Introduction: The six-month course of isoniazid preventive therapy (IPT) has been demonstrated to have significant benefits in mitigating the occurrence of tuberculosis (TB), particularly in high TB burden settings. However, its implementation in Sub-Saharan countries remains subdued for obscure reasons. This study investigated the factors inhibiting IPT uptake in the sub-Saharan country of Lesotho, which has one of the highest rates of TB incidences globally. Material and methods: Data were obtained from 46 healthcare workers, key informants at the Ministry of Health of Lesotho, and representatives of partner organizations, who were purposively selected for their roles in IPT implementation. Data were coded to identify themes, and the emerging themes were benchmarked to previous typologies for evaluating the implementation of best practices in health interventions, namely effectiveness, reach, sustainability, and adaptation. Each major theme was further linked to the World Health Organization's 'six building blocks of a health system'. Results: Challenges affecting the implementation of IPT were as follows: ineffective TB screening due to challenged decentralization of human immunodeficiency virus (HIV)/TB services, late detection of side effects linked to weak monitoring systems, and inefficient health information systems. Further challenges in the health system included interrupted supply chains due to insufficient health system financing, while inadequate healthcare workers' education on IPT implementation was also noted. Conclusions: These findings indicate that a wide spectrum of challenges has affected the implementation of IPT in Lesotho, and this indicates the need for 'health systems approach' to the implementation of IPT in Lesotho and other countries with similar challenges.

Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria −42; fungi −19; plant −28; animal −22; plant and animal −1 and common P450 family −1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study’s results offer new understanding of the dynamic structural nature of P450s.

Background: Tuberculosis (TB) remains a public health problem, particularly in people living with human immunodeficiency virus (PLHIV). Yet, efforts to reduce TB incidence using isoniazid preventive therapy (IPT) have been curtailed by poor uptake of this intervention. This study reviewed the rate of IPT initiation in the sub-Saharan country of Lesotho, which has one of the highest TB incidences in the world.Methods: Time to IPT initiation in randomly sampled medical records of PLHIV was analysed using Cox’s proportional hazards regression. Differences in the periods of enrolment into Human immunodeficiency virus (HIV) care were controlled for by considering the year IPT was launched (2011) as the base year and stratifying the medical records into the 2004–2010 cohort (before the launch of IPT) and the 2011–2016 cohort (after the launch).Results: Out of 2955 patients included in the final analysis, 68.8% had received IPT by the study exit time. However, the overall rate of IPT initiation was 20.6 per 100 person-years, with 135 (6.6%) treatment interruptions. Compared to the 2004–2010 cohort, the 2011–2016 had a significantly (p 0.05) higher rate of initiation (15.8 vs. 27.0 per 100 person-years, respectively). Age group, district category and duration of antiretroviral therapy emerged as the most significant predictors of IPT initiation, while district category and gender significantly predicted IPT therapy interruption.Conclusion: These findings indicate a high uptake of IPT with a slow rate of implementation. Significant factors associated with disparities in the initiation and interruption of IPT therapy in this study are important for policy review.

Background: The South African Expanded Programme on Immunisation (EPI-SA) currently vaccinates against 10 childhood vaccine preventable diseases. Six injections are required for primary vaccination against diphtheria, tetanus, pertussis, polio, Haemophilus influenza type b and hepatitis B: three DTaP-IPV//Hib [Pentaxim ® ] doses and three monovalent Hep B vaccines to children under 12 months of age, with a seventh injection (Pentaxim ® booster) at 18 months. Madhi et al (PIDJ 30:e68 2011) demonstrated no significant difference in the safety and efficacy between Pentaxim ® plus monovalent Hep B and a new fully liquid hexavalent vaccine, Hexaxim ® (DTaP-IPV-Hib-HepB). From a healthcare provider perspective, combination vaccines could reduce costs, simplify logistics and delivery infrastructure, and improve coverage with fewer injections. This study aimed to analyse the cost implications of a switch from the current combination of Pentaxim ® plus monovalent Hep B injections, to a single Hexaxim ® injection, from the public sector perspective. Methods & Materials: Data were collected to derive direct costs, i.e. vaccines' prices (except Hexaxim ® , no price yet available), transportation charges, cold chain storage, vaccine wastage rate, hazardous waste disposal and vaccine administration. All costs were calculated per dose, and expressed in South African Rand (R) (USD 1.00 = R10.19 per 2013 exchange rate). Indirect costs such as individual and societal benefits were excluded. Results: Delivering one dose ofPentaxim ® and Hep B costs R166.30. Reduced volumes result in cost reductions when using Hexaxim ® for: cold storage; hazardous waste disposal; and vaccine administration, resulting in an estimated saving of R10.52 to R29.40 per dose, depending on utilisation of usable cold storage space. Conclusion: Implementation of Hexaxim ® within EPI-SA is highly recommended, because it reduces healthcare provider costs by simplifying logistics and delivery infrastructure. From a community perspective, such vaccines reduce clinic visits, vaccinators' errors, number of injections and side effects, which translate to better acceptability, convenience and increased compliance. As the use of Hexaxim ® demonstrates direct and indirect cost savings, potential public sector introduction should be valued not only in terms of the price of Pentaxim ® and Hep B.

IntroductionThe government of Lesotho introduced tenofovir disoproxil fumarate (TDF) for first-line antiretroviral treatment (ART), as recommended by the World Health Organization (1), in 2008. The use of TDF has been associated with renal toxicity (2); furthermore, renal function outcomes following the use of TDF has not been studied at Roma Health Service Area (RHSA) in Lesotho. Lesotho is a small landlocked country surrounded by South Africa. The study used an analytical design to compare retrospective creatinine clearance (CrCl) data of 312 (64%) antiretroviral treatment naïve adults exposed to TDF and 173 (36%) unexposed patients.MethodsImpaired renal function was defined as CrCl less than 50 mL/min calculated using the Cockcroft-Gault equation. The Ministry of Health and Social Welfare of Lesotho approved the study on 13 January 2012. The study included adult (excluding pregnant females) HIV patients enrolled on ART between December 2006 and December 2012 at St Joseph's Mission Hospital and at Nazareth Health Centre (RHSA). Patients at Nazareth Health Centre and at St Joseph's Mission Hospital made up 80% of the circa 4 116 HIV patients on ART. Only 485 patients met the set inclusion criteria.ResultsIn 56 patients (17.9%), TDF was found to be contraindicated. The use of TDF was marginally significant factor for renal toxicity (p=0.054) in univariate analysis, but was insignificant (p=0.122) in multivariate logistic analysis. Univariate (p<0.1) and multivariate logistic regression (p<0.05) were performed using STATA® 11. Female gender (p=0.016), hypertension (p=0.009), and age>60 (p=0.004) were significantly associated with CrCl<50 mL/min outcome.ConclusionsIn this study, TDF proofed to be a weak contributing factor of renal impairment. Routine baseline renal function screening should however be adopted to prevent patients with impaired renal function receiving TDF.