Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial.

We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar.

Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi.

Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/µl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 µg/ml (2.474 to 5.596 µg/ml), area under the curve from 0 to 24 h (AUC0-∞) of 21.32 µg/ml · h (13.57 to 28.60 µg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 µg/ml (2.979 to 4.544 µg/ml), AUC0-24 of 22.5 (14.75 to 34.59 µg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 µg/ml (30.00 to 41.60 µg/ml), AUC0-24 of 386.6 µg/ml · h (320.0 to 463.7 µg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 µg/ml (1.694 to 3.098 µg/ml), AUC0-24 of 20.41 µg/ml · h (16.18 to 26.27 µg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which the Cmax and AUC0-24 values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P = 0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further.

Impact of injection speed and volume on perceived pain during subcutaneous injections into the abdomen and thigh: a single-centre, randomized controlled trial.

AIM: The aim of this study was to assess pain associated with subcutaneous injection into the abdomen and thigh of different combinations of injection speeds and volumes. METHODS: The study was a single-centre, one-visit, double-blinded, randomized controlled trial in 82 adults with type 1 or type 2 diabetes receiving daily injections of insulin or glucagon-like peptide-1 (GLP-1) agonists. Participants received 17 subcutaneous injections (12 in abdomen, 5 in thigh) of saline at different injection speeds (150, 300 and 450 µl/s), with different volumes (400, 800, 1200 and 1600 µl), and two needle insertions without any injection. Pain was evaluated on a 100-mm visual analogue scale (VAS) (0 mm no pain, 100 mm worst pain) and on a yes/no scale for pain acceptability. RESULTS: Injection speed had no impact on injection pain (p = 0.833). Injection of larger volumes caused significantly more pain [VAS least square mean differences 1600 vs. 400 µl, 7 · 2 mm (95% confidence interval - CI; 4.6-9.7; p < 0.0001); 1600 vs. 800 µl, 7.2 mm (4.4-10.0; p < 0.0001); 1200 vs. 400 µl, 3.5 mm (0.4-6.6; p = 0.025) and 1200 vs. 800 µl, 3.6 mm (0.4-6.7; p = 0.027)]. Significantly more pain occurred in the thigh versus the abdomen [9.0 mm (6.7-11.3; p < 0.0001)]. CONCLUSIONS: Injection speed had no effect on injection pain, whereas higher injection volumes caused more pain. The results of this study may be of value for guiding patients to use the appropriate injection site and technique to reduce their injection pain. Furthermore, these findings may have important implications for the development of new injection devices and drug formulations for clinical practice.

Continuous glucose monitoring: quality of hypoglycaemia detection.

AIMS: To evaluate the accuracy of a (widely used) continuous glucose monitoring (CGM)-system and its ability to detect hypoglycaemic events. METHODS: A total of 18 patients with type 1 diabetes mellitus used continuous glucose monitoring (Guardian REAL-Time CGMS) during two 9-day in-house periods. A hypoglycaemic threshold alarm alerted patients to sensor readings <70 mg/dl. Continuous glucose monitoring sensor readings were compared to laboratory reference measurements taken every 4 h and in case of a hypoglycaemic alarm. RESULTS: A total of 2317 paired data points were evaluated. Overall, the mean absolute relative difference (MARD) was 16.7%. The percentage of data points in the clinically accurate or acceptable Clarke Error Grid zones A + B was 94.6%. In the hypoglycaemic range, accuracy worsened (MARD 38.8%) leading to a failure to detect more than half of the true hypoglycaemic events (sensitivity 37.5%). Furthermore, more than half of the alarms that warn patients for hypoglycaemia were false (false alert rate 53.3%). Above the low alert threshold, the sensor confirmed 2077 of 2182 reference values (specificity 95.2%). CONCLUSIONS: Patients using continuous glucose monitoring should be aware of its limitation to accurately detect hypoglycaemia.

Hume-Rothery stabilization mechanism and e/a determination for RT- and MI-type 1/1-1/1-1/1 approximants studied by FLAPW-Fourier analyses.

