Suicidal ideation in the perinatal period: findings from the Thailand-Myanmar border.

BACKGROUND: Suicide is a leading cause of maternal death globally. Migrant and refugee populations may experience higher risk of suicide. We report data on suicidal ideation from migrant and refugee women living on the Thailand-Myanmar border. METHODS: Women were recruited in their first trimester of pregnancy. Depression status was assessed by diagnostic interview in the first, second and third trimesters and at 1 month post-partum. We calculated prevalence of suicidal ideation and used logistic regression to identify associated socio-demographic factors. RESULTS: During the perinatal period, 5.3% (30/568) women experienced suicidal ideation. Refugee women were more likely to experience suicidal ideation than migrant women (8.0 versus 3.1%; P = 0.01). Most women with suicidal ideation did not have severe depression. Previous trauma (OR 2.32; 95% CI: 1.70-3.15) and unplanned pregnancy (OR 2.74; 95% CI: 1.10-6.86) were significantly associated with suicidal ideation after controlling for all other variables. CONCLUSIONS: Suicidal ideation represents an important symptom among migrant and refugee women on the Thailand-Myanmar border. Screening only those with severe depression may be insufficient to identify women at risk of suicide. Community-level interventions addressing social and gender inequalities and prioritization of family planning programmes are needed alongside targeted suicide prevention initiatives to help lower the rates of people dying by suicide.

Readability and suitability of oral health education pamphlets produced by the Ministry of Health Malaysia.

INTRODUCTION: Printed health education materials can only be effective if they are readable and suitable for the target audience. This study examined the readability and suitability of oral health education (OHE) pamphlets produced by the Oral Health Program (OHP), Ministry of Health (MOH) Malaysia. METHODS: The Khadijah Rohani's Readability Formula (KRRF) and Suitability Assessment of Materials (SAM) instrument were used to assess the readability and suitability of the pamphlets respectively. All 23 Bahasa Malaysia pamphlets retrieved from the official portal of OHP on the 31st January 2019 were assessed for suitability. However, only five pamphlets were found to be eligible for readability assessment because the KRRF, the single formula available for Bahasa Malaysia text is applicable only for materials with 300 words or more. The readability is interpreted based on the level of formal education in Malaysia. RESULTS: All pamphlets achieved superior suitability rating with a minimum and maximum score of 75% and 95% respectively. However, a few pamphlets did not fulfil SAM superior and adequate criteria for the following factors and were rated not suitable: did not include summary (73.9%), have few or no headers (4.3%), did not use captions to explain graphics (17.4%), and did not provide interactive learning (21.7%). Readability of the pamphlets eligible for assessment ranged from primary six to secondary three. CONCLUSIONS: OHE pamphlets produced by the MOH are readable by most Malaysians. Most pamphlets are generally suitable for the intended audience although a few performed poorly in several areas.

Treatment success among Myanmar migrants with TB in Thailand.

SETTING: Two facilities, one providing clinic-based care and another providing residential care to Myanmar migrants with TB, in a Thailand-Myanmar border area.OBJECTIVE: To determine the effects of health insurance, total delay and the model of care on treatment success of TB.METHODS: A prospective study was conducted among adult Myanmar migrants under treatment for newly diagnosed TB. Effects of health insurance, total delay and model of care on treatment success at completion of 6-month treatment were analysed using multiple logistic regression models.RESULTS: Of 191 Myanmar migrants with TB, 167 (87.4%) had treatment success. Median time delays from symptom onset to treatment initiation among migrants with health insurance receiving clinic-based care were significantly shorter than those without health insurance. Those who received residential care had higher odds of treatment success than those under clinic-based care (aOR 6.0, 95% CI 1.5-23.3); having health insurance (aOR 1.0, 95% CI 0.3-2.9) and total delay (aOR 1.7, 95% CI 0.7-4.2) were not significantly associated with treatment success.CONCLUSIONS: A high treatment success rate was associated with receiving residential care among Myanmar migrants with TB on the Thai-Myanmar border. The residential care model, implemented under a non-governmental organisation, was feasible and effective for the migrant population.

High prevalence and incidence of tuberculosis in people living with the HIV in Mandalay, Myanmar, 2011-2017.

