Isolation of a type 3 vaccine-derived poliovirus (VDPV) from an Iranian child with X-linked agammaglobulinemia

Type 3 immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) were isolated from a 15-month-old Iranian boy with acute flaccid paralysis (AFP) who was subsequently diagnosed with X-linked agammaglobulinemia (XLA). VP1 nucleotide sequences of the two isolates differed from Sabin 3 by 2.0% and 2.1% and from each other by 0.6%. Although the key determinant of attenuation and temperature sensitivity in the 5'-untranslated region (U(472)-->C) had reverted, a second capsid-region determinant (VP3:Phe(091)) was unchanged, but a presumptive suppressor (VP1:Ala(054)-->Val) was found. The isolates were Sabin 3/Sabin 1 recombinants, sharing a single recombination breakpoint in the 2C region. Although the two isolates were antigenically distinct from Sabin 3, only one amino acid replacement was found in the neutralizing antigenic sites (VP3:Ser(059)-->Asn in site 3). The patient was placed on intravenous immunoglobulin (IVIG) therapy within 9 days of onset of AFP, and iVDPV excretion ceased thereafter, but the patient remained severely paralyzed until his death approximately 11 months after paralysis. No secondary AFP cases were found, and none of the seven tested contacts of the patient were found to be infected with poliovirus.     

First detection of enterovirus 71 from an acute flaccid paralysis case with residual paralysis in Iran

In an attempt to determine the types of non-polio enteroviruses (NPEVs) in acute flaccid paralysis (AFP) cases in Iran, we detected enterovirus 71 (EV71) in an AFP case with residual paralysis for the first time. Cell culture detected no enteroviruses, while RT-PCR and subsequent sequencing revealed that the specimen was positive for EV71. EV71 is the causative agent of a variety of diseases from hand, foot and mouth disease to severe neurological complications and is now considered as an important cause of childhood acute flaccid paralysis.     

Assessment of IgM enzyme immunoassay and IgG avidity assay for distinguishing between primary and secondary immune response to rubella vaccine

The primary test for the laboratory confirmation of rubella is IgM serology. It is important to distinguish IgM reactivity caused by primary infection from that caused by reinfection or persistence, especially in pregnant women; as termination of pregnancy is considered when primary rubella is diagnosed during the first trimester.

In this study, the performance of rubella IgM enzyme immunoassay (IgM-EIA) and rubella IgG avidity assay were compared using well-defined panels of sera from persons vaccinated against rubella and commercial rubella IgM and IgG enzyme immunoassay kits (Dade Behring, Marburg, Germany).

The sensitivity and specificity of rubella IgM-EIA were found to be 77.4 and 97.9%, respectively, while the results for rubella IgG avidity assay were 100 and 100%. IgG avidity assay showed higher positive and negative predictive values than the IgM-EIA (100 and 100% compare to 96.9 and 82.9%).

In conclusion, the rubella IgG avidity assay is more sensitive and specific than IgM-EIA for differential detection of primary rubella infection from rubella reinfection.     

Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis

Oral polio vaccine (OPV) has been used safely and efficiently for more than 40 years in preventive medicine. Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of OPV due to reversion of the vaccine strain virus to a neurovirulent strain. VAPP can occur in healthy recipients or their close contacts. However, persons with primary humoral immunodeficiencies are at a much higher risk. X-linked agammaglobulinemia (XLA) is a prototypic humoral deficiency caused by mutations in the Bruton’s tyrosine kinase (BTK) gene. In addition to susceptibility to bacterial infections, patients with XLA are especially prone to enteroviruses. Here, we describe the occurrence of VAPP in a 15-month old Iranian boy. The child had received four doses of OPV, administered at birth, 2, 4, and 6 months of age. The patient’s infectious history was unremarkable. Laboratory evaluation revealed low levels of immunoglobulin G and CD19⁺ B cells of less than 1% of the lymphocyte population. A novel insertion (c.685_686insTTAC) in the SH3 domain of the BTK gene was detected as the underlying cause. Immunodeficient recipients of OPV can excrete poliovirus vaccine strains for a long period and are at risk of developing flaccid paralysis. They could also serve as a source of reverted virulent poliovirus to be reintroduced into the general population. This patient presented for the first time with VAPP, without any history of other major infections in 15 months. This suggests that a negative history for recurrent infections does not exclude the presence of a primary defect in the immune system.     

