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17F with fever, anemia and splenomegaly
A case fromBayalpata Hospital (Nyaya Health)
Achham, Nepal
Initial presentation on Oct. 7, 2010• HPI: 17F with fevers, chills and rigors x 4 weeks. Of note, had a normal vaginal
delivery approximately 3 weeks prior (on Sept. 17th 2010) at the government district hospital, discharged after one day. As her fevers didn’t subside, she was readmitted to the same hospital and was treated for about a week with an unknown injectable and oral medicines before she was referred to Bayalpata Hospital.
• PMH: Spontaneous abortion of a 3 month old fetus 1 year ago • Medications: None. No discharge summary or referral letter was received from
the government district hospital so we do not know what she received there. • Allergies: NKDA• SH: Used to live with her husband in Mangalsen (about a 5 hour walk from the
hospital for the locals) prior to her illness. Now lives with her father (about 40 minute walk from the hospital). Has studied till Grade 7 before she got married. Does not smoke or drink. Her husband is a student studying in Mangalsen. She does not have any other children. No travel history outside of Achham, no travel to the Terai.
Patan Hospital, KTM
Bayalpata Hospital,Achham
Nepalgunj MedicalCollege
Doti DistrictHospital
Nyaya Hospital, Bayalpata
Government District Hospital, Mangalsen
Physical Exam
• Vitals: T 99, HR 120, BP 90/50, RR 22• General: Thin, very pale• Skin: No jaundice• HEENT: No icterus, PERRLA, EOMI• Heart: faint, tachycardic, regular rhythm, no audible MRGs• Lungs: CTAB• Abd: Splenomegaly up to the umbilicus. No hepatomegaly.
Non-tender, non-distended. +BS.• Ext: No clubbing, cyanosis, edema, no peripheral stigmata of
endocarditis• No notable LAD
Labs
– Hb: 5.4 mg/dl– WBC: 6000 with N67, L30, E03– PS for Malaria Parasites: Negative– Na: 133, K: 4.3, – Bilirubin: 1.4 (T), 0.6 (D)– BUN: 8 – Creatinine:0.6 – Blood Glucose level: 91
Management at Bayalpata• IV fluids• Ceftriaxone • Metronidazole • Ranitidine • Ferrous sulfate • 24hrs post-admission, the patient’s temperature increased to 106
degrees. Rigors were noted by clinicians. Tachycardia persisted. Chloroquine and primaquine to cover malaria were added.
• At this time, per recommendation of clinicians, family elected to transfer patient to a higher centerSeti Zonal HospitalNepalgunj Medical College
Patan Hospital, KTM
Bayalpata Hospital,Achham
Nepalgunj MedicalCollege
Doti DistrictHospital
Nepalgunj Medical CollegeFurther Diagnostic Tests on Oct. 9, 2010• PT:18sec (normal 13 sec), INR:1.5• Hb: 4.5, WBC:2,300 N63 L32 E04, Platelet Count: 45,000• ESR:130• Malaria smear: Positive• Glucose: 104• Normal Urea, Creatinine, Serum Bilirubin, SGPT,SGOT• Alkaline Phosphatase:1236 • Widal: Negative• General Blood Picture: Pancytopenia, P. Vivax• Abdominal ultrasound: Hepatosplenomegaly and Mild Collection seen in Uterine
Cavity• Normal Urine• Blood Group: AB +ve
Management at NMC
• Treated for Benign Tertian Malaria with Chloroquine and Primaquine
• Also given IV Ceftriaxone• Transfused with 3Units of blood, Hb 4.57• Discharge paperwork mentioned “Pancytopenia
Cause????”• Case referred to Tribhuwan University Teaching Hospital,
Kathmandu. Family members told she likely had a hematologic malignancy. But her parents could not afford to take her to KTM, so she was brought back to Achham.
• What else would we have done in Boston?
Readmission to Bayalpata on Oct. 25
She is still having fever with chills and rigors. • Vitals: T 104.0 F, HR 112, BP 110/80, RR 20, weight 36 Kg • Hb: 6.1 gm/dl , WBC:2500 per cubic mm ( Manually) • Blood glucose: 96 mg/dl , Creatinine: 0.6 mg / dl, BUN: 8 mg/dl , Na+: 133
mmol/L , K+:4.2 mmol/L • Serological test for Malaria Parasite (SD Bioline rapid diagnostic tests):
Negative • Peripheral smear for Malaria Parasite: Negative • Peripheral smear: Pancytopenia with no hemolysis• HIV: Negative
Management: • Quinine + Doxycycline (PO)• Supportive care
Timeline of Events• Oct. 28, 2010: Driven to Doti District Hospital for blood transfusion,
Armed Police Force help• Nov.5, 2010 : Father requested discharge from the hospital so patient
could be seen by a local Jhankri (traditional healer). Fevers better, patient on oral meds so doctors consented.
