Biology of Human Malaria Plasmodia Including Plasmodium Knowlesi

Malaria is a vector-borne infection caused by unicellular parasite of the genus Plasmodium. Plasmodia are obligate intracellular parasites that are able to infect and replicate within the erythrocytes after a clinically silent replication phase in the liver. Four species (P.falciparum, P.malariae, P.ovale and P.vivax) are traditionally recognized as responsible of natural infection in human beings but the recent upsurge of P.knowlesi malaria in South-East Asia has led clinicians to consider it as the fifth human malaria parasite. Recent studies in wild-living apes in Africa have revealed that P.falciparum, the most deadly form of human malaria, is not only human-host restricted as previously believed and its phylogenetic lineage is much more complex with new species identified in gorilla, bonobo and chimpanzee. Although less impressive, new data on biology of P.malariae, P.ovale and P.vivax are also emerging and will be briefly discussed in this review

an 8-year multi-centre observational study

Background Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. Methods The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. Results From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. Conclusion The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events

Report of 4 Cases and Review of the Literature

We reviewed the clinical, microbiologic, and outcome characteristics of 72 patients with human immunodeficiency virus (HIV)-associated histoplasmosis (4 newly described) reported in Europe over 20 years (1984-2004). Seven cases (9.7%) were acquired in Europe (autochthonous), whereas the majority involved a history of travel or arrival from endemic areas. The diagnosis of progressive disseminated histoplasmosis (PDH) was made during life in 63 patients (87.5%) and was the acquired immunodeficiency syndrome (AIDS)-presenting illness in 44 (61.1%). Disease was widespread in 66 patients (91.7%) and localized in 6 (8.3%), with the skin being the most frequent site of localized infection. Overall skin involvement was reported in 47.2% of the patients regardless of whether histoplasmosis was acquired in Africa or South America. Reticulonodular or diffuse interstial infiltrates occurred in 52.8%. The diagnosis was made during life by histopathology plus culture in 44 patients (69.8%), histopathology alone in 18 (28.5%), and culture alone in 1 (1.5%). During the induction phase amphotericin B and itraconazole (74.6%) were the single most frequently used drugs. Both drugs were also used either in combination (10.2%) or in sequential therapy (11.8%). Cumulative mortality rate during the induction phase of treatment was 15.2%. Overall, 37 patients died (57.8%); death occurred early in the course in 18 (28.1%). Seven of 40 patients (17.5%) who responded to therapy subsequently relapsed. Autopsy data in 13 patients confirmed the widespread disseminated nature of histoplasmosis (85%) among AIDS patients with a median of 4.5 organs involved. The results of the present report highlight the need to consider the diagnosis of PDH among patients with AIDS in Europe presenting with a febrile illness who have traveled to or who originated from an endemic area

Trends in the Postmortem Diagnosis of Opportunistic Invasive Fungal Infections in Patients With AIDS

Abstract We retrospectively evaluated autopsy-proven invasive fungal infections (IFIs) in patients with AIDS who died between 1984 and 2002. IFIs were identified in 297 (18.2%) of 1,630 autopsies. Their prevalence significantly decreased over time (from 25.0% in 1984–1988 to 15% in 1998–2002; P = .004), mainly owing to a significant decrease in pneumocystosis (P = .017) and cryptococcosis (P = .003), whereas the prevalence of aspergillosis and histoplasmosis remained relatively stable and of candidiasis and zygomycosis tended to increase in the last years (P = .028 and P = .042, respectively). IFIs were suspected or confirmed during life in only 46.8% of the cases; this proportion did not vary significantly over time (P = .320). The infections contributed to the deaths of 103 patients (34.7%), and their global impact on mortality was 6.3%. Of fatal cases, 38 (36.9%) were characterized by missed antemortem diagnoses, 17 (45%) of which met Goldman criteria for class I errors. The epidemiology of IFIs in patients with AIDS is evolving and not completely mirrored by clinical diagnoses or current diagnostic methods. Our results confirm the valuable role of autopsy data, even with highly effective therapies and advanced technologies

