Treatment Outcomes of Childhood Tuberculous Meningitis in a Real-World Retrospective Cohort, Bandung, Indonesia.

We retrospectively evaluated clinical features and outcomes in children treated for tuberculous meningitis (TBM) at Hasan Sadikin Hospital, Bandung, Indonesia, during 2011-2020. Among 283 patients, 153 (54.1%) were <5 years of age, and 226 (79.9%) had stage II or III TBM. Predictors of in-hospital death (n = 44 [15.5%]) were stage III TBM, hydrocephalus, male sex, low-income parents, seizures at admission, and lack of bacillus Calmette-Guérin vaccination. Predictors of postdischarge death (n = 18 [6.4%]) were hydrocephalus, tuberculoma, and lack of bacillus Calmette-Guérin vaccination. At treatment completion, 91 (32.1%) patients were documented to have survived, of whom 33 (36.3%) had severe neurologic sequelae and 118 (41.7%) had unknown outcomes. Predictors of severe neurologic sequelae were baseline temperature >38°C, stage III TBM, and baseline motor deficit. Despite treatment, childhood TBM in Indonesia causes substantial neurologic sequelae and death, highlighting the importance of improved early diagnosis, better tuberculosis prevention, and optimized TBM management strategies.

Two cases of pre-extensively drug resistant tuberculosis in children in Indonesia.

Few reports are available on children with pre-extensively drug-resistant tuberculosis (pre-XDR-TB), which is defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin plus resistance to either a fluoroquinolone or a second-line injectable drug. Pre-XDR-TB treatment for children usually has been individualized based on drug susceptibility test (DST) results, but treatment remains challenging due to the lack of studies based on existing treatment guidelines in children and lack of availability of the new drugs. We report two cases of pre-XDR-TB in children who have responded well to individualized treatment regimens. Because toxic drugs are used for long duration, close monitoring of adverse drug reactions is important.

Case Report: Severe COVID-19 and Dengue in an Indonesian Infant.

We report a case of a 10-month infant with dual severe infection of COVID-19 and dengue fever who was admitted to the hospital with an influenza-like illness. The patient experienced severe conditions of COVID-19 and dengue fever with shock followed by disseminated intravascular coagulation. The standard of COVID-19 care was given coupled with fluid resuscitation and blood transfusion. The pitfalls of this case are how to differentiate the clinical manifestation of dengue fever in a patient with confirmed COVID-19; the difficulty to monitor the dengue course of illness of the patient in the COVID-19 isolation room; and to differentiate the severe dengue from the multisystem inflammatory syndrome-C when the patient was in critical condition. The infant recovered without sequale, but the management of new probable cases must be improved more thoroughly, especially during dengue peak period in tropical and developing countries such as Indonesia.

Soluble urokinase-type plasminogen activator receptor as a biomarker of treatment response in childhood tuberculosis.

Background: Childhood tuberculosis (TB) is a major health problem worldwide, especially in developing countries. In 2015, there are estimated 950,000 cases of childhood TB. Since most TB in children is paucibacillary, this gives rise not only to problem in diagnosing but also in monitoring the response to anti-TB treatment as well. Soluble urokinase-type plasminogen activator receptor (suPAR), a glycosylphosphatidylinositol-linked membrane protein of various cells of immune system, is one of the potential biomarkers to be used in the management of TB. The objective of this study is to study the decrease of serum suPAR level after anti-TB treatment in children with TB and its association with patient characteristics. Methods: We conducted a prospective study on children suspected of having TB due to a history of contact with active TB case and symptoms such as coughing, fever, and enlarged lymph nodes. The diagnosis of TB is established by history, physical examination including anthropometric examination. Tuberculin skin test using PPD RT-23 and interferon-gamma releasing assay with Quantiferon TB-Gold Plus was performed. Chest X-rays were read by two independent radiologists. Microbiological examination was performed using microscopic examination and Xpert MTB/RIF. The level of suPAR before and after anti-TB treatment was examined with the Elisa method. Results: There was no significant difference of serum suPAR levels before and after anti-TB treatment (mean 0.71 [standard deviation 0.585] ng/mL; P = 0.072). There was no association between ages (P = 0.112), nutritional status (P = 0.228), diagnosis of pulmonary or extrapulmonary TB (P = 0.956), and radiological feature (P = 0.810) with serum suPAR levels decrease. Conclusion: There is no suPAR serum level decrease 2 months after treatment with anti-TB and there is no association with age, nutritional status, pulmonary or extrapulmonary TB diagnosis, and radiological feature.

The laminin binding protein p40 is involved in inducing limb abnormality of mouse fetuses as the effects of methoxyacetic acid treatment.

