The clinical characteristics and outcomes of patients with fever of unknown origin caused by parasitic infection.

ABSTRACT: There are over 200 causes of fever of unknown origin (FUO), and although parasitic infection is an increasingly uncommon cause, a definitive diagnosis remains important to ensure rapid treatment and to prevent adverse sequelae through delay. Here, we studied the clinical features and outcomes of patients admitted with FUO and diagnosed with parasitic infection to improve our understanding of the features of parasitic FUO.Medical records of patients admitted to Peking Union Medical College Hospital between 2013 and 2019 with FUO and diagnosed with parasitic infection were reviewed. The clinical features and outcomes of patients for whom follow-up data were available were summarized.Six patients were admitted with FUO and diagnosed with parasitic infections (6/1013; 0.59%). Patients were more commonly middle-aged men and had a relatively long disease course. Most suffered from hyperpyrexia and other non-specific symptoms. Routine examinations were non-specific, and some patients had positive tumor markers, antinuclear antibodies, or positron emission tomography/computed tomography results. Diagnoses were confirmed by bone marrow smears, serum antibody testing, or feces examination. All 6 cases received anthelmintic treatments and recovered well.Parasitic infections must be screened for and actively excluded in FUO patients so that targeted therapy can be rapidly administered to ensure optimal outcomes.

Etiologic Agents of Fever of Unknown Origin Among Patients Attending Mnazi Mmoja Hospital, Zanzibar.

BACKGROUND: Fever of unknown origin (FUO) remains an important public health problem. With malaria transmission declining in some parts of Africa, the evidence suggests other infectious agents now account for most FUO. The purpose of this study was to identify the etiologic agents of FUO in a cross-section of patients at the Mnazi Mmoja hospital in Zanzibar, Tanzania. METHODOLOGY: A multiplex TaqMan gene expression Array Card (TAC) and plates were used for detection and classification of different pathogens in blood samples obtained from patients with FUO. Logistic regression analyses was performed using pathogens detected and sociodemographic characteristics as outcome and exposure variables respectively. Odd ratios and 95% confidence interval were calculated and statistical significance was set at P < .05. RESULT: Thirty-three different pathogens were detected in 27 patient blood samples. The following pathogens were detected in decreasing order of prevalence; Dengue virus, Plasmodium species, Rickettsia, Brucella species, Salmonella typhi, and less than 1% for each of Bartonella, Coxiella burnetii, Salmonella species, and Leptospira. Co-infections of Plasmodium with Dengue and S. typhi were also detected, including one case with three different pathogens-Plasmodium, Rickettsia and Brucella. There was no association between the etiologic agents of FUO and demographic or clinical characteristics. CONCLUSIONS: Zoonotic and arboviral etiological agents of fever of unknown origin are present among patients at the Mnazi Mmoja hospital in Zanzibar, Tanzania. There is a need to develop a baseline of standardized diagnostic approaches particularly within the hospital setting. In areas with low malaria prevalence like Zanzibar, Dengue, Rickettsia, Coxiella burnetii, Brucellosis should be considered by clinicians in the differential diagnoses of FUO.

Visceral Leishmaniasis in A Patient Presenting with Fever of Unknown Origin: A Case Report From a Low-endemic Region of Turkey

Leishmaniasis is a neglected disease that is prevalent in tropical and subtropical regions of the world. Even though cutaneous leishmaniasis is the most common form, visceral leishmaniasis is associated with high mortality. The case presented herein is a 39 year-old bed-ridden female who presented with fever of unknown origin, tachypnea and pancytopenia. She was initially misdiagnosed as having autoimmune pancytopenia elsewhere and treated with corticosteroids and intravenous immunoglobulin. She had also received wide-spectrum antibiotics for febrile neutropenia. We performed a leishmania rK39 dipstick test which turned out to be positive along with visualisation of amastigote forms of leishmania on bone marrow biopsy. Thus, we made a diagnosis of visceral leishmaniasis and treated her with liposomal amphotericin B. Her clinical course was complicated by respiratory failure necessitating invasive mechanical ventilation. She responded well to treatment and was later extubated, shortly before being discharged. At 6 months of follow-up, no sign of recurrence was observed.

