「双语学习」伤寒⼉童患者重度⾎⼩板较少症⼀例
怎么炒火锅底料
Typhoid fever is a systemic infection caud by Salmonella enterica subsp. enterica rovar Typhi and occasionally Salmonella Paratyphi. Thrombocytopenia is relatively common in typhoid fever, with a reported incidence up to 26% in children. It has been classified as a marker of verity in typhoid fever and indicates a high risk for development of complications. Despite this, its pathophysiology and management in typhoid fever is not well established. We prent a ca of vere thrombocytopenia in a child with typhoid fever and we discuss the published literature.
伤寒是由沙门⽒菌亚种、伤寒沙门菌、偶有甲型副伤寒沙门（⽒）菌引起的全⾝性感染。⾎⼩板减少症常见于伤寒，据报道⼉童发⽣率⾼达26%，是伤寒病情严重的指征之⼀，提⽰并发症⾼风险。虽然如此，⾎⼩板减少症在伤寒中的病理⽣理学和管理尚不完全明确。下述为伤寒⼉童患者重度⾎⼩板较少症⼀例，并对已发表的⽂献予以讨论。
Ca Prentation
病例呈现
A 4-year-old Asian boy prented to the emergency department at a tertiary children’s hospital in Sydn
ey, Australia, 1 day after returning from travel to Bangladesh with a persistent fever for 10 days. He had visited Bangladesh with his parents and stayed for 8 weeks. He had vomiting, diarrhea, and fever 3 weeks after arriving in Bangladesh, for which he was given oral ciprofloxacin for 3 days. The vomiting and diarrhea resolved after 1 week, but he continued to have intermittent fevers up to 38 °C (100.4 °F) for an additional 2 weeks. During the last 10 days of his stay in Bangladesh, his fever became persistent, with peaks of 40 °C (104 °F). He had reduced oral intake and constipation, but no vomiting. His mother reported that she had developed lf-limited vomiting and diarrhea for a few days after the ont of his symptoms. The family denied eating street food or drinking tap water in Bangladesh. There was no history of contact with patients with tuberculosis. The child had been born in Australia to Bangladeshi parents, and his immunizations were up to date, according to the Australian schedule. He did not receive any travel vaccines prior to travel or malaria prophylaxis. His medical history was unremarkable apart from mild asthma.
患者，4岁，亚籍男孩。在孟加拉旅⾏返回1天后开始出现持续性⾼烧，症状持续10天，到悉尼的⼀家三级医院急诊科就诊。患者曾与⽗母在孟加拉旅⾏8周，到达孟加拉3周后出现呕吐、腹泻等症状，⽤药⼝服环丙沙星3天。1周后呕吐和腹泻缓解，但间歇性发烧38 °C⼜持续了2周。在孟加拉的最后10天，出现持续性发烧，最⾼时体温达40 °C。饮⾷减少，便秘，⽆呕吐症状。患者母亲称孩⼦出现症状
⼏天后⾃⼰也出现⾃限性呕吐和腹泻。否认⾷⽤街边⾷物和饮⽔。未与肺结核患者接触。患者出⽣在澳⼤利亚，⽗母是孟加拉⼈，⼀直进⾏免疫接种。旅⾏前未接种任何疫苗和预防疟疾。病史：轻度哮喘，其他不明显。
In the emergency department he appeared unwell and moderately dehydrated. He was febrile at 39.8 °C (103.6 °F), tachycardic with a heart rate of 160 beats per minute, and his respiratory rate was 32 breaths per minute. There was no icterus, pallor, or lymphadenopathy. A skin examination did not reveal any rash, petechiae, or bruising. A chest and cardiovascular examination revealed no abnormalities. His abdomen was soft, mildly tender, and distended with no organomegaly. There was no clinical ascites and his bowel sounds were prent. He was alert and oriented, with a normal neurological examination. He had no bone or joint pains or swelling. Initial investigations showed anemia, leukopenia, and thrombocytopenia. His hemoglobin concentration was 102 g/L and reached a nadir of 89 g/L on day 11 of admission. He had a nadir white cell count of 4.30 × 109/L (neutrophils 2.6 × 109/L and lymphocytes 0.9 × 109/L) on prentation, which gradually improved to 11 × 109/L by day 11. His initial platelet count was 97 × 109/L. His renal function was normal apart from mild hyponatremia, while his liver function tests showed hypoalbuminemia and mild transaminitis with normal bilirubin concentrations. His C-reactive protein level was elevated at 92 mg/L. Considering hi
s clinical prentation, travel history, and the initial investigation results, the differential diagnos included typhoid fever, malaria, and dengue fever. We ordered a blood culture, and thick and thin blood films for malaria parasites and dengue IgM, IgG, and NS1 antigen. He was then commenced on ceftriaxone intravenously and admitted to our hospital. There were no malaria parasites en in two films and dengue rology was also negative. The following day his stool and blood cultures grew Salmonella Typhi. The organism was reported to be susceptible to ceftriaxone and azithromycin, with decread susceptibility to ciprofloxacin. It was reported to be resistant to ampicillin, chloramphenicol, and trimethoprim.