This study is intended to characterize a protein that is linked with mouse limb teratogenicity as the effects of methoxyacetic acid (MAA) treatment. A single dose of MAA (10 mmol/kg body weight) was given by gavage on gestation day (GD) 11, whereas the control group were administered vehicle only. The pregnant mice were killed at 4 h after MAA treatment, and forelimb buds were isolated from both the control and treated group embryos. Proteins from forelimb buds GD 11 + 4 h, which were precipitated out using 40-60% ammonium sulfate, then were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-D SDS-PAGE) technique. The 2-D gels reveal one protein with 41.6 kDa and pI 6.4, which expression was downregulated after MAA treatment. Tentative protein identification via peptide mass database search and definitive protein identification via a primary sequence database search indicate that the protein matches exactly to 34/67 kDa laminin binding protein (LBP; P14206, SwissProt), which is encoded by p40 gene (MGI:105381). The identity was further verified by Western blotting with an antibody against the 67 kDa LBP. The results suggest that MAA treatment to pregnant mice downregulates the LBP-p40 in the forelimb buds.

Critical pertussis in a young infant requiring mechanical ventilation.

Pertussis may likely be misdiagnosed in its initial or catarrhal phase as a common respiratory infection. The earlier diagnosis of pertussis really depends on the capability of the medical professional especially in the first line public health services. The lack of awareness in diagnosis of severe pertussis as one of the causes of severe respiratory problems may likely misdiagnose pertussis as respiratory failure or even septic shock. In fact, pertussis may manifest as a critical pertussis which can be fatal due to the respiratory failure that require pediatric intensive care unit using mechanical ventilation. We reported a confirmed pertussis case of a 7-weeks-old female infant referred to our tertiary hospital with gasping leading to respiratory failure and septic shock requiring mechanical ventilation, aggressive fluid therapy, and antibiotics. Pertussis was diagnosed late during the course of illness when the patient was hospitalized. Improvement was noted after administering macrolide which gave a good response. Bordetella pertussis isolation from Bordet-Gengou media culture yielded positive result.

A teratoproteomics analysis: heat shock protein 70 is upregulated in mouse forelimb bud by methoxyacetic acid treatment.

BACKGROUND: Methoxyacetic acid (MAA) causes fetal limb abnormalities when the substance is administrated on gestation day (GD) 11 in mice. Limb abnormalities are caused mainly by extensive cell death in the mesoderm of the limb plate. This investigation focused on identifying a protein that is linked with mouse limb teratogenicity. METHODS: A single dose of MAA at 10 mmol/kg body weight was administered by gavage on GD 11; controls were administered vehicle only. Dams were killed by cervical dislocation 4 hr after treatment and forelimb buds were isolated from both the control and treated embryos. Proteins in forelimb buds GD 11 + 4 hr were precipitated out using 40-60% ammonium sulfate and were then analyzed by 2D SDS-PAGE. Excised protein spots were identified by mass spectrometry and amino acid internal sequence analysis. Identified protein was further confirmed by Western blotting. RESULTS: Two-dimensional gel analysis indicated that 1 protein spot of 81.7 kDa/pI 7.3 was overexpressed, and the protein matched heat shock protein 70 (HSP70; accession no. P08109, SwissProt). CONCLUSIONS: The results suggest that MAA, when administered to pregnant mice, upregulates HSP70 in the forelimb buds.

Mesoderm formation in the anuranXenopus laevis (Daudin).

UsingXenopus blastulae of stage 9-, recombinates were made of the animal, ectodermal cap (zones I.II) and the vegetative, endodermal yolk mass (zone IV) (see Fig. 1). For the experiments either the entire ectodermal cap (A.B), the single outer layer (A) or the stratified inner layer (B) were used.A comparison of the quantitative composition of the recombinates and the corresponding isolates-on the basis of absolute values expressed in units of section surface area-demonstrates unequivocally that the entire mesoderm originates from the ectodermal "half" of the anuran egg under an inductive influence emanating from the endodermal "half". This holds for recombinates of the vegetative yolk mass with the entire ectodermal cap as well as with its outer or inner layer alone.A comparison of mesoderm formation in recombinates of the entire ectodermal cap or with its outer or inner layer with the vegetative yolk mass shows that in all cases mesoderm formation is proportional to the amount of ectoderm available. In addition, the outer layer of the ectoderm is partially endodermized which may be brought in relation with the fact that in normal development an endodermal lining extends upwards from the endodermal mass, which, among other things, covers the prechordal mesoderm on the outside.The outer layer of the ectoderm has markedly lower neural competence than the inner layer, from which in normal development the bulk of the neural material arises.