- Video-Case from Bayalpata Hospital (Nyaya Health), the doctors and staff there actually wrote up the case as part of the weekly M&M series there. -Nyaya founded by one of our very own residents (Duncan Maru) and ID fellow (Jason Andrews)-Case is very recent, very unfortunate and difficult case both medically and in terms of various socio-cultural issues that it brings up.-I definitely don’t have all the answers so it will be a bit different from the typical morning report cases but I’m hoping that you can help me come to some conclusions in the case.
What would you want to do diagnostically at this stage?
These are essentially all the labs we can get.
Ok what’s on your differential right now? And what would you want to do in terms of management? We can’t do any more diagnostics and the closest facility with slight more diagnostic facilities is about a 14 hour drive away.
Any thoughts on these labs? How does it change your differential? ****[The clinical status of the patient: Patients diagnosed with malaria are generally categorized as having either uncomplicated or severe malaria. Patients diagnosed with uncomplicated malaria can be effectively treated with oral antimalarials. However, patients who have one or more of the following clinical criteria (impaired consciousness/coma, severe normocytic anemia [hemoglobin<7], renal failure, acute respiratory distress syndrome, hypotension, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and/or parasitemia of > 5%) are considered to have manifestations of more severe disease and should be treated aggressively with parenteralantimalarial therapy. (IV quindine / Artesunate)--Chloroquine resistant Vivax malaria is rare in South Asia.What is the risk of malaria in Nepal?Although there are reports of about 5000 malaria cases with 10 deaths per year among the Nepalese, the risk for the average tourist or expatriate seems very low in Nepal. In the 26 year history of the CIWEC Clinic taking care of travelers and expatriates, there have only been 2 cases of Vivaxmalaria that may have been acquired from within Nepal. We believe that there is no malaria risk in Kathmandu, Pokhara or the mountain trekking areas. This being said, malaria does exist in the southern belt of Nepal (the Terai) and risk is highest in the hot, rainy summer monsoon. Most malaria in Nepal is Vivax (90%) and Falciparum is around 10% but the latest WHO statistics report Falciparummalaria rates of 17 %. There are 12 priority districts for malaria. These higher risk districts are Dandeldhura, Kanchanpur, Kailali, Bardia in the far west; Nawalparasi in central terai; Sindhuli, Mahottari, Dhanusha in east central; Morang, Jhapa and Ilam in far east; and Kavre immediately east of Kathmandu valley. These are called priority districts not only because they have had higher number of malaria cases but because they have had higher rates of Falciparummalaria.
--Essentially management at NMC and at Bayalpata was very similar. No additional things.
I wanted to go through an important key piece of the case. Her splenomegaly…****Massive splenomegaly defined as splenomegaly that reaches to the pelvis or which has crossed the midlineinto the right lower or right upper abdominal quadrants. Narrowed differential: (NEJM 345: 682-687, 2001,NEJM 330:775-781, 1994)Many things that cause splenomegaly but few that cause massive splenomegaly.· INFECTION- Kala azar ( visceral leishmaniasis). Sub-saharan Africa, Asia, Mediterranian, LatinAmerica. Transmitted by sandflies. Hematogenous spread. Macrophages infected- main reservoirs ofinfxn in spleen liver and bone marrow. Latency- 2-8 months. Variable clincial course- Intermittentfevers, pancytopenia, hepatosplenomegaly, elevated IgG-Hypperreactive malarial splenomegaly syndrome (also know as tropcialsplenomegaly syndrome,which results from poorly understood abnormal immunologic response to malarial infection. May due toloss of suppressor cells and an alteration in the raiton of CD4:CD8 lymphocytes.Typically lack parasitemiaand fever on presentation. Requires pancytopenia and IgM elevation for dx. High mortality, and mayrequity lifelong antimalarialtx))- AIDS with MAC infxn,-Echinococcal cysts (rarely)· INFILTRATIVE- Gaucher Disease – lysosomalglucocerebrosidase deficiency. Most common inAshkenazi Jews, adult onset form exists-typically non-neuropathic in adult form)-Niemann-Pick disease- Autosomal recessive lysosomal storage disease. HSM, neuro deficits.Childhood onset· PORTAL HYPERTENSION· HEMATOLOGIC- CML, CLL, Hodgkins, heavy chain diseases, amyloid, POEMS(polyneuropathy,organomegaly, endocrinopathy, M protein, and skin lesions-> usually occurs in ptswith osteosclerotic multiple myeloma ), Waldenstroms, MM, Myelofibrosis , polycythemiavera
No IVquinidine available, no Artesunate available—need to obtain from India. What more could we have done at this stage?
