OpiniãoNutrition assessment and counselling
Quality of the evidence:
Not available
Values and preferences:
The panel determined that since people with active TB are often underweight and have experienced weight loss by the time of diagnosis, and that low BMI is associated with increased mortality, nutrition screening and assessment is required to determine appropriate nutrition intervention and care.
Benefits:
Are likely
Harms:
Are unlikely
Acceptability and feasibility:
Health-care workers will need training on targeted nutrition screening and assessment, classification of nutritional status and nutrition counselling. Appropriate devices to measure height/length, weight and midupper arm circumference, and charts to determine weight-for-height and BMI are required. Acceptability of nutrition assessment may be a challenge in areas where health-care workers do not have access to food supplements to give if an individual is found to be undernourished.
Sparse human and equipment resources may decrease the feasibility of this recommendation in some settings.
Resource implications:
The resource implications for TB programmes for assessment and counselling are considered low to moderate, and in some settings this recommendation may not be achievable.
Management of severe acute malnutrition
Management of adults with active TB and severe acute malnutrition
Quality of the evidence:
Very low
Values and preferences:
In the absence of direct evidence that treatment of severe acute malnutrition in people with TB improves TB outcomes, the panel determined that people with active TB and severe acute malnutrition should be treated in the same manner as severely malnourished people without TB, and that the established standards of care should be applied.
Benefits:
Are likely, especially because severe acute malnutrition in people with TB increases mortality risk. Although there is no direct evidence of the benefits of management of severe acute malnutrition in TB patients, there is evidence of benefit in those without TB.
Harms:
Are unlikely
Acceptability and feasibility:
In hospital and non-hospital settings where appropriate therapeutic food products for adults may be unavailable, available products used for children, such as F-100 or ready-to-use therapeutic foods, could be used.
Resource implications:
The resource implications of this recommendation for TB programmes are considered moderate to high and in some settings may not be achievable. Severe acute malnutrition is frequently managed by nutrition programmes, so linking TB services with referral and treatment to appropriate health services responsible for treating severe acute malnutrition may be recommended.
Management of children with severe acute malnutrition and active TB
Quality of the evidence:
Very low
Values and preferences:
While there is substantial evidence of effective nutritional management in children with severe acute malnutrition without TB, there is no direct evidence that treatment of severe acute malnutrition in children who are less than 5 years of age with TB improves TB outcomes. The panel determined that in the absence of direct TB-related evidence, children who are less than 5 years of age with active TB and severe acute malnutrition should be treated the same as severely undernourished children without TB, and the established standards of care should be applied.
Benefits:
Are likely, especially considering that mortality is high in children with severe acute malnutrition
Harms:
Are unlikely
Acceptability and feasibility:
The effectiveness of therapeutic foods for treating severely undernourished children is well established, and such products are generally widely available, though not in all regions.
Resource implications:
The resource implications of this recommendation for TB programmes are considered moderate to high and in some settings may not be achievable. Management of severe acute malnutrition in children should be managed by nutrition programmes in health centres or in community-based programmes. TB programme officers should ensure nutrition referral and treatment by appropriate health-care providers.
Management of moderate undernutrition
Management of adults with moderate undernutrition and active TB
Quality of the evidence:
Low
Values and preferences:
The panel highly valued the need to restore weight and physical functioning and prevent progression to severe acute malnutrition.
The panel valued highly the risks to future growth and development in children and adolescents with moderate undernutrition and TB. The panel also valued highly the potential maternal health risks and infant risks of altered growth and development as a consequence for lactating women with moderate undernutrition and TB.
To allow time for anti-tuberculosis therapy to promote weight gain through a reduction in the energy demands of untreated disease and restoration of appetite, the delay in provision of fortified supplementary food is a compromise between what might be considered optimal care in some settings and the high resource costs of universal provision of supplementary food.
Benefits:
Five randomized controlled trials compared the effect of macronutrient supplements with nutritional advice alone on weight gain in people with TB (82– 86). Macronutrient supplementation probably does improve weight gain during the intensive phase of treatment (moderate quality evidence), although one trial exclusively in HIV–TB coinfected patients found no difference at any time point.
Two studies also report that supplements may improve some measures of quality of life but the studies are too small to give much confidence in this result (low quality evidence).
The available evidence has not yet demonstrated any clear benefits of macronutrient supplementation on TB treatment outcomes.
Harms:
Are unlikely
Acceptability and feasibility:
In many settings, appropriate locally available nutrientrich or fortified foods may not be available, and there are no established recommendations for the general management of moderate undernutrition in many age and life-stage groups. Fortified food products for treatment of malnutrition in children who are less than 5 years of age are generally available in most settings and may be available for use in adults.