在急诊室时，患者表现不适，中度脱⽔，发烧39.8 °C，⼼动过速，⼼率160次/分，呼吸频率32次/分。⽆黄疸、⾯⾊苍⽩、或淋巴结肿⼤。⽪肤检查未发现⽪疹、瘀点或青紫。胸部和⼼⾎管检查未发现异常。腹部质软，轻微压痛，扩张，⽆脏器肿⼤。⽆腹⽔，有肠鸣⾳。患者清醒，定向良好，神经检查正常。⽆⾻或关节疼痛、肿胀。最初检查显⽰贫⾎，
⽆脏器肿⼤。⽆腹⽔，有肠鸣⾳。患者清醒，定向良好，神经检查正常。⽆⾻或关节疼痛、肿胀。最初检查显⽰贫⾎，⽩细胞减少，⾎⼩板减少。⾎红蛋⽩浓度102 g/L，⼊院第11天达到最低89 g/L。⼊院时，最低⽩⾎细胞计数4.30 ×109/L（中性粒细胞2.6 × 109/L，淋巴细胞0.9 × 109/L），⼊院11天后，逐渐升⾄11 × 109/L。最初⾎⼩板计数97 ×109/L。除轻度低钠⾎症外肾功能正常，肝功能检查发
现低蛋⽩⾎症，轻微转氨酶升⾼，胆红素浓度正常。C-反应蛋⽩⽔平升⾼92 mg/L。鉴于患者的临床表现、旅⾏经历及最初的检查结果，鉴别诊断包括伤寒，疟疾和登⾰热。安排了⾎培养，采⽤厚薄涂层以分析疟原⾍和登⾰热IgM，IgG，和NS1抗原。之后患者开始静脉滴注头孢曲松，收⼊我们医院。⾎培养未发现疟原⾍，登⾰热⾎清检查也呈阴性。第⼆天患者粪培养和⾎培养发现伤寒沙门⽒菌。据报道此类有机物对头孢曲松和阿奇霉素敏感，对环丙沙星敏感度降低。有报道称其对氨苄青霉素、氯霉素、甲氧苄氨嘧啶有抗性。
Our patient continued to have fever spikes to 39–40 °C every 4 hours after admission until the fifth day, when the frequency of fever decread to three spikes daily. Further improvement was noticed by day 9, with temperature spikes decreasing to twice daily and less than 39 °C. He required intravenous fluids for a short period to correct his dehydration until his oral intake gradually normalized over the first week in hospital. In addition, he received an albumin infusion on day 5 after he developed clinical ascites with a further drop in his albumin to 17 g/L. Thrombocytopenia was notable in our patient. His platelet count initially fell steadily and reached a nadir of 16 × 109/L on day 5 despite appropriate antibiotic therapy (Fig. 1).