Timeline of events over the next several weeks…
Pedal edema, facial edema
Very difficult decision for a young organization like Nyaya in Achham’s setting. Patient deteriorating—would she survive the trip? If she died in KTM, would it be worse?
Can we really be certain of our diagnosis?
***· INFECTION- Kala azar ( visceral leishmaniasis). Sub-saharan Africa, Asia, Mediterranian, LatinAmerica. Transmitted by sandflies. Hematogenous spread. Macrophages infected- main reservoirs ofinfxn in spleen liver and bone marrow. Latency- 2-8 months. Variable clincial course- Intermittentfevers, pancytopenia, hepatosplenomegaly, elevated IgGLeishmaniasis is transmitted by the bite of infected female phlebotominesandflies. The sandflies inject the infective stage (i.e., promastigotes) from their proboscis during blood meals . Promastigotes that reach the puncture wound are phagocytized by macrophages and other types of mononuclear phagocytic cells. Progmastigotes transform in these cells into the tissue stage of the parasite (i.e., amastigotes) , which multiply by simple division and proceed to infect other mononuclear phagocytic cells . Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral leishmaniasis results. Sandflies become infected by ingesting infected cells during blood meals ( , ). In sandflies, amastigotes transform into promastigotes, develop in the gut (in the hindgut for leishmanial organisms in the Viannia subgenus; in the midgut for organisms in the Leishmania subgenus), and migrate to the proboscis .
Bwh morning report
17F with fever, anemia and splenomegaly<br />A case from<br />Bayalpata Hospital (Nyaya Health) Achham, Nepal<br />
Initial presentation on Oct. 7, 2010<br />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.<br />PMH: Spontaneous abortion of a 3 month old fetus 1 year ago <br />Medications: None. No discharge summary or referral letter was received from the government district hospital so we do not know what she received there. <br />Allergies: NKDA<br />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.<br />
Nyaya Hospital, Bayalpata<br />Government District Hospital, <br />Mangalsen<br />
Physical Exam<br />Vitals: T 99, HR 120, BP 90/50, RR 22<br />General: Thin, very pale<br />Skin: No jaundice<br />HEENT: No icterus, PERRLA, EOMI<br />Heart: faint, tachycardic, regular rhythm, no audible MRGs<br />Lungs: CTAB<br />Abd: Splenomegaly up to the umbilicus. No hepatomegaly. Non-tender, non-distended. +BS.<br />Ext: No clubbing, cyanosis, edema, no peripheral stigmata of endocarditis<br />No notable LAD<br />
Management at Bayalpata<br />IV fluids<br />Ceftriaxone<br />Metronidazole<br />Ranitidine <br />Ferrous sulfate<br /> <br />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. <br />At this time, per recommendation of clinicians, family elected to transfer patient to a higher centerSeti Zonal HospitalNepalgunj Medical College<br />
Nepalgunj Medical College<br />Further Diagnostic Tests on Oct. 9, 2010<br />PT:18sec (normal 13 sec), INR:1.5<br />Hb: 4.5, WBC:2,300 N63 L32 E04, Platelet Count: 45,000<br />ESR:130<br />Malaria smear: Positive<br />Glucose: 104<br />Normal Urea, Creatinine, Serum Bilirubin, SGPT,SGOT<br />Alkaline Phosphatase:1236 <br />Widal: Negative<br />General Blood Picture: Pancytopenia, P. Vivax<br />Abdominal ultrasound: Hepatosplenomegaly and Mild Collection seen in Uterine Cavity<br />Normal Urine<br />Blood Group: AB +ve<br />
Management at NMC<br />Treated for Benign Tertian Malaria with Chloroquine and Primaquine<br />Also given IV Ceftriaxone<br />Transfused with 3Units of blood, Hb 4.57<br />Discharge paperwork mentioned “Pancytopenia Cause????”<br />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. <br />What else would we have done in Boston?<br />
Readmission to Bayalpata on Oct. 25<br />She is still having fever with chills and rigors. <br />Vitals: T 104.0 F, HR 112, BP 110/80, RR 20, weight 36 Kg <br />Hb: 6.1 gm/dl , WBC:2500 per cubic mm ( Manually) <br />Blood glucose: 96 mg/dl , Creatinine: 0.6 mg / dl, BUN: 8 mg/dl , Na+: 133 mmol/L , K+:4.2 mmol/L <br />Serological test for Malaria Parasite (SD Bioline rapid diagnostic tests): Negative <br />Peripheral smear for Malaria Parasite: Negative <br />Peripheral smear: Pancytopenia with no hemolysis<br />HIV: Negative<br />Management: <br />Quinine + Doxycycline (PO)<br />Supportive care<br />
