International Health
Volume 1, Issue 1 , Pages 10-16, September 2009

Improving survival of children with severe acute malnutrition in HIV-prevalent settings

  • Pamela Fergusson

      Affiliations

    • Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
    • Corresponding Author InformationCorresponding author.
    • ,
  • Andrew Tomkins

      Affiliations

    • Centre for International Health and Development, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UK
    • ,
  • Marko Kerac

      Affiliations

    • Centre for International Health and Development, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UK

Received 30 January 2009; received in revised form 11 March 2009; accepted 17 March 2009.

Article Outline

Summary 

The care of severely malnourished children in sub-Saharan Africa is challenging, especially in HIV-prevalent settings. Recent improvements to facility-based individual case management, and increased community-based management focusing on early identification and high programme coverage have led to reductions in mortality. Further interventions are urgently needed to address resistant mortality, mostly attributable to HIV. This paper explores strategies in three main areas to improve survival for children with severe acute malnutrition (SAM): identifying HIV and improving case management for HIV-infected children; strengthening existing strategies to improve outcomes for all children with SAM, regardless of HIV status; and improving early identification and increasing programme coverage. Although interventions to further improve survival among children with SAM in sub-Saharan Africa must firstly ensure best care for all children, HIV-infected children are at particular risks for mortality. Integration of specific interventions for HIV testing and treatment into SAM care is essential. International guidelines should reflect best evidence, and are in urgent need of updating and adapting to local country context. Effective interventions already exist that can improve survival in children with SAM in HIV-prevalent settings. The challenge is to implement what we know and to research what we do not.

Keywords: HIV, AIDS, Africa, Malnutrition, Child survival, Child mortality

 

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1. Introduction 

Severe acute malnutrition (SAM) is responsible for the death of over 1 million under fives per year.1 Improving SAM survival is a global public health priority, key to achievement of international health targets such as Millennium Development Goal 4, reducing child mortality.2 One review of SAM outcomes in therapeutic feeding programmes (TFPs) from 1950 to 1990 reported case fatality rates averaging 20–30%, sometimes as high as 50–60% for children with oedematous malnutrition.3 Although important gains have recently been made in reducing mortality overall for children with SAM, mortality among HIV-infected children remains high.

1.1. Current treatment strategies 

Over the last 10 years, important reductions in SAM mortality have been achieved. Two TFP strategies have played major independent but complementary roles.1, 4, 5, 6, 7 First, traditional inpatient-focused TFP care was improved by WHO using ‘10 steps’ case management guidelines.8 These guidelines includes medical and nutritional care, starting with cautious feeding and moving to a catch-up formula once the child is stabilised and any oedema is resolved.9, 10 Guidelines were first published in 1999,11 and supported by a programme of training courses for staff.12 Research into optimising guideline implementation has shown promising results, in particular when TFP have adequate numbers of trained and committed staff.4, 6, 13, 14

The second TFP strategy, internationally endorsed in 200715 and currently rolling out worldwide, is community management of acute malnutrition (CMAM).16 CMAM programmes use ready-to-use therapeutic foods (RUTFs) to treat the majority of children in their own homes rather than as inpatients. Public health impact is achieved through a network of outpatient treatment (OTP) sites aiming to improve access to care and maximise population coverage. CMAM also emphasizes active case-finding and timely treatment, before infections and other clinical complications of SAM develop and before a child deteriorates to the stage where intensive inpatient medical inputs are needed.1, 7, 16, 17, 18, 19

1.2. Why HIV matters 

Despite CMAM and WHO 10 steps successes, significant challenges in SAM management still remain. Increasing evidence shows that HIV underlying SAM is both prevalent and has profound adverse impacts. A 2008 meta-analysis of 17 studies of children in sub-Saharan Africa undergoing therapeutic feeding reported a weighted mean HIV prevalence of 29.2%. Urban referral hospitals had the highest burden of disease, rural CMAM settings the lowest.20 Before HIV, TFPs typically saw large seasonal variations in SAM admissions related to periods of food insecurity. Now children with HIV-related SAM are admitted throughout the year,21 often with complex and multiple pathologies such as persistent diarrhoea, tuberculosis (TB), pneumonia and oral thrush.22, 23 Of greatest concern, SAM complicated by HIV is proving to be resistant to standard care. Mortality among HIV-infected malnourished children is consistently and significantly higher than in those with SAM alone (30.4 vs. 8.4%, RR=2.81, 95% CI 2.04–3.87).20

1.3. Need for updated SAM guidelines 

Given the clinical complexity and challenges of HIV-related SAM, it is striking that current international guidelines for SAM rehabilitation9, 10, 18 have minimal mention of the issue. This reflects the rapid and recent emergence of evidence, plus the time lag for translation into policy. However, the gap is becoming critical in HIV-prevalent settings and urgently needs to be addressed to tackle poor outcomes, high mortality and strains on already-limited TFP resources.23, 24 There is a dearth of clinicians trained in the management of paediatric SAM,24 and updating guidelines is an important means of supporting non-specialist staff providing the majority of front-line care.

