C Hutchison

Efficacy of malaria prevention during pregnancy in an area of low and unstable transmission: an individually-randomised placebo-controlled trial using intermittent preventive treatment and insecticide-treated nets in the Kabale Highlands, southwestern Uganda

Intermittent preventive treatment of malaria during pregnancy (IPTp) and insecticide-treated nets (ITN) are recommended malaria interventions during pregnancy; however, there is limited information on their efficacy in areas of low malaria transmission in sub-Saharan Africa. An individually-randomised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp, ITNs alone, or ITNs used in combination with IPTp on maternal anaemia and low birth weight (LBW) in a highland area of southwestern Uganda. The overall prevalence of malaria infection, maternal anaemia and LBW was 15.0%, 14.7% and 6.5%, respectively. Maternal and fetal outcomes were generally remarkably similar across all intervention groups (P>0.05 for all outcomes examined). A marginal difference in maternal haemoglobin was observed in the dual intervention group (12.57g/dl) compared with the IPTp and ITN alone groups (12.40g/dl and 12.44g/dl, respectively; P=0.04), but this was too slight to be of clinical importance. In conclusion, none of the preventive strategies was found to be superior to the others, and no substantial additional benefit to providing both IPTp and ITNs during routine antenatal services was observed. With ITNs offering a number of advantages over IPTp, yet showing comparable efficacy, we discuss why ITNs could be an appropriate preventive strategy for malaria control during pregnancy in areas of low and unstable transmission.

Introducing rapid tests for malaria into the retail sector: what are the unintended consequences?

The observation that many people in Africa seek care for febrile illness in the retail sector has led to a number of public health initiatives to try to improve the quality of care provided in these settings. The potential to support the introduction of rapid diagnostic tests for malaria (mRDTs) into drug shops is coming under increased scrutiny. Those in favour argue that it enables the harmonisation of policy around testing and treatment for malaria and maintains a focus on market-based solutions to healthcare. Despite the enthusiasm among many global health actors for this policy option, there is a limited understanding of the consequences of the introduction of mRDTs in the retail sector. We undertook an interpretive, mixed methods study with drug shop vendors (DSVs), their clients and local health workers to explore the uses and interpretations of mRDTs as they became part of daily practice in drug shops during a trial in Mukono District, Uganda. This paper reports the unintended consequences of their introduction. It describes how the test engendered trust in the professional competence of DSVs; was misconstrued by clients and providers as enabling a more definitive diagnosis of disease in general rather than malaria alone; that blood testing made drug shops more attractive places to seek care than they had previously been; was described as shifting treatment-seeking behaviour away from formal health centres and into drug shops; and influenced an increase in sales of medications, particularly antibiotics. Trial registration number NCT01194557; Results.

Financial barriers and coping strategies: a qualitative study of accessing multidrug-resistant tuberculosis and tuberculosis care in Yunnan, China.

BackgroundTuberculosis (TB) and multidrug-resistance tuberculosis (MDR-TB) pose serious challenges to global health, particularly in China, which has the second highest case burden in the world. Disparities in access to care for the poorest, rural TB patients may be exacerbated for MDR-TB patients, although this has not been investigated widely. We examine whether certain patient groups experience different barriers to accessing TB services, whether there are added challenges for patients with MDR-TB, and how patients and health providers cope in Yunnan, a mountainous province in China with a largely rural population and high TB burden.MethodsUsing a qualitative study design, we conducted five focus group discussions and 47 in-depth interviews with purposively sampled TB and MDR-TB patients and healthcare providers in Mandarin, between August 2014 and May 2015. Field-notes and interview transcripts were analysed via a combination of open and thematic coding.ResultsPatients and healthcare providers consistently cited financial constraints as the most common barriers to accessing care. Rural residents, farmers and ethnic minorities were the most vulnerable to these barriers, and patients with MDR-TB reported a higher financial burden owing to the centralisation and longer duration of treatment. Support in the form of free or subsidised treatment and medical insurance, was deemed essential but inadequate for alleviating financial barriers to patients. Most patients coped by selling their assets or borrowing money from family members, which often strained relationships. Notably, some healthcare providers themselves reported making financial and other contributions to assist patients, but recognised these practices as unsustainable.ConclusionsFinancial constraints were identified by TB and MDR-TB patients and health care professionals as the most pervasive barrier to care. Barriers appeared to be magnified for ethnic minorities and patients coming from rural areas, especially those with MDR-TB. To reduce financial barriers and improve treatment outcomes, there is a need for further research into the total costs of seeking and accessing TB and MDR-TB care. This will enable better assessment and targeting of appropriate financial support for identified vulnerable groups and geographic development of relevant services.

Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts.

Preventing emergence of drug resistant tuberculosis in Myanmar's transitioning health system.

