Strengthening surgical and anaesthetic services at district level in the African region: issues, challenges and proposed actions

Health care delivery systems are organized at several levels with the district hospital serving as the first referral for comprehensive care in the majority of countries worldwide. The provision of comprehensive surgical services requires several inputs and tools to be in place, among which are an adequately trained surgical, anaesthesia and obstetric healthcare workforce, infrastructure and functioning equipment, and essential medicines and supplies. These, however, are not in place in the majority of commonly received surgical cases, such as trauma, obstetric, abdominal and orthopedic emergencies, thus limiting the capacity of district hospitals to address them. Global and regional public health initiatives have traditionally neglected the necessity of the provision of surgical services despite the fact that these constitute an essential component of comprehensive primary healthcare (PHC)1. In fact, because surgery so frequently cannot be safely postponed, this deficiency prevents the transfer of patients to a secondary or tertiarylevel hospital where further care can be provided.

The virological durability of first-line ART among HIV-positive adult patients in resource limited settings without virological monitoring: a retrospective analysis of DART trial data.

BACKGROUND: Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. METHODS: DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models. RESULTS: Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32-42) and with a median CD4 cell count of 86 (32-140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI) -non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38-0.62; p < 0.0001). In multivariate analyses, female patients (HR = 0.79, 95% CI: 0.65-0.95; p = 0.02), older patients (HR = 0.73 per 10 years, 95% CI: 0.64-0.84; p < 0.0001) and patients with a higher pre-ART CD4 cell count (HR = 0.64 per 100 cells/mm3, 95% CI: 0.54-0.75; p < 0.0001) had a lower incidence of virological failure after adjusting for adherence to ART. No difference in failure rate between the two randomised monitoring strategies was observed (p= 0.25). CONCLUSIONS: The long-term durability of virological suppression on dual-class NRTI-NNRTI first-line ART without virological monitoring is remarkable and is enabled by high-quality clinical management and a consistent drug supply. To achieve higher rates of virological suppression viral-load-informed differentiated care may be required. TRIAL REGISTRATION: Prospectively registered on 18/10/2000 as ISRCTN13968779

Geo-additive modelling of malaria in Burundi

Abstract Background Malaria is a major public health issue in Burundi in terms of both morbidity and mortality, with around 2.5 million clinical cases and more than 15,000 deaths each year. It is still the single main cause of mortality in pregnant women and children below five years of age. Because of the severe health and economic burden of malaria, there is still a growing need for methods that will help to understand the influencing factors. Several studies/researches have been done on the subject yielding different results as which factors are most responsible for the increase in malaria transmission. This paper considers the modelling of the dependence of malaria cases on spatial determinants and climatic covariates including rainfall, temperature and humidity in Burundi. Methods The analysis carried out in this work exploits real monthly data collected in the area of Burundi over 12 years (1996-2007). Semi-parametric regression models are used. The spatial analysis is based on a geo-additive model using provinces as the geographic units of study. The spatial effect is split into structured (correlated) and unstructured (uncorrelated) components. Inference is fully Bayesian and uses Markov chain Monte Carlo techniques. The effects of the continuous covariates are modelled by cubic p-splines with 20 equidistant knots and second order random walk penalty. For the spatially correlated effect, Markov random field prior is chosen. The spatially uncorrelated effects are assumed to be i.i.d. Gaussian. The effects of climatic covariates and the effects of other spatial determinants are estimated simultaneously in a unified regression framework. Results The results obtained from the proposed model suggest that although malaria incidence in a given month is strongly positively associated with the minimum temperature of the previous months, regional patterns of malaria that are related to factors other than climatic variables have been identified, without being able to explain them. Conclusions In this paper, semiparametric models are used to model the effects of both climatic covariates and spatial effects on malaria distribution in Burundi. The results obtained from the proposed models suggest a strong positive association between malaria incidence in a given month and the minimum temperature of the previous month. From the spatial effects, important spatial patterns of malaria that are related to factors other than climatic variables are identified. Potential explanations (factors) could be related to socio-economic conditions, food shortage, limited access to health care service, precarious housing, promiscuity, poor hygienic conditions, limited access to drinking water, land use (rice paddies for example), displacement of the population (due to armed conflicts).</p

Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

Objectives We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus. Results HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. Conclusions Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility

