Category: 8. Health

You may have noticed vitamin E on the label of your favorite skin-care products. It’s a nutrient that can help protect your skin from UV damage, making it a common ingredient for facial sunscreens. But vitamin E isn’t just applied topically — you also need to get it in your daily diet. Consuming enough vitamin E is crucial because it plays a key role in human development and functioning. The vitamin includes eight compounds, but only one of those — alpha-tocopherol — is used in the human body.

Experts have been debating the pros and cons of vitamin E for many years, so deciding whether to supplement vitamin E in your diet can be confusing. To help, we’ve done the research for you and found the key takeaways you should know. Here are the potential benefits and drawbacks to consider before adding a vitamin E supplement to your daily routine.

What is vitamin E?

Vitamin E is a fat-soluble nutrient found in many foods and is important to the human body in various ways. Vitamin E, in the form of alpha-tocopherol, is a powerful antioxidant that works as a free-radical-fighting machine.

While it is possible to meet daily vitamin E needs through food, oral and topical supplements are also available. However, supplements should be used cautiously, according to directions and after consulting a doctor.

Adding vitamin E to your diet

Nuts, seeds and vegetable oils top the list of the best sources, but vitamin E can be found in many foods. Here are some excellent and versatile food choices to boost your vitamin E. 

• Asparagus
• Avocado
• Boiled or raw spinach
• Dry roasted almonds
• Dry roasted hazelnuts
• Dry roasted sunflower seeds
• Kiwi
• Mango
• Peanut butter
• Pumpkin
• Red bell pepper
• Tomato

Benefits of vitamin E

Vitamin E has been touted as offering many benefits to the human body. Some of those are inconclusive regarding showing true benefit in scientific studies. Here are some vitamin E benefits that have science to back them up. 

1. May lower blood pressure 

High blood pressure (hypertension) is a major risk factor for cardiovascular disease. Some studies have shown that supplementing with vitamin E can help lower blood pressure, although the results were not as favorable for those with severe high blood pressure. 

Although results are mixed on the relationship between vitamin E supplementation and cardiovascular disease, a study that followed 40,000 healthy women for 10 years found that those who supplemented vitamin E had a 24% lower risk of death by a cardiac event. The results were not as positive for those at high risk or who already had heart disease. 

2. Fights free radicals

Vitamin E is known to battle free radicals and protect cells from their damage; fewer free radicals can mean several good things for the human body. 

Cellular damage from free radicals increases the risk for various health issues like cardiovascular disease, inflammatory disease, cataracts and cancer. Antioxidants that fight free radicals, like vitamin E, also fight those chronic conditions. 

A bonus? Vitamin E’s contribution to free radical reduction also reduces skin damage from UV exposure. Less skin damage means a more youthful glow, and who doesn’t want that?

Its anti-inflammatory effects also help to reduce symptoms in chronic inflammatory skin conditions like dermatitis. 

3. Can reduce PMS symptoms

Around 80% to 90% of women experience some degree of premenstrual syndrome during their reproductive years. For some, PMS is painful and disruptive to daily life. Vitamin E may bring some respite if you are one of the 80% to 90%. 

Studies show that supplementing vitamin E with vitamin D may be an effective way to reduce PMS symptoms like cramping, anxiety and cravings. 

Drawbacks to vitamin E supplements

As with any supplement, vitamin E should be used according to instructions and with caution.

Avoid too much of a good thing

Being fat-soluble is not a bad thing. But too much of a good thing can quickly turn into a bad thing. Fat-soluble vitamins like vitamin E dissolve in fat, as opposed to water-soluble vitamins like vitamin C. That means that vitamin E can be stored in your body’s fat tissues and liver for up to six months. 

Because most of our vitamin E needs can be met through food, high doses of vitamin E are rarely needed and can cause serious health conditions. 

You may experience side effects

When taken in small doses, vitamin E rarely causes any negative side effects. However, this is not the case for everyone. Here are some side effects to watch out for:

• Blurred vision
• Diarrhea
• Fatigue
• Headache
• Nausea
• Rash
• Stomach cramps
• Weakness

May cause or worsen certain health conditions

Before supplementing or increasing your dietary intake of vitamin E, consider the following health conditions that could be caused or worsened by vitamin E. 

• Prostate cancer: Although further research is limited, a trial study of 35,533 healthy men concluded that dietary supplementation with vitamin E caused a significant increase in prostate cancer.
• Heart disease: Although there is no research to suggest vitamin E causes heart disease, some research does suggest that vitamin E may worsen the condition and increase the risk of death by heart attack or stroke. 
• Hemorrhage: High doses of vitamin E have been shown to cause bleeding and increase the risk for hemorrhagic stroke.
• Diabetes: Current information supports discouraging people with diabetes from supplementing with vitamin E. 

May interact with certain drugs

If you are taking any prescription medications or supplements, check with your medical provider before supplementing with vitamin E. Vitamin E may counteract the effectiveness of some drugs or supplements like vitamin K, statins, niacin, blood thinners, anti-platelet drugs or even chemotherapy drugs. 

Can vitamin E be taken daily?

For adults, the recommended daily amount of vitamin E is 15 mg. It takes only a small amount of the right foods to reach 15 mg. For example, there is 7.4 mg of vitamin E in one ounce of sunflower seeds and 7.3 mg per one ounce of almonds. Either of those will bring you to around 49% of your daily need for vitamin E. 

Because vitamin E is so accessible in food, and in this case, more is not better, supplementing is not often needed. However, if you’re unable to get the recommended daily amount through food, you should limit your supplementation to 15 mg or less per day to achieve the full benefits of vitamin E. 

If you’re taking any other supplements or drugs, be sure to consult with your medical provider before taking vitamin E. 

ISLAMABAD: Defense Minister Khawaja Muhammad Asif on Saturday rejected the Indian air chief’s assertion his country shot down six Pakistani military aircraft during a standoff between the nuclear-armed neighbors, saying no Pakistani aircraft was hit and adding that wars are won through professional competence, not fabrications.

Indian Air Chief Marshal A.P. Singh told a gathering in New Delhi earlier today his country had downed five Pakistani fighter jets and one large surveillance plane in “the largest ever recorded surface-to-air kill” at a range of 300 kilometers. Singh’s assertion was the first such statement by India months after its worst military conflict in decades with its neighbor.

India targeted what it called “terrorist infrastructure” inside Pakistan earlier this year in May, calling it Operation Sindoor and saying it was in response to a gun attack in Indian-administered Kashmir which it blamed on Pakistan. Islamabad denied any involvement and called for an impartial international probe into the incident.

Pakistan said during the intense, four-day standoff it had shot down six Indian fighter jets, including French-made Rafales, right at the outset of the war. It also gave a technical briefing to the foreign media on how the situation unfolded at the outset of the conflict.

“Not a single Pakistani aircraft was hit or destroyed by Indian,” the minister said in a social media post on X. “Pakistan destroyed 6 Indian jets, S400 air defense batteries and unmanned aircraft of India while swiftly putting several Indian air bases out of action.”

He called it ironic that senior Indian military officials were “used as the faces of monumental failure caused by strategic shortsightedness of Indian politicians,” pointing out that for three months, no such claims were voiced by New Delhi.

He said if the truth was in question, both sides should open their aircraft inventories to independent verification.

“Wars are not won by falsehoods but by moral authority, national resolve and professional competence,” the minister said. “Such comical narratives, crafted for domestic political expediency, increase the grave risks of strategic miscalculation in a nuclearised environment.”

Asif warned that, as demonstrated during his country’s response to India, every violation of Pakistan’s sovereignty and territorial integrity would invite a “swift, surefire and proportionate response,” adding that responsibility for any ensuing escalation would rest entirely with “strategically blind leaders who gamble with South Asia’s peace for fleeting political gains.”

India has previously acknowledged some losses, with its Chief of Defense Staff Anil Chauhan saying in an interview with Bloomberg that his forces had made a “tactical mistake” during the May conflict, but denying that six aircraft were lost.

Responding to a question, Chauhan said it was not important how many Indian planes were downed in the war.

“The good part is we were able to understand the tactical mistake which we made, remedy it, rectify it and then implement it again after two days and flew all our jets, again targeting at long range,” he said.

Separately, France’s air chief, General Jerome Bellanger, has said he has seen evidence of the loss of three Indian fighters, including a Rafale.

The Indian Air Force has not commented on the claims.

With input from Reuters

Initial visit

In December 2021, a 59-year-old woman presented to Shanghai Ninth People’s Hospital with a 1.5-year history of visual acuity decline in her right eye. She had a prior history of resection of a right-sided acoustic neuroma at an external medical facility, complicated by right facial paralysis (House-Brackmann Grade VI) and NK (Mackie stage III). She had undergone right eyelid tarsorrhaphy fifteen months earlier and facial nerve transplantation with nerve anastomosis four months prior. She denied any history of diabetes mellitus, AIDS, or autoimmune conditions such as rheumatoid arthritis.

On examination, the right eye demonstrated a central corneal lesion characterized by epithelial erosion, stromal edema and thickening, and neovascularization. The best-corrected visual acuity (BCVA) was 0.01, and corneal sensation was 0/60 using the Cochet-Bonnet esthesiometer (Luneau Ophtalmologie, Chartres, France). The Cochet-Bonnet esthesiometer stimulates mechanoreceptors and polymodal nociceptors, which constitute approximately 90% of corneal nociceptors [5]. Corneal sensation testing was conducted by the same examiner. During the assessment, the patient was seated indoors under natural lighting, initially fixating straight ahead. The examiner applied perpendicular pressure to the central cornea, starting with a filament length of 60 mm and decreasing in 5 mm increments. The maximum filament length eliciting a positive response was recorded as the corneal sensitivity threshold, with three consecutive verifications [6]. Subsequently, she was instructed to sequentially gaze into each of the four peripheral quadrants to evaluate corneal sensation in each region. Results were documented in millimeters of filament length.

