重视儿童急性白血病化疗并发症的防治——附卡氏肺囊虫肺炎诊治体会

目前,采用正确的化疗方案能使大部分儿童急性白血病获得长期无病生存,尤其是儿童急性淋巴细胞白血病(ALL)的5年以上无病生存率已达70%以上。但是,有效防治强烈化疗后并发症和避免化疗相关死亡等临床措施与疗效有待提高。卡氏肺囊虫肺炎(PCP)多发生于儿童AL缓解期,临床表现为气急、干咳和紫绀。肺部体征不明显,与临床症状不一致。胸部影像学检查显示多样性病变,缺乏特异性表现。静脉滴注足量复方磺胺甲基异口恶唑(SMZco)疗效显著。由于PCP起病较为隐匿,临床诊断有一定难度,如不及时治疗将导致患儿死亡,需要临床高度重视。该文对PCP疾病性质、临床特征和早期诊断治疗经验作了较为详细的讨论。     

Pneumocystis carinii pneumonia in a girl with a midbrain glioma

A 7-year-old girl with a midbrain glioma contracted Pneumocystis carinii pneumonia (PCP) the absence of cytotoxic or corticosteroid therapy. Gliomas are known to cause immunosuppression, in and PCP prophylaxis should be considered for patients with these tumors.     

Pneumocystis carinii in children with severe pneumonia at Mulago Hospital, Uganda

The prevalence of Pneumocystis carinii pneumonia (PCP), its clinical and radiological features and the outcome in 121 children aged 2-60 months presenting with severe pneumonia over a 2-month period at Mulago Hospital, Kampala are described. Children presenting with severe pneumonia had sputum induction using 3% hypertonic saline. The sputum was stained using PCP monoclonal antibodies and viewed with fluorescent microscopy. Twenty children with confirmed PCP were compared with 101 without PCP. The prevalence of PCP was 16.5%, and 12 (60%) were < 6 months of age. Eighteen (42%) of 43 children infected with HIV had PCP and two of 78 not infected with HIV. The outcome in children with PCP was poor with a case fatality rate of 40% compared with 20% in those without HIV. Radiological findings were non-specific. Clinical features associated with PCP included: HIV-positive infants with a small head circumference, AIDS, a clear chest on auscultation and elevated LDH levels. PCP occurs in one in six children < 5 years with severe pneumonia in Mulago Hospital. In developing countries where investigations for PCP are not routinely available, infants suspected of PCP should be treated as an emergency.     

儿童肾病合并肺孢子菌肺炎3例临床分析

目的 提高对肺孢子菌肺炎(PCP)的认识.方法 回顾分析3 例肾病并发PCP患儿的临床资料.结果 3例患儿的共同特点是,PCP起病急,临床以发热、咳嗽起病,伴有低氧血症,症状与体征不平行;早期临床表现无特异性,易漏诊,并发PCP前患儿均长期或大量应用免疫抑制剂、足量泼尼松口服疗程达8周及以上;免疫功能检查均有不同程度的CD4细胞比例下降.结论 提高对PCP的认识,做到早期诊断;适当控制免疫抑制剂应用、改善患儿生活环境、针对高危人群定期检测CD4细胞水平以及酌情应用复方磺胺甲基异噁唑预防均有利于降低肺孢子菌肺炎的发病率.     

Efficacy of 99mTc-DTPA lung clearance test in the diagnosis of PCP in HIV-positive patients

