Congenital tuberculosis with tuberculous meningitis and situs inversus totalis: A case report

INTRODUCTION

Congenital tuberculosis (TB) refers to an infection due to contact between the baby and the TB bacillus in the uterus or during delivery. Maternal TB can be transmitted to the fetus through the placenta or by inhalation of infected amniotic fluid. The former forms primary complexes in the liver of infants, and the latter forms primary lesions in the lungs or gastrointestinal tract[1]. Congenital TB is very rare, and the mortality rate is exceptionally high[2,3]. Respiratory failure is the most common cause of death[2,4,5]. Intracranial infection is one of the most severe complications, seriously affecting the prognosis[3]. Misdiagnosis and untimely treatment are the main reasons for aggravation of the condition. Situs inversus totalis (SIT) is a rare congenital malformation, and some patients may also suffer from defective ciliary motility[6]. The ciliary immobility is involved in the absence of mucociliary transport in the respiratory epithelia[7], which may induce lung infections. We here report a patient who suffered from rare congenital TB, tuberculous meningitis, and SIT. Congenital TB complicated with SIT was not found from the Google Scholar and PubMed databases.

CASE PRESENTATION

Chief complaints

A 19-day-old male newborn was admitted to the hospital with a fever for 6 h.

History of present illness

The child was born at 41 wk of gestation and was delivered smoothly. The birth weight was 2.925 kg. His respiratory rate was 50 breaths/min, weight was 3.93 kg, heart rate was 150 beats/min, and he had no intrauterine distress and no premature rupture of fetal membranes. Fever occurred 6 h before admission, and the highest body temperature was 38.2 ℃.

History of past illness

The baby was delivered normally without a history of allergies.

Personal and family history

The patient’s mother had a history of miscarriage. Both parents denied a history of TB, but his grandmother had TB when she was young.

Physical examination

Lin H, a radiologist, reviewed the literature, participated in the drafting of the manuscript, and interpreted the imaging findings; Teng S and Wang Z reviewed the literature and contributed to manuscript drafting; Liu QY was responsible for the revision of the manuscript for important intellectual content; all authors issued final approval for the version to be submitted.

记者经过楼上活动室时，看到有两位老人正在打乒乓球，看上去身体很硬朗，济南恒协基爱社区养老服务中心主任、山东恒协基爱老年产业投资有限公司公司董事长张振美告诉记者，孙叔和赵叔是老人中身体最好的两位，最爱锻炼，乒乓球室和健身房常被他们俩“霸占”着。

Laboratory examinations

The following parameters were observed in serum: C-reactive protein 46.3 mg/L (reference range: ≤ 6.0 mg/L), procalcitonin 1.23 μg/L (reference range: < 0.054 μg/L), white blood cells (WBC) 22.92 × 10

/L (reference range: 15-20 × 10

/L), neutrophils 0.701, total bilirubin 87.9 μmol/L (reference range: < 26.0 μmol/L), and indirect bilirubin 81.2 μmol/L (reference range: < 14.0 μmol/L). Cerebrospinal fluid (CSF) was cloudy, with a chloride ion level of 117.5 mmol/L (reference range: 120.0-132.0 mmol/L), protein concentration 0.92 g/L (reference range: 0.08-0.43 g/L), glucose 3.15 mmol/L (reference range: 3.9-5.0 mmol/L), adenosine deaminase 0.2 U/L, and WBC 35 × 10

/L (reference range: < 30 × 10

/L). Bacterial testing showed Gram-positive cocci on smears, acid-fast bacilli were found on acid-fast staining, and the tuberculin-γ-interferon release test was positive. Microbial genetic testing detected the

complex.