Prevalence of scrub typhus in pyrexia of unknown origin and assessment of interleukin-8, tumor necrosis factor-alpha, and interferon-gamma levels in scrub typhus-positive patients.

BACKGROUND: Scrub typhus is lesser known cause of fever of unknown origin in India. Even if there have been reports documenting the prevalence of scrub typhus in different parts of India, it is still an unknown entity, and clinicians usually do not consider it as differential diagnosis. The present study was performed to document the prevalence of scrub typhus among febrile patients in western part of Uttar Pradesh and to assess the clinical profile of infected patients on the one hand and knowledge, attitude, and practices among clinicians on the other. MATERIALS AND METHODS: A total of 357 adult patients with fever of more than 5-day duration were recruited. All patients underwent complete physical examination, and detailed clinical history was elicited as per predesigned pro forma. After primary screening to rule out malaria, enteric fever, and leptospirosis infection, secondary screening for scrub typhus was done by rapid screen test and IgM ELISA. RESULTS: Scrub typhus infection was positive in 91 (25.5%) cases. The most common symptoms among the patients were fever (100%), pain in abdomen (79.1%), pedal edema 56 (61.5%), rash 44 (48.3%), headache 44 (48.3%), vomiting 42 (46.1%), constipation 33 (36.2%), cough 28 (30.7%), and lymphadenopathy 20 (21.9%). The median values of interleukin-8, interferon-gamma, and tumor necrosis factor-alpha in healthy controls were 15.54 pg/ml, 7.77 pg/ml, and 54.1 pg/ml, respectively, while the median values of these cytokines in scrub typhus-positive patients were 21.04 pg/ml, 8.74 pg/ml, and 73.8 pg/ml, respectively. CONCLUSION: Our results highlight that scrub typhus infection is an important cause of pyrexia of unknown origin, and active surveillance is necessary to assess the exact magnitude and distribution of the disease.

Trypanosomiasis in a Young Infant from Rural Gujarat, India.

BACKGROUND: Human trypansomiasis due to infection by animal trypanosomes is rarely reported from India. CASE CHARACTERISTICS: We describe clinical presentation of a 2-month-old boyfrom a rat infested house in rural Gujarat who was diagnosed to be havinginfection with the rodent parasite Trypanosoma lewisi. OBSERVATION: The fever and parasitemia resolved on treatment with liposomal amphotericin B, Ceftriaxone and Amikacin, and there was no recurrence of parasitemia over a 2 month follow-up. MESSAGE: The case highlights the need for increased awareness and heightened surveillance for this rare zoonotic infection.

Angiostrongylus cantonensis Infection: A Cause of Fever of Unknown Origin in Pediatric Patients.

Fever of unknown origin (FUO) in children is frequently caused by infectious diseases. Angiostrongylus cantonensis, while a primary cause of eosinophilic meningitis, is rarely a cause of FUO. We present 2 pediatric cases of FUO caused by Angiostrongylus cantonensis acquired in Houston, Texas, outside its usual geographic distribution.

Swamp cancer: a case of human pythiosis and review of the literature.

Pythiosis is an infection caused by the aquatic oomycete Pythium insidiosum. Commonly known as 'swamp cancer' in veterinary pathology, pythiosis is now considered an emerging human disease associated with significant morbidity and mortality. However, because clinical information is limited, many healthcare providers, including dermatologists, are unfamiliar with this diagnosis. To increase awareness of this life-threatening infection, a case of cutaneous pythiosis is presented. We describe a middle-aged man with acute myeloid leukaemia who presented with necrotizing haemorrhagic plaques on his thighs after a weekend of freshwater boating. Histological examination of a biopsy specimen showed invasive fungal hyphae associated with dense perivascular inflammation and vessel damage. Diagnostic testing on tissue culture revealed growth of P. insidiosum. Despite multiple debridements and antifungal therapy, the patient died within 2 weeks of presentation. There are four clinical presentations reported in human pythiosis. Pythium insidiosum infection should be considered in any patient with a suggestive exposure history and fungal elements found on histological examination or in culture. Identification of the organism can be difficult, so polymerase chain reaction and serological assays can be useful in making a diagnosis. To improve clinical outcomes, early combination therapy with antifungals and surgery is needed.

