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This article examines whether it is possible to target vulnerable households within a geographically defined area. It looks first at the justification for targeting and then reviews recent practical experience in actually trying to reach vulnerable groups. As complex emergencies increasingly last longer, strategies to target vulnerable households are common in the protracted phase of the emergency. While this is often necessary because of a decline in resources, it is not always justified by an improvement in nutritional status or food security of the beneficiary population. Common target groups are the poor and the malnourished, but in complex emergencies these are not always the most vulnerable. Moreover, recent practical experience has shown considerable difficulties in targeting the poor. Methods to target the poor rely on community-based relief committees, whose priorities are not necessarily the same as those of external agencies. This paper gives examples of such targeted assistance programmes in Kenya, south Sudan and Tanzania. The paper concludes that situations where targeting vulnerable households is justified and feasible are extremely limited. It is suggested that if targeting has to be done because of scarce resources, this should be done on a geographical basis and on the basis of nutritional status. Case-study material shows that it is essential to understand the political determinants of vulnerability and to design methods that will reach the most vulnerable.

Apoptosis of normal thymocytes was shown to be triggered by several mechanisms (e.g. glucocorticoids, gamma-irradiation). In the present study the authors report on thymocyte apoptosis that is induced by thymic epithelial cells. The thymocytes undergo a massive apoptotic death within 24 h of cocultivation with thymic epithelial cell monolayers derived from primary cultures (PTEC) or from a thymic epithelial cell line (TEC). Non-thymic monolayers were inactive. Apoptosis induction in this experimental model requires direct contact between the thymocytes and the thymic epithelial monolayer and can be blocked by anti-CD2 and anti-LFA-1 antibodies. The immature CD3-/+dull CD4+CD8+ thymocytes were the cells which undergo apoptosis. The fact that the authors are dealing with a massive apoptotic process of immature cells in the absence of exogenous antigen suggests that it involves the nonselected thymocytes. The apoptotic pathway selected by thymocytes following their culturing on TEC involves p53 expression. Indeed it was found that TEC-induced apoptosis, led to the accumulation of p53 protein that preceded the step of DNA fragmentation in freshly isolated thymocytes as well as in a glucocorticoid resistant thymoma cell line. Since glucocorticoid-induced thymocyte apoptosis is p53-independent, glucocorticoids are conceivably not involved in TEC-induced thymocyte death. The in vitro experimental model presented here may reflect the physiological sequence of events leading to thymocyte death in the thymus.

Aim To describe what proportion of acutely malnourished children, aged 0 to Methods A total of 33 programme databases, from 12 countries, collected between 2002 and 2008, with a total of 118 180 individuals (range 59–22 473 per data set), were obtained for analysis as part of the Management of Acute Malnutrition in Infants project. The authors excluded data from 93 511 individuals because they were either duplicates (1389), had age data missing or were ≥60 months (15 643), had sex data missing (15), had programme care type data missing (971) or did not received TFP care (75 493); leaving a final sample of 24 669 individuals. TFP treatment models included day centres (DC), home treatment (HT), stabilisation centres and therapeutic feeding centres. Results Overall, young infants accounted for 16.2% (n=4002) of admissions, ranging from 10.2% to 26.4% in HT and DC programmes, respectively. Prevalence of oedematous malnutrition was lower in young infants than in children (p Conclusions In this study, young infants account for an important proportion of TFP admissions for the treatment of acute malnutrition. Malnutrition profile differed to that in children, with significantly less oedema. Worse infant outcomes suggest the need to improve infant-specific management: neither infants nor children met SPHERE standards for cure (>80% programme cure). There were significantly more infant deaths. Future research is needed to determine whether our findings are representative of all acutely malnourished young infants.

The humoral and cellular components of the antibody-dependent cellular cytotoxicity (ADCC) against allogeneic human colonic tumour cell lines were evaluated. The 2 colon cell lines used in this study (HT-29 and ACC-20) were found by immunofluorescence to have carcinoembryonic antigen (CEA) on their surface, and to become sensitive to the lytic effect of unstimulated lymphocytes after coating with heterologous anti-CEA. This reaction was used to evaluate the ADCC activity of mononuclear cells from the peripheral blood of patients with gastrointestinal cancer (mostly local extensive colo-rectal). Remarkable variability was found in the lytic capability (2-50% specific lysis) of both cancer and non-cancer mononuclear cells, with no significant difference between them. Sera from 127 cancer patients and 91 non-cancer patients were tested, using the reaction with heterologous anti-CEA as positive control and as a reference point. In 46 cases (21%) the sera were reactive in this system, and 43 of them were of Blood Group O. However, there was no difference between the cancer patients and the normal controls. The antigenic determinant involved in this reaction is not the Blood Group A specificity but, most probably, a polypeptide common to CEA and A (as shown in the following publication). In addition, trials for the elimination of the non-tumour-specific reaction, by absorption or inhibition, failed to disclose a tumour-specific one. The value of the ADCC assay in monitoring human tumour immunity, and possible ways of eliminating reactivity to normal antigens in this system, are discussed in the light of these findings.

