The study, led by Rhona C. B. Muyise and Samuel Jjunju of the Infectious Diseases Institute at Makerere University, together with collaborators at the University of Minnesota and other institutions, was designed as a post-hoc analysis of a prospective cohort assembled from the ASTRO, AMBITION, ENACT, and FLOOR clinical trials. Of 1,055 participants diagnosed with cryptococcal meningitis across these trials, 787 survived their initial hospitalization and could be followed for more than ten weeks after discharge. This large, carefully characterized population allowed the investigators to measure not only how often rehospitalization occurred, but why it occurred and what it meant for survival—questions that have remained largely unanswered despite substantial advances in the treatment of cryptococcal disease itself.

The technical details of the cohort underscore how profoundly immunocompromised these patients were. The median CD4 cell count at baseline was just 21 cells per microliter of blood, with an interquartile range of 8 to 58—a level of immune depletion at which the body’s defenses against fungal pathogens are essentially absent. Only 45 percent of participants had prior experience with antiretroviral therapy, meaning that more than half were starting HIV treatment for the first time while simultaneously battling a life-threatening fungal infection of the brain and its surrounding membranes. Cryptococcal meningitis is caused by Cryptococcus neoformans and related species, environmental yeasts that people inhale routinely but that cause disease almost exclusively in severely immunosuppressed individuals.

The headline numbers are stark. Within ten weeks of discharge, 17 percent of the 787 survivors—133 patients—were rehospitalized at least once, and 13 percent—101 patients—died. These categories overlapped in important ways: among the 654 participants who did not report rehospitalization, 11.6 percent, or 76 patients, nevertheless died by the ten-week mark without ever returning to hospital. Among the 133 who were rehospitalized, 18 percent, or 25 patients, died during or after that readmission. The median time from initial discharge to rehospitalization was 20 days, with an interquartile range of 10 to 36 days, meaning that half of all readmissions occurred within roughly three weeks of discharge—a period when many patients in resource-limited settings have limited access to follow-up care.

Perhaps the most clinically valuable contribution of the study is its systematic accounting of why patients returned to hospital. The researchers classified the reasons for all 133 rehospitalizations and found that the largest share—92 cases—stemmed from meningitis-related causes: culture-positive relapse of the original cryptococcal infection, paradoxical immune reconstitution inflammatory syndrome, or elevated intracranial pressure. Each of these mechanisms reflects a distinct biological problem. Relapse occurs when viable fungi persist despite antifungal therapy, often because induction treatment was inadequate or adherence lapsed. Paradoxical immune reconstitution inflammatory syndrome, or IRIS, is the inflammatory storm that can erupt when antiretroviral therapy restores immune function and the revived immune system mounts an exuberant response to residual fungal antigens in the central nervous system. Elevated intracranial pressure, a hallmark of cryptococcal meningitis, can persist or recur even after microbiological cure, causing severe headaches, vision loss, and neurological deterioration that require repeated lumbar punctures to relieve.

Beyond the brain, the readmission diagnoses read like a catalogue of advanced AIDS and its complications. Tuberculosis accounted for 26 rehospitalizations, other opportunistic infections for 39, and malignancy for 9. Hematologic disorders, including anemia and cytopenias, drove 21 admissions, while kidney and electrolyte disorders—conditions that can arise from both HIV-associated nephropathy and the nephrotoxic effects of amphotericin-based antifungal regimens—accounted for 29. Another 23 admissions were attributed to other conditions. The breadth of this list is itself a finding: patients surviving cryptococcal meningitis are not merely at risk of their index infection recurring, but remain extraordinarily vulnerable to the full spectrum of AIDS-defining and treatment-related complications during the fragile weeks after discharge.

In an effort to identify who was most likely to be readmitted, the investigators performed statistical analyses of potential risk factors, and the results were unexpectedly null. No baseline characteristic reliably predicted rehospitalization. This absence of identifiable risk factors carries its own clinical message: readmission risk appears to be distributed broadly across the survivor population rather than concentrated in a recognizable high-risk subgroup. In practical terms, clinicians cannot easily single out which discharged patients warrant the most intensive follow-up on the basis of demographic or clinical features alone, which argues for structured post-discharge monitoring for all survivors rather than targeted surveillance of a presumed vulnerable minority.

Where the analysis did find signal was in mortality. Older age was associated with an increased risk of death during the post-discharge period, while two factors were protective: higher body weight and higher Glasgow Coma Scale scores at baseline. The Glasgow Coma Scale, a standard measure of consciousness and neurological function, is already used to stratify severity in cryptococcal meningitis, and its protective association here confirms that patients discharged with better neurological status fare better. The protective effect of higher weight likely reflects overall nutritional reserve and illness severity—patients who are more wasted by advanced HIV disease and prolonged infection have less physiological buffer against subsequent complications. These mortality associations, unlike the rehospitalization analysis, offer concrete variables that clinicians can incorporate into discharge counseling and triage decisions.

