Reasons for the low bacteriological coverage of tuberculosis reported in Mpumalanga Province,South Africa

Setting: Public sector hospitals and primary health clinics in the Mpumalanga Province of South Africa.Objective: To determine whether failure to adhere to tuberculosis (TB) diagnostic guidelines (i.e., submit sputum for smear microscopy) contributed to the low bacteriological coverage reported for TB in 2008 in Mpumalanga Province.Methods: We reviewed clinical records for new pulmonary TB cases at 30 of 118 randomly selected facilities that met the bacteriological coverage target of 80% and 30/87 facilities that did not. Data for hospital and clinic cases were abstracted into case report forms, captured electronically and compared with data from the electronic TB register (ETR). We assessed age, sex, human immunodeficiency virus (HIV) infection and facility type as potential confounders for recording of smear microscopy results.Results: Age, sex and HIV infection did not influence recording of results. In hospitals, 61.8% of pulmonary TB cases had sputum smear results in their clinical records compared to 93.6% at clinics (P < 0.001). Of the 711 cases (30.3%) that did not have smear results in the ETR, 342 (48.1%) did have smear results in their clinical records.Conclusion: Both poor clinical practice (especially in hospitals) and poor record keeping have contributed to the low bacteriological coverage reported. These shortcomings need to be addressed to improve patient care and programme management.     

Minimal Diversity of Drug-Resistant Mycobacterium tuberculosis Strains,South Africa

Multidrug- (MDR) and extensively drug-resistant tuberculosis (XDR TB) are commonly associated with Beijing strains. However, in KwaZulu-Natal, South Africa, which has among the highest incidence and mortality for MDR and XDR TB, data suggest that non-Beijing strains are driving the epidemic. We conducted a retrospective study to characterize the strain prevalence among drug-susceptible, MDR, and XDR TB cases and determine associations between strain type and survival. Among 297 isolates from 2005–2006, 49 spoligotype patterns were found. Predominant strains were Beijing (ST1) among drug-susceptible isolates (27%), S/Quebec (ST34) in MDR TB (34%) and LAM4/KZN (ST60) in XDR TB (89%). More than 90% of patients were HIV co-infected. MDR TB and XDR TB were independently associated with mortality, but TB strain type was not. We conclude that, although Beijing strain was common among drug-susceptible TB, other strains predominated among MDR TB and XDR TB cases. Drug-resistance was a stronger predictor of survival than strain type. Key words: Mycobacterium tuberculosis, drug resistance, transmission, genotype, South Africa, HIV, bacteria, tuberculosis, tuberculosis and other mycobacteria, antimicrobial resistanceDrug-resistant tuberculosis (TB) has emerged as a substantial threat to advances in global TB control over the past several decades (1). Worldwide, an estimated 630,000 cases of multidrug-resistant (MDR) TB occurred in 2011, and extensively drug-resistant (XDR) TB has now been reported in 84 countries (2). MDR TB and XDR TB are each associated with very high mortality rates (3), and their transmission—both in community and health care settings—remains an ongoing challenge in resource-limited settings and in countries with high rates of HIV co-infection.In South Africa, the incidence of MDR TB has increased 5-fold since 2002 (2,4). MDR TB treatment is now estimated to consume more than half of the budget allocated for TB control in South Africa (5). The emergence of XDR TB, and its associated high mortality rates, have further underscored the need for clarifying the factors driving the drug-resistant TB epidemic to better focus control efforts (3,6,7).Drug-resistant TB is generally considered a human-made phenomenon that occurs when inadequate TB treatment creates selection pressure for the emergence of drug-resistant Mycobacterium tuberculosis subpopulations (acquired resistance) (1). Researchers initially believed that the mutations causing drug resistance would exert a “fitness cost,” rendering those strains too weak to be transmitted (8,9). Nonetheless, transmission of drug-resistant TB strains has now been well-documented (10–13), and laboratory studies have shown that clinical strains may have minimal fitness costs or even none (14). Emerging data suggest that most MDR TB and XDR TB cases in South Africa and worldwide are likely caused by primary transmission of drug-resistant strains (2,15–19).Although the M. tuberculosis W/Beijing strain family has been described among cases of drug-susceptible, MDR TB, and XDR TB in South Africa, numerous other strain types have also been identified (20,21). Little is known about the transmissibility and virulence of M. tuberculosis strains aside from the W/Beijing strain family (22,23). In the Eastern Cape and Western Cape Provinces of South Africa, strains from the W/Beijing family have most often been associated with transmission of drug-resistant TB (24–27). At our study site in KwaZulu-Natal Province, however, the LAM4/KZN strain type has predominated among MDR TB and XDR TB cases and has been linked to nosocomial transmission and high mortality rates (3,16,17,28,29). This strain is a member of the Euro-American strain family and was first described in this region in 1994, evolving into an increasingly resistant phenotype over time (29).The reasons for why the LAM4/KZN strain is prominent in KwaZulu-Natal Province, rather than the Beijing strain, which is seen globally and in other parts of South Africa, is unclear. Moreover, it is unknown whether the higher mortality among patients with MDR TB and XDR TB in KwaZulu-Natal can be explained, in part, by a difference in genotypic prevalence and associated differences in strain virulence (3,6,7,28). In this study, we sought to characterize the genotypic diversity of M. tuberculosis strains among isolates causing drug-susceptible TB, MDR TB, and XDR TB in KwaZulu-Natal Province, South Africa. We also examined the relationship between M. tuberculosis strain, drug resistance, and patient survival.     