The 2-month delay in provision of supplementary food is different from recommendations for children who are under 5 years of age, pregnant women, people with HIV coinfection, and people with MDR-TB. Some programmes may opt to simplify their protocols by providing supplementary food or therapeutic food for all groups with moderate undernutrition at the initiation of treatment. This may be particularly relevant where food assistance is a part of an enabler package to improve access and adherence to TB diagnosis and treatment
As well as limited financial resources, sparse human resources may decrease the feasibility of this recommendation in some settings.
Resource implications:
The resource implications of this provision for TB programmes are considered high and in some settings may not be achievable. Management of moderate undernutrition can be integrated with other health services or nutrition programmes.
Management of children with moderate undernutrition and active TB
Quality of the evidence:
Very low
Values and preferences:
The panel highly valued the risks to current and future growth and development in infants and children with moderate undernutrition and TB. While there is no direct evidence that treatment of moderate undernutrition in children with TB who are less than 5 years of age improves TB outcomes, the panel considered that, in the absence of direct evidence, children who are less than 5 years of age with active TB and moderate undernutrition should be treated the same as children with moderate undernutrition without TB, and the established standards of care should be applied.
Benefits:
Likely, as for undernourished children without TB
Harms:
Are unlikely
Acceptability and feasibility:
The effectiveness of therapeutic foods for treating children with undernutrition is well established. The products are generally available but may not be available in some settings.
Resource implications:
The resource implications of this recommendation for TB programmes are considered moderate to high and in some settings may not be achievable. Management of moderate undernutrition can be integrated with other health services or nutrition programmes.
Management of pregnant women with moderate undernutrition and active TB
Quality of the evidence:
Very low
Values and preferences:
The panel highly valued the observational association between maternal undernutrition in women with TB and increased maternal and neonatal complications.
The panel also recognized the difficulty of detecting moderate undernutrition in pregnant women, in whom BMI and mid-upper arm circumference can be difficult to interpret.
Benefits:
The trials of nutritional supplementation for TB patients did not include pregnant women.
However, from observational evidence, weight loss during pregnancy is common (36, 38, 87) and even with treatment many fail to gain the optimal weight necessary to reduce the risks of low-birth-weight infants, premature birth or intrauterine growth restriction.
Harms:
Are unlikely
Acceptability and feasibility:
Nutrition support, outside of folic acid and iron supplementation, is not a routine part of antenatal care and may place additional burdens on antenatal care and TB programmes. It may be difficult to clinically track weekly or monthly weight gain during pregnancy in many settings. Effective implementation will require effective coordination between these antenatal and TB services.
As well as financial resources, sparse human resources may decrease the feasibility of this recommendation in some settings.
Resource implications:
The resource implications are likely to be moderate.
Management of moderate undernutrition among patients with active multidrug-resistant tuberculosis
Quality of the evidence:
Very low
Values and preferences:
The panel highly valued the need to restore weight and physical functioning and to prevent the progression to severe acute malnutrition.
The panel also recognized that people with MDR-TB are an especially vulnerable group.
Benefits:
The supplementation trials that have been conducted are not known to have included people with MDR-TB.
However, five randomized controlled trials compared the effectiveness of macronutrient supplements against nutritional advice alone on weight gain in people with TB. Macronutrient supplementation probably does improve weight gain during the intensive phase of treatment (moderate quality of evidence). Two studies also report that supplements may improve some measures of quality of life but the studies were too small to have much confidence in this result (low quality of evidence).
The available evidence has not yet demonstrated any clear benefits of macronutrient supplementation on TB treatment outcomes or effects in people with MDR-TB.
Harms:
Are unlikely
Acceptability and feasibility:
In many settings, locally available nutrient-rich or fortified food products for adults may be unavailable, and there are no established recommendations for the general management of moderate undernutrition in various age and life-stage groups. Specialized food products used for children may be considered for use in adults.
The human resources necessary to administer this recommendation may draw valuable resources from other areas.
Resource implications:
The resource implications of this provision for TB programmes are considered moderate because the number of cases with MDR-TB is usually lower than the number of drug-susceptible cases.
Micronutrient supplementation
Micronutrient supplementation in patients with active TB and moderate undernutrition
Quality of the evidence:
Very low
Values and preferences:
The panel highly valued meeting and maintaining established standards of the daily micronutrient intake necessary to maintain good health and the known harms associated with deficiencies. The panel also highly valued that many people in low-resource and foodinsecure settings have a high likelihood of inadequate micronutrient intake, particularly considering their normal plant-based diet.
Benefits:
Low serum levels of essential micronutrients have been commonly reported from cohorts of patients beginning treatment for active TB. However, randomized micronutrient supplementation trials have, as yet, failed to show any significant or consistent clinically important benefit for TB treatment outcomes with doses at or above 1× recommended nutrient intake (88–92).
