Explore UAB

University of Alabama at Birmingham

Gorgas Case 2024-11

Universidad Peruana Cayetano Heredia
We hope you have enjoyed the 2024 series of live cases each week from Peru. The Gorgas Diploma Course runs annually in February and March, and we will be in touch at the beginning of next year's case series. The following patient was seen at the pediatrics inpatient ward of Cayetano Heredia Hospital.
Image for Case 2024-11

History: A previously healthy 6-year-old male patient presented to the outpatient clinic with a 3-month history of disease that started six weeks after experiencing sandfly bites with papular pruriginous lesions on the left cheek and right arm that progressed to painless ulcers and slowly grew (Image A, Image B). He sought medical attention at that time, and with a skin scrape test, a cutaneous leishmaniasis diagnosis was made. The patient received treatment at the outpatient setting of Cayetano Heredia Hospital with one and a half cycles of meglumine antimoniate without marked improvement and was admitted for further management.

Epidemiology: The patient was born and lives in Ancash in a rural area of the district of San Luis, in the highlands of Peru, at an approximate altitude range between 2600 to 3120 meters above sea level. Has no travel history. He lives in a house made of adobe and a dirt floor with his parents and two siblings. His parents are farmers, harvesting vegetables, no animal husbandry. His father had cutaneous leishmaniasis in January this year and healed without treatment. His cousin had cutaneous leishmaniasis last year. When our patient was one year old, he had cutaneous leishmaniasis with a lesion on his right cheek. The rest of his past medical history is otherwise unremarkable.

Physical Examination on admission: HR: 87 bpm, RR: 19 rpm, T: 36.4°C, SatO2: 98% at room air. The patient appeared in a regular general state. His left cheek presented a painless ulcer of 2x2 cm with elevated borders, associated with a cervical painless lymph node of 1cm, and his right arm showed a 2x3 cm lesion of similar characteristics with small nodules to palpation on the surrounding lymphatic chain. The rest of the exam was unremarkable.

Laboratory: Hemoglobin was 14.4 g/dl, hematocrit 43%, Leukocytes were 8800 (Neutrophils 32.9%, Eosinophils 3.5%, Basophils 0.3%, Monocytes 6.1%, Lymphocytes 57.2%), Platelets were 308000. Urea 22 mg/dl, creatinine 0.32 mg/dl, Sodium 143, Potassium 4.26. His AST was 32U/L, ALT 17U/L.

UPCH Case Editors: Carlos Seas, Course  Director / Paola Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director


Diagnosis:
 Cutaneous leishmaniasis

Images for Case 2024-11
image overlay

Discussion: A direct examination of the skin scrape with Giemsa stain showed multiple Leishmania sp. amastigotes (Image C). A leishmanin skin test was not performed, and PCR for speciation was unavailable.

Leishmaniasis is a vector-borne tropical disease caused by parasites of different species of the genus Leishmania. It continues to be one of the neglected infectious diseases associated with significant morbidity and wide geographic distribution, predominantly affecting tropical and subtropical countries in Africa, Asia, and Latin America. Transmission occurs after female sandfly species belonging to Lutzomyia sp. (New World) and Phlebotomus sp. (Old World) genera take a blood meal and inject the promastigote stage of Leishmania sp. through the skin (1).

The three predominant clinical variants are cutaneous, mucosal, and visceral. The most frequent clinical presentation is cutaneous leishmaniasis, with an estimated 1 million new cases worldwide every year (2). Last year (2023), the Peruvian Ministry of Health reported 5257 cases of leishmaniasis, of which 90.02% were cutaneous leishmaniasis and 9.98% were mucocutaneous (3). In Peru, a common species that causes cutaneous leishmaniasis at altitudes between 900 and 3000 meters above sea level is L. peruviana (4).

Cutaneous leishmaniasis is characterized by chronic, painless skin ulcers that progress in size and, in some cases, can heal spontaneously, usually with remnant scarring. Patients can also present with regional lymphadenopathies, satellite nodules, and papules (5). Differential diagnoses include infectious causes such as cutaneous tuberculosis, nontuberculous mycobacteria, sarcoidosis, sporotrichosis, and non-infectious diseases, including basal and squamous cell carcinoma and cutaneous lymphoma (2).

Diagnosis of cutaneous leishmaniasis should be considered in a patient who presents with typical clinical manifestations and a history of epidemiologic exposure. Definitive diagnosis is established with confirmation of the parasite in a sample, usually skin scrape or biopsy, by culture, histology, or molecular analysis such as PCR (5). As in our patient’s case, amastigotes were seen in direct observation of a Giemsa-stained skin scrape sample from the lesions.

The PAHO’s latest guideline (2022) suggests that the prevalence of species in certain areas should be considered, but specific species identification is not required to start treatment. For the pediatric population with cutaneous leishmaniasis, the guideline suggests the use of miltefosine, when it is caused by L. panamensis, L. guyanensis, and L. braziliensis with an efficacy between 63.1% to 82.8%. Pentavalent antimonials are suggested when no other alternative is available, with a reported efficacy of 55.5% to 75%. Also, regarding L. braziliensis and L. amazonensis, intralesional pentavalent antimonials could be used for localized cutaneous leishmaniasis with three or fewer lesions and a maximum of three centimeters in diameter not located on the face or joints. For L. peruviana, more evidence still needs to be established to recommend the best therapy, but the recommendation is a single daily dose of pentavalent antimonials for 20 days (6).

Treatment success can be affected by different factors, such as the parasite species, clinical presentation, and response of the infected individual. Second-line treatments include amphotericin B, pentamidine, or ketoconazole (7). Since being admitted, our patient was started on deoxycholate amphotericin B 0.75 mg/kg/day; due to its toxic renal effects, treatment had to be stopped every other day, and he has so far received a cumulative dose of 14.25mg/kg showing significant improvement of the lesions (Image D, Image E).

References
1. Leishmaniasis [Internet]. Cdc.gov. 2024 [cited July 12, 2024]. Available in: https://www.cdc.gov/dpdx/leishmaniasis/index.html
2. Gurel MS, Tekin B, Uzun S. Cutaneous leishmaniasis: A great imitator. Clin Dermatol. 2020;38(2):140–51. Available in: http://dx.doi.org/10.1016/j.clindermatol.2019.10.008
3. Casos de leishmaniasis, Perú 2000 – 2024 [Internet] Gob.pe. MINSA [cited July 13, 2024]. Available in: https://www.dge.gob.pe/portal/docs/vigilancia/sala/2024/SE04/leishmaniosis.pdf
4. Kato H, Cáceres AG, Seki C, Silupu García CR, Holguín Mauricci C, Castro Martínez SC, et al. Further insight into the geographic distribution of Leishmania species in Peru by cytochrome b and mannose phosphate isomerase gene analyses. PLoS Negl Trop Dis [Internet]. 2019 [cited July 13, 2024];13(6):e0007496. Available in: https://pubmed.ncbi.nlm.nih.gov/31220120/
5. Aronson N, Herwaldt BL, Libman M, Pearson R, Lopez-Velez R, Weina P, et al. Diagnosis and treatment of leishmaniasis: Clinical practice guidelines by the infectious diseases society of America (IDSA) and the American society of tropical medicine and hygiene (ASTMH). Clin Infect Dis [Internet]. 2016 [cited July 13, 2024];63(12):1539–57. Available in: https://pubmed.ncbi.nlm.nih.gov/27941143/
6. Guideline for the treatment of leishmaniasis in the Americas. Second edition. Pan American Health Organization; 2022.
7. Castro M del M, Rode J, Machado PRL, Llanos-Cuentas A, Hueb M, Cota G, et al. Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study. PLoS Negl Trop Dis [Internet]. 2023;17(1):e0011029. Available in: http://dx.doi.org/10.1371/journal.pntd.0011029

 
University of Alabama at Birmingham

Gorgas Case 2024-10

Universidad Peruana Cayetano Heredia
The following patient was seen in our Department of Infectious and Tropical Medicine during the Gorgas Advanced Course in 2024.
Image for Case 2024-10

History: A 22-year-old male presented to the emergency room with a 2-year history of progressive disease following a work injury, where a wooden stick was embedded in his right calf. A year later, the patient developed multiple nodular lesions that progressively grew and fistulized. Later, the patient noticed the elimination of small black grains through these lesions. During the last two weeks, the patient reported pain, erythema, purulent secretion through the sinus tracts, and worsening swelling in the right lower limb, which led to impairment of his daily activities.

Epidemiology: The patient was born and lived in a rural area of Lambayeque on the northern coast of Peru. He works as a farmer, harvesting rice, berries, and asparagus, and frequently comes into contact with stagnant water from the crops. He has no travel history, and his past medical history is otherwise unremarkable.

Physical Examination on admission: HR: 84 bpm, RR: 19 rpm, T: 37°C, BP: 118/70, SatO2: 98% at room air. On physical examination, the patient appeared in a regular general state. The right calf showed marked swelling, erythema, and tenderness, and fistulized nodules and multiple sinuses were suppurating small black grains (Image A, B). No regional lymphadenopathy was noted. The rest of the exam was otherwise unremarkable.

Laboratory: Hemoglobin was 13.8, hematocrit 41.2%, Leukocytes were 10050 (Neutrophils 75%, Eosinophils 0%, Lymphocytes 18%), Platelets were 347000. Glucose 84 mg/dl, urea 17 mg/dl, creatinine 0.92 mg/dl, Sodium 134, Potassium 4.3. His AST was 14 U/L, ALT 11 U/L, AP 86 IU/L, LDH 141 U/L. Total bilirubin was 0.42 mg/dl, direct bilirubin 0.1 mg/dl. CRP was slightly elevated. His HIV and HTLV-1 tests were non-reactive.

UPCH Case Editors: Carlos Seas, Course  Director / Paola Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director


Diagnosis:
 Eumycetoma caused by Madurella mycetomatis with superimposed MRSA infection

Images for Case 2024-10
image overlay

Discussion:  A KOH exam from the black grains revealed thick septate hyphae, some pigmented (Image C, D), and culture-grown Madurella mycetomatis (Image E).

Mycetoma, previously called Madura Foot, is a neglected tropical disease with high morbidity, primarily affecting the barefoot walking population in the tropics and subtropics. It is a chronic inflammatory infection of the skin and subcutaneous tissues, predominantly the foot, caused by fungi (eumycetoma, more common in Africa and India) or bacteria (actinomycetoma, more common in Central and South America) (1). At least 30 fungi species are associated with eumycetoma, but the main agent is Madurella mycetomatis. The classification divides those that produce black grains (most common being Madurella mycetomatis), or whitish grains (Scedosporium boydii, most common being formerly Pseudallescheria boydii). More than 90% of eumycetoma are caused by four agents: M. mycetomatis (most common), M. grisea, P. boydii, and L. senegalensis.

Infection occurs following traumatic inoculation of the causative agent from the soil. The clinical presentation includes a subcutaneous mass, sinus tracts, and grain discharge (2). Lesions are usually painless unless advanced or superimposed with a secondary bacterial infection. Mycetomas have almost no effect on the general condition of the patient, and fever is rare (3). Our patient had a secondary infection that was confirmed after a bacterial culture of the purulent secretion grew methicillin-resistant Staphylococcus aureus.

Although actinomycetoma and eumycetoma have similar clinical presentations, the latter tends to show less inflammation and a less aggressive course, with slower bone invasion. Differential diagnoses include infectious causes such as botryomycosis, actinomycetoma, chromomycosis, and non-tuberculous mycobacterial infection, as well as non-infectious diseases like podoconiosis and malignancies.

To diagnose it, morphologic methods such as direct examination, culture, and histopathology are used to identify genus and species. PCR directly on DNA isolated from grains is also a rapid diagnostic tool (4). Imaging with X-ray, CT, or MRI helps determine the extent of disease. The most common finding is an increase in the volume of the soft tissues (93%), but bone sclerosis and periosteal reactions can be found. The “dot-in-circle sign” in ultrasound and MRI, which consists of spherical hyperintense areas with central hypointense focus, highly suggests a mycetoma. In our patient's case magnetic resonance imaging showed extensive involvement of the fascia and muscle layers, with cutaneous fistulas, with no bone involvement. (Image F). MRI is better for assessing bone destruction, soft tissue damage, and skin sinuses than CT, but it is also an expensive procedure that might delay diagnosis (5,6).

