TWiP 256: Amazing antimalarial drug resistance

TWiP solves the case of the pregnant woman from Tanzania with dehydration and 3 weeks of bloody stool, a situation that would confuse Ockam but not Dr. Hickam. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Hero: Dame Bridget Ogilvie (Interview and Wiki) Letters read on TWiP 261 New Case I feel like the back section of our book has been a bit neglected. The new PD 8th Edition is posted on our website so please download a copy and extra points to anyone who can tell us what that is on the cover. Three individuals are involved here with a rather impressive travel history. We have a mom, a daughter and a son who reach out for guidance. Initially one of them found something small dark and about the size of a poppy seed embedded in their skin. This led to a more involved investigation where they found that all three had similar findings but some of these were larger, some a bit larger, one was actually described as mobile. They all feel fine and report no skin rashes. They have a number of concerns about what these are, if they might carry disease, what to do about removing them and should there be testing or treatment. The interesting travel and exposure history. They report that just prior to this they spent a week on a remote island off the coast of Scotland with extensive hiking in tall grass and boggy areas with deer, rabbits, and lots of sheep. An Island called Harris and Lewis and then just that Saturday hiking in wooded areas around Loch Ness and in the Cairngorns. Sunday out hiking and running on Long Island and then Wednesday when these mystery objects were found they had just been hiking and going for a run in Cape Cod. They report on Cape Cod the trail they followed had a fallen tree and they had to crawl underneath it prompting this skin inspection. -lots of questions here…  What might these be and how do we identify them? Is the travel history relevant? Are there any timing issues that impact what we do? Should we try to remove these and if so how? Any testing or treatment indicated? Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP explains how circadian clocks of parasite and vector circadian mediate efficient malaria transmission. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Clocks mediate malaria transmission (Nat Micro) Hero: Dame Bridget Ogilvie (Wiki) Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP solves the case of the man in the Malaysian city of Kucheng who presents with daily fevers and shaking chills, and serve a new clinical puzzle for you to solve. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Letters read on TWiP 259 New Case Another case from Northern Tanzania, up by the border of Kenya. 32 yo pregnant woman admitted to the hospital, dehydrated, reporting 3+ weeks of diarrhea. Second trimester, second pregnancy, reports stools are sticky and it is hard to get herself clean. She also noticed blood mixed in the stool. No fever, no chills, but she feels weak. While many in the area get their water from boreholes, rivers and rainfall she reports getting hers from a nearby river. She lives with her husband and one child who is 2 years old. She is HIV negative and reports she had been in good health otherwise. She looked tired and worn down when she arrived in the hospital but is already feeling better. Her blood work is notable for a low hemoglobin and elevated creatinine. Stool studies are sent and Ockam would be confused but Dr Hickam would know what to do. Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP describes how a gut commensal protozoan influences respiratory disease outcomes by shaping pulmonary immunity, and body shape variation in lice that parasitize diving hosts. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Gut commensal shapes pulmonary immunity (Cell) The deeper the rounder (Sci Rep) Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP solves the case of the man in the Malaysian city of Kucheng who presents with left arm swelling, and presents a new case for you to decipher. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Letters read on TWiP 257 New Case We are still in Kuching, Malaysia in the northern part of the Island of Borneo. This is the Sarawak portion of Malaysia. A man in his late 30s is admitted to the hospital in December with daily fevers that last for several hours and shaking chills. He had previously been healthy with no medical problems. He lives in the city and works in an office, however, in the few weeks prior to getting admitted he was visiting the jungle. Apparently not too far outside of Kuching, one can go up into the jungle and see Orangutans. He had gone into the jungle but this was 2 weeks prior to the onset of symptoms. Since then he reports no unusual exposures. He lives with his wife and children and they are all healthy. A few days prior to admission he noted fever, chills, and a headache. He is a little nauseated but no vomiting. On exam he has a fast heart rate and appears ill. His respiratory rate is increased and he is not febrile on admission but later does have fever.  No enlargement of the liver or spleen on exam. Otherwise unremarkable. His labs are notable for low white blood cells, anemia, and a platelet count of less than 50k per microL. His coagulation studies are abnormal, serum creatinine is elevated, and there is elevation of his serum aminotransferases. Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP explains a study that carries out selection of Plasmodium falciparum in the presence of inhibitors to identify determinants of drug resistance, and a paleoparasitological analysis of a 5th–16th c. CE latrine. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Naegleria fowleri acquired at splash pad (MMWR) Determinants of P. falciparum drug resistance (Science) Paleoparasitological analysis of 5th–16th c. CE latrine (Parasitol) Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