Pain-relieving effects of Lawsonia inermis on neuropathic pain induced by chronic constriction injury

The aim of this study was to determine the role of Lawsonia inermis (L. inermis) extract in the chronic constriction injury (CCI)-induced neuropathic pain. Following CCI surgery, L. inermis extract (250 mg/kg and 500 mg/kg) and gabapentin (100 mg/kg) were administered intraperitoneally for 14 consecutive days. Heat hyperalgesia and allodynia were assessed by radiant heat, aceton drop, and von frey filament tests, respectively. Rat pain behaviors were evaluated on -1sh, 3rd, 5th, 7th, 10th and 14th days post CCI surgery. At the end of the study, the spinal levels of malondialdehyde (MDA), total thiol, IL1-β, and TNF-α were estimated. Treatment of L. inermis extract reversed the decreased level of thiol and the elevation of MDA level in the spinal cord of CCI rats. Besides, L. inermis extract treatment decreased the elevation of inflammatory markers including IL1-β, and TNF-α in the spinal cord of CCI rats. These results indicated that L. inermis has potential neuroprotective effects against CCI induced neuropathic pain due to its anti-oxidant, and anti-inflammatory effects.

     

Comparison of cell culture with RT-PCR for enterovirus detection in stool specimens from patients with acute flaccid paralysis

Since October 2000, Iran has been declared polio-free by the World Health Organization (WHO). Despite the fact that poliomyelitis caused by polioviruses has been eliminated from Iran, the number of acute flaccid paralysis (AFP) cases has not been reduced. Therefore, it is of great importance to investigate the other viral agents that may cause AFP (mainly nonpolio enteroviruses, which play a significant role in the etiology of neurological syndromes). Some enteroviruses do not grow in the conventional cell lines that are being used for enterovirus detection. Furthermore, the virus titer is an important factor in the sensitivity of cell culture to detect the virus. The fact that cell culture is a time-consuming procedure is another reason to find a more practical method for enterovirus detection. Therefore, a more sensitive and rapid method should be used to detect enteroviruses as efficiently as possible in the stool specimens of AFP cases. The aim of this study was to evaluate cell culture and RT-PCR in enterovirus detection. Findings have shown that RT-PCR can increase the rate of nonpolio enterovirus detection by up to 10% in comparison with cell culture. Also, the rapid detection of enteroviruses by RT-PCR can decrease both the unnecessary use of antibiotics and the costs in clinical practice. For this reason, we find that RT-PCR is a more practical technique for enterovirus detection.     

The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze

Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.     

Vaccine-associated Paralytic Poliomyelitis in Immunodeficient Children, Iran, 1995�C2008

To determine the prevalence of vaccine-associated paralytic poliomyelitis (VAPP) in immunodeficient infants, we reviewed all documented cases caused by immunodeficiency-associated vaccine-derived polioviruses in Iran from 1995 through 2008. Changing to an inactivated polio vaccine vaccination schedule and introduction of screening of neonates for immunodeficiencies could reduce the risk for VAPP infection.     

Comparative Detection of Measles Specific IgM Antibody in Serum and Saliva by an Antibody-Capture IgM Enzyme Immunoassay (EIA)

Laboratory diagnosis of acute measles is usually achieved by serology assays for measle-specific IgM antibody. For comparison of measle-specific IgM antibody in saliva and serum, 95 paired blood and saliva samples were collected 1-14 days after the onset of rash. The specimens were tested for specific IgM antibody by an IgM antibody-capture Enzyme Immunoassay (EIA). Measles IgM antibody was detected in 89 (93.7%) of serum samples and in 85(89.5%) of saliva specimens. Of the 6(6.3%) serum samples that were IgM antibody-negative, 2 (2.1%) of the paired saliva samples were IgM antibody-positive. The sensitivity and specificity of saliva testing compared with serum was 95.5% and 66.7% respectively. Positive predictive value (PPV) and negative predictive value (NPV) of saliva testing were 97.7% and 50.0% respectively and the accuracy of saliva testing was 93.7%. Our results indicate that saliva samples provided Enzyme Immunoassay results that were in good agreement with results from serum samples. Salivary IgM antibody detection is a suitable non-invasive method for diagnosing recent measles infections and epidemiological studies, especially in children.