The study aims to evaluate the efficacy of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) lung clearance test in the diagnosis of pneumocystis carinii pneumonia (PCP) in HIV-positive paediatric patients. Twenty HIV-negative patients with no chest symptoms constituted Group A, 25 HIV antibody positive asymptomatic children formed Group B, while 45 HIV antibody positive children with respiratory infections comprised Group C. Group C was subdivided into C(1) (n = 20, documented PCP on microbiology), C(2) (n = 10, tuberculosis) and C(3) (n = 15, bacterial pneumonias). The mean age group of patients in Group A, Group B and Group C was 4.7 +/- 1.9, 4.2 +/- 1.5 and 4.8 +/- 1.7 years, respectively. All patients were subjected to complete blood count, blood culture, chest radiographs, microscopic staining of sputum (PCP stains, Ziehl-Nielsen staining, Gram staining), ABG and Mantoux test. All these patients underwent dynamic lung scans using (99m)Tc-DTPA aerosols and lung clearance was calculated in terms of half-time transfer value (T(1/2)) value. T(1/2) was compared between different groups and lung scan findings were correlated with radiological and microbiological results. Patients with PCP had T(1/2) in the range of 9.02 +/- 1.35, TB 28.2 +/- 3.03 min and other bacterial pneumonias in the range of 20.5 +/- 3.1 min (range for normal individuals was 49.8 +/- 6.13 min). T(1/2) in patients with PCP was found to be significantly lower when compared with T(1/2) in other groups. Patients with PCP had characteristic biphasic curves while the rest had monophasic curves. Some patients with PCP had low T(1/2) values even when chest radiographs and arterial blood gases were normal. (99m)Tc-DTPA lung clearance test is a sensitive, safe and non-invasive diagnostic tool for the early detection of PCP in HIV-positive paediatric patients.     

Dysfunction of natural killer cells in human immunodeficiency virus-infected children with or without Pneumocystis carinii pneumonia.

The development of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected children with normal T-cell numbers is contrary to previous experience with HIV-infected adults, in whom low CD4+ T-cell numbers predict susceptibility to PCP. To determine whether PCP in HIV-infected children reflects a qualitative T-cell or other immune defect, we studied four HIV-infected children who also had PCP and 10 others without PCP for T-cell and natural killer (NK) cell function. Most of the HIV-infected children had normal T-cell numbers for age, and all had CD4+ T-cell numbers greater than those predictive of PCP in HIV-infected adults. All HIV-infected children had normal T-cell function in vitro. The HIV-infected children as a whole had deficient NK cell cytolysis. We obtained a significant interactive effect of age by health status for NK cell function between patients and age-matched control subjects. All HIV-infected children with defective NK cell function failed to enhance their NK cell cytolysis when their mononuclear cells were stimulated with recombinant interferon alfa (r-IFN-alpha). This NK cell defect in HIV-infected children may facilitate the development of secondary infection.     

Pneumocystis pneumonia in children receiving chemotherapy

Pneumocystis pneumonia (PCP) is a serious complication of chemotherapy-induced immunosuppression. Trimethoprim-sulfamethoxazole (TMP-SMZ) given twice daily, 3 days every week is considered the best form of prophylaxis for PCP. We evaluated PCP prophylaxis in all children up to 18 years of age undergoing cancer chemotherapy over a 2-year period. Four children were diagnosed with PCP over 24 months. Two of 12 children on intravenous pentamidine, 1 of 143 on TMP-SMZ and 1 of 36 on dapsone for PCP prophylaxis developed PCP. Intravenous pentamidine may not be as effective as previously considered and should be used with caution.     

Prognostic factors and life expectancy in children with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia

Eighteen children with the acquired immunodeficiency syndrome (AIDS) were diagnosed as having Pneumocystis carinii pneumonia (PCP) by either open lung biopsy or bronchoalveolar lavage. Seven patients (39%) died during the acute illness. Alveolar-arterial oxygen gradients at the time of presentation and lactate dehydrogenase levels did not distinguish survivors from nonsurvivors. Total lymphocyte and T4 cell counts were low in children who died during the initial PCP infection but had considerable overlap with survivors. Response to phytohemagglutinin was measured in 5 of the 7 patients who died initially. In these patients, the mean phytohemagglutinin response was 1977 cpm. Of the 11 early survivors, 10 died within 27 months after PCP. Mean phytohemagglutinin response was 46,079 cpm in patients who died within 1 year, and 44,768 cpm in those who died later. Only 1 child is still alive 5 years after PCP illness. Children with AIDS and PCP infection have high initial mortality and poor long-term prognosis. Response to phytohemagglutinin is helpful in predicting who will survive initial PCP infection.     

