Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care.

SETTING: Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. OBJECTIVE: To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. METHOD: In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. RESULTS: Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). CONCLUSION: Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings.

Immune modulation in the blue mussel Mytilus edulis exposed to North Sea produced water.

The discharge of oil well produced water (PW) provides a constant source of contaminants to the marine environment including polycyclic aromatic hydrocarbons, alkylated phenols, metals and production chemicals. High concentrations of PW cause adverse effects to exposed biota, including reduced survival, growth and reproduction. Here we explore the effects of PW on immune function in the blue mussel, Mytilus edulis. Mussels were exposed for 21 days to sublethal PW concentrations (0.125-0.5%) and cellular parameters were measured. Cell viability, phagocytosis and cytotoxicity were inhibited after exposure to 0.25% and 0.5% PW, whilst the 0.125% PW treatment produced significant increases in these biomarker responses. This biphasic response was only observed after 7 days exposure; longer exposure periods led to a reduction in immune parameters. Results indicate that PW concentrations close to the discharge point cause modulation to cellular immunity. The implications for longer-term disease resistance are discussed.

Toxicokinetics of heavy metals from a mining spill using Carcinus maenas.

The knowledge of the reproduction and growth background related to the shore crab Carcinus maenas promotes the use of this crab as a model crustacean to asses the potential for endocrine disruption in crustaceans. In addition, an enzyme linked inmunosorbent assay (ELISA), sensitive to the shore crab vitellogenin in serial hemolymph samples allows determination of the extent of disruption of the process of vitellogenesis in female crabs and its likely impact on reproductive output. Intermoult females Carcinus maenas were exposed to concentrations of Cd: 3 microgl(-1), Cu: 15 microgl(-1) and Zn: 700 microgl(-1) determined at the Guadalquivir estuary after the Aznalcóllar mining spill, during 21 days. Crab hemolymph samples, were taken every seven days, and analyzed through an ELISA for Carcinus maenas vitellogenin. Vitellogenin concentration along the time was fitted to a first order kinetic approach. Results showed a good correlation among experimental values and estimated ones. Metal exposure resulted in an increase in vitellogenin concentration in hemolymph, especially for cadmium.

Biomarker responses at different levels of biological organisation in crabs (Carcinus aestuarii) experimentally exposed to benzo(alpha)pyrene.

The aim of this study was to validate a multi-trial biomarker approach for the evaluation of toxicological risk due to benzo(alpha)pyrene. Carcinus aestuarii, exposed to increasing concentrations of B(alpha)P in the water, was used as the bioindicator organism. A set of biomarkers were tested in order to: identify biological materials for biomarker and residue analysis; determine a group of sensitive techniques for the assessment of PAH contamination; investigate correlation between responses at different levels of biological organisation. The results underlined that BPMO activities in hepatopancreas and gills were a good biomarker of exposure to PAH-type compounds. B esterases activities in hemolymph and porphyrin patterns in excreta could be proposed as a non-destructive approach for evaluating chemical exposure in this species.

Induction of a putative monooxygenase of crabs (Carcinus spp.) by polycyclic aromatic hydrocarbons.

As part of a programme to develop biomarker assays for polycyclic aromatic hydrocarbons (PAHs) in marine invertebrates, two species of crabs, Carcinus maenas and Carcinus aestuarii were exposed to benzo(a)pyrene (B(a)P) or crude oil. Microsomes were prepared from the midgut gland (hepatopancreas), examined by gel electrophoresis and Western blotting and assayed for B(a)P monooxygenase activity. In early experiments there was evidence of protein degradation and results were inconsistent and inconclusive. However, when steps were taken to minimize this in subsequent experiments, including the inclusion of four protease inhibitors in the homogenization buffer, there was consistent evidence for an increase of proteins of estimated molecular weight 45-60 kDa, and particularly of a distinct band at c. 48 kDa, following exposure to PAH at levels down to 0.1 ppm in ambient water. In C. aestuarii the increase in this band was found to coincide with an 8-12-fold increaseof B(a)P monooxygenase activity in midgut gland microsomes. These results suggest that one or more forms of cytochrome P450 may be induced by PAHs in these species. However, Western blotting using antibodies raised to vertebrate P450s, and representing four different gene families, failed to recognize any proteins in either the PAH-treated samples or in the controls. The isolation and characterization of induced protein, and the production of antibodies may provide the basis for a biomarker assay to measure a response to environmental PAHs in crabs.

Tuberculous meningitis and co-infection with HIV.