The study’s implications reach well beyond Uganda. Cryptococcal meningitis kills an estimated 180,000 people annually worldwide, with the overwhelming burden in sub-Saharan Africa, and even with newer, more effective and better-tolerated regimens such as the single-dose amphotericin strategy validated in the AMBITION trial, survival after hospital discharge has remained poorly characterized. By demonstrating that a quarter of survivors experience rehospitalization or death within ten weeks, the study reframes the post-discharge period as a distinct phase of care deserving its own clinical infrastructure—structured follow-up visits, early antiretroviral therapy initiation with careful IRIS monitoring, screening for tuberculosis and other opportunistic infections, and management of intracranial pressure. The work also highlights the value of linking large clinical trial cohorts to longitudinal outcomes: because the four trials enrolled participants prospectively with standardized follow-up, the researchers could capture readmissions and deaths with a completeness that routine hospital records rarely allow.

For a disease that has seen genuine therapeutic progress over the past decade, the persistence of this post-discharge crisis is a reminder that antifungal drug regimens, however improved, address only part of the problem. The patients in this cohort left the hospital with CD4 counts in the low double digits, often newly started on antiretroviral therapy, and facing a landscape of competing infectious, inflammatory, renal, hematologic, and malignant threats. The Ugandan team’s data make clear that the ten weeks after discharge are not a quiet convalescence but a high-stakes transition, and that health systems serving populations with advanced HIV disease must plan for it accordingly. Whether interventions such as enhanced follow-up clinics, pre-emptive treatment of residual fungal burden, or earlier detection of IRIS and tuberculosis can bend this curve is now the pressing question the study leaves for the field.

Subject of Research: Rehospitalization and post-discharge outcomes among adults with HIV-related cryptococcal meningitis in Uganda

Article Title: Incidence, reasons, and outcomes of rehospitalization among adults with HIV-related cryptococcal meningitis in Uganda: a post-hoc analysis of a prospective cohort

Article References: Muyise, R. C. B., Jjunju, S., Kwizera, R., Dai, B., Adzemovic, T., Mufti, S. S., Meya, D. B., & Boulware, D. R. (2026). Incidence, reasons, and outcomes of rehospitalization among adults with HIV-related cryptococcal meningitis in Uganda: a post-hoc analysis of a prospective cohort. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14594-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14594-8

Keywords: cryptococcal meningitis, HIV, AIDS, rehospitalization, mortality, Uganda, immune reconstitution inflammatory syndrome, tuberculosis, intracranial pressure, CD4 count, antiretroviral therapy, BMC Infectious Diseases

The research team, led by Ahd Ouladlahsen of the Faculté de Médecine et de Pharmacie at Hassan II University and the infectious diseases service of CHU Ibn Rochd, enrolled 396 consecutive adults newly diagnosed with HIV between January 1 and December 31, 2023. Unlike retrospective chart reviews, this was a prospective cohort: demographic, clinical, laboratory, and treatment outcome data were systematically collected as patients moved through care. The investigators then used multivariable logistic and Cox regression models to identify independent predictors of three key outcomes: advanced HIV disease at presentation, virological failure at six months, and all-cause mortality. The study was approved by the Ethics Committee of the Faculty of Medicine in Rabat and conducted in accordance with the Declaration of Helsinki, with informed consent obtained from all participants.

The demographic profile of the cohort reflects a mixture of social vulnerability and mobility. The median age was 34 years, with a range spanning 18 to 74, and men made up 55 percent of newly diagnosed patients. Most participants were single, 60.1 percent, and nearly half, 46.1 percent, were unemployed. Perhaps the most striking socioeconomic figure is that 83.6 percent of patients had no health insurance, a factor that shapes both access to testing and the ability to remain in care. Nearly one in five patients, 19.9 percent, were of Sub-Saharan African origin, underscoring the role of migration corridors in the regional epidemiology of HIV and the need for screening strategies that reach migrant populations effectively.

Transmission patterns in the cohort were dominated by heterosexual contact, which accounted for 72.0 percent of new diagnoses. That figure matters for public health planning because it signals that HIV in this setting is not confined to networks traditionally classified as key populations; it is embedded in the general adult population. At the same time, the way patients entered care is perhaps the most consequential finding of the entire study: symptoms prompted the diagnosis in 58.9 percent of cases. In other words, the majority of people were not identified through proactive, voluntary testing but because something was already clinically wrong, which almost by definition implies that the virus had been replicating, and the immune system deteriorating, for a considerable period before anyone looked for it.

