Factors predicting 6-month retention among people with opioid use disorders accessing outpatient methadone maintenance therapy in Tshwane, South Africa.

BACKGROUND: In South Africa (SA), increasing illicit opioid use and associated health challenges can be managed with opioid substitution therapy (OST), such as methadone, if the recommended dose and duration of use are prescribed. The Community Oriented Substance Use Programme (COSUP) provides free methadone to patients with opioid use disorder in Tshwane, SA, on need-based criteria. OBJECTIVES: To determine selected sociodemographic and substance use treatment factors associated with retention for at least 6 months among participants receiving methadone as part of OST in COSUP. METHODS: This was a retrospective cohort study using secondary data of patients treated with methadone at 8 COSUP sites. The factors associated with at least 6 months' retention for 575 participants from December 2016 to September 2018 were analysed. RESULTS: There were 91.3% males, 86.4% South Africans and 85.9% black Africans, with a median age of 30 years. At baseline, the majority were injecting heroin (55.5%) and were provided with free methadone (59.3%). The median dose of methadone at 6 months or on leaving the programme was 20 mg; 38.4% of participants were retained for at least 6 months. Of those not retained, the median duration on methadone was 56 days, whereas for those retained for at least 6 months, the median number of days on methadone were 254. After adjusting for sex and age, participants receiving methadone doses <50 mg had lower odds of being retained (0 - 20 mg: adjusted odds ratio (aOR) 0.25; p=0.002; 95% confidence interval (CI) 0.10 - 0.61; >20 - 40 mg: aOR 0.20; p<0.001; 95% CI 0.08 - 0.49) than those administered ≥50 mg. Participants who received free methadone had 3.75 the odds of being retained than those buying it themselves (p<0.001; 95% CI 2.47 - 5.70). Participants treated in the inner city had 5.19 the odds of being retained than those in a suburban setting (p<0.001; 95% CI 2.99 - 9.03). Compared with black African participants, white participants had 3.39 the odds of being retained (p=0.001; 95% CI 1.64 - 7.00). Injecting heroin users had 0.63 the odds of being retained (p=0.032; 95% CI 0.41 - 0.96). CONCLUSIONS: To maximise retention on OST, methadone should be free, with maintenance doses >50 mg. Reasons for lower retention among participants from periurban settings, those who inject and those from previously disadvantaged racial groups need to be explored, and findings used to inform programming.

Pathological margins and advanced cutaneous squamous cell carcinoma of the head and neck.

OBJECTIVE: The recommended treatment for cutaneous squamous cell cancer (CuSCC) of the head and neck is Mohs surgical excision or wide local excision. Excision is recommended to a gross surgical margin of 4-6 mm however this is based on limited evidence and specify a goal histologic margin. The objective of this study was therefore to examine the reported histological margin distance following WLE of advanced CuSCC and its association with recurrence and survival. STUDY DESIGN: Retrospective database review. SETTING: All patients included received treatment at UC Davis Department of Otolaryngology-Head and Neck Surgery and/or Radiation Oncology in Sacramento, California. SUBJECTS AND METHODS: The patients included were treated for advanced CuSCC with primary surgery with or without adjuvant therapy. Kaplan Meier survival curves with log rank analysis were then performed to compare 5-year recurrence free survival, and disease-specific survival for patients with different margin distances. RESULTS: Total number of subjects was 92. The overall 5-year DSS and RFS was 68.8 and 51.0% respectively. When the pathological margin distance was ≥5 mm, 5-year disease specific survival was improved when compared to margin distance less than 5 mm (94.7 vs 60.7 p = 0.034). CONCLUSION: The findings of this study suggest that a histologic margin of at least 5 mm may increase survival in advanced head and neck CuSCC patients.

Physiological and neuroendocrine responses to chronic variable stress in male California mice (Peromyscus californicus): Influence of social environment and paternal state.