Infectious causes of fever of unknown origin.

The causes of fever of unknown origin (FUO) are changing because advances in clinical practice and diagnostics have facilitated the identification of some infections. A variety of bacterial infections can cause FUO, and these can be divided into those that are easy to identify using culture and those that require serological or molecular tests for identification. A number of viral, parasitic and fungal infections can also cause prolonged fever. This article summarises the clinical features and diagnostic strategy of these infections.

[From unexplained fever to visceral leishmaniasis--a case report]. / Od nejasne vrucice do visceralne lismenijaze--prikaz bolesnika.

Visceral leishmaniasis or kala-azar is a systemic infectious vector-borne disease caused by protozoa Leishmania donovani and Leishmania infantum that are transmitted to mammalian hosts by sand flies. It occurrs sporadically in endemic areas, including Mediterranean basin. Southern coastal territories of Croatia have been recognized as the foci of the disease. Dogs are the main reservoir of human infection. Clinical features include prolonged fever, malaise, hepatosplenomegaly, pancytopenia and inversion of albumin-globulin ratio. If left untreated, the disease causes death in majority of cases. We report a 47-year-old Croatian patient who was admitted to hospital with 2-month history of fever of unknown origin. Based on bone marrow aspirate findings and positive serological tests, the diagnosis of visceral leishmaniasis was established. We also considered secondary hemophagocytic lymphohystiocytosis in the differential diagnosis. After a 4-week treatment with sodium-stibogluconate clinical remission was achieved as well as complete recovery of hematopoesis. The aim of our case-report is to stress the importance of considering visceral leishmaniasis in patients with longstanding fever in endemic areas.

A fever of unknown origin workup in the emergency department reveals an unusual pathogen.

The cause of a fever of unknown origin (FUO, fever of >21 days without an identified etiology) may be a common illness, an atypical presentation of a common illness, or an unusual illness. A patient with an FUO occasionally presents to the emergency department (ED). The differential diagnosis of an FUO is extensive. A primary goal for the ED physician is to determine if the patient with an FUO has a disorder that needs immediate recognition and treatment. We describe a case of a teenage boy who presented to our ED with 2 weeks of high fever and back pain. We describe this teenage boy with FUO and a surprising diagnosis.

Standardization of a very specific and sensitive single PCR for detection of Plasmodium vivax in low parasitized individuals and its usefulness for screening blood donors.

Here, we describe the standardization of a very sensitive and specific single Plasmodium vivax polymerase chain reaction (PCR) and its usefulness for diagnosis and screening procedures when a Plasmodium falciparum PCR was also utilized. The P. vivax PCR sensitivity threshold was 0.019 parasites per microliter, and a PCR fragment was only detected when P. vivax DNA was present. Among the 11 febrile patients with negative parasitological examination that attended the malaria service of Fundação de Medicina Tropical do Amazonas, we diagnosed one P. vivax malaria by PCR. Among the 286 individuals considered suitable for blood donation, we also detected by PCR an individual with P. vivax malaria, and conversely, we did not detect any malaria infection in blood donor candidates considered unsuitable due to its past malaria history. We conclude that PCR is the method of choice for low-parasitized individuals and could therefore represent a complementary tool to safely rescue blood donor candidates considered unsuitable on the basis of malaria history.

Resolving diagnostic uncertainty in initially poorly localizable fevers: a prospective study.

