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Home > Topics > Pediatric Summaries > Chronic Gastritis
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Pediatric Case Discussion Summary: 3-Year-Old HIV-Infected Girl with Chronic Gastritis

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Introduction
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The Case
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Question 1: In view of her marked failure to thrive, does the child need ART?
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Question 2: What do you feel about giving cotrimoxazole to a child with a normal CD4 count in a nonmalarious area?
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Question 3: What is the most likely explanation for her X-ray appearance?
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Question 4: What further investigations would you do?
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Question 5: What treatment does she need?
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Expert Opinions
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Follow-Up
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Conclusion: Women, Children, and HIV Analysis
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References
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Introduction

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The Paediatric Internet-based Discussion Group (PDG) assists health care professionals in resolving HIV-related clinical problems through the use of case studies. Summaries of difficult and interesting cases are emailed to group members who email their responses to all participants. This format allows users to consult with one another, share their experiences, and utilize their collective expertise in the treatment of HIV and HIV-related illnesses in an online forum. The following case was presented to a group of South African pediatricians. The opinions of the participants are summarized below, followed by recommendations from experts in the field. Readers should be aware that opinions vary and may be influenced by the availability of resources and differences in standard of care among regions. Clinical judgment, reinforced by data, is of paramount importance.

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The Case

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The case involves a 3-year-old girl from a nonmalarious area of South Africa. She has been sick since 5 months of age. She apparently has had chronic gastritis/esophagitis for a year. She vomits every feed and is constipated. She has an occasional cough. Her diet is reported to be good. An HIV test result was positive. Her family took her to a state antiretroviral therapy (ART) clinic, but was told that her CD4 cell count was too high for her to start ART and she was given cotrimoxazole prophylaxis. The family brought her to see Dr. Leon Levin in desperation.

Her weight was 8.7 kg (64% of expected) and her height was 82 cm (<3rd percentile). There was no edema. There were no palpable lymph nodes and no clubbing of her fingers. Apart from mild oral thrush, there were no other significant findings. Her lungs, heart, abdomen, and central nervous system were normal on examination.

Her CD4 cell percentage was 37% and her HIV viral load was 4,400 copies/µL. The result of a Mantoux skin test was negative. A chest X-ray examination showed right paratracheal fullness and bilateral reticulonodular infiltrates, especially in the bases and right lung field.

Participants were asked to consider the following questions:

  1. In view of her marked failure to thrive, does the child need ART?

  2. What do you feel about giving cotrimoxazole to a child with a normal CD4 count in a nonmalarious area?

  3. What is the most likely explanation for her X-ray appearance?

  4. What further investigations would you do?

  5. What treatment does she need?

Participants:

Chifumbe Chintu Noluthando Mwanba Nsebula Errol Gottlich
Fredrick Sinyinza Joseph Matare Cyprien Baribwira Wedu Ndebele
Grace Ndeezi Richard Cooke Patrick Ajuna Ted Ruel
Laurent Hiffler Moeketsi Mathe Dayo Adetifa Dave Spencer
Michelle Meiring Pierra-Claver Kariyo Israel Kalyesubula Dimitri Van der Linden
Anette Strehlow Daniel Sidler Jane Fleet Stephane Blanche
Gerhard Dippenaar Philippa Musoke Margie Pascoe Grace Phiri
Dorris Dzombo Diana Dickinson Omar F. Jooma Karyn Moshal
Ira Shah Nematswerani Razaq Abdullahi Emmanuel Luyirika
Helena Rabie Denis Nansera Lindi Mabuyangwe Joris Vandelanotte
Nakimbugwe Victoria Ismail Ticklay Alex Ntumba Sam Awe
Sabrina Kitaka Jenny Nash Mark Paterson
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Question 1: In view of her marked failure to thrive, does the child need ART?

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This question was contentious, with strong opinions voiced and varying answers given. Many debated the child's World Health Organization (WHO) clinical staging. Some participants felt that the child was WHO stage III because of her severe weight loss and oral candidiasis. Others felt that, though her viral load was low and her CD4 count was good, she had HIV wasting syndrome and qualified as WHO stage IV. Many participants felt that various other causes of failure to thrive (FTT) such as tuberculosis (TB) or chronic esophagitis should be explored. Most participants believed that the child could not be appropriately classified until further testing ruled out other causes of the FTT and that ART should not be initiated until the tests were completed. Although most participants supported delaying ART until these further tests could be completed, some stressed that any delay in initiating ART could be harmful and that such delays should be as short as possible.

