Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome caused by unregulated immune activation, leading to a "cytokine storm" and multisystem failure. In people living with HIV (PLWH), it is frequently triggered by opportunistic infections like Mycobacterium tuberculosis. This report describes a 28-year-old transgender woman with HIV (on ART, undetectable viral load) admitted with a 20-day history of high fever, diarrhea, and hepatosplenomegaly. Admission labs showed severe pancytopenia (Hb 6.2 g/dL, WBC 1,590/µL, platelets 102,000/µL) and a CD4 count of 164 cells/mm[3]. Investigation revealed extreme hyperferritinemia (peaking at 18,366 ng/mL) and a positive urinary lateral flow urine lipoarabinomannan assay (LF-LAM) test, indicating extrapulmonary tuberculosis (TB). Abdominal CT showed mesenteric and para-aortic lymphadenopathy. Bone marrow biopsy confirmed HLH through frequent hemophagocytosis figures. Despite immediate initiation of antituberculosis therapy (ATT) combined with intravenous immunoglobulin, methylprednisolone pulse, and cyclosporine, the patient developed acute kidney injury and severe hepatitis, progressing to refractory shock and death on the 37th day. This case highlights the diagnostic challenge of HLH due to clinical overlap with sepsis. The LF-LAM test was crucial for rapid TB identification. Although integrated immunomodulation and ATT are recommended, the prognosis remains poor in advanced immunosuppression. High clinical suspicion is vital for early intervention in HIV-positive patients with fever and cytopenias in TB-endemic regions.

We present the case of a 28-year-old male with diarrhea, headache, and significant weight loss. He was diagnosed with HIV in the AIDS stage (CD4: 3 cells/μL), Cryptococcus neoformans meningoencephalitis, and multisystemic tuberculosis. Given the persistence of diarrhea and negative coproparasitological studies, endoscopic studies were performed. Upper digestive endoscopy incidentally showed esophageal erosions coated with fibrin and punched-out ulcers; these findings were identified as herpetic esophagitis by histopathological and immunohistochemical analysis. Treatment with intravenous acyclovir was initiated, followed by oral administration for 14 days. This case highlights the importance of considering herpetic esophagitis in immunosuppressed patients, even in the absence of esophageal symptoms, and emphasizes the value of upper digestive endoscopy with biopsy in the comprehensive diagnosis of HIV/AIDS.

Histoplasmosis is a potentially life-threatening opportunistic fungal infection in patients with advanced human immunodeficiency virus (HIV), particularly in endemic regions such as the Ohio and Mississippi River valleys. Despite advances in antiretroviral therapy, delayed diagnosis, lack of linkage to care, and treatment nonadherence continue to contribute to severe opportunistic infections in individuals with untreated HIV. We present the case of a 43-year-old woman with a 23-year-long history of untreated HIV infection who presented with fever, weight loss, diarrhea, and malaise. Laboratory evaluation revealed a viral load of 327,000 copies/mL and severe immunosuppression with a Cluster of Differentiation (CD4) count of 8 cells/µL, hyponatremia, and elevated liver transaminases. Computed tomography imaging demonstrated extensive mesenteric and retroperitoneal lymphadenopathy. Biopsy of a retroperitoneal lymph node revealed granulomas containing fungal organisms consistent with disseminated histoplasmosis. The patient was initially treated with empiric broad-spectrum antibiotics and intravenous amphotericin B, followed by long-term itraconazole therapy and initiation of antiretroviral treatment, resulting in clinical and immunologic improvement. This case highlights the direct relationship between prolonged untreated HIV infection, advanced immunosuppression, and disseminated histoplasmosis, while underscoring the impact of stigma and barriers to care on delayed diagnosis and disease severity. Early HIV diagnosis, timely linkage to care, and sustained patient engagement remain essential to preventing severe opportunistic infections.

