Hybrid Approach to Estimation of Underreporting of Tuberculosis Case Notification in High-Burden Settings With Weak Surveillance Infrastructure: Design and Implementation of an Inventory Study

BackgroundThe greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings.ObjectiveThis study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting.MethodsRetrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies.ResultsThe hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures.ConclusionsSubnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.     

Laparoscopic Assisted Cystectomy and Lymphadenectomy for Bladder Cancer: Initial Experience

This study discusses our initial experience in the field of laparoscopic management of bladder carcinoma. Ten patients with invasive bladder tumors of variable histology and ranging from stage T2 to T3b were submitted to this procedure. Intraoperative assessment, lateral dissection, posterior dissection, anterior dissection, and urethral transection were achieved laparoscopically. The specimen retrieval and continent pouch construction was performed through a limited abdominal incision. This new regimen allows precise radical lymphadenectomy, early postoperative mobility, fewer wound complications, and shorter hospital stay. The early postoperative results of this procedure are encouraging. Modification and continuous refinement of the technique is still ongoing.     

An epizootic of Rift Valley fever in Egypt in 1997

An epizootic of Rift Valley fever (RVF) occurred in Egypt between April and August 1997. The signs among infected cattle and sheep were high fever, icterus, bloody diarrhoea and abortion. Aborted sheep foetuses and sera from the affected herds were collected in the Aswan and Assiut Provinces, Upper Egypt, for virological and serological examination. A cytopathic effect was detected in Vero cell cultures 48 h after inoculation with the foetal liver and spleen suspensions. The same suspensions caused paralysis and mortalities two to three days post intracerebral injection in mice. The isolated virus was identified using an agar gel precipitation test (AGPT) and a direct fluorescent antibody technique. Serological examination revealed that all tested sheep (57) and cattle (93) gave positive results to serological tests, using a complement fixation (CF), serum neutralisation (SN) and indirect immunofluorescence assay; while only 48 (84.2%) out of 57 sheep sera and 69 (74.2%) out of 93 cattle sera gave positive results using an AGPT. Titration of the serum samples indicated that SN is more sensitive than CF. Importation of infected ruminants, especially camels from the Sudan, is the principal source of infection. Aswan, the nearest Egyptian province to the Sudan, is the focus of RVF virus infection in Egypt. As a result of high insect populations, the epizootics of RVF have usually occurred during the summer in Egypt. Reoccurrence of epizootics from time to time indicates failure of the applied RVF vaccination programme in Egypt.     

Calcium bioavailability of selected Egyptian foods with emphasis on the impact of fermentation and germination

The bioavailability of calcium (Ca) was assessed in 11 foodstuffs of plant or animal origin using rat feeding experiments and the criteria used for assessing the bioavailability were femur Ca and calcium efficiency. The bioavailability of Ca was found to be highest in fishes (Melouha) and cheeses (Mesh) fermented under local processing techniques. Germination of faba beans also enhanced the bioavailability of calcium to a mean value quite comparable to those of some dairy products, such as cottage cheese. The present study clearly demonstrates that the processes of fermentation and germination of selected foods are associated with an enhancement in the bioavailability of calcium. It is suggested that the breakdown of complex proteins under the fermentation or germination process is the underlying mechanism of action.     

Evaluation of the effectiveness of dipstick haematuria and proteinuria in screening Schistosoma haematobium infection among school children in upper Egypt

This study aimed at evaluation of validity and reliability of dipstick haematuria and proteinuria in screening school children for Schistosoma haematobium infection. It included a random sample of 400 school children aged 6-15 years in rural area of Fayoum Governorate, upper Egypt. Urine samples of the studied children were tested parasitologically by urine filtration technique as a reference test and semiquantitatively for haematuria and proteinuria using urine reagent strips as screening tests. Results of the study revealed that haematuria was a better indicator for Schistosoma haematobium infection than proteinuria, as it was more sensitive (85.5% 73.4%, respectively), specific (94.4% 82.9%, respectively) and reliable (kappa=92% 80%, respectively). Moreover, it had stronger relationship with intensity of infection (r=0.88 & 0.67, respectively). A combination of different grades of haematuria and proteinuria did not significantly increase either sensitivity or specificity. Dipstick haematuria could be a valuable technique in screening rural Egyptian school children who are at risk of urinary schistosmiasis.     

Cimetidine — antacid combination as premedication for elective Caesarean section

The effect of premedication with an oral antacid (magnesium trisilicate), oral cimetidine or a combination of both was studied in 80 patients undergoing elective Caesarean section. Twenty patients served as untreated controls. Seventy per cent of the patients were in the high risk range for acid aspiration Pneumonitis (pH < 2.5 plus gastric coment volume > 25 ml). Antacid therapy was effective in raising pH but the gastric volume remained high in 50 per cent of the patients. Cimetidine was effective in decreasing gastric volume and raising pH but the pH was still <2.5 in two patients. None of the patients given the cimetidine-antacid combination were in the high risk range for acid aspiration Pneumonitis. The combination of an oral dose of Cimetidine 400 mg, three to four hours before the operation followed by 20 ml of magnesium trisilicate one hour preoperatively proved to be the most efficacious regimen for prophylaxsis against Mendelson’s syndrome in elective Caesarean section. Recent reports have suggested that non-particulate antacids (e.g., sodium citrate) may be preferable to particulate antacids such as magnesium trisilicate.     

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer

Purpose: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. Methods: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. Results: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml · min) were lower than those of the control patients (88.3 mg/ml · min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. Conclusion: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed. Received: 28 October 1997 / Accepted: 9 March 1998     

Disruption of intracerebral progression of C6 rat glioblastoma by in vivo treatment with anti-CD44 monoclonal antibody

OBJECT: Glioblastoma multiforme (GBM) invasiveness is a complex process that involves recognition and attachment of GBM cells to particular extracellular matrix (ECM) molecules before migrating into proteolytically modified matrix and inducing angiogenesis. The CD44 molecule, which is a transmembrane adhesion molecule found on a wide variety of cells including GBM, has been suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the standard form of CD44 (CD44s, 85-90 kD) might prevent invasion and thus disrupt progression of C6 GBM in vivo. METHODS: Immunostaining demonstrated homogeneous expression of CD44s on the surface of C6 GBM cells and tumors. Flow cytometric analysis demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive (up to 94+/-2.7%; mean +/- standard deviation [SD]) detachment of C6 cells from ECM-coated culture. Blocking of CD44s in vivo resulted in significantly reduced C6 brain tumors (3.6+/-0.4% [SD])--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--compared with untreated (19.9+/-0.9%) or sham-treated (19.2+/-1.1 to 19.3+/-2.5% [SD]) rats. Disruption of C6 GBM progression correlated with an improved food intake; treated rats were significantly less cachectic (166.6+/-16.4 g [SD]) than those that were untreated (83+/-2.7 g [SD]) or sham-treated (83.4+/-1.1 to 83+/-2.2 g [SD]) rats. CONCLUSIONS: The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.