SETTING: Two human immunodeficiency virus (HIV) clinics providing antiretroviral therapy (ART), Mandalay, Myanmar. OBJECTIVE: To assess prevalent TB at enrolment, incident TB during follow-up and associated risk factors in adult people living with HIV (PLHIV) between 2011 and 2017. DESIGN: Cohort study using secondary data. RESULTS: Of 11 777 PLHIV, 2911 (25%) had prevalent TB at or within 6 weeks of enrolment. Independent risk factors for prevalent TB were being male or single/widowed, daily alcohol consumption, CD4 count 200 cells/µl and anaemia. During 6 years follow-up in 8866 PLHIV with no prevalent TB, the rate of new TB was 2.9 per 100 person-years (95%CI 2.6-3.1). Cumulative TB incidence was 9.6%, with 370 (72%) of 517 new TB cases occurring in the first year. Independent risk factors for incident TB were being male and anaemia. Incident TB was highest in the first year of ART, in PLHIV with CD4 counts 200 cells/µl and those not receiving isoniazid preventive therapy (IPT). Incident TB declined with time on ART and rising CD4 counts. CONCLUSION: Prevalent and incident TB were high in PLHIV in the Mandalay clinics. Consideration should be given to earlier TB diagnosis using more sensitive diagnostic tools, effective ART and scaling up IPT.

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

SETTING: Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. OBJECTIVE: To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). DESIGN: A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. RESULTS: Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). CONCLUSION: Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

HIV, HBV and HCV in people who inject drugs and are placed on methadone maintenance therapy, Yangon, Myanmar.

Setting: Two drug treatment centres (DTCs) for people who inject drugs (PWID) and are enrolled in methadone maintenance therapy (MMT), Yangon, Myanmar. Objectives: To determine, in PWID enrolled for MMT from 2015 to 2017, 1) testing uptake and results for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV); 2) risk factors for infection; and 3) retention in care and risk factors for loss to follow-up (LTFU). Design: Cohort study using secondary data. Results: Of 642 PWID, 578 (90.0%) were tested for HIV, HBV and/or HCV. Overall, 404 (69.9%) were infected: 316 (78.2%) had one infection and the remainder had dual/triple infections. Testing uptake was generally better in 2015 and 2016 than in 2017. Prevalence of HIV infection was 15-17%, for HBV it was 4-7%, and for HCV it was 68-76%. Age >30 years, being single and duration of drug use were independent risk factors for infection. Retention in MMT at 6 months was 76% and declined thereafter. Experimental use of drugs and needle sharing were independent risk factors for LTFU. Conclusion: PWID enrolled in MMT in Yangon had high rates of HIV, HBV and HCV, and retention in care declined with time. Ways to improve individual tracing, programmatic retention and linkage to care are needed.

Contexte : Deux centres de traitement de l'addiction (DTC) pour les utilisateurs de drogues injectables (PWID) qui sont enrôlés dans un traitement d'entretien à la méthadone (MMT), Yangon, Myanmar.Objectif : Déterminer parmi les PWID enrôlés en MMT de 2015 à 2017 1) la couverture et les résultats des tests de virus de l'immunodéficience humaine (VIH), de l'hépatite B (HBV) et de l'hépatite C (HCV) ; 2) les facteurs de risque d'infection ; et 3) la rétention en soins et les facteurs de risque de pertes de vue (LTFU).Schéma : Etude de cohorte basée sur des données secondaires.Résultats : Il y a eu 642 PWID, dont 578 (90,0%) ont été testés pour le VIH, le HBV et/ou le VHC. Au total, 404 (69,9%) étaient infectés ; 316 (78,2%) avaient une seule infection et le reste avait deux ou trois infections. La couverture des tests a généralement été meilleure en 2015 et 2016 qu'en 2017. La prévalence de l'infection a été de 15­17% pour le VIH, de 4­7% pour le HBV et de 68­76% pour le HCV. Un âge > 30 ans, le fait d'être célibataire et la durée de la consommation de drogues ont été des facteurs de risque indépendants d'infection. La rétention en MMT à 6 mois a été de 76% et a décliné ensuite. L'usage expérimental de drogues et le partage d'aiguilles ont été des facteurs de risque indépendants de LTFU.Conclusion : Les PWID enrôlés en MMT à Yangon ont eu des taux élevés de VIH, d'HBV et d'HCV et la rétention en soins a décliné avec le temps. Il faut trouver des stratégies visant à améliorer le suivi individuel, la rétention dans le programme et les liens avec la prise en charge.

