Health disparities research in low- and middle-income countries (LMICs) is hampered by the difficulty of measuring economic status in low-resource settings. We previously developed the EconomicClusters k-medoids clustering-based algorithm for defining population-specific economic models based on few Demographic and Health Surveys (DHS) assets. The algorithm previously defined a twenty-group economic model for Cameroon. The aims of this study are to optimize the functionality of our EconomicClusters algorithm and app based on collaborator feedback from early use of this twenty-group economic model, to test the validity of the model as a metric of economic status, and to assess the utility of the model in another LMIC context. We condense the twenty Cameroonian economic groups into fewer, ordinally-ranked, groups using agglomerative hierarchical clustering based on mean cluster child height-for-age Z-score (HAZ), women's literacy score, and proportion of children who are deceased. We develop an EconomicClusters model for Ghana consisting of five economic groups and rank these groups based on the same three variables. The proportion of variance in women's literacy score accounted for by the EconomicClusters model was 5-12% less than the proportion of variance accounted for by the DHS Wealth Index model. The proportion of the variance in child HAZ and proportion of children who are deceased accounted for by the EconomicClusters model was similar to (0.4-2.5% less than) the proportion of variance accounted for by the DHS Wealth Index model. The EconomicClusters model requires asking only five questions, as opposed to greater than twenty Wealth Index questions. The EconomicClusters algorithm and app could facilitate health disparities research in any country with DHS data by generating ordinally-ranked, population-specific economic models that perform nearly as well as the Wealth Index in evaluating variability in health and social outcomes based on wealth status but that are more feasible to assess in time-constrained settings.

Background

Malnourished and young children are particularly susceptible to severe forms of tuberculosis and poor treatment response. WHO dosing guidelines for drugs for tuberculosis treatment are based only on weight, which might lead to systematic underdosing and poor outcomes in these children. We aimed to assess and quantify the population effect of WHO guidelines for drug-susceptible tuberculosis in children in the 20 countries with the highest disease burden.

Methods

We used an integrated model that linked country-specific demographic data at the individual level from the 20 countries with the highest disease burden to pharmacokinetic, outcome, and epidemiological models. We estimated tuberculosis treatment outcomes in children younger than 5 years following WHO guidelines (children are dosed by weight bands corresponding to the number of fixed-dose combination tablets [75 mg rifampicin, 50 mg isoniazid, 150 mg pyrazinamide]) and two alternative dosing strategies: one based on a proposed algorithm that uses age, weight, and available formulations, in which underweight children would receive the same drug doses as would normal weight children of the same age; and another based on an individualised algorithm without dose limitations, in which derived doses results in target exposure attainment for the typical child.

Findings

We estimated that 57 234 (43%) of 133 302 children younger than 5 years who were treated for tuberculosis in 2017 were underdosed with WHO dosing and only 47% of children would reach the rifampicin exposure target. Underdosing and subtherapeutic exposures were more common among malnourished children than among age-matched healthy children. The proposed dosing approach improved estimated rifampicin target exposure attainment to 62% and equalised outcomes by nutritional status. An estimated third of unfavourable treatment outcomes might be resolved with this dosing strategy, saving the lives of a minimum of 2423 children in these countries annually. With individualised dosing approaches, almost all children could achieve adequate exposure for cure.

Interpretation

This work shows that a simple change in dosing procedure to include age and nutritional status, requiring no additional measurements or new drug formulations, is one approach to improve tuberculosis treatment outcomes in children, especially malnourished children who are at high risk of mortality.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development and UK Medical Research Council.

Background

New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage.

Methods

We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP.

Findings

In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective.

Interpretation

Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets.

Funding

Bill & Melinda Gates Foundation, WHO.