Social environment and parental state affect stress responses in mammals, but their impact may depend on the social and reproductive strategy of the species. The influences of cohabitation with a male or female conspecific, and the birth of offspring, on the physiological and endocrine responses to chronic variable stress were studied in the monogamous and biparental California mouse (Peromyscus californicus). Adult male California mice were housed either with a male cage mate (virgin males, VM), a female cage mate (pair-bonded males, PBM), or a female cage mate and their first newborn litter (new fathers, NF). VM, PBM and NF underwent a 7-day chronic variable stress paradigm (CVS, three stressors per day at semi-random times, n=7-8 per housing condition). Compared to control males (CON, n=6-7 per housing condition), CVS caused loss of body mass, increased basal plasma corticosterone concentrations, and increased basal expression of arginine vasopressin (AVP) mRNA in the paraventricular nucleus of the hypothalamus (PVN). These effects were independent of housing condition. Neither CVS nor housing condition altered novel-stressor-induced corticosterone release, spleen or testis mass, or basal expression of corticotropin-releasing hormone (CRH) mRNA in the PVN. Although CVS appeared to increase adrenal mass and reduce thymus mass specifically in NF, these effects were explained by the lower adrenal mass and higher thymus mass of NF compared to PBM and VM under control conditions. These results suggest that neither engaging in a pair bond nor becoming a father attenuates typical responses to CVS, but that fatherhood may provide a buffer against transient mild stressors (i.e., weighing and blood sampling in the control groups) in this monogamous and biparental rodent.

Molecular epidemiological investigation of a typhoid fever outbreak in South Africa, 2005: the relationship to a previous epidemic in 1993.

In 2005, over 600 clinically diagnosed typhoid fever cases occurred in South Africa, where an outbreak had been previously described in 1993. Case-control and molecular investigations, including Salmonella enterica serovar Typhi (S. Typhi) isolates from that area from 1993, 2005 and later, were undertaken. Controls were significantly older than cases (P=0·003), possibly due to immunity from previous infection, and a significantly larger proportion had attended a gathering (P=0·035). Exposure to commercial food outlets and person-to-person transmission was not significant. Pulsed-field gel electrophoresis and multi-locus tandem repeat analysis revealed common clusters of S. Typhi strains identified in 1993 and 2005 as well as in 2007 and 2009. This outbreak probably occurred in a non-immune population due to faecally contaminated water. S. Typhi strains appeared to be related to strains from 1993; failure to address unsafe water may lead to further outbreaks in the area if the current population immunity wanes or is lost.

Bovine tuberculosis: a review of current and emerging diagnostic techniques in view of their relevance for disease control and eradication.

Existing strategies for long-term bovine tuberculosis (bTB) control/eradication campaigns are being reconsidered in many countries because of the development of new testing technologies, increased global trade, continued struggle with wildlife reservoirs of bTB, redistribution of international trading partners/agreements, and emerging financial and animal welfare constraints on herd depopulation. Changes under consideration or newly implemented include additional control measures to limit risks with imported animals, enhanced programs to mitigate wildlife reservoir risks, re-evaluation of options to manage bTB-affected herds/regions, modernization of regulatory framework(s) to re-focus control efforts, and consideration of emerging testing technologies (i.e. improved or new tests) for use in bTB control/eradication programs. Traditional slaughter surveillance and test/removal strategies will likely be augmented by incorporation of new technologies and more targeted control efforts. The present review provides an overview of current and emerging bTB testing strategies/tools and a vision for incorporation of emerging technologies into the current control/eradication programs.

Brief pup exposure induces Fos expression in the lateral habenula and serotonergic caudal dorsal raphe nucleus of paternally experienced male California mice (Peromyscus californicus).