The immunological data confirm just how far disease had progressed by the time of diagnosis. The median baseline CD4 count was 186 cells per cubic millimeter, well below the 200-cell threshold that defines one of the classic boundaries of severe immunosuppression, and 60.6 percent of patients presented with CD4 counts below that mark. Under the Centers for Disease Control and Prevention staging system, 41.4 percent of patients were already at stage C, the stage corresponding to AIDS-defining illness. Tuberculosis was the leading opportunistic infection, affecting 35.1 percent of the cohort. This convergence of low CD4 counts, advanced clinical staging, and rampant tuberculosis coinfection paints a portrait of an epidemic in which the virus is being discovered only after it has done most of its damage, a pattern that global health authorities have repeatedly identified as one of the chief obstacles to ending AIDS as a public health threat.

Treatment outcomes at six months tell a more nuanced story. On the positive side, 75.0 percent of patients achieved viral suppression within half a year of starting therapy, a respectable figure for a cohort in which most patients began treatment profoundly immunocompromised. The backbone of modern first-line therapy in the region is dolutegravir-based antiretroviral therapy, and the suppression rate suggests that when patients reach care and start the recommended regimens, the drugs largely do their job. However, 10.0 percent of patients experienced virological failure at six months, and overall mortality in the cohort reached 8.3 percent. An early death rate approaching one in twelve among newly diagnosed patients is a direct consequence of late presentation: people who arrive with CD4 counts below 200 cells per cubic millimeter and active tuberculosis face a fundamentally different prognosis than those identified early.

The regression analyses sharpen these associations into a hierarchy of risk. For mortality, four independent predictors emerged: a CD4 count below 200 cells per cubic millimeter carried an adjusted hazard ratio of 3.67, by far the strongest signal in the model; age of 40 years or older carried an adjusted hazard ratio of 1.62; active tuberculosis carried an adjusted hazard ratio of 2.56; and higher baseline viral load carried an adjusted hazard ratio of 1.18. Each of these factors is, in principle, addressable. CD4 nadir and viral load at diagnosis are proxies for how long infection went undetected; tuberculosis coinfection can be prevented or caught earlier through integrated TB/HIV screening; and age is a reminder that testing strategies must not neglect middle-aged and older adults who are rarely the focus of HIV awareness campaigns.

Advanced HIV disease at presentation was itself predicted by a distinct cluster of characteristics: age of 40 or older, Sub-Saharan African origin, unemployment, divorced or widowed status, and tuberculosis. Read together, these predictors describe patients who sit at the intersection of biological and social risk. Unemployment and lack of insurance limit both the incentive and the means to seek voluntary testing, while marital status may affect disclosure, support, and health-seeking behavior. For migrants, language barriers, documentation concerns, and discontinuous access to health systems can delay entry into care for years. The finding that virological failure at six months was independently predicted by advanced HIV disease at baseline, with an adjusted odds ratio of 1.85, higher baseline viral load, with an adjusted odds ratio of 1.92 per log10 increase, and receipt of non-TDF/3TC/DTG regimens, with an adjusted odds ratio of 1.89, adds a therapeutic dimension: patients who start treatment with very high viral burdens and non-standard regimens are the ones most likely to fail, reinforcing the case for prompt diagnosis and rapid initiation of preferred first-line therapy.

The authors are careful about the limits of their work. This was a single-center study at a tertiary referral hospital in Casablanca, which means the cohort may overrepresent complicated cases referred from elsewhere while underrepresenting people diagnosed and managed entirely in primary care. Some analyses were restricted to subsets of patients: the advanced disease model included 236 patients with available CD4 data, and the virological failure model included 280 patients with six-month viral load measurements. The investigators themselves call for multi-center validation with extended follow-up, noting that six months captures early treatment outcomes but not the longer arc of retention, adherence, and survival.

Even with those caveats, the policy implications are difficult to ignore. The study argues for expanded community-based screening so that diagnoses are driven by testing rather than by symptoms, integrated TB/HIV services capable of detecting coinfection at or before the moment of HIV diagnosis, socioeconomic support for unemployed and uninsured patients whose life circumstances compete with clinic attendance, and enhanced, culturally competent screening for migrant populations. Dolutegravir-based therapy has already proven capable of suppressing the virus in three-quarters of newly diagnosed patients within six months; the remaining losses, the deaths, the failures, the late presentations, are largely problems of timing and access rather than of pharmacology. In that sense, the Casablanca cohort is less a story about the virus than about the systems that fail to intercept it, and a reminder that in 2023, in a Moroccan tertiary care center, the median person diagnosed with HIV had a CD4 count of 186 cells per cubic millimeter, a number that should be an anachronism but is not.

