Mass testing and treatment for malaria followed by weekly fever screening, testing and treatment in Northern Senegal: feasibility, cost and impact.

BACKGROUND: Population-wide interventions using malaria testing and treatment might decrease the reservoir of Plasmodium falciparum infection and accelerate towards elimination. Questions remain about their effectiveness and evidence from different transmission settings is needed. METHODS: A pilot quasi-experimental study to evaluate a package of population-wide test and treat interventions was conducted in six health facility catchment areas (HFCA) in the districts of Kanel, Linguère, and Ranérou (Senegal). Seven adjacent HFCAs were selected as comparison. Villages within the intervention HFCAs were stratified according to the 2013 incidences of passively detected malaria cases, and those with an incidence ≥ 15 cases/1000/year were targeted for a mass test and treat (MTAT) in September 2014. All households were visited, all consenting individuals were tested with a rapid diagnostic test (RDT), and, if positive, treated with dihydroartemisinin-piperaquine. This was followed by weekly screening, testing and treatment of fever cases (PECADOM++) until the end of the transmission season in January 2015. Villages with lower incidence received only PECADOM++ or case investigation. To evaluate the impact of the interventions over that transmission season, the incidence of passively detected, RDT-confirmed malaria cases was compared between the intervention and comparison groups with a difference-in-difference analysis using negative binomial regression with random effects on HFCA. RESULTS: During MTAT, 89% (2225/2503) of households were visited and 86% (18,992/22,170) of individuals were tested, for a combined 77% effective coverage. Among those tested, 291 (1.5%) were RDT positive (range 0-10.8 by village), of whom 82% were < 20 years old and 70% were afebrile. During the PECADOM++ 40,002 visits were conducted to find 2784 individuals reporting fever, with an RDT positivity of 6.5% (170/2612). The combination of interventions resulted in an estimated 38% larger decrease in malaria case incidence in the intervention compared to the comparison group (adjusted incidence risk ratio = 0.62, 95% CI 0.45-0.84, p = 0.002). The cost of the MTAT was $14.3 per person. CONCLUSIONS: It was operationally feasible to conduct MTAT and PECADOM++ with high coverage, although PECADOM++ was not an efficient strategy to complement MTAT. The modest impact of the intervention package suggests a need for alternative or complementary strategies.

Distinct Biomarker Profiles Distinguish Malawian Children with Malarial and Non-malarial Sepsis.

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 ß [IL-1ß], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1ß, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1ß compared with the other subgroups. IL-1ß best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

A man in his 80s with arthritis and persistent fever. / En mann i 80-årene med leddgikt og vedvarende feber.

BACKGROUND: Febrile illness is a common clinical problem and frequently caused by bacterial and viral infections. When blood cultures are negative and symptoms persist despite empirical antibiotic treatment, clinicians must consider other differential diagnoses including malignancy, rheumatologic disease and parasitic infections. CASE PRESENTATION: A Norwegian male in his eighties experienced febrile illness during a stay in Southern Spain. Upon return to Norway, he was hospitalized with fever, weight-loss, enlarged spleen, pancytopenia and hypergammaglobulinemia. After failing to respond to broad-spectrum antibiotics and antifungals, he was diagnosed with visceral leishmaniasis and Leishmania infantum was confirmed by PCR and sequencing of spleen biopsy and blood. INTERPRETATION: With increasing migration and tourism, doctors in non-endemic countries should be familiar with visceral leishmaniasis.

Brotes emergentes de leptospirosis del Amazonas colombiano / Emerging leptospirosis outbreaks in the Colombian Department of Amazonas

Se describe por primera vez una serie de nueve casos con clínica indicativa de leptospirosis en el municipio Puerto Nariño en el departamento Amazonas, Colombia. Se muestran evidencias serológicas de exposición con Rickettsia del grupo de las fiebres manchadas. Los casos fueron clínicamente considerados como síndrome febril de origen desconocido. Se descartó infección por dengue y malaria. El diagnóstico de Leptospira se realizó mediante el método de reacción en cadena de la polimerasa en tiempo real. Igualmente, se detectó la presencia de anticuerpos contra rickettsias del grupo de las fiebres manchadas por inmunofluorescencia Indirecta. Finalmente, se realiza revisión del tema(AU)

A description is provided for the first time of a series of nine cases with a clinical examination suggestive of leptospirosis in the municipality of Puerto Nariño, Department of Amazonas, Colombia. Serological evidence is presented of exposure to Rickettsia, spotted fever group. The cases were clinically considered as febrile syndrome of unknown origin. Infection with dengue or malaria was ruled out. Diagnosis of leptospirosis was achieved by real-time polymerase chain reaction. Additionally, indirect immunofluorescence detected the presence of antibodies against rickettsia, spotted fever group. Finally, a review was conducted about the topic(AU)

Clinical and laboratory characterizations of hepatic capillariasis.