Treatment success relies on early diagnosis and proper medication to prevent further complications. Based on expert recommendations, standard treatment includes combined medical and surgical treatments if needed (7). So far, the most used treatment is itraconazole, usually over at least twelve months. Surgical debridement might be done to improve the medical treatment and to remove the infection source in cases of long-term medical therapy without clinical improvement (8). Untreated cases have severe impairment of quality of life in 60% of patients, amputation in up to 38.5%, and recurrent long-term disease in 31 to 73% of patients affected by eumycetoma. (9)

Our patient was started on itraconazole 200 mg orally twice daily. For the superimposed infection, during hospitalization, he received vancomycin and linezolid and was discharged with TMP/SMX. He has so far completed one month of treatment, with clinical improvement.

References
1. Emery D, Denning DW. The global distribution of actinomycetoma and eumycetoma. PLoS Negl Trop Dis [Internet]. 2020 [cited July 04, 2024]; Available in: http://dx.doi.org/10.1371/journal.pntd.0008397
2. Zijlstra EE, van de Sande WWJ, Welsh O, Mahgoub ES, Goodfellow M, Fahal AH. Mycetoma: a unique neglected tropical disease. Lancet Infect Dis [Internet]. 2016 [cited July 04, 2024]. Available in: http://dx.doi.org/10.1016/s1473-3099(15)00359-x
3. Ahmed AOA, Abugroun ESAM, Fahal AH, Zijlstra EE, van Belkum A, Verbrugh HA. Unexpected high prevalence of secondary bacterial infection in patients with Mycetoma. J Clin Microbiol [Internet]. 1998 [cited July 04, 2024]; Available in: http://dx.doi.org/10.1128/jcm.36.3.850-851.1998
4. Siddig EE, Nyuykonge B, Mhmoud NA, Abdallah OB, Bahar MEN, Ahmed ES, et al. Comparing the performance of the common used eumycetoma diagnostic tests. Mycoses [Internet]. 2023 [cited July 04, 2024] Available in: http://dx.doi.org/10.1111/myc.13561
5. Bahar ME, Bakheet OELH, Fahal AH. Mycetoma imaging: the best practice. Trans R Soc Trop Med Hyg [Internet]. 2021 [cited July 05, 2024] Available in: https://pubmed.ncbi.nlm.nih.gov/33537774/
6. Me AE-B, Fahal AH. Mycetoma revisited. Incidence of various radiographic signs. Saudi Med J [Internet]. 2009 [cited July 04, 2024] Available in: https://pubmed.ncbi.nlm.nih.gov/19370281/
7. Nenoff P, van de Sande WWJ, Fahal AH, Reinel D, Schöfer H. Eumycetoma and actinomycetoma – an update on causative agents, epidemiology, pathogenesis, diagnostics and therapy. J Eur Acad Dermatol Venereol [Internet]. 2015 [cited July 04, 2024]. Available in: https://pubmed.ncbi.nlm.nih.gov/25726758/
8. Elkheir LYM, Haroun R, Mohamed MA, Fahal AH. Madurella mycetomatis causing eumycetoma medical treatment: The challenges and prospects. PLoS Negl Trop Dis [Internet]. 2020 [cited July 05, 2024]. Available in: http://dx.doi.org/10.1371/journal.pntd.0008307
9. Clark JE, Kim HY, van de Sande WWJ, McMullan B, Verweij P, Alastruey-Izquierdo A, et al. Eumycetoma causative agents: A systematic review to inform the World Health Organization priority list of fungal pathogens. Med Mycol [Internet]. 2024 [cited July 05, 2024] Available in: https://pubmed.ncbi.nlm.nih.gov/38935904/

 
University of Alabama at Birmingham

Gorgas Case 2024-9

Universidad Peruana Cayetano Heredia
This is our last Case of the Week for the Gorgas Diploma Course of 2024. Publishing these case reports would not be possible without the assistance of an extremely dedicated group of people. We would like to thank in particular: Dr. Carlos Seas,  Co-Director and Clinical Rounds Coordinator for the Gorgas Courses, Dr. German Henostroza, Co-Director and Dr. Jorge Nakazaki for case selection and coordination of case summaries and images.
We hope you have enjoyed the 2024 series of live cases each week from Perú.
The following patient was seen on clinical rounds in the Social Security Hospital of Cuzco, Peru, during the Gorgas Course in 2024.
Image for Case 2024-9

History: A 62-year-old male patient presented with a 3-month history of productive cough with yellowish sputum and multiple oral lesions. Three months before admission, the patient presented a productive cough with yellowish sputum without hemoptysis or other upper respiratory symptoms. This was associated with the appearance of multiple well-defined painful oral ulcers. Subjective fevers were added one month before admission, predominantly at night. This was associated with a 10kg weight loss.

Epidemiology: The patient was born in a rural town in the highlands of Cusco, Peru. He grew up and lives in the city of Tambopata in the rainforest of Madre de Dios, where he works as a farmer. Twenty years before admission, he was diagnosed with cutaneous leishmaniasis and received incomplete treatment with pentavalent antimonials. Ten years before admission, his wife passed away from complications of pulmonary tuberculosis.

Physical Examination on admission: BP: 85/60, HR: 98x’, RR: 37x’, T°:36°C. The patient looked cachectic with marked skin pallor. He had well-defined ulcers in the hard palate, but no skin lesions were noted. On auscultation, he had diffuse rhonchi and fine crackles in both lung fields. An umbilical hernia was found with no signs of incarceration. The rest of the exam was within normal limits.

Laboratory: Hemoglobin was 14.8 mg/dL, leucocytes 6180 cells/mL with 4040 neutrophils, 120 eosinophils, no basophils, no monocytes, and 1380 lymphocytes. Platelets were 397 000/mm3. Urea was 36 with a Creatinine of 0.8 mg/dL. AST and ALT were 27 and 37 U/L, respectively. Sodium was 139 mEq/L, potassium 3.6 mEq/L, chloride 109 mEq/L. An ABG revealed a pH of 7.46, pC02 24 mmHg, bicarbonate 17 mmol/L, pO2 55 mmHg, and SpO2 82%. A lumbar puncture revealed an opening pressure of 16 cmH20, 1 lymphocyte, no RBCs, and glucose of 44 with serum glucose of 90. CSF in VDRL, India ink, and Cryptococcal latex agglutination assay were negative. Blood cultures for aerobic and anaerobic bacteria were negative. Acid-fast bacilli (AFB) stains and mycobacterial cultures on sputum, stools, and urine were negative. A peripheral blood smear did not reveal intraerythrocytic organisms. Serologies for HIV, hepatitis B, hepatitis C, and syphilis were negative. An HTLV-1 ELISA was positive. A chest X-ray revealed diffuse and bilateral alveolar and interstitial infiltrates (Images A and B). A brain CT did not reveal focal lesions. A chest CT revealed diffuse nodular and interstitial hiperdensities with discrete pulmonary cavitations in both lung fields (Images C and D).
Samples were collected from the patient's oral ulcers and sputum. India ink stain, KOH, and culture tests were conducted on both samples. The India ink stain of the ulcer and sputum is provided below, showing round structures (Image E).

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE}


Diagnosis:
 Disseminated cryptococcosis in an HTLV-1-infected patient.

Discussion:  India ink stain, KOH, and culture showed positive results for Cryptococcus neoformans. The diagnosis of Cryptococcal disease can be suspected through clinical and radiological findings. The confirmatory diagnosis relies on direct microscopy using specific cultures in fungal media, antigen detection, or histopathologic identification. India ink stain is an effective method for diagnosis in advanced HIV patients with a sensitivity of 80%. In non-HIV patients, this decreases to 50% (1). Silver stains allow for the identification of histopathological samples, revealing the typical 5-10 micron-diameter encapsulated yeasts with narrow-based budding. Cryptococcus spp can grow on fungal and bacterial media with a turn-around time of 3-7 days in untreated patients (2). Antigen detection is a rapid and extremely accurate diagnostic method for invasive cryptococcal disease. Cryptococcal antigen (CrAg) detection by latex agglutination has a sensitivity and specificity higher than 90% (3). This test allows titer quantification, which is relevant for monitoring and prognosis. A rapid lateral flow assay (LFA) is a simple test recently introduced to clinical practice with exceedingly good test characteristics (4). Our patient's diagnosis was confirmed after an India ink stain and sputum culture returned positive.

Cryptococcal disease causes 250,000 deaths annually, affecting mostly HIV-infected patients. Surprisingly, the mortality attributable to cryptococcosis is higher in non- HIV infected compared to HIV- infected patients (5). Pulmonary disease can range from asymptomatic infection to life-threatening acute respiratory distress syndrome. Radiographic characteristics include lobar radio-opacities, single or multiple non-calcified pulmonary nodules, and cavitary lesions (6). Oral mucosal lesions are exceedingly rare. The cases described have resulted from hematogenous spread from primary lung or CNS infections. The co-existence of pulmonary and oral mucosal lesions should raise suspicion for other infectious agents such as disseminated progressive histoplasmosis, disseminated paracoccidioidomycosis, and for non-infectious etiologies such as non-Hodgkin lymphomas and metastatic squamous cell head and neck carcinomas.

HTLV-1 is the first retrovirus described, affecting around 5-10 million people (7). The most common transmission routes are through contaminated blood products and vertically through breastfeeding (8). Most patients remain asymptomatic. A minority can present autoimmune manifestations such as tropical spastic paraparesis (HAM/TSP), malignant complications such as adult T-cell leukemia/lymphoma (ATL), and infectious complications such as crusted scabies, tuberculosis, and strongyloidiasis. The association of HTLV-1 and Cryptococcus spp. has been previously reported. Case reports from Asia and the Caribbean have described mainly pulmonary disease. Interestingly, case reports from Latin America have shown mainly meningeal involvement. (9,10). Disseminated infection was confirmed in our patient after a positive India Ink stain from the oral ulcers was found.

Treatment of disseminated cryptococcosis is based on an induction and a consolidation phase. The first-line induction phase includes intravenous liposomal Amphotericin B and 5-flucytosine. A recent African RCT demonstrated non-inferiority in single-dose liposomal Amphotericin B compared to a 14-day standard regimen (11). Although liposomal Amphotericin B has a better safety profile than Amphotericin B deoxycholate, it still has significant adverse effects, particularly renal involvement. A new study has proposed oral Amphotericin B tablets, which could improve adherence and decrease hospitalization time and quality of life (12). These new advances are still to be included in international guidelines. Management of HTLV-1 infection still revolves around symptomatic management, early detection of complications, and prevention of disease transmission.

A research group is working on an oral formulation of amphotericin B for leishmaniasis. This could reduce the drug's adverse effects, improve adherence, and ultimately decrease treatment time, hospitalization, and quality of life. The oral formulation of amphotericin B could also be used in the future to treat fungal infections such as cryptococcosis, but more studies are needed. These new advances are still to be included in international guidelines (13).