The relationship between carcinoembryonic antigen (CEA) and A antigenic determinants on the cell surface of colon-tumour cells was studied by the ADCC assay. Antiserum prepared in 2 rabbits to an undecapeptide analogous to the amino terminal of CEA(1-11) was found by us either to participate in (Rabbit 2) or specifically inhibit (Rabbit 1) ADCC. The binding spectra of these two antisera and of antiserum to the whole CEA molecule were similar. All of them react with A and non-A colon-tumour cells as well as red blood cells of Type A (RBC-A) and their activity was completely absorbed on RBC-A but not on B or O. O-type, ADCC-reactive human sera always react with A-type colon-tumour cells and RBC-A, and some of them with non-A colon-tumour cells also. The degree of inhibition of their reactivity by anti-CEA(1-11) R1 varied between sera, from none to almost a complete inhibition, and is not related to whether the serum is of cancer or non-cancer origin. Non-reactive O-type sera contain anti-A activity demonstrable by haemagglutination and immunofluorescence. However, they cannot participate in ADCC reaction nor inhibit it. The sera, which contain lymphocyte-dependent antibody to A-type colon-tumour cells, lysed RBC-A, without the addition of lymphocytes or complement, in an immunologically specific way. It is concluded that the reactivity seen in our ADCC system is related to a determinant common to A and CEA (and maybe to other normal cross-reacting antigens) which most probably resides in the amino terminal part of these molecules. This determinant elicits the production of lymphocyte-dependent antibodies in about 50% of people with blood group O. Thus, the amino terminal part of CEA is not a tumour-specific part of the CEA molecule. No specific anti-tumour activity was found in patients' serum by this method, and claims for its demonstration by other methods may well be related to the non-specific activity observed here. ImagesFigure

Recombinant interferon preparations caused a dose-dependent increase of human monocyte cytotoxicity to the K562 and Daudi cell lines. Both rIFN-gamma and rIFN-beta enhanced this function to a similar extent, while rIFN-alpha c had less effect when compared on the basis of their anti-viral effects. Endotoxin and concanavalin A increased basal monocyte cytotoxicity while phagocytosis of latex particles had no effect. The increased monocyte cytotoxic effect of rIFN-beta was completely abrogated by monoclonal antibody to IFN-beta, while monoclonal antibody to IFN-gamma had no effect. However, monoclonal antibody to IFN-gamma only reduced the increased cytotoxic effect caused by rIFN-gamma by 25%. Catalase inhibited both basal monocyte cytotoxicity and the increase in cytotoxicity following addition of rIFN-gamma only slightly, suggesting that mechanisms other than the oxidative burst were active and could be induced by rIFN-gamma.

Herpes and papilloma virus infections will probably be among the first indications for which interferon (IFN) will find its place as a therapeutic agent. The data to be analysed below suggest that, when properly used, interferon offers the combination of efficacy and safety that has not been achieved thus far by any of the other currently available treatments for these two viral infections. However, in order to put this analysis in its proper framework, it will be appropriate to precede it with a short comparative description of the viruses and the diseases caused by them.

The aim of this communication is to increase awareness to specific problems of certain population sectors whose immunological system may be more sensitive to toxic damage than the normally functioning system. Indeed, the title of the presentation was selected with three considerations in mind: (a) It is possible and instructive to compare therapeutic immunomodulation, with which there is relatively more experience, and immunotoxicity, and by doing so to gain better insight into the general rules and potential mechanisms of toxic effects on the immune system. Moreover, therapeutic immunomodulatory agents are known to cause immunotoxicity under certain circumstances (Shoham, 1984a) and, in principle, the reversed situation is also possible. (b) Conditions of “deficiency”,“in sufficiency” or “failure” of the immune system may amplify or modify the effect of either type of agents. Accordingly, these conditions call for more caution and specific attention to potential adverse effects of such agents, which could cause further deterioration of the deficient immune system. Moreover, conditions of immunodeficiency are important targets for the therapeutic use of immunomodulating agents and these conditions may give rise to toxicity rather than benefit as as an outcome of this therapeutic manipulation. (c) There are certain similarities between the effect of age (either too young or too old) and malnutrition on the immune system, which justify considering them together in connection with potential toxic damage.

Native human interferon (IFN) β or γ added to human monocytes in culture increased their leishmaniacidal effect on intracellular Leishmania tropica major amastigotes. This effect was dose dependent and was apparent if the IFN was added either prior to or after infection of the monocyte cultures with the promastigote form of the parasite. IFN-γ was shown to be approximately three times more effective than IFN-β. Recombinant IFN-γ showed similar effects. In addition, IFN-γ increased H2O2 Production from hunan monocytes in culture in a dose dependent manner. Monocytes which had been Infected with L major amastigotes produced less H2O2 than did the control uninfected cultures. Monoclonal antibody to IFN-γ abrogated both its effect on the leishmaniacidal capacity and its increase of H2O2 Production by the monocytes results suggest that IFN-γ may be of therapeutic value in cutaneous leishmaniasis.