Evolving locally appropriate models of care for Indian sickle cell disease.

The sickle cell gene in India represents a separate occurrence of the HbS mutations from those in Africa. Sickle cell disease in India occurs against different genetic and environmental backgrounds from those seen in African patients and there is evidence of clinical differences between the populations. Knowledge of the clinical features of African disease was drawn from the Jamaican Cohort Study, based on prospective follow up of all cases of sickle cell disease detected by the screening of 100,000 consecutive newborns in Kingston, Jamaica, and supplemented by observations from the Cooperative Study of Sickle Cell Disease in the US. Defining the principal causes of early morbidity in African sickle cell disease led to successful interventions including pneumococcal prophylaxis, parental education in the early diagnosis of acute splenic sequestration, and the early detection by trans-cranial Doppler of cerebral vessel stenosis predictive of stroke but their success depended on early diagnosis, ideally at birth. Although reducing mortality among patients with African forms of SS disease, the question remains whether these interventions are appropriate or justified in Indian patients. This dilemma is approached by comparing the available data in African and Indian forms of SS disease seeking to highlight the similarities and differences and to identify the deficiencies in knowledge of Indian disease. These deficiencies could be most readily addressed by cohort studies based on newborn screening and since much of the morbidity of African disease occurs in the first five years of life, these need not be a daunting prospect for Indian health care personnel. Newborn screening programmes for sickle cell disease are already underway in India and appropriate protocols and therapeutic trials could quickly answer many of these questions. Without this knowledge, Indian physicians may continue to use possibly unnecessary and expensive models of care.

Harmonization: the Sample, the Measurement, and the Report

Harmonization of clinical laboratory results means that results are comparable irrespective of the measurement procedure used and where or when a measurement was made. Harmonization of test results includes consideration of pre-analytical, analytical, and post-analytical aspects. Progress has been made in each of these aspects, but there is currently poor coordination of the effort among different professional organizations in different countries. Pre-analytical considerations include terminology for the order, instructions for preparation of the patient, collection of the samples, and handling and transportation of the samples to the laboratory. Key analytical considerations include calibration traceability to a reference system, commutability of reference materials used in a traceability scheme, and specificity of the measurement of the biomolecule of interest. International organizations addressing harmonization include the International Federation for Clinical Chemistry and Laboratory Medicine, the World Health Organization, and the recently formed International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR). The ICHCLR will provide a prioritization process for measurands and a service to coordinate global harmonization activities to avoid duplication of effort. Post-analytical considerations include nomenclature, units, significant figures, and reference intervals or decision values for results. Harmonization in all of these areas is necessary for optimal laboratory service. This review summarizes the status of harmonization in each of these areas and describes activities underway to achieve the goal of fully harmonized clinical laboratory testing.

Seroprevalence of hepatitis A virus and varicella zoster antibodies in a Javanese community (Yogyakarta, Indonesia).

Hepatitis A virus (HAV) cause an acute inflammation of the liver. Varicella-zoster virus (VZV) cause chickenpox (varicella) and herpes zoster. Effective vaccines against hepatitis A and varicella are available for children, adolescents and adults. In order to implement an appropriate vaccination policy, a baseline to assess the potential benefits and sections of the population who would benefit most are required. We investigated seroprevalence of hepatitis A virus and varicella zoster antibodies in a Javanese community. A total of 1,103 subjects were studied. The 600 subjects aged 4 to 9 years were sampled between 23 October and 2 November, 1995. The other subjects were sampled between 12 October and 1 November, 1996. The overall prevalence of anti-HAV in cohort was 28.7%. Anti-HAV seroprevalence rates were below 30% until the age of 15 and below 40% until the age of 25. The anti-varicella seroprevalence showed only in two thirds of seropositive population at the age of 15. The results of the study have implications for vaccination strategies for both hepatitis A and varicella zoster.

Psychological distress among younger siblings of patients with homozygous sickle cell disease in the Jamaican cohort study

The presence of a chronically ill family member may adversely affect the psychological health of siblings. This study used the General Health Questionnaire and the Modified Social Adjustment Scale to assess psychological distress in 20 younger siblings (4 AA, 16 AS genotypes), aged 16-19 years, of patients with homozygous sickle cell (SS) disease. The results were compared with those previously obtained in the 20 older siblings with SS disease and in 89 controls with a normal haemoglobin (AA) genotype. High levels of psychological distress occurred among all three groups. Greater psychological distress and poorer social adjustment occurred among siblings compared to AA controls but these differences disappeared after adjusting for the reduced age of sibings. The two measures were similar in SS patients and AA controls. The level of psychological distress among siblings of SS patients did not differ from that in SS patients or AA controls.

Second report of AIDS related attitudes and sexual practices of the Jakarta Waria (male transvestites) in 1995.

As the second part of a community based educational campaign to convey the risk of HIV/AIDS to commercial sex workers in Jakarta, from May-July 1995, a total of 253 male transvestites (WARIA) were questioned about their sexual behavior patterns and their knowledge and attitude toward HIV/AIDS. In the previous report, 1991-1993, there was one out of 830 WARIA found HIV positive in November 1993. In this study, 1995, a total of two out of 253 WARIA were confirmed of HIV infection in July 1995. Most of them still have incorrect knowledge on HIV/AIDS transmission mode, they are still practicing high risk sexual attitudes such as an exchange partner rate of 5 men per three weeks, low condom use (1.2 out of the last 5 sexual contacts). The reasons for not using condoms were forgetfulness 35.3% and partner does not like condom 38.2% Most of WARIA know about condoms (94.5%), but it is difficult to access condom use from small shops around them. Therefore, to prevent further spread of HIV/AIDS in WARIA, condom should be used constantly and properly. It has been shown from another study, that more information, better availability and better promotion of condoms can increase condom use. Thus, attention should be placed on various ways of distributing condoms for WARIA in Jakarta, especially community-based distribution by peer leaders, social marketing and commercial sales.