• Nov. 8, 2010-Nov. 16th 2010: Patient continues to deteriorate at home as family pursues traditional healing. Multiple visits by Nyaya staff and doctors.
• Nov. 16, 2010: 4th visit by Nyaya staff. Family finally consented for patient to be brought back to the hospital by ambulance. Started on Ceftriaxone and empiric TB treatment (Rifampicin, Isoniazid, Pyrazinamide , Ethambutol)
• Nov. 17, 2010: Sent to Doti Hospital for two units of blood.
Patan Hospital, Kathmandu
• Nov. 22, 2010• After many logistical hurdles (cost,
transportation, risk of dying en route, who would go with the patient, etc):– driven to Dhangadi (9 hour drive from Achham)– boarded a 1 hr 15 min flight to Kathmandu– Taken by ambulance to Patan Hospital
Patan Hospital course
• rk39 antigen test POSITIVE• Diagnosis: Kala-Azar (visceral leishmaniasis)• ???
Leishmaniasis
• Vector-borne disease transmitted by sandflies • Obligate intracellular protozoa of the genus Leishmania• Human infection caused by about 21 of 30 species. E.g.
L. donovani, L. infantum, and L. chagasi, L. mexicana, L. braziliensis, L. peruviana
• Results in 2 main forms of disease, cutaneous leishmaniasis and visceral leishmaniasis (kala-azar)
• Leishmanial species, geographic location, and immune response of the host determine form of disease
Visceral leishmaniasis
Geographical distribution
• More than 90 percent of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil
• Eastern Terai districts of Nepal
Clinical features
• Fever (can be continuous, intermittent, or remittent and it can recur at irregular intervals)
• Weight loss• Enlarged spleen and liver (usually the spleen is bigger
than the liver)• Some patients have LAD• Patients usually have cytopenias (anemia, leukopenia
and thromobycytopenia)• An important opportunistic infection in areas where it
coexists with HIV
Diagnosis
• Examination of Giemsa stained slides of the relevant tissue is still the technique most commonly used to detect the parasite.
• rK39 antigen strip test [It should be noted that a positive test result may be the result of previous (subclinical) infection and therefore not relevant to the current illness]
Treatment
• Pentavalent antimonials, such as sodium stibogluconate (Pentostam) available through the CDC in the US
• Recently, amphotericin B in its liposomal form has been approved and is now considered to be the drug of choice for visceral leishmaniasis
• Liposomal drugs high costprevent the use of liposomal drugs in most countries
• Miltefosine is the sole oral agent that has been shown to be effective
Our patient’s outcome
• Treatment immediately begun with amphotericin, poor response to infusion (HR 150, RR 50)transferred to ICU
• Liposomal amphotericin b not available in Nepal, costly to import from India, 80-100K Rupees per dose
• Vented, transfused, broad spectrum antibiotics• DIC• Pronounced dead on Nov. 27th morning
Original Article Single-Dose Liposomal Amphotericin B for Visceral
Leishmaniasis in India
Shyam Sundar, M.D., Jaya Chakravarty, M.D., Dipti Agarwal, M.D., Madhukar Rai, M.D., and Henry W. Murray, M.D.
N Engl J MedVolume 362(6):504-512
February 11, 2010
Teaching point #1: Differential for massive splenomegaly
• Hematologic (Thalassemia major)• Infectious (Leishmaniasis, hyperreactive malarial
splenomegaly syndrome, MAC)• Infiltrative (lymphoma, myeloproliferative
disorders, Gaucher’s disease)
Teaching Point #2
• Socio-cultural issues and structural barriers to care in Achham’s setting
– Use of traditional healers– Lack of diagnostic capability – Lack of therapeutics, transfusion capacity– Difficulty of referral– Cost– Transportation
Teaching Point #3: Visceral leishmaniasis
• Organism: Vector-borne disease transmitted by sandflies, obligate intracellular protozoa of the genus Leishmania
• Clinical features: Fever, Weight loss, HSM, cytopenias
• Dx: Giemsa stain, rK39 antigen strip test• Tx: liposomal amphotericin, antimonials
Thank you
• Dr. Bikash Gauchan MBBS, Medical Director• Dan Schwarz, Executive Director• Bayalpata Hospital staff• Nyaya team• www.nyayahealth.org
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