A retrospective survey of HIV drug resistance among patients 1 year after initiation of antiretroviral therapy at 4 clinics in Malawi.

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention.

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

BACKGROUND: The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions. METHODS: Patients visiting two ART clinics in South Africa for routine follow-up visits between March 2007 and April 2008 were included in our study. Each patient was screened by non-physician counselors using the handheld device and then received a full clinical assessment. Clinicians' report on whether full clinical assessment had been necessary was used as the gold standard for determining "required referral". Observations were randomly divided into two datasets--989 for developing a referral protocol and 200 for validating protocol performance. RESULTS: A third of patients had at least one physical complaint, and 16% had five or more physical complaints. 38% of patients required referral for full clinical assessment. We identify a subset of questions which are 87% sensitive and 47% specific for recommended patient referral. CONCLUSIONS: The final screening protocol is highly sensitive and could reduce burden on ART clinicians by 30%. The uptake and acceptance of the handheld tool to support implementation of the protocol was high. Further examination of the data reveals several important questions to include in future referral algorithms to improve sensitivity and specificity. Based on these results, we identify a refined algorithm to explore in future evaluations.

Drug resistance surveillance in resource-poor settings: current methods and considerations for TB, HIV, and malaria.

In resource-constrained environments, monitoring the occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), or malaria resistant to the limited number of available drugs is essential for national treatment program success. Countries with limited resources and technical capacity rely on survey designs and methods that are simple and easily integrated into routine clinical activities to minimize the impact on overburdened clinics. This paper reviews the most commonly used methods for drug-resistance surveillance of TB, HIV, and malaria and discusses the strengths and limitations of these different strategies.

Health indicators: eliminating bias from convenience sampling estimators.

Public health practitioners are often called upon to make inference about a health indicator for a population at large when the sole available information are data gathered from a convenience sample, such as data gathered on visitors to a clinic. These data may be of the highest quality and quite extensive, but the biases inherent in a convenience sample preclude the legitimate use of powerful inferential tools that are usually associated with a random sample. In general, we know nothing about those who do not visit the clinic beyond the fact that they do not visit the clinic. An alternative is to take a random sample of the population. However, we show that this solution would be wasteful if it excluded the use of available information. Hence, we present a simple annealing methodology that combines a relatively small, and presumably far less expensive, random sample with the convenience sample. This allows us to not only take advantage of powerful inferential tools, but also provides more accurate information than that available from just using data from the random sample alone.

Estimating the magnitude and direction of bias in tuberculosis drug resistance surveys conducted only in the public sector: a simulation study.

BACKGROUND: Accurate assessment of the burden of drug-resistant TB requires systematic efforts to quantify its magnitude and trend. In approximately half the countries where resistance has been reported, estimates are based on surveys conducted in public sector facilities. However, in locations where a substantial fraction of TB cases seek care with private providers, these surveys may not accurately measure resistance in the entire population. METHODS: We describe a mathematical model to investigate biases associated with sampling only from public sector cases in India, where TB treatment is offered in both public and private sectors. We then propose and demonstrate a weighted estimator as an efficient method for including small numbers of cases from the private sector as a way to recover valid estimates of resistance in the population under study. RESULTS: We find that public sector surveys rarely provide valid estimates of drug-resistance among new and retreatment cases. Further, the magnitude and direction of the bias are sensitive to many parameters describing the health-seeking behaviours and treatment outcomes of tuberculosis patients, disallowing simple adjustments to recover accurate estimates. CONCLUSIONS: In locations where large numbers of tuberculosis patients are diagnosed and treated by private sector practitioners who are not typically included in drug resistance surveys, targeted surveys for assessing drug resistance are required to validly estimate resistance.

An assessment of Lot Quality Assurance Sampling to evaluate malaria outcome indicators: extending malaria indicator surveys.

BACKGROUND: Large investments and increased global prioritization of malaria prevention and treatment have resulted in greater emphasis on programme monitoring and evaluation (M&E) in many countries. Many countries currently use large multistage cluster sample surveys to monitor malaria outcome indicators on a regional and national level. However, these surveys often mask local-level variability important to programme management. Lot Quality Assurance Sampling (LQAS) has played a valuable role for local-level programme M&E. If incorporated into these larger surveys, it would provide a comprehensive M&E plan at little, if any, extra cost. METHODS: The Mozambique Ministry of Health conducted a Malaria Indicator Survey (MIS) in June and July 2007. We applied LQAS classification rules to the 345 sampled enumeration areas to demonstrate identifying high- and low-performing areas with respect to two malaria program indicators-'household possession of any bednet' and 'household possession of any insecticide-treated bednet (ITN)'. RESULTS: As shown by the MIS, no province in Mozambique achieved the 70% coverage target for household possession of bednets or ITNs. By applying LQAS classification rules to the data, we identify 266 of the 345 enumeration areas as having bednet coverage severely below the 70% target. An additional 73 were identified with low ITN coverage. CONCLUSIONS: This article demonstrates the feasibility of integrating LQAS into multistage cluster sampling surveys and using these results to support a comprehensive national, regional and local programme M&E system. Furthermore, in the recommendations we outlined how to integrate the Large Country-LQAS design into macro-surveys while still obtaining results available through current sampling practices.

Cluster designs to assess the prevalence of acute malnutrition by lot quality assurance sampling: a validation study by computer simulation.

Traditional lot quality assurance sampling (LQAS) methods require simple random sampling to guarantee valid results. However, cluster sampling has been proposed to reduce the number of random starting points. This study uses simulations to examine the classification error of two such designs, a 67x3 (67 clusters of three observations) and a 33x6 (33 clusters of six observations) sampling scheme to assess the prevalence of global acute malnutrition (GAM). Further, we explore the use of a 67x3 sequential sampling scheme for LQAS classification of GAM prevalence. Results indicate that, for independent clusters with moderate intracluster correlation for the GAM outcome, the three sampling designs maintain approximate validity for LQAS analysis. Sequential sampling can substantially reduce the average sample size that is required for data collection. The presence of intercluster correlation can impact dramatically the classification error that is associated with LQAS analysis.

Early warning indicators for HIV drug resistance in Malawi.

BACKGROUND: Malawi started rapid scale-up of antiretroviral therapy (ART) in 2004 and by December 2006 had initiated over 85,000 patients on treatment. Early warning indicator (EWI) reports can help to minimize the risk of emerging drug resistance. METHODS: Data collected during the routine quarterly supervision of 103 public sector sites was used to compile the first EWI report for HIV drug resistance (HIVDR) in Malawi, reflecting outcomes for October to December 2006. RESULTS: All sites reach the World Health Organization (WHO) targets for prescribing practices and drug supply continuity. The target for adherence was achieved by 85% of sites and 84% achieved the target for minimizing treatment defaults; however, less than half of all sites reach the WHO target for patient retention. CONCLUSIONS: These results emphasize the importance of defaulter tracing and initiating treatment earlier in the course of HIV infection. As part of a comprehensive HIVDR monitoring programme, the Ministry of Health plans for on-going tracking of these indicators, as well as special data collection from the private sector. Plans are also underway to gather information on other recommended indicators that are not collected during routine supervision.