In vivo confocal microscopy (IVCM) examination was conducted utilizing the Rostock Cornea Module of the Heidelberg Retina Tomograph II (HRT II RCM, Heidelberg Engineering GmbH, Heidelberg, Germany). IVCM demonstrated a significant reduction in subepithelial nerve fibers, with most regions lacking nerve innervation. She was diagnosed with Mackie stage III NK. Given the refractory nature of her NK and inadequate response to conventional therapy, she was indicated for corneal neurotization.

Minimally invasive corneal neurotization

Corneal neurotization procedures are primarily categorized into direct corneal neurotization (DCN) and indirect corneal neurotization, known as MICN [7, 8]. In DCN, the supratrochlear and supraorbital nerves are identified via a coronal incision at the vertex and subsequently dissected [9, 10]. The principle of MICN involves anastomosing the contralateral supraorbital nerve and supratrochlear nerve with a free sural nerve graft through a minimally invasive approach [11, 12]. Approximately 12–14 cm of sural nerve is harvested as the donor nerve [11, 12]. A 2-cm incision is made in the upper eyelid to isolate the nerve branches of the trochlear and supraorbital nerves [12, 13]. The choice of surgical technique depends on the patient’s condition, the extent of trigeminal nerve damage and the availability of donor nerves. The patient had previously undergone craniotomy for acoustic neuroma resection, and DCN could potentially increase the risk of complications such as encephalitis [10]. In DCN, dissection of the supraorbital nerve may result in forehead hypoesthesia. A section of sural nerve was easy to obtain as the donor nerve in this case. Our hospital was the first medical center in China to perform MICN, with the largest case volume to date. Given that both approaches are accepted treatments for NK with comparable clinical outcomes at twelve months, MICN was considered to cause less trigeminal nerve dysfunction and was deemed safer and technically feasible for this patient without compromising therapeutic goals [10]. Thus, she timely underwent MICN and amniotic membrane transplantation (AMT).

Serial examinations at one to three months post-MICN demonstrated gradual but significant improvement in corneal epithelial integrity and stromal clarity (Fig. 1). Corneal sensation in the temporal quadrant improved to 5/60 (Table 1). IVCM revealed elongated, continuous nerve fibers with improved longitudinal trajectories, suggesting nerve regeneration (Table 2). Corneal nerve fiber length (CNFL) refers to the total length of corneal nerves per mm².Five representative images of the central corneal sub-basal nerve plexus and dendritic cells (DCs) were selected for quantitative analysis based on criteria including the complete image of the same layer, optimal contrast and maximal visibility of nerve fibers and DCs. Sub-basal nerve plexus analysis was performed using an automated software ACCMetrics (MA Dabbah, Imaging Science and Biomedical Engineering). DC density was calculated as the total number of DCs per image and was analyzed using ImageJ. Postoperative corneal sensation and nerve density gradually increased. During the first three postoperative quarters (nine months) following MICN, her corneal epithelium, sensation and nerves gradually recovered (Tables 1 and 2).

Postoperative care included: nutritional supplementation (corneal nerve regeneration), glucocorticoids (inflammation control/immune rejection prophylaxis), nocturnal antibiotic ointment (exposure/infection prevention), and artificial tears (adjunctive therapy) (Fig. 1). Low-concentration glucocorticoids were withdrawn at nine months post-surgery.

SARS-CoV-2 infection episode

Thirteen months post-MICN, the patient developed COVID-19 confirmed by antigen testing, manifesting as a self-limited upper respiratory tract infection. Within one week of viral onset, she experienced acute visual deterioration, representing disease recurrence. Ocular examination revealed a white infiltrative corneal lesion adjacent to the limbus at the 4–5 o’clock position in the right eye, characterized by well-demarcated borders, epithelial defect, stromal edema, and increased purulent secretion (Fig. 2). IVCM revealed inflammatory cell infiltration in the lesion area, and no fungal hyphae or other pathogens were detected. Based on clinical experience, we initially suspected that the patient had infectious keratitis, possibly caused by a viral or bacterial infection. Eye drops for antibacterial and antiviral treatment were administered to the patient. However, two weeks later, the corneal ulcer progressed and there was hypopyon. IVCM findings indicated sparse subepithelial nerve fibers, with most regions lacking nerve presence. Additionally, DC density increased from 41.80 ± 26.13 n/frame to 88.60 ± 20.55 n/frame within two weeks (Table 2).

Given the progressive corneal ulceration and hypopyon, she underwent ocular debridement of the right eye and anterior chamber paracentesis for microbiological diagnostics. The anterior chamber was irrigated, and aqueous humor samples were collected for high-throughput sequencing. Corneal exudate culture results were negative and no pathogenic microorganisms were identified through sequencing analysis. Comprehensive autoimmune serology showed normal levels of autoimmune markers and antibodies. Based on the characteristic clinical manifestations, response to treatment, and temporal association with confirmed SARS-CoV-2 infection, a presumptive diagnosis of COVID-19-related NK was established, representing a virus-related keratopathy.

Protracted neurotrophic keratopathy following SARS-CoV-2 infection

Management of COVID-19-related NK comprised: (1) antiviral agents (e.g., ganciclovir) to mitigate herpesvirus reactivation risk potentiated by SARS-CoV-2-induced immune dysregulation; (2) nocturnal antibiotic ointment/gel for corneal exposure protection and infection prophylaxis; (3) nutritional supplementation; (4) glucocorticoids for inflammation control; (5) artificial tears; (6) 5 mg/mL tropicamide phenylephrine eye drops for anterior chamber inflammation prevention; and (7) two AMTs (Fig. 1). During a severe inflammatory phase (approximately 2 months), 1% prednisolone acetate ophthalmic suspension superseded 0.1% fluorometholone therapy. Four months later, the hypopyon subsided, and the lesion became localized but remained Mackie stage III (Fig. 1). Five months later, central tarsorrhaphy was performed. She did not come for follow-up for a year due to personal excuses. Twenty months after SARS-CoV-2 infection, she showed up and reported alleviation of ocular symptoms. Examination revealed the transparent cornea with only residual corneal macula (Fig. 2). Corneal sensation increased to 30–40/60. During the subsequent follow-up, the patient’s condition remained stable and the NK healed, so lysis of tarsorrhaphy was performed.

Reviewing the treatment process, the patient’s corneal sensation exhibited a trajectory characterized by complete loss, partial recovery, relapse, and eventual partial recovery. Corneal nerve innervation shifted from denervation to neurotization, reverted to denervation following viral infection, and ultimately returned to neurotization (Fig. 3 A, B). DC density initially increased, then decreased, and subsequently rose again post-viral infection (Fig. 3 C, D). DCs played dual roles: facilitating corneal nerve regeneration after MICN and aggravating nerve injury via immune-mediated mechanisms following SARS-CoV-2 infection [4, 14]. Following resolution of recurrent NK after MICN, corneal nerve regeneration was observed, demonstrating that MICN effectively promoted corneal nerve regeneration. Neural pathways reconstructed through peripheral nerve transplantation can regenerate despite prolonged viral infection.

Worldwide genetic diversity and population structure of Pv47

The genetic diversity of Pv47 (PVX_083240; PVP01_1208000.1) was established by analyzing 1199 Pv47 gene coding sequences (Supplementary Data 1) obtained in 28 countries worldwide (Table S1). In total, 71 polymorphic sites were identified in the data set, most of which (68%) contained non-synonymous mutations (Table S2). A total of 209 Pv47 haplotypes were identified (Supplementary Data 2), the majority only present in a specific geographic area (Fig. 1A). Most of the Pv47 gene sequence is highly conserved, with amino acid sequence similarity between haplotypes ranging from 95% to 99.8%. However, there are clusters of non-synonymous polymorphisms close to the predicted N-terminus of domain 1 (Pv47-D1) and in the second domain (Pv47-D2), and one polymorphism is also frequently observed in the third domain (Pv47-D3) (Fig. 1B, left panel). Sites with nucleotide diversity (π) >0.05 were found to be non-synonymous substitutions (Fig. 1B).

Pv47 presented high haplotype diversity (Hd) in the overall population (Hd = 0.95; Table S3). Interestingly, Pv47 sequences from East Asia/ Southeast Asia and Oceania had the highest haplotype diversity, Hd = 0.94 and Hd = 0.93, respectively, and the largest average genetic distance between sequence pairs (estimated as nucleotide diversity, π), with π = 0.0026 and π = 0.0035, respectively (Table S3). The rate of nonsynonymous polymorphisms per site was significantly higher than the rate of synonymous polymorphisms in the Pv47-D2, suggestive of natural selection, especially in South Asia, East Asia/Southeast Asia and Oceania’s populations (Table S3). At least three regions of Pv47, associated with non-synonymous polymorphisms in Pv47-D1, D2 and D3, presented Tajima’s D > 2, also suggestive of natural selection (Fig. S1A).