Immune reconstitution inflammatory syndrome (IRIS) is an uncoordinated hyperinflammatory response to latent or de novo active infection in immunocompromised individuals following immune recovery. More specifically, paradoxical IRIS refers to the deterioration of a pre-existing infection, whereas unmasking IRIS can be thought of as the unveiling of a previously undiagnosed infection as immune function reconstitutes. HIV-positive patients with advanced disease who are also coinfected with tuberculosis have a uniquely high risk for this complication once started on highly active antiretroviral therapy (HAART). We present a case of a 58-year-old HIV and tuberculosis (TB)-positive woman from Northern Tanzania who presented to a rural care and treatment clinic (CTC) after a 17-month lapse from HAART. She had previously undergone curative treatment for tuberculosis three years prior, which was also the time of her initial HIV diagnosis and initiation of HAART. She arrived in the clinic cachectic, unwell, and with complaint of malaise and diarrhea. Blood analysis confirmed advanced HIV disease (AHD), and consequently, she was immediately restarted on HAART. Almost three weeks later, she returned to the clinic febrile, severely fatigued, and with grossly evident cervical lymphadenitis. Given her coinfection (HIV and TB positive) history, depleted CD4+ count, new onset of clinical findings, and temporal relationship of symptom appearance from HAART reinitiation, a diagnosis of paradoxical TB-IRIS presenting as TB lymphadenitis was made.

Cryptosporidium parvum and C. hominis possess a remanent mitochondrion called the mitosome, which lacks DNA, the tricarboxylic acid cycle, a conventional electron transport chain, and ATP synthesis. The mitosome retains ubiquinone and iron-sulfur cluster biosynthesis pathways, which require protein import that relies on the membrane potential. It was previously proposed that the membrane potential may be generated by a transhydrogenase (TH) that pumps protons out of the mitosome. This pathway was also proposed to rely on an alternative oxidase (AOX) and type II NADH dehydrogenase (NDH2), which also exists in plants, some fungi, and several protozoan parasites. To examine this model, we determined the location and function of AOX and NDH2 in C. parvum. Surprisingly, we observed that NDH2 was localized to parasite surface membranes instead of the mitosome. Furthermore, a ∆ndh2 knockout (KO) strain was readily obtained, indicating that this protein is not essential for parasite growth. Although AOX exhibited a mitosome-like staining pattern, we readily obtained a ∆aox KO strain, which did not exhibit a difference in MitoTracker, indicating that AOX is likely not involved in membrane potential and is dispensable for parasite growth. The growth of the ∆aox strain was inhibited by the AOX inhibitors, salicylhydroxamic acid and 8-hydroxyquinoline, to the same extent as wild type, indicating that AOX is not the target of these inhibitors in C. parvum. Collectively, our studies indicate that NDH2 and AOX are non-essential genes in C. parvum, supporting an alternative mechanism for maintaining the mitosome membrane potential.

The whole world is undergoing an unprecedented rapid population aging, and the accompanying threat of infectious diseases epidemic among the older people will pose a serious challenge to the national public health.

Cytomegalovirus (CMV) primarily affects immunocompromised individuals and can rarely involve the small bowel, causing deep ulcerations and microperforations. This is most commonly observed in patients with AIDS and CD4 counts below 50 cells/μL who are not receiving antiretroviral therapy (ART). Due to diagnostic challenges and the risk of severe complications, CMV gastrointestinal (GI) disease is associated with high morbidity and mortality. We report the case of a 38-year-old woman from Ecuador, four months postpartum with an unknown cause of infant demise, who presented with a 15-day history of abdominal pain, diarrhea, vomiting, and hypotension. Two exploratory laparotomies revealed multiple small bowel and colonic microperforations requiring bowel resections. CMV leads to both small bowel and colonic perforations primarily through a combination of direct viral cytopathic effects and ischemic injury secondary to vasculitis. Infectious evaluation revealed a new diagnosis of AIDS, and final surgical pathology was positive for CMV. The patient initially recovered from surgery and was started on appropriate systemic therapy, but ultimately left the hospital against medical advice and was noncompliant with ART. She was readmitted three days later with disseminated intravascular coagulation, GI bleeding, multi-organ failure, and disseminated toxoplasmosis. The patient ultimately passed away approximately 45 days after initial presentation. This case underscores the complexities of managing CMV GI disease. Early recognition of immunity status is crucial to broadening the differential to include opportunistic infections. Timely diagnosis and initiation of therapies with good patient compliance could significantly impact outcomes.