Extensively Drug-Resistant Mycobacterium tuberculosis from Aspirates,Rural South Africa

The yield from aspirating lymph nodes and pleural fluid for diagnosing extensively drug-resistant (XDR) tuberculosis is unknown. Mycobacterium tuberculosis was cultured from lymph node or pleural fluid aspirates of 21 patients; 7 (33%) cultures grew XDR M. tuberculosis. Additive diagnostic yield for XDR M. tuberculosis was found in parallel culture of sputum and fluid aspirate.Tuberculosis (TB) is the leading cause of death among HIV-infected persons in sub-Saharan Africa (1). Drug-resistant TB is an emerging public health threat in HIV-prevalent settings, but diagnosis is challenging because of the severely limited laboratory capacity for culture and drug-susceptibility testing (DST). TB diagnosis for HIV-infected patients is particularly challenging because these patients may be more likely to have smear-negative pulmonary disease or extrapulmonary TB (2,3). Extrapulmonary TB often is diagnosed by clinical findings, indirect measures (e.g., chemistry and cell count of cerebrospinal or pleural fluid, ultrasound of lymph nodes, or pericardial effusions), or smear microscopy for acid-fast bacilli from aspirated extrapulmonary fluid. However, drug-resistant TB is impossible to diagnose by these methods, instead requiring mycobacterial culture and DST (4,5).The prevalence of multidrug-resistant and extensively drug-resistant TB (XDR TB) in South Africa has risen exponentially during the past decade. At our rural study site, ≈10% of all TB cases now are drug resistant, and >90% of TB patients are HIV infected (6). Death from XDR TB exceeds 80%; most infected persons die before sputum culture and DST results are known (6). To improve case detection and decrease diagnostic delay of drug-resistant TB among patients with suspected extrapulmonary TB, we initiated a program to aspirate lymph nodes and pleural fluid for culture and DST. We quantified the yield of these lymph node and pleural fluid aspirates for diagnosing XDR TB.     

Double-blind placebo-controlled trial of Mycobacterium vaccae immunotherapy for tuberculosis in KwaZulu, South Africa, 1991-97