Marco de referencia: Dos centros de tratamiento de la drogadicción destinados a las personas que consumen drogas inyectables, inscritas en el tratamiento de mantenimiento con metadona de Yangon, en Birmania.Objetivos: Determinar en las personas que consumen drogas inyectables inscritas en el programa de mantenimiento con metadona del 2015 al 2017 las siguientes características: 1) la utilización de las pruebas diagnósticas de la infección por el virus de la inmunodeficiencia humana (VIH), el virus de la hepatitis B (VHB) y de la hepatitis C (VHC) y sus resultados; 2) los factores de riesgo de contraer la infección; y 3) la proporción de retención en la atención y los factores de riesgo de pérdida durante el seguimiento.Método: Estudio de cohortes a partir de datos secundarios.Resultados: Se inscribieron en los centros 642 consumidores de drogas inyectables, de los cuales 578 (90,0%) recibieron las pruebas diagnósticas del VIH, el VHB o el VHC. En general, 404 personas estaban infectadas (69,9%), de las cuales 316 padecían una monoinfección (78,2%) y el resto una infección doble o triple. En general, la utilización de las pruebas fue mayor en el 2015 y el 2016 que en el 2017. La prevalencia de infección por el VIH fue de 15% a 17%, por el VHB fue de 4% a 7% y por el VHC de 68% a 76%. Los factores de riesgo independientes de padecer una infección fueron la edad superior a los 30 años, el hecho de no tener pareja y la duración del consumo de drogas. La retención en el tratamiento de mantenimiento con metadona a los 6 meses fue 76% y en adelante disminuyó. Los factores de riesgo independientes de pérdida durante el seguimiento fueron el consumo experimental de drogas y el uso compartido de agujas.Conclusión: Las personas que consumen drogas inyectables que se inscriben en el programa de mantenimiento con metadona en Yangon exhibieron tasas altas de infección por el VIH, el VHB y el VHC y su retención en la atención disminuyó con el transcurso del tiempo. Se precisan estrategias que mejoren el seguimiento individual, la retención en los programas y la vinculación con la atención.

How many sputum samples should be examined during follow-up of tuberculosis patients in Myanmar: two or one?

Setting: Ten selected microscopy centres in Sagaing Region, Myanmar, functioning under an external quality assurance system with no reported major errors. Objective: To assess the pattern of serial sputum results (NN, both smear-negative; NP, first smear-negative and second smear-positive; PN, first smear-positive and second smear-negative; and PP, both smear-positive) among follow-up sputum microscopy examinations of tuberculosis (TB) patients (end of intensive phase, mid-continuation phase and end of treatment) conducted from 1 November 2017 to 15 April 2018. Design: Cross-sectional study using secondary data (laboratory registers). Results: Of 2001 examinations, 94 (4.7%) were smear-positive: 66 PP (3.3%), 12 PN (0.6%) and 16 NP (0.8%); 75% of NP results were scanty. The proportion of NP results was 0.8% (95%CI 0.5-1.3), i.e., 125 smears (95%CI 77-200) were required to detect one additional smear-positive result in the second sample. Of the 16 NP results (15 patients), 14 were tested using Xpert® MTB/RIF and none had rifampicin resistance. During the continuation phase of treatment, 13 became smear-negative, one remained smear-positive and one had unknown follow-up smear status. Conclusion: The benefit of the second sputum sample for monitoring anti-tuberculosis treatment was negligible. Given the favourable resource implications (reduced laboratory workload and costs), we recommend changing the policy from two sputum smears to one during follow-up sputum examinations of TB patients.