⾃⼊院到第5天，患者持续发烧（每4个⼩时⼀次），达39–40 °C，第五天起每⽇发烧3次。第9天时情况改善，每⽇发烧2次，且低于39 °C。⼊院第⼀周内，患者请求静脉注射药物以治疗脱⽔，直⾄经⼝
饮⾷恢复正常。此外，在⼊院第5天时，患者出现腹⽔，⽩蛋⽩⽔平降⾄17 g/L，于是接受输注⽩蛋⽩。⾎⼩板减少症较为明显，⾎⼩板计数稳定下降，虽然给予抗⽣素治疗，但是⼊院第5天⾎⼩板计数达最低16 × 109/L。
He was monitored cloly for complications associated with thrombocytopenia: his nsorium remained intact and he did not develop petechiae, bruising, or rectal bleeding during admission. There was no sign of intestinal perforation, with normal bowel sounds and an abnce of bloody stool. At this stage, we considered whether additional therapy for thrombocytopenia would be required, such as platelet transfusion. Upon discussion with our infectious dias team, it was decided to treat him conrvatively with clo obrvation and not to give him a transfusion. His platelet count was monitored on a daily basis, began to improve on day 6 of admission, and finally normalized on day 11 and then climbed to supra-normal levels by day 15. Likewi, his transaminas were abnormal throughout admission, peaking on day 5 (Fig. 1), but started to improve before discharge. By day 9 of admission, his oral intake improved and oral azithromycin was added to transition to oral therapy. He completed a 12-day cour of ceftriaxone in hospital and was discharged in a good condition, although he still had occasional fever spikes to 39 °C. He continued to have intermittent elevated temperatures (<38 °C) at home, but his parents reported that
he returned to his previous energy level and activity. After he completed a total 7-day cour of azithromycin, he was reviewed in an outpatient clinic where he was afebrile with a normal examination.
密切监视患者⾎⼩板减少症相关的并发症：感觉中枢完好，住院期间未出现瘀点、瘀斑、或直肠出⾎。⽆肠穿孔症状，肠鸣⾳正常，⽆⾎便。我们考虑是否需要额外治疗⾎⼩板减少症，如输注⾎⼩板。与传染病专家组讨论后，决定给予保守治疗，并密切观察，不予以输注⾎⼩板。每⽇监测⾎⼩板发现，⼊院第6天时，患者⾎⼩板计数开始改善，第11天时恢复正常，第15天时达到超正常⽔平。同样，住院期间患者转氨酶⽔平异常，第5天达到峰值（图1），出院前开始好转。⼊院第9天，经⼝饮⾷改善，加⽤⼝服阿奇霉素，过渡到⼝服治疗。住院期间患者接受头孢曲松⼀个疗程（12天），出院时状况良好，偶尔发烧 39 °C。出院后仍存在间歇性体温升⾼（<38 °C），患者⽗母称能量和活动⽅⾯已恢复。接受⼀个疗程（7天）阿奇霉素后，门诊检查时⽆发烧，⼀切正常。
图1：⾎⼩板减少和转氨酶变化过程
Discussion
讨论
Typhoid or “enteric” fever is a systemic infection caud by Salmonella enterica subsp. enterica rovar Typhi and occasionally Salmonella Paratyphi. It is characterized by vere systemic illness, often prenting with features of fever, constipation, and abdominal pain. Its incidence in endemic countries can be as high as 540 cas per 100,000 population, making it a public health challenge. In an Australian tting, it particularly affects returned travelers from the Asian subcontinent.
Important differential diagnos of typhoid fever in a returned traveler from South and Southeast Asia include dengue fever and malaria. In addition, acute murine typhus can have similar prentation to typhoid fever. It is common, yet underdiagnod, in travelers from this region. Thompson et al. found rologic evidence of acute murine typhus in 17%多动症表现
underdiagnod, in travelers from this region. Thompson et al. found rologic evidence of acute murine typhus in 17% of patients who prented with undifferentiated febrile illness at a tertiary referral hospital in Nepal. All patients had sterile blood cultures with no cas of murine typhus found among tho with confirmed enteric fever. We did not investigate our patient for murine typhus or other rickettsial infection becau typhoid fever was confirmed promptly on day 2 of his admission.