Imaging examinations

The imaging manifestations of congenital TB have specific characteristics. Early imaging of lesions may include interstitial pneumonia[12], and miliary pneumonia and multiple pulmonary nodules may appear when the condition worsens. Multiple pulmonary nodules are considered disease progression[12]. Peng

[3] suggested that miliary TB on chest imaging 4 wk postpartum should be used as one of the diagnostic criteria for congenital TB, which can provide a timely basis for diagnosis and treatment. If

spreads to the liver and spleen

the blood, it can form a primary complex. Abdominal CT showed hepatosplenomegaly, and multiple low-density primary complexes were also seen. In our case, the baby's chest radiography and chest CT showed scattered high-density nodules in both lungs, thickened lung texture, enlarged hilar lymph nodes, and normal size and density of the liver and spleen. In addition, the dextrocardia and internal organs were reversed (Figures 1 and 2). Therefore, we believe that the cause in this case was the infant inhaling or ingesting amniotic fluid contaminated by

.

FINAL DIAGNOSIS

The baby was finally diagnosed with congenital TB with tuberculous meningitis and SIT.

The mortality rate of congenital TB is very high, close to 50%, usually due to delayed diagnosis and treatment[5]. The clinical manifestations do not improve after antibiotic treatment, and the condition of 96% of children may worsen[3]. Early diagnosis and timely anti-TB treatment can significantly reduce infant mortality and improve prognosis[3]. Newborns with congenital TB should receive isoniazid (10-15 mg/kg/d), rifampicin (10-20 mg/kg/d), pyrazinamide (20-40 mg/kg/d), and streptomycin (20-40 mg/kg/d) intravenously for 2 mo; isoniazid and rifampicin should be continued for 6 mo[25]. Our patient only started anti-TB treatment on the 10

day after admission, but his condition continued to deteriorate, and he eventually developed severe pneumonia and tuberculous meningitis and died of respiratory failure at 38 d.

TREATMENT

Following admission, the patient underwent repeated tests for viruses and bacteria, including

and other pathogens. The test samples included blood, sputum, gastric juice, and CSF. The test results in the first 10 d were all negative. Amoxicillin and clavulanate potassium were given on the day of admission. Potassium retinoic acid (0.117 g IV q8h) was discontinued the next day and changed to oseltamivir phosphate granules (10 mg oral qd) and ceftazidime (0.19 g IV q8h). Vancomycin (58 mg IV q8h) was administered and the blood concentration of vancomycin was controlled at 7.4 μg/mL (effective range: 7-10 μg/mL). Meropenem (0.15 g IV q8h) was added on the 4

day after admission. However, these anti-infective treatments were ineffective, lung exudation was aggravated, and regular blood oxygen saturation could not be maintained. Invasive ventilation was then used to support the patient's breathing. Neurological symptoms such as epilepsy and irritability were also observed. On the 10

day after admission, acid-fast bacilli were found in the patient's sputum following acid-fast staining. Microbial genetic tests confirmed

complex. Vancomycin, oseltamivir phosphate particles, and ceftazidime were then stopped, and anti-TB treatment was started with niacin injection (0.057 g IV qd), pyrazinamide tablets (0.13 g gastric tube injection qd), and rifampicin injection (0.057 g IV qd). After 7 d of anti-TB treatment, the patient's chest radiography showed improvement in lung exudation (Figure 1). The child was kept alive through invasive ventilation, but eventually died of respiratory failure due to the worsening of the disease.

OUTCOME AND FOLLOW-UP

电池在过充到一定阶段，电池内压过大超过电池盖板与壳体之间的焊接强度时就会发生破裂，随后电池内部的高压气液混合物就会喷出，在喷射过程中遇到氧气，并与空气、电池测试支架摩擦，就会发生爆炸。图2是电池2C过充致爆过程中喷射物的红外热像图片。

DISCUSSION

Congenital TB is a rare disease. In 2005, fewer than 376 cases were reported worldwide[2]. Cantwell

[1] proposed the classic diagnostic criteria for congenital TB, where infants were confirmed to have TB if they had at least one of the followings: Symptoms in the first week after birth, primary liver TB complex, maternal genital tract or placental TB, and postpartum transmission ruled out by thorough investigation of contacts. In this case, the mother's tuberculin skin test was positive, and pelvic CT suggested possible tuberculous peritonitis. Moreover,

was found in the baby's sputum, and chest radiography indicated progressive and disseminated TB. Therefore, our case met these diagnostic criteria.