Hepatic capillariasis is a rare and neglected parasitic disease caused by infection with Capillaria hepatica in human liver. The disease is not well described and the information for the disease's clinical manifestation, laboratory findings and disease management strategy is not well reported. The limited information for this neglected infection often results in the delay of diagnosis or misdiagnosed to other diseases, therefore the real prevalence or severity of the infection may be underestimated. More case report with systemic analysis and features summary of this disease is needed to better understand the serious zoonotic disease. This study included systemic analysis of 16 patients infected with hepatic capillariasis in China between 2011-2017, including clinical manifestations, laboratory/radiative image findings and treatment results. Clinical manifestation included sustained fever (56.25%), respiratory disorder (37.5%), abdominal pain (37.5%), diarrhea (25%), leukocytosis (93.75%) and eosinophilia (100%). No egg was detected in feces of all patients. Over 60% patients showed elevated level of hepatic enzymes and proteins related to liver fibrosis in sera. Ultrasound and MRI examinations displayed scattered parasitic granuloma leisure in affected liver. Liver biopsy revealed parasite eggs, necrotized parasitic granulomas and septal fibrosis. Treatment with albendazole combined with corticoids for several treatment courses cured all patients with capillariasis. The difficulty of diagnosis, apparent damage of liver functions and potential fibrosis make the disease's prevalence and severity underestimated.

Fever and large pericardial effusion after valve surgery: can be malaria.

A 37-year-old man underwent mechanical mitral valve replacement for rheumatic heart disease. One week after discharge, he presented with high-grade fever with chills, malaise, and shortness of breath. Echocardiography showed pericardial effusion with no evidence of vegetation. A blood malaria antigen test was positive for Plasmodium falciparum. One week after initiation of antimalarial medication, echocardiography revealed almost complete resolution of the pericardial effusion. Infective endocarditis is a common cause of fever after valvular heart surgery. Malaria can be considered in the differential diagnosis of fever and pericardial effusion after valvular surgery, especially in malaria-endemic countries.

[Infection or metastases? The amoebic abscess]. / Geïnfecteerd of gemetastaseerd?

BACKGROUND: Cases of Entamoeba histolytica infections in the Netherlands are usually imported diseases. The most common extra-intestinal manifestation of E. histolytica is the amoebic abscess. Patients can present with a clinical picture of colitis with pain in the upper right abdomen, accompanied by fever in cases of liver abscess. Diagnostics focus mainly on the detection of E. histolytica with PCR or ELISA. Infections are treated with metronidazole, with clioquinol as follow-up treatment. CASE DESCRIPTION: A 61-year-old, previously healthy man was admitted to hospital with pain in the upper right abdomen and fever. He had no history of travel in the tropics or sub-tropics. CT imaging revealed liver abscesses or liver metastases. Cultures of abscess fluid were negative. After extensive diagnostics the patient was shown to have an amoebic abscess for which he was successfully treated. CONCLUSION: If the bacterial cultures of liver abscess fluid continue to be negative the possibility of an amoebic abscess should be considered, even with a negative history of travel to the tropics or subtropics.

Fever in a returning traveller: visceral leishmaniasis triggering haemophagocytic lymphohistiocytosis.

We present the case of a 23-year-old student admitted with fever, night sweats and splenomegaly. These non-specific signs and symptoms posed a diagnostic challenge which was further complicated by a history of recent foreign travel. The range of potential diagnoses required a variety of investigations in order to reach the final diagnosis. The incidental finding of an incompetent bicuspid aortic valve and an inflamed gallbladder further clouded the diagnostic process. Despite treatment with broad spectrum antibiotics, the patient continued to deteriorate. Serological testing finally provided a diagnosis of visceral leishmaniasis. The patient subsequently developed haemophagocytic lymphohistiocytosis, a life-threatening immune hyperactivity state that very rarely complicates leishmaniasis infection. With the use of amphotericin B and high-dose steroids, the patient made an excellent recovery.

Leishmania in a Patient with Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia.

