HIV – a cause of pyrexia of unknown origin
We write in response to Wong and Ng's case study from Kuala Lumpur, which described a case of non- Hodgkin lymphoma presenting with fever and a skin nodule (AFP January/February 2012).1 We would like to highlight the importance of considering another cause of pyrexia of unknown origin (PUO) that was not mentioned by the authors, namely human immunodeficiency virus (HIV).
Fever in HIV patients may occur in a number of different situations: virus seroconversion can present with a fever,2 along with symptoms that may be similar to those associated with other viral illnesses such as aches and pains, sore throat and rash. This may go unnoticed by the patient, but on close questioning they may recall such an illness. Tests for HIV may be negative in the early stages of the illness.
HIV infection can underlie a number of important causes of PUO. In a patient with undiagnosed HIV infection with immunodeficiency (particularly if CD4 cell count <250 cells/uL) tuberculosis and lymphoma are more common and can present with fever, as can other opportunistic infections such as Pneumocystis jiroveci pneumonia.3
Human immunodeficiency virus can be transmitted sexually or by unsafe drug injecting practices, thereby increasing the risk of other infections with the same risk factors. Thus, secondary syphilis should be considered as it can present with rash and fevers4 and endocarditis may present as PUO in injecting drug users with undiagnosed HIV infection.3
Early diagnosis of HIV infection has obvious benefit to the individual but there are also public health benefits in the form of reduced HIV transmission. We recommend HIV testing in all cases of PUO, including those due to tuberculosis and lymphoma.
Dr Louise Owen
Sexual health physician and Director Statewide Tasmanian Sexual Health Service, Tas
Dr Tim Read
Sexual health physician Victorian Infectious Diseases Service, Royal Melbourne Hospital and Melbourne Sexual Health Centre, Alfred Hospital, Vic
Cardiac stress testing
I thank Drs McLellan and Prior5 for their article on cardiac stress testing (AFP March 2012). Could you kindly request that they comment on the problem of false positivity of electrocardiogram (ECG) stress testing on patients with low risk of heart disease. It is my understanding that the low risk patient should not be advised to undergo an ECG stress test.
Dr Gillian Deakin
- M cLellan A, Prior D. Cardiac stress testing: stress electrocardiography and stress echocardiography. Aust Fam Physician 2012;41:119–22.
We thank Dr Deakin for highlighting this issue. Exercise stress testing (EST) is most useful in patients with an intermediate pretest probability, as EST can re-stratify the intermediate risk patient to low or high risk and thus alter patient management. A patient's pretest probability of coronary artery disease can be quickly estimated by assessing age, gender and symptoms (refer Table 4, Gibbons et al, 2002). Based on a Bayesian approach, because there is significant percentage of false positive tests with stress ECG, the overwhelming likelihood is that a positive test result in a low risk individual will be a false positive rather than a true positive and will therefore assist little in further risk stratification. For this reason, we agree that stress ECG in the low risk patient is probably not appropriate; if a stress test is required it is more practical to order a test with higher diagnostic accuracy such as a stress echocardiogram that will reduce (but not eliminate) the number of false positive tests.
Dr Alex McLellan
Department of Cardiology St Vincent's Hospital Melbourne, Vic
- Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 Guideline Update for Exercise Testing. 2002. American College of Cardiology Web site. Available at www.acc.org/clinical/guidelines/exercise/dirIdex.htm.
Feeding in the first year of life
The advice on infant feeding in the article by Symon and Bammann7 (AFP April 2012) contradicts that given by the World Health Organization and most major professional and national bodies, including the National Health and Medical Research council (NHMRC), who recommend exclusive breastfeeding to 6 months or 'around 6 months of age'. The American Academy of Pediatrics, who have recently considered all of the new evidence, continue to recommend exclusive breastfeeding to 6 months.8 The United States Surgeon General's report on breastfeeding outlines recent evidence and sets targets for exclusive breastfeeding to 6 months.9 The recommendations to exclusively breastfeed to 6 months are associated with the lowest levels of morbidity and mortality and offer some protection against allergy. In the general population and in atopic families, exclusive breastfeeding for around 6 months can protect against allergic rhinitis, wheezing, asthma and atopy in children. Recent major systematic reviews show the nutritional adequacy of breastfeeding to around 6 months and confirm that this is associated with optimum morbidity and mortality in the long and short term.10
Timing of introduction of solid foods has been of interest since Soothill and others in the 1980s recommended allergen avoidance via delayed introduction of protein containing foods to children at increased risk of allergy.11 This has not been confirmed, and there is evidence that delayed introduction of antigen containing foods can lead to increased risk of allergic disease. The evidence that introduction of solid foods to infants aged less than 6 months is associated with lower rates of allergies is limited, has differing outcomes (including demonstrating increased risks of allergic disease) and is generally of inadequate quality.
