Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

OBJECTIVES: Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. METHODS: Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. RESULTS: During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. CONCLUSION: Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon.

Evolution of an influenza pandemic in 13 countries from 5 continents monitored by protein microarray from neonatal screening bloodspots.

BACKGROUND: Because of lack of worldwide standardization of influenza virus surveillance, comparison between countries of impact of a pandemic is challenging. For that, other approaches to allow internationally comparative serosurveys are welcome. OBJECTIVES: Here we explore the use of neonatal screening dried blood spots to monitor the trends of the 2009 influenza A (H1N1) pdm virus by the use of a protein microarray. STUDY DESIGN: We contacted colleagues from neonatal screening laboratories and asked for their willingness to participate in a study by testing anonymized neonatal screening bloodspots collected during the course of the pandemic. In total, 7749 dried blood spots from 13 countries in 5 continents where analyzed by using a protein microarray containing HA1 recombinant proteins derived from pandemic influenza A (H1N1) 2009 as well as seasonal influenza viruses. RESULTS: Results confirm the early start of the pandemic with extensive circulation in the US and Canada, when circulation of the new virus was limited in other parts of the world. The data collected from sites in Mexico suggested limited circulation of the virus during the early pandemic phase in this country. In contrast and to our surprise, an increase in seroprevalence early in 2009 was noted in the dataset from Argentina, suggestive of much more widespread circulation of the novel virus in this country than in Mexico. CONCLUSIONS: We conclude that this uniform serological testing of samples from a highly standardized screening system offers an interesting opportunity for monitoring population level attack rates of widespread diseases outbreaks and pandemics.

International cooperation in the expansion of a newborn screening programme in Lebanon: a possible model for other programmes.

Tandem mass spectrometry (MS/MS) is rapidly gaining support, even in less-developed nations, as the method of choice for the newborn screening of metabolic disorders, although difficulties in acquiring this technology may at times be major obstacles in several Middle East and North Africa (MENA) countries. In Lebanon, international cooperation allowed this acquisition at the Newborn Screening Laboratory (NSL) of the Saint Joseph University (USJ) in the capital city of Beirut. NSL is currently screening up to 20% of all newborns in Lebanon. The expansion was made possible through initial collaboration with the Metabolic Laboratory at the Hamburg University Medical Center (HUMC) and subsequently with other centres. During phase I of the expansion (2006-2007), blood spots were shipped to HUMC with rapid couriers twice a week and electronic reports were sent back generally within 4 days after shipment. Positive cases were recalled to NSL and new specimens were sent back for confirmation at HUMC. During that first phase, the Beirut staff received training at the HUMC and in other centres. Phase II was a transitory period of 4 months during which machines were installed in Beirut and working procedures were adopted and documented. The activity has now entered a consolidation phase (Phase III) in which all measurements are exclusively performed in Beirut while HUMC acts as a backup centre. International cooperation remains crucial for periodic quality assurance procedures, and for supporting the transformation of the USJ-NSL into a training centre able to transfer MS/MS technology to the MENA region.

The multiplex-PCR-based detection and genotyping of diarrhoeagenic Escherichia coli in diarrhoeal stools.

In several hospitals in Beirut, Lebanon, 77 isolates of Escherichia coli were successfully derived from the stools of patients with diarrhoeal diseases, by culture on MacConkey or MacConkey-sorbitol agar. When the isolates were screened, using a multiplex PCR, 14 (from 14 different patients) were each found positive for one of the various genes defining the enterotoxigenic (five), enteroinvasive (four), enteroaggregative (three) or enteropathogenic (two) groups. Genotyping of these 14 diarrhoeagenic isolates, by pulsed-field gel electrophoresis, indicated that all were genomically distinct with the exception of two of the enteroaggregative isolates (which were of the same genotype). The E. coli apparently involved in diarrhoeal disease in Beirut therefore belong to at least four different diarrhoeagenic groups and show strain variation within each group. Diarrhoea in the absence of diarrhoeagenic E. coli may be the result of infection with bacteria other than E. coli or viral or parasitic enteropathogens.

