Multi-drug-resistant tuberculosis clusters in Mpumalanga province, South Africa, 2013-2016: A spatial analysis.

OBJECTIVE: To identify spatial clusters with unusually high levels of MDR-TB, which are highly unlikely to have arisen by chance in Mpumalanga Province, South Africa. METHODS: Home addresses of all MDR-TB patients were collected from four MDR-TB facilities from 2013 to 2016. We mapped all addresses, linking them to the nearest ward with population estimates. A spatial analysis was conducted using kernel density in ArcGIS to estimate and map the distribution of the disease and used Gertis-Ord Gi to test for significant clustering. RESULTS: A total of 4065 MDR-TB patients were mapped. Ten significant clusters (p-value <0.05) were found across the province in six sub-districts: Mbombela, Nkomazi, Emalahleni, Govan Mbeki, Lekwa and Mkhondo. Mbombela has the highest number of significant clusters. The central region did not have any MDR-TB clusters. CONCLUSION: There is clear evidence of MDR-TB clustering in Mpumalanga. This calls for concentrated TB prevention efforts and proper allocation of resources. Further investigations are needed to identify MDR-TB predictors.

In vitro efficacy of amphotericin B, 5-fluorocytosine, fluconazole, voriconazole and posaconazole against Candida dubliniensis isolates using time-kill methodology.

Candida dubliniensis is a recently described yeast that causes infections in mucosal surfaces as well as sterile body sites. Candida dubliniensis develops resistance to fluconazole (FLC) more rapidly than the closely related species C. albicans. The killing activity of amphotericin B (AMB), 5-fluorocytosine (5FC), FLC, voriconazole (VRC) and posaconazole (POS) was determined against six C. dubliniensis clinical isolates, identified using molecular biological methods and C. dubliniensis CD36 reference strain. Minimum inhibitory concentrations (MICs) were determined using the Clinical and Laboratory Standards Institute standard procedure. Time-kill assays were performed using RPMI-1640 as test media over a 48-h period. AMB proved to be fungicidal at >or=0.5 microg ml(-1) against all clinical isolates after 48 h. 5FC was only fungicidal at 32-64x MIC (4-8 microg ml(-1)) against all C. dubliniensis isolates. FLC, VRC and POS were fungistatic; decrease in colony number was observed only at the highest concentrations tested (8, 4 and 4 microg ml(-1), respectively). Triazoles invariably showed fungistatic effect at concentrations attainable in the serum. In clinical situations when a fungicidal antifungal is desirable, AMB may be used.

Outcomes of community-based HIV testing modalities in a Mpumalanga district, South Africa.

BACKGROUND: Testing for HIV in individuals informs them of their HIV status, which in turn enables them to receive prevention, treatment and care services. HIV services should ideally be accessed before an individual's immune system is severely damaged, which could also increase the prevention of new HIV infections. The national HIV testing services (HTS) programmes aim to identify HIV-infected individuals and link them to prevention, care and treatment services. Community-based (CB) HTS reaches community members who do not have access to such services at healthcare facilities. The Foundation for Professional Development (FPD) provided CB-HTS in a Mpumalanga district, South Africa, from 1 October 2016 to 30 September 2017 (Country Operating Plan (COP16)), where 65 691 clients were tested. OBJECTIVES: To determine which of the FPD CB-HTS modalities used in the Mpumalanga district during COP16 delivered the highest positivity rate, disaggregated by population segmentation. The accompanying objectives were: to describe the demographic characteristics of HTS clients in the district and to compare the different positivity rates of FPD CB-HTS modalities in the district. METHODS: This cross-sectional quantitative study used all the individual, programmatic data collected for all CB-HTS clients in Ehlanzeni during COP16 as secondary data. Descriptive analysis was employed to describe participants' characteristics. The χ2 test was used for comparing variables. RESULTS: The mean age of clients was 29.3 (95% confidence interval (CI) 29.7 - 29.9) years. Of the clients analysed, 56.4% were females. Of the clients who were tested for HIV, 14.1% were tested for the first time; 67.7% of those were between 15 and 49 years old. The positivity rate for each modality was calculated, and it was found that home-based HTS had the best positivity rate (9.1%) in the Mpumalanga district during COP16. CONCLUSIONS: This study provides evidence that home-based HTS delivered the best positivity rate in the Mpumalanga district. The results should be used to replicate the programme in other districts. If similar findings are obtained in other studies, it could inform how future CB-HTS programmes should be rolled out, which could change future strategic planning and resource allocation for CB-HTS programmes.