The clinical manifestations of congenital TB are non-specific, making early diagnosis difficult[1,5]. The most common clinical symptoms are loss of appetite, fever, restlessness, hypoplasia, weight loss, cough, respiratory distress, hepatosplenomegaly, splenomegaly, lymphadenopathy, and abdominal distension[2,8]. Generally, congenital TB is easily misdiagnosed as pneumonia, sepsis, and purulent meningitis[3]. Conventional antibiotic treatment is ineffective and the disease may progress to serious complications such as miliary TB and tuberculous meningitis. These serious complications may be related to the infant's immature innate immunity[9]. The clinical symptoms of the child, in this case, were mainly fever, loss of appetite, restlessness, and respiratory distress. These symptoms are nonspecific.

was not detected in the baby in the first 10 d after admission. The mother had no symptoms of TB infection before and after childbirth. Therefore, TB infection could not be diagnosed early.

Laboratory tests for congenital TB are generally non-characteristic and easily confused with acute infections due to other pathogens[10]. The most common reaction is an increase in the number of WBC and inflammatory indicators. Identifying the presence of tubercle bacilli by fluid body cultures, acid-fast staining, or tissue biopsy is the gold standard for the diagnosis of TB[11]. In our case, bacteria and viruses were tested immediately after admission, and the results were negative. In addition, repeated acid-fast staining of sputum and gastric juice was negative, and tubercle bacilli were not found in the sputum until the 10

day after admission. Delayed diagnosis is a crucial cause of disease aggravation.

所递交的检测流程和结果报告要以书面形式展现，要求环境监测在日常工作中把责任内容分配到每个人身上，把审核制度分成三级：（1）原始采样审核制度；（2）分析原始记录审核制度；（3）报告审核制度。构建完成后，需加大监管审核力度。提高环境监测的质量，是当前环境监测机构的重点内容。环境监测的水平与科学化程度对环境监测质量有很大的影响，所以，要通过制度的约束来提高环境监测的质量。

Chest radiography showed increased texture and thickening of the lungs, scattered with patchy highdensity shadows. In addition, the apex of the heart and gastric bobble was on the right, and the liver was on the left (Figure 1). Chest computed tomography (CT) showed multiple nodules in both lungs, and hilar lymph nodes were enlarged (Figure 2A and B). The heart, liver, and spleen were also completely reversed, showing mirror-like changes (Figure 2B and C).

经过对检测段周围水文地质情况的勘察，发现其进口处的围岩主要是灰色凝灰岩，但是其中夹杂一些夹凝灰质砂页岩，这种岩石的块状结构比较大，且比较完整，但是其抗风化的能力比较弱。而周围的地下水来源主要是地表水和雨水的渗透，因此，受到季节的影响比较大。进行施工时，缺陷段的围岩没有出现渗漏水的现象[1]。而在斜井周围，2个方向的水文地质情况也不相同，虽然周围的岩石都是凝灰岩，但是小里程方向段的围岩质量明显比大里程方向段的好。二者的地下水情况基本相似，都是靠雨水和地表水作为补给源，受季节的影响变化较大。同时，在施工过程中也没有出现渗漏水现象。

2.1.2 采集地点。调查地点为河北省怀安县太平庄乡、阳原县大田洼乡。其土壤为北方典型的干旱半干旱贫瘠类型。河北省怀安县太平庄乡属高寒山区与丘陵区，耕地2 323 hm2，旱地2 306 hm2，旱地占比99.3%。阳原县大田洼乡耕地1 043 hm2，旱地面积705 hm2，旱地占比67.6%。

Inborn anomalies of organ placement are rare developmental abnormalities with an incidence of about 1/8000[21], which can be divided into SIT and incomplete situs inversus[22]. However, in 20%-25% of SIT cases, they also have Kartagener syndrome (KS) (bronchial immobility, bronchiectasis, chronic sinusitis, and male infertility)[23,24]. KS is also known as ciliary immobility syndrome, which can lead to obstruction of mucus drainage from the respiratory tract, which increases the possibility of lung infection. However, we cannot confirm whether the baby has KS and whether KS will increase the prevalence of congenital TB.

