From habits of attrition to modes of inclusion: enhancing the role of private practitioners in routine disease surveillance

Background: Private practitioners are the preferred first point of care in a majority of low and middle-income countries and in this position, best placed for the surveillance of diseases. However their contribution to routine surveillance data is marginal. This systematic review aims to explore evidence with regards to the role, contribution, and involvement of private practitioners in routine disease data notification. We examined the factors that determine the inclusion of, and the participation thereof of private practitioners in disease surveillance activities. Methods: Literature search was conducted using the PubMed, Web of Knowledge, WHOLIS, and WHO-IRIS databases to identify peer reviewed and gray full-text documents in English with no limits for year of publication or study design. Forty manuscripts were reviewed. Results: The current participation of private practitioners in disease surveillance efforts is appalling. The main barriers to their participation are inadequate knowledge leading to unsatisfactory attitudes and misperceptions that influence their practices. Complicated reporting mechanisms with unclear guidelines, along with unsatisfactory attitudes on behalf of the government and surveillance program managers also contribute to the underreporting of cases. Infrastructural barriers especially the availability of computers and skilled human resources are critical to improving private sector participation in routine disease surveillance. Conclusion: The issues identified are similar to those for underreporting within the Integrated infectious Disease Surveillance and Response systems (IDSR) which collects data mainly from public healthcare facilities. We recommend that surveillance program officers should provide periodic training, supportive supervision and offer regular feedback to the practitioners from both public as well as private sectors in order to improve case notification. Governments need to take leadership and foster collaborative partnerships between the public and private sectors and most importantly exercise regulatory authority where needed

Genetic Organisation, Mobility and Predicted Functions of Genes on Integrated, Mobile Genetic Elements in Sequenced Strains of Clostridium difficile

Background: Clostridium difficile is the leading cause of hospital-associated diarrhoea in the US and Europe. Recently the incidence of C. difficile-associated disease has risen dramatically and concomitantly with the emergence of 'hypervirulent' strains associated with more severe disease and increased mortality. C. difficile contains numerous mobile genetic elements, resulting in the potential for a highly plastic genome. In the first sequenced strain, 630, there is one proven conjugative transposon (CTn), Tn5397, and six putative CTns (CTn1, CTn2 and CTn4-7), of which, CTn4 and CTn5 were capable of excision. In the second sequenced strain, R20291, two further CTns were described.Results: CTn1, CTn2 CTn4, CTn5 and CTn7 were shown to excise from the genome of strain 630 and transfer to strain CD37. A putative CTn from R20291, misleadingly termed a phage island previously, was shown to excise and to contain three putative mobilisable transposons, one of which was capable of excision. In silico probing of C. difficile genome sequences with recombinase gene fragments identified new putative conjugative and mobilisable transposons related to the elements in strains 630 and R20291. CTn5-like elements were described occupying different insertion sites in different strains, CTn1-like elements that have lost the ability to excise in some ribotype 027 strains were described and one strain was shown to contain CTn5-like and CTn7-like elements arranged in tandem. Additionally, using bioinformatics, we updated previous gene annotations and predicted novel functions for the accessory gene products on these new elements.Conclusions: The genomes of the C. difficile strains examined contain highly related CTns suggesting recent horizontal gene transfer. Several elements were capable of excision and conjugative transfer. The presence of antibiotic resistance genes and genes predicted to promote adaptation to the intestinal environment suggests that CTns play a role in the interaction of C. difficile with its human host