Rates and predictors of visits to primary care physicians during and after treatment of childhood acute lymphoblastic leukemia: A population-based cohort study

Introduction

Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL).

Methods

Children of age less than 18 years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables.

Results

A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40–0.54; p < .0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2–1.6; p < .0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6–2.5; p < .0001).

Conclusions

Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment.     

儿童非人类免疫缺陷病毒感染重症耶氏肺孢子菌肺炎七例并文献复习

目的总结儿童非人类免疫缺陷病毒(HIV)感染的耶氏肺孢子菌肺炎(PCP)的临床特征及治疗情况。方法回顾性分析2015年5月1日至2021年5月1日在香港大学深圳医院PICU和咸阳彩虹医院PICU住院的7例非HIV感染的重症PCP患儿病例,观察其高危因素、临床表现、实验室检测指标、肺部影像学特征、治疗及转归等。结果7例PCP患儿,男4例,女3例,年龄13~85个月,平均(42.4±26.8)个月,均存在基础疾病,以血液系统恶性肿瘤最为多见;6例患儿有应用复方磺胺甲口,恶唑(TMP-SMX)预防PCP治疗史,其中4例自行停药2~4周发生PCP。7例患儿均存在低氧性呼吸衰竭,氧合指数(OI)30.6±3.4;临床表现为发热、干咳、进行性呼吸困难,早期肺部均未闻及湿啰音,乳酸脱氢酶[(745.7±317.0)U/L]和β-D-葡聚糖[(513.8±225.0)pg/mL]均升高,胸部CT显示双肺弥漫性间质性改变伴肺内多发性渗出。7例患儿均在入院3 d内开始抗耶氏肺孢子菌治疗,其中5例采用静脉TMP-SMX,2例口服TMP-SMX+卡泊芬净,疗程21 d,抗耶氏肺孢子菌同时应用糖皮质激素治疗;2例患儿在PCP治疗3 d后出现病情加重,其中1例死亡,另1例继续用药6 d后开始临床好转,其余5例在治疗3~7 d后开始出现临床好转,最终6例治愈,1例死亡。结论非HIV感染的PCP患儿均存在免疫受损的高危因素,TMP-SMX可有效预防PCP的发生;对于重症PCP患儿,尽早静脉应用TMP-SMX联合糖皮质激素治疗可降低病死率,在无静脉TMP-SMX情况下,也可口服TMP-SMX+卡泊芬净替代。     

Guidelines for Prevention of Pneumocystis carinii Pneumonitis in Children and Adolescents with Cancer

Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population.     

Pneumocystis carinii severe pneumonia among human immunodeficiency virus-infected children in Thailand: the effect of a primary prophylaxis strategy

BACKGROUND: A knowledge of the epidemiology of Pneumocystis carinii pneumonia (PCP) is important for the development of a strategy for primary PCP prophylaxis and empiric treatment for severe pneumonia in HIV-infected children. However, little is known about the epidemiology of PCP in developing countries. Objective. To measure the relative rate of PCP among hospitalized HIV-infected children with severe pneumonia in Bangkok and evaluate the effect of a strategy of primary PCP prophylaxis in HIV-exposed infants. METHODS: All HIV-infected children hospitalized from January, 1996, to December, 1997, for severe pneumonia were investigated for PCP with the use of specimens obtained from bronchoalveolar lavage, endotracheal aspiration or lung tissue necropsy. Characteristics associated with severe pneumonia were described, and the differences between PCP and non-PCP in these severely ill children were analyzed. In June, 1996, a strategy of primary PCP prophylaxis using trimethoprim-sulfamethoxazole in all HIV-exposed infants from 1 to 6 month of age was initiated in our institution. The effect of this strategy was evaluated. RESULTS: Of 279 hospitalized HIV-infected children 128 (46%) were diagnosed with pneumonia and 26 (20%) of these had severe pneumonia. P. carinii was identified in 9 (35%) children with severe pneumonia. After June, 1996, the rate of severe pneumonia among all hospitalized children decreased from 16% from January through June, 1996, to 7% from July, 1996, through December, 1997 (P = 0.02). Cases of PCP decreased from 9 in 1996 to zero in 1997. The percentage of HIV-infected children receiving PCP prophylaxis at the time of admission increased from 53% before June, 1996, to 72% in late 1997 (P = 0.04). The overall percentage of patients with severe pneumonia receiving PCP prophylaxis at the time of admission was 34%. Breakthrough PCP occurred in 2 children with poor compliance. Patients with PCP were significantly younger than those without PCP (mean age, 10.6+/-10.6 vs. 29.8+/-28.3 months, P = 0.02). CONCLUSION: PCP occurred in one-third of cases of severe pneumonia in HIV-infected children in Bangkok. The data suggest that PCP prophylaxis can prevent both PCP and non-PCP.     