The best way of minimising the multiple sources of bias inherent in assessing the risks and benefits of early introduction of solids is through the use of a randomised controlled trial design. Randomisation to breast vs artificial feeding is clearly not feasible and is probably unethical. What is feasible and ethical is to randomise women to a breastfeeding promotion intervention.12 This is what was done for the PROBIT study. 'To our knowledge, PROBIT is the largest randomised trial ever performed in the area of human lactation. Our results confirm previous observational evidence that prolonged and exclusive breastfeeding reduces the risk of gastrointestinal infection and atopic eczema during infancy. But by 6 years the difference had disappeared'.13 In other words, the introduction of solid foods before 6 months had no adverse effects on allergy incidence.
Currently, the available evidence supports the view that the optimal short and long term health of the infant is best served by exclusive breastfeeding until around 6 months. Solid foods should then be introduced while breastfeeding is continued. Other than the requirement of high nutrient density, the provision of essential nutrients and appropriate texture, there are no restrictions on the number of new foods or their order of introduction. Previously it was often advised to avoid exposure to peanuts or eggs during the first 12 months of life, but there is no evidence of benefit from this practice. The draft NHMRC infant feeding guidelines no longer recommend delaying the introduction of potential allergens.
Symons and Bammann support the view that there is a 'window of opportunity' for the introduction of solids in the period between 4 and 6 months of age to minimise the development of allergies. The current NHMRC recommendation to exclusively breastfeed to around 6 months falls within this window. Currently almost all Australian parents are introducing solids by 6 months. The 2010 Australian National Infant Feeding Survey showed that at 6 months of age 91.5 (+1)% of infants had received solid foods within the past 24 hours.14
A full review of the evidence supporting the risks of not breastfeeding is available in the draft NHMRC Infant feeding guidelines for health workers. A final version of this document will be released later in 2012, but it is unlikely that the present advice on breastfeeding will change.
Professor Colin Binns
John Curtin Distinguished Professor of Public Health, Curtin University, WA
Professor David Forbes
Professor of Paediatrics and Child Health University of Western Australia, WA
Professor Jane Scott
Professor of Nutrition and Dietetics, School of Medicine, Flinders University, SA
Ms Maria Pasalich
Research Officer, School of Public Health Curtin University, WA
The writers have been involved in the revision of the NHMRC infant feeding guidelines, but the opinions expressed in this letter are their own and do not necessarily reflect the views of the NHMRC.
- 1. S ymon B, Bammann M. Feeding in the first year of life – emerging benefits of introducing complementary solids from 4 months. Aust Fam Physician 2012;41:226–9.
- 2. American Academy of Pediatrics. Breastfeeding and the use of human milk. Pediatrics 2012;129:e827–41.
- 3. U .S. Department of Health and Human Services. The Surgeon General's call to action to support breastfeeding. Washington, DC: Office of the Surgeon General, 2011.
- 4. N ational Health and Medical Research Council. Infant feeding guidelines for health workers – draft for public consultation, October 2011. Available at http://consultations.nhmrc.gov.au/ public_consultations/archived_consultations/2011 [Accessed 5 May 2012].
- 5. S oothill JF. Dietary antigen avoidance: postponement or prevention? Lancet 1980;1:604.
- 6. Kramer MS. "Breast is best": the evidence. Early Hum Dev 2010;86:729–32.
- 7. Kramer MS, Matush L, Bogdanovich N, Dahhou M, Platt RW, Mazer B. The low prevalence of allergic disease in Eastern Europe: are risk factors consistent with the hygiene hypothesis? Clin Exp Allergy 2009;39:708–16.
- 8. Australian Institute of Health and Welfare. The 2010 Australian National Infant Feeding Survey: indicator results. Canberra: AIHW, 2011.
The response to our article amplifies our concerns. We continue to emphasise that there is clear evidence for benefits of breastfeeding but limited evidence that these benefits are amplified by making it exclusive. The single validated exception is a lower risk of gastroenteritis. We have been unable to find evidence that the significant benefits of breastfeeding to mother and child are diluted or diminished by additional supportive feeding while maintaining breastfeeding.
We do not dispute that a number of international organisations support exclusive breastfeeding for 6 months (EBF6). Conversely however, the Australasian Society of Clinical Immunology and Allergy, the peak professional body of clinical immunologists and allergists in Australia and New Zealand, now recommend introducing solids from 4–6 months.15 The position paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition discusses the introduction of complementary feeding 'from 17 weeks and not later than 26 weeks'.16
Recent papers have also raised concerns on the quality of evidence behind this important public health advice.17,18 It is clear that there are significant concerns internationally about the focus on exclusivity. We have also been unable to find any evidence for a lowering of mortality in developed nations by making breastfeeding exclusive for 6 months.
Extensive research has failed to produce convincing consistent evidence that EBF6 offers protection against allergy, asthma and eczema. High quality papers show both increased and decreased levels of allergy with EBF6.19,20 Particularly in the area of food allergy, the preponderance of new evidence is that earlier introduction of an increased range of food allergens will decrease long term and, in some cases, permanent food allergies.21,22 In fact, while discussing the PROBIT study Binns et al conclude 'the introduction of solid foods before 6 months had no adverse effects on allergy'. They also report 'delayed introduction of antigen containing food can lead to increased risk of allergic disease'.