This paper explores strategies in three main areas to improve survival for children with SAM: identifying HIV and improving case management for HIV-infected children; strengthening existing strategies to improve outcomes for all children with SAM, regardless of HIV status; and improving early identification and increasing programme coverage.

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2. What can be done 

2.1. Opt-out HIV testing 

The crucial first adaptation for routine SAM management in HIV-prevalent settings is for TFPs to adopt routine, opt-out testing policies. As HIV prevalence among children with SAM is high, TFPs are an important entry point for HIV care. Knowing HIV status has important benefits:25 malnutrition is a clinical criterion for advanced HIV and eligibility for antiretroviral (ARV) treatment;26 performance of clinical diagnostic algorithms is especially poor in high-prevalence settings due to lower positive predictive values;27 and lastly, ruling out HIV infection can be as useful to clinical decision-making as ruling it in.

We recognise the challenges that opt-out testing can involve. Even today, some cite risks of stigma and discrimination,28, 29 but our experience working with HIV in SAM settings suggests that opt-out HIV testing actually decreases stigma when all, rather than only some, patients are called for testing.

Ultimately, risks of testing must be weighed against the benefits for the SAM-affected child, and for his/her entire family. Illustrating acceptance of testing and the increasingly favourable benefit/risk balance, one study exploring HIV and SAM at national level in Malawi found that 523 (91.7%) of parents consented for their malnourished child to be tested; and 368 (70.6%) accepted an offer of testing for themselves.30

2.2. Children <18 months 

Rapid HIV tests detected HIV antibodies in a fingerprick sample of whole blood and are increasingly available and increasingly affordable.31 Several brands of kit perform the same basic task of detecting HIV antibodies in a fingerprick sample of whole blood. There are challenges in the diagnosis of children <18 months. Not testing is not an option: untreated, 35–59% of HIV-infected children in sub-Saharan Africa will die before their second birthday,32 and that proportion would almost certainly be higher among children who have experienced SAM. Rapid tests, however, can give false positive results in children <18 months due to the presence of maternal HIV antibodies taking some time to clear.33 Alternatives are needed for definitive diagnosis.34 Currently, PCR detection of HIV is the recommended method for children <18 months.26 PCR is expensive, however, and not yet widely available. Several strategies offer interim solutions.

•Rapid test results should be done. A reactive rapid test will identify a child as being exposed to HIV, and possibly HIV infected. Co-trimoxazole prophylaxis (inexpensive, effective and widely available) can then be initiated and continued unless HIV can be excluded, either through PCR testing or through a rapid test when the child is >18 months of age.35

•Urgent research is needed on age cut-offs above which a positive rapid test result can be seen as definitive. Some projects have used 15 months for this.36 Even lower limits may be appropriate: one study shows that maternal antibodies mostly clear from an infant's circulation by 9 months.37

2.3. ARV drugs (where available) 

ARVs are the current treatment for HIV. Where they are available, strong evidence supports early treatment. This applies to children with SAM as much as to others. One randomised controlled trial (RCT) showed that early HIV diagnosis and early ARV therapy reduced early infant mortality by 76% and HIV progression by 75%.38

The 2008 Report of the WHO Technical Reference Group, Paediatric HIV/ART Care Guideline Group Meeting stated that all infants (<12 months) with confirmed HIV infection should be initiated on ARV, regardless of clinical or immunological stage. It also recommended that where PCR is unavailable, infants with “clinically diagnosed presumptive severe HIV” should start ARVs, and that confirmation of HIV status should be obtained as soon as possible. Other children (12–59 months) should start ARV at a CD4% <20.

There are a few issues with how this applies to a SAM setting. CD4% is low in HIV-infected children with SAM,39, 40 and low CD4% is linked with increased risk of mortality.40 Furthermore, CD4 count examined by one study in Zambia remained low in all HIV-infected children with SAM, even with apparent nutritional recovery.41 These data confirm the appropriateness of severe malnutrition as a staging criteria for ARV initiation.

Given these uncertainties, what should be done now? We suggest that (resources allowing), the emphasis should be on early treatment whatever the age of the SAM child. Although the most important advantage of early treatment with ARVs is reducing mortality,38 an additional advantage is that starting on ARVs keeps children better engaged with healthcare services. Deferring the start date may mean that by the time children do return into the system, HIV progression may be too advanced and the chances of successful treatment correspondingly lower.