The frequency of the most common Pv47 protein haplotypes (frequency > 0.05) (Figs. 1C, S2) differed widely between geographic regions. Out of 71 polymorphic sites in the Pv47 coding region, 17 SNPs presented population structure with F_ST > 0.05, and 12 non-synonymous SNPs (causing residue changes F22L, F24L, K27E, S57T, S62N, L82V, D156G, V230I, M233I, I262K/T, I273M/V, A373V) had F_ST > 0.2 between some of the continental populations analyzed (Fig. 1C).

While most Pv47 sequences from South America (75.7%) were identical to the reference Pv-Sal I (from a strain collected in El Salvador), alternate Pv47 haplotypes F22L and K27E (Pv47-D1) were frequent (>0.7) in Mexico and other regions of the world. Alternate haplotypes F24L (Pv47-D1) and I262K/T (Pv47-D2) were also frequent beyond the Americas, while M233I (Pv47-D2) was common in South and Southeast Asia, and A373V (Pvs47-D3) was common in Africa, Southeast Asia, and Oceania. Allele encoding V230I and I273V (Pv47-D2) was frequent in Southeast Asia, while haplotype I273M (Pv47-D2) was frequent in Africa and Oceania (Figs. 1C, S2).

In general, haplotype network analysis shows separation of Pv47 haplotypes circulating in different continents (Fig. 2A), except for Africa, where the most frequent haplotypes are shared with Oceania or present at low frequency in Southeast Asia (Fig. 1C). A marked population structure was also obtained for P. falciparum Pfs47 (Table S5), consistent with previous reports^9,18,19,20, which correlates with the different anopheline mosquito species that transmit malaria in a given region⁹.

The largest genetic distances in Pv47 sequences were between populations from South America and those from Africa (F_ST 0.76–0.83), South Asia (F_ST 0.67–0.86), Southeast Asia (F_ST 0.63–0.86) and Oceania (F_ST 0.60–0.70) (Fig. 2B). There were also significant genetic differences between Middle East/South Asia and Southeast Asia (F_ST 0.25–0.66), and between Oceania and Middle East/South Asia (F_ST 0.39–0.50) and Southeast Asia (F_ST 0.28–0.42). Interestingly, significant genetic differences were also found within the New World, between South America and Mexico (F_ST 0.38–0.64) (Fig. 2B).

Worldwide genetic diversity and population structure of Pfs47

Detailed genetic diversity analysis of 4971 Pfs47 (PF3D7_1346800) sequences confirmed previous reports^20,21 indicating that the most frequent non-synonymous polymorphisms in Pfs47 localize close to the predicted N-terminus of domain 1 (Pfs47-D1) and the second domain (Pfs47-D2), while a polymorphism in the third domain (Pfs47-D3) is less frequent (Fig. 1B, right panel). Pfs47 also presented high haplotype diversity in the overall population (Hd = 0.89; Table S4), with the highest haplotype diversity within South Asia (Hd = 0.87, Table S4). Notably, the average genetic distance between sequences from PNG was particularly large (π = 0.0022, Table S4).

The largest genetic differentiation in Pfs47 was between populations from South America and Asia (F_ST 0.79–0.94) followed by South America and Africa (F_ST 0.72–0.94) and Africa and Asia (F_ST 0.73–0.88) (Table S5). Significant population differences were also found within continents, for example, population differentiation of Pfs47 increased from West to East Africa and Madagascar (F_ST 0.32-0.38) (Table S5); while Central Africa (DRC) presented a modest difference with the rest of Africa (F_ST 0.09-0.25). In Asia, a significant population structure was observed between Southeast Asia and South Asia (Bangladesh)/Oceania (PNG) (F_ST 0.45–0.53), while in South America, Pfs47 presented marked population difference across the Andes, between the coastal regions of Colombia/Central America and the Amazonia in French Guyana/Peru/Brazil (F_ST 0.51–1.0; Table S5). Four regions of Pfs47, associated with non-synonymous polymorphisms in Pfs47-D1 and D2 presented Tajima’s D > 2, suggesting balancing selection, although other causes are possible (Fig. S1B).

Several Pfs47 amino acid polymorphisms differed between geographic regions. Pfs47 haplotypes private to South America differed from African haplotypes in non-synonymous polymorphisms in Pfs47-D2 (T236I, S242L, V247A, and I248L) which are nearly fixed between continents. These are polymorphisms that have been previously shown to be important for mosquito immune system evasion and parasite compatibility with anophelines^9,10,11. Asian private Pfs47 haplotypes also differed from African haplotypes mostly in polymorphisms altering residues in Pfs47-D2 (I224N, T236I, L240I, I248L and N272Y) and one in Pfs47-D1 (L28I) (Fig. S3).

Within Africa, the frequency of the alternate Pfs47 haplotype E27D was high in East Africa, while in Central Africa haplotypes with E188D and N272Y/I were more frequent. In the New World, there was a major difference in Pfs47 populations between Colombia and Amazonia, with the non-reference haplotype I178V being fixed in coastal areas of Colombia, while the reference genotype encoding T68M was fixed in Amazonia. In Asia, there were also significant genetic differences in Pfs47 between Southeast Asia and Bangladesh, mostly due to differences in polymorphisms L28I, E55K, L240I and N272Y bp (Fig. S3).

Experimental evidence of selection of Pv47 by anopheline vectors

An. albimanus is the main vector of P. vivax in the lowlands of Chiapas, Mexico, while An. pseudopunctipennis is the main vector in the piedmont of the Sierra Madre mountain range¹⁴. Previous studies showed that the geographic distribution of three genetically distinct P. vivax populations correlates with the geographic distribution of these two vectors. Furthermore, side-by-side experimental infections in which both mosquito vectors were fed on blood from the same infected human host showed that genetically distinct P. vivax populations differed in their ability to infect these two mosquito vectors^14,22. The authors suggested that the observed P. vivax population structure in Chiapas could be explained by differences in compatibility with these two vector species.

We investigated whether polymorphisms in Pv47 could explain the observed differences in vector compatibility by genotyping Pv47 in 43 isolates previously tested in experimental infections¹⁴ in which the infection prevalence was at least 2-fold higher in one of these two mosquito species and the difference in infection prevalence was statistically significant (Chi-square, p < 0.05) (Table S6). Of these P. vivax isolates, 15 had higher infections in An. albimanus, while 28 infected An. pseudopunctipennis more efficiently (Fig. 3A, Table 1, Table S6). A total of six Pv47 haplotypes were identified (Table 1). Three non-synonymous polymorphisms were present in single isolates (2%), while two of them F22L (88%) and K27E (65%), were frequent (Table 1). The K27E polymorphism in Pv47-D1, in proximity to the predicted N-terminal of Pv47, had a perfect correlation with the differences in vector compatibility. Those isolates with a positively charged lysine (K27) in this position had a significantly higher infection intensity in An. albimanus (Mann-Whitney; ****, P < 0.001), while those with a negatively charged glutamic acid (E27) had a significantly higher intensity of infection in An. pseudopunctipennis (Mann-Whitney; ****, P < 0.001), (Table 1, Fig. 3A).

Predicted molecular structure of Pv47 and Pfs47

In silico modeling of Pv47 and Pfs47 proteins using Alphafold2²³ predicted very similar structures despite having a modest level of amino acid identity (43%) (Fig. 3B). Both proteins consist of three 6-Cys s45/48 domains⁸ with a characteristic ß-sandwich fold formed by antiparallel and parallel ß-sheets (Fig. 3B). Domains D1 and D3 have the canonical 6-Cys pattern. In contrast, D2 is a shorter and degenerate s48/45 domain with only two cysteines, which is linked to the other two domains by flexible, less organized regions. Interestingly, the major polymorphisms in Pv47-D1, close to its N-terminal end, are predicted to be in spatial proximity to the protein surface where the major polymorphisms in Pv47-D2 are present. The major polymorphisms in Pfs47-D2 are known to be critical for immune evasion of the mosquito immune system and are major determinants of compatibility with different mosquito vector species through interaction with the Pfs47 receptor in the mosquito gut^6,9,10. The predicted 3-D structure suggests that D1 amino acid polymorphisms in Pv47 -including K27E- may also interact with the mosquito Pfs47Rec to mediate immune evasion.

Introduction

Congenital heart disease (CHD) is a common congenital malformation caused by abnormal development of the heart and large blood vessels during embryonic development, accounting for about one-third of common birth defects.¹ In recent years, the incidence and mortality of CHD have been increasing globally.^2,3 The number of children with CHD in the world accounts for 0.8%~1% of live births, and the incidence of CHD in China is 0.6%~ 0.9%.⁴ CHD not only causes pain to the child, but also brings a serious economic burden to the family and society.⁵

Due to its complex pathogenesis, CHD presents a variety of disease classification. According to the presence or absence of blood shunt between the left and right sides of the heart and the great vessels, it can be divided into left-to-right shunts types (such as atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA)),⁶ right-to-left shunts types (such as tetralogy of Fallot (TOF), and transposition of the great arteries),⁷ and non-shunt type (such as pulmonary artery stenosis (PAS), and aortic coarctation).⁸ Different types of CHD differ significantly in anatomical structure, hemodynamic changes and clinical manifestations, which brings great challenges to the diagnosis and treatment of the disease.^9,10 Left-to-right shunt CHD is a common one in children. One of the common characteristics of this disease is the presence of abnormal channel between the left and right chambers of the heart, or between the aorta and the pulmonary artery. It causes blood to shunt from the higher pressure left cardiac system to the lower pressure right cardiac system.^6,11 Left-to-right shunt CHD accounts for approximately 50% to 60% of all CHDs, and 0.3‰ to 1.0‰ among newborns.¹² It is a key type of pediatric cardiovascular disease that requires priority intervention.

