The need for an integrated approach for chronic disease research and care in Africa.

With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.

Antenatal intravenous immunoglobulin in chronic immune thrombocytopenic purpura: case report and literature review.

Immune thrombocytopenic purpura (ITP) may complicate pregnancy and, uncommonly, may cause severe neonatal thrombocytopenia. However, it is difficult to predict which neonates are at risk of severe thrombocytopenia. Direct fetal sampling is not commonly done, as it poses significant risks to the fetus. Furthermore, appropriate antenatal treatment of neonates is controversial. We describe the case of a 32-year-old woman with chronic severe ITP and a previous severely affected infant, pregnant with trichorionic triplets, who was successfully managed with the use of weekly intravenous immunoglobulin 1 g/kg without recourse to direct fetal sampling.

Development of a process for the production of the anticancer lead compound pleurotin by fermentation of Hohenbuehelia atrocaerulea.

Pleurotin is a naphthoquinone antibiotic originally isolated from Pleurotus griseus. Two pleurotin producing strains of Hohenbuehelia atrocaerulea have been identified, which, on solid substrate fermentation for 2 months yield 1-2 mg/l of the antibiotic. Described here is the lengthy developmental process which resulted in a production protocol being developed which reliably yields pleurotin from liquid fermentation at >300 mg/l. Critical to obtaining this increase in titer was inclusion in the media of an aqueous extract of alder wood.

Platelet indices during normal pregnancy and pre-eclampsia.

Platelet count and mean platelet volume (MPV) were estimated in 349 normal pregnancies at various gestational stages, and in 30 cases of pre-eclampsia. A probability plot was constructed from these data using discriminant analysis of MPV versus platelet count for the pre-eclamptic versus normal pregnancies. The sensitivity for pre-eclampsia was 90% (27/30) and the specificity was 83.3%. This plot may be of use in confirming risk of pre-eclampsia.

Antenatal diagnosis and management of fetomaternal alloimmune thrombocytopenia.

Fetomaternal alloimmune thrombocytopenia (FMAT) arises from maternal-fetal platelet antigen incompatibility, which stimulates the production of maternal immunoglobulin G (IgG) platelet-specific antibody. Transplacental passage of this antibody results in fetal platelet destruction and consequent thrombocytopenia. Sequelae of thrombocytopenia may be observed in both the fetus and neonate with intracranial hemorrhage occurring in approximately 10 to 30% of affected infants. No antenatal universal screening test is currently available to detect the 50% of cases occurring in the first pregnancy. The recurrence rate in subsequent pregnancies is 75 to 85%, with a tendency to increasing disease severity. Paternal platelet genotyping is recommended to assist in risk counseling following an affected pregnancy. Prenatal therapeutic strategies are aimed at elevating the fetal platelet count in affected pregnancies and thus decreasing hemorrhagic sequelae. The most effective treatment regimen is uncertain, but encouraging results are reported with the use of maternal intravenous gamma globulin. We report our experience in the antenatal diagnosis and management of FMAT.

Antenatal platelet antibody testing by flow cytometry--results of a pilot study.

BACKGROUND: Maternal platelet antibodies can cause fetomaternal alloimmune thrombocytopenia (FMAT), which has significant mortality and morbidity even in a first pregnancy. Prenatal diagnosis of FMAT has not previously been possible in the first affected pregnancy. STUDY DESIGN AND METHODS: Using flow cytometry, a sensitive, inexpensive test for the detection of platelet antibodies has been developed. It was adapted for use as a possible antenatal screening test, and 600 pregnant women were tested in a pilot study. RESULTS: In the study group, two women tested positive for platelet-specific IgG antibodies, one for anti-HPA-1a and the other for anti-HPA-1a with anti-HLA. In each case, the fetus was found to be affected in utero, and treatment was initiated before successful delivery. Another woman was shown to have a platelet-reactive autoantibody without IgG specificity, and her infant was unaffected. A total of 95 (15.8%) of the women tested had HLA antibodies alone, and the majority demonstrated IgG specificity. On follow-up of 62 infants born to these women, none had thrombocytopenia; thus HLA antibodies were not shown to lead to FMAT in this study. CONCLUSION: The flow cytometry-based test for platelet antibodies can detect clinically significant maternal antibodies, and it may be that early diagnosis and treatment in utero can enhance outcome in FMAT. A population screening program is planned to determine the predictive power of this test, in addition to its sensitivity, specificity, and efficiency.

Feto-maternal alloimmune thrombocytopenia associated with anti-HPA-5a--the first Australian case.

Maternal alloantibodies to platelet specific antigens are a rare but important cause of severe thrombocytopenia in the fetus and neonate. Feto-Maternal Alloimmune Thrombocytopenia (FMAT) is most often due to anti-HPA-1a (PLA-1) or anti-HPA-5b (Bra). Anti-HPA-5a (Brb) however is extremely uncommon, with only 4 cases previously described. We report the first Australian case of feto-maternal alloimmune thrombocytopenia due to anti-HPA-5a.

A fatal case of necrotizing enterocolitis in a neonate with polyagglutination of red blood cells.