References
1. Thuy Le, 45 - Systemic Mycoses, Editor(s): Jeremy Farrar, Patricia Garcia, Peter Hotez, Thomas Junghanss, Gagandeep Kang, David Lalloo, Nicholas White, Manson's Tropical Diseases (Twenty-Fourth Edition), Elsevier, 2024, Pages 495-509, ISBN 9780702079597, https://doi.org/10.1016/B978-0-7020-7959-7.00045-2. (https://www.sciencedirect.com/science/article/pii/B9780702079597000452)
2. Nalintya E, Kiggundu R, Meya D. Evolution of Cryptococcal Antigen Testing: What is new? Curr Fungal Infect Rep. 2016 Jun;10(2):62-67. doi: 10.1007/s12281-016-0256-3. Epub 2016 Apr 12. PMID: 27158322; PMCID: PMC4858186.
3. Hevey MA, George IA, Rauseo AM, Larson L, Powderly W, Spec A. Performance of the Lateral Flow Assay and the Latex Agglutination Serum Cryptococcal Antigen Test in Cryptococcal Disease in Patients with and without HIV. J Clin Microbiol. 2020 Oct 21;58(11):e01563-20. doi: 10.1128/JCM.01563-20. PMID: 32848037; PMCID: PMC7587084.
4. Chisale MR, Salema D, Sinyiza F, Mkwaila J, Kamudumuli P, Lee HY. A comparative evaluation of three methods for the rapid diagnosis of cryptococcal meningitis (CM) among HIV-infected patients in Northern Malawi. Malawi Med J. 2020 Mar;32(1):3-7. doi: 10.4314/mmj.v32i1.2. PMID: 32733652; PMCID: PMC7366160.
5. Motoa G, Pate A, Chastain D, Mann S, Canfield GS, Franco-Paredes C, Henao-Martínez AF. Increased cryptococcal meningitis mortality among HIV negative, non-transplant patients: a single US center cohort study. Ther Adv Infect Dis. 2020 Jul 8;7:2049936120940881. doi: 10.1177/2049936120940881. PMID: 32685148; PMCID: PMC7346692.
6. Howard-Jones, A.R.; Sparks, R.; Pham, D.; Halliday, C.; Beardsley, J. Chen S.C.- A. Pulmonary Cryptococcosis.J. Fungi 2022, 8 1156. https://doi.org/10.3390/jof8111156
7. Gotuzzo H, E., Verdonck B, K., González L, E., & Cabada S, M. (2004). Virus linfotrópico humano de células T tipo 1 (HTLV-1): Una infección endémica en el Perú. Revista Peruana de Medicina Experimental y Salud Publica, 21(4), 253–260.
8. Carneiro-Proietti, A. B. F., Amaranto-Damasio, M. S., Leal-Horiguchi, C. F., Bastos, R. H. C., Seabra-Freitas, G., Borowiak, D. R., Ribeiro, M. A., Proietti, F. A., Ferreira, A. S. D., & Martins, M. L. (2014). Mother-to-child transmission of human T-cell lymphotropic viruses-1/2: What we know, and what are the gaps in understanding and preventing this route of infection. Journal of the Pediatric Infectious Diseases Society, 3 Suppl 1(suppl_1), S24-9.
9. Concha-Velasco Fátima, Seas Carlos, Gotuzzo Eduardo, Bustamante B, HTLV-1 and cryptococcosis infection, an underdiagnosed association: Case series and literature review, Open Forum Infectious Diseases, 2024;, ofae022, https://doi.org/10.1093/ofid/ofae022
10. Motoa G, Powers HR, Brumble LM. Disseminated cryptococcosis in a patient with newly diagnosed HTLV-1 infection. BMJ Case Rep. 2021 Jan 28;14(1):e235794. doi: 10.1136/bcr-2020-235794. PMID: 33509855; PMCID: PMC7845708.
11. Jarvis JN, Lawrence DS, Meya DB, Kagimu E, Kasibante J, Mpoza E, Rutakingirwa MK, Ssebambulidde K, Tugume L, Rhein J, Boulware DR, Mwandumba HC, Moyo M, Mzinganjira H, Kanyama C, Hosseinipour MC, Chawinga C, Meintjes G, Schutz C, Comins K, Singh A, Muzoora C, Jjunju S, Nuwagira E, Mosepele M, Leeme T, Siamisang K, Ndhlovu CE, Hlupeni A, Mutata C, van Widenfelt E, Chen T, Wang D, Hope W, Boyer-Chammard T, Loyse A, Molloy SF, Youssouf N, Lortholary O, Lalloo DG, Jaffar S, Harrison TS; Ambition Study Group. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. N Engl J Med. 2022 Mar 24;386(12):1109-1120. doi: 10.1056/NEJMoa2111904. PMID: 35320642; PMCID: PMC7612678.
12. Boulware DR, Atukunda M, Kagimu E, Musubire AK, Akampurira A, Tugume L, Ssebambulidde K, Kasibante J, Nsangi L, Mugabi T, Gakuru J, Kimuda S, Kasozi D, Namombwe S, Turyasingura I, Rutakingirwa MK, Mpoza E, Kigozi E, Muzoora C, Ellis J, Skipper CP, Matkovits T, Williamson PR, Williams DA, Fieberg A, Hullsiek KH, Abassi M, Dai B, Meya DB. Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial. Clin Infect Dis. 2023 Dec 15;77(12):1659-1667. doi: 10.1093/cid/ciad440. PMID: 37606364; PMCID: PMC10724459.
13. Wasan E, Mandava T, Crespo-Moran P, Nagy A, Wasan KM. Review of Novel Oral Amphotericin B Formulations for the Treatment of Parasitic Infections. Pharmaceutics. 2022 Oct 28;14(11):2316. doi: 10.3390/pharmaceutics14112316. PMID: 36365135; PMCID: PMC9697626.

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-8

Universidad Peruana Cayetano Heredia
The 2024 Gorgas Course participants saw the following patient in the pediatrics inpatient ward of Cayetano Heredia Hospital in Lima.
Image for Case 2024-8

History: A 3-year-old male patient with no significant past medical history was transferred from the National Cancer Institute to Cayetano Heredia Hospital with seven weeks of fever, lymphadenopathies, and malaise. Seven weeks before admission, based on the information provided by the patient's mother, the patient had been feeling unwell with a fever of 38.5º C. Although the fever subsided partially with symptomatics, no other systemic symptoms were reported. Four weeks before admission, the fever persisted, and the mother noticed progressive swelling in the left cervical region that was painful to the touch. Three weeks before admission, the mother detected multiple mobile nodes in the neck and groin areas and progressive abdominal distension. On the day of admission, the patient was taken to the local hospital and then transferred to our National Cancer Institute for further evaluation of a presumptive lymphoproliferative disorder.

Epidemiology: The patient was born in Villa Rica, a town in Pasco, in the high jungle of Peru. He has resided in that town for his entire life. His family is involved in coffee harvesting. His mother says he usually accompanies her in her activities, but most of the time, he stays at their humble home, which has basic amenities and a dirt floor. The child mostly eats soups and bananas. He has never traveled outside of his community before.

Physical Examination on admission: HR: 138 bpm, RR: 35 bpm, T: 38.2°C, BP: 90/60, SatO2: 97% (breathing room air). The child appeared to be chronically malnourished and in good hygienic condition. The skin seemed pale and without swelling. A palpable lymph node on the left side of the neck, measuring 8 x 8 cm, was painful to the touch (Image A). Multiple lymph nodes were found in the retroauricular, submandibular, axillary, and inguinal regions, which were mobile and painless. There was mild swelling in the left periorbital region, and no injuries were found in the mouth. The abdomen appeared distended but non-tender. The liver was palpable 5 cm below the costal margin, indicating hepatomegaly. There was also splenomegaly (Image B). Overall, the rest of the examination was unremarkable.

Laboratory: Hemoglobin was 9 mg/dL, and hematocrit was 28 %. WBC was 25100/uL with 0 bands, 17670 neutrophils, 2360 eosinophils, 180 basophils, 1280 monocytes, and 3640 lymphocytes. Platelets were 1 138 000/uL. Glucose 77 mg/dL, Creatinine 0.25 mg/dL. LDH was 326 UI/L. AST was 20 U/L. Sodium was 139 mEq/L, potassium was 4.87 mEq/L, chloride was 100 mEq/L, and ionic calcium was 1.2 mmol/L. HIV was negative. AFB from a gastric aspirate was negative three times. A CT scan from the chest (Image C) showed ground-glass opacities at both bases and reticulo-nodular opacities. Additionally, a CT scan from the abdomen (Image D) confirmed the presence of hepatosplenomegaly. Height-for-age: moderate chronic malnourishment (-3 S.D < Z < -2 S.D). Weight-for-age: moderate acute malnourishment (-3 S.D < Z < -2 S.D)

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE}


Diagnosis:
 Juvenil paracoccidioidomycosis.

Images for Case 2024-8
image overlay

Discussion:  Based on the evaluation of clinical symptoms, epidemiological factors, medical images, and laboratory results, an aspirate biopsy of the neck tumor was decided upon. The results of the aspirate biopsy showed the presence of multiple fungal structures in the shape of a ship's wheel and "Mickey Mouse" with the Gomori-Grocott staining. These findings confirmed the diagnosis of paracoccidioidomycosis (Image E). Additionally, another slide showed chronic necrotizing granulomatous lymphadenitis.

Paracoccidioidomycosis (PCM) is one of Latin America's most common systemic mycoses. It is mainly caused by the fungus Paracoccidioides brasiliensis. This fungal disease predominantly affects individuals in jungle rural areas of Central and South America. The disease is contracted through the inhalation of conidia in the air and is commonly found in male rural workers (1).

It is most commonly contracted during the first two decades of life, with the highest incidence occurring between 10 and 20 years of age. PCM can be present in different forms, such as the juvenile form in our case. The acute/subacute form of the disease, known as the juvenile type, affects both boys and girls equally and has a prevalence of 5% to 25% of cases. It can also affect young adults and those between 30 and 40 (2,3).

The disease takes around four to twelve weeks to evolve and usually affects the lungs, although it can also spread to other parts of the body, such as the skin, mucous membranes, lymph nodes, and internal organs (3). According to several studies, the most commonly reported symptoms are generalized or localized lymphadenopathy, fever, weight loss, hepatosplenomegaly, lytic lesions in bones, jaundice, and cutaneous mucosal involvement. Pulmonary involvement is less common in comparison to the adult chronic form of the disease (4). In laboratory tests, the most frequently found conditions are anemia, leukocytosis with left shift added, and significant eosinophilia in 30% to 50% of cases (5).

Paracoccidioidomycosis is typically diagnosed through clinical evaluation, imaging studies (such as chest X-ray or CT scan), and laboratory tests. The laboratory tests aim to detect the presence of the fungus or its components in specimens such as sputum or tissue samples. These tests are based on identifying the yeasts of Paracoccidioides brasiliensis, which are multi-sized yeasts with multiple budding, in fresh samples, such as sputum, scrapings of skin lesions, or lymph node aspirate. Additionally, observing these yeasts in a biopsy of skin, mucosa, or lymph nodes can also be helpful for diagnosis. For a biopsy, Gomori-Grocott or PAS staining is used. Tests based on identifying antibodies and antigens are also beneficial for diagnosing and monitoring the response to therapy (6).

The usual treatment for fungal infections involves using antifungal medications such as itraconazole or sulfonamides for an extended period. In severe cases, amphotericin B may be used. For mild to moderate forms, itraconazole is the first line of treatment administered for 9 to 18 months, with an average of one year. For severe and disseminated forms, amphotericin B is used for 2 to 4 weeks, followed by an azole for a prolonged period. Trimethoprim/sulfamethoxazole is an option for pediatric patients due to its good bioavailability and syrup formulation (5,6,7).

References
1. Marques SA. Paracoccidioidomycosis. Clin Dermatol. 2012 Nov-Dec;30(6):610-5. doi: 10.1016/j.clindermatol.2012.01.006. PMID: 23068148.
2. Ferreira, M. S. (2009). Paracoccidioidomycosis. Paediatric respiratory reviews, 10(4), 161-165.
3. Romaneli MTDN, Tardelli NR, Tresoldi AT, Morcillo AM, Pereira RM. Acute-subacute paracoccidioidomycosis: A paediatric cohort of 141 patients, exploring clinical characteristics, laboratorial analysis and developing a non-survival predictor. Mycoses. 2019 Nov;62(11):999-1005. doi: 10.1111/myc.12984. Epub 2019 Sep 4. PMID: 31408548.
4. Buccheri R, Khoury Z, Barata LC, Benard G. Incubation Period and Early Natural History Events of the Acute Form of Paracoccidioidomycosis: Lessons from Patients with a Single Paracoccidioides spp. Exposure. Mycopathologia. 2016 Jun;181(5-6):435-9. doi: 10.1007/s11046-015-9976-0. Epub 2015 Dec 19. PMID: 26687074.
5. Shikanai-Yasuda, M. A., Mendes, R. P., Colombo, A. L., Queiroz-Telles, F. D., Kono, A. S. G., Paniago, A. M., & Martinez, R. (2017). Brazilian guidelines for the clinical management of paracoccidioidomycosis. Revista da Sociedade Brasileira de Medicina Tropical, 50, 715-740.
6. Da Silva sh, Grosso Dde M, Lopes JD, et al. Detection of Paracoccidioides brasiliensis gp70 circulating antigen and follow-up of patients undergoing antimycotic therapy. J Clin Microbiol. 2004;42:4480-4486
7. Borges SR, Silva GM, Chambela MC, Oliveira RV, Costa RL, Wanke B, et al. Itraconazole vs. trimethoprim– sulfamethoxazole: a comparative cohort study of 200 patients with paracoccidioidomycosis. Med Mycol. 2014;52(3):303-10.

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-7

Universidad Peruana Cayetano Heredia
The 2024 Gorgas Course participants saw the following patients in clinical rounds at Cayetano Heredia Hospital in Lima.
Image for Case 2024-7

History: A 57-year-old male with no significant past medical history presented to the Emergency Department with a six-day history of malaise, fever, and myalgias. Six days before being admitted, he complained of a fever of 38.5°C, generalized malaise, and calve pain. Symptoms persisted, and four days before admission, he presented jaundice and difficulty breathing. One day later, he began experiencing nausea and vomiting, and his breathing difficulty worsened. On the day of admission, his symptoms persisted, and his difficulty breathing worsened even when at rest. He was taken to the emergency department, where it was decided he should be admitted for further evaluation.