To investigate Mycobacterium vaccae immunotherapy in the treatment of human tuberculosis and to assess longer-term outcomes following treatment for tuberculosis patients, a double-blind placebo-controlled Phase-2 clinical trial was set up in the Mseleni and Manguzi health wards in north-eastern KwaZulu, South Africa. In 1991-93, 204 patients admitted with clinical tuberculosis to the 2 hospitals were allocated to receive single intradermal doses of 0.1 mL M. vaccae NCTC 11659 or 0.1 mL tetanus toxoid alongside standard 6-months chemotherapy with rifampicin, isoniazid, pyrazinamide and ethambutol. The main outcome measures were sputum bacteriology culture conversion to negativity, clinical assessment, weight gain, erythrocyte sedimentation rate and chest radiography. Patients were followed-up after 4 years to determine their health status. M. vaccae cases gained weight more quickly during the first 8 weeks compared with 'placebo' patients. Regression analysis found a synergistic relationship between BCG positive scar status and M. vaccae-induced weight gain. No further difference was found between treatment groups. The bacterial conversion rate to negativity at 2 months was much lower than expected (44.8% active, 38.8% placebo). Mortality was considerably higher than expected after treatment (7.1% each group) and after 4 years (25.8% active, 21.0% placebo; death from tuberculosis 14.5% and 16.1%, respectively). Immune sensitization to environmental mycobacteria may explain the geographical variability of M. vaccae efficacy, as occurs with BCG vaccination and occurred with Koch's tuberculins of the late 19th century. Multiple doses of M. vaccae may be more effective. Further work is required to link the ability of M. vaccae to modulate protective cytokine profiles to favourable outcome in clinical studies. The high mortality found in this study suggests urgent reviews of chemotherapy and monitoring of patients are necessary in KwaZulu.     

Extensively drug-resistant tuberculosis in women, KwaZulu-Natal, South Africa

To determine whether women in KwaZulu-Natal, South Africa, with drug-resistant tuberculosis (TB) were more likely than men to have extensively drug-resistant TB, we reviewed 4,514 adults admitted during 2003-2008 for drug-resistant TB. Female sex independently predicted extensively drug-resistant TB, even after we controlled for HIV infection. This association needs further study.     

Assessing the Food Safety Attitudes and Awareness of Managers of School Feeding Programmes in Mpumalanga,South Africa

The managers of school feeding programmes are responsible for ensuring the safety of the food which is provided to schoolchildren, but very few studies have been conducted on the food safety knowledge and awareness of these managers. The objective of this study is to evaluate the food safety attitudes and awareness of managers of the National School Nutrition Programme (NSNP) in schools in Mpumalanga, a province of South Africa. A cross-sectional survey study was conducted in which questionnaires were used to collect data from 300 NSNP food service managers. The majority of schools offering NSNP meals were located in informal settlements and most were found to lack basic resources such as electricity (power supplies to the food preparation facility) and potable tap water in their kitchens. No school was found to have implemented the hazard analysis and critical control points (HACCP) programme, and only a few staff had received food safety training. Food safety implementation is worst in informal schools in rural areas due to limited resources and infrastructure. The NSNP food service managers in some schools—especially those located in rural settlements—were found to have little knowledge and awareness of HACCP. These results indicate an urgent need to provide NSNP managers with food safety training and resources (potable water supplies, electricity, dedicated food preparation facilities), particularly in schools in rural settlements.     

Increasing drug resistance in extensively drug-resistant tuberculosis, South Africa

We expanded second-line tuberculosis (TB) drug susceptibility testing for extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa. Of 19 patients with extensively drug-resistant TB identified during February 2008-April 2009, 13 (68%) had isolates resistant to all 8 drugs tested. This resistance leaves no effective treatment with available drugs in South Africa.     

IS6110 Restriction Fragment Length Polymorphism Typing of Drug-resistant Mycobacterium tuberculosis Strains from Northeast South Africa

Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide; 95% of TB cases, with 98% of death occur in developing countries. The situation in South Africa merits special attention. A total of 21,913 sputum specimens of suspected TB patients from three provinces of South Africa routinely submitted to the TB laboratory of Dr. George Mukhari (DGM) Hospital were assayed for Mycobacterium tuberculosis (MTB) growth and antibiotic susceptibility. The genetic diversity of 338 resistant strains were also studied. DNA isolated from the strains were restricted with Pvu II, transferred on to a nylon membrane and hybridized with a PCR-amplified horseradish peroxidase 245 bp IS6110 probe. Of the 338 resistant strains, 2.09% had less than 5 bands of IS6110, and 98% had 5 or more bands. Unique restriction fragment length polymorphism (RFLP) patterns were observed in 84.3% of the strains, showing their epidemiological independence, and 15.7% were grouped into 22 clusters. Thirty-two strains (61.5%) from the 52 that clustered were from Mpumalanga, 16/52 (30.8%) from Gauteng, and 4/52 (9.6%) from Limpopo province. Clustering was not associated with age. However, strains from male patients in Mpumalanga were more likely to be clustered than strains from male patients in Limpopo and/or Gauteng province. The minimum estimate for the proportion of resistant TB that was due to transmission is 9.06% (52-22=30/331). Our results indicate that transmission of drug-resistant strains may contribute substantially to the emergence of drug-resistant tuberculosis in South Africa.Key words: Drug resistance, Epidemiology, IS6110, M. tuberculosis, PCR-RFLP, South Africa     