BACKGROUND Leishmaniasis is a parasitic infection spread by the bite of infected sand flies that are usually present in the Middle East, Africa, and some parts of Asia and Europe. Leishmaniasis manifests in 3 different forms: Visceral (also known as Kala Azar), which is the most serious type; cutaneous, which is the most common type; and mucocutaneous. The symptoms of this infection range from a silent infection to fever, enlargement of the liver and spleen, weight loss, and pancytopenia. CASE REPORT In this case report, we discuss a 73-year-old man known to have chronic lymphocytic leukemia (CLL), presenting with unremitting fever and who to our surprise was found to have Kala Azar. CONCLUSIONS Early diagnosis and treatment are very important in treating visceral leishmaniasis. While the conventional treatment in immunocompromised patients is liposomal amphotericin B, our patient responded to corticosteroids.

A case of amebiasis with negative serologic markers that caused intra-abdominal abscess.

A 23-year-old Japanese woman presented with abdominal distention following fever, diarrhea, and abdominal pain during a stay in Taiwan. Serology for the detection of amebic-antibodies and stool microscopic examination were both negative. A computed tomography scan showed a 13 cm diameter abscess spreading from the lower abdominal wall to the pelvic retroperitoneal space. Needle aspiration of the abscess was done under computed tomography guidance, and microscopy of the aspirated fluid revealed trophozoites of Entamoeba. The patient was diagnosed as amebiasis with negative serologic markers that caused intra-abdominal abscess. Intravenous metronidazole treatment for two weeks did not result in any improvement of the abscess. After irrigation and drainage of the abscess, her symptoms resolved. This case report highlights that amebiasis should be considered when indicated by patient history, including travelers returning from endemic areas, and that further evaluation is necessary for diagnosis, even if the serology and stool test are negative.

Hematologic manifestations of babesiosis.

BACKGROUND: Babesiosis, a zoonotic parasitic infection transmitted by the Ixodes tick, has become an emerging health problem in humans that is attracting attention worldwide. Most cases of human babesiosis are reported in the United States and Europe. The disease is caused by the protozoa of the genus Babesia, which invade human erythrocytes and lyse them causing a febrile hemolytic anemia. The infection is usually asymptomatic or self-limited in the immunocompetent host, or follows a persistent, relapsing, and/or life threatening course with multi-organ failure, mainly in the splenectomized or immunosuppressed patients. Hematologic manifestations of the disease are common. They can range from mild anemia, to severe pancytopenia, splenic rupture, disseminated intravascular coagulopathy (DIC), or even hemophagocytic lymphohistiocytosis (HLH). CASE PRESENTATION: A 70 year old immunocompetent female patient living in New York City presented with a persistent fever, night sweats, and fatigue of 5 days duration. Full evaluation showed a febrile hemolytic anemia along with neutropenia and thrombocytopenia. Blood smear revealed intraerythrocytic Babesia, which was confirmed by PCR. Bone marrow biopsy was remarkable for dyserythropoiesis, suggesting possible HLH, supported by other blood workup meeting HLH-2004 trial criteria. CONCLUSION: Human babesiosis is an increasing healthcare problem in the United States that is being diagnosed more often nowadays. We presented a case of HLH triggered by Babesia microti that was treated successfully. Also, we presented the hematologic manifestations of this disease along with their pathophysiologies.

[Ambiguous hepatic mass and fever after stay in Turkey]. / Unklare Leberraumforderung und Fieber nach Türkeiaufenthalt.

We report the case of a 76-year old female patient with a hepatic mass after staying in eastern Turkey. There were no indices for malignancy or an infection with Echinococcus or Entamoeba histolytica. Finally we diagnosed a Fascioliasis (liver fluke) and cured the patient successfully.

Microbial Products and Cytokines in Sleep and Fever Regulation.

