Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Using models to shape measles control and elimination strategies in low- and middle-income countries: A review of recent applications.

After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct regular situation analyses and to leverage models to adapt interventions to local needs. Here, we review applications of models to develop locally tailored interventions to support control and elimination efforts. In general, statistical and semi-mechanistic transmission models can be used to synthesize information from vaccination coverage, measles incidence, demographic, and/or serological data, offering a means to estimate the spatial and age-specific distribution of measles susceptibility. These estimates complete the picture provided by vaccination coverage alone, by accounting for natural immunity. Dynamic transmission models can then be used to evaluate the relative impact of candidate interventions for measles control and elimination and the expected future epidemiology. In most countries, models predict substantial numbers of susceptible individuals outside the age range of routine vaccination, which affects outbreak risk and necessitates additional intervention to achieve elimination. More effective use of models to inform both vaccination program planning and evaluation requires the development of training to enhance broader understanding of models and where feasible, building capacity for modelling in-country, pipelines for rapid evaluation of model predictions using surveillance data, and clear protocols for incorporating model results into decision-making.

Campylobacter colitis.

A patient is described in whom a campylobacter enteritis closely resembled ulcerative colitis on clinical, sigmoidoscopic, and histological grounds. Selective stool culture techniques may be necessary to differentiate campylobacter colitis from ulcerative colitis proper.

The histological diagnosis of chronic gastritis in fibreoptic gastroscope biopsy specimens.

The advent of the fibreoptic gastroscope with biopsy facilities has provided the means of obtaining biopsy specimens under direct vision from any part of the stomach. This creates new opportunities for the study of chronic gastritis, and, in particular, its evolution, topographical location, and causal relationships. On the basis of an experience with more than 2,500 biopsy specimens we have outlined a method for their systematic examination and have proposed a classification of chronic gastritis. This classification includes the type of mucosa, the type and stage of activity of the gastritis, and the presence and type of metaplasia. The classification is sufficiently flexible to allow within it quantitative assessment of individual histological features.

Luminal ions and short chain fatty acids as markers of functional activity of the mucosa in ulcerative colitis.

Luminal concentrations of short chain fatty acids (SCFA), ammonia, sodium and potassium were measured in colonic dialysate of 16 control subjects and in 65 cases with ulcerative colitis (UC), which were graded according to mucosal changes into mild (1), moderate (2), or severe (3) inflammatory activity. Sodium concentrations were mildly but not significantly increased in severe ulcerative colitis while luminal potassium concentrations were markedly decreased in severe ulcerative colitis (p less than 0.025). Concentrations of SCFA were increased in severe ulcerative colitis. Butyrate concentrations were significantly raised in all stages of active ulcerative colitis even when other fatty acids were not raised. Of all the parameters a lowered pH and raised butyrate concentration most strikingly correlate with the severity of mucosal change. Results indirectly suggest that control of luminal pH, potassium secretion and utilisation of butyrate by the colonic mucosa are impaired with progressive mucosal inflammation.

Treatment of chronic gastric ulcer with gefarnate: a long-term controlled therapeutic trial.

A long-term controlled therapeutic trial of gefarnate (600 mg daily) in the treatment of chronic gastric ulcer was carried out in 32 patients. Assessment was based on the clinical course and on repeated radiological and endoscopic examinations, which were performed after 3-months' treatment, at the end of the 1-year trial period, and towards the end of a follow-up period of approximately 2 1/2 to 3 1/2 years. In men with gastric ulcer, gefarnate proved to be highly effective, with 10 out of the 11 patients who received this treatment showing persistent healing of the ulcer compared with only 4 out of the 11 who were on dummy treatment. In the very small group of women it was not possible to show any difference between treatments. No adverse reactions to gefarnate occurred. These results suggest that gefarnate is a safe and effective treatment for chronic gastric ulcer.

Problems associated with the use of merthiolate as a preservative in anti-lymphocytic globulin.

The cytotoxic properties of 2 anti-lymphocytic globulin (ALG) preparations were investigated in vitro by measuring the release of 51Cr from labelled human peripheral blood mononuclear cells, tonsil lymphocytes and Chang cells, incubated with different concentrations of ALG. One of the ALG preparations showed non-selective cytotoxicity in the absence of complement. Evidence was obtained to suggest that this effect was due to merthiolate (sodium ethylmercurithiosalicylate) which had been added to the ALG as a preservative during manufacture. The mercury concentration in the ALG was found to be greater than that stated by the manufacturers. It is conceivable that the clinical use of such as ALG preparation might lead to mercury accumulation in the tissues, with resulting toxic effects. The whole question of the use of merthiolate in the preparation of sera for administration to human subjects needs to be reconsidered.

Factors influencing the early plasma disappearance rate and liver uptake of thyroxine.