Subject of Research: Epidemiological and clinical profile of newly diagnosed HIV patients in Morocco

Article Title: Epidemiological and clinical profile of newly diagnosed HIV patients at a moroccan tertiary care center in 2023

Article References: Ouladlahsen, A., Lkhider, M., Haddaji, A., Bensghir, R., Badi, H., Sodqi, M., Ihbibane, F., Marih, L., Ezzikouri, S., & El Filali, K. M. (2026). Epidemiological and clinical profile of newly diagnosed HIV patients at a moroccan tertiary care center in 2023. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14422-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14422-z

Keywords: HIV, late diagnosis, Morocco, tuberculosis, antiretroviral therapy, dolutegravir, CD4 count, virological suppression, opportunistic infections, Sub-Saharan migrants, public health, Casablanca

The study team, led by Alper Tahmaz and colleagues in the Department of Infectious Diseases and Clinical Microbiology at Antalya Training and Research Hospital, designed the analysis around a single admission per patient. When a patient had been hospitalized more than once during the study window, the researchers selected the chronologically latest admission, irrespective of whether the patient survived. This approach ensured that each individual contributed only one observation to the dataset, avoiding the statistical distortion that repeated admissions can introduce when the same severely ill patients dominate hospital records. The investigators then combed retrospectively through demographic characteristics, immune status, viral load measurements, comorbidities, and the recorded indications for hospitalization, which were treated as non-mutually exclusive categories, meaning a single admission could carry several simultaneous reasons for care.

The demographic and clinical profile of the cohort was striking. The median age of admitted patients was 45 years, and nearly nine in ten participants, 89.8 percent, were male. More revealing were the immunological numbers: at admission, 56.3 percent of patients had CD4 cell counts below 200 cells per cubic millimeter, the threshold that defines advanced immunosuppression and the level at which opportunistic infections become a dominant threat. Only 37.5 percent of the hospitalized patients had a previously established HIV diagnosis, and just 27.3 percent were receiving combined antiretroviral therapy at the time of admission. In other words, the majority of people ending up in hospital beds were either newly diagnosed in the course of their acute illness or had known HIV but were not on suppressive treatment, a pattern that echoes the persistent challenge of late diagnosis documented across many health systems.

The reasons these patients required hospitalization mapped closely onto the classical spectrum of HIV-related disease. Bacterial infections were the most frequently recorded indication, appearing in 58.6 percent of admissions, a reminder that even in the antiretroviral era, bacterial pneumonia, sepsis, and other common bacterial pathogens remain leading causes of serious illness among immunocompromised hosts. Pneumocystis jirovecii pneumonia, the fungal opportunistic infection that once defined the AIDS epidemic, was recorded in 28.9 percent of patients, while cytomegalovirus infection, another hallmark of severe cellular immune deficiency, appeared in 21.9 percent. Because the indications were not mutually exclusive, many patients carried multiple overlapping diagnoses at once, reflecting the compounded vulnerability of bodies whose CD4 defenses had collapsed.

Beyond the classic opportunistic infections, the study also captured the substantial burden of other medical conditions, which were recorded in 67 patients, or 52.3 percent of the cohort. Rather than forcing these into narrow diagnostic boxes, the researchers described them by organ system category, acknowledging that hospitalized people living with HIV frequently present with a tangle of concurrent problems affecting the respiratory tract, the gastrointestinal system, the nervous system, and beyond. This overlap of infectious and non-infectious conditions is one of the study’s central messages: the modern hospitalized HIV patient is rarely admitted for a single clean diagnosis, and clinical management must contend with simultaneous, interacting pathologies.

The severity of these admissions was underscored by intensive care utilization. Nearly a quarter of the cohort, 24.2 percent, required admission to the intensive care unit at some point during their hospital stay. That figure speaks to how far disease had progressed before these patients reached effective care, and it aligns with the broader clinical understanding that late presenters with CD4 counts below 200 cells per cubic millimeter face dramatically elevated risks of respiratory failure, septic shock, and central nervous system complications that demand critical care support.

The primary outcome of the study was documented in-hospital death, and the mortality figure was sobering: 20 of the 128 patients died, an in-hospital mortality rate of 15.6 percent, with a 95 percent confidence interval of 10.3 to 22.9 percent. To identify factors associated with this outcome, the researchers employed an exploratory Firth penalized logistic regression model, a statistical technique specifically designed for situations where the number of outcome events is small relative to the number of predictor variables. Ordinary logistic regression can fail or produce wildly unstable estimates in such sparse-data settings, and the Firth penalty shrinks coefficient estimates toward zero to reduce this small-sample bias. The model included three predictors: age, a CD4 count below 200 cells per cubic millimeter at admission, and a history of malignancy.