旅⾏后的患者出现伤寒重要的鉴别诊断包括登⾰热和疟疾。此外，急性斑疹伤寒的临床表现可能与伤
小学语文学习方法寒相似，可能诊断不出来。Thompson等对尼泊尔⼀家三级转诊医院的患者开展研究，17%的患者出现⽆差别发烧，从⽽发现了急性斑疹伤寒的⾎清学证据。所有受试患者均进⾏⽆菌⾎培养，已证实伤寒的患者中未发现斑疹伤寒。对于本⽂所述患者在⼊院第⼆天即确诊为伤寒，所以未进⾏斑疹伤寒或其他⽴克次体感染检查。
Thrombocytopenia is an important finding in the asssment of returned febrile travelers. It is defined as a platelet count below the lower limit of normal (i.e., <150 × 109/L). It is further subdivided into mild (100–150 × 109/L), moderate (50–99 × 109/L), and vere thrombocytopenia (<50 × 109/L). In a study conducted in an outpatient clinic in Germany, 3.8% of returned travelers had thrombocytopenia. Typhoid/paratyphoid fever was responsible for 14% of the cas, ranking fifth after malaria, acute human immunodeficiency virus (HIV) infection, dengue fever, and Epstein-Barr virus (EBV) infectious mononucleosis. The most frequent travel destination in the study was Asia (42%). Thrombocytopenia is well reported in patients with typhoid fever. Malik reported an incidence of 26% in Malaysian children with typhoid fever and Pohan found it in 61.5% of cas in one study of adults. Despite this, the pathophysiology of thrombocytopenia and its clinical cour in typhoid fever are not well understood. Propod mechanisms of the hematological manifestations of typhoid fever, including thrombocytopenia, include bone marrow suppression, peripheral destruction by the reticulo
endothelial system, autoimmune-induced destruction, and Salmonella endotoxin-induced thrombocytopenia. Bone marrow examination was not performed in our patient but we note he had abnormalities in three hematological cell lines, suggesting possible bone marrow suppression.
⾎⼩板减少症在评估旅⾏后出现发热的患者时是⼀项重要发现，表现为⾎⼩板计数低于正常值下限（即 <150 ×
109/L）。⾎⼩板减少症进⼀步分为轻度（100–150 × 109/L）、中度（50–99 × 109/L）和重度（<50 × 109/L）。德国⼀家门诊诊所进⾏的⼀项研究表明，3.8%的旅⾏后的⼈群出现⾎⼩板减少症。其中伤寒和副伤寒占14%，继疟疾、急性⼈类免疫缺陷病毒（HIV）感染、登⾰热、Epstein Barr病毒（EBV）传染性单核细胞增多症之后排名第五，最常见的患者旅⾏⽬的地为亚洲（42%）。伤寒患者出现⾎⼩板减少症的报道颇多：据Malik报道，马来西亚⼉童伤寒的发病率为26%；Pohan在⼀项针对成年⼈的研究中发现，伤寒发病率为61.5%。尽管如此，⼈们对⾎⼩板减少症的病理⽣理学及其在伤寒时临床过程尚不完全清楚。已有的伤寒（包括⾎⼩板减少症）的⾎液学表现包括：⾻髓抑制、⽹状内⽪系统周围的破坏、⾃⾝免疫引发的症状、以及沙门⽒菌内毒素引起的⾎⼩板减少症。该患者未进⾏⾻髓检查，但注意到其三系⾎细胞异常，提⽰可能存在⾻髓抑制。
Factors that might contribute to the verity of typhoid fever include the duration of illness before the
rapy, the inoculum size, the immune status of the patient, and the previous vaccination against typhoid fever. Our patient had been unwell for veral weeks before prentation and thus the inoculum size at the time of commencing treatment could have been relatively high. He had no known or suspected immunodeficiency, but had not received a typhoid vaccination prior to travel to Bangladesh, which could have prevented this illness. The duration of illness and fever in patients with typhoid strains resistant to ampicillin, chloramphenicol, and trimethoprim can be more prolonged despite receiving antibiotics to which strains are susceptible.