If left-to-right shunt CHD is not timely and effective treatment, abnormal hemodynamic conditions will continue to affect the development of the heart and other systems throughout the body, and even endanger life.¹³ Long-term left-to-right shunt will cause excessive load on the right heart system, gradually leading to right ventricular hypertrophy, and subsequently affecting the pumping function of the heart.¹⁴ At the same time, the lungs remain in a state of congestion for a long time, which is prone to causing repeated pulmonary infections and hindering the growth and development of the child.¹⁵ Surgical treatment is currently the main method for treating left-to-right shunt CHD in clinical practice.¹⁶ Surgical treatment can correct the anatomical deformity of the heart and restore normal hemodynamic function, effectively improving the cardiac function of the children.^17–19

The prognosis of left-to-right shunt CHD in children is influenced by many factors.²⁰ Some children still face the problem of prolonged hospital stay after surgery. It not only has a negative impact on the physical and mental health of the children themselves, but also brings a burden to the families of the children. Prolonged hospital stay is likely to cause anxiety, depression and other psychological problems. Prolonged hospital stay directly leads to an increase in medical costs and increases family economic pressure. In addition, from the perspective of medical resources, the longer hospital stay will reduce the utilization efficiency of medical resources.^21,22 Most existing studies focus on the analysis of a single factor or are specific to a certain disease type (such as VSD), lacking a comprehensive assessment of the overall population with left-to-right shunt CHD. Children and adolescents are in a special stage of growth and development, and their cardiac and pulmonary function reserves, immune status, and postoperative compensatory ability differ significantly from those of adults. Currently, systematic research on this specific population is still scarce, and the interaction and priority relationship among various factors have not been clarified, resulting in difficulties for clinical practice in formulating precise risk prediction models and intervention strategies. It is of great practical significance to explore the influencing factors of prolonged hospital stay after surgery therapy for children and adolescents with CHD for optimizing interventional treatment, shortening hospital stay, improving medical service quality, and rationally allocating medical resources.

Materials and Methods

Study Cohort

A total of 463 children and adolescents with left-to-right shunt CHD who received surgery therapy in Meizhou People’s Hospital from December 2016 to February 2025 were selected. The inclusion criteria of patients were as follows: (1) patients diagnosed with ASD, VSD, PDA by echocardiography (with or without other simple or complex heart malformations); (2) children and adolescents aged between 0–18 years old; (3) patients who meet the indications for surgery therapy for CHD; and (4) had complete clinical data. Exclusion criteria: (1) preoperative patients with acute infection; (2) patients with significantly impaired or defective function of other organs; and (3) clinical records incomplete. This study was approved by the Human Ethics Committees of the Meizhou People’s Hospital.

Data Collection

The collected clinical data included gender, types of CHDs (ASD, VSD, PDA), the results of echocardiography (such as tricuspid insufficiency, mitral insufficiency, pulmonary insufficiency, and pulmonary hypertension), invasive mechanical ventilation, blood transfusion, tracheal intubation, intraoperative blood loss (mL), and length of hospital stay (days). In the study, compound types CHD was defined as patients with more than one type of CHD at the same time. The threshold for prolonged hospital stay was defined based on the third quartile (75th percentile) of length of hospital stay for all patients.

The definitions of tricuspid insufficiency, mitral insufficiency, pulmonary insufficiency, and pulmonary hypertension:

1. Tricuspid insufficiency refers to the inability of the tricuspid to close completely during the cardiac contraction phase, resulting in abnormal valve function and blood flowing retrogradely from the right ventricle into the right atrium.²³ An echocardiogram examination revealed abnormal regurgitation bands at the tricuspid valve orifice during the contraction phase.
2. Mitral insufficiency is a pathological condition where the structure and function of the mitral valve are abnormal, resulting in the inability of the mitral valve orifice to close completely during the cardiac contraction phase, causing blood from the left ventricle to flow back into the left atrium.²⁴ The diagnosis is based on the echocardiographic finding of a backflow signal at the mitral valve orifice during systole.
3. Pulmonary insufficiency refers to a valve disorder where the pulmonary valve fails to close completely during diastole, causing blood to flow back from the pulmonary artery into the right ventricle.²⁵ The echocardiogram shows a retrograde flow beam at the pulmonary valve orifice during diastole.
4. Pulmonary hypertension refers to an increase in the mean pulmonary artery pressure (mPAP) of ≥20 mmHg at rest.²⁶ The degree of pulmonary hypertension is mainly determined by the pulmonary artery systolic pressure (PASP) value measured through cardiac ultrasound examination: ①mild pulmonary hypertension: PASP is 30–49 mmHg, the pulmonary artery pressure is slightly elevated and usually has not yet caused significant adverse effects on cardiac function and hemodynamics; ②moderate pulmonary hypertension: PASP is 50–79 mmHg, the pulmonary artery pressure is moderately elevated and may gradually affect the pumping function of the heart, leading to an increase in the load on the right ventricle; ③severe pulmonary hypertension: PASP is ≥80 mmHg, the pulmonary artery pressure is significantly elevated, severely increasing the burden on the right ventricle and may exhibit symptoms such as shortness of breath, chest tightness, and edema.

Data Processing and Statistical Analysis

Data analysis was performed using SPSS statistical software version 26.0 (IBM Inc., USA). For variables with a missing value proportion less than 5%, the cases with missing values are directly eliminated. For variables with a missing value proportion between 5% and 20%, the multiple imputation method is used for processing. The continuous data that met the normal distribution were expressed as means ± standard deviations and compared using the t-test; the data not meeting the normal distribution were expressed as medians (25th and 75th percentiles) and compared using the Mann–Whitney U-test. Categorical variables were compared using the χ² test or Fisher’s exact test, between CHD patients with prolonged hospital stay and non-prolonged hospital stay. Logistic regression analysis was used to determine the factors influencing prolonged hospital stay for surgical treatment of left-to-right shunt CHD in children and adolescents.

Results

Clinical Features of the Patients with CHD

There were 227 (49.0%) male patients and 236 (51.0%) female patients. The number of ASD, VSD, PDA patients was 155 (33.5%), 128 (27.6%), 62 (13.4%), respectively, and 118 (25.5%) patients with compound types. There were 177 (38.2%), 18 (3.9%)), and 1 (0.2%) patients with mild, moderate, and severe tricuspid insufficiency, respectively; 84 (18.1%), 14 (3.0%), and 3 (0.6%) patients with mild, moderate, and severe mitral insufficiency, respectively; 11 (2.4%) patients with pulmonary insufficiency; 64 (13.8%), 30 (6.5%), and 13 (2.8%) patients with mild, moderate, and severe pulmonary hypertension, respectively. The proportion of patients treated with invasive mechanical ventilation, blood transfusion, and tracheal intubation was 49.0% (227/463), 49.0% (227/463), and 41.0% (190/463), respectively (Table 1). The mean length of hospital stay was 13.00 (7.00, 18.00) days (Table 1).

Table 1 The Clinical Features of the Patients with Congenital Heart Disease

Comparison of the Clinical Characteristics of Congenital Heart Disease Patients with Prolonged Hospital Stay and Non-Prolonged Hospital Stay in Patients Treated with Surgical Treatment

In this study, 330 (71.3%) patients with non-prolonged hospital stay (<18.0 days) and 133 (28.7%) patients with prolonged hospital stay (≥18.0 days). There were statistically significant differences in the distributions of types of CHD (χ²=67.959, p<0.001), severity of mitral insufficiency (χ²=14.171, p=0.002), and severity of pulmonary hypertension (χ²=49.611, p<0.001) between CHD patients with prolonged hospital stay and non-prolonged hospital stay. The proportion of patients with prolonged hospital stay who treated with invasive mechanical ventilation (86.5% vs 33.9%, p<0.001), blood transfusion (88.7% vs 33.0%, p<0.001), and tracheal intubation (70.7% vs 29.1%, p<0.001) were higher than those of patients with non-prolonged hospital stay, respectively (Table 2).

Table 2 Comparison of the Clinical Characteristics of Congenital Heart Disease Patients with Prolonged Hospital Stay and Non-Prolonged Hospital Stay in Patients Treated with Surgical Treatment

Comparison of the Clinical Characteristics of CHD Patients with Prolonged Hospital Stay and Non-Prolonged Hospital Stay in Patients Treated with Blood Transfusion

In patients treated with blood transfusion (n=227), there were 109 patients with non-prolonged hospital stay and 118 patients with prolonged hospital stay. There were statistically significant differences in the distributions of types of CHD (χ²=12.932, p=0.004), and pulmonary hypertension (χ²=13.253, p<0.001) between CHD patients with prolonged and non-prolonged hospital stay. There were no statistically significant differences in the proportions of tricuspid insufficiency, mitral insufficiency, pulmonary insufficiency, invasive mechanical ventilation, and tracheal intubation (Table 3).

Table 3 Comparison of the Clinical Characteristics of Patients with Prolonged Hospital Stay and Non-Prolonged Hospital Stay in CHD Patients Treated with Blood Transfusion

Logistic Regression Analysis of Risk Factors Associated with Prolonged Hospital Stay

The results of univariate analysis indicated that male (odds ratio (OR): 1.650, 95% confidence interval (CI): 1.099–2.478, p=0.016), compound types CHD (OR: 5.553, 95% CI: 3.533–8.730, p<0.001), mitral insufficiency (OR: 1.897, 95% CI: 1.193–3.014, p=0.007), pulmonary hypertension (OR: 3.770, 95% CI: 2.392–5.940, p<0.001), invasive mechanical ventilation (OR: 12.436, 95% CI: 7.199–21.480, p<0.001), blood transfusion (OR: 15.950, 95% CI: 8.893–28.607, p<0.001), and tracheal intubation (OR: 5.875, 95% CI: 3.774–9.145, p<0.001) were associated with prolonged hospital stay (Table 4).

