The stakes of this comparison are straightforward. HIV is transmissible through transfused blood with exceptionally high efficiency, far higher than through most other routes of exposure, because a transfusion delivers infected blood directly into a recipient’s circulation. A single unscreened or inadequately screened donation can therefore establish infection in a recipient with near certainty. This is why wealthy countries long ago adopted multi-layered screening that combines antibody and antigen detection with molecular testing of pooled samples. In many low- and middle-income countries, however, the cost and technical demands of molecular platforms have kept rapid serological tests at the center of blood safety programs, and Mozambique has been no exception.

The routine algorithm evaluated in the study pairs two rapid tests: the Determine HIV 1/2 assay, which detects antibodies to HIV-1 and HIV-2, followed by the Uni-Gold HIV test as a confirmatory or tie-breaking step. This combination is the standard approach for screening blood donor candidates in Mozambique. The researchers also examined two newer rapid tests, the Determine HIV Early Detect assay and the Meriscreen HIV1-2 Western Blot test, both of which are designed to shorten the window period by adding detection of the p24 viral antigen to antibody detection. As a laboratory-based comparator, the team used the Merilisa HIV Gen 4 enzyme-linked immunosorbent assay combined with Uni-Gold, and as a molecular reference they used the cobas MPX test, a nucleic acid amplification platform that detects viral RNA and can identify infection during the earliest phase before antibodies appear.

When the rapid algorithms were benchmarked against the Merilisa HIV Gen 4 enzyme immunoassay plus Uni-Gold, their performance looked reasonably strong on the surface. The routine Determine HIV 1/2 plus Uni-Gold combination achieved a sensitivity of 85.5 percent and a specificity of 99.6 percent. The Determine HIV Early Detect test reached 88.7 percent sensitivity with 99.5 percent specificity, while the Meriscreen HIV1-2 Western Blot assay performed best among the rapid options at 90.0 percent sensitivity and 99.6 percent specificity. In other words, the newer rapid assays caught a somewhat larger share of infections than the routine algorithm while maintaining the very low false-positive rates that blood banks require to avoid discarding safe donations.

The picture changed dramatically, however, when the researchers measured all of the serological approaches against the cobas MPX molecular test. Sensitivity fell steeply across the board. The routine Determine HIV 1/2 plus Uni-Gold algorithm detected only 64.0 percent of the infections identified by the molecular assay, with 99.1 percent specificity. Determine HIV Early Detect rose to 68.6 percent sensitivity at 99.1 percent specificity, and Meriscreen HIV1-2 Western Blot reached 70.8 percent sensitivity at 99.0 percent specificity. Even the laboratory-based Merilisa HIV Gen 4 plus Uni-Gold combination, which one might expect to approach molecular performance, detected just 66.0 percent of molecularly positive samples at 99.4 percent specificity. These figures mean that a substantial fraction of donations carrying HIV, roughly a third by these comparisons, would pass through serological screening undetected.

The clinical translation of those percentages is sobering. The researchers calculated that the probability of an undetected positive result ranged from 5.6 to 6.7 per 1,000 blood donors across the rapid tests and the Merilisa HIV Gen 4 assay. In a country where tens of thousands of donations are collected annually, that residual risk translates into a meaningful number of potentially infectious units entering the blood supply each year. The source of the discrepancy lies in the biology of HIV infection. Serological tests depend on the host immune response, and there is an unavoidable window period between infection and the appearance of detectable antibodies or antigen. During that window, viral RNA circulates at high levels and the donor is highly infectious, yet antibody-based assays return negative results. Molecular tests close much of that gap by directly detecting viral genetic material.

The study’s design deserves attention because it goes beyond a simple head-to-head comparison of commercial kits. By establishing a molecular reference standard and evaluating multiple testing strategies against it, the team was able to quantify not only relative sensitivity and specificity but also the practical consequence of relying on serology alone: an estimated residual transmission risk per thousand donors. This kind of risk estimate is the currency in which blood safety policy is debated, because it allows program managers to weigh the cost of adding nucleic acid testing against the expected number of transfusion-transmitted infections prevented. The authors argue that their results point directly to the need for molecular HIV testing in blood banks in developing countries as a way to improve transfusion safety and contribute to controlling HIV as a public health problem.