Excessive sleepiness and fever are constitutional symptoms associated with systemic infection. Although fevers have been investigated for many years, sleep responses to infectious challenge have only recently been investigated. Inoculation of animals with bacterial, viral, protozoan and fungal organisms result in complex sleep responses dependent upon the microbial agent and route of administration. The general pattern is characterized by an initial robust increase in non-rapid eye movement sleep (NREMS) followed by a period of NREMS inhibition. REMS is inhibited after infectious challenge. The sleep responses are accompanied by fever but the two responses are, in part, independent from each other. Sleep responses, like fevers, may be beneficial to host defense although this area is relatively uninvestigated. Microbial products likely responsible for sleep and fever responses include bacterial muramyl peptides and endotoxin, and viral double stranded RNA. These microbial products induce sleep and fever responses in animal models. The exact mechanism of how these structurally diverse microbial products elicit sleep and fever remain unknown; however these substances share the ability to induce cytokine production. Cytokines such as interleukin-1 (IL-1), tumor necrosis factor, acidic fibroblast growth factor (FGF), and interferon-α (IFN-α) are somnogenic whether given directly into brain or intravenously. Other cytokines lack somnogenic activity, e.g., IL-2, IL-6, IFNß and basic FGF. The somnogenic actions of cytokines probably involve growth hormone-releasing hormone (GHRH) and nitric oxide. Anti-GHRH or inhibition of NO production inhibits normal sleep and inhibits IL-1-induced sleep. In conclusion, cytokines are likely key mediators of fever and sleep responses to infection. The microbial-cytokine altered sleep likely results from an amplification of physiological sleep mechanisms which include cytokines, several neuropeptides and neurotransmitters such as nitric oxide.

[Bone hydatid cyst: a rare localization at the level of the hip bone]. / Un kyste hydatique osseux: une localisation rare au niveau de l'os iliaque.

Hydatid disease is a parasitic disease caused by the development in humans of the larval form of a tapeworm, namely a very small tænia called Echinococcus Granulosus. This anthropozoonosis is characterized by the presence of different types of anatomo-radiologic variants associated with various topographic and evolutionary aspects of the cysts. Bone hydatid disease is a rare condition, it accounts for only 0.9-2.5% of all locations. We report the case of a 9 year old child, who was admitted with febrile lameness and with a mass in the right iliac fossa, revealing a hydatid cyst at the level of the hip bone. Lesion assessment objectified a hydatid cyst of the hip bone with extension into adjacent soft tissues. An infected cyst was detected during surgery, hence the performance of a surgical excision of the cyst with drainage. Hydatic osteopathy is infiltrating, diffuse, slow and gradual, causing delays in diagnosis and compromising the quality of care.

Behavioral fever response in Rhodnius prolixus (Reduviidae: Triatominae) to intracoelomic inoculation of Trypanosoma cruzi

Abstract: INTRODUCTION: Behavioral fever is a response to infections with microorganisms observed in some poikilothermic animals. Rhodnius prolixus is involved in the transmission of two parasites: Trypanosoma cruzi (pathogenic for humans and transmitted in feces) and Trypanosoma rangeli (non-pathogenic for humans, pathogenic for Rhodnius and transmitted by the bite of an infected individual). Only T. rangeli is found in the hemolymph of Rhodnius as it travels to the salivary glands. METHODS: To study vector-parasite interactions, we evaluated possible behavioral fever responses of R. prolixus to intracoelomic inoculation with T. cruzi or T. rangeli. Temperature preferences of fifth-instar nymphs of R. prolixus were evaluated after inoculation with T. rangeli KP1(+), KP1(-), T. cruzi I, or the Trypanosome culture medium. Four different fixed temperatures (25, 30, 35, and 40°C) in two simultaneous experiments (enclosed and free-moving insects) were evaluated. Free-moving insects were marked daily according to their temperature preferences on each of the 15 days after inoculation. Numbers of insects in each temperature shelter and daily mortality were compared with those enclosed shelters of different temperatures. RESULTS: Rhodnius prolixus inoculated with both strains of T. rangeli and with the trypanosome culture medium showed preferences for the lowest temperatures (25°C). However, R. prolixus inoculated with T. cruzi I showed significant preferences for temperatures around 35°C. CONCLUSIONS: This is the first known investigation to demonstrate a behavioral fever response in R. prolixus injected intracoelomically with T. cruzi I.

A High Malaria Prevalence Identified by PCR among Patients with Acute Undifferentiated Fever in India.