Fathers play a substantial role in infant care in a small but significant number of mammalian species, including humans. However, the neural circuitry controlling paternal behavior is much less understood than its female counterpart. In order to characterize brain areas activated by paternal care, male California mice were separated from their female mate and litter for 3 h and then exposed to a pup or a control object (a glass pebble with the approximate size and oblong shape of a newborn pup) for 10 min. All males receiving a pup showed a strong paternal response towards it, whereas males receiving a pebble interacted with it only occasionally. Despite the clear behavioral differences, exposure to a pup did not increase Fos-like immunoreactivity (Fos-LIR) compared to a pebble in brain areas previously found to be associated with parental care, including the medial preoptic nucleus and medial bed nucleus of the stria terminalis. Pup exposure did, however, significantly increase Fos-LIR in the lateral habenula (LHb) and in predominantly serotonergic neurons in the caudal dorsal raphe nucleus (DRC), as compared to pebble exposure. Both the LHb and DRC are known to be involved in the behavioral responses to strong emotional stimuli; therefore, these areas might play a role in controlling parental behavior in male California mice.

Proteomic and physiological responses of leopard sharks (Triakis semifasciata) to salinity change.

Partially euryhaline elasmobranchs may tolerate physiologically challenging, variable salinity conditions in estuaries as a trade-off to reduce predation risk or to gain access to abundant food resources. To further understand these trade-offs and to evaluate the underlying mechanisms, we examined the responses of juvenile leopard sharks to salinity changes using a suite of measurements at multiple organizational levels: gill and rectal gland proteomes (using 2-D gel electrophoresis and tandem mass spectrometry), tissue biochemistry (Na(+)/K(+)-ATPase, caspase 3/7 and chymotrypsin-like proteasome activities), organismal physiology (hematology, plasma composition, muscle moisture) and individual behavior. Our proteomics results reveal coordinated molecular responses to low salinity - several of which are common to both rectal gland and gill - including changes in amino acid and inositol (i.e. osmolyte) metabolism, energy metabolism and proteins related to transcription, translation and protein degradation. Overall, leopard sharks employ a strategy of maintaining plasma urea, ion concentrations and Na(+)/K(+)-ATPase activities in the short-term, possibly because they rarely spend extended periods in low salinity conditions in the wild, but the sharks osmoconform to the surrounding conditions by 3 weeks. We found no evidence of apoptosis at the time points tested, while both tissues exhibited proteomic changes related to the cytoskeleton, suggesting that leopard sharks remodel existing osmoregulatory epithelial cells and activate physiological acclimatory responses to solve the problems posed by low salinity exposure. The behavioral measurements reveal increased activity in the lowest salinity in the short-term, while activity decreased in the lowest salinity in the long-term. Our data suggest that physiological/behavioral trade-offs are involved in using estuarine habitats, and pathway modeling implicates tumor necrosis factor alpha (TNFalpha) as a key node of the elasmobranch hyposmotic response network.

Immune responses in cattle inoculated with Mycobacterium bovis, Mycobacterium tuberculosis, or Mycobacterium kansasii.

Cattle were inoculated with Mycobacterium bovis, Mycobacterium tuberculosis, or Mycobacterium kansasii to compare the antigen-specific immune responses to various patterns of mycobacterial disease. Disease expression ranged from colonization with associated pathology (M. bovis infection) and colonization without pathology (M. tuberculosis infection) to no colonization or pathology (M. kansasii infection). Delayed-type hypersensitivity and gamma interferon responses were elicited by each mycobacterial inoculation; however, the responses by the M. bovis- and M. tuberculosis-inoculated animals exceeded those of the M. kansasii-inoculated animals. Specific antibody responses were detected in all M. tuberculosis- and M. bovis-inoculated cattle 3 weeks after inoculation. From 6 to 16 weeks after M. tuberculosis inoculation, the antibody responses waned, whereas the responses persisted with M. bovis infection. With M. kansasii inoculation, initial early antibody responses waned by 10 weeks after inoculation and then increased 2 weeks after the injection of purified protein derivative for the skin test at 18 weeks after challenge. These findings indicate that antibody responses are associated with the antigen burden rather than the pathology, cellular immune responses to tuberculin correlate with infection but not necessarily with the pathology or bacterial burden, and exposure to mycobacterial antigens may elicit an antibody response in a presensitized animal.