Timeline of Events<br />Oct. 28, 2010: Driven to Doti District Hospital for blood transfusion, Armed Police Force help<br />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.<br />Nov. 8, 2010-Nov. 16th 2010: Patient continues to deteriorate at home as family pursues traditional healing. Multiple visits by Nyaya staff and doctors. <br />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)<br />Nov. 17, 2010: Sent to Doti Hospital for two units of blood. <br />
Patan Hospital, Kathmandu<br />Nov. 22, 2010<br />After many logistical hurdles (cost, transportation, risk of dying en route, who would go with the patient, etc):<br /> driven to Dhangadi (9 hour drive from Achham)<br />boarded a 1 hr 15 min flight to Kathmandu<br />Taken by ambulance to Patan Hospital<br />
Leishmaniasis<br />Vector-borne disease transmitted by sandflies<br />Obligate intracellular protozoa of the genus Leishmania<br />Human infection caused by about 21 of 30 species. E.g. L. donovani, L. infantum, and L. chagasi, L. mexicana, L. braziliensis, L. peruviana<br />Results in 2 main forms of disease, cutaneousleishmaniasis and visceral leishmaniasis (kala-azar)<br />Leishmanial species, geographic location, and immune response of the host determine form of disease<br />
Geographical distribution<br />More than 90 percent of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil<br />Eastern Terai districts of Nepal<br />
Clinical features<br />Fever (can be continuous, intermittent, or remittent and it can recur at irregular intervals)<br />Weight loss<br />Enlarged spleen and liver (usually the spleen is bigger than the liver)<br />Some patients have LAD<br />Patients usually have cytopenias (anemia, leukopenia and thromobycytopenia)<br />An important opportunistic infection in areas where it coexists with HIV<br />
Diagnosis<br />Examination of Giemsa stained slides of the relevant tissue is still the technique most commonly used to detect the parasite.<br />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]<br />
Treatment<br />Pentavalentantimonials, such as sodium stibogluconate (Pentostam) available through the CDC in the US<br />Recently, amphotericin B in its liposomal form has been approved and is now considered to be the drug of choice for visceral leishmaniasis<br />Liposomal drugs high costprevent the use of liposomal drugs in most countries<br />Miltefosine is the sole oral agent that has been shown to be effective<br />
Our patient’s outcome<br />Treatment immediately begun with amphotericin, poor response to infusion (HR 150, RR 50)transferred to ICU<br />Liposomal amphotericin b not available in Nepal, costly to import from India, 80-100K Rupees per dose<br />Vented, transfused, broad spectrum antibiotics<br />DIC<br />Pronounced dead on Nov. 27th morning<br />
Original ArticleSingle-Dose Liposomal Amphotericin B for Visceral Leishmaniasis in India<br />ShyamSundar, M.D., Jaya Chakravarty, M.D., DiptiAgarwal, M.D., MadhukarRai, M.D., and Henry W. Murray, M.D.<br />N Engl J Med<br />Volume 362(6):504-512<br />February 11, 2010<br />
Teaching point #1: Differential for massive splenomegaly<br /><ul><li>Hematologic (Thalassemia major)
Infiltrative (lymphoma, myeloproliferative disorders, Gaucher’s disease)</li></li></ul><li>Teaching Point #2<br />Socio-cultural issues and structural barriers to care in Achham’s setting <br />Use of traditional healers<br />Lack of diagnostic capability <br />Lack of therapeutics, transfusion capacity<br />Difficulty of referral<br />Cost<br />Transportation<br />
Teaching Point #3: Visceral leishmaniasis<br />Organism: Vector-borne disease transmitted by sandflies, obligate intracellular protozoa of the genus Leishmania<br />Clinical features: Fever, Weight loss, HSM, cytopenias<br />Dx: Giemsa stain, rK39 antigen strip test<br />Tx: liposomal amphotericin, antimonials<br />