Again, the current evidence lacks consistency when considering whether EBF6 will protect against atopic disease. There is some evidence that prolonging exclusivity in an atopic mother increases atopic risk in the infant.20
Significant papers have recently been published that do not support a protective impact of EBF6 on eczema or asthma.23,24
In our review of the literature, it was clear in a large number of robust studies that the incidence of exclusive breastfeeding in mothers is so low that obtaining meaningful data is difficult.25 The studies usually allocate benefit to breast milk rather than exclusivity. Unfortunately, many authors then interpret and infer that the benefits as belonging to exclusivity when the evidence does not support that next step.26,27
As clinicians working with breastfeeding mothers on a daily basis, it is evident that some women are unable to meet the full energy needs of their child from their own breast milk. Using the data from the Millennium study it is reported that 1% of women in the United Kingdom are exclusively breastfeeding at 6 months, despite widespread encouragement to do so.28 In Australia, many studies show rates of around 10% exclusive breastfeeding at 6 months.29–33
Finally, we question the complete absence of any warning on risk. In all other therapeutic domains of medicine there is an ethical requirement to warn of risks as well as benefits. The movement in favour of EBF6 implies that this is risk-free advice and will provide 'lowest levels of morbidity and mortality'. There is virtually no caveat about impaired weight gain34 or failure to thrive in some babies, increased risks of coeliac disease35,36 and a possible or even probable increase in risks of long term food allergies.18,21,22
We do not agree that an overwhelming emphasis on exclusivity is supported by robust current evidence and neither do we agree that using the term 'about 6 months' provides enough guidance to mothers that there are likely to be immunological benefits from introducing solids between 4–6 months.
Our article was written in response to the draft document 'Infant feeding guidelines for health workers', which is currently at public review. Binns et al conclude that it is 'unlikely that present advice on breastfeeding will change,' which questions the rationale for the current period of public consultation.
Dr Brian Symon
University of Adelaide, SA
Mr Michael Bammann, SA
- Australian Society of Clinical Immunology and Allergy. Infant feeding advice, 2010.
- Agostoni C, Decsi T, Fewtrell M, et al. Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2008;46:99–110.
- Fewtrell M, Wilson DC, Booth I, Lucas A. Six months of exclusive breast feeding: how good is the evidence? BMJ 2011;342:c5955.
- Prescott SL, Smith P, Tang M, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol 2008;19:375–80.
- Matejek N, Schwamberger H, Böhles MD. The influence of breast feeding on the development of atopic dermatitis. Exclusive breast feeding versus initial short term feeding of a partial hydrolyslate followed by breast milk. Nutrition Research 1998;18:1389–93.
- Giwercman C, Halkjaer LB, Jensen SM, Bonnelykke K, Lauritzen L, Bisgaard H. Increased risk of eczema but reduced risk of early wheezy disorder from exclusive breast-feeding in high-risk infants. J Allergy Clin Immunol 2010;125:866–71.
- Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol 2010;126:807–13.
- Du Toit G, Katz Y, Sasieni P, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol 2008;122:984–91.
- Yang YW, Tsai CL, Lu CY. Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta-analysis of prospective cohort studies. Br J Dermatol 2009;161:373–83.
- Langan SM, Fewtrell M. Does breastfeeding protect against the development of eczema? Br J Dermatol 2011;165:1157–8.
- Ip S, Chung M, Raman G, et al. Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess (Full Rep) 2007;153:1–186.
- Binns CW. Introduction of solids before 4 months is associated with obesity at 3 years among formula- fed infants but not among breast-fed infants. Evid Based Med 2011;16:177–8.
- Symon B, Bammann M. Is recent advice on exclusive breastfeeding consistent with the data presented? Evid Based Med 2012 [Epub ahead of print].
- Quigley MA, Kelly YJ, Sacker A. Breastfeeding and hospitalization for diarrheal and respiratory infection in the United Kingdom Millennium Cohort Study. Pediatrics 2007;119:e837–42.
- Australian Institute of Health and Welfare. 2010 Australian National Infant Feeding Survey: indicator results. Cat. no. PHE 156. Canberra: AIHW, 2011.
- Victorian Child and Wellbeing Survey Technical report, 2006. Published by the State-wide Outcomes for Children Branch, Office for Children, Department of Human Services, 2007.
- Forde KA, Miller LJ. 2006–07 north metropolitan Perth breastfeeding cohort study: how long are mothers breastfeeding? Breastfeed Rev 2010;18:14–24.
- Centre for Epidemiology and Research. 2007–2008 Report on child health from the New South Wales Population Health Survey. Sydney: NSW Department of Health.
- The Health of Queenslanders 2008: prevention of chronic disease. Second report of the Chief Health Officer Queensland. Brisbane: Queensland Health, 2008.
- Kramer MS. Optimal duration of exclusive breastfeeding (review). The Cochrane Collaboration, 2009.
- Norris JM, Barriga K, Hoffenberg EJ, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA 2005;293:2343–51.
- Poole JA, Barriga K, Leung DY, et al. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics 2006;117:2175–82.