Incidence of chromosomal abnormalities in the presence of fetal subcutaneous oedema, such as nuchal oedema, cystic hygroma and non-immune hydrops.

INTRODUCTION: The authors investigated the incidence of chromosomal abnormalities in subcutaneous oedema detected in the fetus by intrauterine ultrasonography. MATERIAL AND METHOD: In the 10-year period, intrauterine karyotyping was performed in pregnancies with positive ultrasound findings for subcutaneous oedema, such as nuchal oedema, cystic hygroma and non-immune hydrops. RESULTS: Intrauterine karyotyping in fetal subcutaneous oedema was carried out in 434 cases. The chromosomal investigation was made in nuchal oedema in 374 cases, in 120 patients the chromosomal examination was made in the first trimester because of nuchal translucency, and in 254 cases in the second trimester because of nuchal thickening. Cystic hygroma cases (27 patients), non-immune hydrops cases (20 patients), and combined cases of non-immune hydrops and cystic hygroma (13 patients) were investigated separately. In nuchal oedema, pathological karyotypes were detected in 8.33% in the first trimester and in 5.51% in the second trimester. Chromosomal abnormality was found in 48.15, 20, and 53.8% in cystic hygroma, non-immune hydrops, and combined occurrence of non-immune hydrops and cystic hygroma, respectively. Considering all of the changes accompanied by subcutaneous oedema, 50, 25 and 18.75% of the pathological karyotypes was X-monosomy, trisomy 18 and trisomy 21, respectively. DISCUSSION: It was important to distinguish nuchal oedema and cystic hygroma, and in the case of non-immune hydrops, it was also important to discuss cases with or without cystic hygroma separately. During the investigations, cases of non-immune hydrops with or without cystic hygroma were evaluated as separate categories. CONCLUSIONS: The authors emphasize the differentiation of the various types of subcutaneous oedema and the importance of precise information about the risks, provided during genetic counselling.

Prenatal diagnosis of abnormal course of umbilical vein and absent ductus venosus--report of three cases.

An abnormal course of the umbilical vein is a rare anomaly. Its association with the congenital absence of the ductus venosus is common. We found 3 cases of an abnormal course of the umbilical vein and an absent ductus venosus. In 2 of these cases, the umbilical vein turned down and continued in the internal iliac vein, and no ductus venosus was found. One of these pregnancies was terminated. From the continued pregnancy a growth-retarded baby was born. At follow-up examinations, mild microcephaly, mildly elevated levels of ammonia, delayed speech and mild muscular hypotonia were found. In the third case, the umbilical vein turned up from the level of umbilical ring and the anterior of the liver above the diaphragma and connected directly into the right atrium. Associated complex congenital heart malformations - transposition of the great arteries, and ventricular septal defect - were diagnosed prenatally. In the umbilical vein from the placenta to the umbilical ring, the flow was low velocity continuous; from the umbilical ring to the right atrium, the flow was biphasic high velocity (90 cm/s). Such an elevated blood flow could be a sign of increased cardiac preload. The long-term neurological follow-up of babies with prenatally diagnosed venous malformations is necessary.

Spinal anesthesia for cesarean section in a woman with Kartagener's syndrome and a twin pregnancy.