Table 4 Logistic Regression Analysis of Risk Factors Associated with Prolonged Hospital Stay

In multivariate logistic regression analysis, male (OR: 2.137, 95% CI: 1.278–3.574, p=0.004), compound types CHD (OR: 2.021, 95% CI: 1.178–3.469, p=0.011), pulmonary hypertension (OR: 3.179, 95% CI: 1.537–6.572, p=0.002), invasive mechanical ventilation (OR: 4.069, 95% CI: 1.567–10.564, p=0.004), and blood transfusion (OR: 5.128, 95% CI: 2.421–10.862, p<0.001) were independently associated with prolonged hospital stay (Table 4).

Discussion

The study of the factors influencing the prolonged hospital stay in children with left-to-right shunt CHD has important clinical significance in many aspects, such as optimizing the allocation of medical resources, reducing medical costs, improving treatment plans and improving the prognosis of children. This study found that male, compound types CHD, pulmonary hypertension, invasive mechanical ventilation, and blood transfusion were independently associated with prolonged hospital stay in CHD patients.

Studies have shown that complex CHDs, such as TOF and complete transposition of great arteries, have extremely complex anatomical structure, difficult operation, slow postoperative recovery, and significantly longer hospital stay than simple CHDs, such as atrial septal defect and ventricular septal defect repair.^27,28 This is because the operation of complex CHDs requires more delicate operation, long cardiopulmonary bypass time, great damage to the body, and postoperative complications are prone to occur.^29,30 In addition, the combination of other systemic diseases before surgery (such as lung infection, liver and kidney insufficiency), will reduce the patient’s tolerance to surgery, increase the difficulty of postoperative recovery, and lead to prolonged hospital stay.³¹

CHD patients often have abnormal cardiac structure and function, which lead to hemodynamic changes in pulmonary circulation, and then lead to pulmonary hypertension.³² The persistence of pulmonary hypertension can seriously affect the recovery of cardiopulmonary function.³³ On the one hand, pulmonary hypertension increases right cardiac afterload, leading to right cardiac insufficiency.³⁴ The right ventricle needs to overcome higher pressure to pump blood into the pulmonary circulation, which makes the heart muscle do more work, energy consumption is intensified, and it is easy to cause right heart failure.³⁵ Some studies have shown that the incidence of postoperative right heart failure in CHD patients with pulmonary hypertension is significantly higher than that in patients without pulmonary hypertension, and right heart failure will further lead to systemic circulation congestion,³⁶ liver enlargement,³⁷ lower limb edema³⁸ and other symptoms, which seriously affect the recovery process of patients and prolong hospital stay. On the other hand, pulmonary vascular remodeling caused by pulmonary hypertension increases pulmonary vascular resistance and impairs gas exchange function.³⁹ Pulmonary circulation blood flow is reduced, oxygen dispersion disorders, resulting in poor oxygenation of patients, the body is in a state of hypoxia.⁴⁰ This hypoxic environment will not only affect the function of the heart, liver, kidney and other important organs, but also inhibit wound healing and tissue repair, further delaying the recovery of patients, resulting in prolonged hospital stay.^41,42

There was a significant correlation between mechanical ventilation and length of stay. A long period of mechanical ventilation means that the patient’s respiratory function is slow to recover, and it is not possible to breathe independently from the ventilator as soon as possible.⁴³ On the one hand, this may be due to the serious impact of the operation itself on the cardiopulmonary function. After the reconstruction of the heart structure, it takes a long time to restore the pumping function, which in turn affects the pulmonary circulation and makes it difficult to stabilize the respiratory function in the short term.⁴⁴ On the other hand, patients’ own basic conditions, such as infants’ imperfect respiratory system development, higher dependence on mechanical ventilation, and more difficult to take offline, lead to a significant extension of hospital stay.

Blood transfusion, as an important therapeutic method for correcting anemia and maintaining circulatory stability after surgery in CHD, has a complex and dual impact on the cardiac function of children. On the one hand, anemia can lead to a reduction in oxygen supply to the myocardium, increasing the burden on the myocardium’s work.⁴⁵ Especially for children with left-to-right shunt CHD, there may already be varying degrees of increased ventricular volume load before the operation.⁴⁶ At this time, reasonable blood transfusion can raise the hemoglobin level, enhance the blood’s oxygen-carrying capacity, improve myocardial oxygen supply, thereby maintaining myocardial contractility and cardiac output.⁴⁷ On the other hand, the potential negative impact of blood transfusion on cardiac function cannot be ignored. Blood transfusion may alter the rheological properties of blood. Transfused red blood cells may lead to increased blood viscosity, increase the heart’s pumping burden, and affect the recovery of heart function.⁴⁸ Especially for some CHD patients with weak heart function itself, this effect is more obvious. In addition, blood transfusion may interfere with cardiac tissue repair and regeneration by affecting the body’s inflammatory response and oxidative stress state.⁴⁹ Bioactive substances contained in blood products may activate inflammatory cells, trigger an inflammatory cascade response, damage heart microvascular endothelial cells, and affect myocardial perfusion.⁵⁰ Therefore, blood transfusion has a “double-edged sword” effect on the postoperative cardiac function of children and adolescents with left-to-right shunt congenital heart disease. In clinical decision-making, it is necessary to dynamically monitor the hemoglobin level, cardiac function indicators, and circulatory volume status of the children. A personalized balance point needs to be found between correcting anemia and avoiding volume overload and inflammatory damage, in order to maximize the protective effect of blood transfusion on cardiac function.

In addition, Martins RS et al found that longer aortic cross clamping time and postoperative kidney injury are factors for prolonged length of stay in adults with CHD after surgery.⁵¹ Martins RS et al found that length of some procedures during surgery, and postoperative kidney injury were associated with longer intensive care unit (ICU) stay in adults with CHD after surgery.⁵² Huang et al found that malnutrition was associated with prolonged hospital stay.⁵³ Several studies have also explored predictive markers for longer hospital stays in patients with CHD. Troponin T,⁵⁴ N-terminal pro-brain natriuretic peptide (NT-proBNP),^55,56 and preoperative albumin level⁵⁷ were potential markers of length of ICU stay in CHD children undergoing surgery. PErioperative Adult Congenital Heart disease (PEACH) score was a predictor of prolonged ICU stay in adults with TOF.⁵⁸

This study found some valuable information about the factors that influence the length of hospital stay after surgical treatment in patients with CHD, it still has several limitations. First, the types and severity of CHD are diverse. Due to the limited number of cases included, this study could not compare CHD patients with different diseases, different age groups and different clinical manifestations. Second, it a single-center retrospective study that lacks more comprehensive variable inclusion and long-term follow-up data. Third, this study only analyzed the influencing factors of longer hospital stay in CHD patients, and did not evaluate the predictors of longer hospital stay in CHD patients.⁵⁴ In the future, we expect to include more variables for more adequate preoperative, intraoperative and long-term follow-up to evaluate the factors that influence the short- and long-term prognosis of CHD after surgical treatment.

Conclusion

Male, compound types CHD, pulmonary hypertension, invasive mechanical ventilation, and blood transfusion were independently associated with prolonged hospital stay in CHD patients. Based on this conclusion, in order to shorten the hospital stay of children and adolescents with left-to-right shunt CHD who undergo surgical treatment, in clinical practice, a comprehensive assessment of the patient’s condition should be conducted before the surgery, and the surgical method and timing should be scientifically selected. Of course, the indicators revealed by this information related to longer hospital stay in CHD patients need to be further explored in prospective cohort studies.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval

The study was performed under the guidance of the Declaration of Helsinki and approved by the Ethics Committee of Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences (Clearance No.: 2024-C-60). The parents or legal guardians of all neonates signed informed consent forms.

Acknowledgments

The author would like to thank other colleagues whom were not listed in the authorship of Department of Pediatrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences for their helpful comments on the manuscript.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This study was supported by the Science and Technology Program of Meizhou (Grant No. 2019B0202001).

Disclosure

The authors declare that they have no competing interests in this work.

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Available evidence reveals that there has been a limited number of reported cases of neonatal mpox in Nigeria [20, 21] and worldwide [22,23,24,25,26,27] despite the recognition of human mpox in 1970 and widespread demographic distribution as an endemic virus in Africa. The age group of 0–4 years only accounts for about 0.039% of documented mpox cases globally, with a paucity of information on the clinical management of mpox in this special population [28].

To the best of our knowledge, this is the first reported case of laboratory-confirmed neonatal mpox that was diagnosed in the early neonatal period (the first 7 days of life). The majority, if not all, of documented neonatal mpox in the literature were diagnosed in the late neonatal period, typically between days 8 to 10 of life, thereby creating a dilemma for clinicians and researchers on ascertaining the likely route of mpox acquisition (transplacental or postnatal transmission). This has been an area of uncertainty in the neonatal mpox disease landscape, with the majority of researchers aligning with the general categorization of a perinatal transmission of MPXV since all the documented neonatal mpox cases were diagnosed at the later stages of the newborn’s life [22,23,24,25,26,27].