Family Caregiver Marginalization is Associated With Decreased Primary and Subspecialty Asthma Care in Head Start Children

Background

Urban minority children are at risk for poor asthma outcomes and might not receive appropriate primary or subspecialty care. We hypothesized that preschool children with asthma whose caregivers reported more barriers to care would be less likely to have seen their primary care provider (PCP) or an asthma subspecialist and more likely to have had a recent emergency department (ED) visit for asthma.

Pneumocystis carinii pneumonia in South African children infected with human immunodeficiency virus

BACKGROUND: Pneumocystis carinii pneumonia (PCP) has been regarded as uncommon in HIV-infected patients in Africa, but diagnostic difficulties and geographic variability may partly account for this. There is little information on the incidence of PCP in HIV-infected children in Africa. AIM: To investigate (1) the incidence and associated features of PCP in African HIV-infected children and (2) the usefulness of sputum induction and nasopharyngeal aspirates (NPAs) for diagnosis of PCP. METHODS: HIV-infected children hospitalized with pneumonia were prospectively enrolled in a 1-year study in South Africa. History, examination, chest radiology and blood tests (including HIV testing) were performed. Sputum induction (5% NaCl nebulization) or nondirected bronchoalveolar lavage in intubated patients was performed for P. carinii identification using immunofluorescence and silver stain; immunofluorescence was also done on nasopharyngeal aspirates (NPAs). RESULTS: Of 151 HIV-infected children [47% female; median age, 9 (range, 3 to 23) months], 87 had been previously diagnosed with HIV whereas 64 (42.4%) were found to be HIV-positive at the time of admission. PCP occurred in 15 children (9.9%; 95% confidence interval, 5.9 to 15.5) and was the AIDS-defining infection in 13 of 64 (20.3%; 95% confidence interval, 11.8 to 31.5). Only 1 of 59 children receiving prophylaxis (1.7%) developed PCP compared with 14 of 92 (15.2%) not taking prophylaxis [relative risk, 0.11 (0.02 to 0.82), P = 0.007]. PCP-infected children were younger [3 (range, 3 to 4) vs. 10 (range, 4 to 24) months, P < 0.001] and presented with more severe pulmonary disease as indicated by a higher respiratory rate [63 (range, 60 to 73) vs. 50, (range, 40 to 60) P < 0.001], heart rate [160 (range, 136-180) vs. 140 (range, 120-152) P = 0.025] and a greater incidence of cyanosis (53% vs. 26%, P = 0.025). Clinical signs of HIV infection, occurring in 96% of children, were equally prevalent in both groups. High serum lactate dehydrogenase was the only laboratory investigation that distinguished PCP-infected from uninfected children [626 (range, 450 to 1098) vs. 307 (range, 243 to 465) units/l], P < 0.001. No radiologic features were found to be diagnostic of PCP. P. carinii was identified in 9 sputa and 6 bronchoalveolar lavage specimens, but all corresponding NPAs were negative. Seven of 15 (47%) children with PCP died while hospitalized compared with 24 of 136 (18%) without PCP [relative risk, 1.21 (range, 0.99 to 1.47), P = 0.008]. CONCLUSION: PCP is an important pathogen in HIV-infected infants in South Africa and is associated with a high mortality. Induced sputum is effective for obtaining lower respiratory tract secretions for diagnosis of PCP but an NPA is not useful.     