Evaluation of environmental sampling and culture to determine Mycobacterium avium subspecies paratuberculosis distribution and herd infection status on US dairy operations.

The objectives of this study were to determine the distribution of Mycobacterium avium subspecies paratuberculosis (MAP) in the environment and assess the relationship between the culture status of MAP in the farm environment and herd infection status. The National Animal Health Monitoring System's Dairy 2002 study surveyed dairy operations in 21 states. One component of the study involved collection and culturing of environmental samples for MAP from areas on farms where manure accumulated from a majority of a herd's cows. Operations were selected for inclusion based on perceived risk factors for MAP infection identified in a previously administered questionnaire. Individual animal and environmental samples were collected and used to determine the efficiency of environmental sampling for determination of herd infection status. Individual animal fecal, serum, and milk samples were used to classify herds as infected or not infected based on the presence of at least one test-positive animal in the herd. A total of 483 environmental samples (approximately 5 per farm) were collected, and 218 (45.1%) were culture-positive for MAP. A similar percentage of environmental cultures collected from all designated areas were positive [parlor exits (52.3%), floors of holding pens (49.1%), common alleyways (48.8%), lagoons (47.4%), manure spreaders (42.3%), and manure pits (41.5%)]. Of the 98 operations tested with the environmental sample culture, 97 had individual serum ELISA results, 60 had individual fecal culture results, and 34 had individual milk ELISA results. Sixty-nine of the 98 operations (70.4%) had at least one environmental sample that was culture-positive. Of the 50 herds classified as infected by fecal culture, 38 (76.0%) were identified by environmental culture. Two of the 10 operations classified as not infected based on individual animal fecal culture were environmental culture-positive. Of the 80 operations classified as infected based on serum ELISA-positive results, 61 (76.3%) were identified as environmental-positive, whereas 20 of the 28 (71.4%) operations identified as infected based on milk ELISA were detected by environmental sampling. Environmental sample culturing is less costly than individual animal sampling, does not require animal restraint, and identified more than 70% of infected operations. Environmental sampling is another diagnostic tool that veterinarians and dairy producers can use to determine herd infection status for MAP.

Neonatal tetanus elimination in Mpumalanga Province, South Africa.

Neonatal tetanus (NNT) is a serious but preventable disease, and the World Health Organization (WHO) wants to eliminate NNT globally by reducing its incidence to <1 case per 1000 live births. South Africa adopted this goal in 1995, but Mpumalanga, a rural province, has consistently reported cases of NNT despite an appropriate vaccination strategy to eliminate the disease. The aim of the study was to investigate the completeness of the passive notification system and to explore reasons for ongoing NNT cases despite implementation of the provincial vaccination strategy. We reviewed all hospital admissions in the province between 1996 and 2000 meeting the case definition for NNT and interviewed mothers of the NNT cases reported in 2000. We identified 26 NNT cases, of which only 14 (54%) were reported through the routine notification system. Most cases occurred as a result of the cultural practice of applying cow dung or rat faeces to the umbilical stump in the neonatal period. Although all districts met the WHO elimination target during the review period, there is scope to prevent unnecessary NNT deaths through culturally acceptable public awareness campaigns aimed at changing harmful practices, and encouraging hygienic births and postnatal cord care.

Leprosy in Mpumalanga Province, South Africa--eliminated or hidden?