Contexte : Dix centres de microscopie sélectionnés de la région de Sagaing, Myanmar, fonctionnant avec un système d'assurance de qualité externe sans erreurs majeures rapportées.Objectif : Evaluer les profils de séries de résultats de crachats (NN, deux frottis négatifs ; NP, premier frottis négatif et deuxième frottis positif ; PN, premier frottis positif et deuxième frottis négatif ; et PP, deux frottis positifs) parmi les examens de suivi de microscopie de crachats de patients TB (à la fin de la phase intensive, au milieu de la phase de continuation et à la fin du traitement) réalisés du 1e novembre 2017 au 15 avril 2018.Schéma : Etude transversale grâce à des données secondaires (registres de laboratoire).Résultats : Sur 2001 examens, 94 (4,7%) ont eu un frottis positif : 66 (3,3%) PP ; 12 (0,6%) PN ; 16 (0,8%) NP ; 75% des NP avaient de rares bacilles. La proportion de NP a été de 0,8% (IC95% 0,5­1,3), impliquant qu'il a fallu 125 frottis (IC95% 77­200) pour détecter un frottis positif supplémentaire dans un deuxième échantillon. Sur les 16 NP (15 patients), 14 ont été testés par Xpert® MTB/RIF et aucun n'a eu de résistance à la rifampicine. Lors de la continuation du traitement, 13 sont devenus à frottis négatif, un patient est resté à frottis positif et un autre a eu un frottis de suivi « indéterminé ¼.Conclusion : Le bénéfice du deuxième échantillon de crachats pour le suivi du traitement antituberculeux a été négligeable. Devant les implications favorables en termes de ressources (charge de travail et coûts réduits pour le laboratoire), nous recommandons de modifier la politique de deux frottis de crachats à un seul lors du suivi de patients TB par examens des crachats.

Marco de Referencia: Diez centros de microscopia escogidos en la región de Sagaing de Birmania, que funcionan con un sistema externo de garantía de la calidad y no notifican errores importantes.Objetivos: Evaluar el perfil de los resultados seriados del esputo (NN, ambas baciloscopias negativas; NP, primera baciloscopia negativa y segunda positiva; PN, primera baciloscopia positiva y segunda negativa; y PP, ambas baciloscopias positivas) en las baciloscopias de esputo de seguimiento de los pacientes con tuberculosis (TB) (al final de la fase intensiva, en medio de la fase de continuación y al final del tratamiento), realizadas del 1° de noviembre del 2017 al 15 de abril del 2018.Métodom: Fue este un estudio transversal que utilizó datos secundarios (los registros de laboratorio).Resultados: De las 2001 baciloscopias realizadas, 94 (4,7%) fueron positivas, a saber: 66 (3,3%) PP; 12 (0,6%) PN; 16 (0,8%) NP; 75% de los resultados NP se notificaron como 'escasos bacilos'. La proporción de resultados NP fue 0,8% (IC95% 0,5­1,3), lo cual indica que se precisaron 125 baciloscopias a fin de detectar una baciloscopia positiva adicional en la segunda muestra (IC95% 77­200). De los 16 casos NP (15 pacientes), 14 se examinaron mediante la prueba Xpert® MTB/RIF y ninguno exhibió resistencia a rifampicina. Durante la fase de continuación del tratamiento, en 13 casos la baciloscopia se hizo negativa, uno permaneció positivo y en otro caso el resultado de la baciloscopia de seguimiento era 'desconocido'.Conclusión: La utilidad de una segunda muestra de esputo en la supervisión del tratamiento antituberculoso fue insignificante. Teniendo en cuenta sus repercusiones económicas favorables (disminución de la carga de trabajo y los costos de laboratorio), se recomienda cambiar la norma de practicar dos muestras de esputo por una sola muestra, durante las baciloscopias de seguimiento de los pacientes con TB.

Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar.

SETTING: Integrated HIV Care programme, Mandalay, Myanmar. OBJECTIVES: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. DESIGN: Retrospective cohort study. RESULTS: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm(3) had a four times higher risk of an unsuccessful outcome. CONCLUSIONS: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV.