Of these three candidates, one emerged with a statistically clear signal. A history of malignancy was associated with roughly fourfold higher odds of in-hospital death, with an adjusted odds ratio of 4.00 and a 95 percent confidence interval of 1.25 to 12.37, yielding a p-value of 0.020. The authors are careful to frame this as an exploratory finding, and for good reason: with only 20 deaths in the entire cohort, the confidence interval is wide, spanning from just over one to more than twelve, which means the true strength of the association could plausibly range from modest to very large. The direction of the result, however, is biologically coherent. Cancer history in people living with HIV can reflect prior AIDS-defining malignancies such as lymphomas, the immunosuppressive effects of chemotherapy, and generally diminished physiological reserve, all of which plausibly compound the danger of an acute infectious admission.

The authors themselves are explicit about the limitations that should temper interpretation. The cohort was drawn from a single tertiary referral hospital, which selects for the most complex and severe cases in a region and limits generalizability to primary care settings or to the broader population of people living with HIV who never require admission. The retrospective design depends on the completeness and accuracy of medical records, and the regression model adjusted for only a small number of covariates, leaving open the possibility of confounding by unmeasured factors such as treatment adherence, nutritional status, or the specific pathogens involved. The selection of the latest admission per patient, while methodologically defensible, also means the analysis captures a particular snapshot of each patient’s trajectory rather than the full arc of their hospitalizations.

Even with those caveats, the study lands on a set of conclusions that resonate far beyond one Turkish hospital. The finding that more than half of hospitalized patients had CD4 counts below 200 cells per cubic millimeter, and that fewer than three in ten were on antiretroviral therapy, points to failures upstream of the hospital door: missed opportunities for earlier testing, gaps in linkage to care, and interruptions in treatment continuity. The authors argue that their findings support greater attention to timely HIV diagnosis, sustained continuity of care, and systematic comorbidity assessment in this population. As antiretroviral therapy transforms HIV into a manageable chronic condition for people who are diagnosed early and treated consistently, studies like this one document what happens in the gap between that promise and its delivery, and they quantify, in hard numbers, the cost of arriving at the hospital too late.

Subject of Research: Hospitalization indications, clinical course, and in-hospital mortality among people living with HIV/AIDS

Article Title: Indications for hospitalization, clinical course, and mortality analysis among patients with HIV/AIDS in a tertiary care hospital: a 5-year retrospective study (2021–2025)

Article References: Tahmaz, A., Yildiz Dikmen, M., Ersari, S. S., Dinç, E., & Seyman, D. (2026). Indications for hospitalization, clinical course, and mortality analysis among patients with HIV/AIDS in a tertiary care hospital: a 5-year retrospective study (2021–2025). BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14560-4

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14560-4

Keywords: HIV, AIDS, hospitalization, in-hospital mortality, CD4 count, opportunistic infections, Pneumocystis jirovecii pneumonia, cytomegalovirus, antiretroviral therapy, late diagnosis, malignancy, retrospective study

The study, conducted by Bao Linh Nguyen and Thanh Binh Ngo of the University of Medicine and Pharmacy at Ho Chi Minh City, enrolled adults with HIV and microbiologically confirmed pulmonary tuberculosis at a tertiary referral hospital for tuberculosis and lung diseases between December 2022 and September 2023. Rather than averaging findings across the cohort, the researchers deliberately stratified patients by CD4 count, the standard laboratory measure of immune destruction, and tracked how three separate axes of the disease shifted across those strata: the radiographic appearance of the lungs on chest X-ray, the microbiological yield of sputum tests, and the presence of additional pulmonary pathogens sharing the same airways.

The patients themselves tell much of the story. The median CD4 count in the cohort was a startling 40.5 cells per microliter of blood, a level at which the immune system is barely functional; healthy counts sit above 500. Most patients were not yet taking antiretroviral therapy, and many were learning of their HIV diagnosis for the first time when they arrived at the hospital. This is the face of late presentation, and it is common in settings where HIV stigma, fragmented testing services and limited access to care delay diagnosis until opportunistic infections force patients through the door. Vietnam’s HIV epidemic, concentrated in certain regions and populations, continues to feed such late presentations into its tuberculosis wards.