The clinical, laboratory and radiological features of 30 children with clinically diagnosed tuberculous meningitis (TBM) who were HIV-seronegative were compared with those of ten HIV-infected children with TBM. Such comparative data are not currently available in the literature and so are an important addition to our knowledge of the HIV-TB co-infection epidemic. In comparison with the HIV-negative children, those infected with HIV were younger, had a shorter duration of symptoms and were more often Mantoux-negative (HIV-positive 23% vs HIV-negative 70%; p = 0.01). On presentation, all children in both groups were in MRC TBM stages II or III. Clinical features were similar in both groups but computed tomography of the brain showed more ventricular enlargement (HIV-positive 80% vs HIV-negative 63%), gyral enhancement (HIV-positive 60% vs HIV-negative 17%; p = 0.01) and cerebral atrophy (HIV-positive 40% vs HIV-negative 17%). Outcome was considerably worse in the HIV-positive children, of whom 30% died (vs HIV-negative 0/30; p = 0.01) and the remainder were moderately (HIV-positive 30% vs HIV-negative 24%) or severely (HIV-positive 30% vs HIV-negative 19%) handicapped at the end of treatment. While clinical features were not markedly different in HIV-infected and uninfected children with TBM, abnormal radiological findings were more common in the HIV-infected group and outcome was considerably worse. Co-existing HIV encephalopathy and diminished immune competence undoubtedly contributed to the more severe clinical and neuro-radiological features.

Effects of the human immunodeficiency virus on tuberculosis in children.

SETTING: Human immunodeficiency virus (HIV) infection has altered the epidemiological and clinical profile of tuberculosis (TB) worldwide. In children however, unlike in adults, very little has been documented about the interaction between the two diseases. OBJECTIVE: To examine the clinical features and response to TB treatment in children with TB and HIV, and compare them with those with TB alone. DESIGN: A prospectively enrolled case study with systematically selected controls was conducted between 1992 and 1994 at King George V tuberculosis hospital, in Durban. Forty children with TB and HIV (Group A) were compared with 40 children with TB alone (Group B). The diagnosis of TB was made in accordance with established criteria. Measures of comparison between the groups included: history of contact with a TB case, clinical presentation on admission, presence of bacille Calmette-Guérin (BCG) scar, reaction to tuberculin test, clinical response to anti-tuberculosis treatment (mean weight gain per month, improved appetite, resolution of chest signs, decreasing size of visceromegaly), radiological response to treatment (assessed according to an objective score on admission, at 6 months and on discharge), other associated diseases, nosocomial infections and survival. RESULTS: The mean age of the children in Group A was 25 months and in Group B 31 months. The clearest differences between the groups on admission were clinical features and response to tuberculin testing. Group A were more frequently anergic to tuberculin testing (P < 0.0001) and more often had symptoms and signs suggestive of TB (P = 0.002). Clinical response to treatment on discharge was worse in Group A than in Group B (P = 0.005). Radiological response to treatment at six months and on discharge was poorer in Group A than in Group B (P = 0.46; P = 0.006, respectively). Six children in group A and none in group B died (P = 0.012). The mean duration of treatment (and therefore period until discharge) was 8.9 months in Group B and 8.5 months in Group A for those who survived. History of contact, evidence of BCG inoculation and nosocomial infections were similar in both groups. CONCLUSION: HIV infection adversely affects the outcome of TB in children as assessed by response to treatment and survival.

Heterogeneity of disease phenotype in monozygotic twins concordant for rheumatoid arthritis.

The objective of the study was to investigate the genetic contribution to the clinical expression of rheumatoid arthritis (RA) by comparison of disease features in RA-concordant monozygotic (MZ) twin pairs. Fourteen RA-concordant MZ twin pairs recruited from a nation-wide study were examined to determine the degree of similarity in: (a) age of disease onset; (b) pattern of joint involvement; (c) pattern of extra-articular disease; (d) toxic reactions to drugs; (e) disease course; and (f) serology for rheumatoid factor (RF) and antinuclear antibody. There was considerable within-pair diversity in the variables studied. Some similarity within twin pairs was observed for the ages at disease onset (R = 0.63), presence of erosive changes (kappa = 0.61) and the presence of IgM RF (R = 0.87). No important similarity was seen, however, in the pattern of joint involvement, the occurrence of extra-articular disease, adverse drugs reactions, clinical disease course and reported disability level. There is heterogeneity in the genetic contribution to the clinical expression of RA. The overall lack of similarity for the majority of clinical variables indicates the importance of non-genetic factors on the expression of disease.

A comparison of the performance of different methods of disease classification for rheumatoid arthritis. Results of an analysis from a nationwide twin study.