AIMS: Prospective, observational data collection of fever patients with regard to aetiology and means of detecting it particularly noting the factors, which quickly helped resolve diagnostic uncertainty. METHODS: Prospective follow-up of patients with clinically non-localizable fever admitted to Manipal Teaching Hospital, Pokhara, Nepal, documenting their temperature response, clinical and lab findings and diagnoses with their response to treatment. RESULTS: Enteric fever 56.8% (25), urinary tract infection 15.9% (7), malaria 9% (4), TB (pulmonary) 4% (2), abscess 4% (2) and hydatid cyst 4% (2). Remaining 4% were due to some other systemic causes. Culture positive: Salmonella typhi positive 32% (8), S. paratyphi positive 20% (5) and culture negative 48%. Response to treatment: enteric fever--(i) first-line drugs (ampicillin/cotrimoxazole) 16% (4), (ii) second-line drugs (ciprofloxacin) 20% (5) and (iii) ceftriaxone 44% (11). CONCLUSIONS: Fever charting as a means to localize Salmonella vs other fevers is still an invaluable clinical tool in adult patients in Nepal. If used judiciously, it can be used as an effective means to diagnose and treat patients of initially non-localizable fevers. Patience must be exercised in starting antibiotics, not until the fever pattern of 2 days suggests enteric, and also while waiting for a response to first-line drugs for Salmonella before one switches over to costlier second-line drugs, with the possible exception of quinolones which may even be used first line owing to their reduced costs (at the danger of wielding a double-edged sword).

Utility of thick smears of bone marrow aspirate in pyrexia of unknown origin.

OBJECTIVE: To determine the diagnostic efficacy of Giemsa stained thick smear of bone marrow aspirate for evidence of malaria in febrile individuals in whom the diagnosis was otherwise unknown. DESIGN: Descriptive case-series study. PLACE AND DURATION OF STUDY: This study was conducted at the Department of Medicine, Sandeman Provincial Hospital, Quetta, in the Balochistan province of Pakistan, between January 1994 and December 1998. SUBJECTS AND METHODS: A total of 80 patients were included in the study, who presented with history of fever for more than 3 weeks with splenomegaly and pancytopenia. The bone marrow specimens of all these patients were examined. The bone marrow was aspirated from the posterior superior iliac spine. Three sets of smears were made. One set of thin smears was stained by Leishman's stain after air-drying and the second set of thin smears was air-dried, fixed with 97% methanol and later stained with 5% Giemsa stain. The third set of smears was a thick smear stained unfixed with 5% Giemsa stain. A temperature of 37 degrees C and a pH of 7.2 was maintained during the staining process. The presence of malarial parasite in the bone marrow was determined. Besides, the degree of megaloblastic change in erythroid series and the bone marrow cellularity were evaluated. The results obtained were recorded and statistically analyzed. RESULTS: Of the 80 bone marrows examined, 32(40%) showed the presence of malarial parasites, 19(23.75%) showed haematological malignancies, 16(20%) showed bone marrow suppression while 12(15%) showed megaloblastic changes. One (1.25%) case showed Leishman-Donovan bodies. Out of 32 cases showing the presence of malarial parasite in bone marrow, only 5(15.6%) revealed parasites, i.e. Plasmodium falciparum gametocytes on thin smear while 32(100%) cases showed Plasmodium falciparum trophozoites and gametocytes on thick smear. The ratio was 1:6.4. These 32 patients were divided into two groups, one group having mild anaemia (>8 g/dL) and the other severe anaemia (Hb<8 g/dL). In this study 20 patients had mild and 12 had severe anaemia. Megaloblastic changes were seen in 15 cases. Hypocellularity was seen in 3 patients with falciparum malaria while 28 showed normocellularity. The marrow was hypercellular in one patient. CONCLUSION: In patients presenting with prolonged fever, splenomegaly and pancytopenia, the Giemsa stained thick smear of bone marrow aspirates for evidence of malarial parasites was far superior to thin smear in diagnosing Plasmodium falciparum malaria.

Searching for antibodies against Trichinella spiralis in the sera of patients with fever of unknown cause.

Human cases of trichinellosis are often difficult to identify because the signs and symptoms of the disease, if the infection produces any at all, are non-specific, being similar to those observed in several other infectious diseases. In an investigation of Mexican patients with fever of unknown aetiology, attempts were made to develop a serodiagnostic test for the detection of antibodies specific for Trichinella spiralis. The excretory and secretory products of T. spiralis larvae (from the muscle tissue of experimentally infected rats) were used as the antigens in an enzyme-linked immuno-electrotransfer blot assay. The sera tested came from patients with fever of unknown cause (N=250), patients confirmed to have infectious or parasitic diseases other than trichinellosis (N=134) and 168 apparently healthy subjects. Overall, 4% of the samples from the febrile group, 1.8% of those from the healthy subjects but none of the sera from those with 'other diseases' reacted with the antigens of interest (of 45, 49 and 55 kDa). The results not only confirm that human infection with T. spiralis may be asymptomatic but also indicate that such infection may be mis-diagnosed.