Contexte : Programme intégré de prise en charge du virus de l'immunodéficience humaine (VIH), Mandalay, Myanmar.Objectifs : Chez les patients atteints de tuberculose (TB) et VIH enrôlés entre 2011 et 2014, déterminer la date du début du traitement antirétroviral (TAR) en relation avec le traitement antituberculeux (ATT) et son association avec le résultat d'ATT.Schéma : Etude rétrospective de cohorte.Résultats : Sur 1708 patients TB-VIH, 1565 (92%) ont débuté l'ATT en premier et 143 (8%) ont commencé le TAR en premier. Le résultat du traitement a été manquant pour 226 patients qui n'ont pas été inclus. Chez les patients ayant débuté l'ATT en premier, le délai médian de mise en route du TAR a été de 8,6 semaines. L'initiation du TAR a été retardée d'un délai médian de 8 semaines chez 830 (53%) patients. Parmi ces patients, 7% ont eu un résultat médiocre, avec une anémie qui a constitué un facteur de risque indépendant. Chez les patients ayant débuté le TAR en premier, le délai médian de mise en route de l'ATT a été de 21,6 semaines. L'ATT a été initié au cours des 3 mois chez 56 (39%) patients. Le traitement a échoué chez 12% des patients et chez 20% de ceux qui ont débuté l'ATT dans les 3 mois. Les patients ayant des CD4 <100/mm3 ont eu un risque quatre fois plus élevé d'échec.Conclusions: La chronologie du TAR en rapport avec l'ATT n'a pas été un facteur de risque indépendant d'échec du traitement. Un dépistage extensif de la TB avec des tests de diagnostic rapides et sensibles chez les personnes infectées par le VIH et un suivi étroit de l'anémie et de l'immunosuppression sont recommandés afin d'améliorer encore le résultat du traitement de TB parmi les patients TB-VIH.

Marco de referencia: El programa integrado de atención de la infección por el virus de la inmunodeficiencia humana (VIH) en Mandalay, en Birmania.Objetivos: Determinar el lapso entre el comienzo del tratamiento antirretrovírico (ART) y el inicio del tratamiento antituberculoso (ATT) en los pacientes coinfectados registrados del 2011 al 2014 y su asociación con el desenlace del ATT.Método: Fue este un estudio retrospectivo de cohortes.Resultados: De los 1708 pacientes coinfectados por el VIH y la tuberculosis (TB), 1565 iniciaron primero el ATT (92%) y 143 comenzaron en primer lugar el ART (8%). Se excluyeron 226 casos que carecían de registro del desenlace terapéutico. En los pacientes que iniciaron en primer lugar el ATT, la mediana del lapso hasta el comienzo del ART fue 8,6 semanas; este tratamiento se inició después de 8 semanas en 830 pacientes (53%). Se observó un desenlace terapéutico desfavorable en 7% de estos pacientes; la principal variable independiente asociada fue la presencia de anemia. Cuando el ART se inició en primer lugar, la mediana hasta el comienzo del ATT fue 21,6 semanas; este tratamiento se inició durante los 3 primeros meses en 56 pacientes (39%). Se observó un desenlace terapéutico desfavorable en 12% de estos pacientes y en 20% de los pacientes que iniciaron el ART en los primeros 3 meses. El riesgo de un desenlace desfavorable fue cuatro veces más alto en los pacientes con un recuento de linfocitos CD4 <100 células/mm3.Conclusión: La coordinación cronológica del ART y el ATT no representó un factor independiente de riesgo de obtener un desenlace desfavorable. Se recomienda la detección sistemática de la TB en los pacientes infectados por el VIH mediante pruebas diagnósticas rápidas y sensibles y una supervisión cuidadosa de la anemia y la inmunodepresión, con el objeto de obtener aun mejores desenlaces del ATT en los pacientes aquejados de coinfección TB-VIH.

Human cerebral malaria: a pathological study.

The following report using light and electron microscopic and immunological techniques is based on a series of 19 Burmese patients who died of cerebral malaria. The principal change was blockage of cerebral capillaries by Plasmodium falciparum-infected erythrocytes. Ring hemorrhages and segmental necrosis of cerebral capillaries were common. Cerebral edema was variable in these cases. Electron-dense knobs, 40 X 80 nm in size, which protruded from the membrane of infected erythrocytes, formed focal junctions between endothelial cells and erythrocytes. These junctions resulted in the entrapment of erythrocytes and caused blockage in the capillary lumen. Immunoperoxidase study revealed that P. falciparum antigens and IgG deposits in the capillary basement membrane. This implies that damage to the cerebral capillary could be related to immune mechanisms.

Knob antigen deposition in cerebral malaria.

Plasmodium falciparum-infected erythrocytes attach to the endothelial cells via electron-dense knobs and this attachment has been suggested as one of the contributing factors in the development of cerebral malaria. Monoclonal antibodies against an 80-95 Kd knob protein were prepared and applied to brain tissue from cerebral malaria patients. The deposition of the 80-95 Kd knob protein antibodies was observed in the basement membrane of cerebral capillaries by the peroxidase anti-peroxidase method. This result indicates involvement of knob protein deposition in the pathogenesis of cerebral malaria.