That recommendation is not without challenges. Nucleic acid amplification testing requires sophisticated laboratory infrastructure, trained personnel, cold-chain logistics, reliable electricity, and quality management systems, and it is considerably more expensive per sample than rapid testing. Many programs address the cost by testing donations in minipools, in which multiple samples are combined and screened together, with individual follow-up testing only when a pool is reactive. The cobas MPX platform used as the molecular comparator in this study is precisely the kind of multiplex nucleic acid test that supports such pooled screening strategies, and it can simultaneously detect HIV, hepatitis B virus, and hepatitis C virus, extending the safety benefit beyond HIV alone. Whether such platforms can be sustainably deployed in Mozambique and similar settings will depend on financing, laboratory capacity, and political commitment to blood safety as an integral component of HIV control.

The findings also carry implications for how rapid tests are selected and deployed in the interim. The newer assays that incorporate antigen detection, Determine HIV Early Detect and Meriscreen HIV1-2 Western Blot, outperformed the routine antibody-only algorithm in both comparisons, suggesting that upgrading the rapid testing algorithm could deliver incremental gains while molecular capacity is being built. The differences were modest, however, and the study makes clear that no serological strategy, whether rapid or laboratory-based, can match the sensitivity of direct viral detection during early infection. Specificity remained uniformly high across all tests, above 99 percent in every comparison, which means the problem is not false alarms but silent misses, the most dangerous failure mode in a transfusion setting.

Ultimately, the study provides the kind of local, context-specific evidence that global guidelines often lack. International recommendations on blood screening assume a level of diagnostic capacity that many national programs cannot yet deliver, and country-level performance data are essential for making the economic and public health case for investment. By quantifying the residual risk of HIV transmission through transfusion under the current Mozambican screening algorithm, Mabunda and colleagues have converted an abstract concern into a concrete number that policymakers can act on. As the authors conclude, introducing molecular testing into blood banks in developing countries would improve transfusion safety and strengthen the broader effort to bring HIV under control, a goal that depends on closing every remaining route of transmission, including the one that runs through the blood supply.

Subject of Research: Analytical performance of HIV serological screening tests for blood donor candidates in Mozambique

Article Title: High transmission risk of Human Immunodeficiency Virus in blood transfusions: A critical evaluation of blood bank serological tests in Mozambique

Article References: Mabunda, N., Matola, O., Sambo, J., Chelene, I., Munguambe, A., Abílio, N., Vubil, A., Loquiha, O., & Jani, I. (2026). High transmission risk of Human Immunodeficiency Virus in blood transfusions: A critical evaluation of blood bank serological tests in Mozambique. PLOS Global Public Health, 6(9), e0007398. https://doi.org/10.1371/journal.pgph.0007398

Image Credits: AI Generated

DOI: 10.1371/journal.pgph.0007398

Keywords: HIV, blood transfusion, blood banks, serological tests, rapid diagnostic tests, ELISA, molecular testing, Mozambique, transfusion safety, sub-Saharan Africa, screening, public health

The biological characteristics of newborns further complicate management. The neonatal immune system is not yet fully developed, so once sepsis occurs, infants are prone to rapid progression toward septic shock and multiple organ dysfunction syndrome. At the same time, the metabolic and enzyme systems of the liver and kidneys remain immature, limiting the ability to clear drugs. Antibiotics routinely used in adults, such as fluoroquinolones and sulfonamides, cannot be directly administered to neonates. Against this backdrop, researchers have increasingly focused on adjunctive therapies built upon standard antibiotic treatment, and plasma transfusion has emerged as one of the most debated candidates. Yet the timing and precise indications for plasma transfusion in neonates remain deeply controversial, prompting a new editorial in the World Journal of Pediatrics by Fang-Rui Ding and Xiao-Yan Li that systematically examines the theoretical foundation, risks, and current clinical application of this approach.