Comparative analysis between Pseudomonas aeruginosa genotypes and severity of symptoms in patients with unilateral or bilateral otitis externa.

Random amplified polymorphic DNA (RAPD) analysis was done on 32 isolates of Pseudomonas aeruginosa. These isolates were obtained from 22 patients who presented to the emergency room in a major medical center in Beirut, Lebanon, during a 5-month period with the diagnosis of either unilateral or bilateral otitis externa. Patients had yellowish to greenish discharge, moderate to severe external auditory canal swelling, moderate to severe pain, and periauricular cellulitis. None of these patients had intrinsic predisposing factors. An ear swab was obtained from both ears of patients, cultured on trypticase soy agar. P. aeruginosa was identified on the basis of pyocyanine production and API identification kits. RAPD analysis was done by using two primers (10 mer and 21 mer primers) and appropriate PCR conditions on extracted DNA. Our data have shown 23 RAPD patterns (A-W) distributed among the 32 P. aeruginosa isolates. RAPD patterns were reproducible. Twenty of 32 isolates were recovered from 10 patients with bilateral otitis externa. The remaining 12 of 32 isolates were recovered from 12 different patients with unilateral otitis externa. Eleven RAPD patterns (A,B,C,D,E,F,H,I,R,U,V) were associated with severe clinical symptoms, including severe pain, severe external auditory canal swelling, periauricular cellulitis, and a yellowish discharge. The remaining RAPD patterns were not associated with severe infections. This denotes a possible association between certain genotypes and severity of symptoms.

[Blood and leukocyte glutathione and glutathione S-transferase: relationship to cholesterolemia in healthy volunteers]. / Glutathion et glutathion S-transférase sanguins et leucocytaires: relation avec la cholestérolémie chez des volontaires sains.

Hypercholesterolemia increases the oxidation of low density lipoprotein (LDL) which subsequently leads to atherogenesis. The oxidized LDL are also known to increase in vitro macrophage synthesis of glutathione. The purpose of this study was to investigate the relationship between lipid parameters and the glutathione system (glutathione, glutathione S-transferase) in total blood and within leukocytes. The glutathione and glutathione S-transferase were evaluated by spectrophotometric methods in sixty-two healthy volunteers (32 women, 30 men, mean age 39.9 +/- 7.7). No correlation was found between the level of blood cholesterol and the values of the blood glutathione system. However, a positive correlation between the values of glutathione and glutathione S-transferase in leukocytes and the blood cholesterol level was only found in women (r = 0.55 and r = 0.50 respectively, p < 0.01). We also found in men a positive correlation between body mass index and glutathione S-transferase in total blood and within leukocytes (r = 0.38, p < 0.05, r = 0.5, p < 0.01 respectively). No correlation was found between age, smoking and the values of the glutathione system. Our results suggest that the glutathione system in leukocytes is related to blood cholesterol levels. The fact that this positive correlation was only observed in women points to a possible role of estrogens in the regulation of the glutathione system which merits to be further studied.

Rapid laboratory confirmation of human brucellosis by PCR analysis of a target sequence on the 31-kilodalton Brucella antigen DNA.

We developed a PCR-based assay for the rapid and specific laboratory diagnosis of human brucellosis directly from whole blood. Specimens were collected in EDTA tubes from 17 patients with acute serologic brucellosis and 3 patients with chronic relapsing brucellosis as determined by serologic tests and the patient's clinical picture. DNA was extracted from peripheral mononuclear cells obtained from the blood of patients with brucellosis and control individuals. Specific primers for the PCR amplification of a 223-bp region on the sequence encoding the 31-kDa immunogenic Brucella abortus protein (BCSP 31) were used. All amplicons had the expected size of 223 bp. The specificity of amplification was determined by Southern hybridization and restriction endonuclease analysis. DNA extracted from blood taken from 30 healthy individuals as well as from 9 patients with typhoid fever did not show any amplification with the primers used. The test proved to be rapid and specific for the laboratory confirmation of acute human brucellosis. Further studies must be conducted to assess the utility of this test on additional patients with chronic relapsing brucellosis as well as patients under treatment.