Hemophagocytic lymphohistiocytosis-how common and how severe is it as a complication of malaria? Retrospective case series and review of the literature.

BACKGROUND: Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria. METHODS: We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria. RESULTS: We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection). CONCLUSION: Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings.

Investigation on birth weight outcomes in schistosomiasis and praziquantel research: a correspondence.

Infection with Schistosoma sp. during pregnancy can cause low birth weight of the newborn. To allow a better differentiation between newborns with low birth weight and those with normal weight, the terms of intrauterine growth restriction (IUGR), small for gestational age (SGA) or fetal growth restriction (FGR) should be used. FGR describes the relationship between birth weight and gestational age and is defined as the incapability of a fetus to achieve expected growth with birth weight below the 10th percentile for gestational age. Additional investigations of the proportion of newborns with FGR should obtain more certainty about the effect of praziquantel and schistosomiasis on fetal growth.

The implementation of the Kinyoun staining technique in a resource-limited setting is feasible and reveals a high prevalence of intestinal cryptosporidiosis in patients with HIV.

OBJECTIVES: In resource-limited settings, intestinal Cryptosporidial or coccidian infections are common causes of chronic diarrhea but usually remain undiagnosed by routine stool investigation. Here, the addition of the Kinyoun staining technique after stool concentration was evaluated as an easy and inexpensive method for diagnosis of intestinal parasitic infection in patients with HIV. METHODS: This cross-sectional study investigated patients with HIV with diarrhea and randomly selected patients with HIV without diarrhea as controls. Stool samples were examined by wet mount microscopy and Kinyoun staining after stool concentration. Clinical, sociodemographic, and behavioral data were collected. Statistical analysis was performed using chi-squared test and multivariate regression analysis. RESULTS: In total, 163 participants were included (62.0% female, mean age 38.2 [SD ± 10.7] years). Diarrhea was present in 52.1% (85/163). The prevalence of intestinal parasites was 18.4% (30/163). Cryptosporidial infections were more frequent among patients with diarrhea (12.9% [11/85] vs 1.3% [1/78], P = 0.005) and in patients with CD4+ cell count <200 cells/µl (25.9% [7/27] vs 3.7% [5/136], P = 0.001). Risk factors for intestinal parasitic infections were diarrhea and the habit of regularly eating uncooked food. Kinyoun staining was necessary for the detection of cryptosporidiosis. CONCLUSION: In our cohort, the prevalence of intestinal parasitic infection was high, especially after additional use of Kinyoun staining for detection of Cryptosporidia or intestinal coccidia. Considering its clinical relevance, particularly in individuals at risk, the implementation of this technique should be considered in resource-limited settings.

Suitability of current typing procedures to identify epidemiologically linked human Giardia duodenalis isolates.

BACKGROUND: Giardia duodenalis is a leading cause of gastroenteritis worldwide. Humans are mainly infected by two different subtypes, i.e., assemblage A and B. Genotyping is hampered by allelic sequence heterozygosity (ASH) mainly in assemblage B, and by occurrence of mixed infections. Here we assessed the suitability of current genotyping protocols of G. duodenalis for epidemiological applications such as molecular tracing of transmission chains. METHODOLOGY/PRINCIPAL FINDINGS: Two G. duodenalis isolate collections, from an outpatient tropical medicine clinic and from several primary care laboratories, were characterized by assemblage-specific qPCR (TIF, CATH gene loci) and a common multi locus sequence typing (MLST; TPI, BG, GDH gene loci). Assemblage A isolates were further typed at additional loci (HCMP22547, CID1, RHP26, HCMP6372, DIS3, NEK15411). Of 175/202 (86.6%) patients the G. duodenalis assemblage could be identified: Assemblages A 25/175 (14.3%), B 115/175 (65.7%) and A+B mixed 35/175 (20.0%). By incorporating allelic sequence heterozygosity in the analysis, the three marker MLST correctly identified 6/9 (66,7%) and 4/5 (80.0%) consecutive samples from chronic assemblage B infections in the two collections, respectively, and identified a cluster of five independent patients carrying assemblage B parasites of identical MLST type. Extended MLST for assemblage A altogether identified 5/6 (83,3%) consecutive samples from chronic assemblage A infections and 15 novel genotypes. Based on the observed A+B mixed infections it is estimated that only 75% and 50% of assemblage A or B only cases represent single strain infections, respectively. We demonstrate that typing results are consistent with this prediction. CONCLUSIONS/SIGNIFICANCE: Typing of assemblage A and B isolates with resolution for epidemiological applications is possible but requires separate genotyping protocols. The high frequency of multiple infections and their impact on typing results are findings with immediate consequences for result interpretation in this field.