Multidrug-resistant tuberculosis (MDR-TB) is a particular threat to the populations of resource-limited countries. Although inadequate treatment of TB has been identified as a major underlying cause of drug resistance, essential information to inform changes in health service delivery and policy is missing. We investigate factors that may be driving the emergence of MDR-TB in Myanmar, a country where investment and health system reforms are ongoing to address the unexplained, high occurrence of MDR-TB. We conducted a multi-centre, retrospective case-control study in 10 townships across Yangon. Cases were 202 GeneXpert-confirmed MDR-TB patients with a history of prior first-line treatment for TB. Controls were 404 previously untreated smear-microscopy confirmed TB patients who had no evidence of resistance to anti-TB drugs. Information on patient and health service factors was collected through face-to-face patient interviews and hospital record reviews. Multivariable logistic regression analysis indicated that the following TB patient groups are at higher risk of developing MDR-TB after initial TB treatment: those who have diabetes (aOR 2.10; 95% CI 1.17-3.76), those who missed taking drugs during the initial treatment more than once weekly (aOR 2.35; 95% CI 1.18-4.65) and those with a higher socioeconomic (aOR 1.99; 95% CI 1.09-3.63) or educational status (aOR 1.78; 95% CI1.01-3.13). Coinciding with a surge in funding to improve health in Myanmar, this study identifies practices of patients and healthcare organizations that can be addressed, and high-risk TB patient groups that can be prioritized for treatment support. Specifically, the study shows that TB patients who experience frequent, short interruptions in treatment and those with diabetes may require enhanced treatment support and monitoring by health services in order to prevent further generation of drug resistance.

Risk factors that may be driving the emergence of drug resistance in tuberculosis patients treated in Yangon, Myanmar

Background The majority of new tuberculosis cases emerging every year occur in low and middle-income countries where public health systems are often characterised by weak infrastructure and inadequate resources. This study investigates healthcare seeking behaviour, knowledge and treatment of tuberculosis patients in Myanmar—which is facing an acute drug-resistant tuberculosis epidemic—and identifies factors that may increase the risk of emergence of drug-resistant tuberculosis. Methods We randomly selected adult smear-positive pulmonary tuberculosis patients diagnosed between September 2014 and March 2015 at ten public township health centres in Yangon, the largest city in Myanmar. Data on patients’ healthcare seeking behaviour, treatment at the township health centres, co-morbidities and knowledge was collected through patient interviews and extraction from hospital records. A retrospective descriptive cross-sectional analysis was conducted. Results Of 404 TB patients selected to participate in the study, 11 had died since diagnosis, resulting in 393 patients being included in the final analysis. Results indicate that a high proportion of patients (16%; 95% CI = 13–20) did not have a treatment supporter assigned to improve adherence to medication, with men being more likely to have no treatment supporter assigned. Use of private healthcare providers was very common; 59% (54–64) and 30.3% (25.9–35.0) of patients reported first seeking care at private clinics and pharmacies respectively. We found that 8% (6–11) of tuberculosis patients had confirmed diabetes. Most patients had some knowledge about tuberculosis transmission and the consequences of missing treatment. However, 5% (3–8) stated that they miss taking tuberculosis medicines at least weekly, and patients with no knowledge of consequences of missing treatment were more likely to miss doses. Conclusions This study analysed healthcare seeking behaviour and treatment related practices of tuberculosis patients being managed under operational conditions in a fragile health system. Findings indicate that ensuring that treatment adherence support is arranged for all patients, monitoring of response to treatment among the high proportion of tuberculosis patients with diabetes and engagement with private healthcare providers could be strategies addressed to reduce the risk of emergence of drug-resistant tuberculosis.

Are global tuberculosis control targets overlooking an essential indicator? Prolonged delays to diagnosis despite high case detection rates in Yunnan, China

Delay in treating active tuberculosis (TB) impedes disease control by allowing ongoing transmission, and may explain the unexpectedly modest declines in global TB incidence. Even though China has achieved TB control targets under the global Directly Observed Treatment, Short course (DOTS) strategy, TB prevalence in western provinces, including Yunnan, is not decreasing. This cross-sectional study investigates whether prolonged delay in identifying and correctly treating TB patients, which is not routinely monitored, persists even when there is a well-functioning TB control programme and global targets are being met. Records of adult smear-positive pulmonary TB patients diagnosed with between 2006 and 2013 were extracted from the Yunnan Centre for Disease Control electronic database, which contains information on the entire population of TB patients managed across 129 diagnostic centres. Delay was investigated at three stages: delay to DOTS facility (period between symptom onset and first visit to at a CDC unit providing standardized treatment); delay to TB confirmation (period between reaching a CDC unit and confirmation of smear-positive TB) and delay to treatment (period between confirmation of TB and initiation of treatment). Data from 76 486 patients was analysed. Delay to reaching a DOTS facility was by far the largest contributor to total delay to treatment initiation. The median delay to reaching a DOTS facility, to TB confirmation and to treatment was 57 days (IQR 25-112), 2 days (IQR 1-6) and 1 day (IQR 0-1) respectively. Prolonged delays to reaching a facility providing standardized TB care occurred in a substantial subset of the population despite all TB control targets being met; overall, 32% (24 676) of patients experienced a delay of more than 90 days to reaching a DOTS facility. Policies that focus on reducing delays in accessing appropriate health services, rather than only on increasing overall case-detection rates, may result in greater progress towards reducing TB incidence.