Kartagener's syndrome is an inherited disease characterized by a triad of symptoms: bronchiectasis, situs inversus and sinusitis resulting from defective cilial motility. There are few reports in the literature regarding the optimum anesthetic technique in patients with Kartagener's syndrome. The main anesthetic considerations are related to the respiratory system and increased risk of infection. We report the case of a woman with Kartagener's syndrome and a twin pregnancy conceived by in-vitro fertilization-embryo transfer, who underwent cesarean section under spinal anesthesia. Despite recurrent pulmonary problems, the twin pregnancy resulted in a successful outcome. This was facilitated by a close working relationship between the obstetrician, anesthesiologist and patient.

Antiproliferative effect of 4-thiouridylate on OCM-1 uveal melanoma cells.

PURPOSE: Brachytherapy is a well-established, effective treatment for uveal melanoma with a failure rate of 15%. The fatal consequence of unsuccessful treatments offers reason for improvement of the method. The authors propose using an apoptosis inducing agent locally, concomitantly with the well-established therapy, to sensitize the tumor cells. The authors propose a new nontoxic moderately active apoptosis inducing agent, 4-thio-uridylate (s4UMP), for this purpose. METHODS: OCM-1 uveal melanoma cells were treated with various concentrations of s4UMP and its effect was monitored by measuring the cell viability (MTT assay). The following apoptosis detecting methods were performed to reveal the mechanism of decreased cell viability: light microscopy, DNA fragmentation assay, determination of caspase 9 activity, and FACS analysis. RESULTS: The viability of uveal melanoma cells was decreased by 32%, 40%, and 9% after 24, 48, and 72 hours of treatment with 10 microg/mL (30 microM) s4UMP. The effect was not dose dependent; it rather followed a saturation-type inhibition and the cells at lower drug concentration recovered after 72 hours. Characteristic apoptotic cell morphology and DNA fragmentation was detected in treated cells. The caspase-9 was activated upon treatment showing maximal activity at 48 hours suggesting the induction of apoptosis. The annexin binding activity further verified the apoptogenic activity of s4UMP. CONCLUSIONS: Uveal melanoma, more than other solid tumors, is resistant to most of the chemotherapeutic protocols as indicated by the high mortality rate of metastatic disease. The authors showed that s4UMP, a naturally occurring nucleotide, could induce apoptosis in uveal melanoma cells, suggesting a potential supplementary therapeutic application of the compound.

Urinary osmolality in lithium and non-lithium treated psychiatric patients.

A study was conducted to determine the prevalence of urine concentrating defect in 57 psychiatric patients who were treated with lithium and 42 patients who were not treated with lithium. Analysis of results indicated that there was no statistically significant difference between the lithium treated and control groups in their random 12 hour fluid deprivation urine osmolality, 0.5 greater than p greater than 0.1, t-test. The authors suggest that impaired urinary concentrating ability occurs frequently in both lithium and nonlithium treated psychiatric patients. This isolated finding alone is insufficient to warrant the diagnosis of lithium nephrotoxicity.

Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase.

OBJECTIVE: To investigate the potential perinatal effects of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase C677T polymorphism in preeclamptic women. STUDY DESIGN: One hundred twenty preeclamptic women (N = 120) and 101 healthy pregnant controls (N = 101) were recruited and evaluated for frequency of Leiden and 5,10 methylenetetrahydrofolate reductase (MTHFR) mutations using polymerase chain reaction (PCR). Perinatal outcomes were then recorded and analyzed for all study participants and their neonates. RESULTS: Laboratory analysis yielded 22 (18.33%) heterozygous carriers of Factor V Leiden mutation among preeclamptic women and 3 (2.97%) heterozygous carriers among the healthy controls; differences between the two groups were found to be statistically significant [p < 0.001, the relative risk (RR) = 6.17, 95% confidence interval (95% CI) = 1.90-20.02]. Homozygous MTHFR mutations were found in 8 of 120 (6.67%) preeclamptic women and in 6 of the 101 (5.94%) healthy controls evaluated. Among preeclamptic women, episodes of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome were reported in 7 of 22 (31.81%) of those with Factor V Leiden mutation and in 11 of 98 (11.22%) of those who were negative for the mutation. Group differences were determined to be statistically significant (p < 0.015, RR = 2.83, 95% CI = 1.24-6. 48). Perinatal indicators collected from the two groups included frequency of intrauterine growth retardation, birth weight, and gestational age. No statistically different perinatal outcomes were found between Factor V Leiden positive and negative preeclamptic women. In addition, MTHFR gene polymorphism did not appear to be correlated with the development of preeclampsia. CONCLUSION: Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.