Niacin status of schoolchildren in Transvaal Province, South Africa

Niacin status was evaluated in groups of school children (n = 25) in Transvaal Province, South Africa, by measuring the urinary excretion of the metabolite 2-pyridone. In an urban Indian group of low socioeconomic status, and a white middle-class group, 12% and 4% respectively exhibited low or deficient levels of the metabolite. In a rural black village, 28% had evidence of low or deficient levels of niacin, even though two of the 3 locally available brands of maize meal (their dietary staple) claimed to be fortified with nicotinamide. It is concluded that external monitoring of the voluntary maize meal fortification scheme will be necessary to effectively combat deficiency of niacin in traditional maize meal consumers.     

The social epidemiology of tuberculosis in South Africa: a multilevel analysis

Increased risk of tuberculosis is widely recognized to be associated with increased poverty, yet there have been few analyses of the social determinants of tuberculosis, particularly in high-burden settings. We conducted a multilevel analysis of self-reported tuberculosis disease in a nationally representative sample of South Africans based on the 1998 Demographic and Health Survey (DHS). Individual and household-level demographic, behavioral and socioeconomic risk factors were taken from the DHS; data on community-level socioeconomic status (including measures of absolute wealth and income inequality) were derived from the 1996 national census. Of the 13,043 DHS respondents, 0.5% reported having been diagnosed with tuberculosis disease in the past 12 months and 2.8% reported having been diagnosed with tuberculosis disease in their lifetime. In a multivariate model adjusting for demographic and behavioral risk factors, tuberculosis diagnosis was associated with cigarette smoking, alcohol consumption and low body mass index, as well as a lower level of personal education, unemployment and lower household wealth. In a model including individual- and household-level risk factors, high levels of community income inequality were independently associated with increased prevalence of tuberculosis (adjusted odds ratio for lifetime tuberculosis comparing the most unequal quintile to the middle quintile of inequality: 2.37, 95% confidence interval: 1.59-3.53). These results provide novel insights into the socioeconomic determinants of tuberculosis in developing country settings, although the mechanisms through which income inequality may affect tuberculosis disease require further investigation.     

High prevalence of tuberculosis in previously treated patients, Cape Town, South Africa

The tuberculosis (TB) notification rate is high and increasing in 2 communities in Cape Town, South Africa. In 2002, we conducted a prevalence survey among adults > or = 15 years of age to determine the TB prevalence rate; 15% of households in these communities were randomly sampled. All persons living in sampled households were eligible for chest radiography and sputum examination. Of the 3,483 adults who completed a questionnaire, 2,608 underwent chest radiography and sputum examination. We detected 26 bacteriologically confirmed TB cases and a prevalence of 10.0/1,000 (95% confidence interval [CI] 6.2-13.8 per 1,000). We found 18 patients with smear-positive TB, of whom 8 were new patients (3.1/1,000, 95% CI 0.9-5.1/1,000). More than half of patients with smear-positive TB (10, 56%) had previously been treated. Such patients may contribute to transmission of Mycobacterium tuberculosis and the high TB prevalence rate. Successful treatment of TB patients must be a priority.     

Pilot study to develop a rapid assessment of tuberculosis care-seeking and adherence practices in rural Limpopo Province, South Africa

Studies of factors influencing tuberculosis (TB) care-seeking and treatment adherence in high TB/HIV co-burden African countries have typically surveyed urban patients' sociodemographic characteristics. To understand community perceptions and guide rapid assessment interviews, we interviewed key informants (nurses, tribal leaders, n = 9) and local researchers (n = 3) in poor, rural areas of South Africa. HIV-related stigma and misperceptions about TB causes and symptoms were cited as barriers. Key informants said older people preferred traditional healers; local researchers heard a preference for "western" care and suggested supporting clinic staff travel to remote villages with health education and diagnostic services. Key informants said not understanding the consequences of incomplete treatment and reluctance to relinquish disability grants decreased adherence. All reported that nonfamily DOTS supporters provided invaluable support. Rapid assessment should include drop-outs, re-treated, and co-infected patients and ask questions examining origins of misperceptions, stigma of testing, and pre-test messages to improve community perceptions about TB care-seeking and treatment adherence.     