Detection of bacterial blight resistant gene xa5 using linked marker approaches

Rice is the primary source of food for 57% of the world’s population. Genetic resistance is important to control many kinds of pathogenic diseases. Bacterial blight caused by Xanthomonas oryzae pv oryzae(Xoo) decreases rice production by 20 – 30% and up to about 90% loss of grain weight. xa5 is an important recessive bacterial blight resistant gene, which is effective and important in Asian rice breeding program. It was also used in combination by incorporation with various recessive anddominant BB resistant genes. The purpose of our study was to identify the bacterial blight resistant genes xa5 in Pakistani rice germplasm including Basmati varieties. The seeds were collected from different research institute and then sowed in the National Institute for Biotechnology and Genetic Engineering (NIBGE) in pots. DNAs were extracted and surveyed for polymorphism by using DNA marker linked to xa5 gene. During this polymorphic survey, out of 88 germplasm lines, 45 lines showed the presence of xa5 gene like MB 2, MB 33 MB 57 and MB 66. All these lines showed the amplification of 240 bp corresponding to resistant source IRBB-5 line, while 43 germplasm lines showed no such fragment and elucidated same bands as susceptible source IR-24 having fragment of about 230 base pair. The 10 Pakistani Basmati varieties were also surveyed for xa5 gene. It was observed that none of our cultivated basmati varieties exhibited the presence of xa5 gene. The purpose of screening of xa5 gene in Pakistani rice germplasm is to utilize the local source of xa5 gene for elite molecular breeding program being carried out at NIBGE in future including pyramiding of different disease resistant gene in Basmati varieties

HIV-1 subtype A infection in a community of intravenous drug users in Pakistan

BACKGROUND: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. METHODS: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA). RESULTS: We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. CONCLUSION: Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country

Resource allocation within the National AIDS Control Program of Pakistan: a qualitative assessment of decision maker's opinions

BACKGROUND: Limited resources, whether public or private, demand prioritisation among competing needs to maximise productivity. With a substantial increase in the number of reported HIV cases, little work has been done to understand how resources have been distributed and what factors may have influenced allocation within the newly introduced Enhanced National AIDS Control Program of Pakistan. The objective of this study was to identify perceptions of decision makers about the process of resource allocation within Pakistan's Enhanced National AIDS Control Program. METHODS: A qualitative study was undertaken and in-depth interviews of decision makers at provincial and federal levels responsible to allocate resources within the program were conducted. RESULTS: HIV was not considered a priority issue by all study participants and external funding for the program was thought to have been accepted because of poor foreign currency reserves and donor agency influence rather than local need. Political influences from the federal government and donor agencies were thought to manipulate distribution of funds within the program. These influences were thought to occur despite the existence of a well-laid out procedure to determine allocation of public resources. Lack of collaboration among departments involved in decision making, a pervasive lack of technical expertise, paucity of information and an atmosphere of ad hoc decision making were thought to reduce resistance to external pressures. CONCLUSION: Development of a unified program vision through a consultative process and advocacy is necessary to understand goals to be achieved, to enhance program ownership and develop consensus about how money and effort should be directed. Enhancing public sector expertise in planning and budgeting is essential not just for the program, but also to reduce reliance on external agencies for technical support. Strengthening available databases for effective decision making is required to make financial allocations based on real, rather than perceived needs. With a large part of HIV program funding dedicated to public-private partnerships, it becomes imperative to develop public sector capacity to administer contracts, coordinate and monitor activities of the non-governmental sector

Share of afghanistan populace in hepatitis B and hepatitis C infection's pool: is it worthwhile?

There is a notable dearth of data about Hepatitis B Virus (HBV) and Hepatitis C Virus(HCV) prevalence in Afghanistan. Awareness program and research capacity in the field of hepatitis are very limited in Afghanistan. Number of vulnerabilities and patterns of risk behaviors signal the need to take action now

TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities.

The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders. TMX2 encodes one of the five TMX proteins of the protein disulfide isomerase family, hitherto not linked to human developmental brain disease. Our mechanistic studies on protein function show that TMX2 localizes to the ER mitochondria-associated membranes (MAMs), is involved in posttranslational modification and protein folding, and undergoes physical interaction with the MAM-associated and ER folding chaperone calnexin and ER calcium pump SERCA2. These interactions are functionally relevant because TMX2-deficient fibroblasts show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity. Intriguingly, under basal conditions TMX2 occurs in both reduced and oxidized monomeric form, while it forms a stable dimer under treatment with hydrogen peroxide, recently recognized as a signaling molecule in neural morphogenesis and axonal pathfinding. Exogenous expression of the pathogenic TMX2 variants or of variants with an in vitro mutagenized TRX domain induces a constitutive TMX2 polymerization, mimicking an increased oxidative state. Altogether these data uncover TMX2 as a sensor in the MAM-regulated redox signaling pathway and identify it as a key adaptive regulator of neuronal proliferation, migration, and organization in the developing brain