Considering that our index case developed skin lesions which was confirmed as mpox on the fourth day of life and the fact that mpox has an incubation period of 5–21 days, it is therefore likely that the newborn may have been incubating the virus in utero thereby making the likelihood of a transplacental transmission of MPXV plausible. Furthermore, mpox typically begins with a prodromal phase of febrile illness, followed after 2 to 3 days by vesiculopustular skin eruptions marked on the face and limbs as well as enlarged lymph nodes. This presentation argues for a transplacental route of MPXV transmission in our patient. While postnatal exposure from the mother or the environment cannot be entirely ruled out, this is highly unlikely as the mother no longer had active skin lesions at the time of delivery and, as such, was no longer shedding the virus. Another argument in favour of postnatal transmission is that mpox infection in pregnancy tends to have adverse outcomes, including spontaneous fetal loss, stillbirth, and preterm delivery, which were not observed in this case [29]. Nevertheless, the history of maternal illness at 34th week of gestation, 3 weeks before delivery, supports an intrauterine transmission of MPXV in our patient.

The consideration of a transplacental route of MPXV transmission in this case supports earlier calls by researchers that MPXV should be included in the list of viral TORCH (an acronym for toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex) infection although, this requires further comprehensive fetal and maternal surveillance in pregnancies complicated by mpox [28]. A similar call was made for the inclusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the list of vertically transmitted viral infections during the coronavirus disease-2019 (COVID-19) pandemic based on documented evidence of transplacental transmission of SARS-CoV-2 to the foetus [29,30,31]. Although there is documented evidence of congenital mpox [16,17,18,19], the absence of MPXV-specific neonatal IgM, placental histopathology, in utero imaging, and maternal PCR confirmation at the time of delivery in this case weakens the hypothesis for a vertically transmitted infection. Moreover, most viral TORCH infections typically present with structural anomalies such as microcephaly, chorioretinitis, neurological sequelae, and chronic in utero infections, which were not reported in our case.

Our patient presented with the typical febrile rash syndrome characterized by a centrifugal pattern of distribution, which is pathognomonic for mpox. This is in contrast to other reported cases of neonatal mpox in the literature that reported a disseminated pattern of presentation [22,23,24,25,26,27]. Clinicians should therefore consider mpox as a differential in a newborn presenting with a vesiculo-pustular rash in addition to the traditional differential of varicella, herpes simplex, bacterial sepsis and other poxviruses such as molluscum contagiosum (in the context of a HIV exposed but uninfected newborn), especially if there is a history of similar rash in the family and an endemic region. Although varicella, the closest differential diagnosis of mpox, was negative in this case, the absence of testing for other key congenital infections is an acknowledged limitation of this paper. This underscores the diagnostic challenges in low-resource settings such as Nigeria.

The neonatal immune system is a plastic, highly adaptive system that transitions from a near-sterile environment to a plethora of new organisms after delivery [15]. Due to the immaturity of the immune system, the neonate is highly susceptible to infections that can be devastating when compared to older persons [32]. The detection of mpox in the newborn and the observation of similar symptoms in his parents also aligns with the trend that mpox transmission in Nigeria presently occurs as limited, smaller outbreaks driven by human-to-human transmission among household and non-household contacts [12, 13].

An overlooked important contributory factor to the development of poor clinical outcomes of mpox in the paediatric population is the impact of concurrent or sequential infections [33]. The development of secondary bacterial skin co-infection with MRSA, a WHO priority pathogen known for its virulence and resistance to commonly available antibiotics, may have been responsible for the persistent fever and the prolonged clinical illness in the index case evidenced by the prolonged time to skin lesion resolution of 48 days. The MRSA co-infection is likely to be of nosocomial origin since an initial wound swab microbiology done during the newborn’s admission identified no pathogen. Additionally, physiological decline and marrow suppression from sepsis could have contributed to the anaemia that was recorded in the index patient.

The management of the patient involved a multidisciplinary team of neonatologists, infectious diseases specialists, dermatologists, and other experts in clinical medicine. In line with the NCDC case management guidelines, our index case was optimized on supportive care, which included nutrition, skin care, careful attention to fluid status and fluid management, blood transfusion, and the use of targeted antibiotics to address bacterial skin MRSA co-infection. Similar to previously reported cases of neonatal mpox, our patient recovered following a prolonged clinical course and illness, indicating that timely diagnosis and institution of management potentially lead to good clinical outcomes [23,24,25,26,27].

As there are currently no completed randomized controlled trials investigating the effectiveness of mpox-specific therapeutics such as tecovirimat, brincidofovir, and cidofovir in the paediatric population, children must be prioritized in future clinical trials assessing the efficacy of novel or repurposed therapeutics for mpox. The utilization of the home-based case (HBC) model and telemedicine in the clinical management of this patient has emerged as an important adaptive approach in mpox case management, especially in resource-limited settings witnessing surge activities in their treatment centers. This is especially true given the tendency of mpox to present with non-severe disease.

In conclusion, neonatal mpox infection is rare and could lead to prolonged morbidity and mortality. Clinicians should always maintain a high index of suspicion and consider mpox in the differential diagnosis of a neonatal vesiculo-pustular rash, particularly if there is a history of similar rash in the family, as early disease recognition and early treatment are associated with improved outcomes. Further studies are needed to better understand the transmission routes of MPXV in newborns.

Modern convenience can carry an unseen price. A new analysis of more than 100,000 Americans finds that people who eat the most ultra-processed food (UPF) face a 41 percent higher risk of developing lung cancer than those who eat the least.

Lung cancer remains the world’s deadliest malignancy, causing an estimated 2.2 million new cases and 1.8 million deaths in 2020.. Those grim numbers make any avoidable risk factor worth close attention.

“Worse still, over the past two decades, the consumption of UPF has significantly increased worldwide, regardless of development or economic status,” said lead author Dr. Kai Wang of Chongqing University Cancer Hospital.

Lung cancer and UPF

Researchers mined the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), focusing on 101,732 adults aged 55 to 74.

Participants logged their diets once at enrollment, then their health was tracked for a dozen years, during which 1,706 lung cancers emerged.

Compared with the lowest quarter of UPF eaters, the top quarter had hazard ratios of 1.41 for all lung cancer, 1.37 for non-small cell lung cancer and 1.44 for small cell lung cancer.

Those figures held after accounting for smoking, overall diet quality, body size and many other variables.

Lunch meat, diet sodas and white bread were the biggest single contributors to UPF intake in this cohort. The median participant still averaged nearly three servings of these packaged products each day.

Study statisticians noted a non linear dose response curve, meaning risk climbed fastest between the first and third daily servings, then rose more slowly. Still, no amount of UPF appeared protective.

Most people eat way too much UPF

UPF already supply more than half the calories eaten at home in the United States, rising from 51 percent in 2003 to 54 percent in 2018. Globally, market growth echoes that trend as manufacturers push shelf stable snacks into every aisle.

“Greater exposure to ultra processed food was associated with a higher risk of adverse health outcomes,” reported Melissa Lane, lead author of a 2024 umbrella review. Her team linked UPF to 32 different problems, from heart disease to depression.

These products are rich in added sugars, salt, saturated fats and chemical additives while lacking dietary fiber and micronutrients. They often replace oatmeal, fruit and vegetables on busy mornings and rushed lunches.

Marketing targets all ages but especially children, creating taste preferences that can persist for decades. That lifelong exposure may magnify the cancer risk flagged in the new study.

Possible biological pathways

Poor nutrient density is only part of the story. Industrial formulation changes the food matrix, altering how nutrients and contaminants interact with human tissue.

Heating and smoking meats can produce acrolein, a reactive aldehyde also abundant in cigarette smoke. Laboratory work shows acrolein damages mitochondrial DNA, triggers mitochondrial fission and promotes cell stress in human lung cells.

Package leaching adds another layer of concern. Serum studies have linked elevated polychlorinated biphenyls to higher lung cancer odds, possibly via estrogen receptor signaling in lung tissue.

Food dyes, emulsifiers and preservatives likewise influence gut bacteria, systemic inflammation and insulin regulation. A 2023 meta-analysis tied each 10 percent rise in daily UPF calories to an 11 percent jump in cardiovascular events.

Taken together, these mechanisms suggest UPF do more than crowd out wholesome fare. They may foster a biochemical environment where rogue cells thrive.

Even non-smokers at risk

Smoking still drives most lung tumors, yet one quarter occurs in non smokers. For them, diet, air pollution and occupational exposures loom larger.

Interestingly, Dr. Wang’s subgroup analysis hinted that never smokers experienced a steeper relative risk from heavy UPF intake than current or former smokers. When baseline risk is lower, every harmful exposure carries more weight.

Passive smoke combines with UPF related contaminants such as acrolein, compounding oxidative stress. Add sedentary habits and excess body fat, and non smokers may unknowingly accumulate multiple small hits to lung tissue over time.

The study controlled for body mass index, yet obesity itself may mediate some dietary effects through chronic inflammation. Further work is needed to tease apart these overlapping pathways.

Cancer risks and UPF habits

Because participants reported diet only once, shifts in eating style went unrecorded. People who quit UPF midway, or adopted them later, all looked the same on paper.

Smoking intensity details were unavailable, leaving residual confounding possible. Yet the researchers calculated an eValue of 2.17, meaning only an undiscovered factor with a hazard ratio stronger than heavy smoking could erase the observed link.

The cohort was mostly non-Hispanic White and well educated. Findings may differ in younger, more diverse or lower income settings where UPF represents an even larger calorie share.

Longer follow up could reveal whether risk falls after dietary change, but randomized trials are unlikely for ethical reasons.