Full-potential linearized augmented plane wave (FLAPW) electronic band calculations were performed for two RT- (rhombic triacontahedron) and five MI- (Mackay icosahedron) type 1/1-1/1-1/1 approximants plus several complex metallic compounds in Al-TM (TM = transition metal element) binary alloy systems in order to elucidate the origin of a pseudogap from the viewpoint of Fermi surface-Brillouin zone (FsBz) interactions. The square of the Fermi diameter (2k(F))(2) and square of the critical reciprocal lattice vector |G|(2) or the critical set of lattice planes, with which electrons at the Fermi level E(F) are interfering, can be extracted from the FLAPW-Fourier method. We revealed that a pseudogap in both RT- and MI-type 1/1-1/1-1/1 approximants universally originates from interference phenomenon satisfying the matching condition (2k(F))(2) = |G|(2) equal to 50 in units of (2π/a)(2), where a is the lattice constant. The multi-zone effect involving not only |G|(2) = 50 but also its neighboring ones is also claimed to be responsible for constituting a pseudogap across E(F). The value of e/a for Mn, Fe, Re and Ru elements in the periodic table is deduced to be positive in the neighborhood of unity. All 1/1-1/1-1/1 approximants, regardless of RT- or MI-type atomic cluster involved, are stabilized at around e/a= 2.7, while their counterpart quasicrystals are at around e/a= 2.2. A new Hume-Rothery electron concentration rule linking the number of atoms per unit cell, e/uc, with a critical|G|(2) holds well for all complex intermetallic compounds characterized by a pseudogap at E(F).

Simple measures are as effective as invasive techniques in the diagnosis of pulmonary tuberculosis in Malawi.

SETTING: Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis (TB) control. Methods to augment sputum collection are available, but their additional benefit is uncertain in resource-limited settings. OBJECTIVE: To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. DESIGN: Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients provided physiotherapy-assisted sputum and induced sputum, followed the next morning by gastric washing and bronchoalveolar lavage (BAL) samples. RESULTS: A total of 150 patients diagnosed with smear-negative PTB by the hospital service were screened; 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled in the study; 89% were human immunodeficiency virus positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. Of the 46 smear-positive cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy-assisted samples. CONCLUSIONS: For countries such as Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using BAL after induced sputum is limited.

Hypoadrenalism is not associated with early mortality during tuberculosis treatment in Malawi.

SETTING: In the developing world, early mortality within 1 month of commencing tuberculosis (TB) treatment is high, particularly with human immunodeficiency virus (HIV) co-infection. In Malawi, 40% of those who die do so in the first month of treatment. Reasons remain unclear and may include delayed diagnosis, opportunistic infections, immune restoration inflammatory syndrome (IRIS) or malnutrition. One possible contributing factor is underlying hypoadrenalism associated with TB-HIV, exacerbated by rifampicin (RMP) induction of P450 and glucocorticoid metabolism. OBJECTIVE: To assess the prevalence of hypoadrenalism in TB patients before and after commencement of TB treatment, and relationship with early mortality. DESIGN: Prospective descriptive study assessing hypoadrenalism before and after anti-tuberculosis treatment, HIV status and outcome up to 3 months post-treatment. RESULTS: Of 51 patients enrolled, 29 (56.9%) were female (median age 32 years, range 18-62). Of 43 patients HIV-tested, 38 (88.3%) were HIV-positive and 15.7% died within the first month. At 3 months, 11 (21.6%) were known to have died. Adequate cortisol levels were found in 49/51 (95.9%) before commencing RMP. Neither of the two with reduced response died. All 34 patients revealed adequate cortisol responses at 2 weeks. CONCLUSION: No evidence of hypoadrenalism was found in this first study to assess adrenal function and outcome of anti-tuberculosis treatment.

Malawians permit research bronchoscopy due to perceived need for healthcare.