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Question 2: What do you feel about giving cotrimoxazole to a child with a normal CD4 count in a nonmalarious area?

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Because the girl had a high CD4 percentage and a low viral load, some participants felt that the cotrimoxazole prophylaxis was unnecessary. There seemed to be some dispute about whether cotrimoxazole was beneficial for children in nonmalarious areas. Participants noted recent studies from Zambia and Uganda that have demonstrated significant benefits of cotrimoxazole in reducing morbidity and mortality for HIV-infected children in malarious areas, but doubted the benefit for children in nonmalarious areas.

Participants who felt that the child could be classified as WHO stage III or IV also felt that cotrimoxazole was important for the child's health. Some respondents noted that, although the child had a good immunologic and virologic profile, the presence of oral candidiasis suggested that she was not as immunologically sound as her lab test results indicated; this led some respondents to conclude that cotrimoxazole prophylaxis was indeed appropriate for the girl. South African HIV care guidelines state that any HIV-infected child not receiving ART should be given cotrimoxazole prophylaxis. ( 1 )

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Question 3: What is the most likely explanation for her X-ray appearance?

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The general consensus was that the X-ray findings were indicative of either TB or lymphoid interstitial pneumonia (LIP). Some participants felt that the child might have Pneumocystis jiroveci pneumonia (PCP), though the CD4 count was not consistent with this diagnosis. A few participants mentioned possible lymphoma.

To many participants, the absence of enlarged lymph nodes, splenomegaly, and clubbed fingers ruled out LIP. Others cited empiric evidence that LIP could be diagnosed in HIV-infected children without these classic symptoms. Many participants wondered if the child had been exposed to TB at home. If the child was severely immunocompromised (despite her high CD4 percentage), the negative Mantoux test would not necessarily mean that she was TB negative. If this were the case, the X-ray findings would be more meaningful than the test. The majority of participants suggested further testing for TB or empiric treatment to definitively answer this question.

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Question 4: What further investigations would you do?

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The most troubling aspects of this case for participants were the child's FTT and her chest X ray. Participants were eager to get to the root of the FTT. Many felt that if TB or a lymphoma could be diagnosed and appropriately addressed, the FTT could reverse course. Despite the child's age, participants said that they ideally would do a sputum induction through bronchial aspiration to perform an acid-fast bacillus (AFB) smear in order to definitively diagnose TB. One participant suggested that doing the lavage in the early morning could improve the accuracy of the test results.

To assess for other causes of the FTT, participants suggested gastric lavage and a barium swallow to assess whether paratracheal fullness might be compressing the esophagus. Many participants suggested ultrasound of the abdomen for paraaortic lymphadenopathy. Some participants worried that the family's report of the child's "good diet" was not accurate and suggested conducting a thorough family history, social history, and an assessment of the home's hygiene, water, and food supply, including a true calorie count.

Other suggested tests included stool microscopy, culture, and sensitivity; a complete blood count and organism analysis to rule out other sources of infection; urine analysis to exclude a urinary tract infection; liver function tests; a sweat test to rule out cystic fibrosis; growth hormone measurements; and measurements of the alpha 1 -antitrypsin reducing substance, C-reactive protein, and erythrocyte sedimentation rate.

Several participants suggested fundoscopy to look for evidence of increased intracranial pressure. Many felt it would be beneficial to repeat the chest X-ray screening, the CD4 count, and the viral load test to ensure the accuracy of the first results.

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Question 5: What treatment does she need?

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The majority of participants felt that the child needed TB treatment immediately. It was agreed that obtaining a sputum sample from such a young child might not be possible, but most participants felt she would benefit from empiric TB treatment. Some argued that a period of TB treatment could prepare the family for ART and give them the opportunity to receive ART adherence counseling. All who addressed the issue of the oral candidiasis felt that the child should receive systemic fluconazole or oral nystatin tablets.