Observational evidence, mechanistic data and consistent signals across health outcomes build a persuasive narrative nonetheless.

Smart swaps for everyday meals

Swapping one sugary drink for water or unsweetened tea each day eliminates a key UPF source. Replacing lunch meat with roasted chicken or hummus on whole grain bread cuts sodium and nitrate exposure.

Frozen vegetables, plain yogurt and canned beans demonstrate that convenience need not equal heavy processing. Look for ingredient lists shorter than a tweet, and favor foods your grandparents would still recognize.

Meal planning on weekends can reduce midweek reliance on instant noodles and microwave entrées. Community programs that subsidize fresh produce make those choices easier for households on tight budgets.

Public health advocates call for front of pack warnings, advertising restrictions and taxes similar to soda levies. Whether policy shifts or personal habits change first, the Thorax findings add urgency to reducing UPF on our plates.

The study is published in Thorax.

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Introduction

According to the World Health Organization (WHO), approximately 60 million HCWs worldwide are exposed to hazardous biological agents daily.¹ Healthcare workers (HCWs) are vulnerable to infectious diseases due to occupational exposure, posing risks to themselves, their families, and patients.² Vaccination is a crucial strategy for reducing the incidence and severity of infectious diseases by lowering the risk of infection, alleviating symptoms, and decreasing disease-related morbidity and mortality.^3,4 Furthermore, even in Western countries, influenza vaccine uptake has been persistently insufficient in the European region over the past decade.^2,5 Although there has been commendable COVID-19 primary series vaccination coverage among healthcare professionals in the United States at 84.1%, the vaccination uptake for the bivalent booster remains comparatively low at 38.6%.⁶

The WHO recommends that HCWs receive either primary or booster doses for vaccines such as Bacillus Calmette–Guérin (BCG), Diphtheria, Hepatitis B, Influenza, Measles, Meningococcal, Pertussis, Polio, Rubella, Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), and Varicella. HCWs should be up to date on all recommended vaccines, with documented proof of immunity or immunization required for employment and training.⁷ Low vaccination coverage among HCWs has become a pressing issue, particularly during the COVID-19 pandemic, as it poses risks to both healthcare providers and patients. Despite the availability of vaccines, many healthcare systems struggle with low vaccination rates, which can lead to increased transmission, nosocomial infections, and avoidable deaths.⁸ A multicenter cross-sectional study indicated that vaccination coverage rates among HCWs were low, with many unable to recall their immunization status.⁹ Other research has highlighted that even HCWs who administer vaccines can exhibit vaccine hesitancy, often driven by concerns about vaccine safety.¹⁰

Despite the Saudi Ministry of Health’s commitment to promote vaccination among HCWs and provide free vaccinations at government health facilities, there is a significant prevalence of vaccine hesitancy among healthcare providers, leading to a low willingness to receive vaccines.^11,12 Consequently, understanding and addressing this hesitancy is essential for improving vaccination coverage and ensuring a safer healthcare environment. This study aimed to address the issue of vaccination coverage among HCWs at primary care facilities in Najran City, Saudi Arabia by measuring the prevalence of vaccine hesitancy within this crucial workforce and identifying the contributing factors. Understanding this issue is essential for establishing a safer healthcare environment, preventing disease transmission, improving overall public health, and further enhancing efforts to improve vaccination coverage.

Methodology

Study Design, Setting, and Duration

To assess vaccination coverage among HCWs in Healthcare facilities and identify factors contributing to vaccine hesitancy, a descriptive and analytical cross-sectional study was conducted throughout August 2023, encompassing over 50 healthcare facilities within both the public and private sectors in Najran City, a strategically situated city in south-western Saudi Arabia near the Yemeni border, which poses a threat of communicable diseases.^11,13,14 Primary healthcare facilities were selected based on their provision of primary care services to patients. Furthermore, this study adhered to the Declaration of Helsinki guidelines for human research.

Sample Size

The sample size was calculated using the Raosoft sample size calculator, assuming a 95% confidence interval, 50% response distribution, and 5% margin of error, yielding a target sample size of 377 HCWs. Anticipating 10% attrition, we aimed for a minimum of 424 participants. However, to enhance statistical power and minimize bias, we collected 591 fully completed questionnaires, which were all included in the final analysis.

Study Sample and Sampling

The study targeted HCWs at Najran’s Primary Healthcare facilities, (including primary healthcare centers (PHC), hospital outpatient clinics, hospital emergency departments, and polyclinics) specifically physicians, dentists, pharmacists, nurses, and technicians, who had worked there for at least six months. All eligible HCWs who agreed to participate were included, whereas those with less experience (<11 months) or those on leave during data collection were excluded. A multistage cluster sampling technique was used to obtain a representative sample of HCWs. This involved the random selection of HCWs from each category, and has an equal chance of being chosen for a sample. HCWs including physicians, pharmacists, dentists, nurses, laboratory technicians, radiology technicians and paramedics; subsequently, the willing HCWs within those facilities were clustered, ensuring proportional representation from each type of facility and category.

Data Collection and Tools

Data were collected by a self-administered questionnaire which was developed by the researcher following WHO and Centers for Disease Control and Prevention (CDC) guidelines.¹⁵ It comprised three distinct sections: The first section: “sociodemographic variables, for example, healthcare workers” age, sex, family status, nationality, job title, position, qualifications, healthcare facility, workplace, and years of experience. The second section: medical characteristics, for example, use of immunosuppressant medications, caring for immunocompromised patients, current pregnancy, contraceptive method, feeling burned out, taking unhealthy food, physical inactivity, having abnormal body weight, having sleep problems, and tobacco smoking. The third section: vaccination profile was assessed using a checklist comprising nine items about the vaccination status of the most recommended vaccines for HCWs including annual influenza, third and seasonal booster doses against COVID-19, hepatitis B infection vaccination course, primary chickenpox (varicella) infection vaccination course, primary measles, mumps, and rubella (MMR) vaccination course, primary tetanus, diphtheria, pertussis (Tdap) vaccination course, either a Td or Tdap booster shot every ten years, and Tdap dose during each pregnancy in pregnancy cases. Additionally, four items evaluated the documentation of immunization, encompassing the recording of vaccines, laboratory evidence of immunization, laboratory confirmation of disease, and diagnosis or verification of disease history by a healthcare provider. Participants self-reported their vaccination status and documentation of immunization, selecting from response options of “Yes”, “No”, or “I do not know”. After the initial draft of the questionnaires, three professionals including one researcher was evaluated the questionnaires and independently given their inputs on the suitability, content and flow. Later the questionnaires were subjected pilot study among randomly selected HCWs. The reliability was determined using Cronbach alpha value which was found to be 0.74, suggesting that questionnaires reliable to carry out the study.

Response Interpretation

The researcher analyzed survey responses from participants regarding their vaccination status (items 1–9), classifying participants into four categories:

• Fully vaccinated: those who answered “Yes” to all relevant vaccination questions.
• Partially vaccinated: those with a mix of “Yes” and “No” answers for different vaccinations.
• Unvaccinated: those who answered “No” to all or most vaccination questions.
• Unsure: those who marked “I don’t know” for all or most vaccination questions.

Vaccination rates were calculated for each category, allowing examination of patterns or differences among various HCW groups. Additionally, responses to items 10–13 were analyzed to assess documentation of immunization, using similar criteria (complete, partially complete, incomplete, and unsure documentation). The researcher also considered potential discrepancies between participant reports regarding their immunization documentation. In this study, burnout was defined as a work-related stress syndrome characterized by chronic exposure to job stress.^16,17 Abnormal body weight was defined as a body mass index (BMI) outside the healthy range, including both underweight and overweight/obesity.^18–20

Statistical Analysis

Descriptive statistics were presented as counts and percentages for categorical variables. The Chi-square test was used to analyse the relationship between vaccination profiles and socio-demographic/medical characteristics. Multivariate logistic regression model identified independent predictors of non-compliance to vaccination and incomplete immunization documentation, employing odds ratios and 95% confidence intervals, with significance set at p<0.05. Data analysis was conducted using SPSS version 26.²¹

Results

A total of 591 HCWs participated in the survey. Most (45.8%) were aged 31–40 years, with approximately 60% male. Married HCWs made up 66.9%, and Saudi nationals were 59.8%. Nurses (25.9%) and physicians (21.8%) were the most common types, with 60.9% holding bachelor’s degrees, as shown in Table 1.

Table 1 Socio-Demographic Characteristics of Participants (n=591)

Regarding the medical characteristics of participants, only three respondents used immunosuppressant medications, and seven participants reported currently carrying immunocompromised medications. Only 2.4% were currently pregnant, and 5.8% were using contraceptive methods. HCWs who ate unhealthy foods, had physical inactivity, abnormal body weight, sleep problems, tobacco smoking, and burnout constituted 13.2%, 34.9%, 24%, 16.4%, 10.8%, and 11.2%, respectively. The vaccination profile of HCWs showed the highest compliance for the third COVID dose (86.3%), followed by hepatitis B (81.2%) and influenza (78.3%). The lowest compliance was for Tdap during pregnancy (27.7%). Immunization documentation indicated evidence through vaccine records (67.5%), lab tests (51.8%), disease confirmation (36.9%), and historical verification (36.7%), as shown in Table 2.

Table 2 Vaccination Profile of Participants (n=591)

In Figure 1, 70.9% of HCWs were considered partially vaccinated, 19.1% were fully vaccinated, and 10% were considered unvaccinated. As shown in Figure 2, 57% of HCWs had partial completion of immunization documentation, 15.7% had complete documentation, and 27.2% had incomplete documentation.