The rationale for using plasma transfusion in sepsis originated in trauma care. Trauma and sepsis share a striking degree of pathophysiological similarity. Both conditions trigger acute intravascular volume depletion and tissue hypoperfusion, as systemic vasodilation and elevated vascular permeability drive massive fluid extravasation, destabilizing the circulation and rapidly progressing to shock. Both disorders also induce severe coagulopathy, marked by excessive consumption of coagulation factors, disrupted anticoagulant pathways, and dysregulated fibrinolysis. Given these overlapping mechanisms, and given that multiple studies have demonstrated that early and active plasma transfusion in trauma patients significantly improves survival and clinical outcomes, it is biologically plausible to infer that plasma might confer comparable benefits in sepsis. This reasoning has shaped clinical intuition for decades, even in the absence of direct evidence in septic patients.

Neonates, especially preterm infants, have inherently low levels of coagulation factors, insufficient immunoglobulins and complement, and a fragile vascular endothelial barrier. When sepsis strikes, the systemic inflammatory response further consumes immune and coagulation-related mediators, worsening disease progression. In theory, plasma transfusion could rapidly replenish these deficient bioactive substances. Immunoglobulin supplementation could strengthen specific immune defenses against pathogens, neutralize toxins, and facilitate infection control. Coagulation factors and fibronectin could optimize hemostasis, preventing and treating sepsis-associated coagulopathy. Complement components could boost bacteriolytic and opsonizing capacity, promoting pathogen clearance. Colloid supplementation might also help maintain blood volume and plasma osmotic pressure, improving tissue perfusion and correcting septic shock. These mechanisms form a coherent and appealing therapeutic hypothesis.

Animal studies have lent support to these theoretical inferences. In a septic rat model, Chang and colleagues found that plasma transfusion raised the 48-hour survival rate from 14 percent to 57 percent compared with normal saline resuscitation. In foals, McTaggart and colleagues demonstrated that plasma transfusion elevated serum immunoglobulin G levels in both healthy and septic animals, and although it exerted no benefit on neutrophil function in healthy foals, it significantly improved neutrophil activity in septic ones. More strikingly, Pereira and colleagues studied neonatal puppies with sepsis and found that combined treatment with plasma and antibiotics improved immune and metabolic parameters, including blood glucose, white blood cell counts, and IgM levels, within 24 hours, shortened recovery of leukocyte indices, reduced lactate levels, and resulted in zero mortality, compared with a 22 percent mortality rate in the antibiotic-only group. Despite these encouraging results, the editorial’s authors caution that no high-grade human evidence has confirmed clinical efficacy, and findings from animal models may not be directly applicable to human neonates because of inherent species and environmental differences.

In humans, the picture grows considerably murkier. Clinical studies of plasma transfusion in sepsis have produced conflicting results, and some have associated transfusion with increased incidence of complications and poorer prognosis. Qin and colleagues, analyzing data from the Medical Information Mart for Intensive Care III database, found that both 28-day and 90-day mortality were significantly higher in the plasma transfusion group than in the non-transfusion group, and plasma transfusion did not improve prognosis even among sepsis patients with coagulopathy, regardless of coagulation state. In a pediatric study by Duan and colleagues involving 262 children with sepsis, 28-day mortality, in-hospital mortality, and multiple organ dysfunction syndrome morbidity were all significantly higher in the plasma transfusion group. Plasma transfusion demonstrated no benefit and was instead significantly associated with an increased risk of adverse outcomes, findings that directly challenge the intuitive appeal of the therapy.