BACKGROUND: Approximately one million malaria cases were reported in India in 2015, based on microscopy. This study aims to assess the malaria prevalence among hospitalised fever patients in India identified by PCR, and to evaluate the performance of routine diagnostic methods. METHODS: During June 2011-December 2012, patients admitted with acute undifferentiated fever to seven secondary level community hospitals in Assam (Tezpur), Bihar (Raxaul), Chhattisgarh (Mungeli), Maharashtra (Ratnagiri), Andhra Pradesh (Anantapur) and Tamil Nadu (Oddanchatram and Ambur) were included. The malaria prevalence was assessed by polymerase chain reaction (PCR), routine microscopy, and a rapid diagnostic test (RDT) with PCR as a reference method. RESULTS: The malaria prevalence by PCR was 19% (268/1412) ranging from 6% (Oddanchatram, South India) to 35% (Ratnagiri, West India). Among malaria positive patients P. falciparum single infection was detected in 46%, while 38% had P. vivax, 11% mixed infections with P. falciparum and P. vivax, and 5% P. malariae. Compared to PCR, microscopy had sensitivity of 29% and specificity of 98%, while the RDT had sensitivity of 24% and specificity of 99%. CONCLUSIONS: High malaria prevalence was identified by PCR in this cohort. Routine diagnostic methods had low sensitivity compared to PCR. The results suggest that malaria is underdiagnosed in rural India. However, low parasitaemia controlled by immunity may constitute a proportion of PCR positive cases, which calls for awareness of the fact that other pathogens could be responsible for the febrile disease in submicroscopic malaria.

[Visceral leishmaniasis in adults: about twelve cases]. / La leishmaniose viscérale chez l'adulte à propos de douze cas.

Visceral leishmaniasis is a vector-borne disease essentially associated with Leishmania infantum infection in the Mediterranean basin. Although rare in adults, its prevalence has recently increased even among immunocompetent individuals. The aim of our study is to reveal the epidemiological features of visceral leishmaniasis in adults and the importance of biological diagnostic in the identification of this disease. Our study spanned six years from January 2009 to January 2014 and data were collected from twelve patients hospitalized at University Hospital Hassan II, Fez. Alteration of general state and splenomegaly dominated the clinical picture. Biologically, anemia was almost constant. Diagnosis was confirmed by parasite identification at the level of bone marrow. The response to treatment was favorable for all our patients. Thus, visceral leishmaniasis recrudescence in adults and its nonspecific clinical picture must lead the clinicians to suspect it when fever accompanying splenomegaly occurs, thus enabling early diagnosis and therapeutic management.

Under seize: neurocysticercosis in an immigrant woman and review of a growing neglected disease.

Neurocysticercosis (NCC) is a significantly neglected tropical disease and, with increasing globalisation, a notable emerging infection in the developed world. We describe a case of ventricular NCC in a 22-year-old Mexican-American woman with a history of seizures, who presented with 2 weeks of headaches and intermittent fevers progressing to altered mental status and vomiting. Initial imaging revealed a cystic mass at the posteroinferior aspect of the third ventricle superior to the aqueduct of Sylvius, calcifications scattered throughout the parenchyma, and enlargement of the lateral and third ventricles. Initial laboratories were unrevealing and serum investigations for Taenia solium antibody were negative, but T. solium antibody was subsequently returned positive from cerebrospinal fluid. This case highlights important issues regarding the clinical presentation, diagnostic evaluation and treatment of NCC relevant to providers not only in areas with endemic disease but, importantly, in locales with diverse immigrant populations.

Fulminant amoebic colitis: a clinicopathological study of 30 cases.

AIMS: To review the clinical and pathological factors associated with fulminant amoebic colitis (FAC) requiring colonic resection and its outcome. METHODS: We retrospectively identified adult patients admitted to our centre between June 2007 and December 2011 with FAC who underwent colonic resection and were diagnosed with amoebic colitis based on the presence of trophozoites on histological examination. The clinical details were extracted from the medical notes and correlated with the pathological findings. RESULTS: Thirty patients (18 men and 12 women) met the inclusion criteria. Their mean age was 50.1 years (range 21-89). The most frequent symptoms were abdominal pain, vomiting and fever. More than half the patients (16/30) had underlying conditions associated with immunosuppression including diabetes mellitus and tuberculosis. Pathological investigation of colonic resections showed predominantly right-sided involvement with geographic colonic ulcers covered with a creamy-white pseudomembrane, perforations, gangrenous changes, amoeboma and lesions mimicking inflammatory bowel disease. All showed basophilic dirty necrosis with abundant nuclear debris and amoebic trophozoites on histological examination. 21/30 patients (70%) had involvement beyond the caecum. 17/30 patients (57%) died. Those with involvement beyond the caecum were more likely to die (15/21, 71.4%) than those with less extensive disease. CONCLUSIONS: FAC presents as acute abdomen and can mimic appendicitis, ischaemic bowel disease, tuberculosis and malignancy. Comorbidities causing immunosuppression frequently associated. Mortality remains high despite surgery, so FAC should be suspected in every case of acute abdomen with colonic perforation if associated with typical gross and microscopic findings and a history of stay in an endemic area.