method to combat new viral pandemics.

Differences in prevalence of hepatitis B virus infection and genotypes between ethnic populations in Suriname, South America.

Epidemiological data on hepatitis B virus (HBV) are needed to benchmark HBV elimination goals. We recently assessed prevalence of HBV infection and determinants in participants attending the Emergency Department in Paramaribo, Suriname, South America. Overall, 24.5% (95%CI = 22.7-26.4%) of participants had anti-Hepatitis B core antibodies, which was associated with older age (per year, adjusted Odds Ratio [aOR] = 1.03, 95%CI = 1.02-1.04), Afro-Surinamese (aOR = 1.84, 95%CI = 1.52-2.19) and Javanese ethnicity (aOR = 1.63, 95%CI = 1.28-2.07, compared to the grand mean). 3.2% of participants were Hepatitis B surface Ag-positive, which was also associated with older age (per year, aOR = 1.02, 95%CI = 1.00-1.04), Javanese (aOR = 4.3, 95%CI = 2.66-6.95) and Afro-Surinamese ethnicity (aOR = 2.36, 95%CI = 1.51-3.71). Sex, nosocomial or culturally-related HBV transmission risk-factors were not associated with infection. Phylogenetic analysis revealed strong ethnic clustering: Indonesian subgenotype HBV/B3 among Javanese and African subgenotypes HBV/A1, HBV/QS-A3 and HBV/E among Afro-Surinamese. Testing for HBV during adulthood should be considered for individuals living in Suriname, specifically with Javanese and Afro-Surinamese ancestry.

Corrigendum to 'Should treatment of low-level rifampicin mono-resistant tuberculosis be different?' [JCTUBE 23 (2021) 100241].

[This corrects the article DOI: 10.1016/j.jctube.2021.100241.].

Ethnic disparities in tuberculosis incidence and related factors among indigenous and other communities in ethnically diverse Suriname.

BACKGROUND: In Suriname, a country home to many ethnic groups, a high incidence of tuberculosis (TB) has been found among Indigenous Trio Amerindians. However, whether wider ethnic disparities in TB incidence and its associated risk factors (e.g., diabetes mellitus and HIV) exist in Suriname, is not known. We sought to investigate disparities in TB incidence and its risk factors on ethnicity in Suriname, as this could give way to targeted TB intervention programs. METHODS: Anonymized patient data from 2011 to 2015 was extracted from the National TB Registry and analyzed. Differences in the five-year incidence rates of TB for the six largest ethnic groups-Creole, Hindustani, Indigenous, Javanese, Maroon, and Mixed-were assessed using a chi-square goodness-of-fit test, and TB patient differences regarding ethnicity were evaluated for selected factors using a multinomial logistic regression with Creole patients as reference. RESULTS: 662 Patients were eligible for analyses with the following ethnic makeup: Creole (36.4%), Hindustani (15.6%), Indigenous (8.6%), Javanese (10.6%), Maroon (15.1%), and Mixed ethnicity (13.7%). Differences in five-year incidence rates for TB were significant, χ 2(5, N = 662) = 244.42, p < .001, and the highest TB rates were found for Indigenous (280 per 100,000) and Creole people (271 per 100,000). HIV coinfection was a TB risk factor for Creoles (38.2% of these patients were HIV positive). Several variables (i.e., those for drug use) had high levels of incomplete or missing data. CONCLUSIONS: Our study has demonstrated that ethnic disparities in tuberculosis incidence exist in Suriname and that they are associated with specific, known risk factors such as HIV (especially for Creole people). For Indigenous people, risk factors may include diminished access to health care facilities and low socioeconomic status. However, direct data on these factors was unavailable. These findings call for targeted national intervention programs-with special attention given to the vulnerabilities of susceptible ethnic groups-and improved data collection.

Should treatment of low-level rifampicin mono-resistant tuberculosis be different?