Beyond questions of efficacy, plasma transfusion carries substantial safety risks. Allergic reactions occur at an approximate incidence of 1 to 3 percent. Transfusion-related acute lung injury, or TRALI, has an estimated incidence of 0.08 to 15.1 percent in critically ill patients and accounts for 34 percent of transfusion-related fatalities, although improved mechanistic understanding and donor selection have reduced risks in recent years. Transfusion-associated circulatory overload, or TACO, occurs in roughly 1 percent of transfusions overall but reaches 3.6 to 5.8 percent in critically ill patients, with widespread underdiagnosis and underreporting. While donor screening and pathogen inactivation have substantially reduced infection transmission, residual risks persist, with HIV and hepatitis C transmission rates of approximately 0.02 per 10,000 transfusions, and newly emerging pathogens remain a potential threat. Plasma transfusion may also increase nosocomial infection risk through transfusion-related immunomodulation, a phenomenon linked to postoperative infection in critically ill patients.

Current practice reveals a striking gap between guidelines and reality. Plasma transfusion is relatively common in neonatal intensive care units, with use varying dramatically across centers from 0.17 percent to 8.2 percent, and rates are generally higher for surgical cases and extremely preterm neonates. International guidelines are consistent in their core recommendation: plasma should be given only for active bleeding accompanied by coagulation disorders, and prophylactic transfusion is not recommended. No current sepsis guideline recommends plasma for sepsis itself. Yet observational surveys consistently reveal widespread non-adherence. In European countries, only 29.4 percent of plasma transfusions were given for bleeding, while in South Africa 75 percent of transfusions complied with national guidelines. The authors attribute this deviation to two interrelated factors: the lack of effective targeted interventions for neonatal septic shock, which drives clinicians to adopt plasma as a salvage therapy out of clinical urgency, and the extrapolation of trauma resuscitation experience combined with assumptions about neonatal immune and coagulation immaturity.

The limited human studies specific to neonatal sepsis offer mixed signals. A 1994 study by Acunas and colleagues involving 67 infected neonates found that while intravenous immunoglobulin exerted prominent immune-enhancing effects, plasma transfusion failed to elevate key anti-infective IgG or alter inflammatory markers such as C-reactive protein and fibronectin, indicating no clinical benefit. Conversely, a Nigerian retrospective study by Ogunlesi and colleagues in neonatal tetanus with suspected sepsis observed lower mortality in plasma-transfused neonates, though the difference was statistically insignificant due to small sample size, and all blood culture-positive patients in the transfusion group survived. Eisenfeld and colleagues further demonstrated that plasma transfusion significantly improved neutrophil chemotactic function in critically ill neonates with suspected severe sepsis. Data from other neonatal contexts add further complexity, with studies linking plasma transfusion to retinopathy of prematurity, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus, and necrotizing enterocolitis, though results remain contradictory and appear to depend heavily on transfusion timing, indication, and patient characteristics.

The editorial concludes that there are no definitive evidence-based data confirming that plasma transfusion benefits neonatal sepsis, but this does not mean benefits are absent. The authors call for large-sample, multicenter retrospective and prospective randomized controlled trials with carefully defined inclusion criteria, appropriate coagulation and infection outcomes, and stratified analysis by gestational age and weight to enable individualized treatment. They also urge deeper mechanistic research into the roles of immunoglobulins, coagulation factors, complements, and fibronectin in plasma, alongside safety studies addressing both short-term risks such as TACO, viral transmission, and allergic reactions, and long-term neonatal complications. Until such evidence arrives, plasma transfusion in neonatal sepsis remains a therapy caught between biological plausibility and clinical uncertainty, a gap that only rigorous research can close.

Subject of Research: The use of plasma transfusion as an adjunctive therapy for neonatal sepsis, including its theoretical benefits, clinical evidence, safety risks, and guideline recommendations.

Article Title: Plasma transfusion in neonatal sepsis

Article References: Ding, F.-R., & Li, X.-Y. (2026). Plasma transfusion in neonatal sepsis. World Journal of Pediatrics. https://doi.org/10.1007/s12519-026-01095-6

Image Credits: AI Generated

DOI: 10.1007/s12519-026-01095-6

Keywords: neonatal sepsis, plasma transfusion, fresh frozen plasma, neonatal intensive care, coagulopathy, septic shock, transfusion-related acute lung injury, immunoglobulins, randomized controlled trials, preterm infants, transfusion safety, clinical guidelines