Bayesian modelling of the effect of climate on malaria in Burundi

<p>Abstract</p> <p>Background</p> <p>In Burundi, malaria is a major public health issue in terms of both morbidity and mortality with around 2.5 million clinical cases and more than 15,000 deaths each year. It is the single main cause of mortality in pregnant women and children below five years of age. Due to the severe health and economic cost of malaria, there is still a growing need for methods that will help to understand the influencing factors. Several studies have been done on the subject yielding different results as which factors are most responsible for the increase in malaria. The purpose of this study has been to undertake a spatial/longitudinal statistical analysis to identify important climatic variables that influence malaria incidences in Burundi.</p> <p>Methods</p> <p>This paper investigates the effects of climate on malaria in Burundi. For the period 1996-2007, real monthly data on both malaria epidemiology and climate in the area of Burundi are described and analysed. From this analysis, a mathematical model is derived and proposed to assess which variables significantly influence malaria incidences in Burundi. The proposed modelling is based on both generalized linear models (GLM) and generalized additive mixed models (GAMM). The modelling is fully Bayesian and inference is carried out by Markov Chain Monte Carlo (MCMC) techniques.</p> <p>Results</p> <p>The results obtained from the proposed models are discussed and it is found that malaria incidence in a given month in Burundi is strongly positively associated with the minimum temperature of the previous month. In contrast, it is found that rainfall and maximum temperature in a given month have a possible negative effect on malaria incidence of the same month.</p> <p>Conclusions</p> <p>This study has exploited available real monthly data on malaria and climate over 12 years in Burundi to derive and propose a regression modelling to assess climatic factors that are associated with monthly malaria incidence. The results obtained from the proposed models suggest a strong positive association between malaria incidence in a given month and the minimum temperature (night temperature) of the previous month. An open question is, therefore, how to cope with high temperatures at night.</p

Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa.

Background: Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. Patients and methods: A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). Results: At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-treated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 (3.4, P  =   0.01). There was a small reduction in tenofovir susceptibility (FC 0.7 and 1.0, respectively, P  =   0.18). Conclusions: Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring

Improving a Mother to Child HIV Transmission Programme through Health System Redesign: Quality Improvement, Protocol Adjustment and Resource Addition

Health systems that deliver prevention of mother to child transmission (PMTCT) services in low and middle income countries continue to underperform, resulting in thousands of unnecessary HIV infections of newborns each year. We used a combination of approaches to health systems strengthening to reduce transmission of HIV from mother to infant in a multi-facility public health system in South Africa.All primary care sites and specialized birthing centers in a resource constrained sub-district of Cape Metro District, South Africa, were enrolled in a quality improvement (QI) programme. All pregnant women receiving antenatal, intrapartum and postnatal infant care in the sub-district between January 2006 and March 2009 were included in the intervention that had a prototype-innovation phase and a rapid spread phase. System changes were introduced to help frontline healthcare workers to identify and improve performance gaps at each step of the PMTCT pathway. Improvement was facilitated and spread through the use of a Breakthrough Series Collaborative that accelerated learning and the spread of successful changes. Protocol changes and additional resources were introduced by provincial and municipal government. The proportion of HIV-exposed infants testing positive declined from 7.6% to 5%. Key intermediate PMTCT processes improved (antenatal AZT increased from 74% to 86%, PMTCT clients on HAART at the time of labour increased from 10% to 25%, intrapartum AZT increased from 43% to 84%, and postnatal HIV testing from 79% to 95%) compared to baseline.System improvement methods, protocol changes and addition/reallocation of resources contributed to improved PMTCT processes and outcomes in a resource constrained setting. The intervention requires a clear design, leadership buy-in, building local capacity to use systems improvement methods, and a reliable data system. A systems improvement approach offers a much needed approach to rapidly improve under-performing PMTCT implementation programmes at scale in sub-Saharan Africa

A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447]

BACKGROUND: Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown. METHODS: In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ(2 )tests and logistic regression. We analysed continuous variables using Wilcoxon's tests. RESULTS: Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects. CONCLUSION: Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined

Evaluation of equity in informal land development systems in two Nigerian cities

The informal land development system in Sub-Saharan Africa (SSA) is perceived to promote equity and could be leveraged to support sustainable urban development and management. However, scanty empirical evidence exists on the extent of the system’s provision of equity to support policy formulation and practice in the region. Based on stakeholder workshops, focus group discussions and questionnaire surveys, this study analyses the system’s provision of equity in Nigeria. The study finds all categories of people undertake informal developments. Consistent with literature, this finding reflects wide patronage of the informal land development system and its relevance. Nevertheless, contrary to the existing perception, the system’s provision of equity is low. The study recommends for the institution of pro-poor and gender sensitive land development and management policies and programmes to increase the levels of equity to support the achievement of the country’s sustainable urban development and management agenda