[Congenital malaria due to Plasmodium falciparum and Plasmodium malariae]. / Konnatale Malaria durch Plasmodium falciparum und Plasmodium malariae.

Increasing tourism and growing numbers of immigrants from malaria-endemic countries are leading to a higher importation rate of rare tropical disorders in European countries. We describe, to the best of our knowledge, the first case of connatal malaria in Austria. The patient is the first child of a 24 year old mother who was born in Ghana and immigrated to Austria one and a half years before delivery. She did not stay in an endemic region during this period and did not show fever or any other signs of malaria. The boy was healthy for the first six weeks of his life. In the 8th week of life he was admitted to our hospital due to persistent fever of unknown origin. On physical examination he showed only mild splenomegaly. Routine laboratory testing revealed mild hemolytic anemia with a hemoglobin value of 8.3 g/l. In the blood smear Plasmodium falciparum and Plasmodium malariae were detected. Oral therapy with quinine hydrochloride was successful and blood smears became negative for Plasmodia within 6 days. This case shows that congenital malaria can occur in children of clinically healthy women who were born in malaria-endemic areas even one and a half year after they have immigrated to non-endemic regions.

Unexplained fever-analysis of 233 cases in a referral hospital.

A study was conducted to analyse the causes of fever of unknown origin (FUO) in a teaching hospital in central India. Study subjects consisted of 233 patients having FUO admitted in the medical ward. Specific causes of FUO were identified in 73.4% cases. The commonest causes (46.4%) were of infectious diseases origin foremost being enteric fever (29.6%) followed by malaria (9.0%) and tuberculous fever (5.2%). Chloroquine responsive fever accounted for 26% cases of FUO. Enteric fever were seen more commonly in younger adults less than 50 years, tuberculous fever presented usually after four weeks of onset of symptoms and more in elderly patients aged 50 years or more. Intermittent type of fever was more commonly recorded in infectious diseases. Approach to causes of FUO should be focused primarily on infectious diseases followed by other specific investigations. Empirical treatment of cases having intermittent fever with chloroquine seems justifiable even in absence of malarial parasite in peripheral blood smear.

Epidemiological, clinical and laboratory studies on parasitic infections as a cause of fever of undetermined origin in Dakahlia Governorate, Egypt.

Forty-three patients who fulfilled the international criteria for prolonged fever were exposed to thorough history taking, clinical and laboratory investigations. The latter included urine and stool examination, urine and blood culture, haemogram, liver and renal function tests, chest X-ray, tuberculin test, bone marrow, liver biopsy, blood films, serological tests including ELISA, IHA and IFA for detection of schistosomiasis, toxoplasmosis and malaria. Parasitic infections were detected in 30/43 (69.7%), 55.8% of whom had pure parasitic infection and 14% had in addition other causes. The majority of cases with positive etiology were coming from rural areas. The pattern of fever was predominantly intermittent especially with malaria and schistosomal cases. Fever of 21-41 days duration was noted in 70% of patients and 23.3% lasted up to more than 56 days. Visceromegaly (hepatomegaly and/or splenomegaly) was observed in all patients except one case. Lymphadenopathy was detected in ten cases, six of whom were visceral leishmaniasis. The IHA test for leishmaniasis detected ten cases at titres of 256, 512 and 1024 reciprocally. The dot-ELISA gave seropositivity in only 8/10 cases diagnosed by IHA test. So eight cases of VL were diagnosed by two serological tests at high titres. The detection of seropositive cases of visceral leishmaniasis in the studied area, suggests a focus or foci and warrants epidemiological study to establish the actual situation. Generally speaking, parasitic aetiology should be in mind in any case of FUO in Dakahlia. Serological tests are valuable, simple and safe tools for conforming the diagnosis of schistosomiasis, leishmaniasis, toxoplasmosis and malaria.