As more children in more countries are started on ARVs, it is important to watch for new patterns of disease. Many TFPs are admitting increasing numbers of children already on ARVs (Dr James Bunn, Queen Elizabeth Hospital/College of Medicine, Malawi, personal communication,). It is important to unravel whether their malnutrition is due to immune reconstitution, poor ARV compliance, ARV failure/resistance or any one of a multitude of other causes.

Despite the benefits of ARVs in a general paediatric population, their impact on HIV-infected children recovering from SAM remains unknown. Many children with SAM are identified late, with very low CD4%,39, 40 and thus high risk of death whatever the treatment. One recent study33 showed that 69.2% of HIV-infected children with SAM had advanced stage 3 or 4 HIV,40 according to age-based, WHO clinical criteria.26 Although ARVs are likely to reduce mortality among HIV-infected children with SAM, HIV should ideally be identified and treated before the onset of advanced and complicated SAM.

2.4. Co-trimoxazole (when ARVs are not available) 

All children with a positive rapid test for HIV should immediately start long-term co-trimoxazole therapy. Given its relatively low risks, low cost and wide availability, it is especially useful in settings without ARVs or other HIV-specific resources. Despite proven benefits,42, 43 it is currently underused.43 Positioning TFPs as an entry point to HIV-related care could play a role in changing this: both for children with SAM, but also for other family members who use the opportunity to be tested. ARV treatment programmes are currently scaling up in many countries but are not yet widely available everywhere. Co-trimoxazole could make the crucial difference to a child's survival until ARVs arrive.

2.5. First-line antibiotics 

Current TFP protocols give all admitted SAM children an empiric first-line antibiotic, usually 7 d of amoxicillin. High-quality RCT evidence is urgently needed to determine whether this remains best choice in HIV-prevalent settings. Of the few related studies currently available, one from Uganda looked at SAM-related pathogens and found high rates of in-vitro resistance to amoxicillin. The authors of that study suggested that either ceftriaxone or ciprofloxacin be used instead.44 We suggest that more studies in more settings are needed before widespread policy change–bearing in mind that first-line antibiotic choice will influence what is available for second- and third-line treatment (ceftriaxone is currently second or third line in many countries).

A particularly urgent issue to explore is the use of co-trimoxazole, especially for CMAM outpatient settings where children have SAM on the basis of low weight-for-height or mid-upper arm circumference (MUAC) but are clinically ‘uncomplicated’ (thus by definition without serious infection). Given mortality reductions when used for HIV prophylaxis (even when in-vitro resistance is high),42 it is plausible that co-trimoxazole will also be beneficial as first line for uncomplicated SAM. Favourable risk/benefit outcomes are also likely for HIV-negative children–while the transition to long-term co-trimoxazole treatment might be facilitated for those who are HIV-positive.

2.6. Second-line antibiotics 

In HIV, systemic, respiratory and gastrointestinal infections are more common, more serious and more diverse in terms of underlying pathogen than in children without HIV. This must be reflected in local TFP protocols for second- and third-line antibiotics, used when a child is particularly sick on admission or if he/she deteriorates having already had first line. If a child is sick enough to need second-line antibiotics, it is normally safer to also admit for inpatient care. Specific pathogens to consider include Pneumocystis pneumonia (PCP; causing severe pneumonia) and non-typhoid Salmonella spp. (causing systemic infection). Occasionally additional treatments might be needed, such as steroids in PCP (although the efficacy of these in SAM remains to be proven). Other common HIV-related infections, such as Cryptosporidium diarrhoea, have no specific effective treatments.

What to use for second- and third-line treatment depends on the setting. Site-specific recommendations dependent upon local microbiology and antibiotic availability are likely to be better than a single universal policy.

Knowing HIV status may trigger different treatment thresholds for second- or third-line antibiotics: in an otherwise well HIV-negative child, treating a single fever spike may be unnecessary and may lead even to unnecessary inpatient referral/prolongation of inpatient stay. In an HIV-positive child, however, mortality risk is higher and it may be appropriate to initiate more intensive treatments sooner rather than later.

2.7. TB 

TB is a major cause of mortality in HIV-associated SAM. Yet diagnosis alone is a major challenge.45 A careful contact history is important, especially to distinguish TB from other HIV-associated lung pathologies such as lymphocytic interstitial pneumonitis (LIP).46 Investigations such as chest X-rays and tuberculin skin tests are useful (if available) only if positive, as sensitivity is low. Newer antigen-based tests (QuantiFERON and ELISPOT) are still expensive and have not yet been sufficiently validated in children or in HIV.47

Treatment is possible with currently available therapies.48 WHO's 2006–2015 ‘Stop TB’ strategy lists several more general interventions that could be integrated into SAM guidelines.