The early disappearance from plasma (T 1/2) of i.v. administered thyroxine (T4) labelled with 131I was studied in order to find a simple biochemical parameter with which it could be correlated in health and disease. The radioactivity of the liver was also measured by surface counting to determine the time for the peak liver count rate. The T 1/2 for the 131I-T4 showed a correlation of borderline significance with T4 in plasma but a good correlation was found with T4-binding globulin (TBG) in plasma and an even better with the T3-test. The T3-test showed a significant correlation with TBG but when the T4-binding capacity of prealbumin (TBPA) was taken into account the correlation was even better indicating that the result of the T3-test was not only dependent on the TBG concentration in plasma but also on the TBPA. The T 1/2 correlated best with the time for the liver peak count rate. The study supports the hypothesis that in the early distribution phase of T4, the free binding sites extracellularly and the available intracellular binding locations compete for T4 until a state of equilibrium is reached.

Evolution of olsalazine.

Sulphasalazine was first produced nearly 50 years ago through the inspiration of a Swedish doctor, Dr Nanna Svartz. Later, in controlled trials, this compound was shown to reduce substantially the frequency of recurrent attacks of ulcerative colitis when used as long-term maintenance therapy. Studies into the metabolism of sulphasalazine have shown that, when taken orally, most of the ingested dose reaches the colon intact, and within the colonic lumen, bacteria split sulphasalazine into two breakdown products, sulphapyridine and 5-ASA. 5-ASA was shown to be the active therapeutic moiety while sulphapyridine served simply as a carrier. Olsalazine was developed to retain the property of sulphasalazine of reaching the colon intact, but also to liberate two molecules of 5-ASA with no residual carrier.

The treatment of ulcerative colitis.

The present state of the art in medical treatment of ulcerative colitis is reviewed in the light of lifelong clinical experience with this disease. The importance of treating the acute episode early and efficiently is emphasized, and a differentiated therapeutic regimen according to disease activity is outlined. Salazopyrin has proved to be the only effective drug in reducing the incidence of recurrences. The criteria for surgical treatment are discussed.

Effect of prednisolone on prostaglandin synthesis by rectal mucosa in ulcerative colitis: investigation by laminar flow bioassay and radioimmunoassay.

The effect of two concentrations of prednisolone on synthesis of prostaglandin E2 (PGE2) by 40 rectal biopsies in organ culture was investigated using both laminar flow bioassay and radioimmunoassay (RIA). Prednisolone (concentration 8.33 x 10(-7)M) reduced mean synthesis of PGE2 to 36.4% of control values (measured by bioassay) or 26.2% of control values (measured by RIA). With prednisolone (concentration 5.66 X 10(-4) M) synthesis of PGE2 was 7.7% of control values (RIA). The two concentrations are similar respectively to those achieved in plasma after oral prednisolone and delivered topically by prednisolone enemata. Inhibition of PG synthesis may thus explain prednisolone's anti-inflammatory action in the treatment of ulcerative colitis.

Treatment of irritable bowel syndrome with lorazepam, hyoscine butylbromide, and ispaghula husk.

A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam, hyoscine butylbromide, and ispaghula husk in 12 randomised blocks of eight patients with the irritable bowel syndrome (IBS). Each of the three agents caused a sustained symptomatic improvement in some of the patients, although only with ispaghula was the difference between the real and dummy preparation statistically significant. When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial. Seven patients improved among the 12 who received potent preparations of all three agents, and between four and six patients improved in the groups receiving one or two of the potent preparations. These therapeutic results, though far from perfect, show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects. Similar combinations of other therapeutic agents may be more effective, but it will be possible to determine this only by carrying out factorial therapeutic trials.

Comparison of various treatments for irritable bowel syndrome.

A previous therapeutic trial of factorial design showed that a combination of a psychotropic drug, a smooth-muscle relaxant, and a bulk former (lorazepam, hyoscine hydrobromide, and ispaghula husk) relieved symptoms of the irritable bowel syndrome more effectively than the same agents given singly. Another trial of similar design was undertaken to compare each of these three agents with another having the equivalent clinical actions--namely, Motival (fluphenazine/nortriptylene mixture), mebeverine, and bran. Ninety-six patients took part; all received three agents, one from each of the three pairs being compared, and no placebos were used. Fifty-six patients reported a sustained symptomatic improvement, which was a significantly higher incidence than in the previous trial, when placebos were used. Ispaghula was significantly more effective than bran. The combination of ispaghula, Motival, and mebeverine improved 11 out of 12 patients--significantly more than bran, Motival, and hyoscine (five improved), or bran, lorazepam, and mebeverine (four improved). Mebeverine was significantly more effective when combined with Motival (18 out of 24 improved) than with lorazepam (10 improved). These results confirm the value of a combined therapeutic approach to the relief of the irritable bowel syndrome and suggest the possibility of synergism between agents.