判断伤寒严重程度的因素包括治疗前病程、接种量、患者免疫状态、之前接种的抗伤寒疫苗。该患者⼊院就诊前数周出现⾝体不适，因此开始治疗时的接种量可能相对较⾼。患者⽆已知或疑似免疫缺陷，旅⾏前未接种过伤寒疫苗（预防伤寒）。有伤寒菌的患者对氨苄青霉素、氯霉素、甲氧苄氨嘧啶有抗性，易感伤寒菌的患者即使接受了抗⽣素治疗，其病程和发烧持续时间更久。
男护In addition to splenomegaly and leukopenia, thrombocytopenia is considered a sign of vere dia in typhoid fever with a higher risk for development of complications. Thrombocytopenia usually develops during the cour of the illness, but it can be a prenting feature of typhoid fever, as in this ca. Severe complications of typhoid include intestinal perforation, intracranial hemorrhage, and multi-organ failure. Among 102 children with typhoid fever in one study, 33% devel
oped complications, most commonly anicteric hepatitis and bone marrow suppression, but also paralytic ileus, myocarditis, psychosis, cholecystitis, osteomyelitis, peritonitis, and pneumonia. The rate of any complications among tho with thrombocytopenia was 54%. Our patient had anicteric hepatitis, hypoalbuminemia with ascites, and thrombocytopenia, but he remained alert and oriented without any clinical evidence of intracranial hemorrhage despite a platelet nadir of 16 × 109/L on day 5 of admission. He also did not have any clinical evidence of intestinal perforation and his renal function remained normal throughout his admission. Considering our patient’s pancytopenia, we considered the possibility of infection-associated hemophagocytic syndrome as a complication of his typhoid fever, becau this has been previously reported. Given that he was slowly improving clinically, we
最美的散文his typhoid fever, becau this has been previously reported. Given that he was slowly improving clinically, we decided to obrve him cloly without performing additional invasive tests, such as bone marrow examination. Further investigation, including consideration of hemophagocytic syndrome, would have been required if he had failed to improve.
除了脾肿⼤和⽩细胞减少症，⾎⼩板减少症也被视为伤寒中的严重症状，且并发症风险⾼。⾎⼩板减少常出现于伤寒过程中，可视为伤寒的特征表现（如本⽂所述）。伤寒较为严重的并发症包括肠穿孔，谏太宗十思疏原文
颅内出⾎，多器官功能衰竭。⼀项研究纳⼊102例伤寒⼉童患者，其中33%出现并发症，⽆黄疸型肝炎和⾻髓抑制最为常见，还有⿇痹性肠梗阻、⼼肌炎、精神病、胆囊炎、⾻髓炎、腹膜炎、肺炎。⾎⼩板减少症患者出现上述并发症的⼏率为54%。该患者出现⽆黄疸型肝炎、低蛋⽩⾎症伴腹⽔和⾎⼩板减少症，清醒，定向良好，⼊院第5天⾎⼩板达最低值16 × 109/L，⽆颅内出⾎证据。住院期间未出现肠穿孔，肾功能检查显⽰正常。鉴于其全⾎细胞减少，我们将感染相关的噬⾎细胞综合征作为伤寒的⼀种并发症（之前曾有相关报道）。由于患者临床症状逐渐改善，我们决定密切观察，不予以额外的有创性检查，如⾻髓检查。若患者情况未改善，则应进⾏进⼀步检查包括考虑噬⾎细胞综合征。
Becau the risk of hemorrhage is incread when the platelet count falls below 20 × 109/L, this level was traditionally considered the threshold for prophylactic platelet transfusion. Later prospective studies have proved that lowering this trigger to 10 × 109/L in stable patients with cancer or blood disorders is still safe. However, platelet count should not be the only indicator for deciding transfusions. Other important elements that indicate the patient is at incread risk of bleeding, and thus likely to have an incread need for platelet transfusion, include raid body temperature, psis, and rapid decrea in platelet count. Like most blood products, platelet transfusions are not free of adver effects. The include blood-borne infections, although now rare owing to good screening; bacterial contamination; febrile transfusion reactions; transfusion-related acute lung injury; and anaphylactic reactions.