Falciparum malaria-induced secondary hemophagocytic lymphohistiocytosis successfully treated with ruxolitinib.

JAK/STAT signaling plays a major role in the pathogenesis of secondary hemophagocytic lymphohistiocytosis. This case report on a critically ill patient with secondary hemophagocytic lymphohistiocytosis due to falciparum malaria treated successfully with ruxolitinib, demonstrates that JAK1/2 inhibition might be a promising treatment option for severe cases.

Outbreak of Louse-Borne Relapsing Fever among Urban Dwellers in Arsi Zone, Central Ethiopia, from July to November 2016.

We report epidemiological and clinical aspects of an outbreak of louse-borne relapsing fever (LBRF) in Asella in Arsi Zone, central Ethiopia, from July to November 2016. A total of 63 LBRF cases were reported. The overall case fatality rate was 13% among treated patients. In this article, the first-line epidemiological assessment, individual prevention and control measures, and public health investigations and interventions in relation to this outbreak are described. Treatment recommendations for resource-limited settings are discussed by review of the latest literature.

Improvement of a tissue maceration technique for the determination of placental involvement in schistosomiasis.

Schistosomiasis in pregnancy may cause low birth weight, prematurity and stillbirth of the offspring. The placenta of pregnant women might be involved when schistosome ova are trapped in placental tissue. Standard histopathological methods only allow the examination of a limited amount of placental tissue and are therefore not sufficiently sensitive. Thus, placental schistosomiasis remains underdiagnosed and its role in contributing to schistosomiasis-associated pregnancy outcomes remains unclear. Here we investigated an advanced maceration method in order to recover a maximum number of schistosome ova from the placenta. We examined the effect of different potassium hydroxide (KOH) concentrations and different tissue fixatives with respect to maceration success and egg morphology. Placental tissue was kept either in 0.9% saline, 5% formalin or 70% ethanol and was macerated together with Schistosoma mansoni infested mouse livers and KOH 4% or 10%, respectively. We found that placenta maceration using 4% KOH at 37°C for 24 h was the most effective method: placental tissue was completely digested, egg morphology was well preserved and alkaline concentration was the lowest. Ethanol proved to be the best fixative for this method. Here we propose an improved maceration technique in terms of sensitivity, safety and required skills, which may enable its wider use also in endemic areas. This technique may contribute to clarifying the role of placental involvement in pregnant women with schistosomiasis.

Ultrasonography of gallbladder abnormalities due to schistosomiasis.

After malaria, schistosomiasis remains the most important tropical parasitic disease in large parts of the world. Schistosomiasis has recently re-emerged in Southern Europe. Intestinal schistosomiasis is caused by most Schistosoma (S.) spp. pathogenic to humans and leads to chronic inflammation and fibrosis of the colon as well as to liver fibrosis. Gallbladder abnormalities usually occur in patients with advanced hepatic portal fibrosis due to Schistosoma mansoni infection. Occasionally, gallbladder abnormalities have been seen also in children and occurring without associated overt liver abnormalities.The specific S. mansoni-induced gallbladder abnormalities detectable by ultrasound include typical hyperechogenic wall thickening with external gallbladder wall protuberances. The luminal wall surface is smooth. The condition is usually clinically silent although some cases of symptomatic cholecystitis have been described. The ultrasonographic Murphy response is negative. Gallbladder contractility is impaired but sludge and calculi occur rarely. Contrary to other trematodes such as liver flukes, S. mansoni does not obstruct the biliary tract. Advanced gallbladder fibrosis is unlikely to reverse after therapy.

Clinical implications of a gradual dormancy concept in malaria.

Malaria recurrences after an initially successful therapy and malarial fever occurring a long time after infection are well-known problems in malariology. Currently, two distinct types of malaria recurrences are defined: recrudescence and relapse. A recrudescence is thought to originate from circulating Plasmodium blood stages which do not cause fever before a certain level of a microscopically detectable parasitemia is reached. Contrary, a relapse is thought to originate from quiescent intracellular hepatic parasite stages called hypnozoites. Recrudescences would typically occur in infections due to Plasmodium falciparum. Plasmodium knowlesi, and Plasmodium malariae, whereas relapses would be caused exclusively by Plasmodium vivax and Plasmodium ovale. This schematic view is, however, insufficiently supported by experimental evidence. For instance, hypnozoites of P. ovale have never been experimentally documented. On the other hand, the nonfinding of P. malariae hypnozoites turned into the proof for the nonexistence of P. malariae hypnozoites. Clinical relapse-type recurrences have been observed in both P. ovale and P. malariae infections, and decade-long incubation times have also been reported in P. falciparum infections. We propose a gradual hypothesis in accordance with the continuity concept of biological evolution: both, relapse and recrudescence may be potentially caused by all Plasmodium spp. We hypothesize that the difference between the various Plasmodium spp. is quantitative rather than qualitative: there are Plasmodium spp. which frequently cause relapses such as P. vivax, particularly the P.v. Chesson strain, species which cause relapses less frequently, such as P. ovale and sometimes P. malariae, and species which may exceptionally cause relapses such as P. falciparum. All species may cause recrudescences. As clinical consequences, we propose that 8-aminquinolines may be considered in a relapse-type recrudescence regardless of the causal Plasmodium sp., whereas primaquine relapse prevention might not be routinely indicated in malaria due to P. ovale.