OBJECTIVES: Bronchoalveolar lavage obtained at bronchoscopy is useful for research on pulmonary defence mechanisms. Bronchoscopy involves some discomfort and risk to subjects. We audited the process of consent, experienced adverse effects and reasons for participation among research bronchoscopy volunteers. DESIGN: 100 consecutive volunteer research subjects attending for bronchoscopy, repeat bronchoscopy or routine recruitment clinic were interviewed. Information was gathered about volunteer motivation, perception of the consent process and adverse effects of bronchoscopy. Suggestions for improvement were requested. Responses were themed by a second investigator prior to data analysis. RESULTS: 81 bronchoscopy-experienced subjects (total of 263 procedures) and 19 new volunteers were interviewed. 19 subjects (21%) reported adverse symptoms during or after bronchoscopy, but no symptoms were of sufficient severity that they would not repeat the procedure. The frequency of symptoms was not related to gender, the quality of the lavage or the HIV status of the subject. 76 subjects (94%) reported that the information given pre-procedure was useful and adequate but 43 (56%) had further questions mostly relating to their own results. The reasons given for research participation were access to health assessment (75 subjects), access to treatment when ill (61 subjects), desire to participate in research (15 subjects) and remuneration (6 subjects). 7 subjects complained that the remuneration was inadequate. CONCLUSIONS: The main incentive to participation in research bronchoscopy was access to healthcare. Informed consent and procedure technique were adequate but subjects would value more feedback about individual and project results.

[Emigration of physicians from Africa: focus on Malawi]. / Emigratie van artsen uit Afrika, in het bijzonder uit Malawi.

The migration of physicians out of developing nations to rich, western countries contributes heavily to the healthcare problems in Africa. African physicians emigrate primarily to the USA, UK and Canada. In their land of origin, there is often a severe shortage of physicians, while the need for physicians has increased due to HIV/AIDS and the introduction of antiretroviral therapy. Training capacity in Africa is limited. Of the 256 physicians who have graduated from the College of Medicine in Malawi, 60% reside in Malawi; most work in the public sector. Of those who moved abroad, 59% are obtaining specialised postgraduate training. The problem of brain drain in Malawi appears to be limited at this time. However, given the severe shortage of physicians, training capacity should be increased and career prospects, remuneration and working conditions should be improved.

Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial.

SETTING: Zomba and Blantyre, Malawi, Africa. OBJECTIVES: To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB). DESIGN: A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months. RESULTS: A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults. CONCLUSIONS: Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.

Vulnerability and revictimization: Victim characteristics in a Dutch assault center.

Sexual and family violence are highly prevalent problems with numerous negative health consequences. Assault centres, such as the Centre for Sexual and Family Violence (CSFV) in the Netherlands, have been set up to provide optimal care to victims. We wanted to gain insight into characteristics of the population that presented to the Centre in order to customize care to their needs. File analysis was conducted of victims who attended the CSFV between 2013 and 2016. Data were analyzed in SPSS. A total of 121 victims entered the Centre, 93% of them being female. Forty-two per cent were adult victims of sexual violence, 28% minor victims of sexual violence and 30% adult victims of family violence. One-third of sexual and two-third of family violence victims had experienced prior abuse. Current use of psychosocial services and psychiatric medication was high, and a cognitive disability was present in 18% of the sexual violence victims. Half the victims reported, but when the perpetrator was a recent contact, e.g., someone met at a party, reporting rates went down. Sexual and family violence victims share characteristics that indicate vulnerability, suggesting that care for both groups might best be combined in one single assault centre. In this way, victims can make use of the same services and knowledge of gender-based violence. One of the major aims of assault centres is to provide psychosocial follow-up care and facilities for reporting. The victims' needs in these matters deserve further research.

[The introduction of antiretroviral therapy in Malawi]. / De introductie van antiretrovirale therapie in Malawi.

The prevalence of HIV infection in Malawi is high. Until mid 2004, antiretroviral therapy (ART) was only available for a fee; later, a programme for free distribution was started. When ART was started, no laboratory tests other than an HIV test were felt to be necessary. After an introductory period in which hospitals were assessed for the presence of sufficient infrastructure and health workers were trained in ART, the number of public and private clinics where ART was distributed rose to 60. By end 2005, the number of patients on ART was 37,840, which is 45% of the target in the so-called '3-by-5' initiative of the WHO/Joint United Nations Programme on HIV/ AIDS (UNAIDS). The goal of this initiative was to have half (85,000) ofthe estimated 170,000 HIV-infected individuals in Malawi for whom ART is indicated on treatment by end 2005. After 12 months of follow-up, 81% of the patients treated were still alive and on treatment, while the mortality was 10%, 8% no longer visited the outpatient clinic, and 1% had stopped ART. Despite facing various challenges, intensive collaboration with all stakeholders involved, under strong leadership of the Ministry of Health, has laid the foundation for this thus far successful programme.