Because the child's nutritional status was very disconcerting to most participants, many felt that immediate nutritional supplementation was urgently needed. Suggestions for nutritional support included thickening any milk feedings, providing multivitamin therapy, giving the child additional vitamin A, and providing parenteral nutritional treatment. Additionally, several participants suggested increasing the girl's fluid intake to help address the problem of constipation and to improve her health status. Antacids and deworming medication also were recommended. Participants felt the child's nutritional status would improve with treatment of the gastroesophageal reflux disease and regular follow-up, perhaps separately from the care provided by an ART clinic.

Participants who thought the X-ray findings were indicative of LIP felt the child should be treated for the disease.

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Expert Opinions

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After the participants discussed the case and contributed their suggestions for treating the patient, the details were presented to a panel of experts. The members of the panel were:

  • Gordon Schutze --Professor of Pediatrics, Baylor College of Medicine

  • Andy Pavia --Chief of Pediatric Infectious Diseases, Professor of Pediatrics and Medicine, University of Utah

  • Daniel Sidler --Pediatric surgeon and ethicist, Tygerberg Children's Hospital, Stellenbosch University, Cape Town, South Africa

  • Louise Cooke --Pediatric gastroenterologist, Tygerberg Children's Hospital, Stellenbosch University, Cape Town, South Africa

  • Gareth Tudor Williams --Consultant, Pediatric HIV and Infectious Diseases, Saint Mary's NHS Trust Hospital, London, UK

Although the experts differed in their interpretations of the child's X-ray findings, most of them believed that the girl would benefit from delaying the initiation of ART until further testing could be performed. Dr. Schutze felt that the X-ray findings were suggestive of LIP. In his opinion, the child should be started on ART and should continue cotrimoxazole prophylaxis. After the child was stabilized on ART, the X-ray images could be reevaluated. Conversely, Dr. Pavia and most of the other experts thought that TB was the most likely diagnosis and that the child would benefit from TB treatment before starting ART. They repeated the suggestion that starting the child on TB treatment before ART would give the family a chance to receive adequate antiretroviral adherence counseling.

In Dr. Pavia's opinion, the cotrimoxazole prophylaxis was prudent for all HIV-infected children in tropical and subtropical resource-poor environments because of the protection it provides against bacteremia and meningitis caused by pneumococcus. Many of the experts consulted declined to address the cotrimoxazole issue without more research on the benefits of the drug in nonmalarious areas.

The experts all thought that the child's FTT was of primary importance to her overall well-being. The FTT was attributed largely to some kind of esophageal blockage. Most experts felt that more invasive diagnostic tests were necessary to definitively understand what was causing the child's difficulties with nutrient absorption and FTT. All suggested gastric lavage or barium swallow examinations.

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Follow-Up

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Dr. Levin followed up with the group about his own investigations into the case:

  • Because of the child's persistent vomiting, I requested a barium swallow. A Hexabrix swallow showed tight stricture at the gastroesophageal junction that appeared smooth, regular, and benign. There was proximal dilation of the esophagus with very slow emptying into the stomach and reflux of contrast proximally due to the stricture.

  • I subsequently referred her to the pediatric surgery department of a large academic hospital where she underwent 3 dilatations of her stricture. There was a marked improvement and weight gain (she weighed 11.3 kg 3 months later on October 4, 2006) even though there was still some vomiting (now from gastroesophageal reflux). As a result, she underwent a laparoscopic Nissen fundoplication on October 13, 2006. Since then, there has been no further vomiting, and when I saw her on November 2, 2006, she weighed 12 kg. Her CD4 percentage was 32% and her viral load was 1,242 copies/µL.

  • On October 4, 2006, I started her on TB treatment because her chest X-ray findings had deteriorated, but by then she had already gained almost 3 kg.

  • I have not started her on ART but will continue to monitor her clinically and immunologically.

  • To answer the other questions, her chest X-ray appearance could be either LIP or TB.

  • As far as the cotrimoxazole is concerned, I would refer you to an article by Dr. David Spencer in the September 2006 edition of the South African Journal of HIV Medicine , which discusses this issue. It seems we should not necessarily extrapolate data from one region to another. This case illustrates the point that we must listen carefully to our patients and that if things do not make sense, we should investigate further.

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Conclusion: Women, Children, and HIV Analysis

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Several of the issues concerning the diagnosis and treatment of this child deserve additional comments.

