Annex I. Case studies

Splenomegaly and weight loss has to be checked. rK39 can be done if the patient has splenomegaly and weight loss. Another approach can be checking for the platelet count and bleeding risk. If no bleeding tendency and platelet count is >40,000/µl, splenic aspiration can be done. Otherwise, bone marrow aspiration can be done and the tissue aspirate examined by microscopy.

In the first few hours after splenic aspiration is done, patient should be followed for possible complications of splenic aspiration, importantly intra-abdominal bleeding from the spleen. The symptoms mentioned in this patient are most likely due to intra-abdominal bleeding and anemia. Abdominal examination for sign for free fluid (percussion, shifting dullness and fluid trill) should be done. Abdominal ultrasound can show the collection of free fluid. Needle aspiration (paracentesis) can be done and diagnosis confirmed if blood is aspirated.

The patient has to be made to sleep on the side of the spleen (splint), IV line has to be opened, fresh blood and platelet concentrates need to be transfused, abdominal girth followed. Autotransfusion can be done from the hemoperitoneum, however, this blood will not have platelets. Such patients need a lot of platelet concentrate transfusion to recover. Surgery (splenectomy) will not be feasible intervention without adequate platelet transfusion and control of bleeding.

The VL in this patient is confirmed parasitologicaly. rK39 has lower performance in East Africa region (lower sensitivity and specificity). The negative rK39 result in this patient just reflects its lower performance.

VL patients have hypergammaglobulinemia with increased circulating non-specific antibodies that can react and give positive results for different serological tests (like the first HIV RDT in this patient). So it is possible to have a false positive HIV serology test result. On the other hand, the severe immunosuppression may also prohibit production of specific antibodies in response to infections and serology tests can become negative in the presence of the infection (like the second and third) HIV rapid tests in this patients. Discordant serology tests in the serial or parallel testing algorithm with rapid HIV test kits is frequent among VL patients. Thus, more reliable diagnostic kits are recommended.  Or else, it is wise to repeat the tests after the VL is treated and cured.

As this patient has the clinical case definition for VL and is rK39 positive, he has a positive predictive value for VL of 86-93%. He has to be treated for VL. Baseline assessments for organ functions (liver, kidney) should be done to choose safe drugs. The first line regimen for treatment of uncomplicated primary VL is SSG 20mg/kg IV or IM per day for 17 days and Paromomycin 15mg/Kg IM for 17 days.

Patient is HIV co-infected, this is third episode of VL, creatinine is elevated, has severe pancytopenia

There is no proven antileishmania drug or regimen to treat VL relapse and VL in HIV. However, for safety reasons in patients with impaired renal function tests, it is better to avoid paromomycin and antimonials. Thus, ambisome and miltefosine will remain to be the best options for safety. High dose AmBisome (40mg/Kg in 8 divided doses) with or without Miltefosine 50mg BID for 28 days can be used. Patient has to be assessed for parasitological cure at the end of treatment and decision on prolonging the treatment be considered if parasite remain in the tissue aspirate.

Additionally, patient needs ART. It has to be started as soon as the patient is stabilized and ready to start. Renal function may improve with rehydration (patient has diarrhea). TDF-3TC-EFV can safely be started. AZT is not safe as the patient has severe anemia and recovery of anemia may take longer. Co-trimezaxole prophylaxis should be started. 

SSG induced pancreatitis, elevated serum amylase and lipase strengthens the diagnosis.

For persistent symptoms the drugs should be on hold until symptoms resolve and the pancreatic enzymes normalize. Once the symptoms are resolved the medicines can be resumed. If the medicines are interrupted more than three days, doses have to be compensated. If symptoms are severe and persistent requiring more than five days of drug interruption, it is better to change the antileishmania regimen to safe alternatives – ambisome. Prolonged interruption may risk treatment failure and development of resistance. 

This is PKDL. In East Africa region it occurs typically in the first six months of VL treatment. Diagnosis can be confirmed by demonstration of LD bodies on microscopy of scraps from skin lesions. This patient had grade three PKDL on this presentation and needs treatment. Antimonials with 20mg/Kg IV or IM daily dosing for 30 days can be used. However, most patient will need prolonged treatment (~ 2 months).

This patient is a relapse within a short time. Twice treated with SSG and still high parasitemia. Therefore, it is better to change the regimen to alternative option. AmBisome or Ambisome in combination with miltefosine will be better alternative treatment to continue for this patient.

There is no proven vaccine or primary prophylaxis to date. Preventive strategies to be advices for travelers are: clothes should cover the whole body, use bed nets impregnated with insecticides, avoid staying outdoors at dusk and dawn, keep ventilators on during the night in the bed rooms, avoid insect breeding and living sites like cracks of soil, termite hills, bushy and ruin areas.