Congenital myasthenic syndrome: a tale of two siblings.

Congenital myasthenic syndromes are a group of rare neuromuscular junction disorders. Traditional anticholinesterase inhibitors may not help in congenital myasthenic syndromes and in some variants may actually cause deterioration of symptoms. In this report, we describe a rare case of congenital myasthenic syndrome with heterozygous mutations in CHRNE gene (c.128A > T; heterozygous; exon 11) and COLQ gene (c.1201T > A; heterozygous; exon 16), which did not show improvement on neostigmine test but responded to treatment with oral salbutamol.

Plasmodium vivax vaccine candidate MSP1 displays conserved B-cell epitope despite high genetic diversity.

The polymorphic nature of merozoite surface protein 1(MSP1) raises doubts whether it may serve as a vaccine target against Plasmodium vivax malaria. This study analyses the impact of genetic variability on the epitope organization of different Pvmsp1 blocks. Ten blood samples collected from P. vivax infected malaria patients from West Bengal, India were used to analyze sequence and antigenic diversities of block 2 region of Pvmsp1. An additional 48 block 2 sequences from other countries were also analyzed. Global genetic framework of Pvmsp1 block 2 was represented by 12 indel clusters & 33 haplotypes (haplotype diversiy = 0.965 ± 0.024). Parasite sequences pertaining to other Pvmsp1 modules, namely block 6 and 10 displayed 14 & 29 (haplotype diversiy = 0.975 ± 0.003) and 22 & 30 indel clusters and haplotypes (haplotype diversiy = 0.947 ± 0.004), respectively. In spite of this remarkable genetic diversity, a small number of conserved epitopes were detected in all three PvMSP1 blocks. This novel finding substantiates that MSP1 could serve as a promising vaccine candidate against vivax malaria.

Clinical Profile and Therapeutic Response of Scrub Typhus in Children: A Recent Trend from Eastern India.

OBJECTIVE: The aim of this study was to assess the clinico-laboratory parameters, complications and therapeutic responses in children with scrub typhus in Eastern India. MATERIALS AND METHODS: In this prospective, observational study, all children (age, <12 years) with suspected scrub typhus with a compatible clinical scenario were enrolled consecutively over six months. Cases confirmed by means of a positive IgM serology or a positive Weil-Felix reaction (OXK = 1/80 or above) were administered enteral doxycycline (4.5 mg/kg/day). RESULTS: Out of 94 recruited children, 61 had confirmed scrub typhus (mean age = 6.1 years, M:F = 1.1:1) with or without complications and having a considerably higher incidence of neurological presentation (meningoencephalistis n = 21, 34.4%). The most frequent manifestations included vomiting (n = 39, 63.9%), abdominal pain (n = 33, 54.1%), lymphadenopathy (n = 36, 59%), hepatosplenomegaly (n = 32, 52.5%), pedal edema (n = 32, 52.5%) and eschar formation (n = 30, 49.2%). Low hemoglobin levels, leukocytosis, thrombocytopenia, hypoalbuminemia, hyponatremia, increased liver enzymes and increased C-reactive protein were associated with delayed defervescence (>48 h). CONCLUSION: Scrub meningoencephalitis, with a notably higher incidence, showed favorable therapeutic response. Prompt and empiric doxycycline therapy could be lifesaving.

Diversity analysis of MSP1 identifies conserved epitope organization in block 2 amidst high sequence variability in Indian Plasmodium falciparum isolates.

BACKGROUND: Despite its immunogenicity, the polymorphic nature of merozoite surface protein 1, an important vaccine candidate for Plasmodium falciparum malaria, remains a concern. This study analyses the impact of genetic variability and parasite population structure on epitope organization of different MSP1 segments. METHODS: Altogether 98 blood samples collected from P. falciparum infected mild and severe malaria patients of Chhattisgarh and West Bengal were used to sequence regions encoding block 2 and MSP1-19 of msp1. Sequences were analysed using MEGA7, DnaSPv5, Arlequin3.5 and BepiPred. RESULTS: All three major MSP1 block 2 allele families namely K1, MAD20 and RO33 were detected in the samples and they together resulted in 41 indel variants. Chhattisgarh samples displayed an average MOI of 2.07 ± 1.59 which was higher in mild malaria and in age group < 18 years. Ultra-structure of block 2 alleles revealed that mutation and repeat expansion were two major mechanisms responsible for allelic variability of K1 and MAD20. Regions flanking block 2 were highly variable in Chhattisgarh with average mismatch differences (k) ranging from 1.198 to 5.156 for three families. In contrast, region encompassing MSP1-19 exhibited limited heterogeneity (kChhattisgarh = 1.45, kWest Bengal = 1.363). Of the 50 possible B cell linear epitopes predicted from block 2 variants, 94.9% (131 of 138) of the parasites could be represented by three conserved antigens. CONCLUSIONS: Present data indicates that natural selection and transmission intensity jointly play a role in controlling allelic diversity of MSP1 in Indian parasite isolates. Despite remarkable genetic variability, a limited number of predominant and conserved epitopes are present in Indian parasite isolates reinstating the importance of MSP1 as a promising malaria vaccine candidate.

Recurrent intracranial hemorrhage in brain tumor.

There are only a few causes of recurrent intracranial hemorrhage among which a brain tumor like glioblastoma multiforme is one. Glioblastoma multiforme in children under 14 years of age is relatively uncommon than adults. We report a case of unusual presentation of glioblastoma multiforme with recurrent intratumoral bleed with hemiparesis with symptoms free period in between.

Acute osteomyelitis in congenital hypofibrinogenemia.

A 10-month-old female child presented with intermittent high grade fever, pain and diffuse swelling in the left knee joint with history of ecchymosis in different areas of the body. There was radiological features of acute osteomyelitis, low fibrinogen level and bacteremia due to the presence of coagulase positive staphylococcus aureus. The child responded nicely to the treatment for acute osteomyelitis and congenital hypofibrinogenemia. So, in congenital hypofibrinogenemia, a joint swelling might be a resultant of an acute osteomyelitis, not mere hemarthrosis.