2.8. Strengthening existing TFP strategies 

Although HIV-infected SAM patients may be at most individual risk of death, it is important to remember that the majority of children with SAM are uninfected with HIV, and still carry a high risk of mortality.3, 49 Maximal child survival impact remains dependent on overall improvements in SAM outcomes. Both inpatient and outpatient TFP staff need to be well trained, well resourced and committed to assessing and managing sick children whatever their HIV status.

In TFPs, HIV-specific activities should enhance and complement previous 10 steps and CMAM attempts at quality/outcome improvement, rather than distract or displace resources from the (usually) much larger numbers of HIV-negative patients.50 Although some new elements of HIV-specific care will be necessary to improve survival in HIV-prevalent settings, an overall focus on improving care for all children is also essential.

2.9. Early identification and coverage 

Most of the data available on SAM and HIV is drawn from studies conducted in old-style inpatient centres (nutrition rehabilitation units), which do not have the supporting outpatient elements of CMAM. It is important to recognise that this is a select patient group, whose data do not reflect HIV and SAM prevalence and mortality at population level. TFPs run at hospital facilities usually provide services to a large catchment area. This requires patients to travel long distances to access care, and inpatient nutrition rehabilitation requires the child with SAM and their carer to remain at the facility until nutritional recovery is attained. The distance to travel to access a TFP will influence uptake of services.

Figure 1 illustrates this problem of coverage. Even in countries where paediatric nutrition rehabilitation and/or HIV care programmes are reporting that a high proportion of children with SAM in their TFPs are nutritionally recovering; if these children are only a small proportion of those in need at the population level, then the TFP success is limited.

These problems of coverage can be improved through an integrated programme of facility and CMAM.19 CMAM has increased coverage and service provision for SAM at the community level, including community-based case-finding.18, 19 This has increased the proportion of all children with SAM who are identified and treated.1, 7 Increased coverage and earlier identification of SAM has led to reduced morality in paediatric SAM.1, 7, 20 As HIV-infected children are more likely to become malnourished, HIV testing in CMAM will also increase the proportion of HIV-infected children identified.

2.10. HIV testing at the community level 

Integrating HIV testing into programmes for the treatment of SAM at the community level is challenging; HIV testing requires supplies and trained staff, and HIV testing at community level may increase the risk of stigma.51 Strong community links and credibility built through CMAM can assist with improving community HIV education and testing uptake,18 and uptake of testing at community level has already been demonstrated to be high in CMAM programmes.52 In 2008 Bahwere et al. reported that HIV infection was more common in children with low MUAC.52 It is important to continue to share lessons learned in this emerging area of practice, and integrate these into CMAM guidelines.

Community-based nutrition rehabilitation may assist in identifying HIV-infected children earlier in their disease, and referring them for appropriate treatment.53 Children with SAM who are identified as infected with HIV must be linked to HIV services, both for immediate assessment and treatment and also long-term follow-up and care after nutritional recovery. Children who are not initiated on ARVs upon assessment should be followed-up to track their growth, CD4 count and clinical characteristics with regular reassessments of the need for ARVs.

Although it is now well established that children with SAM in sub-Saharan Africa, especially those treated in large, urban referral hospitals, have a high proportion of HIV infection, little is known about the proportion of HIV among moderately malnourished children. Integrating HIV testing and treatment services into supplementary feeding and growth monitoring programmes may help to identify HIV-infected children earlier in their infection. If these moderately malnourished children are able to then access supplementary feeding as well as HIV treatment, this may prevent these children from developing SAM, and delay HIV progression. There are currently no published data available on the prevalence of HIV among children with moderate malnutrition, and these data are urgently needed. Also, improving early infant diagnosis of HIV and enrolling children on ARVs at <12 months will improve survival and may decrease the proportion of HIV-infected children who develop SAM.

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3. Conclusions 

The care of severely malnourished children in sub-Saharan Africa is challenging, especially in HIV-prevalent settings. Recent improvements to facility-based individual case management and increased community-based management focusing on early identification and high programme coverage have led to reductions in mortality. Further interventions are urgently needed to address resistant mortality, mostly attributable to HIV. Although interventions to further improve survival among children with SAM in sub-Saharan Africa must firstly ensure best care for all children, HIV-infected children are at particular risk for mortality. Integration of specific interventions for HIV testing and treatment into SAM care is essential. International guidelines should reflect best evidence, and are in urgent need of updating and adapting to local country context. Effective interventions already exist that can improve survival in children with SAM in HIV-prevalent settings. The challenge is to implement what we know and to research what we do not.

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Authors’ contributions 

PF, MK and AT were involved in the review of the literature and undertook all the duties of authorship. PF is guarantor of the paper.

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Funding 

None.

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Conflicts of interest 

None declared.

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Ethical approval 

Not required.

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PII: S1876-3413(09)00004-7

doi:10.1016/j.inhe.2009.03.001

International Health
Volume 1, Issue 1 , Pages 10-16, September 2009

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