•The quality of evidence for the use of ribavirin is very low, stemming largely from a single non-randomized clinical trial with historic controls and high risk of bias.•Based on this trial patients ...with severe Lassa fever seem to benefit from ribavirin treatment.•Treatment of mild Lassa fever may lead to an increase in mortality.•Re-assessment of ribavirin in the treatment of Lassa fever is urgently required.
Lassa fever (LF) causes annual outbreaks in endemic regions with high mortality of symptomatic patients. Ribavirin is recommended as standard treatment for LF in national and international guidelines but the evidence base for this recommendation has been questioned recently.
We conducted a systematic review and included 6 studies providing efficacy data of ribavirin treatment for LF (PROSPERO protocol CRD42018103994).
Besides retrospective case series, the evidence mostly relies on a single prospective clinical trial with critical risk of bias. In this trial, LF associated mortality is reduced for patients with elevated aspartate aminotransferase (AST) when treated with ribavirin (OR 0.41, 95% CI 0.23–0.73), while mortality is higher for patients without elevated AST (OR 2.37, 95% CI 1.07–5.25).
Based on the available data, current treatment guidelines may therefore put patients with mild LF at increased risk of death. The role of ribavirin in the treatment of LF requires urgent reassessment.
Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the ...understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria.
This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported.
Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale's first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.
Since the onset of the ongoing civil war in Syria, the governmental surveillance system for leishmaniasis has lost access to provinces of northern Syria. The MENTOR Initiative, an international ...not-for-profit organization, was commissioned to implement an integrated leishmaniasis control program, providing an opportunity to reassess the epidemiology of leishmaniasis in northern Syria. Epidemiologic data and biologic samples for molecular species diagnostics were collected from collaborating local health centers. Incidence peaked in March 2015 at 7,743 estimated monthly cases. High levels of transmission were observed in traditional endemic regions but extended to previously hypoendemic regions, such as Al-Raqqa and Al-Hasakah. Incidence decreased to 3,209 in July 2015. Data indicate that the prewar trend of increasing incidence of cutaneous leishmaniasis accelerated during the beginning of armed conflict but declined after implementation of the comprehensive control program by the MENTOR Initiative. Molecular analysis revealed a spectrum of Leishmania species and sporadic cases of visceral leishmaniasis.
Management of imported malaria in Europe Askling, Helena H; Bruneel, Fabrice; Burchard, Gerd ...
Malaria journal,
09/2012, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In this position paper, the European Society for Clinical Microbiology and Infectious Diseases, Study Group on Clinical Parasitology, summarizes main issues regarding the management of imported ...malaria cases. Malaria is a rare diagnosis in Europe, but it is a medical emergency. A travel history is the key to suspecting malaria and is mandatory in patients with fever. There are no specific clinical signs or symptoms of malaria although fever is seen in almost all non-immune patients. Migrants from malaria endemic areas may have few symptoms.Malaria diagnostics should be performed immediately on suspicion of malaria and the gold- standard is microscopy of Giemsa-stained thick and thin blood films. A Rapid Diagnostic Test (RDT) may be used as an initial screening tool, but does not replace urgent microscopy which should be done in parallel. Delays in microscopy, however, should not lead to delayed initiation of appropriate treatment. Patients diagnosed with malaria should usually be hospitalized. If outpatient management is preferred, as is the practice in some European centres, patients must usually be followed closely (at least daily) until clinical and parasitological cure. Treatment of uncomplicated Plasmodium falciparum malaria is either with oral artemisinin combination therapy (ACT) or with the combination atovaquone/proguanil. Two forms of ACT are available in Europe: artemether/lumefantrine and dihydroartemisinin/piperaquine. ACT is also effective against Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi, but these species can be treated with chloroquine. Treatment of persistent liver forms in P. vivax and P. ovale with primaquine is indicated after excluding glucose 6 phosphate dehydrogenase deficiency. There are modified schedules and drug options for the treatment of malaria in special patient groups, such as children and pregnant women. The potential for drug interactions and the role of food in the absorption of anti-malarials are important considerations in the choice of treatment.Complicated malaria is treated with intravenous artesunate resulting in a much more rapid decrease in parasite density compared to quinine. Patients treated with intravenous artesunate should be closely monitored for haemolysis for four weeks after treatment. There is a concern in some countries about the lack of artesunate produced according to Good Manufacturing Practice (GMP).