Improving care for victims: a study protocol of the evaluation of a centre for sexual and family violence.

INTRODUCTION: Worldwide, sexual and family violence are highly prevalent problems. Victims of sexual and family violence often do not seek formal help in the acute phase. When they do seek help, they encounter a system of scattered care. For this reason, a centre for sexual and family violence was launched in Nijmegen, the Netherlands. The centre provides multidisciplinary care for victims of acute sexual and/or family violence. With the study described in this study protocol, we want to evaluate the implementation process and the reach of the Center for Sexual and Family Violence Nijmegen (CSFVN). METHODS AND ANALYSIS: We will conduct a mixed-methods study including quantitative and qualitative methods of data collection and analysis. Data about the implementation process will be obtained via semistructured interviews and focus group discussions. Content analysis will be done in software program Atlas.ti. Analysis of file data will be undertaken to assess the reach of the CSFVN (patient characteristics and characteristics of the care they received). The data will be analysed in SPSS. ETHICS AND DISSEMINATION: The Medical Ethics Committee of the Radboud University Nijmegen Medical Center approved the study protocol under file number 2012-1218. Dissemination will be done by submitting scientific articles to academic peer-reviewed journals. We will present the results at relevant international, national and local conferences and meetings. We will send press releases to relevant media. We will share the results with the network of assault centres in the Netherlands.

Differential diagnosis of stroke in a setting of high HIV prevalence in Blantyre, Malawi.

BACKGROUND AND PURPOSE: The differential diagnosis of stroke in Africa in areas with high HIV prevalence includes brain infections. We studied causes of stroke in Blantyre, Malawi, where HIV prevalence among medical inpatients is 70%. METHODS: In a descriptive study of 8-month duration, all patients presenting at Queen Elizabeth Central Hospital, Blantyre, with central neurological deficit of acute onset (<24 hours) had baseline investigations, including full blood count, blood glucose, serology for toxoplasmosis, syphilis, and HIV, ECG, echocardiogram, ultrasound of the carotid arteries, and computerized tomography scan of the brain. A lumbar puncture was performed unless contraindicated. RESULTS: Ninety-eight consecutive patients (49 males) were studied. In those who were HIV positive (48%), the mean age was 37.5 years; ischemic stroke was the commonest diagnosis (n=25; 58%), followed by infection (n=11; 23%; including tuberculous [n=4] and cryptococcal [n=2] meningitis; toxoplasmic encephalitis [n=1]; neurocysticercosis [n=1]; brain abscess [n=1]; and progressive multifocal leucoencephalopathy [n=2]). No clinical or laboratory parameters could be identified as predictors for infection, but 3 of 5 patients with fever on admission had tuberculous meningitis. In HIV-negative patients (mean age 58.6 years), 55% had ischemic stroke and 31% had intracerebral hemorrhage; no brain infection was diagnosed. Presence of vascular disease correlated with age but not with HIV status. CONCLUSIONS: Ischemic stroke was found in half of patients irrespective of HIV status. In those who are HIV positive, brain infection should be considered for which the presence of fever and examination of cerebrospinal fluid seem most useful in diagnosis.

[Medical specialist training at the College of Medicine in Malawi; the value of the Dutch contribution]. / De artsenopleiding aan het College of Medicine in Malawi; het nut van Nederlandse inbreng.

Malawi, one of the world's poorest nations, has been until recently largely dependent on foreign doctors. In 1991 the College of Medicine was founded in Blantyre, Malawi, to train doctors locally, using a curriculum that meets international standards and is tailored to local needs. The Dutch government has supported this initiative financially and by providing medical specialists to help develop the curriculum, to teach and to assist in clinical and research tasks. The College has been remarkably successful. Most graduates remain to practice in Malawi and student numbers have increased from 30 to 65 per year. A training programme for medical specialists has been recently started that is aimed at providing university staff who can take over from the expatriates. It will still take several years before the College is able to train sufficient, qualified local teaching staff. Continued support from the Dutch government is essential as well as intensified cooperation with Dutch academic centres in medical education, specialist training and research.