Impact of climate change on children's health in Limpopo Province, South Africa

This paper examines the impact of climate change on children's health, in the Limpopo Province of South Africa. Twenty one years climatic data were collected to analyse climatic conditions in the province. The study also employs 12 years hospital records of clinically diagnosed climate-related ailments among children under 13 years to examine the incidence, spatio-temporal, age and sex variations of the diseases. Regression analysis was employed to examine the relationships between climatic parameters and incidence of diseases and also to predict distribution of disease by 2050. The results show that the most prevalent diseases were diarrhea (42.4%), followed by respiratory infection (31.3%), asthma (6.6%) and malaria (6.5%). The incidence varied within city, with the high density areas recording the highest proportion (76.7%), followed by the medium (9.4%) and low (2.5%) density residential areas. The most tropical location, Mussina, had the highest incidence of the most prevalent disease, diarrhea, with 59.4%. Mortality rate was higher for males (54.2%). Analysis of 21 years of climatic data show that maximum temperature is positively correlated with years in four cities with r coefficients of 0.50; 0.56, 0.48 and 0.02, thereby indicating local warming. Similarly rainfall decreased over time in all the cities, with r ranging from -0.02 for Bela Bela to r = 0.18 for Makhado. Results of the regression analysis show that 37.9% of disease incidence is accounted for by the combined influence of temperature and rainfall.     

河南省临床分离的553株结核分枝杆菌基因分型研究

目的了解河南省结核分枝杆菌基因类型分布及主要流行基因群。方法对河南省各地市分离的553株结核分枝杆菌临床分离株采用间隔区寡核苷酸分型方法(spoligotyping)进行基因分型。分型结果与SITVIT数据库进行比对,并用Bionumeric 7.6软件进行基因聚类分析。结果 553株结核分枝杆菌Spoligotyping分型后与SITVIT数据库比对后得到46种不同的基因型,其中33种型别有对应的SIT编号,剩下的13种未在数据库找到与其匹配的型别。553株菌除了14(2.53%)株菌基因型没有对应的家族用UN表示外,余下536株菌分别属于4个不同的家族,其中Beijing家族共481株,占总数的86.98%;其次是T家族共53株,占总数的9.58%;MANU家族2株(0.36%)(MANU2);LAM家族1株(0.18%)(T5RUS1)。结论河南省结核分枝杆菌基因型别呈现多样性,北京家族和T家族为主要的流行基因群。     

Transmission of tuberculosis in a high incidence urban community in South Africa

BACKGROUND: The objective of this study was to identify risk factors for ongoing community transmission of tuberculosis (TB) in two densely populated urban communities with a high incidence rate of TB in Cape Town, South Africa. METHODS: Between 1993 and 1998 DNA fingerprints of mycobacterial isolates from TB patients were determined by restriction fragment length polymorphism (RFLP). Cases whose isolates shared identical fingerprint patterns were considered to belong to the same cluster and to be attributable to ongoing community transmission. RESULTS: The average annual notification rate of new smear positive TB was 238/100000. In all, 1023/1526 reported patients were culture positive, and RFLP was available for 768 (75%) of the isolates from these patients. Since some patients experienced more than one infection during the study period, 797 cases were included in the analysis. Of the cases, 575/797 (72%) were clustered. Smear-positive cases and those who were retreated after default were more likely to be clustered than smear-negative and new cases, respectively. Patients from Uitsig were more often part of large clusters than were patients from Ravensmead. Age, sex, year of diagnosis, and outcome of disease were not risk factors for clustering, nor for being the first case in a cluster, although various analytical approaches were used. CONCLUSIONS: The incidence and proportion of cases that are clustered in this area are higher than reported elsewhere. An overwhelming majority of TB cases in this area is attributed to ongoing community transmission, and only very few to reactivation. This may explain the lack of demographic risk factors for clustering.