An infant of 30 weeks gestation developed necrotizing enterocolitis (NEC) 8 days after birth and died 2 days later after a fulminating course. During her illness she received two blood transfusions, both of which produced sub-optimal rises in her haemoglobin and were associated with evidence of haemolysis. Retrospective analysis demonstrated T antigen (Tk) polyagglutination of the infant's red blood cells and donor plasma. Although bacterial cultures were negative throughout the course of the illness in this case, T antigen exposure is associated with certain anaerobic infections and with severity of NEC. Infants with NEC should be regularly screened for T antigen exposure and if this test is positive, plasma (immunoglobulin) containing infusions should be avoided.

Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia.

We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non-lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI.

A reappraisal of pre-transfusion testing procedures in a hospital blood bank.

In recent years, experience with screening protocols for the detection of red cell antibodies has led to a reappraisal of pre-transfusion testing procedures. In the U.S.A. in particular, it has become accepted practice to perform only an antiglobulin crossmatch when an antibody screen has been negative. There is now debate in that country regarding the necessity of retaining even the antiglobulin crossmatch. In this laboratory, as is usual in Australia, room temperature, enzyme and antiglobulin tests are used for both antibody screening and crossmatching. A review was therefore conducted of the results of screening 58,227 samples from approximately 40,000 patients, involving 126,771 crossmatched blood units over a 53 mth period. Eight hundred and seventy-two red cell antibodies were detected in 718 patients. Forty-four of these antibodies were detected only in the crossmatch, and of these 23 were of potential clinical significance. Fourteen of the 23 were detected by the antiglobulin test, 8 by an enzyme test and only 1 by the saline method. Of 107 antibodies detected only in the room temperature phase, none were of clinical significance. The results indicate that exclusion of room temperature tests from all pre-transfusion testing, and deletion of enzyme tests from the crossmatch will not compromise patient safety.

Inhibition of serological reactions with enzyme-treated red cells by complement binding alloantibodies.

Complement-binding antibodies (2 examples of anti-Jka and 2 anti-kell) which inhibit agglutination of enzyme-treated cells have been investigated in the sera of 4 patients. The sera containing anti-Jka also contained rhesus antibodies (c + E and D + C) which could not be readily identified by an enzyme technique due to failure of the Jka+ cells of the corresponding Rh phenotype to react. The inhibition of the enzyme test reactivity was revealed using a control reagent added to each test after the initial examination for agglutination. Addition of ethylenediaminetetraacetic acid to the sera prior to testing resulted in identifiable reactivity with panel red cells. Failure to recognise this phenomenon in sera containing antibodies reacting only by an enzyme technique could result in misidentification, delay in providing compatible blood and transfusion of incompatible blood. Routine control of enzyme tests to detect false-negative results is recommended.

Evaluation of an enzyme-linked antiglobulin test for the detection of red cell antibodies.

An enzyme-linked antiglobulin test (ELAT) using low ionic strength saline for the initial red cell sensitisation phase, and alkaline phosphatase conjugated antiglobulin (AP-AHG), has been compared with a conventional low ionic strength antiglobulin test in testing 222 red cell antibodies of various specificities. A wide variation in absorbance values was observed at all levels of haemagglutination strength. Relatively higher absorbance values were obtained with anti-K compared with the agglutination gradings. Haemolysis was eliminated by modifying the substrate buffer used for diluting the AP-AHG, since fixation of red cells prior to sensitisation significantly reduced the sensitivity of the ELAT. Five commercial AP-AHG reagents compared to tests with D, Fya, K and Jka antibodies varied markedly in performance, some being unsatisfactory. The ELAT can be effectively used for antibody detection as well as quantitative determinations but requires automation to realise its full potential.

A serum factor which inhibits serologic reactions with enzyme-treated red blood cells.

Two patients' sera inhibited agglutination of enzyme-treated red blood cells by antibodies. This blocking effect was detected by using a mixture of antibodies as an enzyme test reagent for the routine control of a two-stage papain test. The blocking factor appeared to be IgG and its effect was complement dependent. It blocked reactions with red blood cells treated with papain, bromelin, or ficin. Reactions with both IgM and IgG antibodies of various specificities were blocked. The presence of the blocking factor in a patient's serum may result in failure to detect clinically significant antibodies unless a control system is used which will confirm that the cells in each test can be agglutinated by enzyme reacting antibodies.

Lymphocytic lymphoma presenting with peripheral bony manifestations and with massive renal infiltration responsive to BACOP combination therapy.

A 26-year-old man with diffuse lymphocytic lymphoma presented with painful peripheral bone involvement and with acute renal failure associated with massive lymphomatous renal infiltration. Renal function returned to near normal following combination chemotherapy with bleomycin, adriamycin, cyclophosphamide, vincristine and prednisolone (BACOP).

Auto anti-M antibody following renal transplantation.

A 25-year-old man with rapidly progressive glomerulonephritis developed an autoantibody with anti-M specificity following haemodialysis and renal transplantation. The patient's red cells typed as MN. The antibody was an IgM globulin which displayed marked dosage effect and variable pH dependence. The thermal range of reactivity extended to 37 degrees C. The stimulus for the production of the antibody is uncertain.