13号线推荐采用最高运行速度为100 km/h的列车。当列车过站速度为100 km/h时，在不同的站间距条件下，快车少停1站所节约的时间约为25～30 s。另外，考虑在城市轨道交通中，平均停站时间为30～35 s。综上所述，13号线快车若少停1站，可节省时间55～65 s。

The newborn underwent anti-TB treatment, but due to delays in diagnosis and treatment, his condition continued to deteriorate and he eventually developed severe pneumonia and tuberculous meningitis, and died of respiratory failure at 38 d.

CONCLUSION

Congenital TB is very rare, and concurrent tuberculous meningitis and congenital SIT have not been reported. It is not clear whether they are related or not. The clinical manifestations of congenital TB are non-specific, the detection of pathogenic bacteria is difficult, it is easily misdiagnosed, the fatality rate of the disease is high, and it can progress to severe tuberculous meningitis. Early diagnosis and anti-TB treatment are the keys to reducing mortality and improving infant prognosis. For infants with a high suspicion of TB infection, empirical anti-TB treatment should be administered.

作为现实社会的延伸，网络空间也同样充满了各国之间的分歧和冲突。个别西方国家依靠自己的网络技术优势，垄断网络资源和网络话语权，实施网络霸权。某些西方发达国家为了惩罚或推翻非亲西方的发展中国家，往往会以切断其国家的网络服务为借口进行要挟，逼迫发展中国家就范；或者利用网络空间对于发展中国家进行意识形态渗透，造成社会的混乱；更有甚者直接利用网络工具煽动和策划发展中国家内部的反政府力量进行推翻现有政府的活动。这些活动必然会加深发展中国家与这些发达国家之间关于网络规则、网络秩序和网络治理理念的分歧与对抗。

FOOTNOTES

Breath sounds were rough in both lungs, with an increased breathing rate and wet rales could be heard.

In recent decades, neonatal tuberculous meningitis has rarely been reported[13-15]. Common neurological symptoms and signs include drowsiness, meningeal irritation, cranial nerve palsy, epilepsy, hemiplegia, alteration of consciousness, coma,

[16]. About half of all tuberculous meningitis infections cause severe disability or death[17]. When TB meningitis is suspected, magnetic resonance imaging (MRI) should be selected, as it is unique in assessing early and late disease and is effective in children with suspected TB meningitis[18,19]. In this case, the infant's neurological symptoms were irritability, convulsions, and poor response. The number of WBCs and protein concentrations in the CSF were increased, and the concentrations of glucose and chloride ions were decreased. Combined with the detection of TB and multiple pulmonary nodules following sputum analysis, this was consistent with the diagnostic criteria for tuberculous meningitis[20]. Unfortunately, head MRI was not performed at that time.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

No conflicting relationship exists for any author.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

但自从有了这些电子产品，许多带给我的很多惹我焦虑的事物倒不再是问题了。比如从前每次开会，听人念报告，我都有大声唱歌的冲动，就像在大合唱的时候很想放声尖叫。而现在，当别的同事掏出本子，我会默默地打开Kindle，反正Kindle的保护壳和开会用的黑皮本很像。再比如家长会，一听见那个分贝大、底气足、语气坚定、音色尖锐的校长在广播里讲着不容置疑的道理，我浑身的神经元细胞都紧张起来——好在有手机。

China

Hu Lin 0000-0003-2365-8254; Shuang Teng 0000-0002-4074-4026; Zhong Wang 0000-0002-6391-9140; Qi-Yu Liu 0000-0002-8166-3134.

Fan JR

为推进生态旅游治理提供有力执法和司法保障。用严格的法律制度引领生态旅游治理措施，保护生态环境，为推进生态旅游治理的实施提供执法和司法保障。首先，加大执法力度，对干扰管理活动、破坏生态环境的行为要给予严厉打击。其次，细化和完善现有环境侵权责任法律制度，引导社区居民利用法律武器保护自身生态权益。再次，加大对破坏生态、妨碍治理行为的法律责任追究力度，对损害生态环境的恶劣行为给予严厉制裁。

Wang TQ

Fan JR

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