Influx of diverse, drug resistant and transmissible Plasmodium falciparum into a malaria-free setting in Qatar

Background: Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission. Methods: This study examined imported malaria cases reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated both total parasite and gametocyte density, using qPCR and qRT-PCR, respectively. We also examined ten neutral microsatellites and four genes associated with drug resistance, Pfmrp1, Pfcrt, Pfmdr1, and Pfkelch13, to assess the genetic diversity of imported P. falciparum strains, and the potential for propagating drug resistance genotypes respectively. Results: The majority of imported malaria cases were P. vivax, while P. falciparum and mixed species infections (P. falciparum / P. vivax) were less frequent. The primary origin of P. vivax infection was the Indian subcontinent, while P. falciparum was mostly presented by African expatriates. Imported P. falciparum strains were highly diverse, carrying multiple genotypes, and infections also presented with early- and late-stage gametocytes. We observed a high prevalence of mutations implicated in drug resistance among these strains, including novel SNPs in Pfkelch13. Conclusions: The influx of genetically diverse P. falciparum, with multiple drug resistance markers and a high capacity for gametocyte production, represents a threat for the reestablishment of drug-resistant malaria into GCC countries. This scenario highlights the impact of mass international migration on the reintroduction of malaria to areas with absent or limited local transmission

Mucolipidosis Type IV in Omani Families with a Novel MCOLN1 Mutation: Search for Evidence of Founder Effect

Mucolipidosis Type IV (MLIV) is caused by a deficiency of the mucolipin cation channel encoded by Mucolipin TRP Cation Channel 1 gene (MCOLN1). It is a slowly progressive neurodevelopmental and neurodegenerative disorder causing severe psychomotor developmental delay and progressive visual impairment, which is often misdiagnosed as cerebral palsy. We describe six patients with MLIV from two Omani families with a novel c.237+5G>A mutation in the MCOLN1 gene predicted to affect mRNA splicing. Mutation screening with a high-resolution melting (HRM) assay in a large population sample did not detect this mutation in control subjects. This report highlights the importance of considering MLIV in the differential diagnosis of patients in a pediatric age group with cerebral palsy-like presentation. Although the same rare mutation was seen in two apparently unrelated families, this was not seen in the sample screened from the general population. The HRM assay provides a cost-effective assay for population screening for the c.237+5G>A mutation

Intrauterine Fetal Blood Transfusion: Descriptive study of the first four years’ experience in Oman

Objectives: Haemolytic disease of the fetus and newborn (HDFN) causes hydrops fetalis. The successful treatment of HDFN has been reported with intrauterine blood transfusion (IUT). This study aimed to describe the initial experience with IUT procedures in Oman. Methods: This retrospective observational study took place at the Royal Hospital and Sultan Qaboos University Hospital Blood Bank, Muscat, Oman, and included all women who underwent IUT procedures in Oman between March 2012 and March 2016. Gestational and neonatal outcomes were assessed, including complications, morbidity, neurodevelopmental sequelae and mortality. Results: A total of 28 IUT procedures for 13 fetuses carried by 11 women were performed. Gestational age at the time of referral ranged from 13–30 weeks, while the median gestational age at first IUT procedure was 26 weeks (range: 19–30 weeks). Indications for the procedure included HDFN caused by anti-D (n = 6), a combination of anti-D and anti-C (n = 4), anti-K (n = 1) and anti-Jsb (n = 1) antibodies and nonimmune hydrops fetalis due to a congenital parvovirus infection (n = 1). Median fetal haemoglobin levels at the beginning and end of the procedure were 4.6 g/dL and 12.8 g/dL, respectively. Most procedures were transplacental intravascular transfusions through the placental umbilical cord root (71.4%), followed by transamniotic intravascular transfusions (14.3%). The overall survival rate was 61.5%, with five deaths; of these, four were intrauterine and one was an early neonatal death due to non-resolved hydrops and severe cardiac dysfunction. Conclusion: As a relatively novel obstetric procedure in Oman, IUT seems to result in a favourable outcome for hydropic fetuses

Intrauterine Fetal Blood Transfusion: Descriptive study of the first four years’ experience in Oman

Objectives: Haemolytic disease of the fetus and newborn (HDFN) causes hydrops fetalis. The successful treatment of HDFN has been reported with intrauterine blood transfusion (IUT). This study aimed to describe the initial experience with IUT procedures in Oman. Methods: This retrospective observational study took place at the Royal Hospital and Sultan Qaboos University Hospital Blood Bank, Muscat, Oman, and included all women who underwent IUT procedures in Oman between March 2012 and March 2016. Gestational and neonatal outcomes were assessed, including complications, morbidity, neurodevelopmental sequelae and mortality. Results: A total of 28 IUT procedures for 13 fetuses carried by 11 women were performed. Gestational age at the time of referral ranged from 13–30 weeks, while the median gestational age at first IUT procedure was 26 weeks (range: 19–30 weeks). Indications for the procedure included HDFN caused by anti-D (n = 6), a combination of anti-D and anti-C (n = 4), anti-K (n = 1) and anti-Jsb (n = 1) antibodies and nonimmune hydrops fetalis due to a congenital parvovirus infection (n = 1). Median fetal haemoglobin levels at the beginning and end of the procedure were 4.6 g/dL and 12.8 g/dL, respectively. Most procedures were transplacental intravascular transfusions through the placental umbilical cord root (71.4%), followed by transamniotic intravascular transfusions (14.3%). The overall survival rate was 61.5%, with five deaths; of these, four were intrauterine and one was an early neonatal death due to non-resolved hydrops and severe cardiac dysfunction. Conclusion: As a relatively novel obstetric procedure in Oman, IUT seems to result in a favourable outcome for hydropic fetuses