Epidemiology: He was born in Cajamarca, a region in the northern highlands of Peru, and currently resides in Lima. He frequently travels to Cajamarca for personal reasons. He works as a motorcycle taxi driver in Lima and at a vineyard in Lunahuana, a valley in the southern part of Lima. Two weeks before experiencing symptoms, he traveled to Lunahuana and stayed there for two days. During his stay, he entered a water ditch from the river and remained there for four hours on two occasions. While cleaning the ditch, he was not wearing protective clothing, and the water reached his knees.

Physical Examination on admission: BP was 104/76 mmHg, HR was 119 bpm, RR was 23 bpm, and SatO2 was 95% while using a nasal cannula with 5 liters of oxygen. The patient seemed to be in poor overall condition and was breathing rapidly. The skin appeared jaundiced. Crackles were heard in both lungs, mainly at the bases. The cardiovascular exam showed tachycardia and no heart murmurs. Edema was observed in the face, both legs and up to the knees (Image A). The rest of the examination was unremarkable.

Laboratory: Hb was 12.7 g/dl; WBC was 21 100 (2% bands, 83% neutrophils, 1% eosinophils, 10% monocytes, 0 basophils, 4% lymphocytes); platelets were 17 000; INR: 1; creatinine 5.52 mg/dl; urea 199 mg/dl; AST 83 U/L; ALT 97 U/L; total bilirubin 25 mg/dl; direct bilirubin 24.2mg/dl; sodium: 147; potassium 6.62; chloride 112; creatine phosphokinase 110; LDH 416 U/L; C reactive protein 1/32 (192); prothrombin time 13.2 seconds; activated partial thromboplastin time 39.1 seconds; INR 1. Urine analysis: protein was 100 mg/dl. A chest X-ray showed no abnormalities (Image B). His condition deteriorated over the next three days, and he developed hemoptysis and needed intubation; blood was aspirated from the endotracheal tube. The chest x-ray at that time shows diffuse bilateral alveolar infiltrates (Image C).

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE}


Diagnosis:
 Weil's disease (severe leptospirosis).

Discussion:  The patient was admitted and began receiving initial treatment with meropenem. Due to the clinical and epidemiological exposure, meropenem was switched to ceftriaxone, and the microscopic agglutination test (MAT) for Leptospira and IgM ELISA was ordered. The IgM ELISA was positive. The baseline MAT was 1/400 for serovar icterohaemorrhagiae, which increased to 1/3200 two weeks later. The patient was then transferred to the special care unit for closer monitoring.

Leptospirosis is a disease caused by the spirochete Leptospira interrogans. It can be transmitted to humans from mammals. Although it is found worldwide, it is more common in tropical and subtropical regions (1). Transmission is possible when the bacteria enter the body through open wounds, eyes, or mouth. It can also happen if humans come into contact with water or soil or consume food or drinks contaminated with infected animal urine (2).

The clinical symptoms of this illness range from a self-limiting acute febrile syndrome with myalgias, which are usually worse in the calves, and conjunctival suffusion, which is the most common manifestation reported by patients. In severe cases, the disease can cause liver failure with jaundice, acute kidney injury, and pulmonary hemorrhage, which is known as Weil's syndrome. Other severe symptoms include other hemorrhagic manifestations and rarer conditions like myocarditis and central nervous system involvement (2).

Liver involvement can range from mild hyperbilirubinemia and transaminasemia to fulminant liver failure. A signature of this disease is the development of intrahepatic cholestasis characterized by the presence of markedly elevated direct bilirubin, which can reach up to 80 mg/dL in the absence of marked elevated transaminases which rarely surpass 200 IU/L(3). Histopathological findings demonstrate marked cholestasis with mononuclear cell infiltration. There is minimal to no hepatocellular necrosis, which is in marked contrast to hepatotropic viral hepatitis and arboviral hepatitis, i.e., Yellow Fever (4).

Kidney involvement is characterized by acute intrarenal kidney injury. Renal biopsies demonstrate a tropism for the renal interstitium with acute interstitial nephritis. Less commonly, immune-complex-mediated infectious glomerulonephritis can develop (5). Of note, acute kidney injury caused by leptospirosis is usually accompanied by hypokalemia, caused by the impairment of sodium reabsorption and the increased distal delivery of sodium and water, which induce potassium wasting (6).

Pulmonary hemorrhage (PH) is a common complication of Leptospirosis, and it is a serious concern because it can significantly increase the mortality rate. Our patient showed signs of blood leakage through the respiratory tract during the endotracheal tube placement, indicating the presence of PH. Invasive ventilation is often necessary to manage PH, just like our patient received (7, 8).

Leptospirosis is a disease that usually goes away without any medication. For people with mild symptoms, take doxycycline 100 mg orally twice daily for seven days, or azithromycin 500 mg once daily for three days is recommended. For adults who need to be hospitalized, using penicillin 1.5 million units IV every six hours, doxycycline 100 mg IV twice daily, ceftriaxone 1 to 2 g IV once daily (as in the case of our patient), or cefotaxime 1 g IV every six hours, is described. In severe cases, antibiotic treatment lasts for seven days, and patients may also require supportive care such as renal replacement therapy, ventilatory support, and blood products (9). Additional measures such as the use of steroids, plasma exchange, and extracorporeal membrane oxygenation in patients with PH have been used, but there is a lack of evidence of beneficial effects.

Our patient was treated with a 10-day course of ceftriaxone and needed hemodialysis and mechanical ventilation. He recovered uneventfully and is being followed up at our outpatient clinic.

References
1. Rajapakse S. Leptospirosis: clinical aspects. Clin Med (Lond). 2022 Jan;22(1):14-17. doi: 10.7861/clinmed.2021-0784. PMID: 35078790; PMCID: PMC8813018.
2. Crecelius EM, Burnett MW. Leptospirosis. J Spec Oper Med. 2020 Winter;20(4):121-122. doi: 10.55460/8YBJ-0DLP. PMID: 33320325.
3. Brito de T, Penna DO, Hoshino S, Pereira VG, Caldas AC, Rothstein W. Cholestasis in human leptospirosis: a clinical, histochemical, biochemical and electron microscopy study based on liver biopsies. Beitr Pathol Anat. 1970;140:345-61.
4. Abdulkader RC, Seguro AC, Malheiro PS, et al. Peculiar electrolytic and hormonal abnormalities in acute renal failure due to leptospirosis. Am J Trop Med Hyg. 1996;54:1–6.
5. Libório AB, Braz MB, Seguro AC, et al. Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury. Am J Trop Med Hyg. 2015;92:611–616.
6. Lim TK, Siow WT. Pneumonia in the tropics. Respirology. 2018 Jan;23(1):28-35. doi: 10.1111/resp.13137. Epub 2017 Aug 1. PMID: 28763150; PMCID: PMC7169137.
7. Fonseka CL, Dahanayake NJ, Mihiran DJD, Wijesinghe KM, Liyanage LN, Wickramasuriya HS, Wijayaratne GB, Sanjaya K, Bodinayake CK. Pulmonary haemorrhage as a frequent cause of death among patients with severe complicated.
8. Leptospirosis in Southern Sri Lanka. PLoS Negl Trop Dis. 2023 Oct 16;17(10):e0011352. doi: 10.1371/journal.pntd.0011352. PMID: 37844119; PMCID: PMC10602373.
9. Charan J, Saxena D, Mulla S, Yadav P. Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials. Int J Prev Med. 2013 May;4(5):501-10. PMID: 23930159; PMCID: PMC3733179.

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-6

Universidad Peruana Cayetano Heredia
The following patient was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2024 Gorgas Course participants.
Image for Case 2024-6

History: A 45-year-old woman arrived at the emergency department with persistent watery diarrhea and abdominal pain that had been going on for four weeks. Four weeks before being admitted, the patient started experiencing diarrhea, which did not contain mucus or blood and happened approximately five to six times a day. Two weeks before admission, the frequency of diarrhea increased to eight to nine times a day, and the patient began to feel weak. She sought medical attention, was given hydration, and was discharged. The patient had been experiencing persistent symptoms for a week before admission. She began to feel moderate to severe colicky abdominal pain, which continued to worsen. On the day of admission, her condition deteriorated further, and she started experiencing crampy muscle pain and tremors in her hands. These symptoms prompted her to seek medical attention at the emergency room, and she was subsequently admitted to the Infectious Diseases service.

Epidemiology: The patient was born in Lima and resides in San Martin de Porres, Lima, Peru. In her medical history, she had pulmonary tuberculosis at the age of five, which was treated successfully with first-line medications. In 2019, she was diagnosed with HTLV-1 after experiencing a condition similar to the current one, and at that time, she was diagnosed with cystoisosporiasis. In 2021, she was diagnosed and treated for syphilis. Her mother has also been diagnosed with HTLV-1, which is a part of the family's medical history.

Physical Examination on admission: BP: 102/72 mmHg; RR: 16 bpm; HR: 120 bpm; T: 36.9 °C; SatO2: 99% on room air. The patient appeared to be in good overall health. Their skin was warm and supple, and her capillary refill was less than two seconds. Breath sounds were audible in both lungs, and no crackling sounds were detected. The patient was tachycardic, but no heart murmurs were present. Her abdomen had normal bowel sounds, was soft and not tender, and showed no signs of enlarged organs. During the neurological examination, the patient was alert and oriented to time, place, and person, with a GCS score 15/15. No signs of meningitis or focal neurological issues were noted.

Laboratory: The patient's hemoglobin was 10.6 mg/dL. The WBC count was 15,330/mm3, with 3500 neutrophils/mm3, 80 eosinophils/mm3, 90 basophils/mm3, 820 monocytes/mm3, and 10,840 lymphocytes/mm3. The platelet count was 241,000/mm3. Hypokalemia was observed with a potassium level of 3.18 mmol/L, while sodium (141 mmol/L) and chloride (99 mmol/L) levels were normal. Albumin level was 3.78 g/dL, and C-reactive protein was negative. The patient's serum creatinine level was 0.78 mg/dL. Liver function showed mild elevation of transaminases, with AST 109 U/L and ALT 82 U/L. The glucose level was 98 mg/dL. Hypercalcemia was detected, with a level of 11.5 mg/dL (ionic calcium 1.57 mmol/L). The HIV test was negative. The chest X-ray was normal (Image A).

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE}


Diagnosis:
 Acute phase of Adult T - Cell Leukaemia/lymphoma

Image for Case 2024-6

Discussion: After being hospitalized, the patient underwent an extensive diagnostic workup. A stool ova and parasite test using modified acid-fast staining showed the presence of Cystoisospora belli (Image B).

A peripheral blood smear (Image C) showed lymphocytosis, with 50% atypical lymphocytes and 5% flower cells. Based on these test results, the patient was diagnosed with acute adult T-cell leukemia/lymphoma.

HTLV-1 is a single-stranded RNA retrovirus belonging to the Retroviridae family and the Deltaretroviridae genus. It was first discovered in 1979 and affects approximately 5-10 million individuals globally, especially those in tropical and subtropical regions like South America, Central America, Japan, and West Africa.(1)

HTLV-1 can spread through three main routes: vertical transmission through breast milk, sexual contact, and parenterally. The most common transmission route associated with the development of ATL is vertical transmission through breast milk. This retrovirus is associated with infectious, inflammatory, and malignant complications.

Around 90% of people infected with HTLV-1 don't show any symptoms. However, in a small minority, developing clinical symptoms can take several decades after infection (2). The symptoms of HTLV-1 can range from mild, such as infectious dermatitis, to more severe, potentially fatal conditions like Adult T-cell Leukemia/Lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The respective risks of developing these conditions are 3% and 5% (2, 3).

Cystoisospora belli infection can cause acute and chronic watery diarrhea in immunocompromised patients. Individuals with HTLV-1 are also at risk of getting persistent parasitic co-infections that include Strongyloides stercoralis and C. belli. The link between HTLV-1 and SS is the most commonly reported and well-documented. However, the possible connection between HTLV-1 and C. belli has not been thoroughly studied beyond case reports (4).

HTLV-1 and Strongyloides stercoralis, a soil-transmitted helminth, share many of the same endemic areas, including almost the entire South American territory. A relationship has been identified between both pathogens in which the frequency and severity of clinical manifestations of one increase in the presence of the other. Patients coinfected with HTLV-1 and SS develop ATL earlier than non-coinfected patients (mean age: 39 vs. 70 years) (5). Likewise, coinfected patients develop more frequently disseminated strongyloidiasis and hyperinfection syndrome. Other infectious complications include crusted scabies, tuberculosis, and parasitic chronic diarrhea.