BACKGROUND: Rifampicin resistant tuberculosis (RR-TB) was frequently detected in Suriname after the introduction of Xpert MTB/RIF in 2012. Subsequent phenotypic drug-susceptibility testing (DST) was not conclusive at that moment, while RR-TB patients treated with first-line tuberculostatics had good treatment outcome. In our study, we analysed this interesting observation. METHODS: We collected demographic and clinical characteristics and treatment outcome of TB patients from May 2012-December 2018 and performed a univariate and multivariate analysis to assess possible associations with resistance to rifampicin. Secondly, we conducted whole genome sequencing on all available Mycobacterium tuberculosis isolates that had a rifampicin resistance in the Xpert MTB/RIF test and performed phenotypic DST on selected isolates. FINDINGS: RR-TB was detected in 59 (9.6%) patients confirmed by Xpert. These patients were treated with rifampicin-containing regimens in most (88%) of the cases. In all 32 samples examined, a D435Y mutation in the rpoB gene was identified; only one isolate revealed an additional isoniazid mutation. Phenotypic DST indicated low-level rifampicin resistance. In multivariate analysis, the Creole ethnicity was a factor associated with rifampicin resistance (aOR 3.5; 95%CI 1.9-6.4). The treatment success rate for patients with RR-TB (78.0%) was comparable to the treatment outcome in non-RR-TB patients 77.8%. INTERPRETATION: This study confirms a low-level rifampicin mono-resistance in TB patients of Suriname. These patients could benefit from a first-line regimen with high dose rifampicin (or rifabutin), rather than from the lengthy treatment regimens for rifampicin-resistant and multi-drug resistant TB, a concept of stratified medicine also advocated for the treatment of TB. FUNDING: None.

Predictors of antimalarial self-medication in illegal gold miners in French Guiana: a pathway towards artemisinin resistance.

BACKGROUND: Malaria is endemic in French Guiana (FG), South America. Despite the decrease in cases in the local population, illegal gold miners are very affected by malaria (22.3% of them carried Plasmodium spp.). Self-medication seems to be very common, but its modalities and associated factors have not been studied. The aim of this study was to evaluate parasite susceptibility to drugs and to document behaviours that could contribute to resistance selection in illegal gold miners. METHODS: This multicentric cross-sectional study was conducted in resting sites along the FG-Surinamese border. Participating gold miners working in FG completed a questionnaire and provided a blood sample. RESULTS: From January to June 2015, 421 illegal gold miners were included. Most were Brazilian (93.8%) and 70.5% were male. During the most recent malaria attack, 45.5% reported having been tested for malaria and 52.4% self-medicated, mainly with artemisinin derivatives (90%). Being in FG during the last malaria attack was the main factor associated with self-medication (adjusted OR = 22.1). This suggests that access to malaria diagnosis in FG is particularly difficult for Brazilian illegal gold miners. Treatment adherence was better for persons who reported being tested. None of the 32 samples with Plasmodium falciparum presented any mutation on the pfK13 gene, but one isolate showed a resistance profile to artemisinin derivatives in vitro. CONCLUSIONS: The risk factors for the selection of resistance are well known and this study showed that they are present in FG with persons who self-medicated with poor adherence. Interventions should be implemented among this specific population to avoid the emergence of artemisinin resistance.

[Insulin-like growth factor (IGF)-II in human hepatocarcinogenesis--a potential therapeutic target?]. / Insulin-like growth factor (IGF)-II in der humanen Hepatokarzinogenese--eine potentielle therapeutische Zielstruktur?

Several studies have examined the expression profiles of human hepatocellular carcinomas (HCCs) using high density microarray technology, but subtyping with potential mechanistic and therapeutic impact has not been achieved so far. Here we have analysed the expression pattern of human HCCs and HCC cell lines in comparison to normal liver. A characteristic of one group of HCCs and all HCC cell lines was overexpression of insulin-like growth factor (IGF)-II. Moreover, IGF-II expression was mutually exclusive to induction of several IFN-related genes. In vitro, treatment of HCC cells with IFNgamma leads to a strong reduction of IGF-II expression. Equally, specific reduction of IGF-II was achieved using RNAinterference in HCC cells. Therefore, IGF-II may represent an excellent target for IFNgamma-treatment and specific siRNA-mediated therapeutic intervention.

[Tuberculosis among Trio-Indians in Surinam]. / Tuberculose onder Trio-indianen in Suriname.

OBJECTIVE: Evaluation of the extent and possible causes of the increased incidence of tuberculosis among Amazonian Indians in Surinam. DESIGN: Descriptive. METHOD: In two cross-sectional surveys in 1998 and 2000, the inhabitants of Kwamalasamutu, a village of Trio-Indians in Surinam, were examined for the presence of active and latent tuberculosis. Previous cases from the period 1995-2000 were evaluated retrospectively by consulting individual physicians and the archives of the 'Medische Zending' (Medical Mission), the 'Diakonessenhuis' hospital, the clinic for pulmonary diseases, and the Central Laboratory. Family ties and other factors that might be associated with tuberculosis were examined. Spoligotyping was done on all patient isolates. RESULTS: Between 1995 and 2000, active tuberculosis was diagnosed in 25 Indians from Kwamalasamutu, equal to 4.2 cases/1000 person-years (95% CI: 2.7-6.1). Tuberculin skin tests were positive in 105/733 Indians (14.3%). Cases of tuberculosis were found predominantly within certain families, who were genetically related. Spoligotyping of 5 Mycobacterium tuberculosis isolates from Trio-Indians showed unique patterns, which were also found in 34 isolates from elsewhere in Surinam. CONCLUSION: Tuberculosis was relatively common among Trio-Indians, clustering in certain families. This isolated tribe may have a genetic predisposition for tuberculosis, but their lifestyle and limited access to health care certainly play a role as well.