Obstetric anaesthesia in Hungary.

A nation-wide survey of pain relief in childbirth in Hungary was carried out in 1993. Information was provided on 104 137 deliveries in 98 units. The frequencies of different methods of pain relief for vaginal delivery were as follows: systemic opiates in 7387 cases (8.3%), epidural analgesia in 4611 cases (5.2%) and inhalational analgesia (nitrous oxide) in 4470 cases (5%). Epidural analgesia was available in 36 units (36.7%). For 71 744 vaginal deliveries (80.5%) no pain relief was provided at all. For caesarean section (n = 13240) the rate of spinal or epidural anaesthesia was 36.7%. It was concluded that despite an increasing rate of pain relief in labour elsewhere, the numbers of epidurals are still rather low in Hungary.

[Effect of preeclampsia on neonatal morbidity]. / A praeeclampsia hatása a neonatális morbiditásra.

In this study the outcome of two groups of premature infants born by caesarean section were compared from 52 hypertensive mothers with severe pre-eclampsia and from 30 normotensive mothers. The indication of caesarean section in pre-eclampsia was: proteinuria (> 500 mg/24 h), high blood pressure (> 160/100 mmHg), abnormal cardiotocogram and abnormality in flowmetry (fetal distress). Every infant was premature as well as in the control group. Significantly smaller mean birthweight and longer nursing-time in neonatal intensive care unit (NICU) were found in the pre-eclamptic group. Neonatal illnesses and complications are more frequent in the pre-eclamptic group. The time of ventilation was also longer. There are more early neurological disorders in the pre-eclamptic group than in the control one. The authors can establish that pre-eclamptic toxemia increases the morbidity in the neonatal period. This is due to the chronic intrauterine fetal distress as well as the retardation.

[Gynecologic and obstetric anesthesia in Hungary 1993]. / A szülészeti és nögyógyászati anesztézia helyzete Magyarországon 1993-ban.

Authors publish findings of a nationwide survey of pain relief in childbirth in Hungary carried out during the year of 1993. Informations were provided on 104,137 deliveries in 98 units. At 71,744 vaginal deliveries (81%) not any types of pain relief were used. The frequency ot different types of pain reliefs at vaginal deliveries were as follows: systemic opioids at 7387 cases (8.3%), epidural analgesia at 4611 cases (5.2%) and inhalational analgesia (nitrous oxide) at 4470 cases (5.0%). The availability of epidural analgesia at 62 units was absent. The rate of spinal--epidural analgesia at Cesarean sections was 37% (n = 13,240). At gynaecological laparotomies (n = 18,219) the rate of general anaesthesia was 98%, this rate at vaginal hysterectomies was 56.8% (n = 1568). Authors conclude that the rate of pain relief in labour in Hungary is unreasonably low. The reason of it is the lack of anaesthetists and also the traditional view, which does not recognize the importance of the pain relief in labour.

[Pre- and perinatal aspects of hemophilia A and B]. / A haemophilia A és B prae- és perinatalis vonatkozásai.

