Gorgas Case of the Week - 2024 Series

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


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

Images for Case 2024-5
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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).

 
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
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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.

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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
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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.>

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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

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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

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