The two main complications associated with HTLV-1 infection are tropical spastic paraparesis (TSP) and adult T-cell leukemia/lymphoma (ATL). TSP is caused by autoimmune reactions, resulting in CNS inflammatory lesions. The condition is characterized by spastic weakness in both lower limbs that worsens over time. Patients may also experience hyperreflexia, urinary retention, constipation, and difficulty walking (6).

On the other hand, ATL is a hematological malignancy that usually emerges 20-30 years after infection. The disease is caused by viral gene products, such as HBZ and Tax protein, which alter the host's protein functions. This leads to the induction of proliferation genes, inhibition of apoptosis, and repression of genes controlling the cell cycle, among other things. ATL is classified depending on its clinical presentation in aggressive forms (acute and lymphomatous) and non-aggressive forms (chronic and smoldering). The acute form, such as this case, of ATL, is the most common and presents with nodules, ulcerative lesions, generalized papular rash, lytic bone lesions, and lung infiltrates. Furthermore, atypical T cells, named flower cells due to their nucleic pattern, can be found in the blood smear (7).

Chemotherapy or antiviral treatment is usually the first choice of treatment for aggressive types of ATL, such as acute or chronic with unfavorable features. For smoldering and favorable chronic subtypes, antiviral treatment or watchful waiting is an appropriate first-line treatment. In severe cases, allogeneic stem cell transplantation may be required. Ultraviolet radiation can be used to treat skin lesions (8,9). For our patient's case, chemotherapy was prescribed using drugs such as cyclophosphamide, doxorubicin, vincristine, and prednisone, which is known as the CHOP regimen.

References
1. Gessain A, Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Vol. 3, Frontiers in Microbiology. Frontiers Research Foundation; 2012.
2. Murphy EL, Figueroa JP, Gibbs WN, Lofters WS, Camp Bell M, Goedert JJ, et al. Modeling the risk of Adult T- Cell Leukemia/ Lymphoma in Persons infected with Human T- Lymphotropic Virus Type I. Vol. 43, Int. J. Cancer. 1989.
3. Orland JR, Engstrom; J, Fridey ; J, Sacher ; R A, Smith ; J W, Nass ; C, et al. Prevalence and clinical features of HTLV neurologic disease in the HTLV Outcomes Study. 2003.
4. Nakazaki JCF, et al. Cystoisospora Belli Infection in HTLV-1 Patients and Progression to Acute T-Cell Leukemia. Virol Immunol J 2024, 8(1): 000344. DOI: 10.23880/vij-16000344
5. Plumelle Y, Gonin C, Edouard A, Bucher BJ, Thomas L, Brebion A, et al. Effect of Strongyloides stercoralis Infection and Eosinophilia on Age at Onset and Prognosis of Adult T-Cell Leukemia [Internet]. Vol. 107, Original Article) Am J Clin Pathol. 1997. Disponible en: http://ajcp.oxfordjournals.org/
6. Nakamura T. HAM/TSP Pathogenesis: The Transmigration Activity of HTLV-1-Infected T Cells into Tissues. Pathogens. 2023 Mar 21;12(3):492. doi: 10.3390/pathogens12030492. PMID: 36986415; PMCID: PMC10057245.
7. Phillips AA, Harewood JCK. Adult T Cell Leukemia-Lymphoma (ATL): State of the Art. Curr Hematol Malig Rep. 2018 Aug;13(4):300-307. doi: 10.1007/s11899-018-0458-6. PMID: 30047026.
8. Mehta-Shah N, Ratner L, Horwitz SM. Adult T-Cell Leukemia/Lymphoma. J Oncol Pract. 2017 Aug;13(8):487-492. doi: 10.1200/JOP.2017.021907. PMID: 28796966; PMCID: PMC6366298.
9. Durer C, Babiker HM. Adult T-Cell Leukemia. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558968/

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-5

Universidad Peruana Cayetano Heredia
The following patient was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2024 Gorgas Course participants.
Image for Case 2024-5

History: A 33-year-old female patient with no significant medical history presents to the emergency room with pleuritic chest pain and a four-year history of non-productive cough. Four years before admission, the patient developed a nonproductive cough. Occasionally, she experienced a salty taste in her mouth when coughing. The cough persisted for the next three years without any other accompanying symptoms. One year before being admitted, she noticed blood-tinged sputum during coughing and decided to travel to Lima to seek medical attention. The surgeon informed her that her condition required surgery; however, she declined to undergo the procedure. One week before being admitted, she began experiencing constant pleuritic chest pain, for which she went to the Emergency Department at Cayetano Heredia Hospital, where she was admitted. The patient did not experience shortness of breath or any other respiratory symptoms.

Epidemiology: The patient was born in Huancavelica, Junín, in Peru's central highlands. At the age of 13, she moved to La Oroya, Junín, and then, at 18, she proceeded to move to Huancayo, another city in the central mountains of Peru. She traveled to Huancavelica and Huancayo to visit her relatives last year. The patient is a housewife, and throughout her life, she has lived on a farm with her family, where they raised cows, pigs, sheep, horses, dogs, and cats. Additionally, the family fed the dogs the entrails of dead cattle. The patient resides in Huancayo, where her home has all the essential resources, such as water, drainage, and electricity. There is no known contact with tuberculosis. She states that her diet is standard, including occasional raw seafood such as ceviche and unpasteurized cheese.

Physical Examination on admission: BP: 113/75 mmHg; RR: 18; HR: 85; T: 36.9 °C, Sp02 98% on room air. The patient seems to be in a stable condition and doesn't appear to be in any acute distress. She is a well-built, well-nourished, and healthy-looking lady. There are no skin rashes. No signs of lymphadenopathy. There is decreased mobility while breathing on the right hemithorax, decreased breath sounds, and dull percussion in the base of the right lung. Her abdomen has normal bowel sounds, is soft and non-tender, and there's no organomegaly. The neurological exam shows a Glasgow Coma Scale (GCS) of 15/15, with no focal deficits or meningeal signs. The rest of the exam appears normal.

Laboratory: Hemoglobin was 13.6, and hematocrit 41%. WBC was 8700/uL with 0 bands, 4640 neutrophils, 250 eosinophils, 30 basophils, 470 monocytes, and 3310 lymphocytes. Platelets were 269000/uL. Glucose 125 mg/dL, Creatinine 0.85 mg/dL. PT was 13.9 sec, and PTT was 38.1 sec. Albumin was 4.6 g/dL. Sodium was 139 mEq/L, potassium was 4.23 mEq/L, and chloride was 100 mEq/L. A chest X-ray and CT scan were performed a year before the admission. On the chest X-ray, a well-defined round radiopacity was observed in the lower lobe of the right lung (Image A). CT scan is consistent with the findings on the chest X-ray (Image B).

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE}


Diagnosis:
 Lung and liver cystic hydatid disease caused by Echinococcus granulosus.

Images for Case 2024-5
image overlay

Discussion: Hydatid cysts can be easily identified through their distinct radiological features on an X-ray or CT scan. The appearance of the cyst may differ depending on the stage of development and the organ involved. Generally, hydatid cysts appear as well-defined, round, or oval cystic lesions on an X-ray or CT scan, as this patient showed (Images A and B). These cysts are filled with fluid and have a thin, smooth wall. Daughter cysts (smaller cysts found inside the main cyst) may also be present and usually appear as structures separated by septa within the main cyst. This patient’s CT scan showed it (Images C and D). [1, 2] The diagnosis of lung and liver cystic hydatid disease was made based on the image's findings and the clinical-epidemiological presentation.

Human echinococcosis, or hydatid disease, is a parasitic illness caused by tapeworms of the Echinococcus genus. Echinococcus granulosus is the most common type of tapeworm responsible for this disease. [3] These tapeworms are carried by definitive hosts like dogs and other canids in a subclinical form. Initially, humans are asymptomatic, but as the larvae grow and form cysts in vital organs such as the liver and lungs, the illness can become complicated and severe in the future. [4,5]

In about 70% of cases, parasitic infection is found in the liver parenchyma, followed by the lung parenchyma in order of frequency. Many infections are acquired during childhood but do not cause clinical manifestations until adulthood. The initial phase of primary infection is always asymptomatic, and the signs and symptoms may depend on the organ involved. [6] Symptoms may arise due to mass effects within the organs, such as compression, obstruction, erosion of different structures, or complications, such as rupture with an allergic reaction or secondary bacterial infections. Cyst rupture may occur spontaneously or due to trauma. [7,8]

The diagnosis can be confirmed with a classical image, with a positive serologic test, after aspiration of the contents, or at surgery, demonstrating the presence of protoscolices, hooklets, or hydatid membranes. The patient underwent surgery for the pulmonary hydatid cyst days. According to the chest surgeon’s operative report, the following procedure was carried out: "We performed a right lower lobectomy, during which we discovered a fibrous cyst that occupied 80% of the right lower lobe. The inferior pulmonary vein was found to have firm adhesions, and the right lower lobe was also found to have adhesions to the mediastinum and diaphragm. There were no incidents or complications, and hemostasis was adequate." Biopsies of the pulmonary hydatid cyst were taken, shown below. Image E is a biopsy (H&E stain) of the hydatid cyst. A: acellular laminar layer. B: Protoscolices. C: A detached germinal layer. The adventitia (host tissue) is not visible in this field. Image F is a higher magnification of the previous image showing the protoscolices. Hooks can be seen inside (A).

Cystic echinococcosis treatment depends on the infection site, the lesion's characteristics, and size. All liver cysts, except uncomplicated CE4 and CE5 cysts, require antiparasitics with albendazole +/- praziquantel. Percutaneous aspiration-injection-reaspiration drainage (PAIR) is a safe, effective, and less complex procedure than surgery indicated for CE1 and CE3a cysts larger than 5cm. CE2 and CE3b complicated cysts require antiparasitics and surgical or non-PAIR percutaneous drainage. Extrahepatic cysts require almost universally surgical treatment [9]. The patient is recovering well after surgery, and she is scheduled to undergo surgery for a liver cyst next month.

References
1. Mehta P, Prakash M, Khandelwal N. Radiological manifestations of hydatid disease and its complications. Trop Parasitol. 2016 Jul-Dec;6(2):103-112. doi: 10.4103/2229-5070.190812. PMID: 27722098; PMCID: PMC5048696.
2. Malik A, Chandra R, Prasad R, Khanna G, Thukral BB. Imaging appearances of atypical hydatid cysts. Indian J Radiol Imaging. 2016 Jan-Mar;26(1):33-9. doi: 10.4103/0971-3026.178284. PMID: 27081221; PMCID: PMC4813071.
3. CDC - DPDx - Echinococcosis (2019) Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/dpdx/echinococcosis/index.html (Accessed: 05 March 2024).
4. Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang W, McManus DP. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev. 2019 Feb 13;32(2):e00075-18. doi: 10.1128/CMR.00075-18. PMID: 30760475; PMCID: PMC6431127.
5. Tamarozzi F, Hou A, Morales ML, Giordani MT, Vilca F, Mozo K, Bascope R, White AC, Brunetti E, Chen L, Cabada MM. Prevalence and Risk Factors for Human Cystic Echinococcosis in the Cusco Region of the Peruvian Highlands Diagnosed Using Focused Abdominal Ultrasound. Am J Trop Med Hyg. 2017 Jun;96(6):1472-1477. doi: 10.4269/ajtmh.16-0882. PMID: 28719254; PMCID: PMC5462589.
6. Arezo M, Pacheco de Caldas E, Casas N, Del Grande L, Del Río V, Gavidia C, et al. Prevención y control de la hidatidosis en el nivel local: iniciativa sudamericana para el control y vigilancia de la equinococosis quística/hidatidosis. Centro Panamericano de Fiebre Aftosa. Organización Panamericana de la Salud. Organización Mundial de la Salud. Río de Janeiro: PANAFTOSA - OPS/ OMS; 2017.
7. Gómez-Angulo Montero P, García Galera A, Cañete C, Villarejo Ordóñez A, Núñez Delgado Y, López Martin M, et al. La hidatidosis: epidemiología, manifestaciones radiológicas y complicaciones asociadas. SERAM 2014; S-0240. Disponible en: https://epos.myesr.org/poster/esr/seram2014/S-0240
8. Pedrosa I, Saiz A, Aráosla J, Ferreirós J, Pedrosa C. Hydatid disease: radiologic and pathologic features and complications. Radiographics. 2000;20:795-817.
9. Echinococcosis - World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/echinococcosis (Accessed: 05 March 2024).