Acute anuria after a family vacation to Corsica/France.

A 12-year-old male patient suffered hematuria. Histopathology of a biopsy showed granulomata suspicious for schistosomiasis. The patient had never travelled outside Europe during his entire lifetime. He had taken frequent bathes in various rivers during his last family holidays 5 months earlier in Corsica. Microfiltration of urine revealed viable ova of Schistosoma haematobium with alterated size and shape. Ultrasonography showed a large focal echopoor mass attached to the bladder roof. Four days after antihelminthic therapy, the patient suffered inferior abdominal pain and acute anuria. Ultrasound revealed an approximately 5-cm mass in the bladder lumen suspicious for a large blood clot. After taking non-invasive measures such as drinking high amounts of fluid and treating the lower abdomen with a warm water bag and massage, the clot was excreted with urine and symptoms subsided. The further course was uneventful until 11 months later when hematuria recurred. This time, parasitological urine examination confirmed non-viable schistosome ova. Hematuria was likely due to erosion of the bladder mucosa by calcified non-viable ova.

Introgressive hybridizations of Schistosoma haematobium by Schistosoma bovis at the origin of the first case report of schistosomiasis in Corsica (France, Europe).

This study concerns the first urinary schistosomiasis case observed in Corsica (France, Europe) occurring in a 12-year-old German boy. The aim was to identify the relationship between this Schistosoma haematobium infection and other schistosomes of the Schistosoma group with terminal-spined ova. Morphological and molecular analyses were conducted on the ova. The results showed that the schistosome responsible for the emergence of schistosomiasis in Corsica was due to S. haematobium introgressed by genes from S. bovis.

Severe liver fibrosis caused by Schistosoma mansoni: management and treatment with a transjugular intrahepatic portosystemic shunt.

Liver diseases are common in inhabitants and migrants of tropical countries, where the liver can be exposed not only to toxins but also to many viral, bacterial, fungal, and parasitic infections. Schistosomiasis--a common parasitic infection that affects at least 240 million people worldwide, mostly in Africa--is regarded as the most frequent cause of liver fibrosis worldwide. We present a case of a 19-year-old male refugee from Guinea with recurrent oesophageal variceal bleeding due to schistosomal liver fibrosis refractory to endoscopic therapy. This case was an indication for portosystemic surgery, which is a highly invasive non-reversible intervention. An alternative, less invasive, reversible radiological procedure, used in liver cirrhosis, is the placement of a transjugular intrahepatic portosystemic shunt (TIPS). After thorough considerations of all therapeutic options we placed a TIPS in our patient. In more than 3 years of observation, he is clinically well apart from one episode of hepatic encephalopathy related to an acute episode of viral gastroenteritis. Bleeding from oesophageal varices has not recurred. In this Grand Round, we review the diagnostic approaches and treatment options for portal hypertension due to schistosomal liver fibrosis.

The WHO ultrasonography protocol for assessing morbidity due to Schistosoma haematobium. Acceptance and evolution over 14 years. Systematic review.

In 2000, the World Health Organization (WHO) published an ultrasound field protocol for assessing morbidity due to schistosomiasis. The present study aims to review the acceptance of the WHO protocol for Schistosoma haematobium. A PubMed literature research using the keywords "ultrasound OR ultrasonography (US) AND schistosomiasis," "US AND S. haematobium," "US AND urinary schistosomiasis" from 2001 through 2014 was performed. Thirty-eight eligible publications reporting on 17,861 patients from 13 endemic and 2 non-endemic countries were analysed. Of these, 33 referred to field studies on 17,317 patients. The Niamey protocol was applied to 15,367/17,317 (88.74%) patients in 23/33 (69.70%) of field studies (all studies: 15,649/17,861 [87.61%] patients (25/38 [68.42%] studies). The acceptance of the protocol by single country in field studies varied from 0 to 100%. It varied over time between 55.56% (5/9) in the period from 2001 to 2004, to 87.50% (7/8) from 2005 to 2008, to 62.50% (5/8) from 2009 to 2011 and 75.00% (6/8) from 2012 through 2014 (all studies: 50% [5/10], 88.89% [8/9], 62.50% [5/8], 63.64% [7/11], respectively). The Niamey protocol was applied also in 2/5 hospital studies in 282/544 (51.84%) patients.The usefulness of the WHO protocol for S. haematobium infections is confirmed by its worldwide acceptance. Some simplifications might facilitate its use also for focused ultrasound examinations performed by less skilled examiners. Organ abnormalities due to schistosomiasis detectable by ultrasonography not yet covered by the WHO protocol should be added to the additional investigations section.