The radiographic findings were the study’s most striking result. Among patients in the highest CD4 stratum, every single patient showed cavitation on chest radiography, and nearly nine in ten showed consolidation, the dense opacities that mark the body’s attempt to wall off infection with an intact inflammatory response. Large nodules appeared in two-thirds of this group. In the lowest CD4 stratum, the picture inverted almost completely: cavitation was seen in just 3.8 percent of patients, consolidation in 30.8 percent, and large nodules in 9.6 percent. Instead, half of the most immunosuppressed patients displayed ground-glass opacity, a hazy, frosted-glass pattern that in this population strongly evokes Pneumocystis jirovecii pneumonia or other non-tuberculous pathology. All four of these radiographic trends remained statistically significant after correction for multiple comparisons, with adjusted q-values of 0.025 or lower.

The biological explanation is straightforward but consequential. Cavitation in tuberculosis is not the work of the bacterium alone; it is the work of the immune response to it. Caseous necrosis, the destruction of lung tissue into a cheese-like core that can liquefy and drain into airways, depends on a vigorous CD4 T-cell driven inflammatory reaction. When CD4 cells are scarce, the lung cannot mount that reaction, so the bacilli multiply diffusely without forming cavities, and the radiograph shows vague haziness rather than the textbook cavity. The practical implication is that clinicians who dismiss tuberculosis because the X-ray lacks classic features may be precisely wrong in the patients at greatest risk, since atypical, ground-glass-predominant disease is a marker of the deepest immunosuppression.

That overlap with Pneumocystis is where the study becomes clinically urgent. Ground-glass opacity showed an unadjusted association with Pneumocystis positivity, with an odds ratio of 5.67, meaning patients with this pattern were more than five times as likely to harbor the fungus. Yet the diagnostic workup for Pneumocystis was strikingly incomplete: among patients with CD4 counts at or above 200 cells per microliter, only four of nine were ever tested, and none of those tested was positive. Overall, at least one additional pulmonary organism was documented in 28 of 92 patients, or 30.4 percent of the cohort. In other words, nearly a third of these patients were fighting more than one lung infection simultaneously, a reality that complicates every treatment decision, from empiric antibiotic choices to the timing and composition of antiretroviral initiation, where immune reconstitution inflammatory syndrome looms as a hazard.

On the microbiological axis, the study delivered a clear verdict on diagnostics. Sputum smear microscopy, the century-old workhorse of tuberculosis diagnosis in high-burden countries, detected acid-fast bacilli in only 63.3 percent of patients. The molecular Xpert MTB/RIF assay, which amplifies Mycobacterium tuberculosis DNA and simultaneously screens for rifampicin resistance, was positive in 91.1 percent. The paired comparison, analyzed with exact McNemar testing, produced a p-value below 0.0001, leaving little doubt that the molecular assay outperforms smear across every level of immunosuppression. Notably, neither test showed a significant ordered trend across CD4 strata, suggesting that the well-known paucibacillary appearance of tuberculosis in advanced HIV does not translate into a simple, predictable gradient of test positivity in real-world sputum samples.

Perhaps the most pragmatic finding concerns a test that almost any district laboratory can perform. The researchers explored whether the absolute lymphocyte count, a routine component of a complete blood count, could serve as a proxy for CD4 depletion. In exploratory receiver-operating-characteristic analysis, the absolute lymphocyte count discriminated patients with CD4 counts below 200 cells per microliter with an area under the curve of 0.89, with a 95 percent confidence interval of 0.79 to 0.96. An AUC near 0.9 represents strong discriminatory power, approaching the threshold often considered excellent. The authors are careful to frame this correctly: the lymphocyte count may provide a supportive indicator of advanced immunosuppression where CD4 testing infrastructure is unavailable, but it must not substitute for direct CD4 measurement, which remains the gold standard for staging HIV disease and guiding prophylaxis against opportunistic infections.

The study’s limitations deserve honest weight, and the authors acknowledge them directly. This was a single-center, cross-sectional investigation at a specialized referral hospital, which means the patients may not represent the broader population of people with HIV and tuberculosis in Vietnam or elsewhere. The design captures a snapshot rather than a trajectory, so it can describe associations but cannot establish how individual patients’ disease evolves as immune function changes. The Pneumocystis findings rest on microscopy, an insensitive method, and the testing gaps among higher-CD4 patients make the true prevalence of coinfection uncertain. The lymphocyte count analysis was explicitly exploratory. The authors describe their conclusions as hypothesis-generating and call for prospective confirmation, a framing that reflects appropriate scientific caution rather than weakness.