Post-kala-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.

Antibody reactivity to conserved linear epitopes of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of protein antigens are involved in adhesion of P. falciparum infected erythrocytes to the capillary endothelium of the host. Antibodies to variable regions of these proteins, measured by agglutination, correlates with clinical protection against falciparum malaria. In this study we investigated the occurrence of antibodies to conserved sequences of these very variable proteins in a population living in an area endemic for falciparum malaria. Using the ELISA method, we were able to measure an antibody response to three synthetic peptides derived from conserved regions of PfEMP1. The antibody responses to these peptides increased with age and were higher in individuals with asymptomatic P. falciparum infection compared to individuals presenting with fever attributable to falciparum malaria. This indicates that antibodies recognising the conserved regions of PfEMP1 arise upon exposure to the parasite, and that these may be involved in the development of protection against malaria. Antibodies to the Pfalhesin peptide of the human aniontransporter, band3, were measured by the same method. The magnitude of this antibody response did not correlate with neither age nor clinical protection.

Endemic kala-azar in eastern Sudan: post-kala-azar dermal leishmaniasis.

In a longitudinal study between 1991 and 1993 in an endemic area in eastern Sudan, 85 cases of kala-azar (visceral leishmaniasis) were diagnosed, of whom 48 (56%) developed post-kala-azar dermal leishmaniasis (PKDL). Another four cases of PKDL had no clinical history of kala-azar. In children, PKDL was more frequent in the very young; seven of nine kala-azar cases (78%) in the group 0-1 years of age and 13 of 16 (81%) in the group 2-3 years of age developed PKDL. On the average, PKDL occurred 56 days (mean; range 0-180) after the end of treatment of kala-azar. To assess the severity of PKDL, a classification was developed using three grades of severity based on differences in density and distribution of lesions. In young children, PKDL was more severe. Incomplete treatment of kala-azar may be important in the pathogenesis of PKDL. Thirty-one patients were followed-up for at least six months; of these, 20 were not treated (17 healed, two improved, and in one, the condition was unchanged), three healed after incomplete treatment with sodium stibogluconate, and eight were cured after treatment but two required two courses. Considerable morbidity was caused by PKDL and should be taken into consideration in the management and follow-up of kala-azar patients. The high incidence of PKDL may have important implications in transmission.

Endemic kala-azar in eastern Sudan: a longitudinal study on the incidence of clinical and subclinical infection and post-kala-azar dermal leishmaniasis.

Between April 1991 and April 1993, a longitudinal study was performed in the village of Um-Salala (1,430 inhabitants) in the endemic area of kala-azar (visceral leishmaniasis) in eastern Sudan. During the two years, a total of 92 kala-azar cases were diagnosed (male:female ratio = 1.8:1, mean age 6.6 years). The annual incidence rates were 38.4/1,000 and 38.5/1,000 person-years, respectively. The ratio of clinical to subclinical cases was 1.6:1 in the first year and 2.4:1 in the second year. Post-kala-azar dermal leishmaniasis occurred in 48 (56%) of 85 kala-azar cases that were followed-up for at least six months. Kala-azar occurred only in previously leishmanin-negative individuals. The majority of the population had a positive leishmanin skin test result, probably due to previous exposure to Leishmania major causing cutaneous leishmaniasis in their homeland in western Sudan from which they had migrated in the 1980s. It was thus postulated that previous cutaneous leishmaniasis might protect against kala-azar but this could not be proved.

Congenital kala-azar and leishmaniasis in the placenta.

During an epidemic of visceral leishmaniasis in the Sudan, two cases of congenital kala-azar were seen. The first child, whose mother had contracted kala-azar in southern Sudan, was born in Khartoum, where no transmission of leishmaniasis is currently occurring. At seven months, the child had fever, lymphadenopathy, and hepatosplenomegaly; leishmania parasites were detected in the bone marrow. The child died and an autopsy showed leishmania parasites in all tissues including the lungs, kidneys, and thymus. In the second case, parasites were found in the placenta of a five-month-old fetus. These two cases demonstrate the importance of follow-up of infants born to mothers with leishmaniasis.