Renal pathology in Saimiri monkeys during a vaccine trial using the recombinant circumsporozoite protein of Plasmodium vivax.

Renal specimens of squirrel monkeys (Saimiri sciureus boliviensis) were studied by light microscopy and immunohistochemistry to examine the pathologic changes during vaccine trials with four recombinant circumsporozoite (CS) proteins (rPvCS-1, rPvCS-2, rPvCS-3, NS1(81) V20) of Plasmodium vivax. The monkeys were vaccinated and later challenged with P. vivax sporozoites. Among the 33 posttrial biopsies, 17 had mild to moderate mesangial proliferation and nine had interstitial nephritis. Immunohistochemistry by the peroxidase-antiperoxidase (PAP) method revealed IgG deposits in only three of 24 specimens and failed to demonstrate C3 deposits and P. vivax antigens in their glomeruli. There was no relationship between the severity of nephropathy and intensity of parasitemia. The intensity of parasitemia was the same in the vaccinated and control groups. Vaccinated monkeys from the groups (rPvCS-1, rPvCs-2, rPvCS-3) had no differences in renal pathology from the unvaccinated controls, but one group vaccinated with NS1(81) V20 did not develop renal changes.

The pathology of human cerebral malaria.

Blockage of the cerebral microvasculature by Plasmodium falciparum-infected erythrocytes appears to be the principal cause of human cerebral malaria. Knobs which appear on the membrane of the infected erythrocytes adhere to the endothelium, causing the obstruction of cerebral microvessels. Protein molecules such as CD36, thrombospondin, and intercellular adhesion molecule-1, which are present on the membrane of endothelial cells, may act as receptors for the attachment of knobs of P. falciparum-infected erythrocytes. Each of these candidate host molecules for infected-cell recognition and attachment are expressed in microvessels of the human brain. The presence of HRP1 and HRP2 in the cerebral microvessels of cerebral malaria patients may indicate the involvement of knob proteins in the pathogenesis of cerebral malaria. Owl monkeys infected with P. falciparum do not develop cerebral malaria. There is no blockage of cerebral microvessels by infected erythrocytes and knob proteins are absent. These findings support the contention that cerebral microvessel blockage and the presence of knob proteins are the probable causes of cerebral malaria.

Heparin therapy for myocardial infarction: an unusual trigger for pituitary apoplexy.

A 68-year-old man with coronary artery disease was admitted for chest pain and ventricular tachycardia. After electric cardioversion, therapeutic heparinization was started for myocardial ischemia and nontransmural infarction. On day 3, headache and fever developed, followed by an altered sensorium and hyponatremia. Infectious etiology for the fever was excluded, and results of computed tomography of the brain were normal. Later magnetic resonance imaging (Day 10) demonstrated a pituitary macroadenoma with hemorrhage. Treatment for panhypopituitarism with stress-dose steroids stabilized the patient, and the fever and hyponatremia resolved. Transsphenoidal resection of the pituitary adenoma was performed without incident. This is the first reported case of pituitary apoplexy after heparin anticoagulation for acute myocardial infarction, although chronic anticoagulation in other settings has been reported as a precipitant of apoplexy. The uncommon presentation of a "central" fever and confusion in a patient with previously undiagnosed adenoma posed a diagnostic challenge. Subtle presentations of panhypopituitarism, knowledge of which should lead to suspicion and early diagnosis of pituitary apoplexy, will prevent anticoagulant-induced central nervous system catastrophes and potential fatalities.

Peritrophic matrix proteins of Anopheles gambiae and Aedes aegypti.

Little is known about the composition and function of the mosquito peritrophic matrix (PM), a physical barrier that pathogens must traverse to complete their life cycles. Anopheles gambiae and Aedes aegypti PM proteins induced by blood or by a protein-free meal have been characterized by the use of 2-D gel electrophoresis and lectin-binding affinity assays. More than forty proteins have been identified in both species. Over half of the PM proteins of both mosquitoes migrate identically. Many PM proteins appear to be glycosylated, primarily by high mannose N-linked glycosyl groups.

Isolation of Entamoeba histolytica from arthritic knee joint.