Outcomes and duration of Pneumocystis jiroveci pneumonia therapy in infants with severe combined immunodeficiency

This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jiroveci pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoietic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment.     

Intermittent oral trimethoprim/sulfamethoxazole on two non-consecutive days per week is effective as Pneumocystis jiroveci pneumonia prophylaxis in pediatric patients receiving chemotherapy or hematopoietic stem cell transplantation

Pneumocystis jiroveci pneumonia (PCP) is a serious complication in patients receiving chemotherapy or hematopoietic stem cell transplantation. Current recommendations for trimethoprim-sulfamethoxazole (TMP-SMZ) dosing as PCP prophylaxis in immunocompromised patients are based on either daily dosing or dosing three consecutive days per week. We report our experience of prophylaxis with TMP-SMZ twice daily on two non-consecutive days per week in 145 immunocompromised children with hematologic disorders, cancer, or metabolic disorders following chemotherapy or hematopoietic stem cell transplantation. There were no breakthrough cases of PCP. We therefore conclude our prophylaxis regimen is effective against PCP in immunocompromised children.     

Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency.

BACKGROUND: Pneumocystis carinii is an important pathogen in immunodeficiency but may be an unrecognised cause of respiratory compromise. OBJECTIVES: To ascertain the incidence of P carinii pneumonia (PCP) at presentation of severe combined immunodeficiency (SCID), whether it had been diagnosed, and the effect of treatment on outcome. SETTING: The supraregional paediatric bone marrow transplant unit for primary immunodeficiencies at Newcastle General Hospital. METHODS: Retrospective case note review of infants referred with a diagnosis of SCID from 1992 to 1998. RESULTS: Ten of 50 infants had PCP at presentation; only one was diagnosed before transfer. Eight were diagnosed by bronchoalveolar lavage and two by lung biopsy. In only one was P carinii identified in nasopharyngeal secretions. Five required ventilation for respiratory failure but all were successfully treated with co-trimoxazole and methylprednisolone with or without nebulised budesonide. Nine survived to bone marrow transplantation and four are long term survivors after bone marrow transplantation; no deaths were related to PCP. CONCLUSIONS: PCP is a common presenting feature of SCID but is rarely recognised. Bronchoalveolar lavage or lung biopsy are needed for diagnosis. Treatment with co-trimoxazole is highly successful.     

Pulmonary manifestations of pediatric HIV infection

Vertically acquired HIV infection is becoming increasingly common in India. The main clinical manifestations of HIV in childhood are growth failure, lymphadenopathy, chronic cough and fever, recurrent pulmonary infections, and persistent diarrhoea. Pulmonary disease is the major cause of morbidity and mortality in pediatric AIDS, manifesting itself in more than 80% of cases. The most common causes are Pneumocystis carinii pneumonia (PCP), lymphocytic interstitial pneumonitis (LIP), recurrent bacterial infections which include bacterial pneumonia and tuberculosis. The commonest AIDS diagnosis in infancy is PCP, presenting in infancy with tachypnea, hypoxia, and bilateral opacification on chest-X-ray (CXR). Treatment is with cotrimoxazole. LIP presents with bilateral reticulonodular shadows on CXR. It may be asymptomatic in the earlier stages, but children develop recurrent bacterial super infections, and can progress to bronchiectasis. LIP is a good prognostic sign in children with HIV infection in comparison to PCP. HIV should be considered in children with recurrent bacterial pneumonia, particularly with a prolonged or atypical course, or a recurrence after standard treatment. Pulmonary TB is common in children with HIV, but little data is available to guide treatment decisions. Much can be done to prevent PCP and bacterial infections with cotrimoxazole prophylaxis and appropriate immunisations, which may reduce hospital admissions and health care costs.     

Pneumocystis carinii pneumonia: Pitfalls of prophylaxis

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.