Ulcerative colitis and pregnancy.

A survey has been made of pregnancy occurring in patients who were attending the Ulcerative Colitis Clinic at Oxford during the 20-year period, 1960-79 inclusive. There were 256 married women of child-bearing age who attended during this period. Of these, 100 were excluded from the survey for various reasons, such as that they had completed their family before the onset of the ulcerative colitis, had already had an hysterectomy, or had a proctocolectomy before their first pregnancy. Of the remaining 156 patients, nine could not be traced. Full details were obtained from 147 patients, virtually all of whom were interviewed. The fertility of these patients was normal. Of the 147 women, 119 (81%) had conceived and only 10 (6.8%) were involuntarily infertile. The size of family approximated to that found in the general British population. The overall outcome of the pregnancies was similar to that in the general British population. The patients in whom the disease was quiescent at the start of pregnancy fared particularly well. Those with active disease had a somewhat lower chance of producing a normal live baby. The small group of patients in whom the disease was severe had a much lower chance of a normal outcome. Patients in whom the ulcerative colitis was quiescent at the beginning of pregnancy had a good chance of remaining symptom-free throughout the pregnancy and puerperium. Even if the colitis recurred, it was likely to be mild and responsive to medical treatment. By contrast, when the ulcerative colitis was active at the start of pregnancy, most patients continued to have symptoms in spite of medical treatment. Some patients had their first attack of ulcerative colitis during pregnancy or the puerperium. In contrast to previous experience the attacks were generally mild and responded to medical treatment. Medical treatment with corticosteroids or sulphasalazine appeared to have no obvious deleterious effects on the fetus or new-born child.

A therapeutic trial of anti-lymphocytic globulin in acute ulcerative colitis.

The results of the preliminary part of a controlled therapeutic trial of antilymphocytic globulin (ALG) in severe acute ulcerative colitis are presented. 10 patients have been studied in this part of the trial, 5 receiving standard treatment with corticosteroids, and 5 receiving ALG, in a dose of 1 g daily for 5 days, in addition to the standard treatment. No difference has been observed in the clinical course of the patients in the two groups. A continuation of the trial is in progress, using ALG in a larger dose (2 g daily for 5 days).

Cytotoxic effect of anti-lymphocytic globulin on human lymphoid cells.

The cytotoxic activity of two anti-lymphocytic globulin (ALG) preparations was investigated by measurement of 51Cr release from human peripheral blood mononuclear cells and tonsil lymphocytes incubated with ALG in the presence of complement. Both types of ALG had a greater complement-dependent cytotoxic effect on tonsil lymphocytes than on peripheral blood mononuclear cells. The ALG preparations were more cytotoxic for a population of tonsil lymphocytes enriched in non-T cells than for one enriched in T cells. This finding does not support the view that ALG has a selective action on T lymphocytes.

Proctocolectomy for ulcerative colitis.

The majority of patients with ulcerative colitis can be managed satisfactorily throughout their lives by medical treatment, but a minority require colectomy. In severe attacks, emergency surgery is often required to save the patient's life. In chronic disease not responding well to medical treatment, elective colectomy will restore the patient to good health. Colectomy is also necessary for certain local complications, such as cancer, severe fistulas, and strictures. Prophylactic colectomy is indicated in patients with long-standing disease in whom there are factors associated with a high risk of developing cancer of the large bowel. For all these indications, it is our opinion that single-stage proctocolectomy is the operation of choice in the great majority of patients. Finally, we consider that the best results are obtained when the physician and the surgeon work together in the closest possible cooperation.

Method of preparing isolated colonic epithelial cells (colonocytes) for metabolic studies.

Suspensions of isolated colonic epithelial cells (colonocytes) have been obtained from rats by incubating everted lengths of colon with EDTA at 37 degrees C in Krebs-Henseleit saline from which calcium was omitted and containing 0.25% (w/v) bovine serum albumin. Measurements of oxygen consumption and lactate production by cell suspensions indicate that they are metabolically active for at least one hour. The method has been modified for the preparation of isolated epithelial cells from the human colon by including an enzyme digestion step and by increasing the concentration of EDTA to 10 mM. Human colonocytes have been obtained either from normal mucosa (ascending and descending colon) or from the mucosa in ulcerative colitis (descending colon). Oxygen consumption of human cell suspensions is lower than in the rat but in colonocytes from both species the rate is increased by glucose and by n-butyrate, a normal constituent of the colonic lumen. The method yields metabolically active cell suspensions from diseased colonic mucosa and promises to be of value for biochemical studies of ulcerative colitis.