In South Africa, leprosy has been a notifiable condition since 1921. Although the WHO elimination target of less than one case per 10,000 population has been achieved at country level, the distribution of leprosy in the country is distinctly heterogeneous, with a prominent 'leprosy belt' of greater prevalence stretching across Mpumalanga Province into northern Kwa-Zulu Natal. The highest prevalence in this 'belt' has historically been in Ermelo District. Recent trends of few newly detected leprosy patients in this district raised concerns that health system changes may have resulted in failure to detect leprosy cases. Thus a large-scale community awareness campaign was conducted followed by an intensively advertised screening programme of 3-month duration at schools and central gathering points in villages and farms from 1 June to 31 August 2000. One thousand one hundred and seventy-seven people presented for clinical screening at designated points, while 790 scholars were screened at schools and an additional 1433 people were screened at their homes by the field team. Forty-four people with skin or nervous system lesions compatible with leprosy were referred for specialized assessment and biopsy where indicated. Four new leprosy patients were diagnosed, including an elderly lady with pronounced disability. Two of these patients had prior contact with the health service due to dermatological manifestations of leprosy without diagnosis being made. All patients provided a history of close prolonged contact with known leprosy patients. Ongoing intense tracing and follow-up of close contacts of proven leprosy cases may be a more efficient method of detecting leprosy cases in areas with relatively stable populations that have accomplished 'leprosy elimination', than resource intensive community surveys.

The use of hospital-based nurses for the surveillance of potential disease outbreaks.

OBJECTIVE: To study a novel surveillance system introduced in Mpumalanga Province, a rural area in the north-east of South Africa, in an attempt to address deficiencies in the system of notification for infectious conditions that have the potential for causing outbreaks. METHODS: Hospital-based infection control nurses in all of Mpumalanga's 32 public and private hospitals were trained to recognize, report, and respond to nine clinical syndromes that require immediate action. Sustainability of the system was assured through a schedule of regular training and networking, and by providing feedback to the nurses. The system was evaluated by formal review of hospital records, evidence of the effective containment of a cholera outbreak, and assessment of the speed and appropriateness of responses to other syndromes. FINDINGS: Rapid detection, reporting and response to six imported cholera cases resulted in effective containment, with only 19 proven secondary cholera cases, during the two-year review period. No secondary cases followed detection and prompt response to 14 patients with meningococcal disease. By the end of the first year of implementation, all facilities were providing weekly zero-reports on the nine syndromes before the designated time. Formal hospital record review for cases of acute flaccid paralysis endorsed the value of the system. CONCLUSION: The primary goal of an outbreak surveillance system is to ensure timely recognition of syndromes requiring an immediate response. Infection control nurses in Mpumalanga hospitals have excelled in timely weekly zero-reporting, participation at monthly training and feedback sessions, detection of priority clinical syndromes, and prompt appropriate response. This review provides support for the role of hospital-based nurses as valuable sentinel surveillance agents providing timely data for action.

A serosurvey of water-borne pathogens amongst canoeists in South Africa.

Certain health risks have been associated with recreational exposure to faecally polluted water. Canoeing in certain South African waters is considered to be a high risk activity with regard to schistosomiasis, gastroenteritis and possibly hepatitis. In a cross-sectional study, a serosurvey was conducted amongst canoeists to ascertain whether or not they had a higher seroprevalence to hepatitis A virus, Norwalk virus and Schistosoma spp. than non-canoeists. In comparisons between the two groups, a significant association could not be demonstrated between canoeing and antibody response to hepatitis A and Norwalk viruses (P-values for age-adjusted chi 2 were 0.083 and 0.219 respectively), but a significant association could be demonstrated between canoeing and the antibody response to Schistosoma spp. (P < 0.001; age-adjusted).

Variant translocations (9;11): identification of the critical genetic rearrangement.

The t(9;11)(p22;q23) is a recurring abnormality in acute nonlymphocytic leukemia. The analysis of complex 9;11 translocations will aid in the identification of the conserved chromosomal junction or the critical genetic alteration created by the rearrangement; however, variant translocations involving chromosomes #9 and #11 have not been reported. We have identified such variants in two patients who had acute myelomonocytic leukemia and acute monocytic leukemia, characterized by a t(9;11;18)(p22;q23;q12) and a t(9;11;13)(p22;q23;q34), respectively. The conserved junction resulting from these rearrangements is created by the translocation of chromosomal material from 9p to 11q.