Authors investigate in a retrospective study obstetrical and genetical data in 20 years period of 149 pregnancies of patients turning to genetical counselling because of haemophilia A and B. In case of heterozygote mother there have been fetal determination of sex, and in case of male fetus, there have been DNA examination in 23 of the 35 cases. In case of sick male fetus the couple made a decision on keeping the pregnancy or not, knowing well the genetical risk. Haemophilia A occurred in case of 135 pregnancies (98 pregnancies of 55 heterozygote mothers, and 37 pregnancies from 20 sick fathers). Haemophilia B occurred in case of 14 pregnancies (9 pregnancies of 3 heterozygote mothers, and 5 pregnancies from 4 sick fathers). In case of haemophilia A heterozygote pregnant women there were 32 proven male fetuses, and in 22 cases there have been DNA examinations. In 16 cases there have been artificial abortions (in 10 cases proven disease by DNA examination), and 4 sick male newborns were born from the 16 deliveries (the disease was proven during pregnancy by DNA examination). One male newborn (healthy) was born from the 3 proven male fetuses of haemophilia B heterozygote pregnant women, in 2 cases there have been artificial abortions (in one case on the basis of DNA diagnostics). In cases of heterozygote mothers (haemophilia A and B altogether) the ration of the spontaneous abortions was 13.1%. The rations of the premature deliveries (8.2%) and the Caesarean sections (8.2%) were not higher than the national average. The ration of the bleeding complications during pregnancy was 18.7%, in 2.7% of the cases transfusion was necessary. In case of sickness of the father (in heterozygote female fetuses the haemostasis may change from the fetal side) the ration of the bleeding complications during pregnancy was 18.2%. In connection with delivery, obstetrical bleeding complications occurred in 12.2%, atonia in 2%, abrasion after delivery in 4.1, transfusion in 10.2% in cases both of haemophilia A and B heterozygote mothers. From the neonatological complications in one case there was cerebral haemorrhage, and in one case bleeding from the umbilical stump. (Both newborns were male with haemophilia.) In connection with delivery there was no haematoma developing on the skull of the newborns, there was no need of giving transfusion. In case of sickness of the fathers the ration of the instrumental uterine examination was 6.7%, there were no neonatological and other obstetrical complications.

South African communities' perceptions and priorities for well-being.

Surveys were conducted using a pre-tested questionnaire in 1991 and 1993 in South Africa to find out how the people perceive the government's social responsibility with special reference to the provision of free health care and other determinants of well-being. Provision of jobs for the unemployed and free education were identified to be the main priorities. Free health care ranked as the fifth priority. The study supports the call for increasing participation of communities in determining and prioritising their needs. It also calls on health care professionals to support the communities by advocating for policies that are directed towards the perceived needs of the community and to use the present available resources efficiently.

Efficacy of a single 6 mg/kg versus two 3 mg/kg caspofungin doses for treatment of disseminated candidiasis caused by Candida albicans in a neutropenic mouse model.

We compared the efficacy of single six mg/kg and 2x3 mg/kg caspofungin doses to the traditional one mg/kg daily against C. albicans in a neutropenic murine model. In lethality experiments, all regimens improved survival (p<0.0014 for all three isolates); differences among the treated groups were not statistically significant. We calculated kidney fungal burdens on each study day for six days postinfection using two isolates in two experiments. In the first three days, only the six mg/kg dose produced significant decrease on all study days (p<0.05-0.001), but differences between the three treatment arms disappeared by 4-6 days postinfection (p<0.05 for all isolates on all days).

Difference in killing activity of caspofungin and paradoxical growth between Candida albicans and C. krusei clinical isolates in different media.

Minimum fungicidal concentration (mFC) of caspofungin was determined against 16 Candida albicans and 16 C. krusei in Rpmi-1640 and antibiotic medium 3 (Am3). time-kill tests were performed on six C. albicans and four C. krusei strains at 0.06-16 mg/l caspofungin. mFC ranges after 48 h were 0.5-1 and 1-2 mg/l for C. albicans and C. krusei, respectively; one C. albicans and the C. krusei reference strain showed paradoxical growth (pG) in Rpmi-1640, respectively. in killing experiments, after 48 h caspofugin was fungicidal against two and four C. albicans in Rpmi-1640 (at 16 mg/l) and in Am3 (at >0.5 mg/l), respectively; pG was noted in three and two cases, respectively. Caspofungin at >2 and 0.5 mg/l was fungicidal against all tested C. krusei strains even after 24 h in Rpmi-1640 and Am3, respectively. Killing activity of caspofungin against C. albicans and C. krusei could be exactly measured only by killing curves.