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-4

Universidad Peruana Cayetano Heredia
The following patient was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2024 Gorgas Course participants.
Image for Case 2024-4

History: A 22-year-old female without any significant past medical history presented to the ED with a 3-day history of fever, headache, and arthralgias. Three days before admission, the patient presented abrupt onset fever quantified at 40 °C and pulsatile retro-orbital headache. She attended the ED, where she received IV fluids and antipyretics and was discharged home. Two days before admission, severe arthralgias and abdominal pain associated with nausea and vomiting were added. On the day of admission, she noticed abnormal vaginal bleeding and bloody stools, for which she attended the ED at Cayetano Heredia Hospital and was admitted.

Epidemiology: The patient is a native of a northern Lima, Peru district, where she lives with her parents and brother. Their house is in front of a park that gets watered every night, leaving water ponds until the next day. Her last trip was six months ago to Ica, located in the southern part of the Peruvian coast. Two weeks before her admission, her mother and brother experienced fever and headaches for approximately five days, which resolved spontaneously. Several neighbors had recently presented with a similar clinical syndrome.

Physical Examination on admission: BP: 100/60 mmHg, HR 114, RR 18, Sat02 96% on room air, T 39.8 C (103.6 F). The patient has widespread blanching erythema, primarily in the front of the chest, abdomen, and back (Image A), but no petechiae or ecchymosis was observed. There was no bleeding from the gums. The chest was normal on auscultation, and the abdomen was tender on palpation. No organomegaly or rebound tenderness was observed. However, bleeding was detected on rectal examination. A tourniquet test was carried out, and it was positive (Image B).

Laboratory: Hb was 13.5 mg/dL and remained stable during her hospitalization. Hematocrit was 42%. Platelets were 150 000 and dropped to a nadir of 62 000 the next day. Leucocytes were 2000 cells/mL with 980 Neutrophils, 0 Eosinophils, 240 Monocytes, and 770 Lymphocytes. A peripheral blood smear revealed decreased platelet count, but no schistocytes or intracellular organisms were noted. PT 13.7, PTT 46.4 with an INR of 1. LDH was 433 IU/L. Urea was 16 mg/dL with a Creatinine of 0.59 mg/dL. Liver chemistry revealed a total bilirubin of 0.3 mg/dL, AST 85, ALT 44, and Alkaline phosphatase 85. A urinalysis revealed no RBCs and 1-2 WBCs. A chest X-ray was performed, which was unremarkable (Image C).

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE

Diagnosis: Dengue with warning signs

Images for Case 2024-4
image overlay

Discussion: The epidemiology and characteristic clinical picture suggested dengue with warning signs as the most likely diagnosis. The diagnosis of dengue in this patient was established after the nonstructural protein 1 (NS1) antigen test returned positive. The NS1 antigen can be detected up to 9 days after symptom onset (1) and is used to establish the diagnosis during the first week of disease with a sensitivity exceeding 90 percent in primary infections (2). Another diagnostic option for early diagnosis is the use of a Nucleic Acid Amplification Test (NAAT) with similar sensitivity and specificity with the added benefit of being able to differentiate the four different serotypes (DENV 1-4) (3), which is relevant epidemiologically and individually because future exposures to different DENV serotypes increase the risk of development of severe dengue. Serological tests are the test of choice in patients more than seven days after symptom onset. Specific IgM antibodies appear 3-5 days after infection and specific IgG 9-10 days after infection (2,4)

The classification of Dengue has experienced significant changes over the years. In 1997, the WHO proposed three categories of severity: Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue shock syndrome (DSS) (4). In 2009, this was reviewed, and a new and still current classification was proposed: dengue without warning signs, which is defined as a febrile syndrome with two or more of the following: nausea/ vomiting, rash, headache, eye pain, muscle ache or joint pain, leukopenia or positive tourniquet test in an epidemiologically compatible patient. Dengue with warning signs: as above plus one or more of abdominal pain or tenderness, persistent vomiting, capillary leak (ascites, pleural effusion), mucosal bleeding, lethargy or restlessness, hepatomegaly or hemoconcentration with rapid thrombocytopenia. Severe dengue: one or more of shock, fluid accumulation with respiratory distress, severe bleeding, AST/ALT ≥ 1000 UI/L, impaired consciousness, or organ failure. Our patient met the following criteria for dengue with warning signs: abdominal pain, persistent vomiting, and mucosal bleeding. (4,5)

Two essential laboratory markers for tracking dengue's progression are hemoglobin (hematocrit) and platelets. The total platelet count and hematocrit/hemoglobin are commonly used for monitoring the disease. Our team constantly followed those labs, as shown in the table below.

The patient experienced bleeding in their gums on the day after being hospitalized, which lasted only one day. On the sixth day of their illness, she developed a rash commonly seen in dengue fever (Image D). This type of rash is characterized by not disappearing when pressed (non-blanching) and may have small areas of normal skin within the rash, referred to as "islands of white in a sea of red." Typically, this rash appears as the fever subsides and lasts for about a week before gradually fading. (6) The patient did not show any fever after the fourth day of their illness, and the rash began to disappear on the ninth day of the disease.

The patient's condition was closely monitored and managed according to WHO guidelines. The treatment of dengue depends on the clinical severity, the patient's comorbidities, and the phase of the disease. The febrile phase lasts between 2-7 days and, after defervescence, can either improve spontaneously or be followed by severe capillary leak and hemorrhage. Afterward, patients who experience capillary leak present reabsorption of the extravasated fluid in the recovery phase, lasting between 48-72 hours. Patients such as the one presented in this case who present Dengue with warning signs should be hospitalized and receive IV crystalloids with close monitoring of their volume status and hematocrit. The patient received hydration with normal saline; her fever was managed with acetaminophen, and her rash was managed with symptomatics. Currently, there are no definitive antiviral medications available for this disease. (7,8)

References
1. Casenghi M, Kosack C, Li R, Bastard M, Ford N. NS1 antigen detecting assays for diagnosing acute dengue infection in people living in or returning from endemic countries. Cochrane Database Syst Rev. 2018 May 21;2018(5):CD011155. doi: 10.1002/14651858.CD011155.pub2. PMCID: PMC6494571.
2. Chaterji S, Allen JC Jr, Chow A, Leo YS, Ooi EE. Evaluation of the NS1 rapid test and the WHO dengue classification schemes for use as bedside diagnosis of acute dengue fever in adults. Am J Trop Med Hyg. 2011 Feb;84(2):224-8. doi: 10.4269/ajtmh.2011.10-0316. PMID: 21292888; PMCID: PMC3029171.
3. Jiang K, Lee JH, Fung TS, Wu J, Liu C, Mi H, Rajapakse RPVJ, Balasuriya UBR, Peng YK, Go YY. Next-generation diagnostic test for dengue virus detection using an ultrafast plasmonic colorimetric RT-PCR strategy. Anal Chim Acta. 2023 Sep 15;1274:341565. doi: 10.1016/j.aca.2023.341565. Epub 2023 Jun 26. PMID: 37455070; PMCID: PMC10291885.
4. World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. New Ed. Geneva: World Health Organization; 2009. PMID: 23762963.
5. Yuan K, Chen Y, Zhong M, Lin Y, Liu L. Risk and predictive factors for severe dengue infection: A systematic review and meta-analysis. PLoS One. 2022 Apr 15;17(4):e0267186. doi: 10.1371/journal.pone.0267186. PMID: 35427400; PMCID: PMC9012395.
6. Huang HW, Tseng HC, Lee CH, Chuang HY, Lin SH. Clinical significance of skin rash in dengue fever: A focus on discomfort, complications, and disease outcome. Asian Pac J Trop Med. 2016 Jul;9(7):713-8. doi: 10.1016/j.apjtm.2016.05.013. Epub 2016 May 30. PMID: 27393104.
7. Schaefer TJ, Panda PK, Wolford RW. Dengue Fever. 2022 Nov 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 28613483.
8. Tayal A, Kabra SK, Lodha R. Management of Dengue: An Updated Review. Indian J Pediatr. 2023 Feb;90(2):168-177. doi: 10.1007/s12098-022-04394-8. Epub 2022 Dec 27. PMID: 36574088; PMCID: PMC9793358.

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-3

Universidad Peruana Cayetano Heredia
The following patient was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2024 Gorgas Course participants.
Image for Case 2024-3

History: A 70-year-old male patient with a past medical history of essential hypertension treated with Losartan 50 mg QD attended the outpatient dermatology clinic after three years of multiple non-painful, pruritic, erythematous circular plaques on the anterior part of the thorax, abdomen, back and legs. Three years before admission, the patient's daughter, during a visit to her father, noticed multiple erythematous, pruritic, non-painful patches on the anterior chest and abdomen. Two years before admission, the lesions progressed to scaly plaques that extended to the back of the trunk and lumbar area. One year before admission, the lesions spread to the extremities. Additionally, he noticed dryness in both eyes and numbness in his hands and feet. Her daughter noticed a partial loss of both eyebrows. The patient came to our outpatient dermatology clinic, where some tests were performed, a diagnosis was made, and treatment began.

Epidemiology: The patient was born in Jaen (Cajamarca), a region in the high jungle of Peru, until he was 55 years old. After that, he moved to Shamboyacu, San Martin, also high jungle, for six years. Then, he has lived in Pampa Hermosa, Loreto (low jungle), until now. Due to his illness, he has moved to Lima. He works as a farmer; he grows yucca and bananas in his village, but before that, he was a cattle rancher and coffee farmer. It is common for these activities to be done without shoes. No known contact with tuberculosis. He states that his diet is standard, including occasional raw seafood such as ceviche and unpasteurized cheese. The patient reports that the same condition he is experiencing was suffered by two people many years ago in the community where he lives, but neither of them developed complications. His current house lacks a water supply and artificial light. He has been in contact with wild animals (armadillos, snakes, monkeys, etc.).

Physical Examination on admission: BP: 128/72, HR: 78 bpm, RR: 17x, T: 37.1 °C, SatO2: 97% at room air. On physical examination, the patient shows a regular general appearance. The skin is warm, slightly pale, and not very elastic. Capillary refill is less than two seconds. There is a presence of multiple circular plaque-type lesions with erythematous edges with a scaly hypochromic center on the anterior surface of the thorax (Image A), back (Image B), and abdomen, predominantly confluent at the level of the anterior surface of the right hemithorax with hypoesthesia. Also, an erythematous, scaly plaque-like lesion with well-defined borders covers the middle and lower third of the anterior surface of both lower limbs, on the anterolateral surface of the left lower limb, and in the dorsal region of both forearms (Image C). Additionally, there is an erythematous, scaly plaque-type lesion in the left anterior region of the neck. Scaly plaques on the face in the zygomatic and perioral areas and bilateral madarosis are also noted (Image D). On neurological examination, the patient is alert and oriented in his three spheres, GCS 15/15. No meningeal signs or signs of focalization. There is hypoesthesia in the central area of the lesions, as well as in both hands and feet. Also, peripheral nerve thickening of the following nerves: right great auricular, and both ulnar, radial cutaneous, common peroneal, and posterior tibial. Decreased muscle strength in the territory of both ulnar, right medial, and left common peroneal nerves. Atrophy of the thenar, hypothenar, lumbricals, and interossei muscles of both hands. There are no corneal reflexes in both eyes. The rest of the examination was unremarkable.

Laboratory: Hemoglobin was 12.6, hematocrit 38%, MCV 90.7, MCH 30.2, MCHC 33.3, Leukocytes were 6700 with 0 bands, 3580 neutrophils, 980 eosinophils, 40 basophils, 540 monocytes, 1560 lymphocytes. Platelets were 190000. Glucose 85 mg/dl, urea 34 mg/dl, creatinine 0.85 mg/dl. PT was 14 sec., PTT was 30 sec., and INR was 1.05. A urine exam revealed 0-3 leukocytes per field, 0-2 red blood cells per field, some epithelial cells, and it was negative for proteins and bacteria. His HIV test and HBsAg were non-reactive. AST was 36 U/L, ALT was 31 U/L, and LDH was 205 IU/L. Total cholesterol was 155 mg/dl, triglycerides were 152 mg/dl, LDL was 90.6 mg/dl, HDL was 34 mg/dl, and VLDL was 30.4 mg/dl. Chest X-ray was reported as having only aortic calcification (Image E).

UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE

Diagnosis: Type I reversal reaction in mid-borderline leprosy. Multibacillary leprosy according to the WHO classification. Mid borderline (BB) leprosy according to the Ridley-Jopling classification.

Images for Case 2024-3
image overlay

Discussion: Leprosy is a disease of peripheral nerves and skin. Leprosy can be diagnosed clinically in any patient with simultaneous skin lesions and sensory loss over the lesions unless there is hyperkeratosis. In this patient, a biopsy was taken from an abdominal lesion, and it showed the epidermis with mild acanthosis and mild spongiosis; the dermis presented a moderate lymphohistiocytic inflammatory infiltrate with a linear pattern with the formation of epithelioid granulomas without necrosis and the presence of multinucleated giant cells (Image F and G) [1].