Michelle Labrunda joins TWiP to solve the case of the Georgian in Guinea with fever and dry cough, and describe a new case for you to solve. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Guest: Michelle Labrunda Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Letters read on TWiP 255 New Case A man who is on eculizumab, a recombinant humanized monoclonal antibody that targets complement protein C5 which serves as a terminal complement inhibitor, comes in with left arm swelling. He lives in a city in the north part of the island of Borneo. He is being managed by a doctor in the Malaysian City of Kuching. Now the doctor caring for this man is married to an Infectious Disease expert and she raises concerns that this might be due to a parasitic disease. She is told by the husband that the disease of which she is thinking is not present in the region. She is not swayed and admits him for nightly blood smears which are negative. She then does a rapid immunochromatographic dipstick test that is positive. He lives in a community outside the city and they go to that village and find others with limb swelling issues who are also positive on antigen testing. He is treated with an antibiotic, not antiparasitic for 4 weeks and the arm improves.  Hint: this is not Wuchereria Bancrofti. Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP explains a study which finds that tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei, then remembers our departed colleague Dickson Despommier. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Click arrow to play Download TWiP #254 (88 MB .mp3, 61 minutes) Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Tissue spaces are reservoirs of antigenic diversity for T. brucei (Nature) Understanding trypanosome antigenic variation (Emerg Top Life Sci) Tissue resident T. brucei (PLoS Path) Hero – Dickson Despommier Despommier Photo Art Parasitology Course (YouTube) Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees TWiP explains a study which finds that tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei, then remembers our departed colleague Dickson Despommier. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Tissue spaces are reservoirs of antigenic diversity for T. brucei (Nature) Understanding trypanosome antigenic variation (Emerg Top Life Sci) Tissue resident T. brucei (PLoS Path) Hero – Dickson Despommier Despommier Photo Art Parasitology Course (YouTube) Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP solves the case of the man with somnolence and something extra-erythrocytic, and presents a new puzzle for you to solve. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Letters read on TWiP 253 New Case 26-year-old female with no past medical history.  Patient is from Georgia in the US and is volunteering in Hérico, Guinea (town in the Lélouma Prefecture in the Labé Region of northern-central Guinea). She arrived in Guinea in December  2023.  She was taking doxycycline for malaria prophylaxis and says that she has not missed any doses On October  2024 she presented with fever and dry cough.  Lab work was done and follow up planned for the following day.  The patient slept poorly, was febrile to 104 and had ongoing cough.  The next day she went to the hospital and was evaluated in the ER for acute febrile illness of unclear etiology.   In the hospital, VS were 97.9F, BP 105/70, P 94 Oxy sat 98%, normal physical exam. She was started on Augmentin and Coartem. Pause here to think about the differential at this point and maybe some more history and what testing you might want WBC 14, Hb 13, HCT 40, PLT 285, Neut abs 8, Eos Abso0.80; BUN/creat  normal, AST normal; ALT 44, GGT 125 Stool parasite screen + for some sort of eggs, malaria smear negative, CXR with b/l infiltrates She was given a medication (vomited 30 min after dose received).  She then received a second dose of medication 5 hours after the first) and was discharged. The following day the patient returned to the ER, stating that she felt worse.  Her temperature had climbed to 104 overnight, and she developed watery diarrhea and nausea.  There were no additional episodes of vomiting.  She was given an additional dose of a medication, ibuprofen, and started on ceftriaxone 1 gm IV Q12 hrs.  During the day she continued to have low grade fevers and developed abdominal pain.  That night she was again febrile to 104 F.    She remained admitted for 5 days with ongoing symptoms of diarrhea, nighttime fevers and diffuse abdominal discomfort.  Three more malaria tests were negative (rapid test and slide review) Blood cultures collected – no growth She continued to have mild elevation of WBC and slight elevation of AST and ALT. The patient was transferred to a different hospital. They give her a different medication, and within 24 hours symptoms resolve.  What is the diagnosis and what happened here with management? Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees

TWiP discusses a study of the safety and immunogenicity of a late liver-stage attenuated malaria parasite delivered by mosquito bite. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Live attenuated malaria vaccine (NEJM) Plasmodium metabolism during hepatic development (Cell) Heroes – Jimmy and Rosallyn Carter, and the Carter Center The Carter Center Guinea Worm Eradication Programme Guinea Worm data visualisations (Our World in Data) Become a patron of TWiP  Send your questions and comments to [email protected] Music by Ronald Jenkees