Amoebae were isolated from an arthritic knee of a male patient. The organisms grew in Egg Yolk Infusion medium, and in Diamond's Biosate Iron-Serum-33 medium, which contained Trypanosoma cruzi, and were identified microscopically as Entamoeba histolytica. Furthermore, amoebae-like organisms in aspirate and cultures were immunocytochemically identified using monoclonal antibodies against E. histolytica. On the basis of the morphologic and immunologic observations, it was concluded that the knee lesion was caused by infection with E. hystolytica. The knee lesion resolved following treatment with metronidazole. This case is the first report of an amoebic infection of the knee joint.

Abdominal tuberculosis in patients infected with the human immunodeficiency virus.

We compared the presentation of abdominal tuberculosis in 43 patients infected with the human immunodeficiency virus (HIV) and in 35 patients without HIV infection. Fever, weight loss, and extraabdominal lymphadenopathy were more common in HIV-infected patients, whereas ascites and jaundice were more frequent in patients without HIV infection. Intraabdominal lymphadenopathy and visceral lesions, visualized on computed tomography scans, were more common in HIV-infected patients, whereas ascites and omental thickening were more frequent in patients without HIV infection. Aspirates of abdominal lymph nodes were the only samples revealing acid-fast bacilli in eight HIV-infected patients, yielding a rapid diagnosis. Disseminated tuberculosis was present in 93% of the HIV-infected patients, compared with 31% of those without HIV infection; tuberculosis contributed to death in 23% of HIV-infected patients and in 31% of those without HIV infection. We conclude that abdominal tuberculosis in HIV-infected patients is almost invariably a manifestation of disseminated disease and results in significant mortality.

Successful liver allografts in mice by combination with allogeneic bone marrow transplantation.

Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.

Thymic rudiments are responsible for induction of functional T cells in nu/nu mice.

Congenitally athymic nude (nu/nu) mice have been thought to exhibit no T cell functions despite the presence of some Thy-1 positive (Thy-1+) cells. However, we detected a significant number of Con A-responsive cells in spleens of nu/nu mice after the age of 2 months when the spleen cells were cultured in a medium containing 5% human plasma or human serum, but not when they were cultured in fetal calf serum. Cytotoxic test using anti-Thy-1.2 antibody plus complement has revealed that these Con A-responsive cells are indeed Thy-1+. The Con A-responsive T cells increase with age. PHA-responsive and alloreactive T cells are also detected in the spleens of 11-month-old nu/nu mice. To probe the origins of the T-lymphocytes of the nu/nu mice we examined extensively and systematically the thymic remnants in the mediastinum and neck region of the nu/nu mice in search for T cell development in thymic rudiments. In these investigations we regularly found small accumulations of cells comprising almost entirely Thy-1+ lymphocytes surrounding accumulations surrounded by epithelial cells. These findings suggest that apparent sites of T cell development in thymic rudiments are indeed present in nude mice and appear to be functioning to induce expression T cell markers on precursor cells in the lymphoid lineage. Together with our prior findings the evidence presented in this report shows that a pathway exists in nude mice. In the converse these findings suggest that the thymus is the sole site for induction of the differentiation of stem cells or precursor T cells into mature T-lymphocytes. The findings suggest that indications of alternative differentiation pathways for T-lymphocytes must seek the location of these pathways within the thymus itself.

Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice.

CD4 cell counts in human immunodeficiency virus-negative patients with tuberculosis.

We evaluated 85 human immunodeficiency virus (HIV)-negative patients with tuberculosis for clinical features and CD4 cell counts. Thirty-seven patients had low CD4 cell counts (mean +/- SD, 341 +/- 116 cells/microL), and 48 patients had normal CD4 cell counts (mean +/- SD, 830 +/- 254 cells/microL). CD4 cell counts were most strongly correlated with total lymphocyte counts (r = 0.84). If total lymphocyte count was excluded, depressed CD4 cell counts were significantly associated with low serum albumin levels, extensive pulmonary disease, low body-mass index, and low hematocrit. Of these four variables, multivariate linear discriminant analysis revealed that the serum albumin level was the best single predictor of low CD4 cell counts and that the other three variables did not improve predictive value. Because these four variables are markers of severe tuberculosis, these findings suggest that disease severity is associated with greater depression of the total lymphocyte and CD4 cell counts. The CD4 cell counts returned to normal levels in most patients after 1 month of therapy.