Penicillin resistant streptococcus pneumoniae in a Jamaican patient with homozygous sickle cell disease

Penicillin prophylaxis against infection by Streptococcus pneumoniae is now routine in young children with homozygous sickle-cell (SS) disease and the emergence of penicillin-resistant strains is a serious clinical concern. The first death associated with such resistance in a Jamaican child with SS disease is reported

A non-invasive assessment of hepatitis B virus carrier status using saliva samples.

A non-invasive testing method to determine hepatitis B virus (HBV) carrier status in pregnant women was evaluated. Paired serum and saliva samples were collected and assessment of hepatitis B markers were performed. Of the 502 women enrolled, 5.6% (28/502) of their sera were found to be positive for HBV surface antigen (HBsAg). Assessment of 28 HBsAg seroreactive and 200 HBsAg sero-non-reactive paired saliva samples showed that 17 saliva contained HBsAg. Fourteen of the saliva reactive samples were matched to the serum reactive samples (50% sensitivity); and 3 saliva samples were positive for HBsAg among 200 subjects seronegative for HBsAg (98.5% specificity). Seven of the 28 HBsAg positive sera were found to be reactive for HBV envelope antigen (HBeAg) (25%). One of seven HBeAg seroreactive and 16 HBeAg seronegative paired saliva samples tested were non-reactive for HBeAg. This report found a non-invasive saliva testing method to be a possible alternative approach for determining chronic HBV carrier status if the sensitivity of the test can be improved.

Prevalence of antibodies to hepatitis C virus and other markers in Jamaica

Three population groups, 1500 blood donors, 513 antenatal women representing a normal population group and 250 sicklers representing a multiply transfused group were studied to determine the prevalence of hepatitis C viral (HCV) infection in Jamaica. The relationship to liver enzyme levels, hepatitis B infection, syphilis and HIV infection was also investigated. Sera were screened by enzyme-linked immunoassay (EIA) for anti-HCV C100-3 and subsequently tested by a supplementary second generation recombinant immunoblot assay (RIBA). In the blood donors, the prevalence of anti-HCV was low, 0.3 per cent - 0.4 per cent, the same level as that reported by several European countries. In the multiply transfused sicklers, the prevalence was more than seven times higher. No HCV infection was detected in the antenatal group. There was little correlation between HCV infection and surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) and no correlation with sexually transmitted diseases.

Testosterone deficiency and extreme retardation of puberty in homozygous sickle-cell disease

Homozygous sickle-cell (SS) disease is associated with retardation of physical and sexual development but most Jamaican children commence their adolescent growth spurt before 16 years of age. Analysis of growth from children in the Jamaican Cohort Study noted extreme growth retardation , defined as an absence of the adolescent growth spurt and pre-pubertal sexual development (Tanner stage 1 or 2) at age 16 years, in 8/52(15 per cent) SS boys. These and two boys from the general sickle-cell clinic with a similar growth pattern provided a study group of 10 boys who were investigated for a possible endocrine explanation for their extreme retardation of physical maturation. A sub-optimal testosterone response (<10 nmol/l) to human chorionic gonadotrophin and an exaggerated gonadotrophin hormone releasing hormone was consistent with poor testicular function in 5 boys. Retardation of adolescent growth and development is common in boys wit SS disease but, when extreme, requires early investigation to identify potentially correctable mechanisms

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropinthytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testiculat axis.

A randomized controlled trial of Solcoseryl and DuoDerm in chronic sickle-cell ulcers

A randomized controlled trial of Solcoseryl, DuoDerm and conventional conservative therapy with Eusol has been performed in 32 patients with homozygous sickle-cell (SS) disease. After 12 weeks' baseline observation, patients were randomized to one of three therapies and monitored for a further 12 weeks. Of 44 ulcerated legs, 20 received control treatment, 12 Solcoseryl and 12 DuoDerm. DuoDerm was generally unacceptable, and two-thirds of the patients defaulted from this treatment. Solcoseryl increased ulcer healing compared to the controls but the difference was not significant. Solcoseryl was well tolerated and may have a role in the treatment of chronic leg ulcers of sickle-cell disease.

Portal vein thrombosis in a child with homozygous sickle-cell disease

A 13-year old boy with homozygous sickle-cell (SS) disease died suddenly at home folllowing a short history of abdominal pain. Autopsy revealed venous thrombosis of the hepatic, portal, superior mesenteric and splenic veins. Venous thrombosis is rare in SS disease and thrombosis of mesenteric vessels is most frequently seen in chronic myeloproliferative disorders. Its occurrence in SS disease raises the possibility of a common pathogenesis and adds another pathology to the causes of abdominal painful crisis.

challenge of sickle cell disease in Saudi Arabia

The sickle cell gene is common in the Kingdom of Saudi Arabia, the sickle cell trait reaching frequencies of 25% in the Eastern Province and generally lower levels in the Southwest. In the Eastern Province the disease is generally mild, associated with high levels of H[b]F, and a specific beta globin haplotype. In the Southwest, the disease is generally more severe, associated with lower H[b]F levels, and an African [Benin] beta globin haplotype. In both areas relational and other forms of alpha thalassemia reach heterozygous frequencies of approximately 50%. The roles of alpha thalassemia and of high levels of H[b]F in ameliorating the expression of homozygous sickle cell disease are controversial. The Saudi population offers unique opportunities for clarifying these relationships