Anaphylactic shock ensuing therapeutic puncture of an echinococcal cyst.

Cystic echinococcosis (CE) is a widespread zoonosis. For treating single echinococcal cysts during the last decades, therapeutic puncture of the cyst, aspiration, injection of a scolicide, and re-aspiration (PAIR) has been established as a minimal-invasive alternative method to surgery. A recent review on the complications of therapeutic cyst punctures has shown that dangerous complications occur much less frequently than previously assumed. A case is described where an allergic acute bronchospasm and arterial hypotension led to a life-threatening shock immediately after echinococcal cyst puncture. Fortunately, the situation could be managed by an experienced and well-equipped anesthesiology team. Life-threatening allergic phenomena after puncture of echinococcal cysts may occur less frequently than generally assumed; nevertheless, they must be taken into account, and precautions must be taken to manage serious adverse events.

The WHO ultrasonography protocol for assessing hepatic morbidity due to Schistosoma mansoni. Acceptance and evolution over 12 years.

The aim of this study is to review the worldwide acceptance of the World Health Organization (WHO) ultrasound protocol for assessing hepatosplenic morbidity due to Schistosoma mansoni since its publication in 2000. A PubMed literature research using the keywords "schistosomiasis and ultrasound," "schistosomiasis and ultrasonography," and "S. mansoni and ultrasound" from 2001 to 2012 was performed. Case reports, reviews, reports on abnormalities due to parasites other than S. mansoni, organ involvement other than the human liver, and reports where ultrasound method was not described were excluded. Six studies were retrieved from other Brazilian sources. Sixty studies on 37,424 patients from 15 countries were analyzed. The WHO protocol was applied with increasing frequency from 43.75% in the years 2001 to 2004 to 84.61% in 2009 to 2012. Results obtained using the pictorial image pattern approach of the protocol are reported in 38/41 studies, whereas measurements of portal branch walls were applied in 19/41 and results reported in 2/41 studies only. The practical usefulness of the pictorial approach of the WHO protocol is confirmed by its wide acceptance. This approach alone proved satisfactory in terms of reproducibility, assessment of evolution of pathology, and comparability between different settings. The measurements of portal branches, also part of the protocol, may be omitted without losing relevant information since results obtained by these measurements are nonspecific. This would save resources by reducing the time required for each examination. It is also more feasible for examiners who are not specialized in medical imaging. As with all protocols, incipient liver fibrosis is difficult to distinguish from normal ultrasound findings of the liver. The ability of this protocol to predict complications in severe cases should be further evaluated in a higher number of patients.

Pneumocystis pneumonia (PCP) and Pneumocystis jirovecii carriage in renal transplantation patients: a single-centre experience.

BACKGROUND: The Pneumocystis pneumonia is an increasing problem in transplanted patients: up to 25% suffer from Pneumocystis pneumonia, occurring during the first 6 months after transplantation. METHODS: From 2001 to 2009, we investigated 21 patients with pneumonia after renal transplantation for the presence of Pneumocystis jirovecii. The laboratory diagnosis was established by Grocott and Giemsa staining methods and Pneumocystis-specific mitochondrial transcribed large subunit nested polymerase chain reaction (PCR). The PCR was also used for the differentiation of Pneumocystis pneumonia from Pneumocystis carriage. RESULTS: Of 21 patients, 7 had a Pneumocystis pneumonia, 6 were Pneumocystis carriers and 8 patients were negative. Four out of seven Pneumocystis pneumonia patients and two out of six patients with Pneumocystis carriage had a delayed graft function. An acute cytomegalovirus infection after transplantation was not detectable in the patients with Pneumocystis pneumonia, but in three patients with Pneumocystis carriage. CONCLUSIONS: Pneumocystis pneumonia was present in 33.3% of transplanted patients with suspected pneumonia. An association between acute rejection or co-infections and Pneumocystis pneumonia or carriage in patients after renal transplantation cannot be excluded. In three out of seven Pneumocystis pneumonia patients, an overlapping of hospitalisation times and an onset of Pneumocystis pneumonia 6 months after transplantation was found. Thus, person-to-person transmission seems probable in these cases.