Imported Loa Loa Filariasis: Three Cases and a Review of Cases Reported in Non-Endemic Countries in the Past 25 Years

Summary Objectives The aim of this study was to highlight the increasing chance of Western physicians encountering patients (both immigrants and expatriates/travelers) seeking help for loiasis. Methods We describe three cases of imported loiasis observed at two hospitals in Italy and France, and present a review of all previously published cases in the medical literature in the last 25 years (1986–2011). The search was performed using PubMed and Scopus databases using the terms " Loa loa " AND "loiasis". Results We reviewed 101 cases of imported loiasis of which 61 (60.4%) were reported from Europe and 31 (30.7%) from the USA. Seventy-five percent of infestations were acquired in three countries: Cameroon, Nigeria, and Gabon. Overall, peripheral blood microfilariae were detected in 61.4% of patients, eosinophilia in 82.1%, eye worm migration in 53.5%, and Calabar swellings in 41.6%. However, Calabar swellings and eosinophilia were more common among expatriates/travelers, whereas African immigrants were more likely to have microfilaremia. Eye worm migration was observed in a similar proportion in the two groups. Only 35 patients (including the three described here) underwent clinical follow-up for a median period of 10.5 months (range 1–84 months); clinical relapse occurred in three of these patients and persistence or reappearance of blood microfilaria in another two. Conclusions Due to increasing travel and the migration of people from the endemic countries of West Africa to Europe and the USA, we speculate on the possible emergence of loiasis. Western physicians should be aware of the typical (eye worm migration and Calabar swellings) as well as unusual clinical presentations

Neglected Tropical Diseases in Italy: introducing IN-NTD, the Italian network for NTDs

The World Health Organization (WHO) defines neglected tropical diseases (NTDs) as a diverse group of primarily infectious diseases, which disproportionately affect poor and marginalized populations worldwide. In this context, NTDs are responsible for important morbidity and mortality and justify a global response. Moreover, NTDs are relatively neglected by research and development as well as by funding, if compared with the magnitude of the public health problem they represent. This happens even though, unlike other infectious diseases, they can be prevented, controlled and eliminated by targeted public health interventions. NTDs are mainly prevalent in communities from low-income countries in tropical and sub-tropical areas but are also present in upper–middle-income countries, including several in Europe. Here, we provide an update on the most relevant parasitic endemic or imported NTDs in Italy and illustrate the rationale for the establishment of the Italian network on NTDs, an alliance of scientific societies, institutes, foundations, universities and non-profit organizations united to fight NTDs

Risk of COVID-19 in-hospital mortality in people living with HIV compared to general population according to age and CD4 strata: data from the ICONA network

OBJECTIVES: We aimed to study whether people living with HIV (PLWH) are at higher risk of in-hospital COVID-19 mortality compared to the general population (GenPop). METHODS: This was a retrospective study in 19 Italian centers (February 2020 to November 2022) including hospitalized PLWH and GenPop with SARS-CoV-2 infection. The main outcome was in-hospital mortality. Competing risk analyses by Fine-Gray regression model were used to estimate the association between in-hospital mortality and HIV status/age. RESULTS: A total of 7399 patients with COVID-19 were included, 239 (3.2%) PLWH, and 7160 (96.8%) GenPop. By day 40, in-hospital death occurred in 1283/7160 (17.9%) among GenPop and 34/239 (14.2%) among PLWH. After adjusting for potential confounders, compared to GenPop 350 (aSHR 1.11 [95% CI 0.41-2.99]). CONCLUSIONS: In PLWH aged <65 years a CD4 ≤350 rather than HIV itself seems the driver for the observed higher risk of in-hospital mortality. We cannot however rule out that HIV infection per se is the risk factor in those aged ≥65 years

Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study

Background Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.Methods We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least &gt;= 24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.Results The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index &gt;= 3, dialysis, concomitant COVID-19, and INCREMENT score &gt;= 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.Conclusions Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy

Severe malaria in Europe: an 8-year multi-centre observational study

Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events