Sustainability of pyrethroid-impregnated bednets for malaria control in Afghan communities.

Between 1992 and 1995 a series of studies was undertaken to assess the long-term suitability of pyrethroid-impregnated bednets (PIBs) for malaria control in Afghan refugee communities in two villages in North-West Frontier Province, Pakistan. During 1992, 86% of bednet owners volunteered to have their bednets re-impregnated, and a further 15% of families purchased nets at two-thirds of cost price. From 1992 onwards, 27% of the villagers returned to Afghanistan, and annual house spraying campaigns were introduced to protect those still resident but sleeping without bednets. Within 3 years, these campaigns, together with PIBs, reduced the annual incidence of malaria by 87%, from 597 to 78 cases per 1000 population. Nevertheless, 65% of resident families continued to re-impregnate their nets annually with permethrin. To assess whether PIBs were still being used and were still protective, in view of these reduced transmission rates, we carried out a case--control study in 1994 on febrile or otherwise symptomatic patients presenting at village health centres. Comparison of the slide-positivity rates of PIB users and those without bednets showed that regular usage reduced the odds of contracting falciparum and vivax malaria to 0.22 (95% confidence interval (CI): 0.09-0.55) and 0.31 (95% CI: 0.19-0.51), respectively. There was no evidence of a sex- or age-bias in bednet use or in protective effect. The results indicate that a community-based PIB programme is an appropriate malaria control measure in areas where management or security problems make traditional house-spraying campaigns impossible. A relevant finding for those involved in the monitoring of bednet distribution projects is that the local coverage of bednets and the local impact on malaria, even when introduced to remote areas, can be estimated very cheaply by health centre microscopists who simply catalogue blood film diagnoses according to patients'' bednet use practices.     

Pancreatoblastoma (infantile pancreatic carcinoma)--a case report

Pancreatoblastoma or infantile pancreatic carcinoma is a rare pancreatic tumor with distinct acinar and squamoid cell differentiation that generally affects infants and young children. Ultrasound and CT scan may be useful but preoperative diagnosis is often quite difficult. The outcome is generally favourable. A such case of 10 years old boy with an abdominal mass is being presented.     

Glibenclamide treatment in a Cantú syndrome patient with a pathogenic ABCC9 gain‐of‐function variant: Initial experience

Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain‐of‐function mutations in the regulatory (SUR2) and pore‐forming (Kir6.1) subunits of K_ATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg^–1 kg^–1 day^–1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg^?1 kg^?1day^?1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS.     

Studies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89.6P challenge in DNA/MVA-vaccinated macaques

Here, we study immune responses in four DNA/MVA-vaccinated macaques following an SHIV-89.6P challenge and a subsequent CD8 cell depletion. Both post-challenge and post-depletion peaks of viremia contracted with the expansion, or re-emergence, of CD8 T cells. Post-depletion, CD8 cells expanded in the presence of higher levels of neutralizing Ab and CD4 help than post-challenge and had superior maturational characteristics as measured by expression of the anti-apoptotic protein Bcl-2, the IL-7 receptor CD127 and co-production of IFN-gamma and IL-2. Pre-challenge and pre-depletion titers of neutralizing Ab correlated inversely with peaks of viremia and directly with peaks for anti-viral CD4 cells. Thus, our results reveal CD8 cells playing a central role, and neutralizing Ab, a supporting role in SHIV-89.6P control. They also suggest a dynamic relationship between neutralizing Ab, antigen load and anti-viral CD4 cells in the maturation of high-quality anti-viral CD8 T cells.     

Enhanced factor H binding to sialylated Gonococci is restricted to the sialylated lacto-N-neotetraose lipooligosaccharide species: implications for serum resistance and evidence for a bifunctional lipooligosaccharide sialyltransferase in Gonococci

We isolated serologically identical (by serovar determination and porin variable region [VR] typing) strains of Neisseria gonorrhoeae from an infected male and two of his monogamous female sex partners. One strain (termed 398078) expressed the L1 (Galalpha1 --> 4 [corrected] Galbeta1 --> 4Glcbeta1 --> 4HepI) lipooligosaccharide (LOS) structure exclusively; the other (termed 398079) expressed the lacto-N-neotetraose (LNT; Galbeta1 --> 4GlcNAcbeta1 --> 3Galbeta1 --> 4Glcbeta1 --> 4HepI) LOS structure. The strain from the male index case expressed both glycoforms and exhibited both immunotypes. Nuclear magnetic resonance analysis revealed that sialic acid linked to the terminal Gal of L1 LOS via an alpha2 --> 6 linkage and, as expected, to the terminal Gal of LNT LOS via an alpha2--> 3 linkage. Insertional inactivation of the sialyltransferase gene (known to sialylate LNT LOS) abrogated both L1 LOS sialylation and LNT LOS sialylation, suggesting a bifunctional nature of this enzyme in gonococci. Akin to our previous observations, sialylation of the LNT LOS of strain 398079 enhanced the binding of the complement regulatory molecule, factor H. Rather surprisingly, factor H did not bind to sialylated strain 398078. LOS sialylation conferred the LNT LOS-bearing strain complete (100%) resistance to killing by even 50% nonimmune normal human serum (NHS), whereas sialylation of L1 LOS conferred resistance only to 10% NHS. The ability of gonococcal sialylated LNT to bind factor H confers high-level serum resistance, which is not seen with sialylated L1 LOS. Thus, serum resistance mediated by sialylation of gonococcal L1 and LNT LOS occurs by different mechanisms, and specificity of factor H binding to sialylated gonococci is restricted to the LNT LOS species.