Three-day artemisinin-based combination therapy (ACT) is the current standard of care for the treatment of malaria. However, specific drug resistance associated with reduced efficacy of ACT has been ...observed, therefore necessitating the clinical development of new anti-malarial drugs and drug combinations. Previously, Single Encounter Radical Cure and Prophylaxis (SERCAP) has been proposed as ideal target-product-profile for any new anti-malarial drug regimen as this would improve treatment adherence besides ensuring complete cure and prevention of early reinfection. Arguably, this concept may not be ideal as it (1) necessitates administration of an excessively high dose of drug to achieve plasmodicidal plasma levels for a sufficient time span, (2) increases the risk for drug related adverse drug reactions, and (3) leaves the patient with a one-time opportunity to achieve-or not-cure by a single drug intake. Over the past years, SERCAP has led to the halt of promising drug development programmes, leading to potentially unnecessary attrition in the anti-malarial development pipeline. One proposition could be the concept of single-day multi-dose regimens as a potentially better alternative, as this allows to (1) administer a lower dose of the drug at each time-point leading to better tolerability and safety, (2) increase treatment adherence based on the intake of the anti-malarial drug within 24 h when malaria-related symptoms are still present, and (3) have more than one opportunity for adequate intake of the drug in case of early vomiting or other factors causing reduced bioavailability. In line with a recently published critical viewpoint on the concept of SERCAP, an alternative proposition is-in contrast to the current World Health Organization (WHO) treatment guidelines-to aim for less than three days, but still multiple-dose anti-malarial treatment regimens. This may help to strike the optimal balance between improving treatment adherence, maximizing treatment effectiveness, while keeping attrition of new drugs and drug regimens as low as possible.
Highlights • Haemolysis following treatment of severe malaria with artemisinin drugs is a common clinical phenomenon typically occurring in the second week after initiation of antimalarial therapy. • ...The observed decrease of haemoglobin is clinically significant and the majority of reported cases required repeated administration of blood transfusions. • All artemisinin derivatives and all routes of administration (intravenous, intra-muscular, intra-rectal and even oral administration) may be associated with late haemolysis. • Hyperparasitaemia is the most consistent risk factor for haemolysis, however not all patients with hyperparasitaemia will develop haemolysis following treatment with artemisinins. • Despite the occurrence of haemolysis following treatment with artemisinin drugs, parenteral artesunate remains the first line treatment for severe malaria. • Patients treated with artemisinin derivatives for severe malaria should be followed-up for clinical and laboratory investigations at least once weekly for a 4 to 6 week period to screen for signs of haemolysis.
Human subcutaneous dirofilariasis is an emerging mosquitoborne zoonosis. A traveler returning to Germany from India experienced Dirofilaria infection with concomitant microfilaremia. Molecular ...analysis indicated Dirofilaria repens nematodes of an Asian genotype. Microfilaremia showed no clear periodicity. Presence of Wolbachia endosymbionts enabled successful treatment with doxycycline.
Abstract
Background
Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites. Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce. The aim of this ...prospective study was to characterize the reappearance patterns of ovale parasites.
Methods
P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia. Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria.
Results
At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri. The median duration of follow-up was 35 weeks. Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32. Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi.
Conclusion
These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated. Interestingly, no relapse of P. ovale wallikeri was observed.
The formation of hypnozoites and consequential relapse of tertian malaria is a widely accepted theory that lacks, however, confirmation for Plasmodium ovale spp. This study clinically and molecularly evaluates reappearing P. ovale spp. parasites to provide new evidence.
Coronavirus disease 2019 (COVID-19) which is caused by the novel SARS-CoV-2 virus is a severe flu-like illness which is associated with hyperinflammation and immune dysfunction. The virus induces a ...strong T and B cell response but little is known about the immune pathology of this viral infection. Acute
malaria also causes acute clinical illness and is characterized by hyperinflammation due to the strong production of pro-inflammatory cytokines and a massive activation of T cells. In malaria, T cells express a variety of co-inhibitory receptors which might be a consequence of their activation but also might limit their overwhelming function. Thus, T cells are implicated in protection as well as in pathology. The outcome of malaria is thought to be a consequence of the balance between co-activation and co-inhibition of T cells. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8
and CD4
T cells of PBMC of
= 20 SARS-CoV-2 patients compared to
= 10
infected patients and
= 13 healthy controls. Overall, acute COVID-19 and malaria infection resulted in a comparably elevated activation and altered differentiation status of the CD8
and CD4
T cell populations. T effector cells of COVID-19 and malaria patients showed higher frequencies of the inhibitory receptors T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene-3 (LAG-3) which was linked to increased activation levels and an upregulation of the transcription factors T-bet and eomes. COVID-19 patients with a more severe disease course showed higher levels of LAG-3 and TIM-3 than patients with a mild disease course. During recovery, a rapid normalization of these inhibitory receptors could be observed. In summary, comparing the expression of different co-inhibitory molecules in CD8
and CD4
T cells in COVID-19 vs. malaria, there is a transient increase of the expression of certain inhibitory receptors like LAG-3 and TIM-3 in COVID-19 in the overall context of acute immune activation.
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