Outbreak of amebiasis in a family in The Netherlands.

Human-to-human transmission of Entamoeba histolytica is rare in industrialized countries. We describe an outbreak of amebiasis in a family in The Netherlands, demonstrating that even with Western standards of hygiene, persistent cyst passage may result in the transmission of E. histolytica to household contacts. If E. histolytica is isolated from a person living in an area of nonendemicity, it may be worthwhile to test all family members for cyst passage.

Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome.

BACKGROUND: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients. METHODS: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day. FINDINGS: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup. INTERPRETATION: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.

Susceptibility to Plasmodium berghei infection in rats is modulated by the acute phase response.

Brown Norway (BN) and Sprague Dawley (SD) rats are known to differ in their susceptibility to infection with sporozoites of Plasmodium berghei, as measured by the density of liver schizonts. Because of the known inhibitory effect of non-specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. LPS induced IL-6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. SD rats, which are the least susceptible to P. berghei sporozoites, showed significantly higher IL-6 production by macrophages from both sources. When LPS was administered in vivo, SD rats also had a significantly higher IL-6 response. Hepatocytes from both strains were cultured in the presence of IL-6. After three days of culture, alpha 2-Macroglobulin concentrations in the supernatants of SD hepatocytes were much higher than those from BN rats. Kupffer cell depletion in both BN and SD rats was correlated with a significant increase in liver schizont density, but did not abrogate the difference in susceptibility. From these results we conclude that the higher cytokine production capacity of SD rats compared to BN rats, may contribute to the difference in susceptibility to P. berghei sporozoites between these strains, but that other yet unknown factors are also involved.

Inhibition of Plasmodium berghei liver schizont development and reduction of cytokine production capacity in rats by dietary fish oil supplementation.

Experimental primary infection with Plasmodium berghei in rats is known to be influenced by several cytokines. Dietary supplementation of n-3 fatty acids has been shown to influence cytokine production capacity and to protect mice from cerebral malaria. We investigated the effect of dietary fish oil (FO) supplementation on cytokine and nitric oxide production and liver schizont development in male brown Norway rats. Control groups were fed either a corn oil-supplemented diet (CO) or standard lab chow (LC). After six weeks on either diet, rats given supplementary FO had a significantly lower production of interleukin-1 (IL-1) and IL-6 after stimulation with lipopolysaccharide, and also had significantly lower numbers of liver schizonts compared with CO- or LC-fed animals. We conclude that in rats, an FO-supplemented diet reduces the production capacity of IL-1 and IL-6 and inhibits schizont development after intravenous inoculation of P. berghei sporozoites. Fish oil did not influence nitric oxide production by peritoneal macrophages.

The role of Kupffer cells in the clearance of malaria sporozoites from the circulation.

In the past decade, one of the most intriguing subjects in understanding the mechanism of malaria infection has been explanation of the role of Kupffer cells. These liver cells, which play an important part in the body's defense against infection, seemed to have on essential supportive role in the homing o f sporozoites. Do Kupffer cells favor the establishment of primary malaria infection? Extensive research has revealed much, but still not everything we need to know about the sporozoite-Kupffer cell affair.

Kupffer cell elimination enhances development of liver schizonts of Plasmodium berghei in rats.

We investigated the development of exoerythrocytic forms (EEF) of Plasmodium berghei in livers of normal and macrophage-depleted Brown Norway rats. Macrophages were depleted by use of liposome-encapsulated dichloromethylene diphosphonate. Upon inoculation of sporozoites, macrophage-depleted rats had significantly larger numbers of EEF than untreated rats. We also investigated the effect of macrophage impairment by silica treatment on the development of EEF and confirmed that silica induces a significant reduction of EEF development. Intravenous administration of silica induced high levels of interleukin-6 in plasma within a few hours. The seemingly contradictory results for EEF development may be explained by our previous observation that interleukin-6 strongly inhibits sporozoite penetration and EEF development in vivo. We conclude that in experimental infections with sporozoites, Kupffer cells inhibit rather than enhance EEF development.