Even with those caveats, the findings land at a consequential moment. Tuberculosis remains the leading cause of death among people with HIV worldwide, and the World Health Organization’s targets for ending the dual epidemic depend on finding cases earlier and treating them correctly the first time. This study from Ho Chi Minh City distills that challenge into concrete clinical rules of thumb: in a patient with advanced HIV, a hazy chest X-ray without cavitation should raise, not lower, suspicion of tuberculosis; molecular testing should replace smear wherever possible; a substantial fraction of patients harbor secondary pulmonary pathogens that demand broader diagnostic thinking; and where CD4 counters are scarce, a simple lymphocyte count can flag the patients most likely to be dangerously immunosuppressed. For the clinicians working on the front lines of the HIV-tuberculosis collision, these are not abstractions. They are the difference between a diagnosis made in time and one made too late.

Subject of Research: Clinical, radiographic and microbiological presentation of HIV-associated pulmonary tuberculosis across CD4 count strata

Article Title: Clinical, radiographic and microbiological manifestations of newly diagnosed pulmonary tuberculosis across CD4 strata in adults with advanced HIV disease: a real-world cross-sectional study in southern Vietnam

Article References: Nguyen, B. L., & Ngo, T. B. (2026). Clinical, radiographic and microbiological manifestations of newly diagnosed pulmonary tuberculosis across CD4 strata in adults with advanced HIV disease: a real-world cross-sectional study in southern Vietnam. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14507-9

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14507-9

Keywords: pulmonary tuberculosis, HIV, advanced HIV disease, CD4 count, chest radiography, ground-glass opacity, Xpert MTB/RIF, sputum smear microscopy, Pneumocystis jirovecii, coinfection, absolute lymphocyte count, Vietnam

Bartonella species are vector-borne, Gram-negative bacteria that invade red blood cells and the cells lining blood vessels. More than 45 species have been described, but three dominate human disease: B. henselae, the agent of cat scratch disease, transmitted chiefly by cat fleas and scratches from infected cats; B. quintana, the agent of trench fever, spread by the human body louse; and B. bacilliformis, restricted largely to South America. In immunocompetent people, cat scratch disease typically resolves on its own within two to four months, presenting as swollen lymph nodes, skin lesions, fatigue, and headache. In contrast, B. quintana infection spans a broad clinical spectrum, from recurrent fever with severe leg pain to chronic bacteremia, culture-negative infective endocarditis, bacillary angiomatosis, and bacillary peliosis, conditions that emerge mainly when the immune system cannot contain the organism.

That distinction matters because the host immune response is the central determinant of how Bartonella infection unfolds. In people with intact immunity, the pathological response is typically granulomatous and suppurative, effectively walling off the bacteria. In immunocompromised individuals, including organ transplant recipients and people with HIV, the same organisms can drive proliferative vascular lesions that grow rapidly. Patients with CD4 T-cell counts below 50 cells per microliter are considered especially vulnerable to severe disease and chronic opportunistic infection. Iran has already seen warning signs: the first molecularly confirmed case of B. quintana bacillary angiomatosis in an HIV-infected patient was reported there in 2021, and more than eight Bartonella species have since been identified in insects and livestock reservoirs across the country, five of them known to cause human disease.

To quantify the scale of exposure, the research team enrolled 200 participants between September 2023 and May 2024: 150 patients with HIV infection recruited from the Infectious Diseases Department and HIV clinic at Imam Khomeini Hospital, a referral university hospital in Tehran, and 50 randomly selected healthy controls. Within the HIV-positive group, 39 individuals met the criteria for AIDS, defined by CD4 counts below 200 cells per microliter or clinical AIDS-defining conditions, while 111 had higher counts. Each participant provided five milliliters of venous blood after informed consent, completed a structured questionnaire covering demographics, animal contact, tick and flea exposure, social status, and transfusion history, and had serum separated and stored at minus 20 degrees Celsius under cold chain conditions at the Pasteur Institute.

The serological workhorse of the study was the indirect immunofluorescence assay, or IFA, the technique recommended by the US Centers for Disease Control and Prevention for detecting antibodies against B. henselae and B. quintana. Because the samples came from HIV-positive individuals, all sera were first treated with Triton X-100 for 30 minutes at 37 degrees Celsius to reduce biocontamination risk, a pretreatment shown to inactivate HIV particles without compromising antibody detection. For IgG testing, sera were serially diluted from 1:64 up to 1:2048 and applied to slides coated with fixed bacterial antigens; after incubation and washing, a fluorescein-labeled anti-human IgG conjugate was added, and fluorescence was read at 400-fold magnification. The highest dilution showing distinct apple-green fluorescence defined the endpoint titer, with 1:64 or above scored as positive. IgM testing followed a parallel protocol on a randomly selected subset of 48 participants, using IgG sorbent to strip competing IgG antibodies before dilution, with titers of 1:24 or above considered positive.