Skin biopsies, though helpful in determining the extent of involvement, are not essential to diagnosis. The diagnosis of leprosy can be made based on one of three cardinal signs: definite loss of sensation in a pale or reddish skin patch, thickened or enlarged peripheral nerves with loss of sensation or weakness in the corresponding muscles, or the presence of AFB in a slit-skin smear. In higher resource settings, PCR-based assays may improve diagnostic accuracy, but they are not necessary for diagnosis. The clinical picture in the presented patient, then, was sufficient to make a diagnosis of leprosy.

Patients with leprosy are classified as either paucibacillary (PB), if they have negative smears at all sites, or multibacillary (MB), if they have positive smears at any site. The Fite-Faraco stain from our patient was positive for Mycobacterium leprae (Image H). These results are compatible with multibacillary leprosy.

Leprosy, also known as Hansen's disease, is a bacterial infection caused by Mycobacterium leprae, which affects the peripheral nerves, skin, and sometimes other organs. According to the Ridley-Jopling classification, leprosy can present in various clinical forms depending on the host’s immune response against leprosy bacilli [2]. The spectrum of disease ranges from tuberculoid leprosy (TT), in which there are few or no AFB in the lesions, and there is good cell-mediated immunity against leprosy bacilli, to lepromatous leprosy (LL), in which there are many AFB and no cell-mediated immunity, with intermediate (borderline) forms also existing. However, the 2018 World Health Organization (WHO) Guidelines [3] recommend a different classification system when there are no microscopic facilities, which categorizes cases of leprosy only as paucibacillary or multibacillary to guide treatment. Paucibacillary cases present with 1-5 skin lesions, and multibacillary cases have more than five skin lesions. These criteria make it easy to discern between the two types of leprosy and determine the best course of treatment, even when slit-skin smears and biopsies cannot be performed.

According to the Ridley-Jopling classification, this patient can be classified as mid- borderline leprosy (BB). The BB form of leprosy is considered unstable; patients can rapidly upgrade or downgrade toward either the TT pole of the disease or the LL pole. BB leprosy is characterized by multiple asymmetric plaque lesions. The characteristic lesion typically appears as a ring-shaped patch with a well-defined center and sloping outer edges that may look like a doughnut or Swiss cheese (punched-out lesions) [4]. We can see multiple of these characteristic lesions in many images from the present case. (Image A, B, C, D)

Patients with leprosy can present two significant forms of reactions. These reactions can occur at any stage of the disease, even without treatment. In our case, a delayed-type hypersensitivity (type IV) reaction is represented by a type 1 reaction, which is only seen in cases of borderline leprosy. Treatment usually involves anti-inflammatory medications such as corticosteroids to suppress the immune response [5]. For multibacillary (MB) patients, the keystone of the WHO regimen is rifampin in conjunction with daily doses of dapsone and clofazimine. MDT for multibacillary TB comprises rifampin, 600 mg once a month; dapsone, 100 mg/day; and clofazimine, 300 mg once a month and 50 mg/day, for 12 months. Paucibacillary (PB) patients are treated with the same regimen for six months [3].

Based on WHO guidelines, the treatment was started. However, three months later, the patient went to the ER complaining of fatigue and weakness. During the examination, it was discovered that the patient's hemoglobin level was 5.6 g/dL. The anemia was ascribed to G6P-D deficiency, and dapsone was changed for minocycline. Additionally, the patient received a short course of steroids, EPO, and blood transfusion. After a couple of weeks, the patient's hemoglobin level improved to 10 g/dL.

The lesions substantially improved since the diagnosis was made and the treatment began. (Image I).

References
1. Laboratory diagnostics [Internet]. Cdc.gov. 2018 [Cited February 20, 2024]. Available in: https://www.cdc.gov/leprosy/health-care-workers/laboratory-diagnostics.html
2. Britton WJ, Lockwood DNJ (2004) Leprosy. Lancet Lond Engl 363:1209–1219
3. WHO Guidelines for the Diagnosis, Treatment, and Prevention of Leprosy. 2018. Available in: https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf?ua=1
4. Alrehaili J. Leprosy Classification, Clinical Features, Epidemiology, and Host Immunological Responses: Failure of Eradication in 2023. Cureus. 2023 Sep 6;15(9):e44767. doi: 10.7759/cureus.44767. PMID: 37809252; PMCID: PMC10557090.
5. Froes LAR Junior, Sotto MN, Trindade MAB. Leprosy: clinical and immunopathological characteristics. An Bras Dermatol. 2022 May-Jun;97(3):338-347. doi: 10.1016/j.abd.2021.08.006. Epub 2022 Apr 2. PMID: 35379512; PMCID: PMC9133310.>

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-2

Universidad Peruana Cayetano Heredia
The following patient was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2024 Gorgas Course participants.
Image for Case 2024-2

History: A 27-year-old male patient with no significant past medical history presented to the ED with a one-year history of intense low back pain. Twelve months before admission, the disease started with a non-radiating low back pain of moderate intensity that was partially relieved with analgesics. Eleven months before admission, the patient noticed the appearance of a painful mass of approximately 3 x 3 cm in the right and left inguinal region that grew to 10 x 10 cm in a month, for which surgical drainage was performed, revealing 185cc of purulent material which came back negative for Gram stain and bacterial culture. The surgical team considered it non-surgical, so it was drained and washed without finding any apparent source of the infection. The patient was discharged with a course of oral antibiotics. Eight months before admission, the patient noticed a soft, non-erythematous, and slightly painful mass on the lower lateral aspect of the left knee, which impeded ambulation. Two months later, the patient noticed increased volume in the area of the left hip and buttock, associated with pain and limiting movement. The patient also reports an additional mass in the external infrapatellar area of the right knee with similar characteristics to the left knee. The lower back pain increased considerably in the following months, leading him to prostration, which is the reason why he was hospitalized.

Epidemiology: The patient was born and raised in Pucallpa, Ucayali. Recently, they moved to Lima for work purposes. However, he frequently travels back to Pucallpa to trade monkeys. He has a history of epilepsy, which was diagnosed at the age of 5; his last seizure was nine years ago, and he was treated with Valproate and Lamotrigine until 2017. No known contact with tuberculosis. He states that his diet is standard, including occasional raw seafood such as ceviche and unpasteurized cheese.

Physical Examination on admission: BP: 117/66, HR: 100 bpm, RR: 20x, T: 37 °C, SatO2: 98% at room air. During the examination, it was observed that there was a fistula with purulent and bloody drainage in the right iliac fossa, but no rashes were found. Some crackles were heard on the left upper lung during chest auscultation. The abdomen had normal bowel sounds, and although there was mild tenderness in the lower part, no masses were felt. The left lower limb appeared non-swollen in the left hip, left knee, and infra-patellar region with local warmth (Image A), but there were no signs of inflammation. The deformity in the left hip was not painful on palpation. A mass with characteristics similar to the left knee in the right infrapatellar area. During the neurological examination, the patient was awake, oriented in 3 spheres, without meningeal or focal signs. He had preserved sensitivity in both lower limbs. The right lower limb had slightly decreased muscular strength, but reflexes were normal. In the left lower limb, muscle strength and deep tendon reflexes could not be evaluated due to pain. The left lower limb appeared atrophic compared to the right. The rest of the examination was unremarkable.

Laboratory: Hemoglobin was 10.1 mg/dL. Leucocytes 8200 (absolute count: 0 bands, 81.3% segmented, 0.8% eosinophils, 0.8% basophils, 2% monocytes, 15.1% lymphocytes). Platelets were 478 000. Total bilirubin 0.2 (direct 0.1 mg/dL). Alkaline phosphatase 111, ALT 32, AST 27. Urea 11, Creatinine 0.38 mg/dl. Glucose 88. Na 141, K 4.09, Cl 108. HIV Elisa 4th generation, and RPR was negative. HCV was reported as non-reactive. HTLV-1 was reported as reactive. Rose Bengal's test was negative. The rheumatoid factor was negative.

Left knee synovial fluid

Result

Gram

No germs

WBC

900 (80%PMN)

Glucose

138

Proteins

6

Acid-fast bacilli

Negative


Due to the involvement of the lower limbs, it was also decided to perform an x-ray, which showed a moderate degree of periostitis in the left knee with a certain degree of decrease in the joint line of the same knee (Image B). An x-ray was also performed in the lumbar region, which showed lumbar involvement (e.g., decreased lumbar intervertebral space) and destruction of the left coxofemoral joint (hip joint). (Image C) The lumbar findings can be seen better in the CT performed on the patient, where a mass emerges from the psoas muscle and dissects the tissues in the direction of the lower limb. The mass seen on CT is consistent with a psoas abscess. (Image D) In the chest x-ray (Image E), cavitation can be observed in the upper left region, and a few smaller ones appear nearby.


UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator

UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE

Diagnosis: Disseminated tuberculosis.

Images for Case 2024-2
image overlay

Discussion: Our patient needed various tests to reach the diagnosis, and samples from different sites were required. Samples for culture and AFB were collected from different locations, as seen in the table below. TB cultures results from every sample are pending.

Sample

Acid-fast bacilli

Common bacteria culture

Synovial fluid from the left knee

Negative

Negative

Sputum x3

Negative x3

Negative

Left leg abscess (cold abscess)

Positive

Negative

Left psoas abscess

Negative

Negative

Right leg abscess (cold abscess)

Negative

Negative



The acid-fast bacilli of the left cold abscess was positive (Image F). Auramine was positive from the left psoas abscess (Image G). Also, GenXpert MTB/RIF ULTRA from left psoas abscess: MTB was detected, and Rifampicin resistance was not detected.

Then, the diagnosis of disseminated tuberculosis was made in our patient. Tuberculosis is an infection caused by the Mycobacterium tuberculosis. It usually affects the lungs but can also affect other body organs and systems, known as extrapulmonary TB or disseminated tuberculosis (depending on which system the mycobacteria affects). The symptoms and severity of the disease can vary depending on which organs are affected. [1]

The most common site of extrapulmonary involvement are ganglionar and pleural, follow by skeletal depending on the series. Half of skeletal TB being tuberculous spondylitis, also called Pott's disease. Tuberculosis of the hip accounts for around 15% of all cases of osteoarticular tuberculosis and commonly affects people in their second and third decades of life, like our patient in this case. The diagnosis was primarily based on clinicoradiological presentation alone. When radiological changes appear on a plain X-ray, the disease has moderately advanced. [2] Pott's disease causes inflammation of the intervertebral joints and can result in spinal cord compression. Pott's disease may be identified earlier as vertebral osteomyelitis with local complications, such as secondary psoas abscess [3, 4], which commonly result from the spread of Mycobacterium tuberculosis from an adjacent structure, such as the spine or vertebral discs, to the psoas muscle or, less frequently, after blood-borne infection. [5]

Patients presenting with a psoas abscess may experience deep-seated lower back pain, hip pain, and ambulatory difficulties [5]. As the abscess grows, it can compress nearby structures, and cold abscesses may develop. Skin fistulization is uncommon and usually only observed when treatment is delayed. There is much debate over how to treat cold abscesses due to the rarity of the disease. However, prompt diagnosis and treatment can lead to a favorable prognosis [6]. Large psoas abscess can penetrate the sheath and descend to thigh adductors even after percutaneous drainage. Imaging techniques, such as CT scans or MRI, are frequently employed to visualize the abscess and determine its extent. Muscle involvement is typically secondary and caused by an extension from underlying tubercular synovitis and osteomyelitis, direct inoculation from a tuberculous abdominal lymph node, or a hematogenous route [6]. Laboratory tests may include cultures and molecular testing to confirm the presence of Mycobacterium tuberculosis. If left untreated, or if diagnosis and treatment are delayed, tuberculous psoas abscess can lead to complications such as septic femoral head necrosis or fistula formation, as demonstrated in our case. [1, 4] 

It is usually accepted that patients who are HIV positive are at higher risk for developing TB and disseminated TB. In our patient, while no HIV was detected, he was found with Human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is a retrovirus present in diverse regions of the world. Silent transmission occurs, which is associated with unprotected sex, breastfeeding, and blood transfusions. Its transmission is active in many areas, such as parts of Africa, South and Central America, the Caribbean, Asia, and Melanesia. [7] It causes severe diseases in humans, including adult T-cell leukemia/lymphoma (ATL) and an incapacitating neurological disease called HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), besides other afflictions such as uveitis, rheumatic syndromes, and predisposition to helminthic and bacterial infections, like TB among others. [8] This was mainly addressed and observed in a cohort of patients from Lima, Peru, in which there was an association of a history of TB among patients infected with HTLV-1.[9]

The diagnosis and management of extrapulmonary tuberculosis (EPTB) had significant challenges. Typically, symptomatic patients undergo radiologic imaging of the affected organs to guide a more precise diagnostic approach. Fine-needle aspiration or biopsy is often used to initiate effective treatment to obtain extrapulmonary samples for microscopy, histopathology, culture, biochemical/immunological, molecular, and drug susceptibility testing. [4] The sensitivity and specificity of diagnostic tests for EPTB vary widely; however, new molecular-based techniques, such as Xpert MTB/RIF and Xpert Ultra, with a sensitivity of 96 to 97%, facilitate faster and more precise diagnosis. In our patient, tuberculosis diagnosis was confirmed using the GeneXpert MTB/RIF ULTRA from a left psoas abscess, with MTB detected and no detection of rifampicin resistance. [10, 11]

The treatment protocol for extrapulmonary tuberculosis (EPTB) mirrors that of pulmonary tuberculosis (PTB) for both drug-sensitive and resistant cases. However, brain or bone involvement may require longer treatment than the standard regimen. [12] In this specific case, the treatment plan is extended due to bone involvement, resulting in a two-month combination therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by ten months of isoniazid and rifampicin. Patients who do not have a satisfactory response to chemotherapy or those experiencing neurological deficits, cord compression, or spinal instability may require surgical intervention. In this case, which involves cold abscesses, which are typically observed in patients with HIV, debridement or drainage is necessary [10, 11, 12].