The child in the case, who we can assume was perinatally infected, is not a rapid progressor, and LIP is associated with long-term survival in children who were infected with HIV perinatally.( 2 , 3 ) However, two of the most obvious clinical manifestations of LIP are chronic parotid swelling and diffuse lymphadenopathy, neither of which was present in this patient. Other causes, particularly infectious agents, must be found in order to explain the child's X-ray findings. Appropriately, TB was considered the most likely explanation for the X-ray findings but, given the unusual presentation in this child, other treatable opportunistic infections such as Mycobacterium avium complex (MAC) also should have been considered. Two additional diagnostic procedures could have been helpful: a bone marrow aspiration and a lung biopsy with cultures and microscopic examination.

The presence of thrush in this child in the absence of previous antibiotic treatment is indicative of immunodeficiency regardless of the CD4 percentage. The CD4 cell count or percentage reflects the number of CD4 lymphocytes but not necessarily their function. Lack of immunity to a specific infectious agent can therefore occur in individuals with normal CD4 cell counts/percentages, as reflected in this child who has Candida infection of the mucous membranes. Such immunodeficiency would qualify her for ART. It is important to remember that national and international guidelines on ART initiation criteria are meant as suggestions only. Clinical judgment that takes into account the individual patient's circumstances and needs should always prevail.

The cotrimoxazole discussion is important. However, the questions about the relevance of clinical trial results from Uganda and Zambia (areas where malaria is endemic) to other geographic settings seem to miss several points:

  • Cotrimoxazole is used as prophylaxis against bacterial infections that are common in individuals who are immunocompromised. Cotrimoxazole prophylaxis protects against PCP, bacteremia, pneumococcal meningitis, toxoplasmosis, and isosporiasis, all potentially lethal complications in HIV-infected children not receiving ART. It is not meant to be used for protection against malaria, although there is evidence that it may indeed provide such protection.( 4 ) The studies that have been reported suggest it is effective regardless of whether or not patients have malaria.( 5 )

  • Cotrimoxazole prophylaxis has been part of the standard of care for preventing PCP and toxoplasmosis in nontropical resource-rich countries since the early 1990s, and there is ample evidence from both randomized clinical trials and observational studies it is effective in preventing PCP in infants and children.( 5 , 6 , 7 )

  • The ethics of performing additional controlled trials on cotrimoxazole prophylaxis efficacy in HIV-infected children living in nonmalarious areas are highly questionable. Indeed, the recent Zambian CHAP study met strong criticism from some quarters for using a placebo-controlled study design in an investigation of a prophylactic agent that is known to be effective.

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References

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1. transparent gif Department of Health, Republic of South Africa, Guidelines for the Management of HIV-infected Children. 2005. Available at: http://www.doh.gov.za/docs/factsheets/guidelines/hiv/part2.pdf .
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2. transparent gif Kline MW, Paul ME, Bohannon B, et al. Characteristics of children surviving to 5 years of age or older with vertically acquired HIV infection . Pediatr AIDS HIV Infect. 1995 Dec;6(6):350-3.
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3. transparent gif Nielsen K, McSherry G, Petru A, et al. A descriptive survey of pediatric human immunodeficiency virus-infected long-term survivors . Pediatrics. 1997 Apr;99(4):E4.
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4. transparent gif Thera MA, Sehdev PS, Coulibaly D, et al. Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease . Journal of Infectious Diseases, 2005, 192:1823-1829.
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5. transparent gif Mulenga V, Ford D, Walker AS, et al; CHAP Trial Team. Effect of cotrimoxazole on causes of death, hospital admissions and antibiotic use in HIV-infected children . AIDS. 2007 Jan 2;21(1):77-84.
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6. transparent gif Chintu C, Bhat GJ, Walker AS, et al; CHAP trial team. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial . Lancet, 2004, 364:1865-1871.
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7. transparent gif World Health Organization. Guidelines on Cotrimoxazole Prophylaxis for HIV-Related Infections among Children, Adolescents and Adults in Resource-Limited Settings: Recommendations for a Public Health Approach. August 07, 2006. Available at: http://www.who.int/hiv/pub/guidelines/WHO%20CTX.pdf .
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