Figure 1 Vaccination status.

Figure 2 Documentation of immunization for HCWs in Najran’s primary health care facilities, 2023.

When determining the relationship between the vaccination status and sociodemographic characteristics of the HCWs (Table 3), it was observed that male (p=0.001), Saudi nationality (p=0.030), and technician/paramedic HCWs (p<0.001) were more likely to be unvaccinated compared to other HCWs.

Table 3 Relationship Between Vaccination Status and Sociodemographic Characteristics of Participants (n=591)

Regarding the relationship between vaccination status and medical characteristics of HCWs, only feelings of burnout showed a significant relationship with vaccination status; HCWs who experienced burnout were more likely to be unvaccinated (p=0.006). However, there was no significant relationship between vaccination status and having a chronic disease, current pregnancy, contraceptive use, unhealthy eating, physical inactivity, abnormal body weight, sleep problems, or tobacco use. When conducting a multivariate regression analysis (Table 4), it was observed that only the job titles remained significant for the vaccination status, suggesting that compared to physicians, technicians/paramedics were predicted to have a higher chance of being unvaccinated by at least 2.74 times (AOR=2.743; 95% CI=1.140–6.600; p=0.024), whereas sex, nationality, and feeling burnout had no significant relationship with the vaccination status after adjustment to a regression model (p>0.05).

Table 4 Multivariate Regression Analysis to Determine the Independent Significant Predictors of Non-Compliance to Vaccination (n=591)

The analysis of the relationship between the immunization documentation and the sociodemographic and medical characteristics revealed that the older age group (p=0.037), pharmacists/dentists (p=0.001), and those working in hospital-outpatient clinics (p<0.001) were more likely to have incomplete documentation. Additionally, physically inactive HCWs (p<0.001), those with abnormal body weight (p=0.005), and those experiencing burnout (p=0.001) also showed a higher likelihood of incomplete immunization documentation. A multivariate regression model (Table 5) revealed that, compared to physicians, nurses had decreased odds of having incomplete documentation for their immunization status by at least 55% (AOR=0.446; 95% CI=0.221–0.902; p=0.025). Compared to HCWs working in PHC centers, HCWs working in hospital emergency departments had decreased odds of having incomplete immunization documentation by at least 74% (AOR=0.256; 95% CI=0.074–0.887; p=0.032) and decreased odds of 79% among those who were working in polyclinics (AOR=0.212; 95% CI=0.059–0.756; p=0.017). In contrast, HCWs who experienced burnout were 2.69 times more likely to have incomplete immunization documentation than those who did not experience burnout (AOR=2.696; 95% CI=1.336–5.441; p=0.006).

Table 5 Multivariate Regression Analysis to Determine the Independent Significant Predictor of Incomplete Documentation of Immunization (n=591)

Discussion

This study aimed to measure vaccine hesitancy among HCWs in Najran’s primary healthcare facilities and identify influential factors. The study revealed significant gaps in vaccination coverage among respondents: a striking 70.9% were only partially vaccinated, while just 19.1% achieved full vaccination status, leaving 10% completely non-compliant. This aligns with a study from Tanzania, which reported an 18% full vaccination rate.²² In contrast, a study in China noted higher vaccination rates in 2020–2021 (43.7%) compared to 2021–2022 (35.4%), highlighting low coverage among Chinese HCWs.³ Similar trends increased during the post-COVID-19 era were observed in Tunisia,⁴ Italy,⁹ and Saudi Arabia.¹¹ Addressing vaccination compliance is crucial particularly in primary health care settings, as healthcare facility-acquired infections significantly impact health resources and service quality. This highlights a critical need for targeted interventions to improve vaccine uptake on the frontline.

The study’s results indicate that male HCWs, Saudi nationality, technicians/paramedics, and perceived burnout influence non-compliance with vaccination coverage. However, in the predictive model, only technicians/paramedics emerged as significant independent predictors (p=0.024). This may result from a low perception of risk due to inadequate education about vaccination. A literature review in Italy found vaccine hesitancy linked to low-risk perception, lack of behavioural control, negative attitudes, insufficient knowledge, and limited access to vaccination.² Additionally, some HCWs believed natural immunity was superior to vaccination (p<0.001) and expressed concerns about the potential long-term effects of vaccines (p=0.044).²³

Conversely, other studies highlight factors influencing vaccine uptake. Cherif et al noted that confidence in influenza vaccine efficacy significantly boosts uptake among HCWs.⁴ Schumacher et al found that nurses had vaccination rates 2.7 times higher than other professions.⁸ In this study, non-Saudis showed higher compliance with vaccination coverage, though not statistically significant (p=0.422). Additionally, no associations were found between vaccination status and medical characteristics such as chronic diseases, pregnancy, contraceptive use, unhealthy eating, physical inactivity, abnormal body weight, sleep problems, or smoking (p>0.05).

The assessment of the vaccination status of HCWs for the most recommended vaccines revealed the highest compliance for the third dose of the COVID-19 vaccine (86.3%), hepatitis B vaccine (81.2%), primary chickenpox vaccine (71.9%), and primary MMR vaccine (71.2%). Conversely, adherence to the Tdap booster (35.7%) and Tdap doses during pregnancy (27.7%) was low, potentially influenced by the inclusion of both male and female HCWs. This contrasts with Oygar et al, who reported higher Tdap rates (57.8%).²⁴ However, in a study conducted by Kumbul and Özgür, the prevalence was higher for the hepatitis B vaccine (67.5%), followed by tetanus (62.3%), MMR (39.5%), varicella (28.8%), hepatitis A (20.1%), and influenza (6.3%) in that order.²⁵ Variations in vaccination rates may reflect regional differences and the timing of studies, especially post-COVID-19.

The study highlights a troubling in the documentation of immunizations among HCWs, revealing that only 15.7% possess complete records, while 57% have partial documentation and 27.2% are inadequately documented. In Saudi Arabia, the Ministry of Health’s (MOH) immunization programs and National Health Strategy (2019–2025) guide public health policy on vaccines for healthcare workers (HCWs).^26–28 The MOH mandates vaccinations against influenza, Hepatitis B, and measles, mumps, and rubella for HCWs.²⁹ To promote vaccination, the MOH implements initiatives that include educating HCWs on vaccine benefits and risks, organizing vaccination campaigns, tracking coverage, and evaluating program effectiveness. Additionally, the MOH provides guidelines for safe vaccine administration.^29,30

This may be the first research of its kind in Saudi Arabia, underscoring an urgent need for further investigation into vaccination practices. The WHO advocates for HCWs to maintain up-to-date records of all recommended vaccinations, as the absence of such documentation poses a significant risk of infections not only to patients but also to the wider community.⁷ Consequently, work restrictions for susceptible HCWs—ranging from limited patient contact to complete exclusion from duty—may be necessary to mitigate these risks, emphasizing the critical importance of compliance with vaccination protocols to safeguard both healthcare professionals and those they care for.³¹

The study highlights that nurse practitioners in emergency departments and polyclinics are more likely to have documented immunization statuses compared to other HCWs. However, burnout among HCWs adversely affects this documentation, as regression analysis reveals that those experiencing burnout often have incomplete records. Given the inverse relationship between stress and immune function, which underscores the need for preventive measures against infections, it is crucial to emphasize the importance of vaccinations and their proper documentation. This focus is essential not only for patient safety but also for managing the psychological stress faced by HCWs. This study has several limitations. Firstly, the findings are based on a single region in Saudi Arabia, limiting their generalizability to other regions and international contexts. Secondly, the reliance on self-reported data may introduce biases, such as social desirability and recollection bias, as healthcare workers may have provided answers they perceived as desirable. To mitigate these limitations, future studies could consider alternative data collection methods, such as focus groups, to enhance the accuracy and reliability of the findings.

Conclusion

This study highlights significant gaps in vaccination coverage among HCWs in Najran’s primary healthcare facilities, with only 19.1% fully vaccinated. Factors influencing vaccine hesitancy included male gender, Saudi nationality, and perceived burnout, particularly among technicians and paramedics. The results underscore the critical need for enhanced vaccination compliance to mitigate the risk of healthcare facility-acquired infections. The findings also reveal a low level of immunization documentation, which poses risks to both HCWs and patients. Addressing these issues through targeted education, mobile vaccination units, and awareness campaigns is essential. In future studies, it is important to investigate the underlying causes of vaccine hesitancy among healthcare workers (HCWs) and design tailored interventions to address this issue. It is also essential to explore the relationship between burnout and vaccine hesitancy in more detail, including potential interventions to mitigate burnout and improve vaccine uptake. Additionally, conducting follow-up studies to assess the impact of vaccination programs on vaccine coverage and hesitancy among HCWs is necessary. Overall, improving vaccination rates and documentation is vital for safeguarding public health and ensuring the well-being of healthcare professionals.

Data Sharing Statement

All data generated and analyzed are included in this research article is available upon request to the corresponding author.

Ethical Approval

This study was approved by the Scientific Research and Conferences Committee at the Faculty of Medicine, Najran University (CSR/NU/2023/1041, dated February 12, 2023). Prior to data collection, participants were informed that their information would be kept confidential, used solely for research purposes, and that they had the right to withdraw from the study at any time.

Informed Consent

The participants provided verbal informed consent for participation in the study.

Acknowledgments

The author would like to thank Editage (www.editage.com) for English language editing.

Funding

This research did not receive funds.

Disclosure

The author declares no conflicts of interest in this work.

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