References

1. Vasigh M, Karoobi M, Montazeri M, Moradi G, Asefi H, Gilani A, Meshkati Yazd SM. Isolated psoas abscess caused by Mycobacterium tuberculosis: A rare case report. Clin Case Rep. 2022 May 27;10(5):e05823. doi: 10.1002/ccr3.5823. PMID: 35664522; PMCID: PMC9136494.
2. Babhulkar, Sushrut MS, MCh; Pande, Sonali MS, MCh. Tuberculosis of the Hip. Clinical Orthopaedics and Related Research 398():p 93-99, May 2002.
3. Roggeman S., Buyck G., Petrovic M., Callens S., Van Braeckel E. Case report: a student of Asian origin with Pott's disease. Acta Clin. Belg. 2016;71:340–342. doi: 10.1080/17843286.2016.1139318. [PubMed] [CrossRef] [Google Scholar]
4. Maron R., Levine D., Dobbs T.E., Geisler W.M. Two cases of Pott's disease associated with bilateral psoas abscesses: case report. Spine (Phila. Pa.) 2006;31:E561–E564. Doi 10.1097/01.brs.0000225998.99872.7f. 1976. [PubMed] [CrossRef] [Google Scholar]
5. Kabiri EH, Alassane EA, Kamdem MK, Bhairis M, Amraoui M, El Oueriachi F, El Hammoumi M. Tuberculous cold abscess of the chest wall: A clinical and surgical experience. Report of 16 cases (Case series). Ann Med Surg (Lond). 2020 Feb 13;51:54-58. doi: 10.1016/j.amsu.2020.02.001. PMID: 32099646; PMCID: PMC7029049.
6. Malhotra MK. Cold abscess of the anterior abdominal wall: an unusual primary presentation. Niger J Surg. 2012 Jan;18(1):22-3. doi: 10.4103/1117-6806.95481. PMID: 24027388; PMCID: PMC3716239.
7. Gessain A, Cassar O. Epidemiological Aspects and World Distribution of HTLV-1 Infection. Front Microbiol. 2012 Nov 15;3:388. doi: 10.3389/fmicb.2012.00388. PMID: 23162541; PMCID: PMC3498738.
8. Eusebio-Ponce E, Anguita E, Paulino-Ramirez R, Candel FJ. HTLV-1 infection: An emerging risk. Pathogenesis, epidemiology, diagnosis, and associated diseases. Rev Esp Quimioter. 2019 Dec;32(6):485-496. Epub 2019 Oct 25. PMID: 31648512; PMCID: PMC6913074.
9. Verdonck K, González E, Henostroza G, Nabeta P, Llanos F, Cornejo H, Vanham G, Seas C, Gotuzzo E. HTLV-1 infection is frequent among out-patients with pulmonary tuberculosis in northern Lima, Peru. Int J Tuberc Lung Dis. 2007 Oct;11(10):1066-72. PMID: 17945062.
10. Mbuh TP, Ane-Anyangwe I, Adeline W, Thumamo Pokam BD, Meriki HD, Mbacham WF. Bacteriologically confirmed extrapulmonary tuberculosis and treatment outcome of patients consulted and treated under program conditions in the littoral region of Cameroon. BMC Pulm Med. 2019 Jan 17;19(1):17. doi: 10.1186/s12890-018-0770-x. PMID: 30654769; PMCID: PMC6337766.
11. Lee JY. Diagnosis and treatment of extrapulmonary tuberculosis. Tuberc Respir Dis (Seoul). 2015 Apr;78(2):47-55. doi: 10.4046/trd.2015.78.2.47. Epub 2015 Apr 2. PMID: 25861336; PMCID: PMC4388900.
12. Dartois, V.A., Rubin, E.J. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat Rev Microbiol 20, 685–701 (2022). https://doi.org/10.1038/s41579-022-00731-y

{/slide}
 
University of Alabama at Birmingham

Gorgas Case 2024-1

Universidad Peruana Cayetano Heredia
The Gorgas Courses in Clinical Tropical Medicine are given at the Tropical Medicine Institute at Cayetano Heredia University in Lima, Perú. For the 24th consecutive year, we are pleased to share interesting cases seen by the participants that week during the February/March course offerings. Presently the 9-week Gorgas Course in Clinical Tropical Medicine is in session. New cases will be sent by email every Tuesday/Wednesday for the next 9 weeks. Each case includes a brief history and digital images pertinent to the case. A link to the diagnosis and a brief discussion follows.

Carlos Seas and German Henostroza
Course Directors


The following patient was seen on the inpatient ward of Cayetano Heredia Hospital in Lima by the 2024 Gorgas Course participants.
Image for Case 2024-1

History: Six days after returning from Kitwe, Zambia, a 46-year-old male patient with no significant past medical history presented to the ED for evaluation of a febrile illness of 4-day duration. The disease started with high fever accompanied of profuse watery diarrhea, diaphoresis, nausea and vomiting. The following day, diffuse myalgias and arthralgias were added. Two days after, late at night, he attended our ED, where a peripheral blood thin smear was performed, and a presumptive diagnosis of non-severe vivax malaria was made. He was discharged with instructions to return the following day for antimalarial treatment. The next day, the patient returned with extreme generalized weakness, jaundice, somnolence, and dyspnea on exertion, for which he was hospitalized.

Epidemiology: The patient returned for annual vacation to his home country (Peru), from Kitwe, Zambia, 10 days before admission, where he moved 20 years ago due to his work as a hydraulics mechanic. He reports one past malaria episode 6 years before (2018), for which he received Artemeter/Lumephantrine (Coartem®). He denies having ever taken malaria prophylaxis even though it is available for free at his worksite. He is unsure if he received the yellow fever vaccine and denies exposure to freshwater.

Physical Examination on admission: BP: 109/79 mmHg; RR: 30; HR: 125; T: 37.2 °C, Sp02 95% on room air. The patient was in acute distress. The skin exam noted marked pallor and jaundice, but no rash or petechiae were present. On chest auscultation, bibasilar crackles were heard. The abdomen had normal bowel sounds; on palpation, it was soft and non-tender, and mild hepatosplenomegaly was found. The patient was somnolent but oriented with a GCS of 15/15. There were no focal deficits and no meningeal signs. Additionally, a PA chest x-ray was performed and showed mild bilateral pleural effusion and bilateral infiltrates. (Image A).

Laboratory: Hemoglobin was 14 mg/dL, the lowest value was 9.4 mg/dl on day 4. Leucocytes 5100 (absolute count: 0 bands, 3780 segmented, 10 eosinophils, 30 basophils, 510 monocytes, 770 lymphocytes). Platelets 80 000 that dropped to 37 000 on day 2 to normalize on day 8. Total bilirubin 4 (direct 1.5 mg/dL). Alkaline phosphatase 99, ALT 107, AST 61. PT 16.2, PTT 33.1, INR 1.23. Urea 39, Creatinine 0.9 mg/dl that increased to 2.72 mg/dl on day 2 to normalize on day 4. Glucose 152. Na 135, K 3.84, Cl 97. The thin smear (Image B) from the initial ED visit is shown.


UPCH Case Editors: Carlos Seas, Course  Director / Jorge Nakazaki, Associate Coordinator

UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

{slide=CLICK HERE FOR DIAGNOSIS & DISCUSSION OF THE CASE ABOVE

Diagnosis: Severe falciparum malaria.

Images for Case 2024-1
image overlay

Discussion: On review of the original slide from the night visit, multiple RBCs in the same field infected with ring forms (trophozoites) of Plasmodium falciparum (Images B, C) were seen.(1) Some individual RBCs are infected with multiple rings which are delicate in nature and several cells have applique forms (rings touching the edge of the RBC; both these features only occur in P. falciparum. P. vivax rings are larger and thicker with only a single ring per RBC and some more mature forms (schizonts) are seen. Although no % parasitemia was calculated, it is evident from the thin smear that a parasitemia higher than 2% was present. Non-falciparum malaria never has a parasitemia >2%.(2)

Additionally, a Rapid Diagnostic Test (RDT) done after eventual admission corroborated the diagnosis (Image D) and with bands positive for P. falciparum and negative for P. vivax. The choice of RDT depends on the type of infection in the region. If P. falciparum is expected, an RDT distinguishing only P. falciparum from non-falciparum malaria may suffice. An RDT that distinguishes between species is best for areas with multiple parasite types. The RDT utilized in our hospital detected both Pf-specific histidine-rich protein- II (pHRP-II) and Pv-specific lactate dehydrogenase (Pv-LDH) and has a reported sensitivity and specificity for Pf of 91.6% and 97.9%, respectively, when compared to a thin smear (3). The use of HRP-2 as a diagnostic target has been increasingly under scrutiny after multiple reports of HRP-2 gene-deficient Pf strains (4).

Pf may progress quickly to meet severe malaria criteria; only 30 hours elapsed in this patient and due to high transmission intensity should be rigorously ruled out by an experienced expert slide reader in persons exposed in Africa. The night-shift reader may have mistaken the multiply infected RBC as an immature blood schizont. If present schizonts would be compatible with P. vivax.

This patient had criteria for severe malaria, including prostration, hyperlactatemia, and jaundice to accompany his hyperparasitemia. Patients with severe malaria should be offered intravenous artesunate therapy. The latest WHO guidance (5) recommends early transition to oral therapy after clinical stability has been achieved. It is crucial to avoid over-resuscitation with IV fluids since these patients are at risk of capillary leak, which can lead to pulmonary edema and worsen the respiratory compromise. Our patient received IV artesunate therapy for 3 days, with almost complete resolution of symptoms in 24-48 hours and clearance of parasitemia after 12 hours of therapy. This was followed by oral artesunate and mefloquine for 3 days, and before discharge, a single dose of primaquine for transmission interruption was administered according to WHO guidance. Intravenous ceftriaxone to prevent bacteria pneumonia which is commonly seen was started but subsequently discontinued due to negative blood culture results and rapid clinical response. IV artesunate dosing in the US varies in that a switch to oral therapy is allowed after 24 hours is allowed if the parasitemia is less than 1%.

References

1. Malaria [Internet]. Cdc.gov. 2020 [citado el 31 de enero de 2024]. Available in: https://www.cdc.gov/dpdx/malaria/index.html
2. Walker IS, Rogerson SJ. Pathogenicity and virulence of malaria: Sticky problems and tricky solutions. Virulence. 2023.
3. ALam MS, Mohon AN, Mustafa S, Khan WA, Islam N, Karim MJ, et al. Real-time PCR assay and rapid diagnostic tests for the diagnosis of clinically suspected malaria patients in Bangladesh. Malar J. 2011
4. Gamboa D, Ho MF, Bendezu J, Torres K, Chiodini PL, Barnwell JW, et al. A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: Implications for malaria rapid diagnostic tests. PLoS One. 2010 Jan 25;5(1).
5. WHO consolidated guidelines for malaria, 16 October 2023. Available in: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria

{/slide}
 
-->