OBJECTIVE: We have assessed the importance of the distinction between classification criteria for rheumatoid arthritis (RA) that recognize the presence of currently active disease from those that, in addition, incorporate evidence of past disease activity in ascertaining disease occurrence. We applied 7 classification schemes to a population of twins with inflammatory arthritis to determine (a) the number of individuals classified as RA positive by each scheme and hence the effect on the estimate of disease concordance in the twins and (b) their performance in correctly assigning a diagnosis compared with a physician's opinion. METHODS: The schemes assessed were the 1958 ARA (Rome) criteria which detect active disease, the 1966 New York (using both the 2/4 and 3/4 published cutoffs) which detect "ever" disease and 4 variants of the 1987 ARA criteria. These were the 4/7 and decision tree approaches applied on the basis of the relevant features (1) being present at the time of the study and (2) being present ever and allowing current joint deformity to substitute for absent joint swelling. RESULTS: In all, 283 individuals with a history of joint swelling were assessed, 255 of whom were considered to have RA by their physician. Criteria used to recognize "current" RA identified only about 70% of those which recognized RA ever. These differences in ascertainment level produced a marked effect on the monozygotic twin RA concordance estimates with percentages ranging from 10 to 18%. The results from receiver operating curves confirmed that criteria used to assess only current RA were too insensitive to be of value. Of the criteria that recognized RA status ever the 1987 ARA performed best overall. CONCLUSION: The use of classification methods that incorporate past as well as current evidence of disease activity is essential to avoid important misclassification in epidemiological and family studies. The 1987 criteria, applied retrospectively and allowing joint deformity to substitute for swelling, are of enhanced value over other existing schemes.

A history of sexually transmitted diseases in Thailand: policy and politics.

This paper provides a brief history of sexually transmitted diseases (STDs) in Thailand. The presentation is divided into three main sections: the period up to the 1930s; the period from the 1930s until the end of the early 1980s; and the period from the early 1980s until the present, the so-called 'AIDS Era'. The discussion in each of these sections focuses, as far as sources permit, on the epidemiological picture, as well as describing public and official responses to these diseases. In the final part of the paper consideration is given to these findings in relation to the present situation in Thailand regarding the HIV/AIDS epidemic.

PIP: Sexually transmitted diseases (STDs) have afflicted Thais since premodern times. Medical descriptions of STDs in the 1800s addressed the link between prostitution and STDs. During 1910-1925, STD rates in Bangkok were estimated to be 75-80% of adult males. Movement of people across the borders of China and Laos contributed to the spread of STDs in the early 1900s, as it does today. In 1908, Thailand enacted a law which required all female prostitutes to undergo a regular medical examination to become registered. It also set up brothels. Policymakers wanted to prevent STD transmission from prostitutes to men. They did not address male clients' responsibility. They were not concerned with the women. This official pattern persists. Beginning in 1930, Bank Rak Hospital housed the Control Unit to Reduce Venereal Diseases. The 1908 law was still in force during 1930-1949 despite attempts to ban sex work. In 1952, the UN provided Thailand assistance for STD education for students. During 1950-1965, businessmen and government officials profited from prostitution. In 1960, Thailand passed a law banning prostitution. In the late 1960s and early to mid 1970s, US military personnel in Thailand sought prostitutes, resulting in expansion of illegal prostitution. At the same time, Thailand was promoting itself as a tourist destination. One high-profile deputy premier, banker, and businessman asked provincial governors to promote sex tourism. In the mid 1980s, STDs spread rapidly in Thailand. The first AIDS case was in 1984. In 1987, there were 8 AIDS cases and 112 HIV-positive cases, most of whom were gay males (50% foreigners). It took just a few months for about 100,000 IV drug users to be HIV infected. In one year, the HIV infection rate among prostitutes in Chiang Rai Province jumped from 1 to 37%. HIV/AIDS is expected to reach all population groups by 2000. The official response to the AIDS epidemic was first denial, then active monitoring and public education, and now increased community support for sufferers and multisectoral development programs.

The operculum syndrome: an unusual complication of tuberculous meningitis.

The operculum syndrome, not previously documented as a complication of tuberculous meningitis, is described in a three-year-old African boy. The appearance on CT scan correlates radiographically with anatomical descriptions of the operculum syndrome, and is useful in distinguishing the condition from pseudobulbar palsy.

Transplantation of the gonads of hypogonadal (hpg) mice.

Testes from hypogonadal (hpg) mice transplanted under the tunica albuginea of the testes of normal mice displayed full spermatogenic activity after 84 days. When ovaries of hpg mice were transplanted to the periovarian capsule of ovariectomized normal females ripe follicles and corpora lutea developed. Although small remnants of normal ovary were found after this operation, the fact that 5 out of 11 normal females bearing transplanted ovaries and mating with heterozygous males raised litters containing hpg mice shows that the ovary of the mutant is capable of producing ova which can be fertilized.