In the early stages of treatment, micronutrient supplementation may improve plasma levels of zinc, selenium and vitamins D and E, but this has not been shown to have any clinically significant benefit on TB treatment. Plasma levels of vitamins A and D and zinc appear to normalize by the end of treatment, regardless of supplementation.
A multiple micronutrient supplement includes vitamin B6, which protects against isoniazid-induced peripheral neuropathy, and has the added benefit of provision of other micronutrients in addition to vitamin B6.
Harms:
Supplementation is very unlikely to be harmful but micronutrient supplements could increase the financial burden on TB patients unless they are provided free of charge.
Acceptability and feasibility:
Given the already high pill burden experienced by people undergoing treatment of TB, and the lack of convincing evidence for benefit on TB treatment outcome from micronutrient supplementation, patients may choose not to purchase or consume micronutrient supplements.
Resource implications:
The resource implications for programmes to provide this supplementation are considered low.
Micronutrient supplementation in pregnant and lactating women with active TB
Quality of the evidence:
Very low
Values and preferences:
The panel determined that the increased physiological requirements during pregnancy and lactation, and the likelihood of undernutrition and inadequate dietary intake, make it extremely unlikely that TB patients would require fewer micronutrients than the HIV-positive population. Since there is no evidence of micronutrient supplementation in pregnant and lactating women with TB, the evidence of benefits with multiple micronutrient supplementation in pregnant women with HIV was considered adequate to justify supplementation during TB treatment.
The panel also considered that, in the absence of direct evidence that pregnant women with either active TB or signs of undernutrition should receive more or less calcium, folic acid or iron, the established standards of care should be applied.
Benefits:
Trials assessing supplementation in pregnant women with TB have not been conducted. However, trials in pregnant women with HIV infection have shown that multiple micronutrient supplementation at ≥1× the recommended nutrient intake improves both infant and maternal outcomes.
There is some evidence that pregnant women with TB are at increased risk of pre-eclampsia and should receive a calcium supplement in accordance with the WHO recommendation for pregnancy (6, 42). For the prevention of pre-eclampsia, the current WHO recommendation is to provide calcium supplementation during pregnancy in areas where dietary calcium intake is low, and for pregnant women at higher risk of developing pre-eclampsia (42).
Harms:
Harms to the mother or child are unlikely.
Acceptability and feasibility:
Given the already high pill burden experienced by people undergoing treatment of TB, combined with the additional calcium and United Nations Multiple Micronutrient Preparation supplementation (5), women may choose not to purchase or consume micronutrient supplements.
WHO recommends that all pregnant women living in areas with high rates of anaemia be provided with iron and folic acid supplements during pregnancy, regardless of maternal iron status. These are routinely given to pregnant women through antenatal programmes. Because the United Nations Multiple Micronutrient Preparation is a prenatal supplement that includes iron and folic acid, additional supplementation of these two nutrients is not needed for women with TB receiving the United Nations Multiple Micronutrient Preparation supplement. In areas of high TB and/or HIV prevalence, programmes may elect to give all pregnant women the United Nations Multiple Micronutrient Preparation supplement rather than the iron and folic acid singly, in order to simplify administration and to not make a special case for women with TB or HIV. Calcium supplementation during pregnancy is recommended to reduce the risk of pre-eclampsia, and continued supplementation after delivery is not needed.
Folic acid and iron are already provided in most settings as a routine part of antenatal care; calcium supplementation is a new WHO recommendation and most likely will be in various stages of implementation in different countries. Regardless, acceptability and feasibility are moderate to high for additional multiple micronutrient supplements, especially if women are educated as to their benefits on both maternal and infant outcomes.
Resource implications:
The resource implications of this recommendation for TB programmes are considered low, and this would ideally be implemented through antenatal care. Coordination with antenatal services is required.
Contact investigation
Nutrition assessment, care and support for household contacts of people with active TB
Quality of the evidence:
Very low
Values and preferences:
The panel highly values the observational evidence that young children and people who are undernourished are at the highest risk of progression to active TB disease. This is particularly important for young children who are less than 5 years of age, who have a higher risk of disease progression, independent of malnutrition. Nutrition screening and assessment can identify highrisk contacts who require rigorous evaluation for active and latent TB.
Benefits:
There is evidence that people who are malnourished are at higher risk of progression from latent to active TB, compared with those who are not malnourished (49, 53–55). No trials in the area of effective chemotherapy have assessed the impact of nutrition support for TB contacts and the subsequent risk of active disease.
Harms:
Are unlikely
Acceptability and feasibility:
In many settings, contact tracing is not implemented; however, in settings where contact investigation is already conducted, screening for undernutrition using simple methods (height, weight, BMI, mid-upper arm circumference) in this high-risk group is likely to have high acceptability and feasibility.
Resource implications:
The resource implications of this provision for TB screening programmes are considered low.