The results revealed substantial background exposure. Across all 200 participants, IgG seroprevalence was 24.0 percent for B. henselae and 22.0 percent for B. quintana, while IgM seroprevalence in the tested subset reached 18.8 percent and 22.9 percent respectively. Strikingly, the healthy controls fared no better: B. henselae IgG was found in 30.0 percent of controls and 30.0 percent of AIDS patients, versus 18.3 percent of HIV-positive patients without AIDS, and B. quintana IgG appeared in 26.0 percent of controls, 28.3 percent of AIDS patients, and 17.3 percent of the HIV-positive group. None of these between-group differences reached statistical significance, suggesting that Bartonella circulation in this region extends well beyond the immunocompromised clinic population.

Risk factor analysis sharpened the picture. In multivariable logistic regression, higher age emerged as protective against B. quintana IgG seropositivity, with an odds ratio of 0.48, while a history of drug use nearly tripled the odds, at 3.28. For B. henselae, every body mass index category above underweight carried significantly lower odds of IgG positivity compared with a BMI below 18.5, with odds ratios falling as low as 0.16, and drug use again raised the odds, at 2.46. Underlying chronic diseases were associated with reduced seropositivity, an odds ratio of 0.31, a counterintuitive finding the authors interpret cautiously. Notably, contact with cats, dogs, or other animals, often assumed to be the main route of exposure, showed no significant association with seropositivity for either species, nor did homelessness or documented flea bites.

The most sobering number came from the immunologically weakest participants. Among the 34 patients with CD4 counts below 200 cells per microliter, 28, or 82 percent, were seropositive for at least one Bartonella antibody class. The authors are careful to note that serology alone cannot establish clinically relevant infection or prove a causal link with immunodeficiency, since IgG positivity reflects past exposure and IgM may signal recent infection that molecular testing would be needed to confirm. Still, the figure aligns with international data: seroprevalence among HIV-infected populations has ranged from 17.3 to 40 percent in prior studies, with a Spanish study reporting 22.3 percent, a Brazilian study 40.8 percent, and a South African molecular study detecting bartonellosis in 10 percent of HIV-positive outpatients.

The authors also confront the inherent limits of antibody-based detection. IFA sensitivity ranges from 50 to 95 percent, and cross-reactivity with Coxiella, Chlamydia, and potentially Mycobacterium species, which are common in HIV patients, can blur specificity. In advanced immunosuppression, impaired humoral responses may blunt antibody production entirely, producing false negatives despite active infection, which means negative serology cannot exclude Bartonella in severely immunocompromised patients. The absence of PCR confirmation in this study likewise prevents a clean separation of past from recent exposure and may have led to slight underestimation of recent infections. When treatment is needed, current evidence favors macrolides such as azithromycin, tetracyclines, particularly doxycycline, and rifampin, which carry the most reliable minimum inhibitory concentration data, having displaced the beta-lactams used historically.

The broader message is one of vigilance rather than alarm. Exposure to Bartonella species appears common in both HIV-infected and non-infected Iranians, and the combination of molecular and serological evidence, including a companion PCR study that detected B. quintana exclusively among immunocompromised patients, supports active circulation of these bacteria in vulnerable populations. The authors argue that the healthcare community should pay closer attention to bartonellosis surveillance and management in people with HIV, particularly those with advanced immunosuppression, and that standardized diagnostic approaches combining serology with molecular methods are critically important. As the study’s findings make clear, a bacterium once associated with trench warfare and stray cats has not disappeared; it has simply been waiting for immune systems to falter.

Subject of Research: Seroprevalence of Bartonella quintana and Bartonella henselae antibodies among HIV-positive patients in Iran

Article Title: A cross sectional seroprevalence study of Bartonella quintana and Bartonella henselae among patients with human immunodeficiency virus (HIV) in Iran

Article References: Latifian, M., Hasannezhad, M., Abbasian, L., Tahmasebi Ashtiani, Z., Arabian, M., Bagheri Amiri, F., & Esmaeili, S. (2026). A cross sectional seroprevalence study of Bartonella quintana and Bartonella henselae among patients with human immunodeficiency virus (HIV) in Iran. New Microbes and New Infections, 73, Article 101841. https://doi.org/10.1016/j.nmni.2026.101841

Image Credits: AI Generated

DOI: Not provided

Keywords: Bartonella quintana, Bartonella henselae, HIV, seroprevalence, immunocompromised patients, cat scratch disease, trench fever, immunofluorescence assay, Iran, opportunistic infection, vector-borne bacteria, CD4 count