由于⾎⼩板计数低于20 × 109/L时出⾎风险升⾼，传统上将这⼀⽔平作为预防性⾎⼩板输注的临界值。后续的前瞻性研究已证明，对于病情稳定的癌症患者和⾎液疾病患者，将这⼀指标降⾄10 × 109/L后，仍处于安全范围。但是，⾎⼩板计数不应作为判断输注的唯⼀因素。其他重要提⽰出⾎风险增⾼，因⽽增加了输注⾎⼩板的必要性的因素包括：体温升⾼，脓毒症，⾎⼩板急速下降。与⼤多数⾎液制品⼀样，输注⾎⼩板也存在副作⽤，如⾎源性感染（⽬前筛查较严格，出现较少）、细菌污染、发热性输⾎反应、输⾎相关的急性肺损伤以及过敏反应。
There are no studies or guidelines addressing the management of thrombocytopenia in typhoid fever. This pos a challenge for clinicians, especially when faced with vere thrombocytopenia, as in this ca. Some ca reports have described platelet normalization shortly after starting antibiotic therapy without a need for platelet transfusion. In one ca, however, the platelet count fell from 154 × 109/L to 14 × 109/L despite antibiotic therapy, and this was associated with multi-organ failure; plasma exchange was given to correct the thrombocytopenia and other abnormalities. One adult patient died from vere hemolytic uremic syndrome attributed to Salmonella Typhi, with failure to respond to a platelet transfusion given along with a blood transfusion and plasmapheresis. Our patient had a relatively slow recovery with fever and hepatitis persisting for 2 weeks, despite appropriate antibiotic therapy, and a slow return to normalization of platelet count on day 11. However, he avoided a platelet transfusion and was well at last follow-up.
关于伤寒中的⾎⼩板减少症的管理尚⽆临床研究和指南。这为临床医师带来了挑战，尤其是重度⾎⼩板减少症患者的诊治（如本⽂患者所⽰）。⼀些病例报告中，作者描述了启动抗⽣素治疗后⾎⼩板即恢复正常，⽆需输注⾎⼩板。但是，有⼀例患者虽进⾏抗⽣素治疗，但其⾎⼩板计数从154 × 109/L降⾄14 × 109/L，这与多器官功能衰竭相关；进⾏了⾎浆置换以治疗⾎⼩板减少症和其他疾病。还有⼀例成年患者死于沙门伤寒菌引起的危重型溶⾎尿毒综合征，进⾏输注⾎⼩板、输⾎及⾎浆置换均⽆效。本⽂所述患者虽然进⾏适当的抗⽣素治疗，发烧和肝炎症状持续2周，之后才缓慢恢复，⾎⼩板计数在第11天才缓慢恢复⾄正常⽔平。不过，患者未进⾏⾎⼩板输注，随访检查⼀切正常。
鹅蛋的作用
Conclusions
结论
We have described a ca of vere thrombocytopenia in typhoid fever with slow clinical and laboratory respon but complete recovery after appropriate antibiotic therapy and supportive care alone, thus avoiding the risks associated with platelet transfusions or plasmapheresis. The optimal management of thrombocytopenia in typhoid fever merits further study to guide clinical practice.
京东双十一晚会本⽂描述了⼀例伤寒症患者出现⾎⼩板减少症。患者只进⾏了适当的抗⽣素治疗和⽀持性治疗，临床和实验室检查指标恢复较慢，最终完全恢复，因⽽避免了⾎⼩板输注或⾎浆置换相关的风险。为指导
临床实践，伤寒症中的⾎⼩板减少症的管控仍有待进⼀步研究。
